gebhart/patrepeval huggingface dataset:
Shear-Thinning Nanocomposite Hydrogels for the Treatment of Hemorrhage (2014)

Internal hemorrhaging is a leading cause of death after traumatic injury on the battlefield. Although several surgical approaches such as the use of fibrin glue and tissue adhesive have been commercialized to achieve hemostasis, these approaches are difficult to employ on the battlefield and cannot be used for incompressible wounds. Here, we present shear-thinning nanocomposite hydrogels composed of synthetic silicate nanoplatelets and gelatin as injectable hemostatic agents. These materials are demonstrated to decrease in vitro blood clotting times by 77%, and to form stable clot-gel systems. In vivo tests indicated that the nanocomposites are biocompatible and capable of promoting hemostasis in an otherwise lethal liver laceration. The combination of injectability, rapid mechanical recovery, physiological stability, and the ability to promote coagulation result in a hemostat for treating incompressible wounds in out-of-hospital, emergency conditions.
Reliability Study of Phase-Change Nonvolatile Memories (2004)

A detailed investigation of the reliability aspects in nonvolatile phase-change memories (PCM) is presented, covering the basic aspects related to high density array NVM, i.e., data retention, endurance, program and read disturbs. The data retention capabilities and the endurance characteristics of single PCM cells are analyzed, showing that data can be stored for 10 years at 110/spl deg/C and that a resistance difference of two order of magnitude between the cell states can be maintained for more than 10/sup 11/ programming cycles. The main mechanisms responsible for instabilities just before failure as well as for final device breakdown are also discussed. Finally, the impact of read and program disturbs are clearly assessed, showing with experimental data and simulated results that the crystallization induced during the cell read out and the thermal cross-talk due to adjacent bits programming do not affect the retention capabilities of the PCM cells.
Staudinger Ligation of Peptides at Non-Glycyl Residues (2006)

The Staudinger ligation provides a means to form an amide bond between a phosphinothioester and azide. This reaction holds promise for the ligation of peptides en route to the total chemical synthesis of proteins. (Diphenylphosphino)methanethiol is the most efficacious of known reagents for mediating the Staudinger ligation of peptides, providing high (> 90%) isolated yields for equimolar couplings in which a glycine residue is at the nascent junction. Surprisingly, the yields are lower (< 50%) for non-glycyl couplings due to an aza-Wittig reaction that diverts the reaction toward a phosphonamide byproduct. Here, the partitioning of the reaction toward Staudinger ligation (and away from the aza-Wittig reaction) is shown to increase with increasing electron density on phosphorus. This electron density can be tuned either by installing functional groups on the phenyl substituents of (diphenylphosphino)methanethiol or by changing the polarity of the solvent. Installing p-methoxy groups and using a solvent of low polarity (such as toluene or dioxane) provide especially high (> 80%) isolated yields for the ligation of two non-glycyl residues. These conditions retain the high chemoselectivity of the reaction and do not lead to a substantial change in reaction rate. The traceless Staudinger ligation is now poised to enable the iterative ligation of peptides with little regard for their sequence, as well as the synthesis of amide bonds for other purposes.
Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover (2002)

Several growth factors are expressed in distinct temporal and spatial patterns during fracture repair. Of these, vascular endothelial growth factor, VEGF, is of particular interest because of its ability to induce neovascularization (angiogenesis). To determine whether VEGF is required for bone repair, we inhibited VEGF activity during secondary bone healing via a cartilage intermediate (endochondral ossification) and during direct bone repair (intramembranous ossification) in a novel mouse model. Treatment of mice with a soluble, neutralizing VEGF receptor decreased angiogenesis, bone formation, and callus mineralization in femoral fractures. Inhibition of VEGF also dramatically inhibited healing of a tibial cortical bone defect, consistent with our discovery of a direct autocrine role for VEGF in osteoblast differentiation. In separate experiments, exogenous VEGF enhanced blood vessel formation, ossification, and new bone (callus) maturation in mouse femur fractures, and promoted bony bridging of a rabbit radius segmental gap defect. Our results at specific time points during the course of healing underscore the role of VEGF in endochondral vs. intramembranous ossification, as well as skeletal development vs. bone repair. The responses to exogenous VEGF observed in two distinct model systems and species indicate that a slow-release formulation of VEGF, applied locally at the site of bone damage, may prove to be an effective therapy to promote human bone repair.
Antipeptide antibodies of predetermined specificity recognize and neutralize the bioactivity of the pan-specific hemopoietin interleukin 3. (1987)

