gebhart/patrepeval huggingface dataset:
Cloning and Characterization of R-PTP-κ, a New Member of the Receptor Protein Tyrosine Phosphatase Family with a Proteolytically Cleaved Cellular Adhesion Molecule-Like Extracellular Region (1993)

We describe a new member of the receptor protein tyrosine phosphatase family, R-PTP-kappa, cDNA cloning predicts that R-PTP-kappa is synthesized from a precursor protein of 1,457 amino acids. Its intracellular domain displays the classical tandemly repeated protein tyrosine phosphatase homology, separated from the transmembrane segment by an uncharacteristically large juxta-membrane region. The extracellular domain of the R-PTP-kappa precursor protein contains an immunoglobulin-like domain and four fibronectin type III-like repeats, preceded by a signal peptide and a region of about 150 amino acids with similarity to the Xenopus A5 antigen, a putative neuronal recognition molecule (S. Takagi, T. Hsrata, K. Agata, M. Mochii, G. Eguchi, and H. Fujisawa, Neuron 7:295-307, 1991). Antibodies directed against the intra- and extracellular domains reveal that the R-PTP-kappa precursor protein undergoes proteolytic processing, following which both cleavage products remain associated. By site-directed mutagenesis, the likely cleavage site was shown to be a consensus sequence for cleavage by the processing endopeptidase furin, located in the fourth fibronectin type III-like repeat. In situ hybridization analysis indicates that expression of R-PTP-kappa in the central nervous system is developmentally regulated, with highest expression seen in actively developing areas and, in the adult, in areas capable of developmental plasticity such as the hippocampal formation and cerebral cortex. The mouse R-PTP-kappa gene maps to chromosome 10, at approximately 21 centimorgans from the centromere.
Harpins, Multifunctional Proteins Secreted by Gram-Negative Plant-Pathogenic Bacteria (2013)

Harpins are glycine-rich and heat-stable proteins that are secreted through type III secretion system in gram-negative plant-pathogenic bacteria. Many studies show that these proteins are mostly targeted to the extracellular space of plant tissues, unlike bacterial effector proteins that act inside the plant cells. Over the two decades since the first harpin of pathogen origin, HrpN of Erwinia amylovora, was reported in 1992 as a cell-free elicitor of hypersensitive response (HR), diverse functional aspects of harpins have been determined. Some harpins were shown to have virulence activity, probably because of their involvement in the translocation of effector proteins into plant cytoplasm. Based on this function, harpins are now considered to be translocators. Their abilities of pore formation in the artificial membrane, binding to lipid components, and oligomerization are consistent with this idea. When harpins are applied to plants directly or expressed in plant cells, these proteins trigger diverse beneficial responses such as induction of defense responses against diverse pathogens and insects and enhancement of plant growth. Therefore, in this review, we will summarize the functions of harpins as virulence factors (or translocators) of bacterial pathogens, elicitors of HR and immune responses, and plant growth enhancers.
Hydrogenation of Carbon Nanotubes and Graphite in Liquid Ammonia (2001)

We have prepared hydrogenated single-wall and multiwall carbon nanotubes, as well as graphite, via a dissolved metal reduction method in liquid ammonia. The hydrogenated derivatives are thermally stable up to 400 °C. Above 400 °C, a characteristic decomposition takes place accompanied with the simultaneous formations of hydrogen and a small amount of methane. Transmission electron micrographs show corrugation and disorder of the nanotube walls and the graphite layers due to hydrogenation. The average hydrogen contents determined from the yield of evolved hydrogen correspond to the compositions of C11H for both types of nanotubes and C5H for graphite. Hydrogenation occurred even on the inner tubes of multiwall nanotubes as shown by the chemical composition and the overall corrugation. The thermal stability and structural results suggest the formation of C−H bonds in nanotubes and graphite.
Minimal Lipidation Stabilizes Protein-Like Molecular Architecture (1998)

