gebhart/patrepeval huggingface dataset:
Amelioration of spinal cord compressive injury by pharmacological preconditioning with erythropoietin and a nonerythropoietic erythropoietin derivative (2006)

These results demonstrate that EPO and its analog do not need to be present at the time of injury to provide tissue protection and that tissue protection is markedly effective when either agent is administered immediately after injury. Furthermore, the findings suggest that asialoEPO is a useful reagent with which to study the dynamics of EPO-mediated neuroprotection. In addition, the findings support the concept of using a nonerythropoietic EPO derivative to provide tissue protection without activating the undesirable effects of EPO.
Tumor necrosis factor‐α‐induced cell death in U373 cells overexpressing α‐synuclein (2003)

Intracellular alpha-synuclein inclusion formation in glial cells is frequently seen in Parkinson's disease and multiple system atrophy. Microglial activation in these neurodegenerative disorders suggests that neuroinflammatory responses might interact with alpha-synuclein and contribute to the pathogenesis of these disorders. To study the role of tumor necrosis factor-alpha (TNF-alpha), an important proinflammatory cytokine produced by microglia, on cells overexpressing alpha-synuclein we have used the astrocytoma cell line U373 engineered to express C-terminally truncated alpha-synuclein as a fusion protein with red or green fluorescent proteins. We demonstrate that alpha-synuclein overexpression augmented TNF-alpha-induced apoptotic cell death in U373 cells by induction of caspase activation. Furthermore, TNF-alpha exposure was associated with significant cytoskeletal changes characterized by altered inclusion composition with loss of cytoskeletal proteins and elevation of high-molecular-weight alpha-synuclein species. We conclude that alpha-synuclein overexpression significantly increases the vulnerability of U373 cells to apoptosis through TNF-alpha-mediated pathways.
Performance analysis and design optimization of near ballistic carbon nanotube field-effect transistors (2005)

A near ballistic carbon nanotube field-effect transistor (CNTFET) that integrates an ultra-short channel, low-barrier metal contacts, and a thin high-K gate insulator is modeled and analyzed using self-consistent quantum simulations. Numerical simulations, which solve a quantum transport equation self-consistently with a 3D Poisson equation using the non-equilibrium Green's function (NEGF) formalism, are used to understand the transistor physics and to suggest design optimization. Important device issues of: (1) how close the transistor operates to its ballistic limit; (2) what are the roles of phonon scattering and higher subband conduction; (3) how to further optimize the CNTFET; and (4) how the CNTFET compares to a state-of-the-art Si MOSFET, are explored and discussed.
Structural Biology of Bacterial Iron Uptake Systems (2001)

Numerous bacterial proteins are involved in microbial iron uptake and transport and considerable variation has been found in the uptake schemes used by different bacterial species. However, whether extracting iron from host proteins such as transferrin, lactoferrin or hemoglobin or importing low molecular weight iron-chelating compounds such as heme, citrate or siderophores, Gram-negative pathogenic bacteria typically employ a specific outer membrane receptor, a periplasmic binding protein and two inner membrane associated proteins: a transporter coupled with an ATP-hydrolyzing protein. Often, studies have shown that proteins with similar function but little amino acid sequence homology are structurally related. Elucidation of the structures of the Escherichia coli outer membrane siderophore transport proteins FepA and FhuA have provided the first insights into the conformational changes required for ligand transport through the bacterial outer membrane. The variations between the structures of the prototypical periplasmic ferric binding protein FbpA from Neisseria and Haemophilus influenzae and the unusual E coli periplasmic siderophore binding protein FhuD reveal that the different periplasmic ligand binding proteins exercise distinct mechanisms for ligand binding and release. The structure of the hemophore HasA from Serratia marcescens shows how heme may be extracted and utilized by the bacteria. Other biochemical evidence also shows that the proteins that provide energy for iron transport at the outer membrane, such as the TonB-ExbB-ExbD system, are structurally very similar across bacterial species. Likewise, the iron-sensitive gene regulatory protein Fur is found in most bacteria. To date, no structural information is available for Fur, but the structure for the related protein DxtR has been determined. Together, these three-dimensional structures complement our knowledge of iron transport systems from other pathogenic bacteria, including Pseudomonas aeruginosa, which has a number of homologous iron uptake proteins. More importantly, the current structures for iron transport proteins provide rational starting points for design of novel antimicrobial agents.
Rescue and Autonomous Replication of Adeno-Associated Virus Type 2 Genomes Containing Rep-Binding Site Mutations in the Viral p5 Promoter (1998)

