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Aim: At least seven North American tribes specifically mention the use of Eryngium (typically roots) as an anti-snake venom therapy. As snake envenomation is an endemic, life-threatening medical risk, is there a scientific basis for the Native American ethnomedicine? Could this be demonstrated in an assay amenable to mechanistic evaluation and high throughput screening for later isolation and possible evaluation as a source for a lead drug? Materials and Methods: Proteases, mainly metalloproteases, are thought to be the main pathological agents in most American snake venoms. Water extracts of four plant parts of Eryngium yuccifolium were tested for enzyme inhibition in three highly sensitive in vitro protease assays, with multiple venoms. Results: Interestingly, activity was found in all plant parts, not just the roots, in the general protease assay, also in the most specific assay for collagenases, but less so for elastases where enzymatic activity was low, and against five species of American snake venoms. Inhibition spared the activity of a mammalian elastase, suggesting it has some specificity. In dose response assays, inhibitory activity in extracts of Eryngium was noticeably more effective than randomly chosen plants and comparable to some others. Conclusions: All data shown here are consistent with pharmacological inhibition of proteases in at least selected venoms of common venomous snakes by Eryngium extracts. Moreover, as the genus is widely distributed in America, the ethnological practice of using this plant as an anti-snake venom treatment is supportable, may have been common, and suggests further bioactivity and phytochemical studies are warranted. © SAGEYA.

Mangels D.R.,University of Pennsylvania | Mohler E.R.,III
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2017

The impact of diet on cardiovascular disease has become an increasingly relevant topic as ongoing epidemiological evidence continues to demonstrate clear associations with disease burden and mortality. Certain diets, such as those high in sodium and saturated fat, are associated with cardiovascular disease states, while other diets can be cardioprotective. However, there is limited knowledge on how the micro- and macronutrients within such cardioprotective diets afford their benefits. One such micronutrient is the catechin class, which are naturally occurring compounds in plant foods, such as teas, cocoa, wine, pears, and apples. Recent evidence reveals that catechins may be a key mediator in cardiovascular health via mechanisms of blood pressure reduction, flow-mediated vasodilation, and atherosclerosis attenuation. This review evaluates the current literature on the interplay between catechins and cardiovascular disease, which may have important implications for nutrition counseling and pharmaceutical drug development. © 2017 American Heart Association, Inc.

Mijalis A.J.,Massachusetts Institute of Technology | Thomas D.A.,III
Nature Chemical Biology | Year: 2017

Here we report a fully automated, flow-based approach to solid-phase polypeptide synthesis, with amide bond formation in 7 seconds and total synthesis times of 40 seconds per amino acid residue. Crude peptide purities and isolated yields were comparable to those for standard-batch solid-phase peptide synthesis. At full capacity, this approach can yield tens of thousands of individual 30-mer peptides per year. © 2017 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

Parsons D.R.,III
Journal of Computational Physics | Year: 2017

This study focuses on an approach to quantify the discretization error associated with numerical solutions of partial differential equations by solving an error transport equation (ETE). The goal is to develop a method that can be used to adequately predict the discretization error using the numerical solution on only one grid/mesh. The primary problem associated with solving the ETE is the formulation of the error source term which is required for accurately predicting the transport of the error. In this study, a novel approach is considered which involves fitting the numerical solution with a series of locally smooth curves and then blending them together with a weighted spline approach. The result is a continuously differentiable analytic expression that can be used to determine the error source term. Once the source term has been developed, the ETE can easily be solved using the same solver that is used to obtain the original numerical solution. The new methodology is applied to the two-dimensional Navier–Stokes equations in the laminar flow regime. A simple unsteady flow case is also considered. The discretization error predictions based on the methodology presented in this study are in good agreement with the ‘true error’. While in most cases the error predictions are not quite as accurate as those from Richardson extrapolation, the results are reasonable and only require one numerical grid. The current results indicate that there is much promise going forward with the newly developed error source term evaluation technique and the ETE. © 2017 Elsevier Inc.