Peptide-amphiphiles with collagen-model head groups and dialkyl chain tails have been shown previously to self-assemble into highly ordered polyPro II-like triple-helical structures when dissolved in aqueous subphases. In the present study, we have examined peptide-amphiphiles containing monoalkyl chain tails for similar self-assembly behaviors. The structure of a collagen-model peptide has been characterized with and without an N-terminal hexanoic acid (C6) modification. Evidence for a self-assembly process of both the peptide and peptide-amphiphile has been obtained from (a) circular dichroism spectra and melting curves characteristic of triple-helices, (b) one-dimensional NMR spectra indicative of stable triple-helical structure at low temperatures and melted triple helices at high temperatures, and (c) pulsed-field gradient NMR experiments demonstrating different self-diffusion coefficients between proposed triple-helical and non-triple-helical species. The peptide-amphiphile appeared to form monomeric triple helices. The thermal stability of the collagen-like structure in the peptide-amphiphile was found to increase as the monoalkyl tail chain length is increased over a range of C6 to C16. The assembly process driven by the hydrophobic tail, albeit monoalkyl or dialkyl, may provide a general method for creating well-defined protein molecular architecture. Peptide-amphiphile structures possessing these alkyl moieties have the potential to be used for biomaterial surface modification to improve biocompatibility or, by mimicing fusion of viral envelopes with cellular membranes, as drug delivery vehicles.
The human transcriptome across tissues and individuals (2015)

Transcriptional regulation and posttranscriptional processing underlie many cellular and organismal phenotypes. We used RNA sequence data generated by Genotype-Tissue Expression (GTEx) project to investigate the patterns of transcriptome variation across individuals and tissues. Tissues exhibit characteristic transcriptional signatures that show stability in postmortem samples. These signatures are dominated by a relatively small number of genes—which is most clearly seen in blood—though few are exclusive to a particular tissue and vary more across tissues than individuals. Genes exhibiting high interindividual expression variation include disease candidates associated with sex, ethnicity, and age. Primary transcription is the major driver of cellular specificity, with splicing playing mostly a complementary role; except for the brain, which exhibits a more divergent splicing program. Variation in splicing, despite its stochasticity, may play in contrast a comparatively greater role in defining individual phenotypes.
Principles of early drug discovery (2010)

Developing a new drug from original idea to the launch of a finished product is a complex process which can take 12-15 years and cost in excess of $1 billion. The idea for a target can come from a variety of sources including academic and clinical research and from the commercial sector. It may take many years to build up a body of supporting evidence before selecting a target for a costly drug discovery programme. Once a target has been chosen, the pharmaceutical industry and more recently some academic centres have streamlined a number of early processes to identify molecules which possess suitable characteristics to make acceptable drugs. This review will look at key preclinical stages of the drug discovery process, from initial target identification and validation, through assay development, high throughput screening, hit identification, lead optimization and finally the selection of a candidate molecule for clinical development.
PREMOTOR AND PARIETAL CORTEX: Corticocortical Connectivity and Combinatorial Computations (1997)

The dorsal premotor cortex is a functionally distinct cortical field or group of fields in the primate frontal cortex. Anatomical studies have confirmed that most parietal input to the dorsal premotor cortex originates from the superior parietal lobule. However, these projections arise not only from the dorsal aspect of area 5, as has long been known, but also from newly defined areas of posterior parietal cortex, which are directly connected with the extrastriate visual cortex. Thus, the dorsal premotor cortex receives much more direct visual input than previously accepted. It appears that this fronto-parietal network functions as a visuomotor controller-one that makes computations based on proprioceptive, visual, gaze, attentional, and other information to produce an output that reflects the selection, preparation, and execution of movements.
10.1016/s0967-0653(97)83554-5 (2000)

