gebhart/patrepeval huggingface dataset:
The family of hepatoma-derived growth factor proteins: characterization of a new member HRP-4 and classification of its subfamilies (2002)

Hepatoma-derived growth factor (HDGF)-related proteins (HRPs) comprise a family of polypeptides named after HDGF, which was identified by its mitogenic activity towards fibroblasts. In the present study, we describe a hitherto unknown HRP, termed HRP-4. The cDNA of bovine HRP-4 (bHRP-4) predicts a polypeptide of 235 amino acids. Northern- and Western-blot analyses of various bovine tissues demonstrated that HRP-4 is only expressed in the testis. Recombinantly produced bHRP-4 and murine HDGF (mHDGF) histidine-tagged polypeptides display growth-factor activity for cultured primary human fibroblasts at an optimum concentration of 1 ng/ml in serum-free medium. The growth-factor activity declines with increasing concentrations to reach background levels at 1 microg/ml. The expression of the fusion proteins, bHRP-4-green fluorescent protein and mHDGF-green fluorescent protein, in HEK-293 cells demonstrates nuclear localization of the proteins. bHRP-4 and mHDGF bind to the glycosaminoglycans heparin and heparan sulphate, but not to chondroitin sulphate. Affinity constants determined for these interactions are between 6 and 42 nM. Comparison of the bHRP-4 amino acid sequence with HRP-1-3 and p52/75/lens epithelium-derived growth factor (LEDGF) shows that these proteins share a conserved N-terminal part of 91 amino acids but have C-termini of different lengths and charge. This demonstrates the modular structure of these proteins and allows its classification into three groups based on charge, size and sequence comparison. HRP-4, HRP-1 and HDGF are small acidic proteins, HRP-3 is a small basic protein, and HRP-2 and p52/75/LEDGF are larger basic proteins.
Studies on the synthesis and properties of novel phospholipid analogous polymers (1996)

Two kinds of phospholipid analogous compounds, methacrylate monomers (4a–b) and acrylamide monomers (5a–b), were prepared and polymerized with a radical initiator in water at room temperature. The viscosity behavior of these charged polymers were investigated in the presence or absence of inorganic salts, and the found inherent viscosity [η] of amide polymer (poly7a) is higher than those of ester polymers (poly6a1 and poly6b). On the other hand, the radical copolymerization of monomer 5b with acrylamide (AAm) was also carried out in water. Based on the x-ray analyses, it is proposed that some of the obtained polymers show ordered bilayer structures in condensed phase. Furthermore, the thermal properties were studied by DSC and TG-DTA measurements. © 1996 John Wiley & Sons, Inc.
Effects of Romosozumab Compared With Teriparatide on Bone Density and Mass at the Spine and Hip in Postmenopausal Women With Low Bone Mass (2016)

Romosozumab, a monoclonal antibody that binds sclerostin, has a dual effect on bone by increasing bone formation and reducing bone resorption, and thus has favorable effects in both aspects of bone volume regulation. In a phase 2 study, romosozumab increased areal BMD at the lumbar spine and total hip as measured by DXA compared with placebo, alendronate, and teriparatide in postmenopausal women with low bone mass. In additional analyses from this international, randomized study, we now describe the effect of romosozumab on lumbar spine and hip volumetric BMD (vBMD) and BMC at month 12 as assessed by QCT in the subset of participants receiving placebo, s.c. teriparatide (20 µg once daily), and s.c. romosozumab (210 mg once monthly). QCT measurements were performed at the lumbar spine (mean of L<sub>1</sub> and L<sub>2</sub> entire vertebral bodies, excluding posterior processes) and hip. One year of treatment with romosozumab significantly increased integral vBMD and BMC at the lumbar spine and total hip from baseline, and compared with placebo and teriparatide (all p < 0.05). Trabecular vertebral vBMD improved significantly and similarly from baseline (p < 0.05) with both romosozumab (18.3%) and teriparatide (20.1%), whereas cortical vertebral vBMD gains were larger with romosozumab compared with teriparatide (13.7% versus 5.7%, p < 0.0001). Trabecular hip vBMD gains were significantly larger with romosozumab than with teriparatide (10.8% versus 4.2%, p = 0.01), but were similar for cortical vBMD (1.1% versus -0.9%, p = 0.12). Cortical BMC gains were larger with romosozumab compared with teriparatide at both the spine (23.3% versus 10.9%, p < 0.0001) and hip (3.4% versus 0.0%, p = 0.03). These improvements are expected to result in strength gains and support the continued clinical investigation of romosozumab as a potential therapy to rapidly reduce fracture risk in ongoing phase 3 studies. © 2016 American Society for Bone and Mineral Research.
Viral vectors as a novel tool for clinical and neuropsychiatric research applications (2018)

