gebhart/patrepeval huggingface dataset:
Upregulation of Neurotoxic Serine Proteases, Prothrombin, and Protease-Activated Receptor 1 Early After Spinal Cord Injury (2000)

Apoptosis, well-established in development and now also in degenerative disease, occurs with regularity in several cell compartments early after controlled contusion spinal cord injury (SCI). Cell death in astrocytic, microglial, and neuronal populations peaks at 3 days, while oligodendroglial apoptosis is found 10-14 days later. In this regard, the executioners of apoptosis, the caspase proteases, are also activated within 3 days of SCI. On the other hand, serine proteases, which have been shown to initiate apoptosis and activate caspases in culture models, have not been extensively studied in regards to nervous system trauma. As part of an ongoing effort to examine the spectrum of genes that are up- and downregulated in the injured rat spinal cord, we synthesized serine protease family specific primers to take advantage of conserved residues in the charge relay system and the codon preferences of these mammalian genes. These primers were then employed in a modified, family-specific differential mRNA display technique. One specific serine protease gene we found that was upregulated after injury was prothrombin. Qualitative and quantitative RT-PCR techniques indicated that this increase occurred early, already evident at 8 h after injury, and reached a maximum level fourfold above baseline at 24 h. Peak expression for prothrombin mRNA occurred prior to peak levels of apoptosis in astrocytic, microglial and neuronal compartments at 72 h. Of additional interest, gene database mining revealed that prothrombin shared approximately 48% similarity with myelencephalon-specific protease (MSP), a neurotoxic serine protease previously found to be increased two- to threefold at 3 days after excitotoxic SCI. Since thrombin induces apoptosis in murine and chick motor and rat hippocampal neurons by activating a member of the novel protease-activated receptor (PAR) gene family known as PAR-1, we also analyzed PAR-1 by similar techniques and found that it, too, was upregulated after SCI with the same kinetics as prothrombin. We confirmed these results with gene array analyses that revealed more than one trypsin subfamily serine protease was activated by SCI. They imply the possibility of using specific, tissue-directed serine protease inhibition at translational or transcriptional levels, and offer a potential paradigm shift in drug discovery for SCI to limit the extent of apoptosis, and consequent functional loss, in the human spinal cord.
Regulation of Escherichia coli secA by Cellular Protein Secretion Proficiency Requires an Intact Gene X Signal Sequence and an Active Translocon (1998)

secA is translationally regulated by the protein secretion proficiency state of the Escherichia coli cell. This regulation was explored by making signal sequence mutations in the gene upstream of secA, gene X, which promotes secA translational coupling. Gene X signal sequence mutants were constitutive for secA expression, while prlA alleles partially restored secA regulation. These results show that interaction of the pre-gene X protein with the translocon is required for proper secA regulation. Furthermore, gene X signal sequence mutations disrupted secA regulation only in the cis configuration. We propose that nascent pre-gene X protein interacts with the translocon during its secretion to constitute the secretion sensor.
RGB-D mapping: Using Kinect-style depth cameras for dense 3D modeling of indoor environments (2012)

RGB-D cameras (such as the Microsoft Kinect) are novel sensing systems that capture RGB images along with per-pixel depth information. In this paper we investigate how such cameras can be used for building dense 3D maps of indoor environments. Such maps have applications in robot navigation, manipulation, semantic mapping, and telepresence. We present RGB-D Mapping, a full 3D mapping system that utilizes a novel joint optimization algorithm combining visual features and shape-based alignment. Visual and depth information are also combined for view-based loop-closure detection, followed by pose optimization to achieve globally consistent maps. We evaluate RGB-D Mapping on two large indoor environments, and show that it effectively combines the visual and shape information available from RGB-D cameras.
Staphylococcus haemolyticus contains two D-glutamic acid biosynthetic activities, a glutamate racemase and a D-amino acid transaminase (1995)