Seasonal variability of the depth-integrated transport in the Indonesian Seas is investigated in detail, together with its driving mechanism, by use of an Indo-Pacific ocean general circulation model that allows the circulation around Australasia. Modeled net throughflow shows an annual mean transport of 9.5 Sv from the Pacific to the Indian Ocean with a maximum (minimum) transport of 11.6 Sv (6.0 Sv) in August (January). Seventy-five percent of this transport flows through the Lombok Strait in the present model. Comparison with the result of Masumoto and Yamagata [1993], in which the circulation around Australasia was not permitted, clarifies that the magnitude of the net interbasin throughflow does not affect the seasonal variations in the depth-integrated transport through the Lombok Strait. Several additional experiments are also carried out by masking winds over particular regions to identify which part of winds is actually effective in the seasonal variations in the depth-integrated transport through the Timor Sea as well as the Lombok Strait. It turns out that the seasonal variability of the transport through the Lombok Strait is almost perfectly governed by the winds over the equatorial Indian and Pacific Oceans. On the other hand, the coastally trapped waves generated by the winds along the western and southern coast of Australia play an important role in the seasonal transport variation through the Timor Sea.
Aldehyde emissions from particleboard and medium density fiberboard products (2000)

Indoor air quality problems resulting from the emission of volatile organic compounds (VOCs) have become an issue of increasing concern. Emissions from building and furnishing materials, which are frequently constructed from particleboard and medium density fiberboard (MDF), are a potentially important contributor of indoor VOCs. In this research, VOC emissions from particleboard and MDF were measured in small (53-L) stainless steel chambers for 4 days. Samples were collected from 53 of the 61 U.S. mills that produce particleboard and MDF. Each mill identified the predominant tree species used to manufacture the panels. Laboratory tests were conducted at room temperature and 45 percent relative humidity. Gas chromatographic/mass spectrometric analysis was used to identify and quantify VOC compounds. The predominant compounds identified in the emissions from particleboard and MDF samples were terpenes and aldehydes, although small straight-chain alcohols and ketones were also found. This study describes the aldehyde emission data, excluding formaldehyde. Emissions of small straight-chain aldehydes, such as hexanal, pentanal, heptanal, octanal, and nonanal, generally exceeded emissions of other compounds and accounted for more than 50 percent oftotal VOC emissions. All 53 particleboard and 16 of 18 MDF samples emitted hexanal, the most prevalent aldehyde found (excluding formaldehyde). The tests showed differences in VOC composition and emission factors by product and tree type. On average, aldehyde emissions from southern pine MDF samples considerably exceeded the aldehyde emissions from southern pine particleboard. Emissions from all other MDF samples, however, were lower than those from particleboard samples in the same species group. With the exception of formaldehyde, aldehydes are not added to the adhesives used to bond wood, and they have not previously been reported as extractable compounds in wood. Degradation ofthe wood or its secondary metabolites is probably responsible for the presence of the aldehydes.
Increased Expression of Id Family Proteins in Small Cell Lung Cancer and its Prognostic Significance (2008)

Changed expression profiles of Id proteins may play important roles in malignant progression of SCLC, and the increased Id2 in cytoplasm is a novel prognostic factor to predict the patient outcomes.
FAMILIAL IDIOPATHIC SCOLIOSIS IN MALE PATIENTS: LOCALISATION TO CHROMOSOME 22Q (2012)

Introduction Clinical studies have shown distinct differences in later-onset idiopathic scoliosis (IS) between men and women, including curve severity, stiffness, and ease of operative intervention. Therefore, significant scoliosis in men was used as criteria to create a phenotypical subset of families with IS. The goal of this study is to identify genetic determinants that relate specifically to men with a scoliotic curvature of 30° or more. Methods We identified 25 families (208 individuals) in which a male was diagnosed with 30° or more IS curvature in adolescence. 123 individuals were affected (48 male; 75 female), and 85 were unaffected (45 male; 40 female). Initially, a genomic screen was done with a modified CHLC (version 9) marker set. After initial linkage analyses, the group underwent finemapping with a custom single-nucleotide polymorphism (SNP) panel and ABI Taqman methodology on an ABI 377 platform. The initial genome-wide screen and subsequent analyses were analysed by model-independent linkage analysis with SIBPAL (SAGE, version 5). Results Genomic screen analyses revealed significant results (=two adjacent STRP markers p LARGE gene, which is integral to the development and maintenance of skeletal muscle, and SFI1 gene, which is responsible for the integrity of the chromosomal centromere complex. Conclusions A subset of families was identified within a cohort of familial idiopathic scoliosis (FIS) families that contained male patients with severe scoliosis, facilitating the study of genetic determinants. Data show a highly significant correlation with a locus containing the LARGE and SFI1 genes on chromosome 22. Future goals include association and sequencing analyses of this region. FIS is a complex genetic disorder. Use of clinical criteria may help to decrease the heterogeneity of any one study population, and enhance the successful identification of specific genes that bring about this disorder. The identification of a genetic locus is of major clinical and therapeutic interest and might improve understanding of spinal growth and stability.
TNF‐related apoptosis‐inducing ligand as a therapeutic agent in autoimmunity and cancer (2006)