Culton J.,III
Proceedings of the International Astronautical Congress, IAC | Year: 2016

Recent advancements in both space related technology and space policy are setting the conditions for the eventual operation of commercial companies in cis-lunar space. However, these proposed activities are testing the limits of both the regulatory environment which allows for commercial activities to occur and commercial funding mechanisms. How can government and industry best accelerate the development of commercial cis-lunar space for the benefit of both? This paper will describe a critical path required to open the cis-lunar frontier to a multitude of potential commercial enterprises that will serve the needs of commercial and government customers alike. The critical path examined in this paper stipulates three necessary pre-conditions that must exist before a broad commercial presence in cis-lunar space will be feasible. These three pre-conditions are: the establishment of a regulatory environment which promotes commercial cis-lunar operations by encouraging private investment, a reduction in space launch/access costs, and the reduction of in-space operations costs. First, by providing a regulatory environment supportive of commercial cis-lunar operations, governments provide the critical starting ingredient that only they can: the legal authority to engage in the specified activity. This, in turn, allows for the operation of commercial funding mechanisms by reducing the investment risk inherent in any environment lacking a clear regulatory regime. Secondly, the cost of space launch/access must be reduced. As one of the single largest cost drivers for any space endeavor, launch costs must be reduced to allow needed capital to be spent on research, development, and deployment of a cis-lunar space architecture. Without a significant reduction in launch costs, the business cases for commercial space operations will remain incredibly difficult to make. Finally, any long stay crewed cis-lunar activity will face another challenge: that of continuous space operations. Sourcing periodic resupply of expendables, such as oxygen, water, and fuel from Earth will likely bankrupt any commercial operation. Thus, step three involves the prerequisite development of a viable in-situ space resource utilization architecture that can supply the expendables required by the wide variety of commercial, and government, operators that will follow and ultimately require these services. By first assessing the current state of the critical path via examination of each step in greater detail, the paper will describe how policy makers and industry can accelerate the development of commercial cis-lunar capabilities via the promotion of commercial investment through regulation and the development of critical foundational space capabilities. Copyright © 2016 by the International Astronautical Federation. All rights reserved.

Medina-Contreras J.M.L.,National Polytechnic Institute of Mexico | Colado-Velazquez J.,III
International Journal of Obesity | Year: 2017

Background:Hypoestrogenic (HE) women are one of the most vulnerable groups for the development of obesity and its complications. Capsaicin and exercise have demonstrated to reduce body weight and to improve insulin sensitivity in different animal models, but it is unknown whether their combination could be useful in HE obese females.Methods:We investigated whether topical capsaicin, exercise or their combination had better therapeutic effects in an obesity-hypoestrogenism model. Ovariectomized Wistar rats were given a 30% sucrose solution (HE-Obese (HEOb)) or purified water (HE) during 28 weeks ad libitum; four experimental groups per each condition. After shaving the abdominal skin, cold cream vehicle was applied to the Sedentary groups (Sed) and capsaicin cream 0.075% (0.6 mg kg-1 per day) to the Capsaicin groups (Cap). Exercise (Ex) groups ran on a treadmill every day for 20 min at speeds from 9 to 18 m per min increased every 10 days; combination groups (Cap+Ex) were given topical capsaicin 90 min before exercise. The treatments were performed for 6 weeks, and caloric intake and body weight were monitored. At the end of the experimental protocol, glucose tolerance tests were performed, the animals were killed by decapitation; blood and organs were obtained to perform oxidative profile, histology, biochemical analyses and Western blot.Results:In HEOb rats, the combined therapy reduced caloric intake, body weight and abdominal fat in a higher proportion than the individual treatments; it also decreased insulin resistance (IR), oxidative stress and pancreatic islet size. It was the only treatment that significantly increased p-AMPK levels in the soleus muscle. In HE rats, topical capsaicin was the only treatment that reduced glucose intolerance and improved the oxidative profile in a higher proportion than the combined therapy or Ex alone.Conclusions:Capsaicin per se or its combination with moderate exercise could be a useful therapy against complications linked to obesity–IR in HE females.International Journal of Obesity advance online publication, 28 February 2017; doi:10.1038/ijo.2017.33. © 2017 Macmillan Publishers Limited, part of Springer Nature.

