gebhart/patrepeval huggingface dataset:
Protein dynamics simulations from nanoseconds to microseconds (1999)

There have been a number of advances in atomic resolution simulations of biomolecules during the past few years. These have arisen partly from improvements to computer power and partly from algorithmic improvements. There have also been advances in measuring time-dependent fluctuations in proteins using NMR spectroscopy, revealing the importance of fluctuations in the microsecond to millisecond time range. Progress has also been made in measuring how far the simulations are able to represent the accessible phase space that is available to the protein in its native state, in solution, at room temperature. Another area of development is the simulation of protein unfolding at atomic resolution.
Origin of myofibroblasts in the fibrotic liver in mice (2014)

Hepatic myofibroblasts are activated in response to chronic liver injury of any etiology to produce a fibrous scar. Despite extensive studies, the origin of myofibroblasts in different types of fibrotic liver diseases is unresolved. To identify distinct populations of myofibroblasts and quantify their contribution to hepatic fibrosis of two different etiologies, collagen-α1(I)-GFP mice were subjected to hepatotoxic (carbon tetrachloride; CCl4) or cholestatic (bile duct ligation; BDL) liver injury. All myofibroblasts were purified by flow cytometry of GFP(+) cells and then different subsets identified by phenotyping. Liver resident activated hepatic stellate cells (aHSCs) and activated portal fibroblasts (aPFs) are the major source (>95%) of fibrogenic myofibroblasts in these models of liver fibrosis in mice. As previously reported using other methodologies, hepatic stellate cells (HSCs) are the major source of myofibroblasts (>87%) in CCl4 liver injury. However, aPFs are a major source of myofibroblasts in cholestatic liver injury, contributing >70% of myofibroblasts at the onset of injury (5 d BDL). The relative contribution of aPFs decreases with progressive injury, as HSCs become activated and contribute to the myofibroblast population (14 and 20 d BDL). Unlike aHSCs, aPFs respond to stimulation with taurocholic acid and IL-25 by induction of collagen-α1(I) and IL-13, respectively. Furthermore, BDL-activated PFs express high levels of collagen type I and provide stimulatory signals to HSCs. Gene expression analysis identified several novel markers of aPFs, including a mesothelial-specific marker mesothelin. PFs may play a critical role in the pathogenesis of cholestatic liver fibrosis and, therefore, serve as an attractive target for antifibrotic therapy.
Tyrosine phosphorylation of protein phosphatase 2A in response to growth stimulation and v-src transformation of fibroblasts. (1994)

The catalytic subunit of protein phosphatase 2A (PP2A) is inactivated by in vitro phosphorylation of Tyr307 by receptor and nonreceptor protein tyrosine kinases (Chen, J., Martin, B. L., and Brautigan, D. L. (1992) Science 257, 1261-1264). Here we show the phosphorylation of PP2A in cells under different growth conditions. In lysates of nontransformed murine 10T1/2 fibroblasts, there were two forms of PP2A at 36 kDa detected after two-dimensional gel electrophoresis and immunoblotting with anti-PP2A peptide antibody. These two forms exactly comigrated with unphosphorylated purified PP2A and the PP2A 32P-labeled by in vitro phosphorylation with p60v-src kinase. The phosphorylated form of PP2A recovered from red blood cells or produced by in vitro phosphorylation was eliminated by incubation with tyrosine-specific phosphatase (PTP1B). Transformation of 10T1/2 cells by expression of p60v-src resulted in most of the PP2A in the cells being converted to a phosphorylated form that was reactive with anti-phosphotyrosine antibody. Serum starvation of cells reduced the amount of phosphorylated PP2A, whereas serum stimulation of quiescent cells caused an increase to the same relative amount of phosphorylated PP2A as in src-transformed cells. Addition of epidermal growth factor to quiescent NeoR cells (10T1/2 fibroblasts overexpressing epidermal growth factor receptors) temporarily increased the level of phosphorylation of PP2A, with a peak at 5-15 min and a return to basal level within 60 min. The results show that PP2A is phosphorylated in intact cells, and the extent of this modification is increased by growth factors or cell transformation, providing evidence for a physiological mechanism of PP2A regulation.
Oncolytic measles viruses displaying a single-chain antibody against CD38, a myeloma cell marker (2003)

