gebhart/patrepeval huggingface dataset:
Two Novel Tau Antibodies Targeting the 396/404 Region Are Primarily Taken Up by Neurons and Reduce Tau Protein Pathology (2013)

Aggregated Tau proteins are hallmarks of Alzheimer disease and other tauopathies. Recent studies from our group and others have demonstrated that both active and passive immunizations reduce Tau pathology and prevent cognitive decline in transgenic mice. To determine the efficacy and safety of targeting the prominent 396/404 region, we developed two novel monoclonal antibodies (mAbs) with distinct binding profiles for phospho and non-phospho epitopes. The two mAbs significantly reduced hyperphosphorylated soluble Tau in long term brain slice cultures without apparent toxicity, suggesting the therapeutic importance of targeting the 396/404 region. In mechanistic studies, we found that neurons were the primary cell type that internalized the mAbs, whereas a small amount of mAbs was taken up by microglia cells. Within neurons, the two mAbs were highly colocalized with distinct pathological Tau markers, indicating their affinity toward different stages or forms of pathological Tau. Moreover, the mAbs were largely co-localized with endosomal/lysosomal markers, and partially co-localized with autophagy pathway markers. Additionally, the Fab fragments of the mAbs were able to enter neurons, but unlike the whole antibodies, the fragments were not specifically localized in pathological neurons. In summary, our Tau mAbs were safe and efficient to clear pathological Tau in a brain slice model. Fc-receptor-mediated endocytosis and the endosome/autophagosome/lysosome system are likely to have a critical role in antibody-mediated clearance of Tau pathology.
Amino acids essential for RNase H activity of hepadnaviruses are also required for efficient elongation of minus-strand viral DNA (1996)

The hepadnavirus P gene contains amino acid sequences which share homology with all known RNases H. In this study, we made four mutants in which single amino acids of the duck hepatitis B virus (DHBV) RNase H region were altered. In two of them, amino acids at locations comprising the putative catalytic site were changed, while the remaining mutants had alterations at amino acids conserved among hepadnaviruses. Transfection of these mutant genomes into permissive cells resulted in synthesis of several discrete viral nucleic acid species, ranging in apparent sizes from approximately 500 to 3,000 bp, numbered I, II, III, IV, and V. While the locations of the species were similar in all mutants, the proportions of the species varied among the mutants. Analysis of the nucleic acid species revealed that they were hybrid molecules of RNA and minus-strand DNA, indicating that the RNase H activity was missing or greatly reduced in these mutants. Primer extension experiments showed that the mutant viruses initiated minus-strand viral DNA synthesis normally. The 3' termini of minus-strand DNA in species II, III, and IV were mapped just downstream of nucleotides 1659, 1220, and 721, respectively. Species V contained essentially full-length minus-strand viral DNA. A parallel amino acid change in the putative catalytic site of the HBV RNase H domain resulted in accumulation of low-molecular-weight hybrid molecules consisting of RNA and minus-strand DNA and similar in size and pattern to those seen with DHBV. These studies demonstrate experimentally the involvement of the C-terminal portion of the P gene in RNase H activity in both DHBV and human hepatitis B virus and indicate that the amino acids essential for RNase H activity of hepadnavirus P protein are also important for the efficient elongation of minus-strand viral DNA.
CMOS handset power amplifiers: Directions for the future (2012)

While the present market for power amplifiers in wireless handsets is largely met by GaAs HBTs, CMOS technology can provide major advantages including high integration levels, scalability, and digital control. This paper reviews possible directions for future CMOS PA development including FET stacking, envelope tracking, digital predistortion, and new architectures based on digital control, that promise to add to the advantages of CMOS in LTE applications.
Total Homocysteine in Pediatric Patients (1997)

Determination of plasma total homocysteine (tHcy; the sum of all forms of thiol derivatives that form homocysteine by reduction) (1) is essential for diagnosis and follow-up of homocystinuric patients (2) and for detection of moderate hyperhomocysteinemia, a risk factor for coronary, cerebral, and peripheral vascular disease (3). In childhood, moderate hyperhomocysteinemia may result from several genetic, nutritional (4), and iatrogenic factors (1), renal failure (5), HIV (6), and cancer (1). Plasma tHcy in children may be a useful biochemical marker for a genetic risk of premature atherosclerosis (1).