Ten peptides that corresponded to portions of the T cell lymphokine pan-specific hemopoietin interleukin 3 (IL 3) were synthesized, coupled to keyhole limpet hemocyanin, and used to raise antipeptide antibodies in rabbits. These antisera reacted to varying degrees with native biologically active IL 3. Antibodies directed against peptides corresponding to residues 1-29 at the NH2 terminus, 123-140 at the COOH terminus, and to residues 64-82 and 91-112 were affinity-purified on peptide columns. Immunoabsorbent columns produced from affinity-purified antibodies to the 1-29, 91-112, and 123-140 although not the 64-82 peptide were effective in depleting biologically active IL 3 from conditioned medium. However, the antibodies specific for peptides 91-112 and 123-140 had only a low affinity for native IL 3 and it was only in the case of the anti-1-29 antibodies that a significant amount of IL 3 remained bound after extensive washing and could be recovered from the column by acid elution. The affinity-purified antibodies directed to peptides 1-29, 91-112, and 123-140 significantly inhibited the biological activity of IL 3, although with different dose-response characteristics. Anti-1-29 antibodies inhibited bioactivity over a wide range of concentrations (down to 20 ng/ml) although the inhibition was never complete. In contrast, the anti-91-112 antibodies, although effective only at high concentrations, produced complete inhibition of biological activity. These experiments demonstrated that antibodies to defined peptides can be used to generate antibodies to native IL 3 and should form useful tools in analyzing the structure and function of the native molecules.
A R2R3-MYB gene, AtMYB30 , acts as a positive regulator of the hypersensitive cell death program in plants in response to pathogen attack (2002)

Hypersensitive response (HR) is a programmed cell death that is commonly associated with disease resistance in plants. Among the different HR-related early induced genes, the AtMYB30 gene is specifically, rapidly, and transiently expressed during incompatible interactions between Arabidopsis and bacterial pathogens. Its expression was also shown to be deregulated in Arabidopsis mutants affected in the control of cell death initiation. Here, we demonstrate that overexpression in Arabidopsis and tobacco of AtMYB30 ( i ) accelerates and intensifies the appearance of the HR in response to different avirulent bacterial pathogens, ( ii ) causes HR-like responses to virulent strains, and ( iii ) increases resistance against different bacterial pathogens, and a virulent biotrophic fungal pathogen, Cercospora nicotianae . In antisense AtMYB30 Arabidopsis lines, HR cell death is strongly decreased or suppressed in response to avirulent bacterial strains, resistance against different bacterial pathogens decreased, and the expression of HR- and defense-related genes was altered. Taken together, these results strongly suggest that AtMYB30 is a positive regulator of hypersensitive cell death.
Drug resistance in castration resistant prostate cancer: resistance mechanisms and emerging treatment strategies. (2015)

Several mechanisms facilitate the progression of hormone-sensitive prostate cancer to castration-resistant prostate cancer (CRPC). At present, the approved chemotherapies for CRPC include systemic drugs (docetaxel and cabazitaxel) and agents that target androgen signaling, including enzalutamide and abiraterone. While up to 30% of patients have primary resistance to these treatments, each of these drugs confers a significant survival benefit for many. Over time, however, all patients inevitably develop resistance to treatment and their disease will continue to progress. Several key mechanisms have been identified that give rise to drug resistance. Expression of constitutively active variants of the androgen receptor, such as AR-V7, intracrine androgens and overexpression of androgen synthesis enzymes like AKR1C3, and increased drug efflux through ABCB1 are just some of the many discovered mechanisms of drug resistance. Treatment strategies are being developed to target these pathways and reintroduce drug sensitivity. Niclosamide has been discovered to reduce AR-V7 activity and synergized to enzalutamide. Indomethacin has been explored to inhibit AKR1C3 activity and showed to be able to reverse resistance to enzalutamide. ABCB1 transport activity can be mitigated by the phytochemical apigenin and by antiandrogens such as bicalutamide, with each improving cellular response to chemotherapeutics. By better understanding the mechanisms by which drug resistance develops improved treatment strategies will be made possible. Herein, we review the existing knowledge of CRPC therapies and resistance mechanisms as well as methods that have been identified which may improve drug sensitivity.
Gene therapy for the Wiskott–Aldrich syndrome (2011)