Live attenuated measles virus (MV-Edm) has potent oncolytic activity against myeloma xenografts in mice. Therapy of multiple myeloma, a disseminated plasma cell malignancy, would require systemic administration of the virus. Thus, the virus should ideally be targeted to infect only myeloma cells to minimize collateral damage to normal tissues: viral binding to its natural receptors must be ablated and a new specificity domain that targets entry into myeloma cells be added. This study covers 2 critical steps toward generating such a retargeted virus: (1) a new specificity domain against the plasma cell marker CD38 was constructed in the form of a single-chain antibody (scFv) and (2) display of that scFv on the measles viral envelope glycoprotein successfully redirected virus entry through CD38 expressed on target cells devoid of the natural MV receptors. The anti-CD38 scFv was tethered to the C-terminus of the hemagglutinin (H) glycoprotein of MV-Edm through a Factor Xa protease cleavable linker. Immunoblot analysis demonstrated that the scFv was efficiently incorporated into recombinant viral particles. Replication of MV-alpha CD38 was not hindered by the scFv, reaching titers comparable to MV-Edm. Chinese hamster ovary (CHO) cells were resistant to infection by MV-Edm and MV-alpha CD38. In contrast, CHO cells expressing CD38 became susceptible to infection by MV-alpha CD38 but not MV-Edm. Removal of the displayed scFv rendered MV-alpha CD38 noninfectious on CHO-CD38 cells. Tumorigenicity of CHO-CD38 cells in immunocompromised mice was significantly attenuated by MV-alpha CD38, resulting in enhanced survival of these mice compared with the control group.
Urban Bias, Rural Sexual Minorities, and the Courts - eScholarship (2013)

This article examines the role of courts in rural sexual minorities’ lives. It focuses first on state action, explaining that courts’ failure to apply heightened scrutiny to sexual orientation classifications harms rural sexual minorities uniquely in family and employment law contexts, where judges explicitly invoke antigay rural norms to justify discriminatory treatment. It argues that by taking rural sexual minorities’ relative political powerlessness into account in Equal Protection claims, courts are more likely to find that all sexual orientation classifications are suspect. It focuses second on private discrimination, and it discusses ways to protect and strengthen rural sexual minorities’ privacy rights. It argues that privacy is central to protecting sexual minorities’ liberty to live, create families, and work in rural environments.
Cytogenetic analysis of 363 consecutively ascertained diffuse large B‐cell lymphomas (1999)

Cytogenetic analysis was performed on 363 biopsy specimens with histologically confirmed diffuse large B-cell lymphoma (DLBCL), consecutively ascertained at the Memorial Sloan-Kettering Cancer Center, New York, between 1984 and 1994. Among 248 samples successfully karyotyped, clonal chromosomal abnormalities were noted in 215 (87%). The salient cytogenetic features of DLBCL from this analysis comprised the following. Breakpoints clustered, in decreasing frequency, at 10 recurring sites: 14q32, 18q21, 1q21, 3q27, 1p36, 8q24, 3p21, 6q21, 1p22, and 22q11. Of these, deletion breaks affecting bands 3p21 and 1p22 and translocation breaks affecting bands 14q32, 3q27, and 1q21 were frequent and distinctive for this subset of lymphomas. Translocations affecting band 14q32 were noted in 110 cases (51%) of which 42 (20%) had t(14;18)(q32;q21), 21 (10%) had t(8;14)(q24;q32) or t(8;22)(q24;q11), 14 (6.5%) had t(3;14)(q27;q32) or t(3;22)(q27;q11), and 33 (15%) had other rearrangements of 14q32. Among 144 new translocations detected in the entire group, the breakpoints in 19 were recurrent and clustered at three sites: 1q21, 3q27, and 14q32. Regions of common cytogenetic deletions were identified at 11 sites, 1p36, 1p33–34, 1p31, 1q32, 3p25–26, 3p21, 3q21, 6q15, 6q21, 6q23–24, and 7q32, suggesting possible loss of candidate tumor suppressor genes associated with DLBCL development. Of these, only those at 6q21, 6q23, and 7q32 have previously been described in lymphoid neoplasms. The group of DLBCL with translocations affecting band 14q32 showed a significantly different pattern of additional cytogenetic changes compared to the group lacking such translocation. This new comprehensive cytogenetic characterization provides the basis for investigations aimed at identifying molecular mechanisms as well as the clinical impact of cytogenetic changes in DLBCL. Genes Chromosomes Cancer 25:123–133, 1999. © 1999 Wiley-Liss, Inc.
Hydrocarbon-fueled scramjet combustor investigation (1992)

