Case Western Reserve University is a private research university in Cleveland, Ohio. The university was created in 1967 by the federation of Case Institute of Technology and Western Reserve University . TIME magazine described the merger as the creation of "Cleveland's Big-Leaguer" university.In U.S. News & World Report's 2013 rankings, Case Western Reserve's undergraduate program ranked 37th among national universities. The University is associated with 16 Nobel laureates. Other notable alumni include Paul Buchheit, creator and lead developer of Gmail; Craig Newmark, founder of craigslist.org; and Peter Tippett, who developed the anti-virus software Vaccine, which Symantec purchased and turned into the popular Norton AntiVirus. Case Western Reserve is particularly well known for its medical school, business school, dental school, law school, Frances Payne Bolton School of Nursing , Department of Biomedical Engineering and its biomedical teaching and research capabilities. Case Western is a member of the Association of American Universities.The university is approximately five miles east of downtown Cleveland in University Circle. It is contained within a 550-acre area containing numerous educational, medical, and cultural institutions. Case Western Reserve has a number of programs taught in conjunction with nearby institutions, including the Cleveland Clinic, the University Hospitals of Cleveland, the Louis Stokes Cleveland Department of Veteran's Affairs Medical Center, Cleveland Institute of Music, the Cleveland Hearing & Speech Center, the Cleveland Museum of Art, the Cleveland Museum of Natural History, and the Cleveland Play House.Case Western Reserve was the site of the famous Michelson-Morley interferometer experiment, conducted in 1887 by Albert A. Michelson of Case School of Applied Science and Edward W. Morley of Western Reserve University. This experiment proved the non-existence of the luminiferous ether and was later cited as convincing evidence in support of special relativity as proposed by Albert Einstein in 1905. Michelson became the first American to win a Nobel Prize in science. The commemorative Michelson-Morley Memorial Fountain is located on campus, near where the actual experiment was performed. Wikipedia.
Case Western Reserve University | Date: 2016-02-29
A system for detecting tumor margins includes a topical protease-specific, fluorescence imaging probe that is activatable by enzymatic activation to produce a visually differentiated signal upon topical application to a targeted cancer cell that secretes an enzyme that activates the protease-specific, fluorescence imaging probe, means for topically administering the imaging probe to the cancer cell; and an imaging device to detect activation of the imaging probe administered to the cancer cell.
Case Western Reserve University | Date: 2016-11-21
A method treating cancer in a subject comprises administering to the subject a therapeutically effective amount of an antimetabolite agent that induces formation of AP sites in cancer cells of the subjects and an amount AP endonuclease inhibitor effective to potentiate the cytotoxicity of the antimetabolite agent to the cancer cells.
Case Western Reserve University | Date: 2016-08-02
A method of treating a T-cell mediated disorders in a tissue includes administering to the tissue of the subject a therapeutically effective amount of a complement antagonist that substantially reduces T-cell differentiation or t-cell inflammatory cytokine generation.
Case Western Reserve University | Date: 2016-09-06
A method of treating a bacterial infection in a subject in need thereof includes administering to the subject therapeutically effective amounts of at least one -lactam antibiotic and at least one triazolylmethyl boronic acid.
Case Western Reserve University | Date: 2016-08-02
Methods, apparatus, and other embodiments associated with classifying a region of tissue using quantified vessel tortuosity are described. One example apparatus includes an image acquisition logic that acquires an image of a region of tissue demonstrating cancerous pathology, a delineation logic that distinguishes nodule tissue within the image from the background of the image, a perinodular zone logic that defines a perinodular zone based on the nodule, a feature extraction logic that extracts a set of features from the image including a set of tortuosity features, a probability logic that computes a probability that the nodule is benign, and a classification logic that classifies the nodule tissue based, at least in part, on the set of features or the probability. A prognosis or treatment plan may be provided based on the classification of the image.
Case Western Reserve University | Date: 2016-09-23
A method of treating root avulsion injury in a subject in need thereof includes administering to the subject a therapeutic agent that inhibits one or more of catalytic activity, signaling, and function of PTP.
Case Western Reserve University | Date: 2016-10-18
A hybrid method is provided for modulating upper airway function in a subject. The method includes applying first and second therapy signals to the subject to modulate at least one extrinsic laryngeal muscle and at least one intrinsic laryngeal muscle to synergistically control laryngeal motion and vocal fold movement, respectively.
Case Western Reserve University | Date: 2015-02-10
A polymer nanofiber scaffold includes a plurality of melt extruded nanofibers that are chemically modified to append surface functionality to the nanofibers.
Case Western Reserve University | Date: 2015-03-17
One aspect of the present disclosure relates a system that can quickly and reversibly block conduction in a nerve. The system can include a first nerve block modality that provides heat to the nerve to block conduction in the nerve. For example, the heat can provide the quick nerve block. The system can also include a second nerve block modality that provides an electrical signal to the nerve to block the conduction in the nerve. For example, the electrical signal can provide the reversibility. In some instances, the heat can be provided by an infrared light signal and the electrical signal can be provided by a kilohertz frequency alternating current (KHFAC) signal or a direct current (DC) signal.
Case Western Reserve University | Date: 2016-11-07
Described herein are systems and methods for the treatment of pain using electrical nerve conduction block (ENCB). Contrary to other methods of pain treatment, the ENCB can establish a direct block of neural activity, thereby eliminating the pain. Additionally, the ENCB can be administered without causing electrochemical damage. An example method can include: placing at least one electrode contact in electrical communication with a region of a subjects spinal cord; applying an electrical nerve conduction block (ENCB) to a nerve in the region through the at least one electrode contact; and blocking neural activity with the ENCB to reduce the pain or other unwanted sensation in the subject.
Case Western Reserve University | Date: 2015-05-06
A process for surface activation or depassivation of an article, in particular an alloy, by immersion of the alloy in an aqueous acid solution. The surface activation methods of the present invention can be performed during a relatively short period of time and achieve reductions in production costs and provide environmental friendliness as compared to prior art processes. In a further embodiment, after surface activation, the article is immersed in a second liquid that prevents re-formation of a passivating oxide layer on the surface of the article. In a further embodiment the surface-activated alloys are subjected to surface engineering by a process that infuses carbon or nitrogen through the surface at a temperature sufficiently low to suppress precipitation of carbides or nitrides.
Case Western Reserve University | Date: 2015-04-28
Methods for co-extruding multiple layers of materials, in particular high viscosity elastomer materials, wherein the method allows the use of either rheologically matched or unmatched elastomers. Devices for practicing the methods are disclosed. Multilayer extrudates exhibiting desirable performance can be formed from materials including high and/or low viscosity elastomers.
Case Western Reserve University | Date: 2016-08-17
Disclosed herein are biomaterials that include a plurality of fibers embedded in a matrix of hydrogel material. The plurality of fibers and hydrogel material are formed during one process step. In one embodiment, the plurality of fibers and hydrogel materials are formed using a multilayer coextrusion process step. Additional process steps can be performed to form a tissue engineering scaffold. Such a scaffold can be used to grow biological matter. In one embodiment, stem cells are applied to the scaffold to grow biological material. Process steps can be controlled to determine certain mechanical properties of the resulting biomaterial. In one embodiment, the process steps are controlled to determine the stiffness of the resulting biomaterial. In such an embodiment, the stiffness of the resulting biological material determines physical properties of the biological material grown on the scaffold.
Case Western Reserve University | Date: 2016-11-08
A cell-permeable polypeptide includes a membrane transduction domain and a polypeptide comprising an amino acid sequence substantially homologous to the amino acid sequence of the TRAF2,3 binding domain, the cell permeable peptide inhibiting binding of TRAF2 to the TRAF2,3 binding domain of CD40 to decrease or inhibit a CD-40 activity or signal transduction pathway associated with a CD40-mediated disease in cells of a subject.
Case Western Reserve University | Date: 2016-06-13
The invention provides for dry spray compositions comprising co-polymers comprising a core, water-soluble polymer and a peptide.
Case Western Reserve University | Date: 2016-10-13
The present invention relates a system that can configure a stimulus for functional electrical stimulation (FES) to maintain a constant muscle force while delaying the onset of muscle fatigue and a related method of use. The stimulus can be delivered to a nerve via a set of multiple electrode contacts according to a stimulation parameter that maximizes a joint moment associated with the stimulus and minimizes the overlap between pairs of contacts. The joint moment can be related to the muscle force, and the overlap can be related to the onset of muscle fatigue.
Case Western Reserve University and University of Oregon | Date: 2016-09-06
A method of treating heart disease and/or injury in a subject includes administering to the subject a therapeutic agent that inhibits one or more of catalytic activity, signaling, and function of PTP.
Case Western Reserve University | Date: 2016-03-21
Methods and apparatus associated with predicting colorectal cancer tumor invasiveness are described. One example apparatus includes a set of circuits, and a data store that stores radiological images of tissue demonstrating colorectal cancer. The set of circuits includes a circumferential resection margin (CRM) prediction circuit that generates a CRM probability score for a diagnostic radiological image, an image acquisition circuit that acquires a diagnostic radiological image of a region of tissue demonstrating colorectal cancer pathology and that provides the diagnostic radiological image to the CRM prediction circuit, and a training circuit that trains the CRM prediction circuit to quantify chemoradiation response in the region of tissue represented in the diagnostic radiological image. The training circuit trains the CRM prediction circuit using a set of composite images.
Case Western Reserve University | Date: 2016-08-02
Methods, apparatus, and other embodiments associated with classifying a region of tissue using textural analysis are described. One example apparatus includes an image acquisition logic that acquires an image of a region of tissue demonstrating cancerous pathology, a delineation logic that distinguishes nodule tissue within the image from the background of the image, a perinodular zone logic that defines a perinodular zone based on the nodule, a feature extraction logic that extracts a set of features from the image, a probability logic that computes a probability that the nodule is benign or that the nodule will respond to a treatment, and a classification logic that classifies the nodule tissue based, at least in part, on the set of features or the probability. A prognosis or treatment plan may be provided based on the classification of the image.
MTD Products Inc. and Case Western Reserve University | Date: 2017-01-18
This invention provides a method for identifying lawn grass comprising capturing an image of the terrain in front of a mower, segmenting the image into neighborhoods, calculating at least two image statistics for each of the neighborhoods, generating a binary representation of each image statistic. The binary representation of each image statistic is generated by comparing the calculated image statistic values to predetermined image statistic values for grass. The method further comprises weighting each of the binary representations of each image statistic, and summing corresponding neighborhoods for all image statistics. A binary threshold is applied to each of the summed neighborhoods to generate a binary map representing grass containing areas and non-grass containing areas.
Colley D.G.,University of Georgia |
Secor W.E.,Centers for Disease Control and Prevention |
King C.H.,Case Western Reserve University
The Lancet | Year: 2014
Human schistosomiasis-or bilharzia-is a parasitic disease caused by trematode fl ukes of the genus Schistosoma. By conservative estimates, at least 230 million people worldwide are infected with Schistosoma spp. Adult schistosome worms colonise human blood vessels for years, successfully evading the immune system while excreting hundreds to thousands of eggs daily, which must either leave the body in excreta or become trapped in nearby tissues. Trapped eggs induce a distinct immune-mediated granulomatous response that causes local and systemic pathological eff ects ranging from anaemia, growth stunting, impaired cognition, and decreased physical fi tness, to organ-specifi c eff ects such as severe hepatosplenism, periportal fi brosis with portal hypertension, and urogenital infl ammation and scarring. At present, preventive public health measures in endemic regions consist of treatment once every 1 or 2 years with the isoquinolinone drug, praziquantel, to suppress morbidity. In some locations, elimination of transmission is now the goal; however, more sensitive diagnostics are needed in both the fi eld and clinics, and integrated environmental and health-care management will be needed to ensure elimination. © Chataway et al. Open Access article distributed under the terms of CC BY.
McGaugh S.S.,Case Western Reserve University |
Schombert J.M.,University of Oregon
Astronomical Journal | Year: 2014
We combine Spitzer 3.6 μm observations of a sample of disk galaxies spanning over 10 mag in luminosity with optical luminosities and colors to test population synthesis prescriptions for computing stellar mass. Many commonly employed models fail to provide self-consistent results: the stellar mass estimated from the luminosity in one band can differ grossly from that of another band for the same galaxy. Independent models agree closely in the optical (V band), but diverge at longer wavelengths. This effect is particularly pronounced in recent models with substantial contributions from TP-AGB stars. We provide revised color-mass-to-light ratio relations that yield self-consistent stellar masses when applied to real galaxies. The B - V color is a good indicator of the mass-to-light ratio. Some additional information is provided by V - I, but neither it nor J - Ks are particularly useful for constraining the mass-to-light ratio on their own. In the near-infrared, the mass-to-light ratio depends weakly on color, with typical values of 0.6 M⊙/L⊙ in the Ks band and 0.47 M⊙/L⊙ at 3.6 μm. © 2014. The American Astronomical Society. All rights reserved.
Schmaier A.H.,Case Western Reserve University |
Schmaier A.H.,University Hospitals Case Medical Center
Journal of Thrombosis and Haemostasis | Year: 2016
Summary: The contact activation system (CAS) and kallikrein/kinin system (KKS) are older recognized biochemical pathways that include several proteins that skirt the fringes of the blood coagulation, fibrinolytic, complement and renin-angiotensin fields. These proteins initially were proposed as part of the hemostatic pathways because their deficiencies are associated with prolonged clinical assays. However, the absence of bleeding states with deficiencies of factor XII (FXII), prekallikrein (PK) and high-molecular-weight kininogen indicates that the CAS and KKS do not contribute to hemostasis. Since the discovery of the Hageman factor 60 years ago much has been learned about the biochemistry, cell biology and animal physiology of these proteins. The CAS is a pathophysiologic surface defense mechanism against foreign proteins, organisms and artificial materials. The KKS is an inflammatory response mechanism. Targeting their activation through FXIIa or plasma kallikrein inhibition when blood interacts with the artificial surfaces of modern interventional medicine or in acute attacks of hereditary angioedema restores vascular homeostasis. FXII/FXIIa and products that arise with PK deficiency also offer novel ways to reduce arterial and venous thrombosis without an effect on hemostasis. In summary, there is revived interest in the CAS and KKS due to better understanding of their activities. The new appreciation of these systems will lead to several new therapies for a variety of medical disorders. © 2016 International Society on Thrombosis and Haemostasis.
Redline R.W.,Case Western Reserve University |
Redline R.W.,University Hospitals Case Medical Center
Seminars in Fetal and Neonatal Medicine | Year: 2012
Acute chorioamnionitis is the principal antecedent of premature birth and an important contributor to specific neonatal and other complications that may extend throughout subsequent life. A large number of studies have addressed surrogate markers of in-utero inflammation including cytokines, chemokines, pathogen-associated molecular patterns, and elicited host proteins. However, chorioamnionitis means inflammation occurring within the chorioamnion and the only practical direct measure available to assess this finding in most placentas is histopathology. The maternal and fetal inflammatory response to the presence of organisms within the placental membranes, so-called histologic chorioamnionitis, is the focus of this review. The issues addressed are the nature and origin of the eliciting antigen, mode of spread to the placenta, general characteristics of placental immunity, and a specific characterization of the spectrum of pathologic lesions observed in placentas with membrane infection. © 2011 Elsevier Ltd.
McGaugh S.S.,Case Western Reserve University |
Schombert J.M.,University of Oregon
Astrophysical Journal | Year: 2015
We estimate the stellar masses of disk galaxies with two independent methods: a photometrically self-consistent color?mass-to-light ratio relation (CMLR) from population synthesis models, and the baryonic Tully?Fisher relation (BTFR) calibrated by gas-rich galaxies. These two methods give consistent results. The CMLR correctly converts distinct Tully?Fisher relations in different bands into the same BTFR. The BTFR is consistent with Mb ∝ Vf 4 over nearly six decades in mass, with no hint of a change in slope over that range. The intrinsic scatter in the BTFR is negligible, implying that the IMF of disk galaxies is effectively universal. The gas-rich BTFR suggests an absolute calibration of the stellar mass scale that yields nearly constant mass-to-light ratios in the near-infrared (NIR): 0.57 M⊙/ L⊙ in Ks and 0.45 M⊙/ L⊙ at 3.6 μm. There is only modest intrinsic scatter (∼0.12 dex) about these typical values. There is no discernible variation with color or other properties: the NIR luminosity is a good tracer of stellar mass. © 2015. The American Astronomical Society. All rights reserved.
Kubit B.,University of California at Davis |
Jack A.I.,Case Western Reserve University
Frontiers in Human Neuroscience | Year: 2013
The right temporo-parietal junction (rTPJ) has been associated with two apparently disparate functional roles: in attention and in social cognition. According to one account, the rTPJ initiates a "circuit-breaking" signal that interrupts ongoing attentional processes, effectively reorienting attention. It is argued this primary function of the rTPJ has been extended beyond attention, through a process of evolutionarily cooption, to play a role in social cognition. We propose an alternative account, according to which the capacity for social cognition depends on a network which is both distinct from and in tension with brain areas involved in focused attention and target detection: the default mode network. Theory characterizing the rTPJ based on the area's purported role in reorienting may be falsely guided by the co-occurrence of two distinct effects in contiguous regions: activation of the supramarginal gyrus (SMG), associated with its functional role in target detection; and the transient release, during spatial reorienting, of suppression of the angular gyrus (AG) associated with focused attention. Findings based on meta-analysis and resting functional connectivity are presented which support this alternative account. We find distinct regions, possessing anti-correlated patterns of resting connectivity, associated with social reasoning (AG) and target detection (SMG) at the rTPJ. The locus for reorienting was spatially intermediate between the AG and SMG and showed a pattern of connectivity with similarities to social reasoning and target detection seeds. These findings highlight a general methodological concern for brain imaging. Given evidence that certain tasks not only activate some areas but also suppress activity in other areas, it is suggested that researchers need to distinguish two distinct putative mechanisms, either of which may produce an increase in activity in a brain area: functional engagement in the task versus release of suppression. © 2013 Kubit and Jack.
Spiess P.E.,H. Lee Moffitt Cancer Center and Research Institute |
Jones J.S.,Case Western Reserve University
European Urology | Year: 2012
Context: The purpose of this paper is to review current salvage cryoablation (SCA) outcomes in patients with locally recurrent prostate cancer (PCa) following primary radiation therapy. Objective: The objectives of this review are (1) to analyze the eligibility criteria for careful patient selection for these salvage modalities and (2) to evaluate the oncologic results and reported complication rates for these respective modalities. Evidence acquisition: A Medline/PubMed literature search was performed of peer-reviewed scientific articles published from 1991 to 2012 regarding salvage therapy for radiorecurrent PCa. The following search terms and various permutations were used: radiorecurrent prostate cancer, local salvage treatment, salvage radical prostatectomy, salvage cryoablation, salvage brachytherapy, and salvage high-intensity focused ultrasound. Only articles written in English were included. Evidence synthesis: SCA is a feasible and efficacious treatment modality, especially using third-generation technology, whereby the biochemical disease-free survival is estimated to be between 50% and 70% at 5-yr follow-up in properly selected patients. Severe complications such as rectourethral fistulas are significantly less common over the last decade than was reported in the past. Because there are no prospective, randomized studies and the definitions of PSA failure vary among many studies, comparisons between these different salvage modalities are limited in terms of cancer-specific outcomes. Nevertheless, in recent years, tertiary care referral centers for prostate cryotherapy have reported their treatment outcomes using rigorous treatment end points and morbidity grading systems, dramatically improving the quality of reported clinical data. Consequently, favorable predictors of treatment outcomes have been identified. Conclusions: The inability to effectively salvage patients with locally recurrent PCa following radiation therapy has in large part resulted from the lack of sufficiently sensitive and specific diagnostic tools to detect local recurrences at an early, potentially curable stage. Consequently, a more stringent definition of biochemical failure, improved imaging techniques, and accurate PCa mapping imaging technology is greatly needed within our diagnostic armamentarium. Additional research and randomized clinical trials are required to determine which salvage modality is superior in terms of oncologic efficacy and reduced morbidity. © 2012 European Association of Urology.
Cooper G.S.,University Hospitals Case Medical Center |
Cooper G.S.,Case Western Reserve University |
Kou T.D.,Case Western Reserve University |
Rex D.K.,Indiana University
JAMA Internal Medicine | Year: 2013
Importance: Deep sedation for endoscopic procedures has become an increasingly used option but, because of impairment in patient response, this technique also has the potential for a greater likelihood of adverse events. The incidence of these complications has not been well studied at a population level. Design: Population-based study. Setting and Participants: Using a 5% random sample of cancer-free Medicare beneficiaries who resided in one of the regions served by a SEER (Surveillance, Epidemiology, and End Results) registry, we identified all procedural claims for outpatient colonoscopy without polypectomy from January 1, 2000, through November 30, 2009. Intervention: Colonoscopy without polypectomy, with or without the use of deep sedation (identified by a concurrent claim for anesthesia services). Main Outcome Measures: The occurrence of hospitalizations for splenic rupture or trauma, colonic perforation, and aspiration pneumonia within 30 days of the colonoscopy. Results: We identified a total of 165 527 procedures in 100 359 patients, including 35 128 procedures with anesthesia services (21.2%). Selected postprocedure complicationswere documented after 284 procedures (0.17%) and included aspiration (n=173), perforation (n=101), and splenic injury (n=12). (Some patients had >1 complication.) Overall complications were more common in cases with anesthesia assistance (0.22% [95% CI, 0.18%-0.27%]) than in others (0.16% [0.14%-0.18%]) (P<.001), as was aspiration (0.14% [0.11%-0.18%] vs 0.10% [0.08%-0.12%], respectively; P=.02). Frequencies of perforation and splenic injury were statistically similar. Other predictors of complications included age greater than 70 years, increasing comorbidity, and performance of the procedure in a hospital setting. In multivariate analysis, use of anesthesia services was associated with an increased complication risk (odds ratio, 1.46 [95% CI, 1.09-1.94]). Conclusions and Relevance: Although the absolute risk of complications is low, the use of anesthesia services for colonoscopy is associated with a somewhat higher frequency of complications, specifically, aspiration pneumonia. The differences may result in part from uncontrolled confounding, but they may also reflect the impairment of normal patient responses with the use of deep sedation. © 2013 American Medical Association. All rights reserved.
Agency: GTR | Branch: ESRC | Program: | Phase: Research Grant | Award Amount: 24.84K | Year: 2012
The World Health Organization (WHO) model of age-friendly cities emphasizes the theme of supportive urban environments for older citizens. These defined as encouraging active ageing by optimizing opportunities for health, participation and security in order to enhance quality of life as people age (WHO, Global Age-friendly Cities, 2007). The goal of establishing age-friendly cities should be seen in the context of pressures arising from population ageing and urbanisation. By 2030, two-thirds of the worlds population will reside in cities, with - for urban areas in high-income countries - at least one-quarter of their populations aged 60 and over. This development raises important issues for older people: To what extent will cities develop as age-friendly communities? Will so-called global cities integrate or segregate their ageing populations? What kind of variations might occur across different types of urban areas? How are different groups of older people affected by urban change? The age-friendly city perspective has been influential in raising awareness about the impact of population ageing. Against this, the value of this approach has yet to be assessed in the context of modern cities influenced by pressures associated with global social and economic change. The IPNS has four main objectives: first, to build a collaborative research-based network focused on understanding population ageing in the context of urban environments; second to develop a research proposal for a cross-national study examining different approaches to building age-friendly cities; third to provide a systematic review of data sets and other resources of relevance to developing a research proposal on age-friendly cities; fourth, to develop training for early career resarchers working on ageing and urban issues. The network represents the first attempt to facilitate comparative research on the issue of age-friendly cities. It builds upon two meetings held at the Universities of Keele and Manchester in 2011 that sought to establish the basis for cross-national work around the age-friendly theme. The IPNS represents brings together world class research groups in Europe, Hong Kong and North America, professionals concerned with urban design and architecture, and leading NGOs working in the field of ageing. A range of activities have been identified over the two-year funding period: (1) Preparation of research proposals for a cross-national study of approaches to developing age-friendly urban environments. (2) Two workshops to specify theoretical and methodological issues raised by demographic change and urbanisation. (3) A Summer School exploring links between data resources of potential relevance to the ageing and urbanisation theme and which might underpin research proposals. (4) Master classes for network members from key researchers in the field of urbanisation and ageing. (5) A workshop with a user-based theme developing older peoples participation in research on building age-friendly communities. (6) Themed workshops (face-to-face and via video-link) to identify research and policy gaps drawing on inter-disciplinary perspectives The IPNS will be sustained in a variety of ways at the end of the funding period. A collaborative research proposal as well as one to maintain the network will be major outputs from the project and work with potential funding bodies will continue after 2014. Dissemination activities will continue through professional networks, symposia at major international conferences, and involvement in expert meetings. The project will continue to be advertised through the maintenance of a website maintained by the host UK HEI. The project will continue to make a contribution to policy development around the theme of age-friendly cities, notably with the main NGOs working in the field.
