gebhart/patrepeval huggingface dataset:
Genetic relationships determined by a DNA heteroduplex mobility assay: analysis of HIV-1 env genes (1993)

The genetic diversity of human immunodeficiency virus (HIV) is a major concern thought to impact on immunologic escape and eventual vaccine efficacy. Here, simple and rapid methods are described for the detection and estimation of genetic divergence between HIV strains on the basis of the observation that DNA heteroduplexes formed between related sequences have a reduced mobility in polyacrylamide gels proportional to their degree of divergence. Reliable phylogenetic subtypes were assigned for HIV-1 strains from around the world. Relationships between viruses were closest when derived from the same or epidemiologically linked individuals. When derived from epidemiologically unlinked individuals, the relationships between viruses in a given geographic region correlated with the length of time HIV-1 had been detected in the population and the number of strains initiating widespread infection. Heteroduplex mobility analysis thus provides a tool to expedite epidemiological investigations by assisting in the classification of HIV and is readily applicable to the screening and characterization of other infectious agents and cellular genes.
Evaluation of voltage interpolation to address process variations (2008)

Post-fabrication tuning provides a promising design approach to mitigate the performance and power overheads of process variation in advanced fabrication technologies. This paper explores design considerations and VLSI-CAD support for a recently proposed post-fabrication tuning knob called voltage interpolation. The paper discusses design tradeoffs between circuit tuning range and static power overheads that can be performed within the synthesis flow of the design process. The paper explores the scheme for a 64-core chip-multiprocessor machine using industrial-grade design blocks and shows that the scheme can be used to mitigate overhead arising from random and correlated within-die process variations. The analysis shows that the scheme can match the nominal delay target with a 10% power cost, or for the same power budget, incur only a 9% delay overhead after variations.
GITR: a multifaceted regulator of immunity belonging to the tumor necrosis factor receptor superfamily (2005)

Glucocorticoid-induced TNFR-related gene (GITR; TNFRSF18), a receptor belonging to the TNFR superfamily (TNFRSF), is activated by GITRL. GITR is expressed at low levels on resting responder T lymphocytes and is up-regulated in T regulatory cells (Treg cells) and in activated T cells. GITRL is expressed in endothelial and antigen-presenting cells. The cytoplasmic region of GITR has a striking homology with other TNFRSF members (4-1BB, CD27, OX40) and binds TRAF molecules and Siva. Over recent years, the role of GITR in the development and in the pathophysiology of the immune system has been actively explored by several groups. GITR triggering induces both pro- and anti-apoptotic effects, abrogates the suppressive activity of Treg cells and co-stimulates responder T cells, with the latter activities over-stimulating the immune system. In vivo, GITR activation causes development of autoimmune diseases and restores immune responses in a persistent retroviral infection model and in a tumor model. Intriguingly, GITR knockout mice demonstrate lower mortality in an ischemia model. The GITR-GITRL system appears crucial in regulating immunity and warrants further study.
Internalization of Exogenously Added Memapsin 2 (β-Secretase) Ectodomain by Cells Is Mediated by Amyloid Precursor Protein (2004)

Memapsin 2 (beta-secretase) is the protease that initiates cleavage of amyloid precursor protein (APP) leading to the production of amyloid-beta (Abeta) peptide and the onset of Alzheimer's disease. Both APP and memapsin 2 are Type I transmembrane proteins and are endocytosed into endosomes where APP is cleaved by memapsin 2. Separate endocytic signals are located in the cytosolic domains of these proteins. We demonstrate here that the addition of the ectodomain of memapsin 2 (M2(ED)) to cells transfected with native APP or APP Swedish mutant (APPsw) resulted in the internalization of M2(ED) into endosomes with increased Abeta production. These effects were reduced by treatment with glycosylphosphatidylinositol-specific phospholipase C. The nontransfected parental cells had little internalization of M2(ED). The internalization of M2(ED) was dependent on the endocytosis signal in APP, because the expression of a mutant APP that lacks its endocytosis signal failed to support M2(ED) internalization. These results suggest that exogenously added M2(ED) interacts with the ectodomain of APP on the cell surface leading to the internalization of M2(ED), supported by fluorescence resonance energy transfer experiments. The interactions between the two proteins is not due to the binding of substrate APPsw to the active site of memapsin 2, because neither a potent active site binding inhibitor of memapsin 2 nor an antibody directed to the beta-secretase site of APPsw had an effect on the uptake of M2(ED). In addition, full-length memapsin 2 and APP, immunoprecipitated together from cell lysates, suggested that the interaction of these two proteins is part of the native cellular processes.
End-Stage Renal Failure and National Resources: The Brazilian Experience (2006)

