gebhart/patrepeval huggingface dataset:
Biosynthesis of monacolins: Conversion of monacolin L to monacolin J by a monooxygenase of Monascus ruber. (1989)

The microbial metabolites monacolins J and L are specific inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme in cholesterol synthesis. The producing strain Monascus ruber M 4681 was found to convert exogenously added monacolin L to J. In this hydroxylation reaction 18O2 was incorporated into monacolin L, giving [18O]-monacolin J. The cell-free extracts of M. ruber quantitatively hydroxylated monacolin L to J, and molecular oxygen was required for the hydroxylation. The enzyme was located in the microsomal fraction and specific for NADPH. The enzyme activity was inhibited by metyrapone, carbon monoxide, sulfhydryl reagents and cytochrome c. The results indicate that monacolin L is the precursor of monacolin J, and that a monooxygenase is involved in this reaction.
Cytokines and their receptor complexes (1995)

The 3-dimensional structures that resulted from X-ray diffraction and nuclear magnetic resonance analyses of a variety of cytokines are reviewed. These proteins form distinct, well-defined superfamilies based on the structures of their monomers, even in the absence of significant sequence homology. However, in several cases, where the active form of a cytokine is a dimer or higher oligomer, these similar monomers adopt very different modes of dimerization. Two examples of complexes of cytokines with receptor molecules are described and the implications for signal transduction are discussed.
An Ensemble-Based Incremental Learning Approach to Data Fusion (2007)

This paper introduces Learn++, an ensemble of classifiers based algorithm originally developed for incremental learning, and now adapted for information/data fusion applications. Recognizing the conceptual similarity between incremental learning and data fusion, Learn++ follows an alternative approach to data fusion, i.e., sequentially generating an ensemble of classifiers that specifically seek the most discriminating information from each data set. It was observed that Learn++ based data fusion consistently outperforms a similarly configured ensemble classifier trained on any of the individual data sources across several applications. Furthermore, even if the classifiers trained on individual data sources are fine tuned for the given problem, Learn++ can still achieve a statistically significant improvement by combining them, if the additional data sets carry complementary information. The algorithm can also identify-albeit indirectly-those data sets that do not carry such additional information. Finally, it was shown that the algorithm can consecutively learn both the supplementary novel information coming from additional data of the same source, and the complementary information coming from new data sources without requiring access to any of the previously seen data.
Solution-processed carbon nanotubes based transistors with current density of 1.7 mA/μm and peak transconductance of 0.8 mS/μm (2017)

High performance field-effect transistors (FETs) are fabricated based on solution processed carbon nanotubes (CNTs) film through improving the density of CNT and optimizing contacts and gate geometry. Based on multiple-transferred CNT films with density of about 160 CNTs/pm, and via adopting stacked contacts and double gates (SCDG), the FETs with gate length of 120 nm exhibit maximum drive current density of 1.7 mA/pm and peak transconductance of 0.8 mS/pm (at Vds = -1 V), which create a new record for CNT FETs, and even exceed Si PMOS FETs at similar gate lengths for the first time. This device structure may potentially promotes the developments of CNT-based high-performance electronics.
AIDS : the safety of blood and blood products (1987)

An international collection of information from leading researchers resulting from the WHO meeting in April 1986 is presented on how to provide safe blood and blood products in relation to AIDS. An overview is given of the LAV/HTLV-III virus together with its expression and natural history. Next is a comprehensive cover of i) industry's data on the use of special procedures to inactivate the AIDS virus during the manufacture of plasma derivatives and ii) strategies that have become essential for screening blood donors - both in the context of increasing the safety of blood products. Finally the currently available methods for anti-LAV/HTLV-III screening are reviewed including donor notification and related psychosocial aspects.
Distinct conformational states of SARS-CoV-2 spike protein (2020)

Intervention strategies are urgently needed to control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The trimeric viral spike (S) protein catalyzes fusion between viral and target cell membranes to initiate infection. Here, we report two cryo-electron microscopy structures derived from a preparation of the full-length S protein, representing its prefusion (2.9-angstrom resolution) and postfusion (3.0-angstrom resolution) conformations, respectively. The spontaneous transition to the postfusion state is independent of target cells. The prefusion trimer has three receptor-binding domains clamped down by a segment adjacent to the fusion peptide. The postfusion structure is strategically decorated by N-linked glycans, suggesting possible protective roles against host immune responses and harsh external conditions. These findings advance our understanding of SARS-CoV-2 entry and may guide the development of vaccines and therapeutics.
Complement Activation: An Emerging Player in the Pathogenesis of Cardiovascular Disease (2012)