Cleveland Clinic and Case Western Reserve University | Date: 2016-04-29
The present disclosure relates generally to using detected bladder events for the diagnosis of urinary incontinence or the treatment of lower urinary tract dysfunction. A system includes a sensing device comprising a pressure sensor to directly detect a pressure within a bladder. The sensing device is adapted to be located within the bladder. The system also includes a signal processing device to: receive a signal indicating the detected pressure within the bladder; detect a bladder event based the detected pressure within the signal; and characterize the bladder event as a bladder contraction event or a non-contraction event. The characterization of the bladder event can be used in the diagnosis of urinary incontinence or the treatment of lower urinary tract dysfunction.
Case Western Reserve University | Date: 2012-12-18
Polymer nanocomposites exhibit a reversible change in stiffness and strength in response to a stimulus. The polymer nanocomposites include a matrix polymer with a comparably low modulus and strength and nanoparticles that have a comparably high modulus and strength. The particle-particle interactions are switched by the stimulus, to change the overall materials mechanical properties. In a preferred embodiment, a chemical regulator Is used to facilitate changes of the mechanical properties. Methods for inducing modulus changes in polymer nanocomposites are also disclosed.
Lubrizol Corporation and Case Western Reserve University | Date: 2014-11-08
Traditionally, the rheological properties, including, for example, the viscosities, of two or more polymers that are to be co-extruded must be well matched in order to obtain acceptable multilayer structures. This limitation severely narrows the processing window for such co-extrusions as well as the combinations of polymers that can be used in such co-extrusions. The technology disclosed herein removes these limitations and allows for the co-extrusion of a wider variety of combinations of polymers, even when the rheological properties of the polymers to be used are significantly different, while still providing acceptable multilayer structures. Stated another way, the technology disclosed herein improves the multilayer structures that can be obtained when processing two or more polymer materials with significantly different rheological properties via layer-multiplying co-extrusion.
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: KBBE.2011.2.2-03 | Award Amount: 11.56M | Year: 2012
Nutrition during early development has an important impact on later health, particularly through greater obesity risk, as demonstrated by FP6 EARNEST. EarlyNutrition explores the current key hypotheses on likely causes and pathways to prevention of early life origins of obesity (specifically adiposity) and associated disorders. We bring extraordinary expertise and study populations of 470,000 individuals to investigate: The fuel mediated in utero hypothesis The accelerated postnatal weight gain hypothesis The mismatch hypothesis. Scientific and technical expertise in placental biology, epigenetics and metabolomics will provide understanding at the cellular and molecular level, and refined strategies for intervention in pregnancy and early post natal life to prevent obesity. Using existing cohort studies, ongoing and novel intervention studies and a basic science programme, we will provide the scientific foundations for evidence based recommendations for optimal EarlyNutrition that incorporate long-term health outcomes, focusing on 4 Target Groups: women before pregnancy; pregnant women; infants (incl. breastfeeding); young children. Evidence is produced from animal and placental studies (Theme 1; T1), prospective cohort studies (T2), and randomised controlled trials in pregnant women and infants (T3). T4 covers scientific strategic integration, recommendation development and dissemination, including systematic reviews and behaviour change approaches. A strong multi-disciplinary team of international leaders in the field including collaborators from USA and Australia achieves balance and complementarity. The projects impact comprises definitive evidence on early nutrition effects on health, enhanced EU and global policies, major economic benefits through obesity prevention and value-added nutritional products, and practical recommendations on optimal nutrition in Target Groups. Wide dissemination will be achieved through active engagement with stakeholders.
News Article | February 17, 2017
The distribution of normal matter precisely determines gravitational acceleration in all common types of galaxies, a team led by Case Western Reserve University researchers reports. The team has shown this radial acceleration relation exists in nearby high-mass elliptical and low-mass spheroidal galaxies, building on last year's discovery of this relation in spiral and irregular galaxies. This provides further support that the relation is tantamount to a new natural law, the researchers say. "This demonstrates that we truly have a universal law for galactic systems," said Federico Lelli, formerly an astronomy postdoctoral fellow at Case Western Reserve University and currently a fellow at the European Southern Observatory. "This is similar to the Kepler law for planetary systems, which does not care about the specific properties of the planet. Whether the planet is rocky like Earth or gaseous like Jupiter, the law applies," said Lelli, who led this investigation. In this case, the observed acceleration tightly correlates with the gravitational acceleration from the visible mass, no matter the type of galaxy. In other words, if astronomers measure the distribution of normal matter, they know the rotation curve, and vice versa. "But it is still unclear what this relation means and what is its fundamental origin," Lelli said. The study is published online in Astrophysical Journal today. Co-authors are Stacy McGaugh, chair of the Department of Astronomy at Case Western Reserve, James Schombert, astronomy professor at the University of Oregon, and Marcel Pawlowski, former astronomy postdoctoral researcher at Case Western Reserve and current Hubble fellow at the University of California, Irvine. The researchers found that in 153 spiral and irregular galaxies, 25 ellipticals and lenticulars, and 62 dwarf spheroidals, the observed acceleration tightly correlates with the gravitational acceleration expected from visible mass. Observed deviations from this correlation are not related to any specific galaxy property but completely random and consistent with measurement errors, the team found. The tightness of this relation is difficult to understand in terms of dark matter as it's currently understood, the researchers said. It also challenges the current understanding of galaxy formation and evolution, in which many random processes such as galaxy mergers and interactions, inflows and outflows of gas, star formation and supernovas, occur at the same time. "Regularity must somehow emerge from this chaos," Lelli said. To make their discovery, researchers combined different tracers of the centripetal acceleration found in different types of galaxies, from which they made 1-to-1 comparisons. The kinematical tracers were cold gas in spiral and irregular galaxies, stars or hot gas in ellipticals and lenticulars, and individual giant stars in dwarf spheroidals. The investigation included so-called ultra-faint dwarf spheroidal galaxies, but due to their lack of light -- which makes them hard to study -- the researchers can't confidently offer a clear interpretation of the radial acceleration relation in these. Nevertheless, the growing proof of the relation, or natural law, requires new thinking about dark matter and gravity, the researchers said. "Within the standard dark-matter paradigm, this law implies that the visible matter and the dark matter must be tightly coupled in galaxies at a local level and independently on global properties. They must know about each other," Lelli said. "Within alternative models like modified gravity, this law represents a key empirical constraint and may guide theoretical physicists to build some appropriate mathematical extension of Einstein's general relativity." The team's research so far has focused on galaxies in the nearby universe. Lelli and his colleagues plan to test the relation in more distant galaxies, just a few billion years after the Big Bang. They are hoping to learn whether the same relation holds during the lifetime of the universe. Reference: "One Law to Rule Them All: The Radial Acceleration Relation of Galaxies," Federico Lelli, Stacy S. McGaugh, James M. Schombert & Marcel S. Pawlowski, 2017 Feb. 20 [http://iopscience.iop.org/article/10.3847/1538-4357/836/2/152, preprint: https://arxiv.org/abs/1610.08981]. Please follow SpaceRef on Twitter and Like us on Facebook.
News Article | February 15, 2017
A new investigational delivery method for localized vaginal estrogen therapy that utilizes an applicator free softgel to alleviate moderate-to-severe vaginal pain during intercourse (dyspareunia), a symptom of vulvar and vaginal atrophy (VVA), received high rates of patient satisfaction among post-menopausal women, according to post-trial survey results published in the journal Menopause. "These survey results show that something as simple as a change to a more elegant delivery system that is easier to use and not messy might empower more post-menopausal women to seek prescription treatment for VVA, and perhaps help them stay with the application guidelines for longer," said study first author Sheryl Kingsberg, PhD, Division Chief, OB/GYN Behavioral Medicine, UH Cleveland Medical Center; Professor of Obstetrics and Gynecology and Psychiatry, Case Western Reserve University School of Medicine; and first author of the survey analysis. "We still have to find better ways to educate the millions of women suffering with VVA about the symptoms, however, so that more of them know it is common, decide to discuss treatment with their healthcare professional, and seek symptom relief with appropriate treatment." The new results were part of a multi-center randomized, placebo-controlled phase 3 clinical trial for TX004HR, an investigational bio-identical 17β-estradiol applicator free vaginal softgel capsule. Previous publications have shown TX004HR to be safe and effective at alleviating symptoms of VVA. The survey, which included 731 respondents with a 96 percent response rate, sought to quantify participants' satisfaction with the application method and overall treatment delivery system. The majority of women taking either TX004HR or placebo (85.4 - 92.1 percent) found the product easy to use. VVA is a chronic condition associated with genitourinary syndrome of menopause (GSM). VVA affects 50 to 70 percent of post-menopausal women, and is characterized by pain with sexual activity, dryness, and discomfort. Current on-the-market treatments for VVA include both over-the-counter creams and moisturizers as well as several safe and effective prescription treatments in cream, tablet, ring or oral form. Previous survey research completed by Dr. Kingsberg and others has shown that while 32 million women may be experiencing symptomatic VVA and suffering from related impacts on sexual function, interpersonal relationships, self-esteem and overall quality of life, only 7 percent are currently using a prescription therapy to alleviate symptoms. Though they may suffer from physical and emotional pain as a result of VVA, women may not feel comfortable discussing these symptoms with a healthcare professional, may not recognize the symptoms as treatable, may not fully understand the treatment options available, or if they did receive treatment, found the current prescription treatment options inconvenient, messy, or uncomfortable to use. Financial disclosure: Dr. Kingsberg has served as a consultant for TherapeuticsMD, the manufacturer of TX004HR, as well as Acerus Pharmaceuticals, AMAG Pharmaceuticals, Bayer Healthcare, Emotional Brain, Materna, Novo Nordisk, Nuelle, Palatin Technologies, Pfizer, Sermonix Pharmaceuticals, Shionogi Inc. and Valeant Pharmaceuticals. Founded in 1866, University Hospitals serves the needs of over 1 million patients per year through an integrated network of 18 hospitals, more than 40 outpatient health centers and 200 physician offices in 15 counties throughout northern Ohio. The system's flagship academic medical center, University Hospitals Cleveland Medical Center, located on a 35-acre campus in Cleveland's University Circle, is affiliated with Case Western Reserve University School of Medicine. The main campus also includes University Hospitals Rainbow Babies & Children's Hospital, ranked among the top children's hospitals in the nation; University Hospitals MacDonald Women's Hospital, Ohio's only hospital for women; and University Hospitals Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center. UH is home to some of the most prestigious clinical and research programs in the nation, including cancer, pediatrics, women's health, orthopedics, radiology, neuroscience, cardiology and cardiovascular surgery, digestive health, dermatology, transplantation and urology. UH Cleveland Medical Center is perennially among the highest performers in national ranking surveys, including "America's Best Hospitals" from U.S. News & World Report. UH is also home to Harrington Discovery Institute at University Hospitals - part of The Harrington Project for Discovery & Development. UH is the second largest employer in northern Ohio with 26,000 employees. For more information, go to UHhospitals.org.
News Article | February 16, 2017
The team has shown this radial acceleration relation exists in nearby high-mass elliptical and low-mass spheroidal galaxies, building on last year's discovery of this relation in spiral and irregular galaxies. This provides further support that the relation is tantamount to a new natural law, the researchers say. "This demonstrates that we truly have a universal law for galactic systems," said Federico Lelli, formerly an astronomy postdoctoral fellow at Case Western Reserve University and currently a fellow at the European Southern Observatory. "This is similar to the Kepler law for planetary systems, which does not care about the specific properties of the planet. Whether the planet is rocky like Earth or gaseous like Jupiter, the law applies," said Lelli, who led this investigation. In this case, the observed acceleration tightly correlates with the gravitational acceleration from the visible mass, no matter the type of galaxy. In other words, if astronomers measure the distribution of normal matter, they know the rotation curve, and vice versa. "But it is still unclear what this relation means and what is its fundamental origin," Lelli said. The study is published online in Astrophysical Journal today. Co-authors are Stacy McGaugh, chair of the Department of Astronomy at Case Western Reserve, James Schombert, astronomy professor at the University of Oregon, and Marcel Pawlowski, former astronomy postdoctoral researcher at Case Western Reserve and current Hubble fellow at the University of California, Irvine. The researchers found that in 153 spiral and irregular galaxies, 25 ellipticals and lenticulars, and 62 dwarf spheroidals, the observed acceleration tightly correlates with the gravitational acceleration expected from visible mass. Observed deviations from this correlation are not related to any specific galaxy property but completely random and consistent with measurement errors, the team found. The tightness of this relation is difficult to understand in terms of dark matter as it's currently understood, the researchers said. It also challenges the current understanding of galaxy formation and evolution, in which many random processes such as galaxy mergers and interactions, inflows and outflows of gas, star formation and supernovas, occur at the same time. "Regularity must somehow emerge from this chaos," Lelli said. To make their discovery, researchers combined different tracers of the centripetal acceleration found in different types of galaxies, from which they made 1-to-1 comparisons. The kinematical tracers were cold gas in spiral and irregular galaxies, stars or hot gas in ellipticals and lenticulars, and individual giant stars in dwarf spheroidals. The investigation included so-called ultra-faint dwarf spheroidal galaxies, but due to their lack of light—which makes them hard to study—the researchers can't confidently offer a clear interpretation of the radial acceleration relation in these. Nevertheless, the growing proof of the relation, or natural law, requires new thinking about dark matter and gravity, the researchers said. "Within the standard dark-matter paradigm, this law implies that the visible matter and the dark matter must be tightly coupled in galaxies at a local level and independently on global properties. They must know about each other," Lelli said. "Within alternative models like modified gravity, this law represents a key empirical constraint and may guide theoretical physicists to build some appropriate mathematical extension of Einstein's General Relativity." The team's research so far has focused on galaxies in the nearby universe. Lelli and his colleagues plan to test the relation in more distant galaxies, just a few billion years after the big bang. They are hoping to learn whether the same relation holds during the lifetime of the Universe. Explore further: Acceleration relation found among spiral and irregular galaxies challenges current understanding of dark matter More information: "One Law to Rule Them All: The Radial Acceleration Relation of Galaxies," Federico Lelli, Stacy S. McGaugh, James M. Schombert & Marcel S. Pawlowski, Astrophysical Journal, 2017 Feb. 20 iopscience.iop.org/article/10.3847/1538-4357/836/2/152 , Arxiv: arxiv.org/abs/1610.08981
News Article | February 15, 2017
Dr. Andrew Lian-Jie Li is a board certified dermatologist by the American Board of Dermatology and fellowship trained Mohs and cosmetic surgeon. After extensive dermatology research training at the National Cancer Institute of the National Institutes of Health, Dr. Li completed his internship in internal medicine at the Emory University and dermatology training at the University of Pennsylvania in Philadelphia. Dr. Li pursued further training in Mohs Micrographic and cosmetic surgery at the University of Louisville. After his fellowship training, Dr. Li served as the director of the dermatology surgery, melanoma, squamous cell carcinoma, and basal cell carcinoma program at Case Western Reserve University. Dr. Li is a clinical associate and teaching Dermatology resident at the University of Pennsylvania. Dr. Andrew Li currently practices in Phillipsburg, NJ 08865, Hackettstown, NJ 07840, Washington, NJ 07882, and Easton, PA 18042. Warren Skin Care Center offers many services for treatments such as the following: Mohs Surgery for Skin Cancer Acne Warts Eczema Hair Loss/Alopecia Areata Sweating/Hyperhidrosis Psoriasis Rosacea Cold sores/Herpes Fat Transfer, Restylane and Botox for Wrinkles Microdermabrasion Chemical Peels Blepharoplasty Surgery Dr. Li also also offers many cosmetic services such as the ones listed below: Warren skin care center is a premier skin care facility dedicated to providing excellence in care for all your skin needs. It is their duty to ensure your highest satisfaction with their care and they will work diligently to make sure that is always the case. Dr. Li is conveniently located in Hunterdon County. For more information and locations you can visit Warren Skin Care Center’s full profile at http://www.njtopdocs.com/DrLiWarrenSkinCare About Us NJ Top Dentists is a comprehensive information resource of Top Doctors, Dentists and Hospitals. We are profiling over 900 Healthcare Providers and have made it convenient for you to find them. NJ Top Dentists allows patients to “meet” these providers online before making their appointment. For more information, please visit http://www.NJTopDocs.com. You can also follow us on Facebook – Twitter – YouTube
News Article | February 25, 2017
WASHINGTON (AP) — Both the transgender teen who sued to use a boys' bathroom and the Virginia school board that won't let him still want the Supreme Court to issue a definitive ruling in their ongoing dispute, even after the Trump administration retreated from an Obama-era policy on bathroom use. The big issue for both sides is whether the main federal law barring sex discrimination in education protects high school senior Gavin Grimm and other transgender students. Grimm was born a girl but identifies as a boy. The Virginia teen has been issued an amended birth certificate identifying him as a male, received hormone treatments and underwent chest reconstruction surgery. His lawyers said in court papers filed Thursday that prohibiting him from using the boys' restroom is discrimination "on the basis of sex." The Gloucester County school board said the law known as Title IX was "intended to erase discrimination against women in classrooms, faculties and athletics." It does not include gender identity, the board said. But the withdrawal on Wednesday of joint Education and Justice Department guidance to school systems gives the high court an easy out if it is seeking to avoid a major ruling on transgender rights. The appeals court that sided with Grimm relied on the Obama administration's reading of the anti-discrimination law and an Education Department regulation to hold that Grimm should be allowed to use a restroom that conforms to his chosen gender. The Trump administration's decision to abandon Obama's restroom guidance set off tensions within the Cabinet. Education Secretary Betsy DeVos expressed reluctance to rescind protections for transgender students and clashed with Attorney General Jeff Sessions, who supported it, according to a person familiar with the conversations but not authorized to speak publicly about internal discussions and so requested anonymity. After Wednesday's the announcement, DeVos released her own statement, stressing that the administration had a "moral obligation" to protect LGBT students, which she said was "not only a key priority for the department, but for every school in America." Speaking Thursday to the Conservative Political Action Conference, however, she framed it as a legal matter, "a very huge example of the Obama administration's overreach." The court on Thursday asked both sides to say what they think it should do following the administration's action. Now that the basis for the appellate ruling has disappeared, the justices could return the case to the 4th U.S. Circuit Court of Appeals in Richmond, Virginia, and direct it to decide for itself what the law and regulation require. No appeals court has yet to do so and the high court typically won't take up a major legal issue until after several courts around the country have weighed in. Similar cases are making their way through other courts of appeal. The temptation to wait may be even stronger because the court has been one justice short for more than a year, since Justice Antonin Scalia's death. President Donald Trump has nominated Judge Neil Gorsuch, but there is no chance Gorsuch could join the court in time for the March 28 argument in the Virginia case. "If I were a justice on the court, my inclination would be to say that I'd much rather be reviewing a lower court opinion that looked at the Title IX question," said Case Western Reserve University law professor Jonathan Adler. Adler signed onto a legal brief in support of the school board that dealt with when courts should defer to federal agencies. That issue is no longer part of the case. There are some reasons why the justices might want to resolve the issue before the court breaks for the summer. Joshua Block, the American Civil Liberties Union lawyer who is representing Grimm, said the administration's actions have created confusion and "only underscore the need for the Supreme Court to bring some clarity here." Some strategic considerations may be at work as well. The outcome is likely to divide the liberal and conservative justices. The four liberal justices would need Justice Anthony Kennedy's vote to form a majority. It's not clear he's with them. Back in August, five justices voted to block the 4th circuit ruling ordering the school district to allow Grimm to use the boys' restroom, at least until the high court finished its review of the case. At the time, Justice Stephen Breyer said he was providing the necessary fifth, majority-making vote as a courtesy to Kennedy and the other more conservative justices. It is impossible to know whether the court was spurred to act in August because of its concern about when courts should rely on agencies' interpretations of laws and regulations, or the larger issue of Title IX protections. Fourteen states already prohibit discrimination against transgender students, according to the Human Rights Campaign.
News Article | February 15, 2017
New U.S. Supreme Court nominee Judge Neil Gorsuch, if confirmed, would fill the vacancy left a year ago by the death of Justice Antonin Scalia, with whom he shares a similar conservative legal philosophy. His past decisions in cases involving health and energy issues indicate he believes it is up to the courts, not government agencies, to interpret laws cast with ambiguous language. This week Pres. Donald Trump selected Gorsuch, who has been on the U.S. Court of Appeals for the 10th Circuit since 2006, from a list that appealed to conservative and evangelical voters. Gorsuch had been considered a top contender early on because of his opinion in a case about the obligations of employers to provide insurance benefits that include contraceptives. When Gorsuch’s circuit court heard Hobby Lobby Stores v. Sebelius, he sided with the Green family, owners of the Hobby Lobby Stores, who wanted no part in providing health insurance to employees for drugs or devices that destroy fertilized eggs. Hobby Lobby argued that the Affordable Care Act’s mandate to provide such insurance violated their religious freedom. Gorsuch said the decision rested on which law should be dominant—the ACA or the another law, the Religious Freedom Restoration Act. He ruled Congress had made it clear the RFRA should override other legal mandates, if and when they encroach on religious liberty. The decision was upheld by the U.S. Supreme Court in 2014. Gorsuch also authored a 2006 book, The Future of Assisted Suicide and Euthanasia, in which he built a legal and moral argument that intentional killing is always wrong because human life is intrinsically valuable. He does not argue against allowing a patient to refuse unwanted medical treatment and life-sustaining care, however. Evangelical leaders were quick to praise his nomination. In a letter organized by Russell Moore, president of the Ethics & Religious Liberty Commission of the Southern Baptist Convention, signers stated “by all indication” Gorsuch would interpret the Constitution in accordance with America’s tradition of limited government and uphold the principles of protecting the unborn, strengthening religious liberty and the biblical definition of marriage and family. Gorsuch has not directly ruled on an abortion case. Still, as a federal appellate judge, Gorsuch has issued hundreds of opinions that offer some idea of where he might stand on health and science issues. In Guitierrez-Brizuela v. Lynch, a 2016 immigration case, Gorsuch waved a red flag against the “Chevron deference”—a doctrine under which courts are supposed to defer to federal agencies on interpretations of rules that developed from a 1984 decision, Chevron v. National Resources Defense Council. “But where in all this does a court interpret the law and say what it is? When does a court independently decide what the statute means and whether it has or has not vested a legal right in a person? Where Chevron applies, that job seems to have gone extinct,” he wrote. Ann Carlson, a professor of environmental law at the University of California, Los Angeles, says a repudiation of Chevron deference “would mark a sea change in administrative and environmental law,” where the U.S. Environmental Protection Agency and other implementing agencies often must interpret ambiguous statutory provisions, she wrote on Legal Planet, a U.C.L.A. blog. She noted legal challenges to the EPA’s Clean Power Plan are centered on such ambiguities. “The big fear many observers have if Chevron is overturned is that it would make agency rule-making even more difficult, more uncertain and more vulnerable to legal challenge. That would be bad news for environmental protection,” she wrote. His rulings do not appear to be anti-environmental regulation, however. On renewable energy, Gorsuch has supported Colorado’s law requiring that at least 20 percent of the electricity sold by producers comes from renewable sources. The Energy and Environment Legal Institute (EELI) challenged the statute, contending that out-of-state, nonrenewable energy companies that sell on the Colorado power grid could lose business. In the 2016 case, Energy and Environmental Legal Institute v. Epel, he rejected the claim. “As far as we know, all fossil fuel producers in the area served by the grid will be hurt equally and all renewable energy producers in the area will be helped equally. If there’s any disproportionate adverse effect felt by out-of-state producers or any disproportionate advantage enjoyed by in-state producers, it hasn’t been explained to this court,” he wrote. In 2016 Gorsuch issued an opinion that offered at least a partial shield to medical device manufacturers that had been sued over off-label uses of the devices. In Patricia Caplinger v. Medtronic he rejected the plaintiff’s claim to hold the Minnesota firm liable, pointing to federal law that bans states from imposing additional requirements on a device’s safety or effectiveness. “Allowing more regulation of medical devices could yield benefits for patient safety. But it could also mean forcing manufacturers to abide not one but 51 sets of requirements, a prospect that could deter or delay access to innovative devices and wind up hurting more patients than it helps,” he wrote. Judge Carlos Lucero, in a partial dissent, argued against such immunity: “The notion that a device manufacturer is immune from liability for harm caused by its device when the manufacturer has pushed the device for a use that the [U.S. Food and Drug Administration] never approved is neither logical nor consistent with the Supreme Court’s prior rulings about the scope of preemption of claims arising from harm caused by medical devices.” Gorsuch considers himself a “textualist” and “originalist” who turns to the plain text of legislation for legal intent and reads the U.S. Constitution as it was construed by the Founding Fathers. He considers Scalia a role model. Last year he aligned himself with Scalia's judicial philosophy in a speech at Case Western Reserve University School of law."The great project of Justice Scalia's career was to remind us of the differences between judges and legislators,” he said. “Legislators may appeal to their own moral convictions and to claims about social utility to reshape the law as they think…but judges should instead strive (if humanly and so imperfectly) to apply the law as it is, focusing backward, not forward, and looking to text, structure and history to decide what a reasonable reader at the time of the events in question would have understood the law to be.” A study by Mercer University law professor Jeremy Kidd found Gorsuch to be among the most Scalia-like of the early Trump contenders for the Supreme Court. The study found him to have a 62.2 to 79.4 percent likelihood of being the most Scalia-like of potential nominees. Gorsuch was born in Denver but spent much of his childhood in Washington State. His mother, Anne Gorsuch, was appointed by Pres. Ronald Reagan as the first woman to head the EPA. She resigned under fire from Congress nearly two years later. During her time at the EPA she proposed deep budget cuts and favored voluntary compliance over strict regulation. Judge Gorsuch earned a bachelor’s degree at Columbia University and a law degree from Harvard University. He then joined a private law firm in Washington, D.C., and later worked at the Department of Justice. He was also a clerk for Supreme Court justices Byron White and Anthony Kennedy.