Brazil is the fifth largest and the fifth most populous nation in the world. Its economy rivals Mexico as the strongest in Latin America and ranks among the 15 largest economies in the world. Despite these achievements, a substantial fraction of the Brazilian population still lives in poverty, and many still have limited access to medical assistance. There are currently about 380 patients on hemodialysis per million populations (pmp), approximately one third of the U.S. prevalence, suggesting that a large fraction of end-stage renal disease (ESRD) patients are not diagnosed and treated properly. In Brazil, access to renal replacement therapy (RRT), including renal transplantation, is universal, and the corresponding costs, including those of medications (immunosuppressors and treatment of ESRD complications), are covered by the Brazilian government. However, given the continuous growth of the ESRD population and of the costs incurred by RRT, the efficacy and reach of this system may be severely limited in years to come. In the current struggle against the ESRD epidemics, the Brazilian medical community and health authorities face a triple challenge: to limit the incidence of renal disease, slow or detain the progression of established chronic nephropathies, and ensure that access to quality RRT remains granted to all those who, despite all efforts, reach ESRD.
Apoptosis in Leukemia Cells Is Accompanied by Alterations in the Levels and Localization of Nucleolin (2003)

Molecular defects in apoptotic pathways are thought to often contribute to the abnormal expansion of malignant cells and their resistance to chemotherapy. Therefore, a comprehensive knowledge of the mechanisms controlling induction of apoptosis and subsequent cellular disintegration could result in improved methods for prognosis and treatment of cancer. In this study, we have examined apoptosis-induced alterations in two proteins, nucleolin and poly(ADP-ribose) polymerase-1 (PARP-1), in U937 leukemia cells. Nucleolin is expressed at high levels in malignant cells, and it is a multifunctional and mobile protein that can shuttle among the nucleolus, nucleoplasm, cytoplasm, and plasma membrane. Here, we report our findings that UV irradiation or camptothecin treatment of U937 cells induced apoptosis and caused a significant change in the levels and localization of nucleolin within the nucleus. Additionally, nucleolin levels were dramatically decreased in extracts containing the cytoplasm and plasma membrane. These alterations could be abrogated by pre-incubation with an inhibitor of PARP-1 (3-aminobenzamide), and our data support a potential role for nucleolin in removing cleaved PARP-1 from dying cells. Furthermore, both nucleolin and cleaved PARP-1 were detected in the culture medium of cells undergoing apoptosis, associated with particles of a size consistent with apoptotic bodies. These results indicate that nucleolin plays an important role in apoptosis, and could be a useful marker for assessing apoptosis or detecting apoptotic bodies. In addition, the data provide a possible explanation for the appearance of nucleolin and PARP-1 autoantibodies in some autoimmune diseases.
Intranasal drug delivery for systemic medications. (1987)

This article is designed to provide a critical literature review on the scientific advances in intra- and transnasal drug delivery for systemic medication. The article discusses the fundamentals, developmental concepts, and biomedical assessment of the transnasal administration of systemically effective drugs which are either easily inactivated when taken orally, due to the extensive hepatic first-pass elimination, or too large in molecular size to be absorbed efficiently, except by i.v. administration.
Aspirin and clopidogrel resistance: an emerging clinical entity (2005)