Various methods to measure tHcy have been described during the last decade, but HPLC with fluorescence detection is the most common (4)(7). Age- and sex-specific reference intervals for adults have been reported (4), considering even vitamin status (8), but data for children are sparse and inconsistent [ 9 , 10] , and no evidence is available in Mediterranean countries, where dietary vitamin content differs from that in Northern Europe or North America.

Our goal was to establish reference values for a pediatric population in our geographical area with our working conditions so that we could compare the values in further studies with those of children at risk for moderate hyperhomocysteinemia.

Specimens were collected from …
Release of Growth Hormone Binding Protein from IM-9 Lymphocytes by Endopeptidase is Dependent on Sulfydryl Group Inactivation* (1988)

The hydrophilic GH-binding protein of serum is a derivative of the GH receptor. Little is known how this GH binding protein is released from the receptor which is firmly anchored in the plasma membrane. The IM-9 lymphocytes provide a useful laboratory model for studying this process because they are richly endowed with GH receptors and, under special conditions, are able to shed these receptors during incubation. Incubation of IM-9 cells for 90 min at 30 C did not result in the appearance of significant [125I]hGH binding in conditioned medium as determined with an ultrogel AcA 44 minicolumn. When iodoacetamide, 20 mM, or N-ethylmaleimide, 5 mM, was added during incubation, the conditioned medium bound 20-35% of [125I]human(h)GH. p-Chloromercuriphenyl sulfonic acid was less effective in promoting shedding of GH-binding protein. In contrast, aprotinin, phenylmethylsulfonylfluoride (PMSF), bacitracin, leupeptin, pepstatin, phosphoramidon, or chloroquine did not promote release of GH binding protein and did not affect iodoacetamide-induced release. Release was not inhibited by the addition of serum lacking GH binding protein. GH binding protein release was markedly temperature sensitive and practically ceased at 4 C. GH binding protein incubated with [125I] hGH was cross-linked with disuccinimidyl suberate. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence of dithiothreitol the complex migrated with an estimated molecular weight of 100,000 whereas [125I]hGH cross-linked to the membrane-bound GH receptor of the IM-9 cells migrated with an estimated molecular weight of 135,000. The smaller size of the binding protein is consistent with its derivation from the extracellular domain of the GH receptor. Because the release of this GH binding is greatly augmented by iodoacetamide and N-ethylmaleimide, two known sulfhydryl reactive reagents, we suggest that a free sulfhydryl group, either on the GH receptor or on a neighboring protein normally maintains the integrity of the receptor. The loss of this sulfhydryl group destabilizes the receptor and permits a membrane endopeptidase to release the GH binding protein. Cleavage is not dependent on lysosomal action and is not inhibited by protease inhibitors.
Therapeutic antibodies as a treatment option for dengue fever (2013)

Dengue fever is the most prevalent mosquito-borne viral disease globally with about 100 million cases of acute dengue annually. Severe dengue infection can result in a life-threatening illness. In the absence of either a licensed vaccine or antiviral drug against dengue, therapeutic antibodies that neutralize dengue virus (DENV) may serve as an effective medical countermeasure against severe dengue. However, therapeutic antibodies would need to effectively neutralize all four DENV serotypes. It must not induce antibody-dependent enhancement of DENV infection in monocytes/macrophages through Fc gamma receptor (FcγR)-mediated phagocytosis, which is hypothesized to increase the risk of severe dengue. Here, we review the strategies and technologies that can be adopted to develop antibodies for therapeutic applications. We also discuss the mechanism of antibody neutralization in the cells targeted by DENV that express Fc gamma receptor. These studies have provided significant insight toward the use of therapeutic antibodies as a potentially promising bulwark against dengue.
Compstatin Inhibits Complement and Cellular Activation in Whole Blood in Two Models of Extracorporeal Circulation (1998)