News Article | February 24, 2017
The adage that kids are growing up too fast these days has yet another locus of applicability. In a new, first-of-its-kind study, researchers from Case Western Reserve University School of Medicine have found a 700-percent surge in infections caused by bacteria from the Enterobacteriaceae family resistant to multiple kinds of antibiotics among children in the US. These antibiotic resistant infections are in turn linked to longer hospital stays and potentially greater risk of death. The research, published in the March issue of the Journal of the Pediatric Infectious Diseases Society, is the first known effort to comprehensively examine the problem of multi-drug resistant infections among patients under 18 admitted to US children's hospitals with Enterobacteriaceae infections. Earlier studies focused mainly on adults, while some looked at young people in more limited geographical areas, such as individual hospitals or cities, or used more limited surveillance data. "There is a clear and alarming upswing throughout this country of antibiotic resistant Enterobacteriaceae infections in kids and teens," said lead author Sharon B. Meropol, MD, PhD, a pediatrician and epidemiologist at Case Western Reserve University School of Medicine and Rainbow Babies and Children's Hospital in Cleveland. "This makes it harder to effectively treat our patients' infections. The problem is compounded because there are fewer antibiotics approved for young people than adults to begin with. Health care providers have to make sure we only prescribe antibiotics when they're really needed. It's also essential to stop using antibiotics in healthy agricultural animals." In the retrospective study, Meropol and co-authors Allison A. Haupt, MSPH, and Sara M. Debanne, PhD, both from Case Western Reserve University School of Medicine, analyzed medical data from nearly 94,000 patients under the age of 18 years diagnosed with Enterobacteriaceae-associated infections at 48 children's hospitals throughout the US. The average age was 4.1 years. Enterobacteriaceae are a family of bacteria; some types are harmless, but they also include such pathogens as Salmonella and Escherichia coli; Enterobacteriaceae are responsible for a rising proportion of serious bacterial infections in children. The researchers found that the share of these infections resistant to multiple antibiotics rose from 0.2 percent in 2007 to 1.5 percent in 2015, a seven-fold-plus increase in a short, eight-year span. Children with other health problems were more likely to have the infections while there were no overall differences based on sex or insurance coverage. The yearly number of discharges with Enterobacteriaceae-associated infections remained relatively stable over the course of the study years. In a key finding, more than 75 percent of the antibiotic-resistant infections were already present when the young people were admitted to the hospital, upending previous findings that the infections were mostly picked up in the hospital. "This suggests that the resistant bacteria are now more common in many communities," said Meropol. For reasons that are unclear, older children and those living in the Western US were more likely to have the infections. The investigators also found that young people with antibiotic-resistant infections stayed in the hospital 20 percent longer than those whose infections could be addressed by antibiotics. Additionally, there was a greater--but not statistically significant--risk of death among pediatric patients infected with the resistant bacterial strains. Previous studies have shown that the problem is even worse elsewhere in the world, with an 11.4 percent global rate of antibiotic-resistant Enterobacteriaceae infections among young people, including 27 percent in Asia and the Pacific, 8.8 percent in Latin America, and 2.5 percent in Europe. "Escalating antibiotic resistance limits our treatment options, worsens clinical results, and is a growing global public health crisis," said Meropol. "What's more, the development of new antibacterial drugs, especially ones appropriate for children, remains essentially stagnant. We need to stop over-using antibiotics in animals and humans and develop new ones if we want to stop a bad problem from getting worse." This work was supported by the National Institute for Allergy and Infectious Diseases at the National Institutes of Health [K23AI097284-01A1].
News Article | February 23, 2017
Infections caused by a type of bacteria resistant to multiple antibiotics are occurring more frequently in U.S. children and are associated with longer hospital stays and a trend towards greater risk of death, according to a new study published in the Journal of the Pediatric Infectious Diseases Society. Previously acquired mostly while children were already in the hospital, the new findings also suggest the infections--caused by bacteria from the Enterobacteriaceae family that are resistant to multiple drugs--may be spreading more often in the community. "Antibiotic resistance increasingly threatens our ability to treat our children's infections," said study author Sharon B. Meropol, MD, PhD, of University Hospitals Rainbow Babies and Children's Hospital in Cleveland and Case Western Reserve University School of Medicine. "Efforts to control this trend are urgently needed from all of us, such as using antibiotics only when necessary, and eliminating agricultural use of antibiotics in healthy animals." In the retrospective study, researchers analyzed data from 48 children's hospitals throughout the U.S., focusing on approximately 94,000 patients under the age of 18 who were diagnosed with Enterobacteriaceae-associated infections between 2007 and 2015. The proportion of these infections caused by bacteria that were resistant to multiple antibiotics increased from 0.2 percent in 2007 to 1.5 percent in 2015, a more than 700 percent increase in prevalence over the eight-year period. Bacterial infections resistant to multiple drugs are especially concerning in children, for whom there are a limited number of stronger antibiotics currently approved for use compared to adults, putting kids at higher risk for worse outcomes. In the study, children with Enterobacteriaceae infections resistant to multiple antibiotics had hospitals stays that were 20 percent longer than patients with infections that were susceptible to antibiotics, the researchers found. The results also suggest a greater mortality risk among pediatric patients infected with the resistant strains, although the increased odds for death were not statistically significant. Most of the resistant infections were present when the children were admitted to the hospital, suggesting the bacteria may be increasingly spreading in the community. Older kids, children with other health conditions, and those living in the Western U.S. were more likely to have the infections, the study found. The results build on previous research reporting rising rates of these infections in adults and outbreaks in hospitalized children, especially in less-developed countries in Latin America and Asia, where antibiotics are available over the counter. Future research should focus on better ways to limit the transmission of resistant Enterobacteriaceae bacteria, including between hospitals and long-term care facilities and their communities, in addition to the development of new antibiotics that are safe and effective to use in children, Dr. Meropol said. "While the march of antibiotic resistance seems inexorable, informed and rigorous efforts to reverse this trend have been successful for other types of organisms, and are urgently needed within this context." * Infections caused by a type of bacteria resistant to multiple antibiotics are increasing in U.S. children and are associated with longer hospital stays and a trend towards greater risk of death. * Caused by members of the Enterobacteriaceae family of bacteria that are resistant to multiple antibiotics, these infections may be increasingly spreading in the community, not just in hospitals. * Efforts to control rising antibiotic resistance, including the appropriate use of antibiotics in humans and animals, and the development of new antibiotics, are urgently needed. Editor's Note: The study was funded by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. For an embargoed copy of the study, please contact Terri Christene Phillips, MSA (email@example.com, 703-299-9865). Published quarterly, the Journal of the Pediatric Infectious Diseases Society represents the spectrum of peer-reviewed, scientific and clinical information on perinatal, childhood, and adolescent infectious diseases. The journal is a publication of the Pediatric Infectious Diseases Society (PIDS), the world's largest professional organization of experts in the care and prevention of infectious diseases in children. PIDS membership encompasses leaders across the global scientific and public health spectrum, including clinical care, advocacy, academics, government, and the pharmaceutical industry. From fellowship training to continuing medical education, research, regulatory issues and guideline development, PIDS members are the core professionals advocating for the improved health of children with infectious diseases both nationally and around the world, participating in critical public health and medical professional advisory committees that determine the treatment and prevention of infectious diseases, immunization practices in children, and the education of pediatricians. For more information, visit http://www. .
News Article | February 17, 2017
The Community for Accredited Online Schools, a leading resource provider for higher education information, has ranked the best two- and four-year colleges with online programs in the state of Ohio for 2017. Among four-year schools a total of 41 made the list, with University of Akron, University of Toledo, University of Cincinnati, Ohio University and Ashland University coming in as the top five schools. The state’s top 18 two-year schools were also honored, with Sinclair College, Cincinnati State Technical and Community College, Belmont College, Edison State Community College and Columbus State Community College taking the top five spots. Schools were ranked based on over a dozen different data points. “Student enrollment in schools within the University System of Ohio has grown 8 percent over the past decade,” said Doug Jones, CEO and founder of AccreditedSchoolsOnline.org. “As more students pursue post-secondary degrees, the schools on our list are providing more flexible, high-quality learning opportunities outside the traditional classroom.” To be included on the Best Online Schools list, colleges must meet specific base requirements, including being institutionally accredited and public or private not-for-profit institutions. Each college is scored based on additional criteria that includes its employment and counseling resources, student/teacher ratios, graduation rates and financial aid availability. For more details on where each school falls in the rankings and the data and methodology used to determine the lists, visit: Ohio’s Best Online Four-Year Schools for 2017 include the following: Ashland University Baldwin Wallace University Bowling Green State University-Main Campus Case Western Reserve University Cedarville University Cleveland State University Defiance College Franciscan University of Steubenville Franklin University God’s Bible School and College Hiram College Kent State University at Kent Kent State University at Salem Kettering College Malone University Miami University-Oxford Mount Carmel College of Nursing Mount Saint Joseph University Mount Vernon Nazarene University Muskingum University Notre Dame College Ohio Christian University Ohio University-Main Campus Otterbein University Shawnee State University The University of Findlay Tiffin University Union Institute & University University of Akron Main Campus University of Cincinnati-Main Campus University of Dayton University of Mount Union University of Northwestern Ohio University of Rio Grande University of Toledo Urbana University Ursuline College Walsh University Wright State University-Lake Campus Wright State University-Main Campus Youngstown State University Ohio’s Best Online Two-Year Schools for 2017 include the following: Belmont College Bowling Green State University-Firelands Central Ohio Technical College Cincinnati State Technical and Community College Clark State Community College Columbus State Community College Cuyahoga Community College Edison State Community College Hocking College Lakeland Community College Lorain County Community College Marion Technical College North Central State College Northwest State Community College Rhodes State College Sinclair College Stark State College University of Akron Wayne College ### About Us: AccreditedSchoolsOnline.org was founded in 2011 to provide students and parents with quality data and information about pursuing an affordable, quality education that has been certified by an accrediting agency. Our community resource materials and tools span topics such as college accreditation, financial aid, opportunities available to veterans, people with disabilities, as well as online learning resources. We feature higher education institutions that have developed online learning programs that include highly trained faculty, new technology and resources, and online support services to help students achieve educational success.
News Article | February 16, 2017
The distribution of normal matter precisely determines gravitational acceleration in all common types of galaxies, a team led by Case Western Reserve University researchers reports. The team has shown this radial acceleration relation exists in nearby high-mass elliptical and low-mass spheroidal galaxies, building on last year's discovery of this relation in spiral and irregular galaxies. This provides further support that the relation is tantamount to a new natural law, the researchers say. "This demonstrates that we truly have a universal law for galactic systems," said Federico Lelli, formerly an astronomy postdoctoral fellow at Case Western Reserve University and currently a fellow at the European Southern Observatory. "This is similar to the Kepler law for planetary systems, which does not care about the specific properties of the planet. Whether the planet is rocky like Earth or gaseous like Jupiter, the law applies," said Lelli, who led this investigation. In this case, the observed acceleration tightly correlates with the gravitational acceleration from the visible mass, no matter the type of galaxy. In other words, if astronomers measure the distribution of normal matter, they know the rotation curve, and vice versa. "But it is still unclear what this relation means and what is its fundamental origin," Lelli said. The study is published online in Astrophysical Journal today. Co-authors are Stacy McGaugh, chair of the Department of Astronomy at Case Western Reserve, James Schombert, astronomy professor at the University of Oregon, and Marcel Pawlowski, former astronomy postdoctoral researcher at Case Western Reserve and current Hubble fellow at the University of California, Irvine. The researchers found that in 153 spiral and irregular galaxies, 25 ellipticals and lenticulars, and 62 dwarf spheroidals, the observed acceleration tightly correlates with the gravitational acceleration expected from visible mass. Observed deviations from this correlation are not related to any specific galaxy property but completely random and consistent with measurement errors, the team found. The tightness of this relation is difficult to understand in terms of dark matter as it's currently understood, the researchers said. It also challenges the current understanding of galaxy formation and evolution, in which many random processes such as galaxy mergers and interactions, inflows and outflows of gas, star formation and supernovas, occur at the same time. "Regularity must somehow emerge from this chaos," Lelli said. To make their discovery, researchers combined different tracers of the centripetal acceleration found in different types of galaxies, from which they made 1-to-1 comparisons. The kinematical tracers were cold gas in spiral and irregular galaxies, stars or hot gas in ellipticals and lenticulars, and individual giant stars in dwarf spheroidals. The investigation included so-called ultra-faint dwarf spheroidal galaxies, but due to their lack of light--which makes them hard to study--the researchers can't confidently offer a clear interpretation of the radial acceleration relation in these. Nevertheless, the growing proof of the relation, or natural law, requires new thinking about dark matter and gravity, the researchers said. "Within the standard dark-matter paradigm, this law implies that the visible matter and the dark matter must be tightly coupled in galaxies at a local level and independently on global properties. They must know about each other," Lelli said. "Within alternative models like modified gravity, this law represents a key empirical constraint and may guide theoretical physicists to build some appropriate mathematical extension of Einstein's General Relativity." The team's research so far has focused on galaxies in the nearby universe. Lelli and his colleagues plan to test the relation in more distant galaxies, just a few billion years after the big bang. They are hoping to learn whether the same relation holds during the lifetime of the Universe.
News Article | February 24, 2017
The adage that kids are growing up too fast these days has yet another locus of applicability. In a new, first-of-its-kind study, researchers from Case Western Reserve University School of Medicine have found a 700-percent surge in infections caused by bacteria from the Enterobacteriaceae family resistant to multiple kinds of antibiotics among children in the US. These antibiotic resistant infections are in turn linked to longer hospital stays and potentially greater risk of death. The research, published in the March issue of the Journal of the Pediatric Infectious Diseases Society, is the first known effort to comprehensively examine the problem of multi-drug resistant infections among patients under 18 admitted to US children’s hospitals with Enterobacteriaceae infections. Earlier studies focused mainly on adults, while some looked at young people in more limited geographical areas, such as individual hospitals or cities, or used more limited surveillance data. “There is a clear and alarming upswing throughout this country of antibiotic resistant Enterobacteriaceae infections in kids and teens,” said lead author Sharon B. Meropol, MD, PhD, a pediatrician and epidemiologist at Case Western Reserve University School of Medicine and Rainbow Babies and Children’s Hospital in Cleveland. “This makes it harder to effectively treat our patients’ infections. The problem is compounded because there are fewer antibiotics approved for young people than adults to begin with. Health care providers have to make sure we only prescribe antibiotics when they’re really needed. It’s also essential to stop using antibiotics in healthy agricultural animals.” In the retrospective study, Dr. Meropol and co-authors Allison A. Haupt, MSPH, and Sara M. Debanne, PhD, both from Case Western Reserve University School of Medicine, analyzed medical data from nearly 94,000 patients under the age of 18 years diagnosed with Enterobacteriaceae-associated infections at 48 children’s hospitals throughout the US. The average age was 4.1 years. Enterobacteriaceae are a family of bacteria; some types are harmless, but they also include such pathogens as Salmonella and Escherichia coli; Enterobacteriaceae are responsible for a rising proportion of serious bacterial infections in children. The researchers found that the share of these infections resistant to multiple antibiotics rose from 0.2 percent in 2007 to 1.5 percent in 2015, a seven-fold-plus increase in a short, eight-year span. Children with other health problems were more likely to have the infections while there were no overall differences based on sex or insurance coverage. The yearly number of discharges with Enterobacteriaceae-associated infections remained relatively stable over the course of the study years. In a key finding, more than 75 percent of the antibiotic-resistant infections were already present when the young people were admitted to the hospital, upending previous findings that the infections were mostly picked up in the hospital. “This suggests that the resistant bacteria are now more common in many communities,” said Dr. Meropol. For reasons that are unclear, older children and those living in the Western US were more likely to have the infections. The investigators also found that young people with antibiotic-resistant infections stayed in the hospital 20 percent longer than those whose infections could be addressed by antibiotics. Additionally, there was a greater—but not statistically significant—risk of death among pediatric patients infected with the resistant bacterial strains. Previous studies have shown that the problem is even worse elsewhere in the world, with an 11.4 percent global rate of antibiotic-resistant Enterobacteriaceae infections among young people, including 27 percent in Asia and the Pacific, 8.8 percent in Latin America, and 2.5 percent in Europe. “Escalating antibiotic resistance limits our treatment options, worsens clinical results, and is a growing global public health crisis,” said Dr. Meropol. “What’s more, the development of new antibacterial drugs, especially ones appropriate for children, remains essentially stagnant. We need to stop over-using antibiotics in animals and humans and develop new ones if we want to stop a bad problem from getting worse.”
Devireddy L.R.,Case Western Reserve University |
Hart D.O.,Howard Hughes Medical Institute |
Goetz D.H.,University of California at San Francisco |
Green M.R.,Howard Hughes Medical Institute
Cell | Year: 2010
Intracellular iron homeostasis is critical for survival and proliferation. Lipocalin 24p3 is an iron-trafficking protein that binds iron through association with a bacterial siderophore, such as enterobactin, or a postulated mammalian siderophore. Here, we show that the iron-binding moiety of the 24p3-associated mammalian siderophore is 2,5-dihydroxybenzoic acid (2,5-DHBA), which is similar to 2,3-DHBA, the iron-binding component of enterobactin. We find that the murine enzyme responsible for 2,5-DHBA synthesis, BDH2, is the homolog of bacterial EntA, which catalyzes 2,3-DHBA production during enterobactin biosynthesis. RNA interference-mediated knockdown of BDH2 results in siderophore depletion. Mammalian cells lacking the siderophore accumulate abnormally high amounts of cytoplasmic iron, resulting in elevated levels of reactive oxygen species, whereas the mitochondria are iron deficient. Siderophore-depleted mammalian cells and zebrafish embryos fail to synthesize heme, an iron-dependent mitochondrial process. Our results reveal features of intracellular iron homeostasis that are conserved from bacteria through humans. © 2010 Elsevier Inc.
Kean T.,Case Western Reserve University |
Thanou M.,King's College London
Advanced Drug Delivery Reviews | Year: 2010
Chitosan is a natural polysaccharide that has attracted significant scientific interest during the last two decades. It is a potentially biologically compatible material that is chemically versatile (-NH2 groups and various Mw). These two basic properties have been used by drug delivery and tissue engineering scientists to create a plethora of formulations and scaffolds that show promise in healthcare. Despite the high number of published studies, chitosan is not approved by the FDA for any product in drug delivery, and as a consequence very few biotech companies are using this material. This review will aim to provide information on these biological properties that affect chitosan's safe use in drug delivery. The term "Chitosan" represents a large group of structurally different chemical entities that may show different biodistribution, biodegradation and toxicological profiles. Here we aim to review research in this area and critically discuss chitosan's potential to be used as a generally regarded as safe (GRAS) material. © 2009 Elsevier B.V. All rights reserved.
Klatt N.R.,National Institute of Allergy and Infectious Diseases |
Funderburg N.T.,Case Western Reserve University |
Brenchley J.M.,National Institute of Allergy and Infectious Diseases
Trends in Microbiology | Year: 2013
The advent of combination antiretroviral therapy (cART) has significantly improved the prognosis of human immunodeficiency virus (HIV)-infected individuals. However, individuals treated long-term with cART still manifest increased mortality compared to HIV-uninfected individuals. This increased mortality is closely associated with inflammation, which persists in cART-treated HIV-infected individuals despite levels of plasma viremia below detection limits. Chronic, pathological immune activation is a key factor in progression to acquired immunodeficiency syndrome (AIDS) in untreated HIV-infected individuals. One contributor to immune activation is microbial translocation, which occurs when microbial products traverse the tight epithelial barrier of the gastrointestinal tract. Here we review the mechanisms underlying microbial translocation and its role in contributing to immune activation and disease progression in HIV infection. © 2012 .
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 159.11K | Year: 2011
DESCRIPTION (provided by applicant): The long term goal of this project is to develop and commercialize a drug to treat sleep apnea. Sleep apnea is a common medical condition and associated with excessive daytime sleepiness and is a composite risk for cardiovascular morbidity and mortality. Presently, there are no effective pharmacotherapies for individuals with sleep apnea. Growing evidence from both clinical and basic research is quickly approaching the concept that alterations of orexins play a role in the pathology of sleep apnea. Basic research has shown that orexins are directly involved in respiratory control, and a lower level of brain orexins accompanies the frequent appearance of ventilationary pauses. This evidence supports the further study of the direct effects of orexin receptor agonists and antagonists on ventilation; it also suggests that a cell assay should be created to pave the way for the development of a pharmaceutical treatment of sleep apnea. This project will determine the effects oforexin-2 receptor (OX2R) agonists and antagonists on the occurrence of sleep apnea in a mouse model, and it will optimize an established cell-based assay of an OX2R cell line. The hypothesis is that OX2R agonists prevent the occurrence of sleep apnea, andOX2R antagonists produce apnea. The project will measure ventilation rhythm by the plethysmography method combined with sleep recording in the mouse model. Animals will be treated with OX2R agonists or agonists plus antagonists or a control agent, such asartificial corticospinal fluid, via intracerebroventricular injection. A sleep apnea-hypopnea index (AHI) will be calculated for a daily 8 hours of recording data. Comparisons between the baseline and the treatment periods as well as among treatment groupswill be evaluated. Optimizing OX2R cell-based assay is the secondary study in this project. Using a cell culture method and a commercially available cell-based assay kit, the project will measure optimal cell response to the OX2R agonist and antagonist treatment. Successful completion of this project will either confirm or refute the hypothesis that OX2R agonists prevent sleep apnea; additionally, it will create a cell line-based assay for the future development of drugs that may eventually lead to effective pharmacotherapy for sleep apnea. PUBLIC HEALTH RELEVANCE: This project will evaluate the potential therapeutic effect of endogenous orexin receptor agonists on sleep apnea in a mouse model and optimize a established cell-based assay for further development in this new direction. Successful completion of this project will establish a strong and solid foundation for the Phase II development of lead compound research in the pharmaceutical treatment of sleep apnea.
Case Western Reserve University and President And Fellows Of Harvard College | Date: 2010-08-18
A method of promoting neural cell regeneration is carried out by contacting a neural cell with a compound that inhibits the binding of a chondroitin sulfate proteoglycan (CSPG) to a cellular (e.g., trans-membrane) PTP protein. The neural cell is associated with an injury or neurodegenerative condition.
