Temple, PA, United States
Temple, PA, United States

Temple University, commonly referred to as Temple, is a comprehensive public research university in Philadelphia, Pennsylvania, United States. The University was founded in 1884 by Russell Conwell. As of 2014, more than 37,000 undergraduate, graduate, and professional students are enrolled in over 400 academic degree programs offered at seven campuses and sites in Pennsylvania, and international campuses in Rome, Tokyo, Singapore and London. Temple is among the nation's largest providers of professional education , preparing the largest body of professional practitioners in Pennsylvania. Wikipedia.


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An alginate and stearic acid composition is described, including methods of molding it into tablets further comprising a drug, and methods of controlling the drug release from the tablets.


Patent
Temple University | Date: 2016-09-09

The dynamic positioning of sensors, which exploit the mechanical and physiological changes in tissues, can significantly increase the performance in characterization of tumors. Here, we disclose the Optical Dynamic Imaging (ODI) System for tumor characterization. ODI System estimates size, depth, elastic modulus and optical properties of embedded objects. The ODI System consists of a tactile imaging sensor (TIS), and a near infrared diffuse spectral imaging. To obtain mechanical properties of the target, we compress the region of interest with the probe, then the light from the probe is scattered and captured by the camera as a tactile image. On the other hand, using a light source and the camera as a detector, we obtain the diffuse spectral images. From these images, we compute the absorption coefficient of the embedded tumor phantom. We move the source-detector simultaneously and collect optical information. We termed this maneuver as dynamic positioning. Optical Dynamic Imaging System also provides position and orientation of the light source and the detectors. The combination of the absorption coefficient and tactile data along with location information improves the size, depth, and elastic modulus estimation.


Patent
Temple University and Onconova Therapeutics, Inc. | Date: 2017-03-08

Substituted phenol derivatives of Formula I:


Flitcroft D.I.,Temple University
Progress in Retinal and Eye Research | Year: 2012

Myopia is the commonest ocular abnormality but as a research topic remains at the margins of mainstream ophthalmology. The concept that most myopes fall into the category of 'physiological myopia' undoubtedly contributes to this position. Yet detailed analysis of epidemiological data linking myopia with a range of ocular pathologies from glaucoma to retinal detachment demonstrates statistically significant disease association in the 0 to -6 D range of 'physiological myopia'. The calculated risks from myopia are comparable to those between hypertension, smoking and cardiovascular disease. In the case of myopic maculopathy and retinal detachment the risks are an order of magnitude greater. This finding highlights the potential benefits of interventions that can limit or prevent myopia progression.Our understanding of the regulatory processes that guide an eye to emmetropia and, conversely how the failure of such mechanisms can lead to refractive errors, is certainly incomplete but has grown enormously in the last few decades. Animal studies, observational clinical studies and more recently randomized clinical trials have demonstrated that the retinal image can influence the eye's growth. To date human intervention trials in myopia progression using optical means have had limited success but have been designed on the basis of simple hypotheses regarding the amount of defocus at the fovea.Recent animal studies, backed by observational clinical studies, have revealed that the mechanisms of optically guided eye growth are influenced by the retinal image across a wide area of the retina and not solely the fovea. Such results necessitate a fundamental shift in how refractive errors are defined. In the context of understanding eye growth a single sphero-cylindrical definition of foveal refraction is insufficient. Instead refractive error must be considered across the curved surface of the retina. This carries the consequence that local retinal image defocus can only be determined once the 3D structure of the viewed scene, off axis performance of the eye and eye shape has been accurately defined. This, in turn, introduces an under-appreciated level of complexity and interaction between the environment, ocular optics and eye shape that needs to be considered when planning and interpreting the results of clinical trials on myopia prevention. © 2012 Elsevier Ltd.