Recently, a C3-binding cyclic synthetic peptide (Compstatin) has been identified that binds to complement component C3 and inhibits complement activation. Here we have examined the influence of Compstatin on complement activation and its indirect effects on cellular responses in whole blood in two models for extracorporeal circulation. Compstatin effectively inhibited the generation of C3a and sC5b-9 and the binding of C3/ C3 fragments to the polymer surface. As a result of the inhibition of complement activation, the activation of polymorphonuclear leukocytes (PMNs; as assessed by the expression of CD11b) and the binding of these cells (CD16+) to the polymer surface were almost completely lost. In contrast, blood cell counts were not affected. Using surface plasmon resonance technology, we have confirmed that Compstatin exerts its inhibitory effect on complement activation by binding to native C3. These data show that complement activation, leading to activation and binding of PMNs to the biomaterial surface, can be abolished by the addition of Compstatin. The properties of Compstatin make Compstatin a promising drug for use in extracorporeal circuits to avoid bioincompatibility reactions, eg, during cardiopulmonary bypass, but also a favorable precursor peptide for the development of an anticomplement drug for oral use. © 1998 by The American Society of Hematology.
The Signal Transduction of the Growth Hormone Receptor Is Regulated by the Ubiquitin/Proteasome System and Continues After Endocytosis (2001)

The growth hormone receptor (GHR) intracellular domain contains all of the information required for signal transduction as well as for endocytosis. Previously, we showed that the proteasome mediates the clathrin-mediated endocytosis of the GHR. Here, we present evidence that the proteasomal inhibitor MG132 prolongs the GH-induced activity of both GHR and JAK2, presumably through stabilization of GHR and JAK2 tyrosine phosphorylation. If proteasomal inhibitor was combined with ligand in an endocytosis-deficient GHR mutant, the same phenomenon occurred indicating that proteasomal action on tyrosine dephosphorylation is independent of endocytosis. Experiments with a GHR-truncated tail mutant (GHR-(1-369)) led to a prolonged JAK2 phosphorylation caused by the loss of a phosphatase-binding site. This raised the question of what happens to the signal transduction of the GHR after its internalization. Co-immunoprecipitation of GH.GHR complexes before and after endocytosis showed that JAK2 as well as other activated proteins are bound to the GHR not only at the cell surface but also intracellularly, suggesting that the GHR signal transduction continues in endosomes. Additionally, these results provide evidence that GHR is present in endosomes both in its full-length and truncated form, indicating that the receptor is down-regulated by the proteasome.
Immediate Cytotoxicity But Not Degranulation Distinguishes Effector and Memory Subsets of CD8+ T Cells (2004)

CD8+ T cells play a central role in the resolution and containment of viral infections. A key effector function of CD8+ T cells is their cytolytic activity toward infected cells. Here, we studied the regulation of cytolytic activity in naive, effector, and central versus effector memory CD8+ T cells specific for the same glycoprotein-derived epitope of lymphocytic choriomeningitis virus. Our results show that the kinetics of degranulation, assessed by a novel flow cytometric based assay, were identical in effector and both subsets of memory CD8+ T cells, but absent in naive CD8+ T cells. However, immediate cytolytic activity was most pronounced in effector T cells, low in effector memory T cells, and absent in central memory T cells, correlating with the respective levels of cytolytic effector molecules present in lytic granules. These results indicate that an inherent program of degranulation is a feature of antigen-experienced cells as opposed to naive CD8+ T cells and that the ability of CD8+ T cells to induce target cell apoptosis/death is dependent on granule protein content rather than on the act of degranulation itself. Furthermore, these results provide a potential mechanism by which central memory CD8+ T cell-mediated death of antigen-presenting cells within the lymph node is avoided.
Structure and Stability of Silver Nanoparticles in Aqueous Solution Produced by Laser Ablation (2000)

Silver nanoparticles were produced by laser ablation of a metal silver plate in aqueous solutions of surfactants, C n H2 n +1SO4Na (n = 8, 10, 12, 16). The nanoparticles thus produced were characterized by electron microscopy and UV−visible absorption spectroscopy. The abundances of the nanoparticles before and after centrifugation were measured as a function of the surfactant concentration. The concentration dependence of the abundance implies that the surfactant coverage and the charge state on the nanoparticle surface are closely related to the stability of the nanoparticles in the solutions. The nanoparticles tend to be aggregated when the coverage is less than unity, while they are very stable when the surface is covered with a double layer of the surfactant molecules.
Training Recurrent Neural Networks With the Levenberg–Marquardt Algorithm for Optimal Control of a Grid-Connected Converter (2014)