Home > Press > Leti Will Demo World’s-first WVGA 10-µm Pitch GaN Microdisplays for Augmented Reality Video at Display Week in Los Angles: Invited Paper also Will Present Leti’s Success with New Augmented Reality Technology That Reduces Pixel Pitch to Less than 5 Microns Abstract: Extending its expertise in high-brightness microdisplay technology for augmented-reality and other applications, Leti will demonstrate the world’s first wide video graphic array (WVGA) GaN microdisplay with 10-micron pixel pitch during Display Week in Los Angeles, May 21-26. The 10-micron pixel pitch technology will help address the growing demand for augmented-reality glasses for consumer and professional users, head-up displays for vehicle drivers and for pico projectors and other compact projectors. This prototype microdisplay, based on a self-emissive GaN-based technology, shows the highest resolution with smallest pixel pitch (10 µm) ever presented. Patterning high-density microLED arrays and hybridizing them on a CMOS circuit, using Leti’s micro-tube technology, enabled Leti to achieve this performance. The demonstrator at Display Week in booth 1315 features a monochrome (blue or green) active-matrix prototype with WVGA resolution of 873 x 500 pixels. “With this result, Leti’s technology has reached an important milestone,” said François Templier, project manager. “We will continue to work towards a 5-micron pixel pitch and, beyond that, on a new technology that will take GaN LED microdisplays to less than a 5-micron pixel pitch.” Leti will present that new technology at Display Week in an invited talk, “A Novel Process for Fabricating High-Resolution and Very Small Pixel-pitch GaN LED Microdisplays”. The presentation at 5 p.m., May 23, will demonstrate the feasibility of LED arrays with pixel pitch as small as 3 µm, which is a world record. These results presented by Leti were obtained under a collaborative work program with III-V Lab. About Leti Leti, a technology research institute at CEA Tech, is a global leader in miniaturization technologies enabling smart, energy-efficient and secure solutions for industry. Founded in 1967, Leti pioneers micro-& nanotechnologies, tailoring differentiating applicative solutions for global companies, SMEs and startups. Leti tackles critical challenges in healthcare, energy and digital migration. From sensors to data processing and computing solutions, Leti’s multidisciplinary teams deliver solid expertise, leveraging world-class pre-industrialization facilities. With a staff of more than 1,900, a portfolio of 2,700 patents, 91,500 sq. ft. of cleanroom space and a clear IP policy, the institute is based in Grenoble, France, and has offices in Silicon Valley and Tokyo. Leti has launched 60 startups and is a member of the Carnot Institutes network. This year, the institute celebrates its 50th anniversary. Follow us on www.leti-cea.com and @CEA_Leti. CEA Tech is the technology research branch of the French Alternative Energies and Atomic Energy Commission (CEA), a key player in innovative R&D, defence & security, nuclear energy, technological research for industry and fundamental science, identified by Thomson Reuters as the second most innovative research organization in the world. CEA Tech leverages a unique innovation-driven culture and unrivalled expertise to develop and disseminate new technologies for industry, helping to create high-end products and provide a competitive edge. About III-V Lab (France) III-V Lab is an Economic Interest Grouping (“Groupement d’Intérêt Economique”) between the CEA, Thales and Nokia, dedicated to industrial research and development of optoelectronic and microelectronic components based on III-V semiconductors, and their integration with silicon circuits. Created in 2004, III-V Lab brings together 120 researchers in the Paris region and actively cooperates with CEA-LETI’s laboratories at Grenoble. III-V Lab has prototyping and production start-up resources to foster the emergence of high added-value component technologies which are then transferred to the industrial entities of the parent companies or their partners. III-V Lab concentrates in a single entity the most advanced industrial research capabilities in the field of III-V semiconductors in Europe. www.3-5lab.fr For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Merker M.,Research Center Borstel | Barry C.E.,III
Nature Genetics | Year: 2015