This Controversies in Research article discusses the hypothesis that protein kinase A (PKA)-mediated phosphorylation of the Ryanodine Receptor (RyR) at a single serine (RyRS2808) is essential for normal sympathetic regulation of cardiac myocyte contractility and is responsible for the disturbed Ca 2+ regulation that underlies depressed contractility in heart failure. Studies supporting this hypothesis have associated hyperphosphorylation of RyRS2808 and heart failure progression in animals and humans and have shown that a phosphorylation defective RyR mutant mouse (RyRS2808A) does not respond normally to sympathetic agonists and does not exhibit heart failure symptoms after myocardial infarction. Studies to confirm and extend these ideas have failed to support the original data. Experiments from many different laboratories have convincingly shown that PKA-mediated RyRS2808 phosphorylation does not play any significant role in the normal sympathetic regulation of sarcoplasmic reticulum Ca2+ release or cardiac contractility. Hearts and myocytes from RyRS2808A mice have been shown to respond normally to sympathetic agonists, and to increase Ca2+ influx, Ca2+ transients, and Ca2+ efflux. Although the RyR is involved in heart failure-related Ca2+ disturbances, this results from Ca 2+-calmodulin kinase II and reactive oxygen species-mediated regulation rather than by RyR2808 phosphorylation. Also, a new study has shown that RyRS2808A mice are not protected from myocardial infarction. Collectively, there is now a clear consensus in the published literature showing that dysregulated RyRs contribute to the altered Ca2+ regulatory phenotype of the failing heart, but PKA-mediated phosphorylation of RyRS2808 has little or no role in these alterations. © 2014 American Heart Association, Inc.


Issa J.P.,Temple University
Blood | Year: 2013

The myelodysplastic syndrome (MDS) is a clonal disorder characterized by increased stem cell proliferation coupled with aberrant differentiation resulting in a high rate of apoptosis and eventual symptoms related to bone marrow failure. Cellular differentiation is an epigenetic process that requires specific and highly ordered DNA methylation and histone modification programs. Aberrant differentiation in MDS can often be traced to abnormal DNA methylation (both gains and losses of DNA methylation genome wide and at specific loci) as well as mutations in genes that regulate epigenetic programs (TET2 and DNMT3a, both involved in DNA methylation control; EZH2 and ASXL1, both involved in histone methylation control). The epigenetic nature of MDS may explain in part the serendipitous observation that it is the disease most responsive to DNA methylation inhibitors; other epigenetic-acting drugs are being explored in MDS as well. Progression in MDS is characterized by further acquisition of epigenetic defects as well as mutations in growth-controlling genes that seem to tip the proliferation/apoptosis balance and result in the development of acute myelogenous leukemia. Although MDS is clinically and physiologically heterogeneous, a case can be made that subsets of the disease can be largely explained by disordered stem cell epigenetics.


Spano F.C.,Temple University
Accounts of Chemical Research | Year: 2010

Electronic excitations in small aggregates, thin films, and crystals of conjugated organic molecules play a fundamental role in the operation of a wide array of organic-based devices including solar cells, transistors, and light-emitting diodes. Such excitations, or excitons, are generally spread out over several molecules: a balance between the delocalizing influence of resonant intermolecular coupling and the localizing influence of static and dynamic disorder determines the coherence range of the exciton. Because of the "soft" nature of organic materials, significant nuclear relaxation in the participating molecules also accompanies the electronic excitations. To properly understand energy or charge transport, one must treat intermolecular (excitonic) coupling, electron-vibrational coupling, and disorder on equal footing. In this Account, we review the key elements of a theoretical approach based on a multiparticle representation that describes electronic excitations in organic materials as vibronic excitations surrounded by a field of vibrational excitations. Such composite excitations are appropriately called Frenkel excitonic polarons. For many conjugated molecules, the bulk of the nuclear reorganization energy following electronic excitation arises from the elongation of a symmetric vinyl stretching mode with energy ∼1400 cm-1. To appreciate the impact of aggregation, we study how the vibronic progression of this mode, which dominates the isolated (solvated) molecule absorption and emission spectra, is distorted when molecules are close enough to interact with each other. As we demonstrate in this Account, the nature of the distortion provides a wealth of information about how the molecules are packed, the strength of the excitonic interactions between molecules, the number of molecules that are coherently coupled, and the nature of the disorder. We show that the aggregation-induced deviations from the Poissonian distribution of vibronic peak intensities take on two extremes identified with ideal H- and J-aggregates. The sign of the nearest neighbor electronic coupling, positive for H and negative for J, distinguishes the two basic aggregate forms. For several decades, researchers have known that H-aggregates exhibit blue-shifted absorption spectra and are subradiant while J-aggregates exhibit the opposite behavior (red-shifted absorption and superradiance). However, the exact inclusion of exciton-vibrational coupling reveals several more distinguishing traits between the two aggregate types: in H(J)-aggregates the ratio of the first two vibronic peak intensities in the absorption spectrum decreases (increases) with increasing excitonic coupling, while the ratio of the 0-0 to 0-1 emission intensities increases (decreases) with disorder and increases (decreases) with increasing temperature. These two extreme behaviors provide the framework for understanding absorption and emission in more complex morphologies, such as herringbone packing in oligo(phenylene vinylene)s, oligothiophenes and polyacene crystals, as well as the polymorphic packing arrangements observed in carotenoids. Figure Presented © 2010 American Chemical Society.