The Rep proteins encoded by the adeno-associated virus type 2 (AAV) play a crucial role in the rescue, replication, and integration of the viral genome. In the absence of a helper virus, little expression of the AAV Rep proteins occurs, and the AAV genome fails to undergo DNA replication. Since previous studies have established that expression of the Rep78 and Rep68 proteins from the viral p5 promoter is controlled by the Rep-binding site (RBS) and the YY1 factor-binding site (YBS), we constructed a number of recombinant AAV plasmids containing mutations and/or deletions of the RBS and the YBS in the p5 promoter. These plasmids were transfected in HeLa or 293 cells and analyzed for the potential to undergo AAV DNA rescue and replication. Our studies revealed that (i) a low-level rescue and autonomous replication of the wild-type AAV genome occurred in 293 but not in HeLa cells; (ii) mutations in the RBS resulted in augmented expression from the p5 promoter, leading to more efficient rescue and/or replication of the AAV genome in 293 but not in HeLa cells; (iii) little rescue and/or replication occurred from plasmids containing mutations in the YBS alone in the absence of coinfection with adenovirus; (iv) expression of the adenovirus E1A gene products was insufficient to mediate rescue and/or replication of the AAV genome in HeLa cells; (v) autonomously replicated AAV genomes in 293 cells were successfully encapsidated in mature progeny virions that were biologically active in secondary infection of HeLa cells in the presence of adenovirus; and (vi) stable transfection of recombinant AAV plasmids containing a gene for resistance to neomycin significantly affected stable integration only in 293 cells, presumably because rescue and autonomous replication of the AAV genome from these plasmids occurred in 293 cells but not in HeLa or KB cells. These data suggest that in the absence of adenovirus, the AAV Rep protein-RBS interaction plays a dominant role in down-regulating viral gene expression from the p5 promoter and that perturbation in this interaction is sufficient to confer autonomous replication competence to AAV in 293 cells.
Biosequence Exegesis (1999)

Annotation of large-scale gene sequence data will benefit from comprehensive and consistent application of well-documented, standard analysis methods and from progressive and vigilant efforts to ensure quality and utility and to keep the annotation up to date. However, it is imperative to learn how to apply information derived from functional genomics and proteomics technologies to conceptualize and explain the behaviors of biological systems. Quantitative and dynamical models of systems behaviors will supersede the limited and static forms of single-gene annotation that are now the norm. Molecular biological epistemology will increasingly encompass both teleological and causal explanations.
The Recombinant T Cell Receptor Strategy: Insights into Structure and Function of Recombinant Immunoreceptors on the Way Towards an Optimal Receptor Design for Cellular Immunotherapy (2002)

A promising approach in adoptive immunotherapy is based on the induction of a specific cellular anti-tumor response by antigen-specific, cytolytic T cells. Due to difficulties in isolating tumor-specific T cells in sufficient amounts, it was proposed to graft cytolytic T cells with an antigen-specific, recombinant T cell receptor. The antigen binding domain of the receptor consists of a single-chain antibody fragment (scFv) that is derived from a monoclonal antibody and binds to a tumor associated antigen. The intracellular signalling domain is derived from the cytoplasmic part of a membrane bound receptor to induce cellular activation, e.g., the Fc epsilon RI receptor gamma-chain or the CD3 zeta-chain. By use of this type of recombinant receptor, the strategy combines the advantages of MHC-independent, antibody-based antigen binding with efficient T cell activation upon specific binding to the receptor ligand. The modular composition of the receptor, moreover, facilitates modification of both the antigen binding and signalling properties. Accordingly, we and others have generated a panel of recombinant T cell receptors with specificities for malignantly or virally transformed cells. Receptor grafted effector cells were demonstrated to mediate a highly efficient immune response towards antigen expressing target cells. However, little is known about the impact of the recombinant receptor modules on recognition of highly heterologous target antigens and on cellular activation in a complex immunological context. This review summarizes the current knowledge about the generation and function of recombinant immunoreceptors and discusses the limitations and perspectives of the methodology for use in cellular immunotherapy.
The external Heapsort (1989)