Antiplatelet therapy is a cornerstone of cardiovascular medicine. Aspirin and clopidogrel have emerged as critical therapies in the treatment of cardiovascular disease. Despite their efficacy, patients on these medications continue to suffer complications. Millions of patients are currently on low-dose antiplatelet therapy but it is unknown how many of these patients are under-treated or on the wrong medication. Aspirin and clopidogrel resistance are emerging clinical entities with potentially severe consequences such as recurrent myocardial infarction, stroke, or death. The mechanism of resistance remains incompletely defined, but there are specific clinical, cellular, and genetic factors that influence therapeutic failure. These factors range from physicians who fail to prescribe these medications despite appropriate indications to polymorphisms of platelet membrane glycoproteins. Rapid and accurate diagnosis of antiplatelet resistance also remains an issue as new bedside tests are developed. By understanding the mechanism of therapeutic failure and by improving the diagnosis of this clinical entity, a new era of individualized antiplatelet therapy may arise with routine measurements of platelet activity in the same way that cholesterol, blood pressure, and blood sugar are followed, thus improving the care for millions of people.
Nanosecond pulse generator using a fast recovery diode (2004)

Design and operation of a fast recovery diode based pulse generator is presented. The generator produces 3 ns wide, 600 V amplitude pulses into a 50 ohm load at the maximum repetition rate of 100 kHz. Pulses shorter than 10 ns are essential for the studies of biological cell response to high electric fields while avoiding ordinary electroporation effects dominant at long pulses. The use of a mass-produced fast recovery surface-mount rectifier diode in this circuit substantially simplifies the generator and results in low cost and very small footprint. Similar diode switched pulse generators have been described in the literature using mostly custom fabricated snap-recovery diodes. Here we give an example of an ordinary low cost diode performing similarly to the custom fabricated counterpart. The diode switched circuit relaxes the requirement on the speed of the main closing switch, in our case a low cost power MOSFET-saturable core transformer combination.
Screening and identification of novel B cell epitopes of Toxoplasma gondii SAG1 (2013)

We have precisely located the epitopes of T. gondii SAG1 using pig sera collected at different time points after infection. The identified epitopes may be useful for the further study of epitope-based vaccines and diagnostic reagents.
Surfactants: Their Critical Role in Enhancing Drug Delivery to the Lungs (2011)

For local lung conditions and diseases, pulmonary drug delivery has been widely used for more than 50 years now. A more recent trend involves the pulmonary route as a systemic drug-delivery target. Advantages such as avoidance of the gastrointestinal environment, different enzyme content compared with the intestine, and avoidance of first-pass metabolism make the lung an alternative route for the systemic delivery of actives. However, the lung offers barriers to absorption such as a surfactant layer, epithelial surface lining fluid, epithelial monolayer, interstitium and basement membrane, and capillary endothelium. Many delivery strategies have been developed in order to overcome these limitations. The use of surfactants is one of these approaches and their role in enhancing pulmonary drug delivery is reviewed in this article. A systematic review of the literature relating to the effect of surfactants on formulations for pulmonary delivery was conducted. Specifically, research reporting enhancement of in vivo performance was focused on. The effect of the addition of surfactants such as phospholipids, bile salts, non-ionic, fatty acids, and liposomes as phospholipid-containing carriers on the enhancement of therapeutic outcomes of drugs for pulmonary delivery was compiled. The main use attributed to surfactants in pulmonary drug delivery is as absorption enhancers by mechanisms of action not yet fully understood. Furthermore, surfactants have been used to improve the delivery of inhaled drugs in various additional strategies discussed herein.
The variety of expressions for heaven and earth in the Rgveda (2010)

This article investigates coordinative nominal constructions in the Rgveda, focusing on grammatical patterns of the so-called dual deities—pairs of gods whose names are joined in dvandva compounds or in other coordinative constructions (i.e. asyndeta, elliptic duals, and syntagms constructed with copulative conjunctions). It overviews the role of dual deities in the Rgveda and emphasizes the significance of the Rgvedic poetic style in the research of dual deities. The main focus of the article is the divine pair dyāvā-pthivī “Heaven and Earth”—the only prominent male-female pair in the Rgveda. It identifies the variety of coordinative constructions comprised of the names of Heaven and Earth, and the stylistic paradigms in which this pair occurs. The article argues that all types of dvandva compounds and other syntagms signifying dual theonyms are a reflection of the style of Rgvedic language and, as shown in the case of Heaven and Earth, the specific stylistic features and the ambiguities of gender of Heaven and Earth reflect the belief in magical power attributed to the names of deities—the frequent articulation of divine names in a variety of coordinative constructions, following specific formulae, was believed to produce greater magical effect in Vedic rituals.
Context Dependent Role of the CD36 - Thrombospondin - Histidine-Rich Glycoprotein Axis in Tumor Angiogenesis and Growth (2012)