Two D-glutamic acid biosynthetic activities, glutamate racemase and D-amino acid transaminase, have been described previously for bacteria. To date, no bacterial species has been reported to possess both activities. Genetic complementation studies using Escherichia coli WM335, a D-glutamic acid auxotroph, and cloned chromosomal DNA fragments from Staphylococcus haemolyticus revealed two distinct DNA fragments containing open reading frames which, when present, allowed growth on medium without exogenous D-glutamic acid. Amino acid sequences of the two open reading frames derived from the DNA nucleotide sequences indicated extensive identity with the amino acid sequence of Pediococcus pentosaceous glutamate racemase in one case and with that of the D-amino acid transaminase of Bacillus spp. in the second case. Enzymatic assays of lysates of E. coli WM335 strains containing either the cloned staphylococcal racemase or transminase verified the identities of these activities. Subsequent DNA hybridization experiments indicated that Staphylococcus aureus, in addition to S. haemolyticus, contained homologous chromosomal DNA for each of these genes. These data suggest that S. haemolyticus, and probably S. aureus, contains genes for two D-glutamic acid biosynthetic activities, a glutamate racemase (dga gene) and a D-amino acid transaminase (dat gene).
The clinical spectrum of heterozygous protein C deficiency in a large New England kindred (1989)

A family with a high incidence of venous thromboembolism was investigated. We performed medical evaluations on 184 of the 411 surviving members of the pedigree, which allowed assignment of individuals into positive, equivocal, or negative categories with respect to their clinical histories of thrombosis. Subjects with antigenic levels of protein C less than 66% of a normal plasma pool were classified as having protein C deficiency. Positive thrombotic histories were found in 13 of the 46 family members determined to be protein-C deficient and in only five of their 138 biochemically unaffected relatives. Statistical analysis of the association between thromboembolic disease and protein-C deficiency was strongly positive chi 2 = 24.95, P less than .0001 with n = 184), indicating that heterozygous protein-C deficiency is an important independent risk factor for the development of thrombotic manifestations in this pedigree. However, the absence of thromboembolic manifestations in many of the protein-C deficient family members to date indicates that other, as yet undefined, factors must play an important role in the clinical expression of this disorder.
Teleology and Tutelage in Plato's Republic (2011)

This chapter contains sections titled: I II III IV V
The Structure of Chondroitin B Lyase Complexed with Glycosaminoglycan Oligosaccharides Unravels a Calcium-dependent Catalytic Machinery (2004)

Chondroitinase B from Pedobacter heparinus is the only known enzyme strictly specific for dermatan sulfate and is a widely used enzymatic tool for the structural characterization of glycosaminoglycans. This beta-helical polysaccharide lyase belongs to family PL-6 and cleaves the beta(1,4) linkage of dermatan sulfate in a random manner, yielding 4,5-unsaturated dermatan sulfate disaccharides as the product. The previously reported structure of its complex with a dermatan sulfate disaccharide product identified the -1 and -2 subsites of the catalytic groove. We present here the structure of chondroitinase B complexed with several dermatan sulfate and chondroitin sulfate oligosaccharides. In particular, the soaking of chondroitinase B crystals with a dermatan sulfate hexasaccharide results in a complex with two dermatan sulfate disaccharide reaction products, enabling the identification of the +2 and +1 subsites. Unexpectedly, this structure revealed the presence of a calcium ion coordinated by sequence-conserved acidic residues and by the carboxyl group of the l-iduronic acid at the +1 subsite. Kinetic and site-directed mutagenesis experiments have subsequently demonstrated that chondroitinase B absolutely requires calcium for its activity, indicating that the protein-Ca(2+)-oligosaccharide complex is functionally relevant. Modeling of an intact tetrasaccharide in the active site of chondroitinase B provided a better understanding of substrate specificity and the role of Ca(2+) in enzymatic activity. Given these results, we propose that the Ca(2+) ion neutralizes the carboxyl moiety of the l-iduronic acid at the cleavage site, whereas the conserved residues Lys-250 and Arg-271 act as Brønsted base and acid, respectively, in the lytic degradation of dermatan sulfate by chondroitinase B.
Glycinebetaine stabilizes the association of extrinsic proteins with the photosynthetic oxygen‐evolving complex (1992)

The photosynthetic oxygen-evolving activity of the photosystem 2 complex, prepared from spinach, was labile when the complex was exposed to high-salt conditions under which the extrinsic proteins were dissociated from the complex. Glycinebetaine prevented the dissociation of the 18-kDa and the 23-kDa extrinsic proteins from the photosystem 2 complex in the presence of 1 M NaCl. It also prevented the dissociation of the 33-kDa extrinsic protein from the complex in the presence of 1 M MgCl2 or 1 M CaCl2. The oxygen-evolving activity of the photosystem 2 complex was stabilized by glycinebetaine when the complex was subjected to treatment with NaCl and MgCl2.
Evaluating the Intrinsic Similarity between Neural Networks (2015)