Recombinant, soluble TNF-related apoptosis-inducing ligand (TRAIL) is currently being developed as a promising natural immune molecule for trial in cancer patients because it selectively induces apoptosis in transformed or stressed cells but not in most normal cells. In cancer patients, phase 1 and 2 clinical trials using agonistic mAbs that engage the human TRAIL receptors DR4 and DR5 have also provided encouraging results. It is now evident that TRAIL suppresses autoimmune disease in various experimental animal models, suggesting that the therapeutic value of recombinant TRAIL and agonistic DR4 and DR5 mAbs might also extend to the suppression of autoimmune disease. This review provides an insight into our current understanding of the role(s) of TRAIL in disease, with a specific focus on cancer and autoimmunity. We also emphasize biological agents and drugs that sensitize tumour cells to TRAIL-mediated apoptosis and discuss the potential molecular basis for their sensitization.
Structure of the Kinase Domain of an Imatinib-Resistant Abl Mutant in Complex with the Aurora Kinase Inhibitor VX-680 (2006)

We present a high-resolution (2.0 A) crystal structure of the catalytic domain of a mutant form of the Abl tyrosine kinase (H396P; Abl-1a numbering) that is resistant to the Abl inhibitor imatinib. The structure is determined in complex with the small-molecule inhibitor VX-680 (Vertex Pharmaceuticals, Cambridge, MA), which blocks the activity of various imatinib-resistant mutant forms of Abl, including one (T315I) that is resistant to both imatinib and BMS-354825 (dasatinib), a dual Src/Abl inhibitor that seems to be clinically effective against all other imatinib-resistant forms of BCR-Abl. VX-680 is shown to have significant inhibitory activity against BCR-Abl bearing the T315I mutation in patient-derived samples. The Abl kinase domain bound to VX-680 is not phosphorylated on the activation loop in the crystal structure but is nevertheless in an active conformation, previously unobserved for Abl and inconsistent with the binding of imatinib. The adoption of an active conformation is most likely the result of synergy between the His(396)Pro mutation, which destabilizes the inactive conformation required for imatinib binding, and the binding of VX-680, which favors the active conformation through hydrogen bonding and steric effects. VX-680 is bound to Abl in a mode that accommodates the substitution of isoleucine for threonine at residue 315 (the "gatekeeper" position). The avoidance of the innermost cavity of the Abl kinase domain by VX-680 and the specific recognition of the active conformation explain the effectiveness of this compound against mutant forms of BCR-Abl, including those with mutations at the gatekeeper position.
Integrin Expression and Function on Human Osteoblast-like Cells (1997)

The integrin family of cell adhesion molecules are a series of cell surface glycoproteins that recognize a range of cell surface and extracellular matrix (ECM)-associated ligands. To date, the precise role of individual integrin molecules in bone cell-ECM interactions remains unclear. Cell binding assays were performed to examine the ability of normal human bone cells (NHBCs) to adhere to different ECM proteins in vitro. NHBCs displayed preferential adhesion to fibronectin over collagen types I, IV, and vitronectin and showed low affinity binding to laminin and collagen type V. No binding was observed to collagen type III. The integrin heterodimers alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, alpha v beta 3, and alpha v beta 5 were found to be constitutively expressed on the cell surface of NHBCs by flow cytometric analysis. The integrins alpha 4 beta 1 and alpha 6 beta 1 were not expressed by NHBCs. Subsequent binding studies showed that NHBC adhesion to collagen and laminin was mediated by multiple integrins where cell attachment was almost completely inhibited in the presence of a combination of function-blocking monoclonal antibodies (Mabs) to alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, and beta 1. In contrast, the adhesion of NHBCs to fibronectin was only partially inhibited (50%) in the presence of blocking Mabs to alpha 3 beta 1, alpha 5 beta 1, and beta 1. The attachment of NHBCs to collagen, laminin, fibronectin, and vitronectin was also found to be unaffected in the presence of a function-blocking Mab to alpha v beta 3. The results of this study indicate that beta 1 integrins appear to be the predominant adhesion receptor subfamily utilized by human osteoblast-like cells to adhere to collagen and laminin and in part to fibronectin.
Overview of Existing Cartilage Repair Technology (2008)