News Article | February 21, 2017
CRANBURY, N.J., Feb. 21, 2017 (GLOBE NEWSWIRE) -- 1ST Constitution Bancorp (NASDAQ:FCCY), parent company of 1ST Constitution Bank, announced that its Board of Directors has increased the size of the Board from nine to ten members, effective March 1, 2017, and has elected William J. Barrett to serve as a director, effective as of March 1, 2017, to fill the vacancy on the Board resulting from the increase in the size of the Board. Mr. Barrett is an experienced business and technology risk management executive with significant strategic and operational leadership responsibilities throughout his 38 year career with Ernst & Young LLP. His leadership experience includes serving as Ernst & Young LLP’s Information Technology Risk and Assurance Leader for the Americas Financial Services Organization and serving on Ernst & Young LLP’s Information Technology Risk and Assurance Executive Council and Global Risk Committee. Mr. Barrett, who is a Certified Public Accountant in New York and California and a Certified Risk Professional from Bank Administration Institute, retired from Ernst & Young LLP on June 30, 2016. Since September 2008, Mr. Barrett has served on the Board of Trustees of LeMoyne College in Syracuse, New York. During his tenure, he has served on the Governance, Finance and Audit, Institutional Advancement, Student Development and Honors Committees. In addition, Mr. Barrett currently serves on the LeMoyne College Madden School Advisory Board, Accounting Advisory Board and Management Information Systems Advisory Board. Mr. Barrett holds a Bachelor of Science degree in Accounting from LeMoyne College and a Master of Business Administration degree in Finance from Case Western Reserve University. He is a member of the American Institute of Certified Public Accountants, the New York Society of Certified Public Accountants and the Information Systems Audit and Control Association (where he was a former Director of the Los Angeles chapter). “We are pleased to have Bill bring his wealth of knowledge in accounting, information technology and risk management to our Board,” said Charles S. Crow, III, Chairman of the Board of 1ST Constitution Bancorp. Mr. Crow added, “We look forward to Bill joining our Board and providing us with his insights and vast experience as a proven executive.” 1ST Constitution Bancorp, through its primary subsidiary, 1ST Constitution Bank, operates 19 branch banking offices in Cranbury (2), Fort Lee, Hamilton, Hightstown, Hillsborough, Hopewell, Jamesburg, Lawrenceville, Perth Amboy, Plainsboro, Rocky Hill, West Windsor, Princeton, Rumson, Fair Haven, Shrewsbury, Little Silver and Asbury Park, New Jersey. 1ST Constitution Bank also operates four residential mortgage loan production offices in Forked River, Flemington, Jersey City and Somerset, New Jersey. 1ST Constitution Bancorp is traded on the Nasdaq Global Market under the trading symbol “FCCY” and can be accessed through the Internet at www.1STCONSTITUTION.com. The foregoing contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements are not historical facts and include expressions about management’s confidence and strategies and management’s expectations about new and existing programs and products, relationships, opportunities, taxation, technology and market conditions. These statements may be identified by such forward-looking terminology as “expect,” “look,” “believe,” “anticipate,” “may,” “will,” or similar statements or variations of such terms. Actual results may differ materially from such forward-looking statements. Factors that may cause results to differ materially from such forward-looking statements include, but are not limited to, changes in the direction of the economy in New Jersey, the direction of interest rates, effective income tax rates, loan prepayment assumptions, continued levels of loan quality and origination volume, continued relationships with major customers including sources for loans, a higher level of net loan charge-offs and delinquencies than anticipated, bank regulatory rules, regulations or policies that restrict or direct certain actions, the adoption, interpretation and implementation of new or pre-existing accounting pronouncements, a change in legal and regulatory barriers including issues related to compliance with anti-money laundering and bank secrecy act laws, as well as the effects of general economic conditions and legal and regulatory barriers and structure. 1ST Constitution Bancorp assumes no obligation for updating any such forward-looking statements at any time, except as required by law.
News Article | March 2, 2017
Platinum, one of the rarest and most expensive metals on Earth, may soon find itself out of a job. Known for its allure in engagement rings, platinum is also treasured for its ability to jump-start chemical reactions. It’s an excellent catalyst, able to turn standoffish molecules into fast friends. But Earth’s supply of the metal is limited, so scientists are trying to coax materials that aren’t platinum — aren’t even metals — into acting like they are. For years, platinum has been offering behind-the-scenes hustle in catalytic converters, which remove harmful pollutants from auto exhaust. It’s also one of a handful of rare metals that move along chemical reactions in many well-established industries. And now, clean energy technology opens a new and growing market for the metal. Energy-converting devices like fuel cells being developed to power some types of electric vehicles rely on platinum’s catalytic properties to transform hydrogen into electricity. Even generating the hydrogen fuel itself depends on platinum. Without a cheaper substitute for platinum, these clean energy technologies won’t be able to compete against fossil fuels, says Liming Dai, a materials scientist at Case Western Reserve University in Cleveland. To reduce the pressure on platinum, Dai and others are engineering new materials that have the same catalytic powers as platinum and other metals — without the high price tag. Some researchers are replacing expensive metals with cheaper, more abundant building blocks, like carbon. Others are turning to biology, using catalysts perfected by years of evolution as inspiration. And when platinum really is best for a job, researchers are retooling how it is used to get more bang for the buck. Catalysts are the unsung heroes of the chemical reactions that make human society tick. These molecular matchmakers are used in manufacturing plastics and pharmaceuticals, petroleum and coal processing and now clean energy technology. Catalysts are even inside our bodies, in the form of enzymes that break food into nutrients and help cells make energy. During any chemical reaction, molecules break chemical bonds between their atomic building blocks and then make new bonds with different atoms — like swapping partners at a square dance. Sometimes, those partnerships are easy to break: A molecule has certain properties that let it lure away atoms from another molecule. But in stable partnerships, the molecules are content as they are. Left together for a very long period of time, a few might eventually switch partners. But there’s no mass frenzy of bond breaking and rebuilding. Catalysts make this breaking and rebuilding happen more efficiently by lowering the activation energy — the threshold amount of energy needed to make a chemical reaction go. Starting and ending products stay the same; the catalyst just changes the path, building a paved highway to bypass a bumpy dirt road. With an easier route, molecules that might take years to react can do so in seconds instead. A catalyst doesn’t get used up in the reaction, though. Like a wingman, it incentivizes other molecules to react, and then it bows out. A hydrogen fuel cell, for example, works by reacting hydrogen gas (H ) with oxygen gas (O ) to make water (H O) and electricity. The fuel cell needs to break apart the atoms of the hydrogen and oxygen molecules and reshuffle them into new molecules. Without some assistance, the reshuffling happens very slowly. Platinum propels those reactions along. Platinum works well in fuel cell reactions because it interacts just the right amount with both hydrogen and oxygen. That is, the platinum surface attracts the gas molecules, pulling them close together to speed along the reaction. But then it lets its handiwork float free. Chemists call that “turnover” — how efficiently a catalyst can draw in molecules, help them react, then send them back out into the world. Platinum isn’t the only superstar catalyst. Other metals with similar chemical properties also get the job done — palladium, ruthenium and iridium, for example. But those elements are also expensive and hard to get. They are so good at what they do that it’s hard to find a substitute. But promising new options are in the works. Carbon is a particularly attractive alternative to precious metals like platinum because it’s cheap, abundant and can be assembled into many different structures. Carbon atoms can arrange themselves into flat sheets of orderly hexagonal rings, like chicken wire. Rolling these chicken wire sheets — known as graphene — into hollow tubes makes carbon nanotubes, which are stronger than steel for their weight. But carbon-only structures don’t make great catalysts. “Really pure graphene isn’t catalytically active,” says Huixin He, a chemist at Rutgers University in Newark, N.J. But replacing some of the carbon atoms in the framework with nitrogen, phosphorus or other atoms changes the way electric charge is distributed throughout the material. And that can make carbon behave more like a metal. For example, nitrogen atoms sprinkled like chocolate chips into the carbon structure draw negatively charged electrons away from the carbon atoms. The carbon atoms are left with a more positive charge, making them more attractive to the reaction that needs a nudge. That movement of electrical charge is a prerequisite for a material to act as a catalyst, says Dai, who has pioneered the development of carbon-based, metal-free catalysts. His lab group demonstrated in 2009 in Science that clumps of nitrogen-containing carbon nanotubes aligned vertically — like a fistful of uncooked spaghetti — could stand in for platinum to help break apart oxygen inside fuel cells. To perfect the technology, which he has patented, Dai has been swapping in different atoms in different combinations and experimenting with various carbon structures. Should the catalyst be a flat sheet of graphene or a forest of rolled up nanotubes, or some hybrid of both? Should it contain just nitrogen and carbon, or a smorgasbord of other elements, too? The answer depends on the specific application. In 2015 in Science Advances, Dai demonstrated that nitrogen-studded nanotubes worked in acid-containing fuel cells, one of the most promising designs for electric vehicles. Other researchers are playing their own riffs on the carbon concept. To produce graphene’s orderly structure requires just the right temperature and specific reaction conditions. Amorphous carbon materials — in which the atoms are randomly clumped together — can be easier to make, Rutgers’ He says. In one experiment, He’s team started with liquid phytic acid, a substance made of carbon, oxygen and phosphorus. Microwaving the liquid for less than a minute transformed it into a sooty black powder that she describes as a sticky sort of sand. “Phytic acid strongly absorbs microwave energy and changes it to heat so fast,” she says. The heat rearranges the atoms into a jumbled carbon structure studded with phosphorus atoms. Like the nitrogen atoms in Dai’s nanotubes, the phosphorus atoms changed the movement of electric charge through the material and made it catalytically active, He and colleagues reported last year in ACS Nano. The sooty phytic acid–based catalyst could help move along a different form of clean energy: It sped up a reaction that turns a big, hard-to-use molecule found in cellulose — a tough, woody component of plants — into something that can react with other molecules. That product could then be used to make fuel or other chemicals. He is still tweaking the catalyst to make it work better. He’s catalyst particles get mixed into the chemical reaction (and later need to be strained out). These more jumbled carbon structures with nitrogen or phosphorus sprinkled in can work in fuel cells, too — and, she says, they’re easier to make than graphene. Rather than design new materials from the bottom up, some scientists are repurposing catalysts already used in nature: enzymes. Inside living things, enzymes are involved in everything from copying genetic material to breaking down food and nutrients. Enzymes have a few advantages as catalysts, says M.G. Finn, a chemist at Georgia Tech. They tend to be very specific for a particular reaction, so they won’t waste much energy propelling undesired side reactions. And because they can evolve, enzymes can be tailored to meet different needs. On their own, enzymes can be too fragile to use in industrial manufacturing, says Trevor Douglas, a chemist at Indiana University in Bloomington. For a solution, his team looked to viruses, which already package enzymes and other proteins inside protective cases. “We can use these compartments to stabilize the enzymes, to protect them from things that might chew them up in the environment,” Douglas says. The researchers are engineering bacteria to churn out virus-inspired capsules that can be used as catalysts in a variety of applications. His team mostly uses enzymes called hydrogenases, but other enzymes can work, too. The researchers put the genetic instructions for making the enzymes and for building a protective coating into Escherichia coli bacteria. The bacteria go into production mode, pumping out particles with the hydrogenase enzymes protected inside, Douglas and colleagues reported last year in Nature Chemistry. The protective coating keeps chunky enzymes contained, but lets the molecules they assist get in and out. “What we’ve done is co-opt the biological processes,” Douglas says. “All we have to do is grow the bacteria and turn on these genes.” Bacteria, he points out, tend to grow quite easily. It’s a sustainable system, and one that’s easily tailored to different reactions by swapping out one enzyme for another. The enzyme-containing particles can speed along generation of the hydrogen fuel, he has found. But there are still technical challenges: These catalysts last only a couple of days, and figuring out how to replace them inside a consumer device is hard. Other scientists are using existing enzymes as templates for catalysts of their own design. The same family of hydrogenase enzymes that Douglas is packaging into capsules can be a launching point for lab-built catalysts that are even more efficient than their natural counterparts. One of these hydrogenases has an iron core plus an amine — a nitrogen-containing string of atoms — hanging off. Just as the nitrogen worked into Dai’s carbon nanotubes affected the way electrons were distributed throughout the material, the amine changes the way the rest of the molecule acts as a catalyst. Morris Bullock, a researcher at Pacific Northwest National Laboratory in Richland, Wash., is trying to figure out exactly how that interaction plays out. He and colleagues are building catalysts with cheap and abundant metals like iron and nickel at their core, paired with different types of amines. By systematically varying the metal core and the structure and position of the amine, they’re testing which combinations work best. These amine-containing catalysts aren’t ready for prime time yet — Bullock’s team is focused on understanding how the catalysts work rather than on perfecting them for industry. But the findings provide a springboard for other scientists to push these catalysts toward commercialization. These new types of catalysts are promising — many of them can speed up reactions almost as well as a traditional platinum catalyst. But even researchers working on platinum alternatives agree that making sustainable and low-cost catalysts isn’t always as simple as removing the expensive and rare metals. “The calculation of sustainability is not completely straightforward,” Finn says. Though he works with enzymes in his lab, he says, “a platinum-based catalyst that lasts for years is probably going to be more sustainable than an enzyme that degrades.” It might end up being cheaper in the long run, too. That’s why researchers working on these alternative catalysts are pushing to make their products more stable and longer-lasting. “If you think about a catalyst, it’s really the atoms on the surface that participate in the reaction. Those in the bulk may just provide mechanical support or are just wasted,” says Younan Xia, a chemist at Georgia Tech. Xia is working on minimizing that waste. One promising approach is to shape platinum into what Xia dubs “nanocages” — instead of a solid cube of metal, just the edges remain, like a frame. It’s also why many scientists haven’t given up on metal. “I don’t think you can say, ‘Let’s do without metals,’ ” says James Clark, a chemist at the University of York in England. “Certain metals have a certain functionality that’s going to be very hard to replace.” But, he adds, there are ways to use metals more efficiently, such as using nanoparticle-sized pieces that have a higher surface area than a flat sheet, or strategically combining small amounts of a rare metal with cheaper, more abundant nickel or iron. Changing the structure of the material on a nanoscale level also can make a difference. In one experiment, Xia started with cubes of a different rare metal, palladium. He coated the palladium cubes with a thin layer of platinum just a few atoms thick — a pretty straightforward process. Then, a chemical etched away the palladium inside, leaving a hollow platinum skeleton. Because the palladium is removed from the final product, it can be used again and again. And the nanocage structure leaves less unused metal buried inside than a large flat sheet or a solid cube, Xia reported in 2015 in Science. Since then, Xia’s team has been developing more complex shapes for the nanocages. An icosahedron, a ball with 20 triangular faces, worked especially well. The slight disorder to the structure — the atoms don’t crystallize quite perfectly — helped make it four times as active as a commercial platinum catalyst. He has made similar cages out of other rare metals like rhodium that could work as catalysts for other reactions. It’ll take more work before any of these new catalysts fully dethrone platinum and other precious metals. But once they do, that’ll leave more precious metals to use in places where they can truly shine. This article appears in the March 4, 2017, issue of Science News with the headline, "Built for speed: More sustainable approaches could get reactions moving."
News Article | February 24, 2017
The deadly fungus, Candida auris, which has been found in hospitals, is resistant to entire classes of antimicrobial drugs, limiting treatment options for those infected. First reported in 2009, the fungus has been linked to invasive infections in nine countries, including the United States, and has caused at least two hospital outbreaks involving more than 30 patients each. Now, in a first-of-its-kind study published in Antimicrobial Agents and Chemotherapy, microbiologists at Case Western Reserve University School of Medicine have provided previously uninvestigated details pertaining to C. auris drug resistance and growth patterns. Based on specimens collected from around the globe, the comprehensive study also provides evidence that a new investigational drug (SCY-078) may help to cure these infections. "This emerging fungal species has started to infect patients globally, causing invasive infections that are associated with a high death rate," said Mahmoud Ghannoum, PhD, MBA, FIDSA, Professor and Director of the Center for Medical Mycology in the Department of Dermatology at Case Western Reserve School of Medicine, and University Hospitals Cleveland Medical Center. "It is multidrug-resistant, and some strains isolated from patients are resistant to all commercially available antifungal drugs. Multidrug-resistance used to be reported for bacteria only, and now we must add fungi to the list." Ghannoum led the investigation of 16 strains of C. auris collected from infected patients in Germany, Japan, Korea, and India. The researchers tested the isolates against a battery of 11 drugs, belonging to different classes of antifungals, to identify drug concentrations that could combat infection. While most samples proved at least partially resistant to drugs tested, low concentrations of an investigational drug (SCY-078) "severely distorted" the fungus and impaired its growth, providing an important step towards the development of this drug to treat C. auris infections. Fungi exposed to the drug could not divide, suggesting it could halt infections or limit their spread. Ghannoum's study is the first to provide details related to the effects of the investigational drug on C. auris. The fungus lurks on catheters in intensive care units, where it forms highly drug-resistant communities, or biofilms. Ghannoum's team exposed fungi in the laboratory to silicone surfaces mimicking catheters. Under high-powered microscopes, they found C. auris formed relatively thin biofilms that weakened when exposed to the investigational drug. The findings were strain-dependent, but suggest applicability for the new drug to combat catheter-associated infections in particular. Previous studies have shown the drug is effective against other Candida species that cause catheter-associated infections, including C. albicans and C. tropicalis. Said Ghannoum, "This drug is especially promising because of its broad anti-Candida activity, including activity against drug-susceptible and resistant strains." The study is also the first to report C. auris does not germinate and produce spores like other fungi, a surprise given its ability to rapidly spread in hospitals. The researchers also discovered only certain strains produce destructive enzymes that commonly help fungi establish infections in body tissue. Despite these apparent weaknesses, the fungus is able to maintain extreme drug-resistance and infect patients. According to the paper, the "multidrug-resistant phenotype of C. auris comes with a major fitness cost." Ghannoum's research provides a foundation for clinical trials to further study the investigational drug and informs doctors desperate for new ways to treat infections caused by C. auris. Said Ghannoum, "Understanding the virulence of C. auris and showing that the investigational drug is effective may lead to the development of new medications to combat this emerging health threat." The Centers for Disease Control and Prevention is actively tracking C. auris infections. Said Ghannoum, "Eradication of Candida auris from hospitals is very difficult and in some cases has led to closing hospital wards." People staying in hospitals for extended periods of time are most at risk. Laboratory workers who identify the species in a patient sample are encouraged to contact state or local public health authorities, or firstname.lastname@example.org. This research was supported in part by Scynexis Inc.; the National Institutes of Health (R01DE024228 to M.A.G. and P.K.M.); and the Swagelok Center for Surface Analysis of Materials, Skin Diseases Research Center (NIAMS P30 AR03970), and Confocal Scanning Laser Microscopy Core of the Genetics Department at Case Western Reserve University. For more information about Case Western Reserve University School of Medicine, please visit: http://case. .
News Article | February 15, 2017
Researchers at Case Western Reserve University will use a $2 million grant from the National Institutes of Health to develop and test a small, portable blood-adhesion monitor for sickle cell disease patients. The engineers and doctors hope to make the device as useful as at-home insulin monitors diabetes patients use to manage their disease. Sickle cell patients suffer painful damage to joints and organs during events called vaso-occlusive crises. These random and unpredictable crises occur when the misshapen and abnormal sticky blood cells that are characteristic of the disease clog blood vessels. Although the proximate causes of vaso-occlusive crises are not well understood, hemoglobin molecules link into long chains inside red blood cells, stiffening the cells and changing cell shape from a donut without a hole to a crescent--thus the name of the disease. Simultaneously, adhesive proteins form on the surface of the cells. These changes hamper the flow of the cells in the bloodstream and increase the likelihood they will clog blood vessels. Early versions of the monitor have proved capable of determining whether cells are sticky and the level of stickiness, "but we don't know if this information will make a difference in patients' lives or in how the disease is managed," said Umut Gurkan, assistant professor of mechanical and aerospace engineering and project leader. Gurkan and colleagues believe the stickiness of a patient's blood cells reflects disease severity and may be used to predict vaso-occlusive crises. If a prodrome, or early symptom indicating the onset of crises, can be identified, strategies can be (and are being) developed to block the generation of the vaso-occlusive episode. The device may also be useful in monitoring new sickle cell drugs designed to either block adhesive proteins on blood-cell surfaces or resolve clogs that block blood vessels and starve joints and organs of oxygen. Currently, there are no easily applicable tests for either scenario, the researchers say. To look for trends associated with crises, a team of researchers will test prototype monitors with patients in Cleveland and New York City (the Bronx) starting this year. Sickle cell disease is actually a group of inherited red blood cell disorders. About 300,000 babies with severe forms are born worldwide annually, the World Health Organization estimates. Life expectancy for those with the disease in the United States has increased the last few decades to a range of 40 to 60 years, the Centers for Disease Control and Prevention says. But the disease remains costly. Hospitalizations and treatments for crises and other harmful affects can amount to $8 million for one patient over a lifetime. "We think that, with much better monitoring and anti-adhesion therapies, the physical and financial cost will be reduced," Gurkan said. "There will be less time spent out of work and in the hospital, reducing stress and suffering by the patient and family and benefitting the health-care system." In the prototype monitor, blood flows through channels as wide as three to four cells across, reproducing microvessel size inside the body. The channel lining mimics the properties of endothelial cells lining blood vessels. Under a microscope, researchers can see cells stick to channel walls and determine the stickiness and number per unit volume of blood. The scientists are working on a way to quickly identify proteins on the surface. About a dozen proteins contribute to adhesion, and different patients have different proteins on their cells, providing an opportunity to customize treatment. Gurkan and Jane Little, associate professor of hematology and oncology at the Case Western Reserve School of Medicine, and an adult hematologist at University Hospitals Cleveland Medical Center, are team leaders on the project. Other members include: Deepa G. Manwani, chief of the Division of Hematology at the Children's Hospital at Montefiore in the Bronx; Karen Ireland, clinical coordinator at Montefiore; Charlotte Yuan and Erina Quinn, research assistants at UH Cleveland Medical Center; Erdem Kucukal, doctoral student in mechanical and aerospace engineering; and Evren G. Cavusoglu, assistant professor of electrical engineering and computer science, specializing in bioinformatics, at Case Western Reserve. The monitors will be tested on adult patients at University Hospital in Cleveland and children at University Hospitals Rainbow Babies & Children's Hospital and Montefiore beginning next year. "The test can be run in a primary care doctor's office during a visit," Gurkan said. Ultimately, take-home versions of the monitor would enable patients or parents to use the test daily to manage their condition. If the monitor proves effective during testing, the researchers plan to commercialize the device, which Gurkan said could have applications in malaria, certain cancers, lead poisoning and other diseases and conditions that cause changes in red blood cell properties.
News Article | February 15, 2017
ABQ Dentures offers a unique and valued specialty to the residents of Albuquerque. While the practice does offer a full menu of services in general dentistry, its primary focus is delivering top quality dentures. Patients benefit from the most preferred full and partial denture options available, including those that are fixed, removable or retained by dental implants. Whether a patient has a few missing teeth or needs a full mouth reconstruction, ABQ Dentures is dedicated to providing affordable and long-lasting solutions. ABQ Dentures is staffed with an experienced prosthodontist, who is recognized as an elite provider of All-On-4 implants. This innovative denture system uses just four dental implants to support a full arch of prosthetic teeth. All-On-4 implants require minimal bone density and can be placed in just 24 hours. ABQ Dentures is proud to be a one-stop shop for patients who need denture services. Not only do they place dentures, but they also offer denture cleanings, denture relines and emergency repairs. Their office environment includes relaxing patient amenities such as warm beverages, an Internet bar, TVs and ergonomic neck pillows. In addition, ABQ Dentures offers easy financing plans and accepts most dental insurance plans as well as Medicaid. “When a patient needs dentures, we want them to know that ABQ Dentures can give them the best experience possible, which includes top quality options, affordable prices and unrivaled service,” says Dr. Darren Norby of ABQ Dentures. More About Dr. Darren Norby and Dr. Peter Roukema: Dr. Darren Norby is a specialist in Prosthodontics. He received his Bachelor of Science (BS) degree from Brigham Young University in 2004 and his Doctor of Medical Dentistry (DMD) degree from Case Western Reserve University School of Dental Medicine in 2008. Dr. Norby studied for 3 additional years at Louisiana State University where he specialized in prosthodontics. He is also a certified dental technician (CDT) in the specialties of Complete Dentures and Ceramics, making him one of an elite group of dentists in the country with this training. Dr. Peter Roukema also leads the practice as a talented family dentist. He earned his bachelor’s degree from the University of Northern Colorado and completed his dental training at Case Western Reserve University School of Dental Medicine in Cleveland, Ohio. Upon graduation, he moved to Albuquerque to receive an Advanced Education in General Dentistry certificate from the University of New Mexico School of Medicine. Dr. Roukema brings extensive experience in placing dentures, with a full understanding of the emotional process of transitioning from natural teeth to prosthetic teeth. For more information about ABQ Dentures or the services they offer, please visit abqdentures.com or call the office directly at (505) 933-8195.