WAS is amenable to hematopoietic stem cell gene therapy. New trials using lentiviral vectors are expected to improve efficacy and safety profiles. Beyond proof of principle, ongoing international efforts to coordinate trials of gene therapy for the WAS may also provide a model for the expedited development of new treatments for other rare diseases.
Characterization of a Novel Arginine Catabolic Mobile Element (ACME) and Staphylococcal Chromosomal Cassette mec Composite Island with Significant Homology to Staphylococcus epidermidis ACME Type II in Methicillin-Resistant Staphylococcus aureus Genotype ST22-MRSA-IV (2011)

The arginine catabolic mobile element (ACME) is prevalent among methicillin-resistant Staphylococcus aureus (MRSA) isolates of sequence type 8 (ST8) and staphylococcal chromosomal cassette mec (SCCmec) type IVa (USA300) (ST8-MRSA-IVa isolates), and evidence suggests that ACME enhances the ability of ST8-MRSA-IVa to grow and survive on its host. ACME has been identified in a small number of isolates belonging to other MRSA clones but is widespread among coagulase-negative staphylococci (CoNS). This study reports the first description of ACME in two distinct strains of the pandemic ST22-MRSA-IV clone. A total of 238 MRSA isolates recovered in Ireland between 1971 and 2008 were investigated for ACME using a DNA microarray. Twenty-three isolates (9.7%) were ACME positive, and all were either MRSA genotype ST8-MRSA-IVa (7/23, 30%) or MRSA genotype ST22-MRSA-IV (16/23, 70%). Whole-genome sequencing and comprehensive molecular characterization revealed the presence of a novel 46-kb ACME and staphylococcal chromosomal cassette mec (SCCmec) composite island (ACME/SCCmec-CI) in ST22-MRSA-IVh isolates (n=15). This ACME/SCCmec-CI consists of a 12-kb DNA region previously identified in ACME type II in S. epidermidis ATCC 12228, a truncated copy of the J1 region of SCCmec type I, and a complete SCCmec type IVh element. The composite island has a novel genetic organization, with ACME located within orfX and SCCmec located downstream of ACME. One PVL locus-positive ST22-MRSA-IVa isolate carried ACME located downstream of SCCmec type IVa, as previously described in ST8-MRSA-IVa. These results suggest that ACME has been acquired by ST22-MRSA-IV on two independent occasions. At least one of these instances may have involved horizontal transfer and recombination events between MRSA and CoNS. The presence of ACME may enhance dissemination of ST22-MRSA-IV, an already successful MRSA clone.
The first evaluation of brain shift during functional neurosurgery by deformation field analysis (2005)

Stereotactic surgery is based on a high degree of accuracy in defining and localising intracranial targets and placing surgical tools. Brain shift can influence its accuracy significantly. Deep brain stimulation of the subthalamic nucleus can markedly change the quality of life of patients with advanced Parkinson's disease, but the outcome depends on the quality of electrode placement. A patient is reported in whom the placement of the second electrode was not successful. Deformation field analysis of pre- and postoperative three dimensional magnetic resonance images showed an intraoperative brain movement of 2 mm in the region of the subthalamic nucleus (the target point). Electrode repositioning resulted in efficient stimulation effects. This case report shows the need to reduce risk factors for intraoperative brain movement and demonstrates the ability of deformation field analysis to quantify this complication.
Function of the Chlamydomonas reinhardtii petD 5′ untranslated region in regulating the accumulation of subunit IV of the cytochrome b6/f complex (1994)