Mycobacterium tuberculosis strains of the Beijing lineage are globally distributed and are associated with the massive spread of multidrug-resistant (MDR) tuberculosis in Eurasia. Here we reconstructed the biogeographical structure and evolutionary history of this lineage by genetic analysis of 4,987 isolates from 99 countries and whole-genome sequencing of 110 representative isolates. We show that this lineage initially originated in the Far East, from where it radiated worldwide in several waves. We detected successive increases in population size for this pathogen over the last 200 years, practically coinciding with the Industrial Revolution, the First World War and HIV epidemics. Two MDR clones of this lineage started to spread throughout central Asia and Russia concomitantly with the collapse of the public health system in the former Soviet Union. Mutations identified in genes putatively under positive selection and associated with virulence might have favored the expansion of the most successful branches of the lineage. © 2015 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

Poruk K.E.,Sloan Kettering Cancer Center | Valero V.,III
Annals of Surgery | Year: 2016

OBJECTIVE:: We assessed circulating tumor cells (CTCs) with epithelial and mesenchymal phenotypes as a potential prognostic biomarker for patients with pancreatic adenocarcinoma (PDAC). BACKGROUND:: PDAC is the fourth leading cause of cancer death in the United States. There is an urgent need to develop biomarkers that predict patient prognosis and allow for better treatment stratification. METHODS:: Peripheral and portal blood samples were obtained from 50 patients with PDAC before surgical resection and filtered using the Isolation by Size of Epithelial Tumor cells method. CTCs were identified by immunofluorescence using commercially available antibodies to cytokeratin, vimentin, and CD45. RESULTS:: Thirty-nine patients (78%) had epithelial CTCs that expressed cytokeratin but not CD45. Twenty-six (67%) of the 39 patients had CTCs which also expressed vimentin, a mesenchymal marker. No patients had cytokeratin-negative and vimentin-positive CTCs. The presence of cytokeratin-positive CTCs (P< 0.01), but not mesenchymal-like CTCs (P= 0.39), was associated with poorer survival. The presence of cytokeratin-positive CTCs remained a significant independent predictor of survival by multivariable analysis after accounting for other prognostic factors (P< 0.01). The detection of CTCs expressing both vimentin and cytokeratin was predictive of recurrence (P= 0.01). Among patients with cancer recurrence, those with vimentin-positive and cytokeratin-expressing CTCs had decreased median time to recurrence compared with patients without CTCs (P= 0.02). CONCLUSIONS:: CTCs are an exciting potential strategy for understanding the biology of metastases, and provide prognostic utility for PDAC patients. CTCs exist as heterogeneous populations, and assessment should include phenotypic identification tailored to characterize cells based on epithelial and mesenchymal markers. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Nussbaum D.P.,Duke University | Blazer D.G.,III
Journal of the American College of Surgeons | Year: 2015

Background The management of 1- to 2-cm appendiceal carcinoid tumors remains controversial. Here we use the National Cancer Data Base (NCDB) to compare long-term outcomes for patients treated via resection of the primary tumor alone vs right hemicolectomy (RHC). Study Design The 1998 to 2011 NCDB User File was queried to identify patients with 1- to 2-cm appendiceal carcinoids. Patients were stratified by surgical technique: Resection of the primary tumor alone vs RHC with regional lymphadenectomy. Multivariable logistic regression was used to compare short-term outcomes. Survival was estimated using the Kaplan-Meier method with comparisons based on the log-rank test. Results A total of 916 patients were identified, including 42% managed with primary resection and 58% with RHC. Patients who underwent RHC had slightly larger tumors and higher-stage tumors; otherwise, there were no baseline differences between groups. The rates of positive margins were similar (5.5% vs 4.5%; p = 0.60). Among all patients, 1- and 5-year survival were 98.1% and 88.7% vs 96.7% and 87.4% (p = 0.52) for those managed via primary resection vs RHC, respectively. Among patients with moderate/high-grade/anaplastic carcinoids, 1- and 5-year survival were 93.3% and 72.0% vs 92.3% and 71.9%, respectively (p = 0.78). After adjustment with Cox proportional hazards modeling, we confirmed that there was no survival benefit for patients undergoing RHC (hazard ratio = 1.14; p = 0.72). Conclusions For 1- to 2-cm appendiceal carcinoids, formal resection of the right colon does not appear to improve survival, even for higher-grade tumors. Our findings suggest that resection of the primary tumor alone is adequate for all carcinoids <2 cm. © 2015 American College of Surgeons.

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