News Article | February 15, 2017
It’s the first day of the big DistribuTech conference in San Diego. Grid giants and startups are unveiling their latest products aimed at connecting utilities with the grid edge. Let’s start with Enbala, the Vancouver, Canada-based startup that has deployed its software platform to turn industrial energy loads like pumps and refrigerators into megawatts' worth of fast-responding grid assets. On Tuesday, it announced its biggest partner yet: Swiss grid giant ABB, which has tapped Enbala’s Symphony software platform as part of a new, jointly developed distributed energy resource management system (DERMS). The term "DERMS" applies to software that can integrate the needs of utility grid operators with the capabilities of flexible demand-side energy resources at the edges of the grid. DERMS platforms come in all shapes and sizes, from grid giants like Siemens and General Electric, to startups like Advanced Microgrid Solutions, Blue Pillar, AutoGrid, Opus One, Power Analytics, Spirae, Smarter Grid Solutions, and the recently acquired Viridity Energy. But for the most part, they’ve typically been organized in two different ways -- top-down extensions of utility or grid operator controls out to customer endpoints, or bottom-up aggregations of customer loads into grid energy markets. Enbala and ABB’s combo DERMS platform intends to erase this distinction, Enbala CEO Bud Vos said. On the utility side, ABB brings a well-known set of tools, like its advanced distribution management software (ADMS) with its “single network model” and “unified geospatial control center operator environment." These are tools used by utility operators to monitor and respond to changes on their distribution grids. “Our platform is an extension of the ADMS platform, and tightly integrated with that ADMS framework,” Vos said. ”It provides cohesiveness, from an operational standpoint and from a data standpoint.” Enbala, in turn, brings a software platform that can tap into hundreds of individual loads per customer, collect and analyze their data, and then start to subtly shift their energy-use patterns in effective and profitable ways. Sometimes that means moving big water-pumping schedules to times of the day when electricity isn’t in high demand. Other times it involves turning thousands of water heaters and refrigerators on and off in response to 4-second signals to help balance grid frequencies. So far, Enbala has been aggregating responsive energy loads on behalf of its customers in frequency regulation markets run by mid-Atlantic grid operator PJM and Ontario's Independent Electricity System Operator. As one of several partners in the PowerShift Atlantic project, it has also used its software platform, managed by employees at its network operations center, to help control customer loads to firm wind power for Canadian utility NB Power. In the past year or so, Enbala has been getting more into the distribution grid side of things. At last year’s DistribuTech, the company was demonstrating pilot projects in Hawaii using rooftop PV solar inverters, and a project in Southern California modeling big industrial and commercial loads’ potential to help balance grid disruptions. “We think we’re going to see hundreds of thousands, if not millions, of connected energy deices coming to market,” Vos said. “You’ve got to be able to optimize millions of assets in seconds, or even sub-second timescales, and with accuracy, to know that power is moving to the right places at the right time.” Enbala has also kicked its computing capabilities up a notch with its latest rollout, he said. “Under the covers of this release, we’ve updated our learning algorithms and optimization algorithms,” he said. It is using a software language called Erlang, originally built for the telecommunications industry, that can run millions of simultaneous transactions at a speed that allows for real-time decision making. It’s hard to define the DERMS competitive landscape, since it’s such a new field. But GTM Research predicts that the North American DERMS market will reach $110 million by 2018, as today’s pilot projects start to become operationalized at utilities in states with lots of distributed energy to handle, like Hawaii and California. And ABB isn’t the only grid giant trying to colonize the DERMS space. Take Siemens, which launched its own DERMS product at DistribuTech on Tuesday, complete with “tools that provide data and visibility across the energy system, from distribution grid planning to market forecasting.” The new DERMS platform is built on Siemens’ work on microgrids, a big focus of the company's efforts at DistribuTech conferences over the past few years. This work includes partnerships with startup Utilidata, as well as adaptations of the company’s Spectrum 7 control software into local grid applications. To date, Siemens has rolled out these capabilities in microgrid projects with universities and government partners, such as the Department of Energy-funded microgrid project with Case Western Reserve University and NASA. But it’s also linking those microgrids to utility systems, said Mike Carlson, president of Siemens Smart Grid North America, in an interview. On the data side, Siemens released an integrated application for its EnergyIP software on Tuesday, combining distributed energy management, virtual power plant capabilities and demand response on one platform. EnergyIP, built on the software of Siemens acquisition eMeter, “is architected for a true real-time, cloud-based IOT system,” Carlson said, capable of giving grid operators second-by-second control and analysis capabilities. “What we built is very modular, or scalable, or agile, components that you can bolt onto existing capabilities, and scale them based on size, or capability,” he said. The costs for standing up a microgrid range from the low six figures for simpler applications, up to the millions of dollars to enable sub-second monitoring required for certain grid applications, he said. But that’s “about half the cost of a traditional enterprise deployment,” since it has already combined all the requisite pieces of the microgrid puzzle. General Electric, which has invested in Enbala through GE Energy Ventures, has also been promising a DERMS offering, built on the work it’s been doing with Duke Energy’s Coalition of the Willing, and the Nice Grid project in southern France. GE has also been working with Enbala on a project under the Department of Energy’s ARPA-E NODES program. Vos noted that Enbala’s work with ABB is a non-exclusive partnership, freeing it to work with multiple partners. Right now the company has six projects, including two contracts for virtual power plants and two regulated utility DERMS contracts that are focused on optimization of distribution feeders. Make sure to attend Greentech Media’s Grid Edge World Forum 2017, our premier conference and exhibition focused exclusively on tomorrow’s distributed energy system. Join us to discuss and debate the latest issues impacting tomorrow’s distributed energy system, and examine the trends and innovation happening at the grid edge. Learn more here.
News Article | February 15, 2017
NEW YORK (Reuters) - Supreme Court nominee Judge Neil Gorsuch is known for questioning how far courts should go in deferring to federal agencies on interpreting the law, a view that could be important for U.S. companies and, perhaps, for President Donald Trump. Nominated by Trump on Tuesday to fill a vacancy on the nation's highest court, the 49-year-old Gorsuch is widely viewed as a sharp-eyed jurist and a crisp writer who has the potential to be a persuasive voice on the court. In a recent case, Gorsuch took a dim view of a landmark 1984 high court ruling, Chevron v. Natural Resources Defense Council. Widely cited, the ruling directed judges nationwide to defer to agencies' interpretation of laws that may be ambiguous. It is known as "Chevron deference." Last August, in a case over immigration rules, Gorsuch called the doctrine the "elephant in the room" that concentrates federal power "in a way that seems more than a little difficult to square with the Constitution." Showing his willingness to tackle the issue head on, he added, "Maybe the time has come to face the behemoth." If Gorsuch can persuade other Supreme Court justices to question Chevron deference, companies arguing before the high court against federal regulations might have a better chance on issues ranging from the environment to immigration. At the same time, broader skepticism of deference to agencies could have long-term consequences for Trump. The new president is moving swiftly to reshape the federal bureaucracy, appointing agency heads who could upend the legacy of President Barack Obama on emissions, health care and internet policy. The court's views on agencies' agendas will be critical. "The idea that President Trump of all people would be the one to choose a justice who might push the court to reduce the executive power is pretty ironic," said John Nagle, a professor at the University of Notre Dame Law School. If the Supreme Court were to overturn or limit the Chevron precedent, lower courts could become more active in deciding the ultimate meaning of a statute, making it less likely that an agency's view would stand, Nagle said. "It could make it more difficult for the Trump administration to defend some of its regulatory actions in federal court," said Case Western Reserve University School of Law professor Jonathan Adler. Republicans in Congress, particularly when Obama was in office, frequently complained about Chevron deference. They have even debated legislation that would override it. The House of Representatives passed such a bill on Jan. 11, although it is unlikely to win approval in the Senate. Gorsuch is not the first judge to take aim at the issue. In 2015, the Supreme Court ruled against the Environmental Protection Agency over its regulations for limiting pollution from mercury and other toxic materials. At that time, conservative Justice Clarence Thomas wrote a separate opinion saying the government's position "raises serious questions about the constitutionality of our broader practice of deferring to agency interpretations of federal statutes." While Thomas has argued the doctrine threatens the Constitutionally-mandated separation of the different branches of government, Chief Justice John Roberts and Justice Anthony Kennedy have said it may threaten individual liberties, said Andrew Grossman, a conservative lawyer who has represented companies challenging government regulations. "Gorsuch may be the one to bring the court together on fundamental questions of administrative power that have sparked so much controversy and divisiveness in recent years," Grossman said. Some court-watchers say that in practice the justices are inclined to support executive actions that are in keeping with their own views. But an analysis of their votes carried out by Jack Beermann, a professor at Boston University School of Law, showed that such an outcome is not uniform.
News Article | March 2, 2017
Since the discovery of penicillin in 1928, antibiotics have made the world a much safer and healthier place. But Shakespeare was onto something when he asked if it's possible to have too much of a good thing. In the case of antibiotics, the answer is increasingly "yes." As a result, Case Western Reserve University School of Medicine and Louis Stokes Cleveland VA Medical Center are teaming up to take on the rising problem of antibiotic resistance. A new entity, Case VA CARES, will combine firepower from both organizations in the battle against antibiotic resistance. Staff will carry out new research, work to modify existing antibiotics, try and discover new ones, and use decoys to trick uncooperative bacteria. More and more, bacteria and other microorganisms are developing resistance to antibiotics which used to kill them off. This resistance, which evolves via natural selection through random mutation, is usually caused by excessive use of antibiotics, including in livestock animals raised as human food. In turn, infections which used to yield to antibiotics can persist and even worsen, putting patients in danger. Not only does antibiotic resistance imperil health, it also adds to healthcare costs as doctors try different medicines to find ones bacteria haven't become resistant to. Sometimes the stronger substitute antibiotics cause serious side effects such as kidney damage. More than two million people develop antibiotic-resistant infections in the U.S. ever year, leading to more than 23,000 deaths. Some experts say that without new inroads, the death toll could top that from cancer by mid-century. The financial costs are already enormous: as much as $20 billion in extra healthcare costs annually. Case VA CARES (CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology) will be located in the CWRU School of Medicine and Cleveland VA with collaborating partner laboratories located around the world. "An immediate goal of this initiative is to boost research into multidrug-resistant Gram negative organisms such as Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae and mycobacteria, which can cause tuberculosis and many other infections," said Pamela B. Davis, MD, PhD, dean of CWRU School of Medicine. "Understanding the mechanistic and molecular bases of resistance is crucial to properly treating patients with serious infections." In addition to research and drug discovery, experts at the center will work with scientists throughout the world to track outbreaks of resistant organisms, discover new drugs, and develop training for physicians, medical students, and residents to recognize and prevent overuse of antibiotics. The director of the center will be Robert A. Bonomo, MD, medicine service chief at the Louis Stokes Cleveland VA Medical Center. Faculty members of the new center will come from throughout both organizations including experts in infectious diseases, microbiology, molecular biology, biochemistry, pharmacology, proteomics, and bioinformatics. Experienced scientists with expertise in bacterial genome sequencing and bioinformatics analyses will be recruited to augment experts from the CWRU Department of Genetics. "In the search for new antibiotics and fresh strategies for existing ones, Case VA CARES will play a prominent role in leading and conducting research needed to design and conduct clinical trials, which will take place at the VA , University Hospitals, MetroHealth, and the Cleveland Clinic Foundation," said Dr. Bonomo, who is a member of the NIH-funded Antimicrobial Resistance Leadership Group (ARLG). The latter group is addressing national priorities for clinical research on antibiotic resistance. Case VA CARES will also benefit from strong working relationships with industry partners of both the School of Medicine, University Hospitals of Cleveland, MetroHealth, the Cleveland Clinic and the VA Medical Center. Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation's top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing healthcare environment of the 21st century. Nine Nobel Laureates have been affiliated with the School of Medicine. Annually, the School of Medicine trains more than 800 MD and MD/PhD students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News & World Report's "Guide to Graduate Education." The School of Medicine is affiliated with University Hospitals Cleveland Medical Center, MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. For more information, visit http://case. . The Louis Stokes Cleveland VA Medical Center is the hub of the Northeast Ohio VA Healthcare System, providing and coordinating primary, acute and specialty care for Veterans. Focusing on treating the whole Veteran through health promotion and disease prevention, the Northeast Ohio VA Healthcare System delivers comprehensive, seamless healthcare and social services for Veterans at 18 locations across Northeast Ohio. The Northeast Ohio VA Healthcare System contributes to the future of medicine through education, training and research programs. For more information visit http://www. .
Ernst O.P.,King's College |
Lodowski D.T.,Case Western Reserve University |
Elstner M.,Karlsruhe Institute of Technology |
Hegemann P.,Humboldt University of Berlin |
And 2 more authors.
Chemical Reviews | Year: 2014
Animal rhodopsins are employed in visual and nonvisual phototransduction, in the maintenance of the circadian clock and as photoisomerases. Animal rhodopsins are specialized G-protein-coupled receptors (GPCRs). Structures of animal and microbial rhodopsins differ largely and are drawn in opposite orientations with respect to the membrane. Light absorption initiates functions of both microbial and animal rhodopsins and the wavelength dependence of the absorption efficiency determines the colors of the proteins. The initial photochemical reaction in microbial and animal rhodopsins is known to be one of the fastest and most efficient chemical events in biology. Judging from the large number of new rhodopsin variants unearthed by genomic and metagenomic sequencing, new interesting functions of retinal proteins will continue to be discovered. This applies to both microbial and animal rhodopsins, and will lead to new breakthroughs in understanding microbial, invertebrate, and vertebrate physiology and evolution.
Dai L.,Case Western Reserve University |
Chang D.W.,Ulsan National Institute of Science and Technology |
Baek J.-B.,Ulsan National Institute of Science and Technology |
Lu W.,Energ2 Inc.
Small | Year: 2012
It is estimated that the world will need to double its energy supply by 2050. Nanotechnology has opened up new frontiers in materials science and engineering to meet this challenge by creating new materials, particularly carbon nanomaterials, for efficient energy conversion and storage. Comparing to conventional energy materials, carbon nanomaterials possess unique size-/surface-dependent (e.g., morphological, electrical, optical, and mechanical) properties useful for enhancing the energy-conversion and storage performances. During the past 25 years or so, therefore, considerable efforts have been made to utilize the unique properties of carbon nanomaterials, including fullerenes, carbon nanotubes, and graphene, as energy materials, and tremendous progress has been achieved in developing high-performance energy conversion (e.g., solar cells and fuel cells) and storage (e.g., supercapacitors and batteries) devices. This article reviews progress in the research and development of carbon nanomaterials during the past twenty years or so for advanced energy conversion and storage, along with some discussions on challenges and perspectives in this exciting field. Progress in the research and development of carbon nanomaterials during the past twenty years or so is reviewed with reference to their use in advanced energy conversion and storage applications. Some discussion of the challenges and perspectives in this exciting field is also presented. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Dai L.,Case Western Reserve University |
Xue Y.,Case Western Reserve University |
Qu L.,Beijing Institute of Technology |
Choi H.-J.,Ulsan National Institute of Science and Technology |
Baek J.-B.,Ulsan National Institute of Science and Technology
Chemical Reviews | Year: 2015
The rising global energy demand and environmental impact of traditional energy resources pose serious challenges to human health, energy security, and environmental protection. One promising solution is fuel cell technology, which provides clean and sustainable power. Besides, the catalytic performance of many non-precious metal catalysts still needs to be further improved to meet the requirement for practical applications. These special physicochemical properties, in turn, allow for controlled structural modifications of fullerenes, leading to the formation of various advanced fullerene derivatives with appropriate properties for many potential applications.
DiMarino A.M.,Pediatric Pulmonology |
Caplan A.I.,Case Western Reserve University |
Bonfield T.L.,Case Western Reserve University
Frontiers in Immunology | Year: 2013
The advent of mesenchymal stem cell (MSC) based therapies for clinical therapeutics has been an exciting and new innovation for the treatment of a variety of diseases associated with inflammation, tissue damage and subsequent regeneration and repair. Applicationbased ability to measure MSC potency and fate of the cells post-MSC therapy are the variables that confound the use of MSCs therapeutics in human diseases. An evaluation of MSC function and applications with attention to detail in the preparation as well as quality control (QC) and quality assurance (QA) are only as good as the assays that are developed. In vivo measures of efficacy and potency require an appreciation of the overall pathophysiology of the model and standardization of outcome measures. The new concepts of how MSC's participate in the tissue regeneration and wound repair process and further, how this is impacted by estimates of efficacy and potency Are important new topics. In this regard,,, this chapter will review some of the in vitro and in vivo assays for MSC function and activity and their application to the clinical arena. © 2013 DiMarino, Caplan and Bonfield.
Qu L.,Beijing Institute of Technology |
Liu Y.,Wenzhou Medical College |
Baek J.-B.,Ulsan National Institute of Science and Technology |
Dai L.,Case Western Reserve University
ACS Nano | Year: 2010
Nitrogen-doped graphene (N-graphene) was synthesized by chemical vapor deposition of methane in the presence of ammonia. The resultant N-graphene was demonstrated to act as a metal-free electrode with a much better electrocatalytic activity, long-term operation stability, and tolerance to crossover effect than platinum for oxygen reduction via a four-electron pathway in alkaline fuel cells. To the best of our knowledge, this is the first report on the use of graphene and its derivatives as metal-free catalysts for oxygen reduction. The important role of N-doping to oxygen reduction reaction (ORR) can be applied to various carbon materials for the development of other metal-free efficient ORR catalysts for fuel cell applications, even new catalytic materials for applications beyond fuel cells. © 2010 American Chemical Society.
Leonard D.A.,Grand Valley State University |
Bonomo R.A.,Case Western Reserve University |
Powers R.A.,Grand Valley State University
Accounts of Chemical Research | Year: 2013
Despite 70 years of clinical use, β-lactam antibiotics still remain at the forefront of antimicrobial chemotherapy. The major challenge to these life-saving therapeutics is the presence of bacterial enzymes (i.e., β-lactamases) that can hydrolyze the β-lactam bond and inactivate the antibiotic. These enzymes can be grouped into four classes (A-D). Among the most genetically diverse are the class D β-lactamases. In this class are β-lactamases that can inactivate the entire spectrum of β-lactam antibiotics (penicillins, cephalosporins, and carbapenems).Class D β-lactamases are mostly found in Gram-negative bacteria such as Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, and Acinetobacter baumannii. The active-sites of class D β-lactamases contain an unusual N-carboxylated lysine post-translational modification. A strongly hydrophobic active-site helps create the conditions that allow the lysine to combine with CO2, and the resulting carbamate is stabilized by a number of hydrogen bonds. The carboxy-lysine plays a symmetric role in the reaction, serving as a general base to activate the serine nucleophile in the acylation reaction, and the deacylating water in the second step.There are more than 250 class D β-lactamases described, and the full set of variants shows remarkable diversity with regard to substrate binding and turnover. Narrow-spectrum variants are most effective against the earliest generation penicillins and cephalosporins such as ampicillin and cephalothin. Extended-spectrum variants (also known as extended-spectrum β-lactamases, ESBLs) pose a more dangerous clinical threat as they possess a small number of substitutions that allow them to bind and hydrolyze later generation cephalosporins that contain bulkier side-chain constituents (e.g., cefotaxime, ceftazidime, and cefepime). Mutations that permit this versatility seem to cluster in the area surrounding an active-site tryptophan resulting in a widened active-site to accommodate the oxyimino side-chains of these cephalosporins. More concerning are the class D β-lactamases that hydrolyze clinically important carbapenem β-lactam drugs (e.g., imipenem). Whereas carbapenems irreversibly acylate and inhibit narrow-spectrum β-lactamases, class D carbapenemases are able to recruit and activate a deacylating water. The rotational orientation of the C6 hydroxyethyl group found on all carbapenem antibiotics likely plays a role in whether the deacylating water is effective or not.Inhibition of class D β-lactamases is a current challenge. Commercially available inhibitors that are active against other classes of β-lactamases are ineffective against class D enzymes. On the horizon are several compounds, consisting of both β-lactam derivatives and non-β-lactams, that have the potential of providing novel leads to design new mechanism-based inactivators that are effective against the class D enzymes. Several act synergistically when given in combination with a β-lactam antibiotic, and others show a unique mechanism of inhibition that is distinct from the traditional β-lactamase inhibitors. These studies will bolster structure-based inhibitor design efforts to facilitate the optimization and development of these compounds as class D inactivators. © 2013 American Chemical Society.
Osiris Therapeutics and Case Western Reserve University | Date: 2010-04-28
The osteoporosis treatment and infusion compositions of the invention increase the number of the patients own progenitor cells (hMSCs) and the reservoir of available bone-forming osteoblasts. They can be used to generate cortical and cancellous bone which has been lost as a result of post-menopausal osteoporosis, male idiopathic osteoporosis, congenital osteoporosis and other bone resorption diseases. Most cases of osteoporosis can be treated with a metered intravenous infusion of the composition of the invention over the course of 15-30 minutes, using customary cell reinfusion therapy techniques.
News Article | March 1, 2017
An enzyme that helps break down cholesterol may also be a therapeutic target to stave off neurologic diseases, including Alzheimer's and a rare genetic disorder, according to a new study published in the Journal of Biological Chemistry. Researchers from Case Western Reserve University School of Medicine, the National Institute of Standards and Technology, and Karolinska Institute in Sweden discovered that a specific enzyme in the brain could reduce the formation of debilitating brain lesions in the two diseases. A clinical trial to test the enzyme's potential as a therapeutic target is planned for later this year. The targeted enzyme's primary purpose is to eliminate excess cholesterol from the brain. But the researchers hypothesized it could also help remove another cholesterol-like molecule—cholestanol. Cholestanol is normally found in very low levels in the body, at least 500 times less often than cholesterol, but spikes in people with a rare, uncurable genetic disease called cerebrotendinous xanthomatosis. Patients with the disease slowly accumulate cholestanol in areas of the brain responsible for muscle coordination, causing seizures, involuntary movements, and cognitive decline. With help from the right enzymes, the debilitating accumulations could be eliminated. "We found that an enzyme called CYP46A1 not only eliminates cholesterol but also cholestanol from the brain," said Irina Pikuleva, PhD, study lead and Professor and Vice Chair of Research in the Department of Ophthalmology and Visual Sciences at Case Western Reserve University School of Medicine. "CYP46A1 also seems to eliminate cholestanol from many regions of the brain except the cerebellum." The findings explain why people with the rare genetic disease end up with toxic levels of cholestanol in their cerebellums specifically. Without the elimination process in that brain region, cholestanol accumulates and wreaks havoc on brain circuitry. The discovery is a huge step forward in understanding the mechanism behind the rare genetic disease and its associated brain lesions that have perplexed doctors for decades. Said Pikuleva, "This paper establishes a biochemical basis for the preferential lesion formation in the cerebrotendinous xanthomatosis brain, a finding that nobody could explain since this disease was described by L. von Bogaert in 1937." The study is also the first to implicate the enzyme CYP46A1 in cholestanol metabolism at all, which could inform other research related to lipid storage disorders. "Cholestanol accumulation in the body reflects an imbalance between its production and its elimination," said Pikuleva. Previous studies, by Pikuleva's study collaborator Ingemar Bjorkhem, PhD of Karolinska Institutet in Sweden, established how cholestanol is produced in the brain. In the new study, the team studied mice genetically engineered to lack enzymes involved in the process to decipher how cholestanol is eliminated. Mice in the experiments metabolized brain cholestanol at different rates in different brain regions, depending on the ratios of cholesterol- and cholestanol-processing enzymes present. Said Pikuleva, "We found there are differences in the way different brain regions eliminate cholesterol and cholestanol." The researchers suggest that enhancing the activity of CYP46A1 in the brain pharmacologically, or finding ways to steer it closer to pockets of cholestanol could help remove the harmful accumulations. The enzyme can be activated in mice by drugs already FDA-approved, including an HIV medication called efavirenz. Pikuleva is currently developing a clinical trial to test whether or not the HIV medication can activate CYP46A1 sufficiently in the human brain. The clinical trial is backed by the Alzheimer's Disease Drug Foundation. Said Pikuleva, "If successful, this trial will identify CYP46A1 as a new pharmacologic target not only for the treatment of people with mild cognitive impairment due to early stage Alzheimer's disease, but also for patients with cerebrotendinous xanthomatosis who do not respond to standard treatment." Explore further: Shape-changing enzyme suggests how small doses of anti-HIV drug might treat Alzheimer's More information: Natalia Mast et al, Cytochrome P450 27A1 Deficiency and Regional Differences in Brain Sterol Metabolism Cause Preferential Cholestanol Accumulation in the Cerebellum, Journal of Biological Chemistry (2017). DOI: 10.1074/jbc.M116.774760
News Article | March 1, 2017
An enzyme that helps break down cholesterol may also be a therapeutic target to stave off neurologic diseases, including Alzheimer's and a rare genetic disorder, according to a new study published in the Journal of Biological Chemistry. Researchers from Case Western Reserve University School of Medicine, the National Institute of Standards and Technology, and Karolinska Institute in Sweden discovered that a specific enzyme in the brain could reduce the formation of debilitating brain lesions in the two diseases. A clinical trial to test the enzyme's potential as a therapeutic target is planned for later this year. The targeted enzyme's primary purpose is to eliminate excess cholesterol from the brain. But the researchers hypothesized it could also help remove another cholesterol-like molecule--cholestanol. Cholestanol is normally found in very low levels in the body, at least 500 times less often than cholesterol, but spikes in people with a rare, uncurable genetic disease called cerebrotendinous xanthomatosis. Patients with the disease slowly accumulate cholestanol in areas of the brain responsible for muscle coordination, causing seizures, involuntary movements, and cognitive decline. With help from the right enzymes, the debilitating accumulations could be eliminated. "We found that an enzyme called CYP46A1 not only eliminates cholesterol but also cholestanol from the brain," said Irina Pikuleva, PhD, study lead and Professor and Vice Chair of Research in the Department of Ophthalmology and Visual Sciences at Case Western Reserve University School of Medicine. "CYP46A1 also seems to eliminate cholestanol from many regions of the brain except the cerebellum." The findings explain why people with the rare genetic disease end up with toxic levels of cholestanol in their cerebellums specifically. Without the elimination process in that brain region, cholestanol accumulates and wreaks havoc on brain circuitry. The discovery is a huge step forward in understanding the mechanism behind the rare genetic disease and its associated brain lesions that have perplexed doctors for decades. Said Pikuleva, "This paper establishes a biochemical basis for the preferential lesion formation in the cerebrotendinous xanthomatosis brain, a finding that nobody could explain since this disease was described by L. von Bogaert in 1937." The study is also the first to implicate the enzyme CYP46A1 in cholestanol metabolism at all, which could inform other research related to lipid storage disorders. "Cholestanol accumulation in the body reflects an imbalance between its production and its elimination," said Pikuleva. Previous studies, by Pikuleva's study collaborator Ingemar Bjorkhem, PhD of Karolinska Institutet in Sweden, established how cholestanol is produced in the brain. In the new study, the team studied mice genetically engineered to lack enzymes involved in the process to decipher how cholestanol is eliminated. Mice in the experiments metabolized brain cholestanol at different rates in different brain regions, depending on the ratios of cholesterol- and cholestanol-processing enzymes present. Said Pikuleva, "We found there are differences in the way different brain regions eliminate cholesterol and cholestanol." The researchers suggest that enhancing the activity of CYP46A1 in the brain pharmacologically, or finding ways to steer it closer to pockets of cholestanol could help remove the harmful accumulations. The enzyme can be activated in mice by drugs already FDA-approved, including an HIV medication called efavirenz. Pikuleva is currently developing a clinical trial to test whether or not the HIV medication can activate CYP46A1 sufficiently in the human brain. The clinical trial is backed by the Alzheimer's Drug Discovery Foundation. Said Pikuleva, "If successful, this trial will identify CYP46A1 as a new pharmacologic target not only for the treatment of people with mild cognitive impairment due to early stage Alzheimer's disease, but also for patients with cerebrotendinous xanthomatosis who do not respond to standard treatment." This work was supported in part by United States Public Health Service Grant GM62882 (to I.A.P) and P30 Core Grant EY11373. For more information about Case Western Reserve University School of Medicine, please visit: http://case. .