An experimental program is being conducted for developing the technology required by a hydrocarbon-fueled engine capable of operating as a scramjet in the Mach 5.6-7.0 range. A series of tests have been run to define scramjet combustor design criteria applicable to a scramjet configuration involving a pair of modular, axisymmetric combustors mounted on the lower surface of a supersonic/hypersonic missile. The airbreathing pilot combustor incorporates an external mainstream fuel injector which serves as the primary fuel injection stage for the supersonic combustor; it has been demonstrated that the pilot promotes the efficient combustion of either gaseous ethylene or preheated JP-5, when they are injected into the mainstream flow as a primary fuel.
The 7TM G‐Protein‐Coupled Receptor Target Family (2006)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
PD-1/PD-L1 Interactions Contribute to Functional T-Cell Impairment in Patients Who Relapse with Cancer After Allogeneic Stem Cell Transplantation (2011)

Tumor relapses remain a serious problem after allogeneic stem cell transplantation (alloSCT), despite the long-term persistence of minor histocompatibility antigen (MiHA)-specific memory CD8(+) T cells specific for the tumor. We hypothesized that these memory T cells may lose their function over time in transplanted patients. Here, we offer functional and mechanistic support for this hypothesis, based on immune inhibition by programmed death-1 (PD-1) expressed on MiHA-specific CD8(+) T cells and the associated role of the PD-1 ligand PD-L1 on myeloid leukemia cells, especially under inflammatory conditions. PD-L1 was highly upregulated on immature human leukemic progenitor cells, whereas costimulatory molecules such as CD80 and CD86 were not expressed. Thus, immature leukemic progenitor cells seemed to evade the immune system by inhibiting T-cell function via the PD-1/PD-L1 pathway. Blocking PD-1 signaling using human antibodies led to elevated proliferation and IFN-γ production of MiHA-specific T cells cocultured with PD-L1-expressing leukemia cells. Moreover, patients with relapsed leukemia after initial MiHA-specific T-cell responses displayed high PD-L1 expression on CD34(+) leukemia cells and increased PD-1 levels on MiHA-specific CD8(+) T cells. Importantly, blocking PD-1/PD-L1 interactions augment proliferation of MiHA-specific CD8(+) memory T cells from relapsed patients. Taken together, our findings indicate that the PD-1/PD-L pathway can be hijacked as an immune escape mechanism in hematological malignancies. Furthermore, they suggest that blocking the PD-1 immune checkpoint offers an appealing immunotherapeutic strategy following alloSCT in patients with recurrent or relapsed disease.
Antiidiotypic antibodies carrying the "internal image" of peptide YIGSR inhibit spontaneous metastasis of Lewis lung carcinoma in mice. (2003)

An anti-Id antimetastatic vaccine may be developed based on YIGSR.
Human Skeletal Muscle Fiber Type Classifications (2001)

2][3] This range of muscle fiber types allows for the wide variety of capabilities that human muscles display.In addition, muscle fibers can adapt to changing demands by changing size or fiber type composition.This plasticity serves as the physiologic basis for numerous physical therapy interventions designed to increase a patient's force development or endurance.Changes in fiber type composition also may be partially responsible for some of the impairments and disabilities seen in patients who are deconditioned because of prolonged inactivity, limb immobilization, or muscle denervation. 2Over the past several decades, the number of techniques available for classifying muscle fibers has increased, resulting in several classification systems.The objective of this update is to provide the basic knowledge necessary to read and interpret research on human skeletal muscle.Muscle fiber types can be described using histochemical, biochemical, morphological, or physiologic characteristics; however, classifications of muscle fibers by different techniques do not always agree. 1 Therefore, muscle fibers that may be grouped together by one classification technique may be placed in different categories using a different classification technique.A basic understanding of muscle structure and physiology is necessary to understand the muscle fiber classification techniques.
Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809 (2011)