Viral vectors play an important role in basic research and clinical applications. To further understand brain function and prevent mental and neurological diseases, we hypothesize that viral vectors could be used along with various advanced technologies, such as sequencing and high-throughput expression analysis in the neuroscience research field.
The Yin and Yang of T Cell Costimulation (1995)

The Perspective by J. Allison and M. Krummel discusses a paper in this issue of Science by Waterhouse et al . ( p. 985 ), which reports the lymphoproliferative phenotype of mice lacking the T cell antigen CTLA-4. The function of this molecule has been elusive, but the pronounced lymphadenopathy of these knockout mice provides strong evidence that it works in opposition to the positive signal generated by the costimulatory T cell antigen receptor-peptide and CD28-B7 interactions.
RANDOM FORESTS CAN HASH (2015)

Hash codes are a very efficient data representation needed to be able to cope with the ever growing amounts of data. We introduce a random forest semantic hashing scheme with information-theoretic code aggregation, showing for the first time how random forest, a technique that together with deep learning have shown spectacular results in classification, can also be extended to large-scale retrieval. Traditional random forest fails to enforce the consistency of hashes generated from each tree for the same class data, i.e., to preserve the underlying similarity, and it also lacks a principled way for code aggregation across trees. We start with a simple hashing scheme, where independently trained random trees in a forest are acting as hashing functions. We the propose a subspace model as the splitting function, and show that it enforces the hash consistency in a tree for data from the same class. We also introduce an information-theoretic approach for aggregating codes of individual trees into a single hash code, producing a near-optimal unique hash for each class. Experiments on large-scale public datasets are presented, showing that the proposed approach significantly outperforms state-of-the-art hashing methods for retrieval tasks.
The levels of ubiquitinated histone H2A are highly upregulated in transformed human cells: Partial colocalization of uH2A clusters and PCNA/cyclin foci in a fraction of cells in S-phase (1995)

The levels and distribution of ubiquitinated histone H2A (uH2A) have been studied in normal and transformed human cells using a monoclonal antibody (mAb E6C5) that reacts specifically with this ubiquitin conjugate as determined by two-dimensional gel western blotting and microsequencing. Immunoblotting experiments demonstrated that the levels of the protein are highly upregulated in SV40-transformed human fibroblasts (WI-38 SV40) and keratinocytes (K14) relative to their normal counterparts, a finding that was further confirmed by indirect immunofluorescence studies of formaldehyde/Triton X-100-treated cells, which showed that about 97% of the transformed cells and 26% of the normal populations reacted with the antibody to yield a fine granular nuclear staining associated with the chromatin. Transformed cells contained in addition clusters of uH2A that were quite abundant and that showed variable size, shape and distribution even within a single cell line. The clusters, which were rare in normal cells, did not colocalize with other known nuclear antigens and may correspond to novel nuclear domains where ubiquitination/deubiquitination takes place. Electron microscopic immunocytochemistry of K14 cells confirmed the existence of the clusters. Double immunofluorescence studies of K14 keratinocytes with proliferating cell nuclear antigen (PCNA)/cyclin antibodies, which react with the nuclei of cells engaged in DNA replication, showed partial colocalization of PCNA/cyclin foci and large uH2A clusters in about 14% of the S-phase cells, and these corresponded mainly to late S-phase cells. Inhibition of DNA replication with hydroxyurea resulted in an overall increase in the intensity of the uH2A staining as well as in a more clear colocalization of uH2A clusters and PCNA/cyclin foci. Taken together, the results support the contention that uH2A plays a role at some stage of DNA replication.
Human CD3+ T lymphocytes that express neither CD4 nor CD8 antigens. (1986)