We present Forward Bipartite Alignment (FBA), a method that aligns the topological structures of two neural networks. Neural networks are considered to be a black box, because neural networks contain complex model surface determined by their weights that combine attributes non-linearly. Two networks that make similar predictions on training data may still generalize differently. FBA enables a diversity of applications, including visualization and canonicalization of neural networks, ensembles, and cross-over between unrelated neural networks in evolutionary optimization. We describe the FBA algorithm, and describe implementations for three applications: genetic algorithms, visualization, and ensembles. We demonstrate FBA's usefulness by comparing a bag of neural networks to a bag of FBA-aligned neural networks. We also show that aligning, and then combining two neural networks has no appreciable loss in accuracy which means that Forward Bipartite Alignment aligns neural networks in a meaningful way.
Defined Folate-PEG-siRNA Conjugates for Receptor-specific Gene Silencing (2012)

Gene silencing mediated by small interfering RNA (siRNA) is a novel approach in the development of new cancer therapeutics. Polycations used for nucleic acid delivery still remain heterogeneous compounds, despite continuous progress in polymer synthetic technologies. Here we report the development of a structural defined folic acid polyethylene glycol (PEG) siRNA conjugate accessible via click chemistry yielding a monodisperse ligand-PEG-siRNA conjugate. The folic acid targeting ligand was synthesized by solid phase supported peptide chemistry. The conjugate was shown to be specifically internalized into folic acid receptor expressing cells. When combined with a structurally defined polycation, again synthesized with the precision of solid phase chemistry, efficient receptor specific gene silencing is achieved.
Interleukin‐2 potentiation of cetuximab antitumor activity for epidermal growth factor receptor‐overexpressing gastric cancer xenografts through antibody‐dependent cellular cytotoxicity (2008)

Cetuximab, a chimeric monoclonal antibody to epidermal growth factor receptor (EGFR), has been proved to have clinically significant antitumor activity against advanced colorectal cancers, but its therapeutic activity for gastric cancers remains unclear. In the present study, we investigated the antitumor effect and action mechanism of cetuximab using EGFR high-expressing (MKN-28) and EGFR low-expressing (GLM-1) gastric cancer cell lines without gene amplification. Cetuximab showed neither significant growth inhibition nor induction of apoptosis in either cell line in vitro, and only slightly inhibited ligand-induced phosphorylation of protein kinase B and extracellular signal-regulated kinase in MKN-28 cells. In contrast, cetuximab significantly inhibited subcutaneous and intraperitoneal tumor growth of MKN-28 cells, but not GLM-1 cells, in nude mice. This antitumor activity was significantly enhanced and diminished in nude mice by treatment with interleukin-2 (IL-2) and antiasialo GM1 antibody, which can expand and deplete natural killer (NK) cells, respectively. Antibody-dependent cellular cytotoxicity (ADCC) of cetuximab, as measured by (51)Cr release assay, was significantly higher in MKN-28 than in GLM-1 cells. This ADCC activity was enhanced by IL-2 and reduced by heat-aggregate of human immunoglobulin G, an inhibitor for FcR-III of NK cells. These results suggest that cetuximab in combination with IL-2 shows significant antitumor activity against EGFR high-expressing gastric cancer mainly through NK cell-mediated ADCC. Combination therapy with cetuximab and IL-2 would thus offer a new potential therapeutic approach for a subset of EGFR-overexpressing gastric cancers.
A Combined Barite–Ilmenite Weighting Material to Prevent Barite Sag in Water-Based Drilling Fluid (2019)