Heapsort is an internal sorting method which sorts an array of n records in place in O(n log n) time. Heapsort is generally considered unsuitable for external random-access sorting. By replacing key comparisons with merge operations on pages, it is shown how to obtain an in-place external sort which requires O(m log m) page references, where m is the number of pages which the file occupies. The new sort method (called Hillsort) has several useful properties for advanced database management systems. Not only does Hillsort operate in place, i.e., no additional external storage space is required assuming that the page table can be kept in core memory, but accesses to adjacent pages in the heap require one seek only if the pages are physically contiguous. The authors define the Hillsort model of computation for external random-access sorting, develop the complete algorithm and then prove it correct. The model is next refined and a buffer management concept is introduced so as to reduce the number of merge operations and page references, and make the method competitive to a basic balanced two-way external merge. Performance characteristics are noted such as the worst-case upper bound, which can be carried over from Heapsort, and the average-case behavior, deduced from experimental findings. It is shown that the refined version of the algorithm which is on a par with the external merge sort.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Flow injection cytometry: A new approach for sample and solution handling in flow cytometry (1993)

A prototype instrument for sample and solution handling in flow cytometry has been constructed. The system is modular and allows the control of any combination of up to 4 pumps, 2 selection valves, and 2 injection valves. These devices are controlled by a computer using TTL-logic. The flow injection instrument is interfaced to the flow cytometer via a 6-port injection valve, thereby facilitating virtually any flow pattern to be implemented without affecting the fluidics of the cytometer. Salient features of the instrument are accurate control of the volume of injected sample and reagent, reproducible timing, and controlled mixing conditions. Results from model experiments of on-line staining of trout erythrocytes with different concentrations of 4',6-diamidino-2-phenylindole (DAPI) and propidium iodide (PI) are shown. Possible ways to improve the performance and utility of the instrument are also discussed.
Mechanochemical switching between growth and differentiation during fibroblast growth factor-stimulated angiogenesis in vitro: role of extracellular matrix. (1989)

The angiogenic factor, basic fibroblast growth factor (FGF), either stimulates endothelial cell growth or promotes capillary differentiation depending upon the microenvironment in which it acts. Analysis of various in vitro models of spontaneous angiogenesis, in combination with time-lapse cinematography, demonstrated that capillary tube formation was greatly facilitated by promoting multicellular retraction and cell elevation above the surface of the rigid culture dish or by culturing endothelial cells on malleable extracellular matrix (ECM) substrata. These observations suggested to us that mechanical (i.e., tension-dependent) interactions between endothelial cells and ECM may serve to regulate capillary development. To test this hypothesis, FGF-stimulated endothelial cells were grown in chemically defined medium on bacteriological (nonadhesive) dishes that were precoated with different densities of fibronectin. Extensive cell spreading and growth were promoted by fibronectin coating densities that were highly adhesive (greater than 500 ng/cm2), whereas cell rounding, detachment, and loss of viability were observed on dishes coated with low fibronectin concentrations (less than 100 ng/cm2). Intermediate fibronectin coating densities (100-500 ng/cm2) promoted cell extension, but they could not completely resist cell tractional forces. Partial retraction of multicellular aggregates resulted in cell shortening, cessation of growth, and formation of branching tubular networks within 24-48 h. Multicellular retraction and subsequent tube formation also could be elicited on highly adhesive dishes by overcoming the mechanical resistance of the substratum using higher cell plating numbers. Dishes coated with varying concentrations of type IV collagen or gelatin produced similar results. These results suggest that ECM components may act locally to regulate the growth and pattern-regulating actions of soluble FGF based upon their ability to resist cell-generated mechanical loads. Thus, we propose that FGF-stimulated endothelial cells may be "switched" between growth, differentiation, and involution modes during angiogenesis by altering the adhesivity or mechanical integrity of their ECM.
Rabies veterinary virus vaccine produced in BHK-21 cells grown on microcarriers in a bioreactor. (1995)