The angiogenic switch is a promising therapeutic target in cancer. Work by our laboratory and others has described an important endogenous anti-angiogenic pathway mediated by interactions of CD36, a receptor on microvascular endothelial cells, with proteins containing thrombospondin (TSP) type I repeat domains (TSR). Recent studies revealed that circulating Histidine Rich Glycoprotein (HRG) inhibits the anti-angiogenic potential of the CD36-TSR pathway by functioning as a decoy receptor that binds and sequesters TSR proteins. As tumors of different origin display variable expression profiles of numerous targets, we hypothesized that the TSP-CD36-HRG axis regulates vascularization and growth in the tumor microenvironment in a context, or tumor type, dependent manner. Growth of Lewis Lung Carcinoma (LL2) and B16F1 Melanoma tumor cell implants in syngeneic wild type (WT), hrg, or cd36 null mice were used as a model to interrogate this signaling axis. LL2 tumor volumes were greater in cd36 null mice and smaller in hrg null mice compared to WT. Immunofluorescent staining showed increased vascularity in cd36 null vs. WT and WT vs. hrg null mice. No differences in tumor growth or vascularity were observed with B16F1 implants, consistent with lack of expression of TSP-1 in B16F1 cells. When TSR expression was induced in B16F1 cells by cDNA transfection, tumor growth and vascularity were similar to that seen with LL2 cells. These data show a role for CD36-mediated anti-angiogenic activity in the tumor microenvironment when TSR proteins are available and demonstrate that HRG modulates this activity. Further, they suggest a mechanism by which tumor microenvironments may regulate sensitivity to TSR containing proteins.
The constitutive and inducible expression of Nurr1, a key regulator of dopaminergic neuronal differentiation, in human neural and non‐neural cell lines (2002)

Nur-related factor 1 (Nurr1), nerve growth factor-induced gene B (NGFI-B) and neuron-derived orphan receptor-1 (NOR-1) constitute the orphan nuclear receptor subfamily of transcription factors. Previous studies showed that midbrain dopaminergic neuronal precursor cells failed to differentiate in Nurr1-deficient mice. To investigate a role of Nurr1 in human neuronal function, Nurr1 mRNA expression was studied in human neural cell lines by RT-PCR and northern blot analysis. Nurr1, NGFI-B and NOR-1 mRNA were coexpressed in all human neural and nonneural cell lines under the serum-containing culture condition, except for SK-N-SH neuroblastoma, in which Nurr1 mRNA was undetectable. The levels of Nurr1, NGFI-B and NOR-1 mRNA were elevated markedly in NTera2 teratocarcinoma-derived neurons (NTera2-N), a model of differentiated human neurons, following a 1.5 or 3 h-exposure to 1 mM dibutyryl cyclic AMP or 100 nm phorbol 12-myristate 13-acetate. NGFI-B mRNA levels were also elevated in NTera2-N cells by exposure to 100 ng/mL brain-derived neurotrophic factor (BDNF). To identify Nurr1-target genes, the mRNA expression of 27 genes potentially involved in dopaminergic neuronal differentiation and survival, including BDNF, glia-derived neurotrophic factor, their receptors, tyrosine hydroxylase and alpha-synuclein, were studied in HEK293 cells following overexpression of Nurr1. None of these genes examined, however, showed significant changes. These results indicate that Nurr1, NGFI-B and NOR-1 mRNA are expressed constitutively in various human neural and non-neural cell lines under the serum-containing culture condition, and their levels are up-regulated in human neurons by activation of protein kinase A or protein kinase C pathway, although putative coactivators expressed in dopaminergic neuronal precursor cells might be required for efficient transcriptional activation of Nurr1-target genes.
Consistent Force Field for Calculations of Conformations, Vibrational Spectra, and Enthalpies of Cycloalkane and n-Alkane Molecules (1968)