Currently, autologous chondrocyte implantation and osteochondral grafting bridge the gap between palliation of cartilage injury and resurfacing via arthroplasty. Emerging technologies seek to advance first generation techniques and accomplish several goals including predictable outcomes, cost-effective technology, single-stage procedures, and creation of durable repair tissue. The biologic pipeline represents a variety of technologies including synthetics, scaffolds, cell therapy, and cell-infused matrices. Synthetic constructs, an alternative to biologic repair, resurface a focal chondral defect rather than the entire joint surface. Scaffolds are cell-free constructs designed as a biologic "net" to augment marrow stimulation techniques. Minced cartilage technology uses stabilized autologous or allogeneic fragments in 1-stage transplantation. Second and third generation cell-based methods include alternative membranes, chondrocyte seeding, and culturing onto scaffolds. Despite the promising early results of these products, significant technical obstacles remain along with unknown long-term durability. The vast array of developing technologies has exceptional promise and the potential to revolutionize the cartilage treatment algorithm within the next decade.
Stochastic pairing of heavy-chain and kappa light-chain variable gene families occurs in polyclonally activated B cells. (1990)

Frequencies of 25 immunoglobulin heavy-chain and kappa light-chain variable (VH + V kappa) gene-family pairings expressed in splenic B-cell populations were determined by hybridization of VH- and V kappa-family-specific DNA probes to mitogen-induced B-cell colonies from C57BL/6 mice or hybridomas derived from BALB/c and NZB mice. Both analyses support the conclusion that VH and V kappa gene families pair without bias; as would be expected for random association, the frequencies of specific VH + V kappa pairs may be estimated by the product of the independent VH and V kappa frequencies. Based upon the frequencies at which 9 VH and 12 V kappa gene families are expressed, we calculated the expected usage for approximately 100 VH + V kappa family pairings in neonatal and adult C57BL/6 mice. Variability in the expression of such VH + V kappa pairings is considerable; pairs representing greater than 10% to less than 0.01% of the splenic B-cell population occur. This variability is most pronounced in the neonate, where 6 VH + V kappa family pairs account for nearly 40% of all mitogen-reactive B cells. As the neonate matures, the distribution of frequencies for VH + V kappa pairings becomes more nearly uniform. This process may underlie the patterned acquisition of humoral immune responsiveness.
Disseminated intravascular coagulation. (2008)

Disseminated intravascular coagulation (DIC) is a serious, life-threatening condition in humans and animals.A secondary complication in a variety of disorders, it is a complex syndrome in which excessive intravascular coagulation leads to microthromboses in and consequential failure of multiple organs with concurrent paradoxical bleeding due to inactivation and excessive consumption of platelets and clotting factors. This article discusses the pathophysiology, diagnosis, and treatment of DIC in dogs and cats. Novel treatments and laboratory tests, some of which are still being experimentally evaluated, are also discussed.
Expression and reconstitution of a biologically active human interferon-gamma receptor in hamster cells. (1990)

We report the expression of the human interferon-gamma (Hu-IFN-gamma) receptor from a cDNA clone in an animal cell where both stable expression of the cloned receptor as well as its biological activity is demonstrated for the first time. Biological activity of the receptor (i.e. expression of surface histocompatibility antigens in response to human interferon-gamma) requires the presence of human chromosome 21 demonstrating the requirement for at least one other species-specific factor in the modulation of receptor action. This system should now facilitate delineation of regions involved in the binding of human interferon-gamma and receptor signal transduction.