News Article | January 27, 2017
Scientists have inched closer to creating a human-animal hybrid as they reported growing human cells inside pig embryos. The feat may eventually lead to growing livers and other human organs in animals that could alleviate the shortage of donated organs for transplant patients. The process involves generating stem cells from the skin of a patient. The stem cells will be used to grow the desired new organ in a large animal such as pigs. The organ is then harvested to be transplanted back into the patient's body. Because the organ is made of the patient's own cells, the risk of immune rejection is little. For their study, the researchers injected pig embryos with three to 10 of human stem cells each and implanted these embryos into sows. After three to four weeks of development, researchers removed and examined 186 embryos and saw human cells after four weeks of development. The cells generated the precursors of heart, muscles, pancreas, liver, and spinal cord tissue in the animal embryos. "Interspecies blastocyst complementation enables organ-specific enrichment of xenogenic pluripotent stem cell (PSC) derivative," the researchers wrote in their study. "Interspecies blastocyst complementation might allow human organ generation in animals whose organ size, anatomy, and physiology are closer to humans." The researchers said that they plan to conduct tests that would focus the human cells to produce specific tissues that would avoid any contribution to the brain, eggs, and sperm will human cells. Among the issues that hamper the creation of chimeras, particularly those that use human cells, is the possibility that animals could be humanized in unintended ways. Human cells that get incorporated into the pig's brain may endow the animal with human qualities. Human cells that come to compose the reproductive tissues of an animal may also result in undesirable outcomes. Despite concerns, the ability to grow human cells in animals also has life-saving implications particularly among organ transplant patients. Human organ transplants tend to be complicated medical procedures that usually results in the patient's body rejecting the donated organ. Because of organ shortage, some patients also die before an organ becomes available. Figures from the U.S. Department of Health and Human Services show that more than 119,000 individuals are on the national waiting for an organ transplant. Twenty-two of those waiting for transplant die every day. Researchers Jason Wu, from the Salk Institute in La, Jolla, California, and colleagues, whose experiment was reported in Cell on Thursday, hope to eventually take human cells from individuals in need of transplant and grow the cells in an animal embryo to be later transplanted back into the patient without being rejected. "There isn't a need to get into a debate about moral humanization if scientists target the organs where the human cells will go," said Insoo Hyun, from Case Western Reserve University. "Scientists are not making chimeras just for fun — it's to relieve the dire shortage of transplantable organs." © 2017 Tech Times, All rights reserved. Do not reproduce without permission.
News Article | March 1, 2017
Carole K. Richards Recognized as a Professional of the Year by Strathmore's Who's Who Worldwide Publication Chagrin Falls, OH, March 01, 2017 --( About Carole K. Richards Ms. Richards is the President and Founder of North Coast Education Services (NCES), which offers Richards Learning Systems (RLS) a research-based multi-sensory systematic language arts curriculum. NCES provides individualized in-home tutoring to individuals and school districts with a specialty in learning disabilities. It serves seven Northeast Ohio counties, and all of Ohio for clients on the Ohio Autism Scholarship Program. She founded NCES in 1985. Ms. Richards created RLS because there is such a huge need for quality literacy instruction. She started a nonprofit in 1992, the Creative Education Institute (CEI), with a mission to effect change through improved literacy. She previously served as a school teacher in Cleveland. Ms. Richards received the NorTech Innovation Award in Cleveland, Ohio, the Intellectual Property Innovation for RICHARDS READ Systematic Language, and placed on the Entrepreneur 360 List in Entrepreneur Magazine. She is a three time winner of the Blue Ribbon Award from the U.S. Chamber of Commerce Small Business, and a 5 time winner of the Ohio Weatherhead 100 from the Weatherhead School of Business at Case Western Reserve University in Cleveland. Ms. Richards received the President’s Award from the National Tutoring Association, a Professional in Residence from Miami University in Oxford, Ohio, was a two time winner of the Top 10 Award from the National Association of Business Owners and a two time winner of the NEO Success Award from Inside Business Magazine in Cleveland. Her published works include the Richards Learning Systems; How to Break the ETR Code, Understand IQ and Achievement Tests, A Workbook & Reference Guide for Parents and Educators, "Tastes Good and Healthy Too Cookbook (allergy-free cooking)" and her monthly column which runs in 4 local newspapers. Ms. Richards is especially proud of how she grew NCES from a dining room business to a service with 300 professional tutors. She founded the Creative Education Institute to improve literacy. Innovation: In a partnership with the Cleveland Metropolitan Schools, CEI is raising funds to create a series of short episodic videos that will train teachers to teach reading at the same time children learn to read. This video project is based on Richards Learning Systems Phonics program published 25 years ago. Born in Cleveland, Ohio, Ms. Richards obtained a B.S. in Elementary Education from Miami University in Ohio in 1971. She married John Kusik on February 15, 2005 and has two children. In her spare time she enjoys travel, tennis, cooking and sewing. For further information, contact About Strathmore’s Who’s Who Worldwide Strathmore’s Who’s Who Worldwide highlights the professional lives of individuals from every significant field or industry including business, medicine, law, education, art, government and entertainment. Strathmore’s Who’s Who Worldwide is both an online and hard cover publication where we provide our members’ current and pertinent business information. It is also a biographical information source for thousands of researchers, journalists, librarians and executive search firms throughout the world. Our goal is to ensure that our members receive all of the networking, exposure and recognition capabilities to potentially increase their business. Chagrin Falls, OH, March 01, 2017 --( PR.com )-- Carole K. Richards of Chagrin Falls, Ohio has been recognized as a Professional of the Year for 2017 by Strathmore’s Who’s Who Worldwide Edition for her outstanding contributions and achievements for over 46 years in the field of education service.About Carole K. RichardsMs. Richards is the President and Founder of North Coast Education Services (NCES), which offers Richards Learning Systems (RLS) a research-based multi-sensory systematic language arts curriculum. NCES provides individualized in-home tutoring to individuals and school districts with a specialty in learning disabilities. It serves seven Northeast Ohio counties, and all of Ohio for clients on the Ohio Autism Scholarship Program. She founded NCES in 1985. Ms. Richards created RLS because there is such a huge need for quality literacy instruction. She started a nonprofit in 1992, the Creative Education Institute (CEI), with a mission to effect change through improved literacy. She previously served as a school teacher in Cleveland.Ms. Richards received the NorTech Innovation Award in Cleveland, Ohio, the Intellectual Property Innovation for RICHARDS READ Systematic Language, and placed on the Entrepreneur 360 List in Entrepreneur Magazine. She is a three time winner of the Blue Ribbon Award from the U.S. Chamber of Commerce Small Business, and a 5 time winner of the Ohio Weatherhead 100 from the Weatherhead School of Business at Case Western Reserve University in Cleveland. Ms. Richards received the President’s Award from the National Tutoring Association, a Professional in Residence from Miami University in Oxford, Ohio, was a two time winner of the Top 10 Award from the National Association of Business Owners and a two time winner of the NEO Success Award from Inside Business Magazine in Cleveland. Her published works include the Richards Learning Systems; How to Break the ETR Code, Understand IQ and Achievement Tests, A Workbook & Reference Guide for Parents and Educators, "Tastes Good and Healthy Too Cookbook (allergy-free cooking)" and her monthly column which runs in 4 local newspapers.Ms. Richards is especially proud of how she grew NCES from a dining room business to a service with 300 professional tutors. She founded the Creative Education Institute to improve literacy.Innovation: In a partnership with the Cleveland Metropolitan Schools, CEI is raising funds to create a series of short episodic videos that will train teachers to teach reading at the same time children learn to read. This video project is based on Richards Learning Systems Phonics program published 25 years ago.Born in Cleveland, Ohio, Ms. Richards obtained a B.S. in Elementary Education from Miami University in Ohio in 1971. She married John Kusik on February 15, 2005 and has two children. In her spare time she enjoys travel, tennis, cooking and sewing.For further information, contact www.northcoasted.com . Carole’s email: email@example.com or firstname.lastname@example.org, (800) 335-7984About Strathmore’s Who’s Who WorldwideStrathmore’s Who’s Who Worldwide highlights the professional lives of individuals from every significant field or industry including business, medicine, law, education, art, government and entertainment. Strathmore’s Who’s Who Worldwide is both an online and hard cover publication where we provide our members’ current and pertinent business information. It is also a biographical information source for thousands of researchers, journalists, librarians and executive search firms throughout the world. Our goal is to ensure that our members receive all of the networking, exposure and recognition capabilities to potentially increase their business. Click here to view the list of recent Press Releases from Strathmore Worldwide
News Article | February 27, 2017
Scientists at Rutgers and other universities have created a new way to identify the state and fate of stem cells earlier than previously possible. Understanding a stem cell's fate -- the type of cell it will eventually become -- and how far along it is in the process of development can help scientists better manipulate cells for stem cell therapy. The beauty of the method is its simplicity and versatility, said Prabhas V. Moghe, distinguished professor of biomedical engineering and chemical and biochemical engineering at Rutgers and senior author of a study published recently in the journal Scientific Reports. "It will usher in the next wave of studies and findings," he added. Existing approaches to assess the states of stem cells look at the overall population of cells but aren't specific enough to identify individual cells' fates. But when implanting stem cells (during a bone marrow transplant following cancer treatment, for example), knowing that each cell will become the desired cell type is essential. Furthermore, many protein markers used to distinguish cell types don't show up until after the cell has transitioned, which can be too late for some applications. To identify earlier signals of a stem cell's fate, an interdisciplinary team from multiple universities collaborated to use super-resolution microscopy to analyze epigenetic modifications. Epigenetic modifications change how DNA is wrapped up within the nucleus, allowing different genes to be expressed. Some modifications signal that a stem cell is transitioning into a particular type of cell, such as a blood, bone or fat cell. Using the new method, the team of scientists was able to determine a cell's fate days before other techniques. "Having the ability to visualize a stem cell's future will take some of the questions out of using stem cells to help regenerate tissue and treat diseases," says Rosemarie Hunziker, program director for Tissue Engineering and Regenerative Medicine at the National Institute of Biomedical Imaging and Bioengineering. "It's a relatively simple way to get a jump on determining the right cells to use." The approach, called EDICTS (Epi-mark Descriptor Imaging of Cell Transitional States), involves labeling epigenetic modifications and then imaging the cells with super resolution to see the precise location of the marks. "We're able to demarcate and catch changes in these cells that are actually not distinguished by established techniques such as mass spectrometry," Moghe said. He described the method as "fingerprinting the guts of the cell," and the results are quantifiable descriptors of each cell's organization (for example, how particular modifications are distributed throughout the nuclei). The team demonstrated the method's capabilities by measuring two types of epigenetic modifications in the nuclei of human stem cells cultured in a dish. They added chemicals that coaxed some of the cells to become fat cells and others to become bone, while another set served as control. Within three days, the localization of the modifications varied in cells destined for different fates, two to four days before traditional methods could identify such differences between the cells. The technique had the specificity to look at regional changes within individual cells, while existing techniques can only measure total levels of modifications among the entire population of cells. "The levels are not significantly different, but how they're organized is different and that seems to correlate with the fact that these cells are actually exhibiting different fates," Moghe said. "It allows us to take out a single cell from a population of dissimilar cells," which can help researchers select particular cells for different stem cell applications. The method is as easy as labeling, staining and imaging cells - techniques already familiar to many researchers, he said. As the microscopes capable of super resolution imaging become more widely available, scientists can use it to sort and screen different types of cells, understand how a particular drug may disrupt epigenetic signaling, or ensure that stem cells to be implanted won't transform into the wrong cell type. - Teal Burrell for the National Institute of Biomedical Imaging and Bioengineering. The study's lead author is Joseph J. Kim, formerly of Rutgers and now at the Stanford University School of Medicine. Other authors include Neal K. Bennett, Mitchel S. Devita, Sanjay Chahar and Michael P. Verzi of Rutgers; Satish Viswanath and Anant Madabhushi of Case Western Reserve University; Eunjee A. Lee, Giyoung Jung and Nathaniel S. Hwang of Seoul National University; Paul P. Shao of Princeton University; Erin P. Childers of the University of Akron; Shichong Liu of the University of Pennsylvania; Anthony Kulesa, formerly of Rutgers and now at MIT; Benjamin A. Garcia of the University of Pennsylvania; and Matthew L. Becker of the University of Akron. The corresponding author and lead PI on the study is Prabhas V. Moghe of Rutgers.
He K.,Case Western Reserve University |
Poole C.,Case Western Reserve University |
Mak K.F.,Cornell University |
Shan J.,Case Western Reserve University
Nano Letters | Year: 2013
We demonstrate the continuous tuning of the electronic structure of atomically thin MoS2 on flexible substrates by applying a uniaxial tensile strain. A redshift at a rate of ∼70 meV per percent applied strain for direct gap transitions, and at a rate 1.6 times larger for indirect gap transitions, has been determined by absorption and photoluminescence spectroscopy. Our result, in excellent agreement with first principles calculations, demonstrates the potential of two-dimensional crystals for applications in flexible electronics and optoelectronics. © 2013 American Chemical Society.
Mieyal J.J.,Case Western Reserve University |
Mieyal J.J.,Louis okes Veterans Affairs Medical Research Center |
Chock P.B.,U.S. National Institutes of Health
Antioxidants and Redox Signaling | Year: 2012
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have become recognized as second messengers for initiating and/or regulating vital cellular signaling pathways, and they are known also as deleterious mediators of cellular stress and cell death. ROS and RNS, and their cross products like peroxynitrite, react primarily with cysteine residues whose oxidative modification leads to functional alterations in the proteins. In this Forum, the collection of six review articles presents a perspective on the broad biological impact of cysteine modifications in health and disease from the molecular to the cellular and organismal levels, focusing in particular on reversible protein-S-glutathionylation and its central role in transducing redox signals as well as protecting proteins from irreversible cysteine oxidation. The Forum review articles consider the role of S-glutationylation in regulation of the peroxiredoxin enzymes, the special redox environment of the mitochondria, redox regulation pertinent to the function of the cardiovascular system, mechanisms of redox-activated apoptosis in the pulmonary system, and the role of glutathionylation in the initiation, propagation, and treatment of neurodegenerative diseases. Several common themes emerge from these reviews; notably, the probability of crosstalk between signaling/regulation mechanisms involving protein-S-nitrosylation and protein-S-glutathionylation, and the need for quantitative analysis of the relationship between specific cysteine modifications and corresponding functional changes in various cellular contexts. © 2012, Mary Ann Liebert, Inc.
Pikuleva I.A.,Case Western Reserve University |
Curcio C.A.,University of Alabama at Birmingham
Progress in Retinal and Eye Research | Year: 2014
Historically understudied, cholesterol in the retina is receiving more attention now because of genetic studies showing that several cholesterol-related genes are risk factors for age-related macular degeneration (AMD) and because of eye pathology studies showing high cholesterol content of drusen, aging Bruch's membrane, and newly found subretinal lesions. The challenge before us is determining how the cholesterol-AMD link is realized. Meeting this challenge will require an excellent understanding these genes' roles in retinal physiology and how chorioretinal cholesterol is maintained. In the first half of this review, we will succinctly summarize physico-chemical properties of cholesterol, its distribution in the human body, general principles of maintenance and metabolism, and differences in cholesterol handling in human and mouse that impact on experimental approaches. This information will provide a backdrop to the second part of the review focusing on unique aspects of chorioretinal cholesterol homeostasis, aging in Bruch's membrane, cholesterol in AMD lesions, a model for lesion biogenesis, a model for macular vulnerability based on vascular biology, and alignment of AMD-related genes and pathobiology using cholesterol and an atherosclerosis-like progression as unifying features. We conclude with recommendations for the most important research steps we can take towards delineating the cholesterol-AMD link. © 2014 Elsevier Ltd.
Zhang J.,Case Western Reserve University |
Zhao Z.,University of North Texas |
Xia Z.,University of North Texas |
Dai L.,Case Western Reserve University
Nature Nanotechnology | Year: 2015
The oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are traditionally carried out with noble metals (such as Pt) and metal oxides (such as RuO2 and MnO2) as catalysts, respectively. However, these metal-based catalysts often suffer from multiple disadvantages, including high cost, low selectivity, poor stability and detrimental environmental effects. Here, we describe a mesoporous carbon foam co-doped with nitrogen and phosphorus that has a large surface area of ∼1,663 m2 g-1 and good electrocatalytic properties for both ORR and OER. This material was fabricated using a scalable, one-step process involving the pyrolysis of a polyaniline aerogel synthesized in the presence of phytic acid. We then tested the suitability of this N,P-doped carbon foam as an air electrode for primary and rechargeable Zn-air batteries. Primary batteries demonstrated an open-circuit potential of 1.48 V, a specific capacity of 735 mAha gZn -1 (corresponding to an energy density of 835 Wh kgZn -1), a peak power density of 55 mW cm-2, and stable operation for 240 h after mechanical recharging. Two-electrode rechargeable batteries could be cycled stably for 180 cycles at 2 mA cm-2. We also examine the activity of our carbon foam for both OER and ORR independently, in a three-electrode configuration, and discuss ways in which the Zn-air battery can be further improved. Finally, our density functional theory calculations reveal that the N,P co-doping and graphene edge effects are essential for the bifunctional electrocatalytic activity of our material. © 2015 Macmillan Publishers Limited. All rights reserved.
Lin Z.,Cornell University |
Lin Z.,Case Western Reserve University
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2010
Objective-: A central function of the endothelium is to serve as a selective barrier that regulates fluid and solute exchange. Although perturbation of barrier function can contribute to numerous disease states, our understanding of the molecular mechanisms regulating this aspect of endothelial biology remains incompletely understood. Accumulating evidence implicates the Kruppel-like factor 2 (KLF2) as a key regulator of endothelial function. However, its role in vascular barrier function is unknown. Methods and results-: To assess the role of KLF2 in vascular barrier function in vivo, we measured the leakage of Evans blue dye into interstitial tissues of the mouse ear after treatment with mustard oil. By comparison with KLF2+/- mice, KLF 2+/- mice exhibited a significantly higher degree of vascular leak. In accordance with our in vivo observation, adenoviral overexpression of KLF2 in human umbilical vein endothelial cells strongly attenuated the increase of endothelial leakage by thrombin and H2O2 as measured by fluorescein isothiocyanate dextrans (FITC-dextran) passage. Conversely, KLF2 deficiency in human umbilical vein endothelial cells and primary endothelial cells derived from KLF2+/- mice exhibited a marked increase in thrombin and H2O2-induced permeability. Mechanistically, our studies indicate that KLF2 confers barrier-protection via differential effects on the expression of key junction protein occludin and modification of a signaling molecule (myosin light chain) that regulate endothelial barrier integrity. Conclusion-: These observations identify KLF2 as a novel transcriptional regulator of vascular barrier function. © 2010 American Heart Association, Inc.
Case Western Reserve University, Rice University, University of Maryland College Park and EnvisionTEC Inc. | Date: 2011-08-22
A process for additive manufacturing of a resorbable implant to be implanted into a patient includes providing a biocompatible resin including a liquid light-polymerizable material that is resorbable after polymerization and an initiator. The process further includes actuating an additive manufacturing apparatus to expose an amount of the biocompatible resin to light to at least partially cure the exposed amount of biocompatible resin to form a layer of the resorbable implant and actuating the additive manufacturing apparatus to expose at least some additional amount of biocompatible resin to light to at least partially cure the exposed additional amount of biocompatible resin to form an additional layer of the resorbable implant and to at least partially overcure previously cured layers to cause at least some interlayer binding between the previously cured layers and the additional layer.
Hospital For Sick Children, Case Western Reserve University, University of North Carolina at Chapel Hill and Johns Hopkins University | Date: 2011-09-30
Disclosed herein are compositions and methods for and treating Cystic Fibrosis lung disease severity and/or secondary manifestations, including meconium ileus and CF related liver disease.
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 125.37K | Year: 2012
DESCRIPTION (provided by applicant): Abnormal urethral sphincter contractions can prevent bladder emptying and cause significant morbidity and reduction in quality of life after neurological disease or injury. Existing treatment options are of limited effectiveness, destructive, or possess systemic side effects, reducing patient acceptance of these therapies. Electrical stimulation of sacral motor nerve roots can restore bladder voiding after SCI; however only when combined with the irreversible surgical transection of the sensory spinal nerve roots (i.e., a dorsal rhizotomy) to eliminate reflex contractions of the urethral sphincter that otherwise prevent voiding. Other effects of the rhizotomy (loss of remaining sensation, reflex sexual function and reflexdefecation) limit the clinical acceptance of this procedure. The goal of this project is to develop a neural prosthesis that uses electrical pudendal nerve block to eliminate urethral sphincter activation and allow bladder voiding. High frequency nerve block provides, rapid, complete and reversible local nerve conduction block. We have demonstrated that bilateral pudendal nerve block can prevent urethral sphincter activation and produce bladder voiding equivalent to nerve transection in animals. We have also demonstrated that pudendal nerve block can be achieved with available nerve cuff electrodes approvable for human studies. Demonstration of electrical pudendal block and improved voiding in humans is the next major milestone to translate this approach tohumans. Implantation of a pudendal nerve cuff electrode for the feasibility study requires FDA approval of an investigational device exemption (IDE). This Phase I project will identify and prepare the necessary components for an FDA investigational deviceexemption (IDE) application and conduct a pre-IDE meeting with the FDA. This process and the pre-IDE FDA meeting will define the effort and resources required to obtain FDA approval to conduct the human feasibility trial in the next phase (next application). This Phase I project will also establish a screening procedure using temporary anesthetic pudendal nerve block and identify initial candidates for the implanted device. At the end of this Phase I project, we will be ready to assemble and submit an IDEto conduct the human feasibility study in the next phase. This approach is expected to expand the population of individuals who could benefit from neural prostheses to control the bladder, and thereby improve their health and quality of life while reducingcosts to the healthcare system. PUBLIC HEALTH RELEVANCE: Abnormal urethral sphincter contractions can prevent bladder emptying. This project begins the translation of a neural prosthesis to restore bladder voiding using electrical pudendal nerve block of the urethral sphincter.