An inductive method for a systematic selection of energy functions of interatomic interactions in large families of molecules is suggested and is applied to the family of cycloalkane and n-alkane molecules. Equilibrium conformations, vibrational frequencies, and excess enthalpies, including strain energies and vibrational enthalpies, are all derived from the same set of energy functions. The energy-function parameters are optimized by a least-squares algorithm to give the best possible agreement with a large amount and variety of observed data. Analytical derivatives of the various calculated quantities with respect to the energy parameters help to facilitate the computational procedures. The resulting agreement with experiment is used as a measure of success of the energy functions with optimized parameters, referred to as “consistent force field” (CFF). Different CFF's are compared and selected according to their relative success. Energy functions commonly used in conformational analysis are examined in preliminary consistent-force-field calculations and are found inadequate. Considerable imporvement is obtained when Coulomb interactions between residual atomic charges are included, and when interactions between atoms bonded to a common atom are represented by a Urey–Bradley-type force field, while Lennard-Jones potentials are used for nonbonded interactions between atoms separated by more than one atom. Vibrational frequencies as well as vibrational molecular enthalpies are derived for all cycloalkanes C5 through C12. The spectroscopic force constants are derived from the CFF as functions of molecular conformations. Agreement with available spectroscopic assignments of frequencies is reasonably good. A few improvements are suggested for cyclopentane assignments. The path and moment of inertia of pseudorotation in cyclopentane are calculated. Cyclodecane frequency assignments, based on the derived conformational C2h symmetry, are suggested for the first time. Calculated excess enthalpies of C5H10 and medium cycloalkanes agree well with observed values. Contributions of vibration–translation–rotation are shown to amount to a significant part of the excess enthalpy.
A Site-Specific Integrated Col2.3GFP Reporter Identifies Osteoblasts Within Mineralized Tissue Formed In Vivo by Human Embryonic Stem Cells (2014)

The use of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) for study and treatment of bone diseases or traumatic bone injuries requires efficient protocols to differentiate hESCs/iPSCs into cells with osteogenic potential and the ability to isolate differentiated osteoblasts for analysis. We have used zinc finger nuclease technology to deliver a construct containing the Col2.3 promoter driving GFPemerald to the AAVS1 site (referred to as a "safe harbor" site), in human embryonic stem cells (H9Zn2.3GFP), with the goal of marking the cells that have become differentiated osteoblasts. In teratomas formed using these cells, we identified green fluorescent protein (GFP)-positive cells specifically associated with in vivo bone formation. We also differentiated the cells into a mesenchymal stem cell population with osteogenic potential and implanted them into a mouse calvarial defect model. We observed GFP-positive cells associated with alizarin complexone-labeled newly formed bone surfaces. The cells were alkaline phosphatase-positive, and immunohistochemistry with human specific bone sialoprotein (BSP) antibody indicates that the GFP-positive cells are also associated with the human BSP-containing matrix, demonstrating that the Col2.3GFP construct marks cells in the osteoblast lineage. Single-cell cloning generated a 100% Col2.3GFP-positive cell population, as demonstrated by fluorescence in situ hybridization using a GFP probe. The karyotype was normal, and pluripotency was demonstrated by Tra1-60 immunostaining, pluripotent low density reverse transcription-polymerase chain reaction array and embryoid body formation. These cells will be useful to develop optimal osteogenic differentiation protocols and to isolate osteoblasts from normal and diseased iPSCs for analysis.
Dynamic nuclear polarization at very low magnetic fields (1998)

The recent developments in dynamic nuclear polarization (DNP) at low magnetic fields are presented. The first part of the paper is dedicated to DNP theory for 14N nitroxide systems. It is shown that the lower the magnetic field, the higher the DNP factor. In the second part the material necessary to perform DNP in a low magnetic field is described. The third part is devoted to potential biological applications such as oximetry and free radical imaging.