BHK-21 cells were grown in microcarriers in the CELLIGEN CL 50 bioreactor to produce a stock of rabies veterinary virus vaccine PV (Pasteur virus) strain. Perfusion mode operation of this bioreactor produced between two- and fourfold larger yields (cells/ml) than traditional stationary cell culture systems (i.e., Blake, and Roller bottles or cell factory multitrays). The method employed harvested 281 of rabies virus in 200 h (infectivity titer 0.6 +/- 1.4 x 10(7) LD50 per ml) in a single operation. The risk of contamination is thus reduced when compared with traditional stationary methods which, in order to obtain the same amount of virus, would require the operation of 285 Blake bottles, or 143 Roller bottles, or 15 Cell Factory multitrays (10 trays). By perfusion mode operation of the bioreactor, 89% of the cell culture medium was recovered as vaccinal virus, which contrasts with the yield of only 50-59% using traditional cell culture systems. On the other hand, only 925 ml of fetal serum was required to obtain the 281 of rabies virus harvest as compared to the 3420 ml required by traditional methods.
Maternal Plasma DNA Analysis with Massively Parallel Sequencing by Ligation for Noninvasive Prenatal Diagnosis of Trisomy 21 (2009)

Massively parallel sequencing-by-ligation of maternal plasma DNA was effective in identifying T21 fetuses noninvasively. The quantitative biases observed among the GRs of certain chromosomes were more likely based on analytical factors than biological factors. Further research is needed to enhance the precision for measuring for the representations of chromosomes 18 and 13.
Automatic arima time series modeling for adaptive I/O prefetching (2004)

Inadequate I/O performance remains a major challenge in using high-end computing systems effectively. To address this problem, we present TsModeler, an automatic time series modeling and prediction framework for adaptive I/O prefetching that uses ARIMA time series models to predict the temporal patterns of I/O requests. These online pattern analysis techniques and cutoff indicators for autocorrelation patterns enable multistep online predictions suitable for multiblock prefetching. This work also combines time series predictions with spatial Markov model predictions to determine when, what, and how many blocks to prefetch. Experimental results show reductions in execution time compared to the standard Linux file system across various hardware configurations.
CARBOHYDRATE NUTRITION OFCHLORELLA VULGARIS (1951)

A substrain of the Pratt–Trelease strain of Chlorella vulgaris was grown at 30 °C. in light (200 ft-c.) and in darkness, on Emerson's medium enriched with various carbohydrates and related compounds in 1% concentration. D-glucose, D-fructose, D-galactose, and β-glucosides such as aesculin, cellobiose, lactose, and methyl-β-D-glucoside, are all good sources of carbon and energy for growth in darkness. Alpha glucosides such as sucrose, maltose, and methyl-α-D-glucoside are poor substrates as are also D-mannose, L-mannose, L-galactose, the pentoses, sugar acids, sugar alcohols, and polysaccharides. Illumination stimulates growth in the presence of D-glucose, D-fructose, and D-galactose more than in the presence of the β-glucosides. With methyl-β-D-glucoside better growth is obtained in darkness than in light. The optimum temperature for growth of the organism is near 35 °C. in the media used. Basal media containing nitrate nitrogen allow better utilization of sugars than those containing ammonia nitrogen. Most of the glucose utilized is converted to cellular material.
HSV-TK Gene Transfer into Donor Lymphocytes for Control of Allogeneic Graft-Versus-Leukemia (1997)