News Article | February 15, 2017
Stories of cabin renovation and family bonding while surrounded by the natural beauty of Supin Lick Moutain in Rockingham Country, Virginia are detailed in William B. Pittard III’s memoir “Once Upon a Ridge.” The book describes over three decades of experiences from the Pittard family of six on the Shenandoah Valley Supin Lick Mountain, including the social mores of the locals. The unique lifestyle of mountain folk is characterized by hard manual labor, awareness of God, willingness to assist those in need, and expectation that personal life decisions are respected by others. “The book is directed to more traditional family oriented readers,” said Pittard “Those who are reassured by spirituality, enjoy nature, and seek outdoor activities will find the book refreshing and rewarding.” While life for Supin Lick Mountain residents has changed in the last century with electricity, telephones, and reliable forms of transportation, its setting of dirt and gravel roadways and expansive trees have provided a peaceful retreat for the Pittard family. “Once Upon a Ridge” highlights the Pittard family experiences in the midst of natural beauty and a unique mountain culture. “Once Upon a Ridge” By William B. Pittard III, MD, PhD, MPH ISBN: 978-1-49179-243-8 (softcover); 978-1-49179-244-5 (eBook) Available on Amazon, Barnes & Noble, and iUniverse About the author William B. Pittard III, MD, PhD, MPH, earned his medical degree from the University of Virginia, a master of public health degree in maternal and child health from the University of Alabama at Birmingham, and a Ph.D. in health services and policy management from the University of South Carolina. He is professor emeritus at the Medical University of South Carolina and formerly taught at Case Western Reserve University. To learn more, please visit http://www.pittardw.com.
Buchner D.A.,Case Western Reserve University |
Nadeau J.H.,Pacific Northwest Diabetes Research Institute
Genome Research | Year: 2015
Quantitative trait loci (QTLs) are being used to study genetic networks, protein functions, and systems properties that underlie phenotypic variation and disease risk in humans, model organisms, agricultural species, and natural populations. The challenges are many, beginning with the seemingly simple tasks of mapping QTLs and identifying their underlying genetic determinants. Various specialized resources have been developed to study complex traits in many model organisms. In the mouse, remarkably different pictures of genetic architectures are emerging. Chromosome Substitution Strains (CSSs) reveal many QTLs, large phenotypic effects, pervasive epistasis, and readily identified genetic variants. In contrast, other resources as well as genome-wide association studies (GWAS) in humans and other species reveal genetic architectures dominated with a relatively modest number of QTLs that have small individual and combined phenotypic effects. These contrasting architectures are the result of intrinsic differences in the study designs underlying different resources. The CSSs examine contextdependent phenotypic effects independently among individual genotypes, whereas with GWAS and other mouse resources, the average effect of each QTL is assessed among many individuals with heterogeneous genetic backgrounds. We argue that variation of genetic architectures among individuals is as important as population averages. Each of these important resources has particular merits and specific applications for these individual and population perspectives. Collectively, these resources together with high-throughput genotyping, sequencing and genetic engineering technologies, and information repositories highlight the power of the mouse for genetic, functional, and systems studies of complex traits and disease models. © 2015 Buchner and Nadeau.
De Rham C.,University of Geneva |
Gabadadze G.,New York University |
Tolley A.J.,Case Western Reserve University
Physical Review Letters | Year: 2011
We construct four-dimensional covariant nonlinear theories of massive gravity which are ghost-free in the decoupling limit to all orders. These theories resum explicitly all the nonlinear terms of an effective field theory of massive gravity. We show that away from the decoupling limit the Hamiltonian constraint is maintained at least up to and including quartic order in nonlinearities, hence excluding the possibility of the Boulware-Deser ghost up to this order. We also show that the same remains true to all orders in a similar toy model. © 2011 American Physical Society.
Salon J.A.,Amgen |
Lodowski D.T.,Case Western Reserve University |
Palczewski K.,Case Western Reserve University
Pharmacological Reviews | Year: 2011
Crucial as molecular sensors for many vital physiological processes, seven-transmembrane domain G protein-coupled receptors (GPCRs) comprise the largest family of proteins targeted by drug discovery. Together with structures of the prototypical GPCR rhodopsin, solved structures of other liganded GPCRs promise to provide insights into the structural basis of the superfamily's biochemical functions and assist in the development of new therapeutic modalities and drugs. One of the greatest technical and theoretical challenges to elucidating and exploiting structure-function relationships in these systems is the emerging concept of GPCR conformational flexibility and its cause-effect relationship for receptor-receptor and receptor-effector interactions. Such conformational changes can be subtle and triggered by relatively small binding energy effects, leading to full or partial efficacy in the activation or inactivation of the receptor system at large. Pharmacological dogma generally dictates that these changes manifest themselves through kinetic modulation of the receptor's G protein partners. Atomic resolution information derived from increasingly available receptor structures provides an entre ́e to the understanding of these events and practically applying it to drug design. Supported by structure-activity relationship information arising from empirical screening, a unified structural model of GPCR activation/inactivation promises to both accelerate drug discovery in this field and improve our fundamental understanding of structure-based drug design in general. This review discusses fundamental problems that persist in drug design and GPCR structural determination. © 2011 by The American Society for Pharmacology and Experimental Therapeutics.
Linder P.,University of Geneva |
Jankowsky E.,Case Western Reserve University
Nature Reviews Molecular Cell Biology | Year: 2011
RNA helicases of the DEAD box family are present in all eukaryotic cells and in many bacteria and Archaea. These highly conserved enzymes are required for RNA metabolism from transcription to degradation and are therefore important players in gene expression. DEAD box proteins use ATP to unwind short duplex RNA in an unusual fashion and remodel RNA-protein complexes, but they can also function as ATP-dependent RNA clamps to provide nucleation centres that establish larger RNA-protein complexes. Structural, mechanistic and molecular biological studies have started to reveal how these conserved proteins can perform such diverse functions and how accessory proteins have a central role in their regulation. © 2011 Macmillan Publishers Limited. All rights reserved.
Li Q.,Indiana University Bloomington |
Zhang S.,Case Western Reserve University |
Dai L.,Case Western Reserve University |
Li L.-S.,Indiana University Bloomington
Journal of the American Chemical Society | Year: 2012
Nitrogen doping has been a powerful way to modify the properties of carbon materials ranging from activated carbon to graphene. Here we report on a solution chemistry approach to nitrogen-doped colloidal graphene quantum dots with well-defined structures. N-doping was demonstrated to significantly affect the properties of the quantum dots, including the emergence of size-dependent electrocatalytic activity for the oxygen reduction reaction. © 2012 American Chemical Society.
Spivak B.,University of Washington |
Kravchenko S.V.,Northeastern University |
Kivelson S.A.,Stanford University |
Gao X.P.A.,Case Western Reserve University
Reviews of Modern Physics | Year: 2010
An overview of the measured transport properties of the two dimensional electron fluids in high mobility semiconductor devices with low electron densities is presented as well as some of the theories that have been proposed to account for them. Many features of the observations are not easily reconciled with a description based on the well understood physics of weakly interacting quasiparticles in a disordered medium. Rather, they reflect new physics associated with strong correlation effects, which warrant further study. © 2010 The American Physical Society.
Case Western Reserve University and The University Of Texas System | Date: 2015-01-12
A method of assessing soil heave includes providing a plurality of determined values of a shear modulus of soil, the determined values being values of the shear modulus of the soil at different times; and determining a change over time in the shear modulus of the soil, based on the plurality of determined values of the shear modulus of the soil. The soil may have been treated by adding a stabilizer to the soil. The soil may be hydrated. A system for assessing soil heave includes a bender element disposed in soil, for determining a change over time of a shear modulus of the soil, and a time domain reflectometer probe disposed in the soil, for determining a change over time of moisture content of the soil. The determined change over time of the shear modulus and the determined change over time of the moisture content are used to assess heaving of the soil.
The University Of Texas System and Case Western Reserve University | Date: 2013-12-17
This application describes methods and compositions for detecting and treating C6Orf150-associated neoplasia. Differential methylation of the C6Orf150 nucleotide sequences has been observed in C6Orf150-associated neoplasia such as colon neoplasia.
News Article | February 8, 2017
This is a frame of the 'Trinity' fireball, .025 seconds after detonation. —How did the moon form? Scientists base their models largely on data from moon rocks and meteorites. But those just provide momentary snapshots, not geological processes in action. To test their models, scientists need to figure out just how, and under what conditions, those rocks may have formed. And one team may have just found a new way of thinking about lunar formation. Moon-building happens on a massive scale, so "we were looking for an analogue that was large-scale enough ... to replicate what we thought was going on during the early process of planet formation," James Day, a geochemist at the University of California San Diego, explains in a phone interview with The Christian Science Monitor. Fortunately for Dr. Day and his colleagues, a real-life massive, super hot explosion took place just a few decades ago: the detonation of a nuclear bomb. And it, too, altered the chemistry of rocks. When the dust settled after a plutonium bomb was tested for the first time near Alamogordo, N.M., in July 1945, some of the red soil had become a light green glass. The glass was dubbed trinitite after the test site, called Trinity. "We can use the Trinity glasses – that came from this very profound experiment that's had a huge effect on human history – to scientific benefit," Day says. By studying the trinitite, Day hoped to glean insight into how the material that formed the moon might have changed during, if it formed according to the canonical model of lunar formation. In that classic "great impact" model, a Mars-sized object slammed into the early Earth, vaporizing some material and blasting other rocks from Earth's surface into a disk in Earth's orbit that then accreted to form the moon. What does that have to do with a nuclear bomb test? The impact from the Mars-sized body was probably violent enough to deplete some of the volatile elements in the material that eventually formed the moon, explains Day. Similarly, he thought, the nuclear explosion might have made the trinitite depleted in volatiles. The researchers focused in on the volatile element zinc. The idea was that the hot, high-pressure conditions of the nuclear explosion would mimic the conditions thought to occur in the great impact model and cause evaporative fractionation. In other words, the lighter isotope of zinc would have been more likely to evaporate in the explosion than the heavier isotope. Similar fractionation of zinc has been identified in some moon rocks, called mare basalts. "Our expectation was that when we measured these trinitites, these glasses that formed in the nuclear detonation, that we were either going to see nothing … that in fact, our hypothesis that there was volatile loss during this event was wrong," Day says, "or that we would approach the theoretical values that have been calculated" for the giant impact model, which suggested more loss than the moon rocks displayed. But, he says, it was "startling" how close the zinc composition of the glasses looked to the lunar rocks. Day and his colleagues report their findings in a paper published Wednesday in the journal Science Advances. Does this really tell us anything about the moon? James Van Orman, a geochemist at Case Western Reserve University who was not part of Day's team studying the trinitite, says it's a "creative and unique" idea to use the products of a nuclear test to better understand how such conditions alter a rock's chemical make-up. "There is no question that this constraint on Zn isotopic fractionation during evaporation will be valuable in modeling volatile loss from the Moon, and comparing the models to data from lunar samples," Dr. Van Orman writes in an email to the Monitor. But to draw conclusions about the moon's formation from this one study may be a bit of a leap, he says. Day agrees that his research can't really say much about the mechanism of how the moon may have formed. "All it tells us is that the conditions that we would expect, of high temperatures, very Hadean-like conditions," he says, "were occurring at the time that the moon formed." But Van Orman says it might not even address the event that formed the moon. "This study shows clearly that evaporative loss of Zn can explain the heavy zinc isotopic composition of the mare basalts," he explains. But that doesn't mean it's the only way to explain that composition. The mare basalts are volcanic rocks that cooled from lavas that may had time to degas before they hardened, he says. "I'm not convinced that the evaporative fractionation was associated with lunar formation, rather than later magmatic degassing," Van Orman says. "You don't have to do it during the giant impact," agrees David Stevenson, a planetary scientist at the California Institute of Technology who also was not involved in the study. "There is a big difference between identifying the results of a process and directly applying the specifics of what happened in the Trinity test with what happens in planet formation," Dr. Stevenson writes in an email to the Monitor. "So I doubt that science by analogy (which is what they're doing) is very useful, but I seen value in their work nonetheless." This new study, he says, "quantifies a process that happens when you severely heat a rock (more precisely a droplet of magma). That's useful." Jay Melosh, a geophysicist at Purdue University, suggests that older crustal moon rocks, perhaps from the lunar highlands, may have been a better choice than the mare basalts to compare with the trinitite. Applying this study to questions about the moon's formation may actually complicate the picture, Dr. Melosh says. Scientists thought they had it all figured out decades ago, he explains in a phone interview with the Monitor. But when researchers got better at measuring isotopic differences, they realized the canonical model had a big problem. Melosh refers to this puzzle as "the isotopic conundrum." In the classic model, researchers would expect to see these isotopic fractionations across other volatile elements in moon rocks, like potassium. "In fact," he says, "we don't." [Editor's note: Following the publication of this article, Day pointed out that a paper published in Nature in October 2016 has found evidence of fractionation of potassium isotopes in lunar rock.] Since this isotopic puzzle has arisen, many scientists have tried to tweak the giant impact model to resolve it. Some have proposed that the impact was particularly violent, while others have thought more "out-of-the-box" and suggested that the moon may actually be made up of many mini-moons. The fact that zinc is isotopically fractionated in the moon rocks but potassium is not "adds to the many mysteries about the moon," Melosh says. "The moon certainly is giving us a lot of puzzles."
News Article | February 21, 2017
21 février 2017 Sophia Antipolis, France Nicox S.A. (Euronext Paris: FR0013018124, COX, éligible PEA-PME), société internationale de Recherche et Développement en ophtalmologie, annonce aujourd'hui la présentation de résultats précliniques pour son nouveau composé donneur d'oxyde nitrique (NO), le NCX 667, à la 13ème réunion scientifique de l'Association for Ocular Pharmacology and Therapeutics (AOPT) qui s'est tenue du 16 au 19 février 2017 à Florence, Italie. Le NCX 667, molécule synthétisée par Nicox, est le composé leader d'une nouvelle classe de donneurs d'oxyde nitrique purs de nouvelle génération conçus pour optimiser la dose d'oxyde nitrique et réduire la pression intraoculaire (PIO) chez des patients atteints de glaucome à angle ouvert (GAO) ou d'hypertension oculaire. Les résultats précliniques du NCX 667 présentés à la réunion annuelle de l'AOPT par Impagnatiello et al1 dans des modèles d'hypertension oculaire et de glaucome chez le lapin et des primates non humains après administration unique ou répétée ont montré une réduction de la pression intraoculaire (PIO) de 20% ou plus indépendante du modèle et de l'espèce animale utilisée. En outre, l'administration répétée du NCX 667 entraîne une réduction prolongée de la PIO sans signes de tachyphylaxie ou d'inconfort oculaire. Des données issues de divers modèles expérimentaux d'animaux couplées à de récentes études cliniques étayent l'importance du rôle de l'oxyde nitrique dans la réduction de la pression intraoculaire en améliorant le drainage de l'humeur aqueuse par la voie d'écoulement conventionnelle. Le glaucome à angle ouvert est une pathologie oculaire fréquente affectant environ 2% de la population adulte de plus de 40 ans et est la deuxième cause de cécité dans le monde2. A propos du NCX 667 Le NCX 667, développé par Nicox, a déjà démontré des résultats précliniques prometteurs dans deux modèles d'hypertension oculaire et de glaucome. Dans ces deux modèles, le NCX 667 s'est révélé bien toléré et efficace pour réduire la pression intraoculaire (PIO). Ces résultats ont été choisis par le comité d'organisation du congrès ARVO 2015 comme « sujet d'intérêt » (Hot Topic), une sélection saluant les travaux de recherche les plus récents et les plus innovants. Notes : NCX 667, a lead nitric oxide (NO)-donating compound for a new class of ocular hypotensive agents F. Impagnatiello1, E. Bastia1, N. Almirante1, C. Toris2, C. Lanzi3, E. Ongini1, E. Masini3, M.V.W Bergamini4 1Nicox Research Institute, Milan, Italy; 2Department of Ophthalmology, Case Western Reserve University, Cleveland, OH, USA; 3Department of NEUROFARBA, University of Florence, Florence, Italy; 4Nicox Ophthalmics, Inc., Fort Worth, TX, USA Glaucoma, Open-angle - https://nei.nih.gov/eyedata/glaucoma, accessed February 13, 2017
News Article | February 21, 2017
February 21, 2017 Sophia Antipolis, France Nicox S.A. (Euronext Paris: FR0013018124, COX), the international ophthalmic R&D company, today announced that preclinical results from its novel nitric oxide (NO) donating compound, NCX 667, were presented at the Association for Ocular Pharmacology and Therapeutics (AOPT) 13th Scientific Meeting, held from February 16-19, 2017, in Florence, Italy. NCX 667, synthesized by Nicox, is the lead compound of a new class of next-generation stand-alone NO-donors, which are designed to optimize NO dosing and enable intraocular pressure (IOP) lowering in patients with open angle glaucoma (OAG) or ocular hypertension. The AOPT 2017 abstract by Impagnatiello et al1 presented preclinical results obtained with NCX 667 in rabbit and non-human primate models of ocular hypertension and glaucoma following single and repeated treatment schedules. NCX 667 appeared to lower IOP by 20% or more regardless of the specific model and animal species used. Furthermore, repeated acute dosing of NCX 667 elicits sustained IOP-lowering activity over time with no signs of tachyphylaxis or ocular discomfort. Data from a variety of experimental animal models coupled with recent clinical studies strongly support an important role of NO in lowering IOP by enhancing aqueous humor drainage via the conventional outflow route. Open angle glaucoma is a common ocular disorder affecting about 2% of the adult population over 40 years old and is the second-leading cause of blindness worldwide.2 About NCX 667 Developed by Nicox, NCX 667 already demonstrated promising preclinical results in two preclinical models of ocular hypertension and glaucoma. In both models, NCX 667 appeared well-tolerated and effective in reducing intra-ocular pressure (IOP). These results were selected by the ARVO 2015 Annual Meeting Program Committee as a 'Hot Topic', as representing the newest and most innovative research being conducted. Notes: NCX 667, a lead nitric oxide (NO)-donating compound for a new class of ocular hypotensive agents F. Impagnatiello1, E. Bastia1, N. Almirante1, C. Toris2, C. Lanzi3, E. Ongini1, E. Masini3, M.V.W Bergamini4 1Nicox Research Institute, Milan, Italy; 2Department of Ophthalmology, Case Western Reserve University, Cleveland, OH, USA; 3Department of NEUROFARBA, University of Florence, Florence, Italy; 4Nicox Ophthalmics, Inc., Fort Worth, TX, USA Glaucoma, Open-angle - https://nei.nih.gov/eyedata/glaucoma, accessed February 13, 2017
Geisler S.,Case Western Reserve University |
Geisler S.,ETH Zurich |
Coller J.,Case Western Reserve University
Nature Reviews Molecular Cell Biology | Year: 2013
The increased application of transcriptome-wide profiling approaches has led to an explosion in the number of documented long non-coding RNAs (lncRNAs). While these new and enigmatic players in the complex transcriptional milieu are encoded by a significant proportion of the genome, their functions are mostly unknown. Early discoveries support a paradigm in which lncRNAs regulate transcription via chromatin modulation, but new functions are steadily emerging. Given the biochemical versatility of RNA, lncRNAs may be used for various tasks, including post-transcriptional regulation, organization of protein complexes, cell-cell signalling and allosteric regulation of proteins. © 2013 Macmillan Publishers Limited. All rights reserved.
Tigno-Aranjuez J.T.,Case Western Reserve University |
Asara J.M.,Beth Israel Deaconess Medical Center |
Asara J.M.,Harvard University |
Abbott D.W.,Case Western Reserve University
Genes and Development | Year: 2010
Upon intracellular bacterial exposure, the Crohn's disease and sarcoidosis susceptibility protein NOD2 (nucleotide oligomerization domain protein 2) binds to the protein kinase RIP2 (receptor-interacting protein 2) to coordinate NF-κB (nuclear factor κ B)-mediated cytokine responses. While RIP2 clearly has kinase activity, the function of its kinase domain has been enigmatic. Although originally classified as a serine-threonine kinase based on homology scans, we find that RIP2 also has tyrosine kinase activity. RIP2 undergoes autophosphorylation on Tyr 474 (Y474). This phosphorylation event is necessary for effective NOD2 signaling and does not occur in the presence of the most common Crohn's disease-associated NOD2 allele. Given this tyrosine kinase activity, a small-molecule inhibitor screen designed to identify pharmacologic agents that inhibit RIP2's tyrosine kinase activity was performed. At nanomolar concentrations, the EGFR (epidermal growth factor receptor) tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva) were found to inhibit both RIP2 tyrosine phosphorylation and MDP (muramyl dipeptide)-induced cytokine release in a variety of NOD2 hyperactivation states. This effect is specific for RIP2 and does not depend on EGFR. The finding that RIP2 has tyrosine kinase activity and the finding that gefitinib and erlotinib, two agents already used clinically for cancer chemotherapy, can inhibit this activity suggest that RIP2's tyrosine kinase activity could be targeted specifically in the treatment of inflammatory diseases. © 2010 by Cold Spring Harbor Laboratory Press.
Mak K.F.,Columbia University |
Lee C.,Sungkyunkwan University |
Hone J.,Columbia University |
Shan J.,Case Western Reserve University |
Heinz T.F.,Columbia University
Physical Review Letters | Year: 2010
The electronic properties of ultrathin crystals of molybdenum disulfide consisting of N=1,2,...,6 S-Mo-S monolayers have been investigated by optical spectroscopy. Through characterization by absorption, photoluminescence, and photoconductivity spectroscopy, we trace the effect of quantum confinement on the material's electronic structure. With decreasing thickness, the indirect band gap, which lies below the direct gap in the bulk material, shifts upwards in energy by more than 0.6 eV. This leads to a crossover to a direct-gap material in the limit of the single monolayer. Unlike the bulk material, the MoS2 monolayer emits light strongly. The freestanding monolayer exhibits an increase in luminescence quantum efficiency by more than a factor of 104 compared with the bulk material. © 2010 The American Physical Society.
Chambers D.A.,National Health Research Institute |
Glasgow R.E.,University of Colorado at Denver |
Stange K.C.,Case Western Reserve University
Implementation Science | Year: 2013
Background: Despite growth in implementation research, limited scientific attention has focused on understanding and improving sustainability of health interventions. Models of sustainability have been evolving to reflect challenges in the fit between intervention and context.Discussion: We examine the development of concepts of sustainability, and respond to two frequent assumptions -'voltage drop,' whereby interventions are expected to yield lower benefits as they move from efficacy to effectiveness to implementation and sustainability, and 'program drift,' whereby deviation from manualized protocols is assumed to decrease benefit. We posit that these assumptions limit opportunities to improve care, and instead argue for understanding the changing context of healthcare to continuously refine and improve interventions as they are sustained. Sustainability has evolved from being considered as the endgame of a translational research process to a suggested 'adaptation phase' that integrates and institutionalizes interventions within local organizational and cultural contexts. These recent approaches locate sustainability in the implementation phase of knowledge transfer, but still do not address intervention improvement as a central theme. We propose a Dynamic Sustainability Framework that involves: continued learning and problem solving, ongoing adaptation of interventions with a primary focus on fit between interventions and multi-level contexts, and expectations for ongoing improvement as opposed to diminishing outcomes over time.Summary: A Dynamic Sustainability Framework provides a foundation for research, policy and practice that supports development and testing of falsifiable hypotheses and continued learning to advance the implementation, transportability and impact of health services research. © 2013 Chambers et al.; licensee BioMed Central Ltd.