This paper investigates how to train a recurrent neural network (RNN) using the Levenberg-Marquardt (LM) algorithm as well as how to implement optimal control of a grid-connected converter (GCC) using an RNN. To successfully and efficiently train an RNN using the LM algorithm, a new forward accumulation through time (FATT) algorithm is proposed to calculate the Jacobian matrix required by the LM algorithm. This paper explores how to incorporate FATT into the LM algorithm. The results show that the combination of the LM and FATT algorithms trains RNNs better than the conventional backpropagation through time algorithm. This paper presents an analytical study on the optimal control of GCCs, including theoretically ideal optimal and suboptimal controllers. To overcome the inapplicability of the optimal GCC controller under practical conditions, a new RNN controller with an improved input structure is proposed to approximate the ideal optimal controller. The performance of an ideal optimal controller and a well-trained RNN controller was compared in close to real-life power converter switching environments, demonstrating that the proposed RNN controller can achieve close to ideal optimal control performance even under low sampling rate conditions. The excellent performance of the proposed RNN controller under challenging and distorted system conditions further indicates the feasibility of using an RNN to approximate optimal control in practical applications.
0.32-μm pitch random line pattern formation by dense dummy pattern and double exposure in KrF wavelength (2000)

0.32 micrometers pitch on-grid random line pattern formation by double exposure in KrF wavelength is proposed based on optical image calculations. For first exposure, mask patterns are generated by combination of designed patterns and dense dummy patterns, al of which are laid out at on- grid positions with a pitch of 0.32 micrometers . An attenuated phase shift mask and an annular illumination are applied. The imaging performance is significantly enhanced because all patterns in this mask are categorized 'dense' with almost the same pitch of 0.32 micrometers . The mask pattern for second exposure are simply generated from the dummy patterns by tone inversion. The image size required for erasing dummy pattern in much larger than that for the first exposure. Consequently, large latitude, to erase the dummy pattern is much lager than that for the first exposure. Consequently, large latitude, to erase the dummy patterns and not to affect the designed patterns, can be obtained by conventional exposure method with low coherent illumination. Even in this method, OPC is required to obtain desirable CD. However, OPC in this method can be performed by simple rules based method, because on-grid restriction to layout much reduces the variation of pattern configuration. As a result, 0.32 micrometers pitch on-grid random line patterns are formed accurately with DOF larger than 0.6 micrometers in KrF wavelength.
Pharmacokinetics and Pharmacodynamics of Remifentanil in Volunteer Subjects with Severe Liver Disease (1996)

The pharmacokinetics of remifentanil and GR90291 are unchanged in persons with severe, chronic liver disease. Such patients may be more sensitive to the ventilatory depressant effects of remifentanil, a finding of uncertain clinical significance, considering the extremely short duration of action of the drug.
Transport of Sugars and Amino Acids in Bacteria (1968)

Abstract Two proteins, a galactose-binding protein and a leucine-binding protein, have been isolated from shock fluid of a mutant of Escherichia coli K12 that lacks galactokinase. They were purified by conventional methods to a homogeneous state as judged by electrophoresis on acrylamide columns and other physicochemical criteria. The leucine-binding protein was crystallized by treatment with ammonium sulfate. Binding activity was measured by means of equilibrium dialysis. The osmotic shock procedure was an essential part of the scheme of purification. The purified galactose-binding protein was substantially free of galactokinase, acid hexose phosphatase, and uridine diphosphoglucose pyrophosphatase activities. Of a number of carbohydrates tested, only galactose and glucose were bound. A number of related sugars, including mannose, fucose, lactose, galactosamine, and galactose 1- and 6-phosphate did not interfere with the binding of galactose. The leucine-binding protein showed specificity for leucine, isoleucine, and valine but not for other amino acids tested. Dissociation constants were measured for the galactose-binding protein with galactose and glucose. The values were in the range of 10-6 m. The binding proteins carried out a reversible binding of galactose or leucine in the absence of any chemical alteration of the substrates.
Effects of various chemical sterilization methods on the crosslinking and enzymatic degradation characteristics of an epoxy-fixed biological tissue (1997)