Homologous recombination repair (HRR) protects cells from the lethal effect of spontaneous and therapy-induced DNA double-stand breaks. HRR usually depends on BRCA1/2-RAD51, and RAD52-RAD51 serves as back-up. To target HRR in tumor cells, a phenomenon called "synthetic lethality" was applied, which relies on the addiction of cancer cells to a single DNA repair pathway, whereas normal cells operate 2 or more mechanisms. Using mutagenesis and a peptide aptamer approach, we pinpointed phenylalanine 79 in RAD52 DNA binding domain I (RAD52-phenylalanine 79 [F79]) as a valid target to induce synthetic lethality in BRCA1- and/or BRCA2-deficient leukemias and carcinomas without affecting normal cells and tissues. Targeting RAD52-F79 disrupts the RAD52-DNA interaction, resulting in the accumulation of toxic DNA double-stand breaks in malignant cells, but not in normal counterparts. In addition, abrogation of RAD52-DNA interaction enhanced the antileukemia effect of already-approved drugs. BRCA-deficient status predisposing to RAD52-dependent synthetic lethality could be predicted by genetic abnormalities such as oncogenes BCR-ABL1 and PML-RAR, mutations in BRCA1 and/or BRCA2 genes, and gene expression profiles identifying leukemias displaying low levels of BRCA1 and/or BRCA2. We believe this work may initiate a personalized therapeutic approach in numerous patients with tumors displaying encoded and functional BRCA deficiency.


Genomic instability is a hallmark of chronic myeloid leukemia in chronic phase (CML-CP) resulting in BCR-ABL1 mutations encoding resistance to tyrosine kinase inhibitors (TKIs) and/or additional chromosomal aberrations leading to disease relapse and/or malignant progression. TKI-naive and TKI-treated leukemia stem cells (LSCs) and leukemia progenitor cells (LPCs) accumulate high levels of reactive oxygen species (ROS) and oxidative DNA damage. To determine the role of TKI-refractory LSCs in genomic instability, we used a murine model of CML-CP where ROS-induced oxidative DNA damage was elevated in LSCs, including quiescent LSCs, but not in LPCs. ROS-induced oxidative DNA damage in LSCs caused clinically relevant genomic instability in CML-CP-like mice, such as TKI-resistant BCR-ABL1 mutations (E255K, T315I, H396P), deletions in Ikzf1 and Trp53, and additions in Zfp423 and Idh1. Despite inhibition of BCR-ABL1 kinase, imatinib did not downregulate ROS and oxidative DNA damage in TKI-refractory LSCs to the levels detected in normal cells, and CML-CP-like mice treated with imatinib continued to accumulate clinically relevant genetic aberrations. Inhibition of class I p21-activated protein kinases by IPA3 downregulated ROS in TKI-naive and TKI-treated LSCs. Altogether, we postulate that genomic instability may originate in the most primitive TKI-refractory LSCs in TKI-naive and TKI-treated patients.


Crino P.B.,Temple University
Acta Neuropathologica | Year: 2013

Over the past decade, there have been numerous advances in our understanding of the molecular pathogenesis of tuberous sclerosis complex (TSC). Following the identification of the TSC1 and TSC2 genes, a link to regulatory control of the mammalian target of rapamycin (mTOR) signaling pathway has paved the way for new therapeutic interventions, and now even approved therapies for TSC. Gene identification has permitted establishment of cell lines and conditional knockout mouse strains to assay how abnormalities in brain structure lead to enhanced excitability, seizures, cognitive disabilities, and other neuropsychological disorders in TSC. Furthermore, work in in vitro systems and analysis of rodent models and human tissue has allowed investigators to study how brain lesions form in TSC. Evolving questions over the next decade include understanding the high clinical variability of TSC, defining why there is a lack of clear genotype-phenotype correlations, and identifying biomarkers for prognosis and stratification. The study of TSC has in many ways reflected a paradigm "bench-to-bedside" success story that serves as a model of many other neurological disorders. © 2013 Springer-Verlag Berlin Heidelberg.

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