Castellani R.J.,University of Maryland, Baltimore |
Smith M.A.,Case Western Reserve University
Journal of Pathology | Year: 2011
With each failure of anti-amyloid-β therapy in clinical trials, new trials are initiated with no hint of slowing down. This may be due, in part, to the fact that the amyloid cascade hypothesis has been so modified over time that it is now impossible to confirm or deny. The hypothesis now states, in effect, that invisible molecules target invisible structures. Still relevant, however, are multiple factors that surely cast some doubt but have either been rationalized or overlooked. Among these are the poor correlation between amyloid-β deposits and disease, the substantial differences between familial and sporadic disease, pathological assessment that indicates the secondary nature of lesions/proteins/cascades, the fact that soluble species are poorly reproducible laboratory phenomena, and the irrelevance of synaptic assessment to pathological interpretation. Although not yet dogma, the premature addition of mild cognitive impairment as the implied in vivo homologue to the soluble toxin-synapse interaction is also problematic. In either case, the amyloid cascade hypothesis continues to dominate the Alzheimer's disease literature and grant applications. The more the neuroscience community perseverates along these lines in the face of accumulating outcome data to the contrary, the more one is left to wonder whether the hypothesis is too big to fail. © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Mak K.F.,Columbia University |
He K.,Case Western Reserve University |
Lee C.,Sungkyunkwan University |
Lee G.H.,Columbia University |
And 3 more authors.
Nature Materials | Year: 2013
Two-dimensional (2D) atomic crystals, such as graphene and transition-metal dichalcogenides, have emerged as a new class of materials with remarkable physical properties. In contrast to graphene, monolayer MoS 2 is a non-centrosymmetric material with a direct energy gap. Strong photoluminescence, a current on/off ratio exceeding 10 8 in field-effect transistors, and efficient valley and spin control by optical helicity have recently been demonstrated in this material. Here we report the spectroscopic identification in a monolayer MoS 2 field-effect transistor of tightly bound negative trions, a quasiparticle composed of two electrons and a hole. These quasiparticles, which can be optically created with valley and spin polarized holes, have no analogue in conventional semiconductors. They also possess a large binding energy (∼ 20 meV), rendering them significant even at room temperature. Our results open up possibilities both for fundamental studies of many-body interactions and for optoelectronic and valleytronic applications in 2D atomic crystals. © 2013 Macmillan Publishers Limited. All rights reserved.
Agency: National Science Foundation | Branch: | Program: STTR | Phase: Phase II | Award Amount: 651.97K | Year: 2015
The broader impact/commercial potential of this Small Business Technology Transfer Phase II project is to demonstrate a low cost, environmentally friendly co-extrusion fabrication method for producing high surface area micro- and nanofiber based nonwoven fuel filter sheets. The micro-/nanofiber nonwoven structures are fabricated from two different hydrophilic and hydrophobic polymers in a melt co-extrusion and subsequent exfoliation processing step. The resulting porous filtration media sheets have been shown to possess superior strength, tailorable pore sizes, and fuel filtration efficiency on par with currently utilized commercial fuel filter products. These accomplishments signify a path forward to a highly scalable manufacturing process for producing low cost thermoplastic filter products in addressing the increasingly stringent EPA regulation of ppm level water contaminant. The reduced manufacturing process complexity in melt co-extrusion is estimated to provide up to 60% reduced production costs when scaled to commercial production quantities. Additionally, a significant environmental impact will be realized through adoption of this novel production technology over competitive processes owing to its ?greener? solvent-free manufacturing aspects that eliminates the annual need for millions of gallons of organic solvents and supporting reclamation equipment currently utilized by the filtration industry in creating elctrospun and wet-laid composite nonwoven filtration media. The objectives of this Phase II research project are to fabricate nano/micro scale nonwoven fibrous filter mats for fuel filters via a novel melt co-extrusion approach, with high fuel/water filtration efficiency and superior mechanical properties, in a commercially relevant production scale, towards addressing the stringent EPA 2010 filtration regulations and its upcoming revisions in 2015. The first generation filter prototypes fabricated in Phase I STTR program exhibited up to a ten-fold increase in surface area, up to a two-fold increase in porosity and up to a six-fold the deformation strength of the commercial filters. The coextruded microporous filter fiber size distribution was comparable to a commercial melt-blown process sample and superior to the leading wet-laid technology samples. Preliminary filtration efficiency experiments on the coextruded micro-fiber filtration media prototypes exhibited 60 to greater than 80 % separation of water from ultra-low sulfur diesel as compared to 80 % water separation using commercial filter under same testing conditions. The commercial interest for the new multilayered, coextruded filtration media processing technique is centered on identification of new filtration media film polymer materials, achieving nano-sized pore distributions for improved filtration efficiency and achieving scale-up production cost savings through the improved filter film processing technique.
Agency: National Science Foundation | Branch: | Program: STTR | Phase: Phase I | Award Amount: 225.00K | Year: 2014
This Small Business Innovation Research (SBIR) Phase I project is geared toward the production of previously unprocessible polymer composite fiber materials aimed at improving performance in membrane and fuel filtering applications through environmentally friendly melt coextrusion processing of polymer fibers. This melt process strategy offers a unique opportunity to fabricate nanofibers that is typically processed by many solvent-based techniques. This proposed STTR program will demonstrate processing of novel composite, micro- and nanolayered fiber materials via a solvent-free fabrication process capable of continuous mass production and membrane formation at a potentially lower production cost than the current state-of-the art manufacturing methods. The unique ability of the polymer layering coextrusion process enables the combination of dissimilar polymer materials, creating composite multifibers of specific size and aspect ratio, hydrophobicity and hydrophilicity. Through proof-of-concept fabrication and optimization trials to melt process the polymer fibers, this project will demonstrate the ability of these materials to fill the void of easily processible, tailorable hydrophobic/hydrophilic fiber materials that are suitable for use in the $12.5 billion/year membrane market, specifically for fuel filter membranes. The broader impact/commercial potential of this project includes initial applications in the membrane and filtration industry. Other applications expected in the field of medicine and biology are scaffolds for cell culture, tissue engineering, and drug delivery platform. Mechanically robust, highly oriented fibrous systems can also be used for clothing and packaging. Novel nanofiber fabrication approach will create a scalable process, which has a potential to create jobs in the United States. Because it is a solvent-free process, this technology is environmentally friendly and, therefore, will reduce carbon footprint and product cost. This program will also contribute to the education of engineering college students through the extensive use of co-op conducting research. The students will be hired from universities for varied duration of 4 to 12 months for this project. In addition, this STTR program also offers a unique opportunity to graduate students from area Universities to work with R & D companies and earn valuable experience. This strongly supports the NSF mission of developing the U.S. science and engineering workforce.
Agency: Department of Defense | Branch: Navy | Program: STTR | Phase: Phase I | Award Amount: 79.98K | Year: 2016
During AM of metallic alloys, a material exhibits several complex physical phenomena that impact the spatial distribution of heterogeneous material properties within a built component. Subsequent post-processing alters the already heterogeneous location-specific material properties. This project is to develop a novel methodology for linking the time and length scales of the various physical phenomena using a microstructure-based ICME approach. It is anticipated that the multi-scale simulations will enable predictions of the interdependencies among deposition process; location specific microstructure with the associated location-specific material behavior which will lead to predictions of the overall component performance in the as deposited and after post-processing conditions.The developed tools will propagate uncertainties in the materials and processing conditions to quantify its impact on the uncertainty in the mechanical behavior of Ti-6Al-4V parts made by additive manufacturing.
News Article | February 24, 2017
The International Association of HealthCare Professionals is pleased to welcome Robert Lupo, MD, Orthopedic Surgeon, to their prestigious organization with his upcoming publication in The Leading Physicians of the World. Dr. Robert Lupo is a highly trained and qualified orthopedic surgeon with an extensive expertise in all facets of his work, especially hip and knee replacement, as well as knee and shoulder arthroscopy. Dr. Lupo has been in practice for more than 18 years and is currently serving patients within the Orthopedic Institute at Saint Vincent, in Erie, Pennsylvania. He is also affiliated with Saint Vincent Health System. Dr. Robert Lupo graduated with his Medical Degree with honors from Case Western Reserve University in Cleveland, Ohio. Following his graduation, he subsequently completed his five year Orthopaedic Surgery residency at Mount Sinai Medical Center. Dr. Lupo is certified by the American Board of Orthopedic Surgery, and has earned the coveted title of and served as the Chairman of the Department of Orthopaedic Surgery and Neurosurgery, and Department Head of Orthopedic Surgery at St. Vincent Medical Center. He is the only surgeon in his region using the Journey 2 Knee System, the only knee designed to replicate normal knee motion. He performs advanced arthroscopic surgeries of the shoulder and knee designed to minimize pain, scarring, and speed recovery. Furthermore, Dr. Lupo is Director of Mako™ Robotic Joint Replacement, and also serves as Director of Orthopaedic Residency at Saint Vincent Health Center. In his free time, Dr. Lupo enjoys golfing. Learn more about Dr. Lupo here: http://drrobertlupo.com/ and be sure to read his upcoming publication in The Leading Physicians of the World. FindaTopDoc.com is a hub for all things medicine, featuring detailed descriptions of medical professionals across all areas of expertise, and information on thousands of healthcare topics. Each month, millions of patients use FindaTopDoc to find a doctor nearby and instantly book an appointment online or create a review. FindaTopDoc.com features each doctor’s full professional biography highlighting their achievements, experience, patient reviews and areas of expertise. A leading provider of valuable health information that helps empower patient and doctor alike, FindaTopDoc enables readers to live a happier and healthier life. For more information about FindaTopDoc, visit http://www.findatopdoc.com
Saleem Y.,Case Western Reserve University
Circulation. Cardiovascular imaging | Year: 2015
BACKGROUND: To examine the association between the American Heart Association's 7 metrics of ideal cardiovascular health (ICH) and the presence of subclinical coronary atherosclerosis as assessed by coronary artery calcification (CAC) using electron-beam computed tomography.METHODS AND RESULTS: This study is a cross-sectional analysis of data obtained on 3121 male and female patients evaluated at the Cooper Clinic in Dallas, Texas, between 1997 and 2007. We included men aged ≥45 and women aged ≥55 without known cardiovascular disease and for whom information on all ICH metrics and a CAC score were available. Patients were grouped into 3 categories according to their number of ICH metrics: favorable (4-7 ICH metrics), intermediate (3 metrics), and unfavorable (0-2 metrics). Patients with favorable ICH profiles had a lower prevalence and severity of subclinical atherosclerosis than those with unfavorable or intermediate ICH profiles as estimated by CAC. This inverse association of CAC with ICH metrics was evident whether the presence of coronary calcium was defined as CAC score>0, CAC score>100, or CAC score>400. Patients with favorable ICH profiles had odds of coronary calcium (CAC>0) less than half of those for patients with unfavorable profiles (odds ratio 0.41; 95% confidence interval, 0.34-0.50) and patients with intermediate ICH profiles had odds of detectable CAC 32% lower (odds ratio 0.68; 95% confidence interval, 0.57-0.82).CONCLUSIONS: A statistically significant association was found between a favorable level of ICH metrics and less or absent subclinical atherosclerosis as measured by CAC underscoring the importance of primordial prevention. © 2014 American Heart Association, Inc.
Shi W.,Case Western Reserve University |
Chance M.R.,Case Western Reserve University
Current Opinion in Chemical Biology | Year: 2011
About one-third of all proteins are associated with a metal. Metalloproteomics is defined as the structural and functional characterization of metalloproteins on a genome-wide scale. The methodologies utilized in metalloproteomics, including both forward (bottom-up) and reverse (top-down) technologies, to provide information on the identity, quantity, and function of metalloproteins are discussed. Important techniques frequently employed in metalloproteomics include classical proteomic tools such as mass spectrometry and 2D gels, immobilized-metal affinity chromatography, bioinformatic sequence analysis and homology modeling, X-ray absorption spectroscopy and other synchrotron radiation based tools. Combinative applications of these techniques provide a powerful approach to understand the function of metalloproteins. © 2010 Elsevier Ltd.
O'Toole J.F.,Case Western Reserve University
Nephron - Physiology | Year: 2011
The genetic contribution to calcium metabolism is well recognized. Many of the proteins that contribute to calcium homeostasis through intestinal absorption, bone deposition and resorption, renal reabsorption and the molecules regulating these processes have been identified. Mutations in many of the genes coding for these proteins have been identified and often have clear clinical phenotypes. These mutations are generally rare with large effect sizes and a high degree of penetrance. As monogenetic diseases, they have a mendelian inheritance pattern and have been identified with traditional family-based linkage studies. A great deal of progress has been made in the understanding of the physiology of calcium metabolism; however, it remains an evolving field. The identification of the monogenetic etiology of disease has contributed greatly to our understanding of calcium handling and homeostasis. Transgenic animal models of these diseases continue to offer new insights into the mechanisms of calcium metabolism and its regulation. The purpose of this review is to briefly outline calcium metabolism focusing on the mechanisms of intestinal absorption and renal reabsorption as a framework to review the monogenic causes of dysregulated calcium metabolism. © 2010 S. Karger AG, Basel.
Ogino T.,Case Western Reserve University
Nucleic Acids Research | Year: 2014
The multifunctional RNA-dependent RNA polymerase L protein of vesicular stomatitis virus catalyzes unconventional pre-mRNA capping via the covalent enzyme-pRNA intermediate formation, which requires the histidine-arginine (HR) motif in the polyribonucleotidyltransferase domain. Here, the effects of cap-defective mutations in the HR motif on transcription were analyzed using an in vitro reconstituted transcription system. The wild-type L protein synthesized the leader RNA from the 3'- end of the genome followed by 5'-capped and 3'- polyadenylated mRNAs from internal genes by a stop-start transcription mechanism. Cap-defective mutants efficiently produced the leader RNA, but displayed aberrant stop-start transcription using cryptic termination and initiation signals within the first gene, resulting in sequential generation of ∼40- nucleotide transcripts with 5'-ATP from a correct mRNA-start site followed by a 28-nucleotide transcript and long 3'-polyadenylated transcript initiated with non-canonical GTP from atypical start sites. Frequent transcription termination and re-initiation within the first gene significantly attenuated the production of downstream mRNAs. Consistent with the inability of these mutants in in vitro mRNA synthesis and capping, these mutations were lethal to virus replication in cultured cells. These findings indicate that viral mRNA capping is required for accurate stop-start transcription as well as mRNA stability and translation and, therefore, for virus replication in host cells. © The Author(s) 2014.
Berger N.A.,Case Western Reserve University
Annals of the New York Academy of Sciences | Year: 2014
Overweight and obesity have reached pandemic levels on a worldwide basis and are associated with increased risk and worse prognosis for many but not all malignancies. Pathophysiologic processes that affect this association are reviewed, with a focus on the relationship between type 2 diabetes mellitus and cancer, lessons learned from the use of murine models to study the association, the impact of obesity on pancreatic cancer, the effects of dietary fats and cholesterol on cancer promotion, and the mechanisms by which the intestinal microbiome affects obesity and cancer. © 2014 New York Academy of Sciences.
Master D.L.,Case Western Reserve University
The Journal of craniofacial surgery | Year: 2010
Mandibular hypoplasia, retrognathia, and micrognathia are commonly encountered problems in pediatric plastic surgery. Mandibular distraction osteogenesis (MDO) is a relatively simple technique that allows for correction of the deformity with minimal morbidity. However, MDO can lead to a wide variety of complications. The PubMed database was queried for all articles describing complications of MDO. Each article was then reviewed, and relevant data were extracted and compiled. Finally, several case reports are presented to illustrate poignant examples of complications. Complications of MDO include relapse (64.8% incidence), tooth injury (22.5%), hypertrophic scarring (15.6%), nerve injury (11.4%), infection (9.5%), inappropriate distraction vector (8.8%), device failure (7.9%), fusion error (2.4%), and temporomandibular joint injury (0.7%). Mandibular distraction osteogenesis can be associated with a wide variety of minor and major complications, but all complications can be avoided with careful planning and technique.
El H.,Hacettepe University |
Palomo J.M.,Case Western Reserve University
Angle Orthodontist | Year: 2014
Objectives: To evaluate, by using cone beam computed tomography, the skeletal, dental, oropharyngeal (OP) airway volume, and nasal passage (NP) volume changes that occur after rapid maxillary expansion (RME). Materials and Methods: Two groups were selected, each with 35 patients (15 males, 20 females), an RME group (mean age, 14.02 6 1.46 years) and a control group (mean age, 14.10 6 1.44 years). The RME group consisted of patients with maxillary constriction who were treated with Hyrax palatal expanders, and the control group comprised age-and sex-matched patients who underwent comprehensive orthodontic treatment without the use of a rapid maxillary expander. Results: All of the transverse skeletal (medial orbital width, lateral nasal width, maxillary width, and mandibular width) and interdental (intermolar, interpremolar, and intercanine) parameters were significantly enlarged in the RME group. A statistically significant increase in airway variables was seen in both groups between pretreatment (T0) and final records (T1). The mean increase of NP airway volume for the RME group (1719.9 6 1510.7 mm3) was twofold compared with the control group (813.6 6 1006.7 mm3), and no intergroup significant difference was found for the OP volume.Conclusions: Rapid maxillary expansion creates a significant increase in nasal passage airway volume but no significant change in the oropharyngeal airway volume. © 2014 by The EH Angle Education and Research Foundation,Inc.
Niazi F.,Case Western Reserve University |
Valadkhan S.,Case Western Reserve University
RNA | Year: 2012
Recent transcriptome analyses have indicated that a large part of mammalian genomes are transcribed into long non-protein-coding RNAs (lncRNAs). However, only a very small fraction of them have been individually studied, and whether the majority of lncRNAs found in large-scale studies have a cellular role is debated. To gain insight into the sequence features and genomic architecture of the subset of lncRNAs that have been proven to be functional, we created a database containing studied lncRNAs manually culled from the literature along with a parallel database containing all annotated protein-coding human RNAs. The Functional lncRNA Database, which contains 204 lncRNAs and their splicing variants, is available at valadkhanlab.org/database. Analysis of the lncRNAs and their comparison to protein-coding transcripts revealed sequence features including paucity of introns and low GC content in lncRNAs, which could explain several biological characteristics of these transcripts, such as their nuclear localization and low expression level. The predicted ORFs in lncRNAs have poor start codon and ORF contexts, which would lead to activation of the nonsense-mediated decay pathways and thus make it unlikely for most lncRNAs to code for even short peptides. Interestingly, our analyses revealed significant similarities between the lncRNAs and the 3′ untranslated regions (3′ UTRs) in protein-coding RNAs in structural features and sequence composition. The presence of these intriguing parallels between the lncRNAs and 3′ UTRs, which constitute the two main components of the RNA-mediated cellular regulatory system, indicates that highly similar evolutionary constraints govern the function of regulatory RNA sequences in the cell. Published by Cold Spring Harbor Laboratory Press. Copyright © 2012 RNA Society.
Gosain A.K.,Case Western Reserve University
Plastic and Reconstructive Surgery | Year: 2010
Background: Nasal tip hemangiomas cause significant parental distress and can negatively affect the psychological development of a child. Treatment is controversial, with numerous modalities available for reconstruction. The authors outline their combined medical and surgical approach to treating nasal tip hemangiomas and describe their preferred surgical technique. Methods: A retrospective review was performed of all nasal tip hemangiomas presenting to the Multidisciplinary Vascular Anomalies Clinics at the Children's Hospital of Wisconsin and Children's Hospital of Michigan from 1999 to 2007. Parameters for review included onset age, symptoms, medical therapies (laser with or without steroid) used, age and status of lesion at time of surgery, outcomes, and complications. Results: Twenty-five patients met inclusion criteria, with a mean onset age of 1.43 months. Most received steroids and pulsed dye laser therapy (mean no. of laser treatments, 3.5) during the proliferative and plateau phases of the tumor's natural history. Surgical resection after involution has been performed using an open rhinoplasty technique on 15 patients thus far. Eleven of them had surgical correction in the postinvolutional phase, and at parental request, four had early surgical correction during the proliferative-plateau phases. In the early treatment cohort, one child developed a hematoma postoperatively; the same patient required a revision rhinoplasty for alar rim asymmetry. Acceptable aesthetic results were obtained in both groups. Conclusions: A combined medical and surgical approach offers the best method to treat the Cyrano nose. The authors' treatment algorithm uses early medical management to accelerate involution of the lesion, providing optimal conditions for excision. Early surgical treatment also allows satisfactory results but may require secondary correction. An open rhinoplasty approach with skin resection is the authors' preferred technique. Copyright © 2010 by the American Society of Plastic Surgeons.
Chim H.,Case Western Reserve University
Plastic and reconstructive surgery | Year: 2010
LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Define the difference between vascular tumors and malformations. 2. Distinguish between the natural history of hemangiomas and that of vascular malformations. 3. Identify the different types of hemangiomas and vascular malformations and understand evaluation, treatment, and complications. 4. Understand the role of lymphaticovenular anastomoses in the treatment of extremity lymphedema. BACKGROUND: The International Society for the Study of Vascular Anomalies classification, which is the most widely accepted classification system in use, divides vascular anomalies into vascular tumors (inclusive of hemangiomas) and malformations. This serves as a guideline for diagnosis, evaluation, and treatment of these lesions. METHODS: Although hemangiomas tend to have a predictable clinical course over the first year of life, going through proliferating, involuting, and involuted stages, vascular malformations demonstrate growth commensurate with age, often becoming more prominent in puberty. In addition, they never regress, and persist throughout life. RESULTS: Different modalities of treatment may be appropriate for vascular tumors and different subsets of vascular malformations. Details are provided in this review. Lymphaticovenular anastomoses provide an excellent addition to our methods of treatment of extremity lymphedema, and are made possible through development of supermicrosurgical techniques. CONCLUSIONS: Vascular anomalies have a high prevalence in the general population. Thus, it is vital that the plastic surgeon has a good understanding of classification, evaluation, and treatment options. Lymphedema is another common condition that is encountered. Understanding of lymphaticovenular anastomoses and their applications aids treatment planning for select patients.
Palczewski K.,Case Western Reserve University
Trends in Pharmacological Sciences | Year: 2010
Knowledge about retinal photoreceptor signal transduction and the visual cycle required for normal eyesight has increased exponentially over the past decade. Substantial progress in human genetics has facilitated the identification of candidate genes and complex networks underlying inherited retinal diseases. Natural mutations in animal models that mimic human diseases have been characterized and advanced genetic manipulation can now be used to generate small mammalian models of human retinal diseases. Pharmacological repair of defective visual processes in animal models not only validates their involvement in vision, but also provides great promise for the development of improved therapies for millions who are progressing towards blindness or are almost completely robbed of their eyesight. © 2010 Elsevier Ltd.
Gupta A.S.,Case Western Reserve University
Nanomedicine: Nanotechnology, Biology, and Medicine | Year: 2011
Nanomedicine approaches have revolutionized the treatment of cancer and vascular diseases, where the limitations of rapid nonspecific clearance, poor biodistribution and harmful side effects associated with direct systemic drug administration can be overcome by packaging the agents within sterically stabilized, long-circulating nanovehicles that can be further surface-modified with ligands to actively target cellular/molecular components of the disease. With significant advancements in genetics, proteomics, cellular and molecular biology and biomaterials engineering, the nanomedicine strategies have become progressively refined regarding the modulation of surface and bulk chemistry of the nanovehicles, control of drug release kinetics, manipulation of nanoconstruct geometry and integration of multiple functionalities on single nanoplatforms. The current review aims to capture the various nanomedicine approaches directed specifically toward vascular diseases during the past two decades. Analysis of the promises and limitations of these approaches will help identify and optimize vascular nanomedicine systems to enhance their efficacy and clinical translation in the future. From the Clinical Editor: Nanomedicine-based approaches have had a major impact on the treatment and diagnosis of malignancies and vascular diseases. This review discusses various nanomedicine approaches directed specifically toward vascular diseases during the past two decades, highlighting their advantages, limitations and offering new perspectives on future applications. © 2011 Elsevier Inc.
Fairman-Williams M.E.,Case Western Reserve University |
Guenther U.-P.,Case Western Reserve University |
Jankowsky E.,Case Western Reserve University
Current Opinion in Structural Biology | Year: 2010
Helicases of the superfamily (SF) 1 and 2 are involved in virtually all aspects of RNA and DNA metabolism. SF1 and SF2 helicases share a catalytic core with high structural similarity, but different enzymes even within each SF perform a wide spectrum of distinct functions on diverse substrates. To rationalize similarities and differences between these helicases, we outline a classification based on protein families that are characterized by typical sequence, structural, and mechanistic features. This classification complements and extends existing SF1 and SF2 helicase categorizations and highlights major structural and functional themes for these proteins. We discuss recent data in the context of this unifying view of SF1 and SF2 helicases. © 2010 Elsevier Ltd.