Due to the nature of bioprostheses, which are mainly biological tissues that cannot be sterilized with heat or irradiation, the sterilization method by choice is generally liquid chemicals. It is known that a number of liquid chemicals can have rapid germicidal effect and can be used to sterilize bioprostheses. The study was to evaluate the effects of various chemical sterilization methods on the crosslinking and enzymatic degradation characteristics of an epoxy-fixed biological tissue. The chemical sterilants employed were: a 70% ethanol solution (EtOH), a 2% epoxy compound + 20% ethanol solution (EX-810), a 2% propylene oxide + 20% ethanol solution (PO), and a 0.625% glutaraldehyde + 20% ethanol + 0.2% polysorbate solution (GA). Both masking and crosslinking of the free amino groups within the epoxy-fixed tissue were observed subsequent to sterilization with GA or EX-810. This improved the resistance of the GA or EX-810 sterilized tissues against collagenase degradation as compared to its nonsterilized counterpart. However, subsequent to sterilization with PO, only masking of the free amino groups within the epoxy-fixed tissue was noted. The inhibition of the collagenase degradation by masking of the free amino groups was traded off by the more random molecular packing of the PO sterilized sample due to the introduction of the side branches. Sterilization of the epoxy-fixed tissue with EtOH may increase its denaturation temperature and tensile strength, while neither masking nor crosslinking of free amino groups within the tissue took place. The resistance to degradation of the EtOH sterilized tissue, however, did not improve as compared to its nonsterilized counterpart.
Biomembrane-permeable and Ribonuclease-resistant siRNA with Enhanced Activity (2005)

Small interfering RNAs (siRNA) could be the ideal inhibitor of specific gene expression if they could be delivered efficiently to their targets. Although siRNAs cannot by themselves cross cell membranes, they can enter cells with the help of transfection reagents via facilitated transport. Inside cells, however, they can still be hydrolyzed by cytoplasmic RNases before reaching their target. Here we show that poly-2'- O-(2,4-dinitrophenyl)-siRNA (DNP-siRNA) can by itself diffuse into mammalian cells and stay in the cells for several days, with no detectable degradation. Using the DNP-RNA targeting to the insulin-like growth factor receptor (IGF-IR) as an example, we demonstrate that the efficacy of this DNP-siRNA for inhibiting the growth of three different types of tumor cells is several-fold higher than that of the corresponding native siRNA. Similar results were obtained from Western blotting assay. As expected, the control siRNAs with mismatched, scrambled, and reverse sequences are all inactive. These results illustrate that both the biomembrane permeability and intracellular stability of siRNA can be greatly improved by DNP derivatization without loss of its sequence specificity.
Neuroprotective Effect of Memantine in Different Retinal Injury Models in Rats (2002)

The protective effect of memantine suggests that excessive stimulation of NMDA receptors by glutamate is involved in causing cell damage in these RGC injury models.
Widespread, hypoxia‐inducible expression of HIF‐2α in distinct cell populations of different organs (2002)

Cellular responses to oxygen are increasingly recognized as critical in normal development and physiology, and are implicated in pathological processes. Many of these responses are mediated by the transcription factors HIF-1 and HIF-2. Their regulation occurs through oxygen-dependent proteolysis of the alpha subunits HIF-1alpha and HIF-2alpha, respectively. Both are stabilized in cell lines exposed to hypoxia, and recently HIF-1alpha was reported to be widely expressed in vivo. In contrast, regulation and sites of HIF-2alpha expression in vivo are unknown, although a specific role in endothelium was suggested. We therefore analyzed HIF-2alpha expression in control and hypoxic rats. Although HIF-2alpha was not detectable under baseline conditions, marked hypoxic induction occurred in all organs investigated, including brain, heart, lung, kidney, liver, pancreas, and intestine. Time course and amplitude of induction varied between organs. Immunohistochemistry revealed nuclear accumulation in distinct cell populations of each tissue, which were exclusively non-parenchymal in some organs (kidney, pancreas, and brain), predominantly parenchymal in others (liver and intestine) or equally distributed (myocardium). These data indicate that HIF-2 plays an important role in the transcriptional response to hypoxia in vivo, which is not confined to the vasculature and is complementary to rather than redundant with HIF-1.