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene that impair the function of CFTR, an epithelial chloride channel required for proper function of the lung, pancreas, and other organs. Most patients with CF carry the F508del CFTR mutation, which causes defective CFTR protein folding and processing in the endoplasmic reticulum, resulting in minimal amounts of CFTR at the cell surface. One strategy to treat these patients is to correct the processing of F508del-CFTR with small molecules. Here we describe the in vitro pharmacology of VX-809, a CFTR corrector that was advanced into clinical development for the treatment of CF. In cultured human bronchial epithelial cells isolated from patients with CF homozygous for F508del, VX-809 improved F508del-CFTR processing in the endoplasmic reticulum and enhanced chloride secretion to approximately 14% of non-CF human bronchial epithelial cells (EC(50), 81 ± 19 nM), a level associated with mild CF in patients with less disruptive CFTR mutations. F508del-CFTR corrected by VX-809 exhibited biochemical and functional characteristics similar to normal CFTR, including biochemical susceptibility to proteolysis, residence time in the plasma membrane, and single-channel open probability. VX-809 was more efficacious and selective for CFTR than previously reported CFTR correctors. VX-809 represents a class of CFTR corrector that specifically addresses the underlying processing defect in F508del-CFTR.
Carbon monoxide mediates vasodilator effects of glutamate in isolated pressurized cerebral arterioles of newborn pigs (2003)

The excitatory neurotransmitter glutamate causes dilation of newborn pig cerebral arterioles in vivo that is blocked by inhibition of carbon monoxide (CO) production. CO, a potent dilator in cerebral circulation in vivo, is produced endogenously in cerebral microvessels via heme oxygenase (HO). In isolated pressurized cerebral arterioles (approximately 200 microm) from newborn pigs, we investigated the involvement of CO and the endothelium in response to glutamate. A CO-releasing molecule, dimanganese decacarbonyl (10(-8)-10(-6) M), dilated cerebral arterioles. Glutamate (10(-6)-10(-4) M) and 1-aminocyclopentane-cis-1,3-dicarboxylic acid (cis-ACPD; 10(-6)-10(-5) M), a N-methyl-D-aspartate (NMDA) receptor agonist, caused cerebral vascular dilation. Dilation of cerebral arterioles to glutamate and cis-ACPD was abolished by chromium mesoporphyrin (CrMP; 10(-6) M), a HO inhibitor. In contrast, CrMP did not alter dilation to isoproterenol, a -adrenergic receptor agonist. Endothelium-denuded cerebral arterioles did not dilate to glutamate or bradykinin (endothelium-dependent dilator), whereas responses to isoproterenol were preserved. These data indicate that cerebral arterioles from newborn pigs may directly respond to glutamate and the NMDA receptor agonists by endothelium-dependent dilation that involves stimulation of CO production via the HO pathway in the endothelium.
Antibody and T‐cell responses specific for the androgen receptor in patients with prostate cancer (2007)

These data demonstrate that some patients with prostate cancer have pre-existing humoral and cellular immune responses specific for the AR, suggesting that tolerance against the AR is not absolute and that the AR may be a potential immunotherapeutic target antigen.
Biodendrimer-Based Hydrogel Scaffolds for Cartilage Tissue Repair (2005)

Photo-crosslinkable dendritic macromolecules are attractive materials for the preparation of cartilage tissue engineering scaffolds that may be optimized for in situ formation of hydrated, mechanically stable, and well-integrated hydrogel scaffolds supporting chondrocytes and chondrogenesis. We designed and synthesized a novel hydrogel scaffold for cartilage repair, based on a multivalent and water-soluble tri-block copolymer consisting of a poly(ethylene glycol) core and methacrylated poly(glycerol succinic acid) dendrimer terminal blocks. The terminal methacrylates allow mild and biocompatible photo-crosslinking with a visible light, facilitating in vivo filling of irregularly shaped defects with the dendrimer-based scaffold. The multivalent dendrimer constituents allow high crosslink densities that inhibit swelling after crosslinking while simultaneously introducing biodegradation sites. The mechanical properties and water content of the hydrogel can easily be tuned by changing the biodendrimer concentration. In vitro chondrocyte encapsulation studies demonstrate significant synthesis of neocartilaginous material, containing proteoglycans and type II collagen.
Virtual face image generation for illumination and pose insensitive face recognition (2003)