Translational control is an important regulatory mechanism in chloroplasts, and is thought to be mediated by cis-acting elements in the 5' untranslated regions (UTRs) of mRNAs. Chloroplast transformation was used to replace the wild-type Chlamydomonas reinhardtii petD 5' UTR with mutated versions. Transformants containing altered 5' UTRs had either a wild-type photosynthetic phenotype, a leaky non-photosynthetic phenotype, or were unable to grow photosynthetically. Among those transformants with a wild-type phenotype were ones containing mutations in a putative Shine-Dalgarno sequence element. The results indicate that two regions of the 362 nucleotide (nt) 5' UTR may act as positive elements for translation, one located between nt 150 and 200, and the other situated approximately 40 nt upstream of the start codon, at nt 320. In every case where translation was compromised, petD mRNA accumulated to a lower level than in wild-type cells, ranging from 15% to 60% in different strains. It was concluded that specific regions of the petD 5' UTR mediate translational activation, and that mRNA stability may be linked to translatability.
HLA-Binding Properties of Tumor Neoepitopes in Humans (2014)

Cancer genome sequencing has enabled the rapid identification of the complete repertoire of coding sequence mutations within a patient's tumor and facilitated their use as personalized immunogens. Although a variety of techniques are available to assist in the selection of mutation-defined epitopes to be included within the tumor vaccine, the ability of the peptide to bind to patient MHC is a key gateway to peptide presentation. With advances in the accuracy of predictive algorithms for MHC class I binding, choosing epitopes on the basis of predicted affinity provides a rapid and unbiased approach to epitope prioritization. We show herein the retrospective application of a prediction algorithm to a large set of bona fide T cell-defined mutated human tumor antigens that induced immune responses, most of which were associated with tumor regression or long-term disease stability. The results support the application of this approach for epitope selection and reveal informative features of these naturally occurring epitopes to aid in epitope prioritization for use in tumor vaccines.
[Changes of arterial blood pressure during various stages in spaceflight activities]. (2001)

Arterial blood pressure (BP) is one of the four life signs in human beings, it could reflect cardiovascular function in some degrees. Thus, BP serves as an important cardiovascular parameter during various stages in foreign spaceflight activities. Although the reports about BP are not always in consistency during spaceflight, hypotension commonly occurs during orthostatic stress after spaceflight. The mechanisms of orthostatic intolerance after spaceflight are virtually the same as that of orthostatic hypotension after spaceflight. This paper simply reviewed the reports on BP during various stages in foreign spaceflight activities and the researches on the mechanism of orthostatic hypotension after spaceflight.
CYSTIC FIBROSIS: GENOTYPIC AND PHENOTYPIC VARIATIONS (1995)

Cystic fibrosis (CF) is a common genetic disorder in the Caucasian population. The gene was identified in 1989 on the basis of its map location on chromosome 7. The encoded gene product, named cystic fibrosis transmembrane conductance regulator (CFTR), corresponds to a cAMP-regulated chloride channel found almost exclusively in the secretory epithelial cells. Although the major mutation that results in a single amino acid deletion (F508) accounts for 70% of the disease alleles, more than 550 additional mutant alleles of different forms have been detected. Many of these mutations can be divided into five general classes in terms of their demonstrated or presumed molecular consequences. In addition, a good correlation has been found between CFTR genotype and one of the clinical variables--pancreatic function status. An unexpected finding, however, is the documentation of CFTR mutations in patients with atypical CF disease presentations, including congenital absence of vas deferens and several pulmonary diseases. Thus, the implication of CFTR mutation is more profound than CF alone.
Comparing and Contrasting Escherichia coliand Mycobacterium tuberculosis Mechanosensitive Channels (MscL) (2000)

Sequence analysis of 35 putative MscL homologues was used to develop an optimal alignment for Escherichia coli and Mycobacterium tuberculosis MscL and to place these homologues into sequence subfamilies. By using this alignment, previously identified E. coli MscL mutants that displayed severe and very severe gain of function phenotypes were mapped onto the M. tuberculosis MscL sequence. Not all of the resulting M. tuberculosis mutants displayed a gain of function phenotype; for instance, normal phenotypes were noted for mutations at Ala(20), the analogue of the highly sensitive Gly(22) site in E. coli. A previously unnoticed intersubunit hydrogen bond in the extracellular loop region of the M. tuberculosis MscL crystal structure has been analyzed. Cross-linkable residues were substituted for the residues involved in the hydrogen bond, and cross-linking studies indicated that these sites are spatially close under physiological conditions. In general, mutation at these positions results in a gain of function phenotype, which provides strong evidence for the importance of the loop region in MscL channel function. No analogue to this interesting interaction could be found in E. coli MscL by sequence alignment. Taken together, these results indicate that caution should be exercised in using the M. tuberculosis MscL crystal structure to analyze previous functional studies of E. coli MscL.
Clinical Applications of CD34 + Peripheral Blood Progenitor Cells (PBPC) (2000)