Barite sag is a serious problem encountered while drilling high-pressure/high-temperature (HPHT) wells. It occurs when barite particles separate from the base fluid leading to variations in drilling fluid density that may cause a serious well control issue. However, it occurs in vertical and inclined wells under both static and dynamic conditions. This study introduces a combined barite-ilmenite weighting material to prevent the barite sag problem in water-based drilling fluid. Different drilling fluid samples were prepared by adding different percentages of ilmenite (25, 50, and 75 wt.% from the total weight of the weighting agent) to the base drilling fluid (barite-weighted). Sag tendency of the drilling fluid samples was evaluated under static and dynamic conditions to determine the optimum concentration of ilmenite which was required to prevent the sag issue. A static sag test was conducted under both vertical and inclined conditions. The effect of adding ilmenite to the drilling fluid was evaluated by measuring fluid density and pH at room temperature, and rheological properties at 120 °F and 250 °F. Moreover, a filtration test was performed at 250 °F to study the impact of adding ilmenite on the drilling fluid filtration performance and sealing properties of the formed filter cake. The results of this study showed that adding ilmenite to barite-weighted drilling fluid increased fluid density and slightly reduced the pH within the acceptable pH range (9-11). Ilmenite maintained the rheology of the drilling fluid with a minimal drop in rheological properties due to the HPHT conditions, while a significant drop was observed for the base fluid (without ilmenite). Adding ilmenite to the base drilling fluid significantly reduced sag factor and 50 wt.% ilmenite was adequate to prevent solids sag in both dynamic and static conditions with sag factors of 0.33 and 0.51, respectively. Moreover, HPHT filtration results showed that adding ilmenite had no impact on filtration performance of the drilling fluid. The findings of this study show that the combined barite-ilmenite weighting material can be a good solution to prevent solids sag issues in water-based fluids; thus, drilling HPHT wells with such fluids would be safe and effective.
Electroporation of Embryonic Stem Cells for Generating Transgenic Mice and Studying In Vitro Differentiation (2003)

The ability to transfect mammalian cell lines stably in culture has enabled countless scientific advances to be made in just a few decades. However, not until about 10 years ago did the true potential for the genetic manipulation of cells become a reality, with the ability to alter a mammalian gene precisely by targeted homologous recombination (1–3). This powerful tool was first devised for gene therapy approaches, but was quickly adopted for the transfection (4) and genetic disruption of genes in embryonic stem (ES) cell lines to produce transgenic animals (5,6). Currently, the most common cell line used is the mouse ES cell, but ES cells have recently been derived for other species (rabbit, rat, and hamster) (7–9).
Controlling Optoelectronic Behavior in Poly(fluorene) Networks Using Thiol–Ene Photo-Click Chemistry (2015)

Thiol–ene photo-click chemistry is used to cross-link poly(fluorene) derivatives incorporating varying length alkene side-chains into conjugated thin film networks with tunable network architecture, offering a systematic handle on network architecture in cross-linked conjugated polymers. Newly reported poly(fluorene)s with 5- and 11-carbon length thiol–ene compatible side-chains are cross-linked using difunctional and tetra-functional thiol cross-linkers to afford networks of varying connectivity which are tracked by FTIR, contact profilometry, and photo calorimetry. Fluorenone “defects” are additionally incorporated into the poly(fluorene) networks and act as a uniquely effective colorimetric indicator of electronic communication within the conjugated network. This provides a novel method for the systematic investigation of the effects of network architecture on cross-linked conjugated polymer films, which opens the door for controlling the optoelectronic properties of organic semiconductor networks as demonstrated by electroluminescent devices with improved efficiency.
Bcl-2 Overexpression Enhances Tumor-Specific T-Cell Survival (2005)

Although immunotherapy based on the adoptive transfer of tumor-specific T lymphocytes has been shown to result in dramatic clinical responses in some patients, the relatively low levels of engraftment and persistence of the adoptively transferred cells may limit these responses in many patients. In an attempt to develop strategies for prolonging the survival of adoptively transferred T cells, we have carried out studies in which T cells obtained from healthy donors as well as tumor-specific T cells were transduced with a retrovirus expressing the human Bcl-2 gene. Our results indicate that these transduced T cells overexpress Bcl-2, are resistant to death, and have a survival advantage following interleukin-2 withdrawal compared with control T cells transduced with a retrovirus expressing green fluorescent protein. Tumor-specific T cells overexpressing Bcl-2 maintained their ability to specifically recognize and respond to target cells. Furthermore, we show that adoptive immunotherapy of an established B16 tumor can be significantly enhanced by overexpressing Bcl-2 in melanoma-specific T-cell receptor transgenic T cells. Our data suggest that adoptive immunotherapy approaches to the treatment of cancer patients may be enhanced using Bcl-2-modified tumor-reactive T cells.
NMR structure of a concatemer of the first and second ligand‐binding modules of the human low‐density lipoprotein receptor (2000)