In allogeneic bone marrow transplantation (allo-BMT), donor lymphocytes play a central therapeutic role in both graft-versus-leukemia (GvL) and immune reconstitution. However, their use is limited by the risk of severe graft-versus-host disease (GvHD). Eight patients who relapsed or developed Epstein-Barr virus-induced lymphoma after T cell-depleted BMT were then treated with donor lymphocytes transduced with the herpes simplex virus thymidine kinase (HSV-TK) suicide gene. The transduced lymphocytes survived for up to 12 months, resulting in antitumor activity in five patients. Three patients developed GvHD, which could be effectively controlled by ganciclovir-induced elimination of the transduced cells. These data show that genetic manipulation of donor lymphocytes may increase the efficacy and safety of allo-BMT and expand its application to a larger number of patients.
HLA-mismatched cord blood transplantation: immunological studies. (1994)

Two cases of HLA partially matched related cord blood transplantation were reported. The first patient remains healthy more than 4 years after graft. The second patient died from acute GVHD. In the first case, the immune reconstitution was studied over a 2 year period after graft: the alloreactive cytotoxic T-cell precursor (CTLp) frequencies were comparable between the donor and the recipient. Indirect evidence suggested that the resolution of GVHD was not due to a specific deletion of CTLp against the HLA antigens unshared between donor and recipient.
Microfabricated transmission-line transformers with DC isolation (2014)

A transmission line transformer (TLT) is a device that transforms a circuit impedance and is implemented with interconnected transmission lines. While traditional TLTs, operating at UHF and low microwave frequencies, are constructed from pairs of coaxial lines wound around ferrite cores, various compact implementations at higher frequency without magnetic materials have been demonstrated with multilayer circuit boards, monolithic microwave integrated circuits (MMIC) and air-filled microcoaxial lines implemented in the PolyStrata <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">®</sup> wafer-scale technology. Microfabricated Guanella TLTs in the microwave range typically span several GHz of bandwidth, but they are not suitable for impedance matching of power amplifiers and active devices because the input and output ports are shorted to ground and therefore lack DC isolation. A compact and DC-isolated TLT would be especially useful in small-size, low-loss and high-speed DC-to-DC converters.
The thymus and myasthenia gravis: immunological and neurophysiological aspects. (1999)

Myasthenia gravis (MG) is an autoimmune disorder, in which end-plate membrane damage is induced by antibodies directed toward various epitopes of the main immunogenic region of the nicotinic acetylcholine receptor (AChR). This article reviews the mechanisms responsible for the development of MG. Recent investigations into the roles of the thymus, antibodies against AChR, cytokines, and neuromuscular transmission have given new insight into the pathogenesis of MG. These new advances have led to a better understanding of the immune mechanisms in MG and have opened new therapeutic horizons.
Secondary structure and signal assignments of human‐immunodeficiency‐virus‐1 protease complexed to a novel, structure‐based inhibitor (1994)

We report comprehensive NMR studies in solution of the human-immunodeficiency-virus (HIV)-1 protease. Stable solutions of the protease were obtained by complexing the protein to a designed cyclic urea inhibitor DMP 323. A variety of triple-resonance experiments provided essentially complete 1H, 13C and 15N NMR signal assignments of the protease. These assignments, together with short-range NOE constraints, coupling constants and hydrogen-exchange data, yielded the secondary structure of the protease in solution. The results reported herein open the way to the determination of the high-resolution three-dimensional solution structures of protease/inhibitor complexes, as well as to studies of protease dynamics and solvent interactions.
Forward body-bias SRAM circuitry on bulk Si withtwin double-well (1997)

A novel SRAM cell suitable for low-voltage adiabatic logic is proposed. This cell uses forward body-bias effects, which are controlled by the stored data, to prevent a passgate transistor from turning on when a large source-to-drain voltage exists.