CD3+ T lymphocytes expressing neither CD4 nor CD8 antigens exist in normal human peripheral blood in low frequency (approximately 3% of lymphocytes). The CD3+,4-,8- phenotype was stably maintained after in vitro culture in IL-2. Culture of CD3+,4-,8- cells in only rIL-2 generated cytotoxic T cells that lysed NK-sensitive and NK-insensitive tumor cell targets without MHC restriction. These experiments clearly show that phenotypically and functionally competent T cells expressing neither CD4 nor CD8 are present in normal peripheral blood.
Identification and Characterization of Gemin7, a Novel Component of the Survival of Motor Neuron Complex (2002)

The survival of motor neurons (SMN) protein is the product of the gene mutated or deleted in the neurodegenerative disease, spinal muscular atrophy. SMN is part of a large macromolecular complex that also contains Gemin2, Gemin3, Gemin4, Gemin5, and Gemin6. The SMN complex functions in the assembly of spliceosomal small nuclear ribonucleoproteins and probably other ribonucleoprotein particles. We have identified a novel protein component of the SMN complex termed Gemin7 using native purified SMN complexes and peptide sequencing by mass spectrometry. Coimmunoprecipitation and immunolocalization experiments demonstrate that Gemin7 is a component of the SMN complex and colocalizes with SMN in the cytoplasm and in gems. Binding experiments show that Gemin7 interacts directly with SMN and Gemin6 and mediates the association of Gemin6 with the SMN complex. The amino acid sequence of Gemin7 does not contain any recognizable motifs with the exception of several arginine and glycine repeats that are necessary for its interaction with SMN. Moreover, Gemin7 interacts with several Sm proteins of spliceosomal small nuclear ribonucleoproteins, in particular, with SmE. With the identification of Gemin7, the inventory of the core components of the SMN complex appears essentially complete.
Similar endometrial development in oocyte donors treated with either high- or standard-dose GnRH antagonist compared to treatment with a GnRH agonist or in natural cycles (2005)

No relevant alteration was observed in the endometrial development in the early and mid-luteal phases in women undergoing controlled ovarian stimulation for oocyte donation following daily treatment with a standard- or high-dose GnRH antagonist. In addition, the endometrial development after GnRH antagonist mimics the natural endometrium more closely than after GnRH agonist.
Heavy Metal Removal from Water by Adsorption Using Pillared Montmorillonite (2006)

Cu~(2+) 的移动， Cr~(3+) 和从由蒙脱石上的吸附的水溶液的 Cd~(2+) 由钠 dodecylsulfate (SDS ) 和 hydroxy-alumino-silicate 修改了() 被调查。实验作为解决方案氢指数，溶质集中，和时间的一个函数被执行。兰米尔模特儿被收养描述单个溶质的吸附等温线，在 theLangmuir，参数直接从在单个溶质的系统获得的那些被拿。金属离子吸附的动力学被检验，伪 first-order 率常数最后被评估。
Exploring Nitrilase Sequence Space for Enantioselective Catalysis (2004)

Nitrilases are important in the biosphere as participants in synthesis and degradation pathways for naturally occurring, as well as xenobiotically derived, nitriles. Because of their inherent enantioselectivity, nitrilases are also attractive as mild, selective catalysts for setting chiral centers in fine chemical synthesis. Unfortunately, <20 nitrilases have been reported in the scientific and patent literature, and because of stability or specificity shortcomings, their utility has been largely unrealized. In this study, 137 unique nitrilases, discovered from screening of >600 biotope-specific environmental DNA (eDNA) libraries, were characterized. Using culture-independent means, phylogenetically diverse genomes were captured from entire biotopes, and their genes were expressed heterologously in a common cloning host. Nitrilase genes were targeted in a selection-based expression assay of clonal populations numbering 10(6) to 10(10) members per eDNA library. A phylogenetic analysis of the novel sequences discovered revealed the presence of at least five major sequence clades within the nitrilase subfamily. Using three nitrile substrates targeted for their potential in chiral pharmaceutical synthesis, the enzymes were characterized for substrate specificity and stereospecificity. A number of important correlations were found between sequence clades and the selective properties of these nitrilases. These enzymes, discovered using a high-throughput, culture-independent method, provide a catalytic toolbox for enantiospecific synthesis of a variety of carboxylic acid derivatives, as well as an intriguing library for evolutionary and structural analyses.
Detection of influenza hemagglutinin interaction with biological membranes by photosensitized activation of [125I]iodonaphthylazide. (1994)