The ligand-binding domain of the human low-density lipoprotein receptor consists of seven modules, each of 40-45 residues. In the presence of calcium, these modules adopt a common polypeptide fold with three conserved disulfide bonds. A concatemer of the first and second modules (LB(1-2)) folds efficiently in the presence of calcium ions, forming the same disulfide connectivities as in the isolated modules. The three-dimensional structure of LB(1-2) has now been solved using two-dimensional 1H NMR spectroscopy and restrained molecular dynamics calculations. No intermodule nuclear Overhauser effects were observed, indicating the absence of persistent interaction between them. The near random-coil NH and H alpha chemical shifts and the low phi and psi angle order parameters of the four-residue linker suggest that it has considerable flexibility. The family of LB(1-2) structures superimposed well over LB1 or LB2, but not over both modules simultaneously. LB1 and LB2 have a similar pattern of calcium ligands, but the orientations of the indole rings of the tryptophan residues W23 and W66 differ, with the latter limiting solvent access to the calcium ion. From these studies, it appears that although most of the modules in the ligand-binding region of the receptor are joined by short segments, these linkers may impart considerable flexibility on this region.
Characterization of truncated forms of hepatitis C virus glycoproteins. (1997)

Hepatitis C virus (HCV) glycoproteins (E1 and E2) both contain a carboxy-terminal hydrophobic region, which presumably serves as a membrane anchor. When they are expressed in animal cell cultures, these glycoproteins, in both mature complexes and misfolded aggregates, are retained in the endoplasmic reticulum. The effect of carboxy-terminal deletions on HCV glycoprotein secretion and folding was examined in this study. Sindbis and/or vaccinia virus recombinants expressing truncated forms of these glycoproteins ending at amino acids 311,330, 354 and 360 (truncated E1), and 661, 688, 704 and 715 (truncated E2) were constructed. When expressed using Sindbis virus vectors, only truncated forms of E1 and E2 ending at amino acids 311 (E1t311) and 661 (E2t661), respectively, were efficiently secreted. Analysis of secretion of truncated forms of E2 glycoprotein expressed by vaccinia viruses indicated that significant secretion was still observed for a protein as large as E2t715. However, only secreted E2t661 appeared to be properly folded. Secreted HCV glycoprotein complexes were also detected in the supernatant of cell culture when E1t311 and E2t661 were coexpressed. Nevertheless, these secreted complexes, as well as E1t311 expressed alone, were misfolded. The effect of coexpression of E1 and E2 glycoproteins on each other’s folding was evaluated with the help of a conformation-sensitive monoclonal antibody (for E2) or by analysing intramolecular disulfide bond formation (for E1). Our data indicate that the folding of E2 is independent of E1, but that E2 is required for the proper folding of E1.
Tripeptide Interference with Human Immunodeficiency Virus Type 1 Morphogenesis (2002)

Capsid assembly during virus replication is a potential target for antiviral therapy. The Gag polyprotein is the main structural component of retroviral particles, and in human immunodeficiency virus type 1 (HIV-1), it contains the sequences for the matrix, capsid, nucleocapsid, and several small polypeptides. Here, we report that at a concentration of 100 micro M, 7 of 83 tripeptide amides from the carboxyl-terminal sequence of the HIV-1 capsid protein p24 suppressed HIV-1 replication (>80%). The three most potent tripeptides, glycyl-prolyl-glycine-amide (GPG-NH(2)), alanyl-leucyl-glycine-amide (ALG-NH(2)), and arginyl-glutaminyl-glycine-amide (RQG-NH(2)), were found to interact with p24. With electron microscopy, disarranged core structures of HIV-1 progeny were extensively observed when the cells were treated with GPG-NH(2) and ALG-NH(2). Furthermore, nodular structures of approximately the same size as the broad end of HIV-1 conical capsids were observed at the plasma membranes of treated cells only, possibly indicating an arrest of the budding process. Corresponding tripeptides with nonamidated carboxyl termini were not biologically active and did not interact with p24.