Face recognition has attracted much attention in the past decades for its wide potential applications. Much progress has been made in the past few years. However, specialized evaluation of the state-of-the-art in both academic algorithms and commercial systems illustrates that the performance of most current recognition technologies degrades significantly due to the variations of illumination and/or pose. To solve these problems, providing multiple training samples to the recognition system is a rational choice. However, enough samples are not always available for many practical applications. It is an alternative to augment the training set by generating virtual views from one single face image, that is relighting the given face images of synthesize novel views of the given face. Based on this strategy, this paper presents some attempts by presenting a ratio-image based face relighting method and a face re-rotating approach based on linear shape prediction and image warp. To evaluate the effect of the additional virtual face images, primary experiments are conducted using our specific substance method as face recognition approach, which shows impressive improvement compared with standard benchmark face recognition methods.
Genetic disruption of both Fancc and Fancg in mice recapitulates the hematopoietic manifestations of Fanconi anemia (2010)

Fanconi anemia (FA) is an inherited chromosomal instability syndrome characterized by bone marrow failure, myelodysplasia (MDS), and acute myeloid leukemia (AML). Eight FA proteins associate in a nuclear core complex to monoubiquitinate FANCD2/FANCI in response to DNA damage. Additional functions have been described for some of the core complex proteins; however, in vivo genetic proof has been lacking. Here we show that double-mutant Fancc(-/-);Fancg(-/-) mice develop spontaneous hematologic sequelae including bone marrow failure, AML, MDS and complex random chromosomal abnormalities that the single-mutant mice do not. This genetic model provides evidence for unique core complex protein function independent of their ability to monoubiquitinate FANCD2/FANCI. Importantly, this model closely recapitulates the phenotypes found in FA patients and may be useful as a preclinical platform to evaluate the molecular pathogenesis of spontaneous bone marrow failure, MDS and AML in FA.
[Effect of sodium humate on animals irradiated with lethal doses]. (1987)

A therapeutic effect of natrium humate given to experimental mongrel rats exposed to 60Co-gamma-radiation of lethal doses has been studied. A single administration of natrium humate, 5-10 min following irradiation with a dose of 193.5 mC/kg (LD100/30) leads to a 43.3 per cent survival of animals after 60 days; with a dose of 232.2 mC/kg (LD100/8) there is a trend toward the increase in the life span of exposed rats.
Highly Active and Selective Catalysts for the Formation of α-Aryl Ketones (2000)

Bulky, electron-rich phosphine ligands with a biphenyl backbone, when combined with Pd(OAc)2, give highly active catalysts for the α-arylation of ketones. The ligand 2-methyl-2‘-dicyclohexylphosphinobiphenyl is particularly effective, and with 0.1−1.0 mol % Pd, a large variety of aryl halides and ketones react efficiently and with high selectivity. For two types of substrates, the ligands BINAP and Xantphos are more effective than the biphenyl-based ligands. It is also shown that K3PO4 can be used as the base in these reactions, and that base-sensitive functional groups are better tolerated if this is used instead of NaOtBu or NaHMDS. In some cases, α-aryl ketones can be produced without adding a ligand to the reaction. Although the substrate scope of the ligandless conditions is limited, some combinations react in high yield, and in one case, 100 000 turnovers were obtained. The results of experiments on the Pd-catalyzed arylation of diethyl malonate, cyclic 1,3-diketones, and nitroalkanes are also reported.
CD4~+ CD25~+-regulatory T cells in peripheral blood from patients with non small cell lung carcinoma (2006)

Objective:To determine the level of CD4+CD25+-regulatory T cells (Tregs) in peripheral blood from non small cell lung carcinoma (NSCLC) patients and evaluate its clinical significance. Methods:The frequency of Tregs in the peripheral blood from 61 NSCLC patients and 30 healthy controls was determined by flow cytometry. Results:Tregs was identified by CD45RA(-) and CD69(-). NSCLC patients showed an increase in Tregs in the peripheral blood compared with healthy control [(14.02±5.42)% vs (27.14±12.74)%,n=61,P0.01]. The percentages of Tregs were increased with NSCLC development [stageⅠ+Ⅱ:(15.50±4.73)%,n=15;stage Ⅲ:(25.97±5.94)%,n=20,P0.01; stage Ⅳ:(35.13±13.27)%,n=26,P0.001)]. Those patients with higher percentages of Tregs had a poorer prognosis. Conclusion:The level of Tregs in the peripheral blood from NSCLC patients was higher than that in healthy control. It was related with tumor development. Depletion of Tregs may induce anti-tumor immunity for NSCLC.