Fusion of influenza virus with cells is triggered by a pH-dependent conformational change in the viral envelope protein, hemagglutinin, which results in exposure of the fusion peptide and its insertion into the target membrane. We have investigated the association of hemagglutinin with erythrocyte membranes by photosensitized labeling with [125I]iodonaphthylazide. This technique relies on the collisional energy transfer from a photosensitizing chromophore to [125I]iodonaphthylazide, which selectively labels proteins in the vicinity of the chromophore. Incubation of influenza virus with erythrocyte membranes containing chromophore and [125I]iodonaphthylazide results in labeling of hemagglutinin under fusogenic conditions (pH 5 and 37 degrees C). We also examined photosensitized labeling of hemagglutinin upon incubation of the X31 strain of influenza virus with labeled erythrocyte membranes in a pre-fusion state (pH 5 and 4 degrees C). There was little hemagglutinin labeling under these conditions, although incubation of bromelain-cleaved hemagglutinin, which lacks the transmembrane region, resulted in rapid labeling. Hemagglutinin was also labeled by [125I]iodonaphthylazide photosensitized by a fluorescent substrate transported through the erythrocyte band 3 sialoglycoprotein. Hemagglutinin labeling decreased after an initial rapid rise, suggesting that the fusion site is close to the sialoglycoprotein and that [125I]iodonaphthylazide photosensitized labeling may be used to assay protein movement during fusion.
Gene therapy and bone marrow transplantation (1995)

Retrovirus-mediated gene transfer into hematopoietic stem cells has been shown in mice, large animals, and humans. Transduction efficiency has been high in mice but has remained low in large animals and humans. Improved transduction efficiency into hematopoietic progenitor cells of large animals and humans has been achieved in vitro by enriching for CD34+ cells, adding growth factors to the transduction culture, extending the exposure time of hematopoietic cells to retrovirus particles, and by using retrovirus vectors pseudotyped with the gibbon ape leukemia virus envelope. Whether these modifications will also result in increased transduction of pluripotent hematopoietic stem cells has yet to be demonstrated by in vivo transplantation studies. Current transduction efficiency of hematopoietic stem cells in large animals and humans appears to be sufficiently high (0.1% to 1%) for gene marking studies. Efficiency needs to be further increased before gene transfer can be used for therapeutic applications.
Developmental roles and molecular characterization of a Drosophila homologue of Arabidopsis Argonaute1, the founder of a novel gene superfamily (2001)

Our results suggest that the dAGO1 protein exerts its developmental functions by binding to RNA either directly or indirectly.
Resistance mutation in HIV entry inhibitors (2002)

This data indicates that there is limited resistance to T-20 in these worldwide populations and that the critical epitopes for effective 5-helix binding are highly conserved across all subtypes. Taken together, these data suggest that T-20 and 5-helix should provide useful additives to current antiretroviral therapy for clinical management of HIV disease.
Beta‐site amyloid precursor protein cleaving enzyme 1 (BACE1) as a biological candidate marker of Alzheimer's disease (2008)