Recently, a number of devices have been developed for the positive selection of CD34(+) peripheral blood progenitor cells (PBPC) for clinical use in autologous or allogeneic transplantation. The rationale for CD34(+) selection is based on clinical studies showing a two- to five-log reduction of contaminating tumor cells in patients with breast cancer, multiple myeloma and low-grade lymphoma. In addition, a three- to five-log reduction of T cells can be obtained by CD34(+) selection in both autologous grafts for patients with autoimmune disease resistant to conventional therapy and allogeneic grafts to reduce the incidence and severity of acute graft-versus-host disease. Transplantation of positively selected autologous CD34(+) PBPC results in a rapid and stable neutrophil and platelet engraftment in patients who received an infused dose of at least 2.0 x 10(6) CD34(+) cells/kg. Results from randomized trials suggest that time to engraftment is not different compared to unmanipulated PBPC autografts. However, close monitoring for infectious complications (e.g., cytomegalovirus disease) is required. Allogeneic CD34(+) PBPC have also been successfully transplanted and, using novel technologies, megadoses of purified CD34(+) PBPC can be obtained and used to overcome histocompatibility differences betweeen allogeneic donor and patient resulting in stable engraftment, even in a haploidentical setting. Additional randomized phase III trials are required to determine whether tumor cell purging or lymphocyte depletion by CD34(+) cell selection will have a significant impact on progression-free and overall survival in both autologous and allogeneic transplantation.
The neurobiology of Alzheimer disease defined by neuroimaging (2012)

These findings have huge implications for research on therapeutic approaches to Alzheimer disease. For instance, while so far only patients with the clinical diagnosis have been treated with immunotherapy targeting abeta removal, a consensus is building that to be effective, this therapy should be given in the preclinical stages of the disease, which are assessed most advantageously by means of neuroimaging.
Determination of Three Disulfide Bonds in a Major House Dust Mite Allergen, <i>Der </i><i>f</i> ll (1993)

Der f II is a major mite allergen consisting of 129 amino acid residues. Der f II contains six cysteine residues, suggesting the existence of three disulfide bonds which would stabilize this small protein. As the first step in revealing the relationship between the structure and the allergenic property of Der f II, the formation of disulfide bonds was examined. Der f II purified from Dermatophagoides farinae was treated with lysyl-endopeptidase or proline-specific endopeptidase, and the peptide fragments thus generated were separated by reverse phase high performance liquid chromatography. Determination of the amino acid sequence of each peptide collected in this way proved the existence of three disulfide bonds between Cys8 and Cys119, Cys21 and Cys27, and Cys73 and Cys78.
Structural Basis for the Synthesis of Indirubins as Potent and Selective Inhibitors of Glycogen Synthase Kinase-3 and Cyclin-Dependent Kinases (2004)

Pharmacological inhibitors of glycogen synthase kinase-3 (GSK-3) and cyclin-dependent kinases have a promising potential for applications against several neurodegenerative diseases such as Alzheimer's disease. Indirubins, a family of bis-indoles isolated from various natural sources, are potent inhibitors of several kinases, including GSK-3. Using the cocrystal structures of various indirubins with GSK-3beta, CDK2 and CDK5/p25, we have modeled the binding of indirubins within the ATP-binding pocket of these kinases. This modeling approach provided some insight into the molecular basis of indirubins' action and selectivity and allowed us to forecast some improvements of this family of bis-indoles as kinase inhibitors. Predicted molecules, including 6-substituted and 5,6-disubstituted indirubins, were synthesized and evaluated as CDK and GSK-3 inhibitors. Control, kinase-inactive indirubins were obtained by introduction of a methyl substitution on N1.