Alzheimer's disease (AD) is characterized by the progressive formation of insoluble amyloid plaques and vascular deposits consisting of the amyloid beta-peptide (Abeta) in the brain. Pathological mechanisms are already active early in the presymptomatic stage of AD. BACE1, beta-secretase, is one of the two key enzymes in amyloid precursor protein (APP) processing; the other being gamma-secretase. The Abeta peptide results from cleavage of APP initially by BACE1 to produce the C99 fragment and releases soluble APPbeta (sAPPbeta); C99 is then further cleaved by gamma-secretase leading to the Abeta peptide. Increased BACE1 activity and elevated levels of insoluble Abeta peptide have been shown in brain tissue of patients with sporadic AD. Since the CSF is in direct contact with the extracellular space of the central nervous system, biochemical changes in the brain can potentially be reflected in CSF. Therefore, CSF-based detection of BACE1 levels and activity might be valuable in aiding early detection and prediction, particularly in preclinical or even presymptomatic subjects who are at risk of AD. Recently, we were among the first groups to quantitatively analyse the enzymatic activities and protein levels of BACE1 in the CSF. Preliminary research using recently developed BACE1 ELISAs, BACE1 enzymatic activity, sAPPbeta and total Abeta1-x ELISAs were used by examining these hypothesis driven functional candidate markers in subjects with clinically diagnosed AD and amnestic MCI. Two sandwich ELISAs were used and BACE1 enzymatic activities were seen by synthetic fluorescence substrate and total Abeta levels by sandwich-ELISA. Moreover, elevated CSF levels of BACE1 protein were associated with an increased risk ratio in MCI. Interestingly, amnestic MCI subjects showed increased levels of BACE1 activity compared to HC and AD patients. For total Abeta and tau, increased CSF levels were associated with a higher risk of MCI compared to HC as well. BACE1 activity was significantly correlated with BACE1 protein concentration and total Abeta levels, with Abeta being itself correlated with the BACE1 protein level. Currently, independent studies are ongoing to validate BACE1 and functionally associated proteins as candidate biomarkers for early detection, prediction, progression as well as for biological activity in AD.
Generation and validation of affinity reagents on a proteome‐wide level (2008)

There is a need for protein-specific affinity reagents to explore the gene products encoded by the genome. Recently, systematic efforts to generate validated affinity reagents on a whole human proteome level have been initiated. There are several issues for such efforts, including choice of antigen, type of affinity reagent, and the subsequent validation of the generated protein-specific binders. The advantages and disadvantages with the different approaches are discussed and the problems related to quality assessment of antibodies to be used in multi-platform applications are addressed. This review also describes the efforts to create a virtual resource of validated antibodies using a community-based portal and summarizes the status and visions for the publicly available human protein atlas (http://www.proteinatlas.org) showing the human protein profiles in a large number of normal and cancer tissues as well as a large set of human cell lines.
[Molecular epidemiology study in Xuanwei: the relationship among  coal type, genotype and lung cancer risk]. (2015)

Lung cancer risks varied among coal subtypes; however, risks were similar between men and women exposed to the same type of coal. The GSTM1-null genotype may enhance susceptibility to air pollution from indoor smoky coal combustion emissions. AKR1C3 and OGG1 genotypes were significantly associated with higher risk of lung cancer, especially among heavily exposed women.
Transglutaminase Induces Protofibril-like Amyloid β-Protein Assemblies That Are Protease-resistant and Inhibit Long-term Potentiation (2008)

An increasing body of evidence suggests that soluble assemblies of amyloid beta-protein (Abeta) play an important role in the initiation of Alzheimer disease (AD). In vitro studies have found that synthetic Abeta can form soluble aggregates through self-assembly, but this process requires Abeta concentrations 100- to 1000-fold greater than physiological levels. Tissue transglutaminase (TGase) has been implicated in neurodegeneration and can cross-link Abeta. Here we show that TGase induces rapid aggregation of Abeta within 0.5-30 min, which was not observed with chemical cross-linkers. Both Abeta40 and Abeta42 are good substrates for TGase but show different aggregation patterns. Guinea pig and human TGase induced similar Abeta aggregation patterns, and oligomerization was observed with Abeta40 concentrations as low as 50 nm. The formed Abeta40 species range from 5 to 6 nm spheres to curvilinear structures of the same width, but up to 100 nm in length, that resemble the previously described self-assembled Abeta protofibrils. TGase-induced Abeta40 assemblies are resistant to a 1-h incubation with either neprilysin or insulin degrading enzyme, whereas the monomer is rapidly degraded by both proteases. In support of these species being pathological, TGase-induced Abeta40 assemblies (100 nm) inhibited long term potentiation recorded in the CA1 region of mouse hippocampus slices. Our data suggest that TGase can contribute to AD by initiating Abeta oligomerization and aggregation at physiological levels, by reducing the clearance of Abeta due to the generation of protease-resistant Abeta species, and by forming Abeta assemblies that inhibit processes involved in memory and learning. Our data suggest that TGase might constitute a specific therapeutic target for slowing or blocking the progression of AD.