A wealth of evidence indicates a fundamental role for inflammation in the pathogenesis of cardiovascular disease (CVD), contributing to the development and progression of atherosclerotic lesion formation, plaque rupture, and thrombosis. An increasing body of evidence supports a functional role for complement activation in the pathogenesis of CVD through pleiotropic effects on endothelial and haematopoietic cell function and haemostasis. Prospective and case control studies have reported strong relationships between several complement components and cardiovascular outcomes, and in vitro studies and animal models support a functional effect. Complement activation, in particular, generation of C5a and C5b-9, influences many processes involved in the development and progression of atherosclerosis, including promotion of endothelial cell activation, leukocyte infiltration into the extracellular matrix, stimulation of cytokine release from vascular smooth muscle cells, and promotion of plaque rupture. Complement activation also influences thrombosis, involving components of the mannose-binding lectin pathway, and C5b-9 in particular, through activation of platelets, promotion of fibrin formation, and impairment of fibrinolysis. The participation of the complement system in inflammation and thrombosis is consistent with the physiological role of the complement system as a rapid effector system conferring protection following vessel injury. However, in the context of CVD, these same processes contribute to development of atherosclerosis, plaque rupture, and thrombosis.
Cloning and characterization of a gene for a 19kDa fibrinogen‐binding protein from Staphylococcus aureus (1994)

Staphylococcus aureus has been shown to interact specifically with fibrinogen. Three different extracellular fibrinogen-binding proteins, two of which have coagulase activity, are produced by S. aureus strain Newman. The role of these fibrinogen-binding proteins during staphylococcal colonization and infection has not yet been fully elucidated. Here we describe the cloning, sequencing and expression of a gene for a 19 kDa fibrinogen-binding protein. This gene, called fib, encodes a 165-amino-acid polypeptide, including a 29-amino-acid signal sequence. The recombinant protein, which has an estimated molecular mass of 15.9 kDa, bound fibrinogen and was recognized by a polyclonal antiserum against the native Fib protein. Homologies between the Fib protein and the fibrinogen-binding domain of coagulase suggest that amino acids within this domain are involved in the binding to fibrinogen.
Type 1 neurofibromatosis: selective expression of extracellular matrix genes by Schwann cells, perineurial cells, and fibroblasts in mixed cultures. (1989)

Cutaneous neurofibromas, characteristic lesions of neurofibromatosis 1, are composed of an abundant extracellular matrix and nerve connective tissue-derived cell types: Schwann cells, perineurial cells, and fibroblasts. In this study, the extracellular matrix gene expression by these cells was examined under culture conditions that allowed them to be metabolically active and readily identifiable by morphologic and immunocytochemical criteria. Northern hybridizations demonstrated expression of genes for type I, III, IV, and VI collagens, as well as for fibronectin, laminin, and elastin. In situ hybridizations revealed that all three cell types expressed pro alpha 1 (I), pro alpha 2 (VI), and laminin B1 chain genes. However, fibroblasts did not contain [35S]cDNA-mRNA hybrids specific for type IV collagen, whereas both Schwann cells and perineurial cells expressed these genes. Perineurial cells and fibroblasts readily expressed the fibronectin gene whereas Schwann cells were essentially devoid of the corresponding mRNA. Perineurial cells also expressed the gene for laminin A chain. The results indicate that the extracellular matrix gene expression profiles of Schwann cells, perineurial cells, and fibroblasts are distinct: all three cell types are capable of expressing some of the genes for extracellular matrix components, such as type I and VI collagens, whereas Schwann cells and perineurial cells may have the primary role in synthesizing basement membrane zone components, type IV collagen and laminin. These observations potentially relate to the mechanisms of growth and development of human neurofibromas. The results attest to the applicability of the methodology utilized here to study other human tumors with mixed cell populations.
Multi-optimization power management for chip multiprocessors (2008)

The emergence of power as a first-class design constraint has fueled the proposal of a growing number of run-time power optimizations. Many of these optimizations trade-off power saving opportunity for a variable performance loss which depends on application characteristics and program phase. Furthermore, the potential benefits of these optimizations are sometimes non-additive, and it can be difficult to identify which combinations of these optimizations to apply. Trial-and-error approaches have been proposed to adaptively tune a processor. However, in a chip multiprocessor, the cost of individually configuring each core under a wide range of optimizations might be prohibitive under simple trial-and-error approaches.
Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis (2016)

Bone metastasis is a frequent occurrence in breast cancer, affecting more than 70% of late stage cancer patients with severe complications such as fracture, bone pain, and hypercalcemia. The pathogenesis of osteolytic bone metastasis depends on cross-communications between tumor cells and various stromal cells residing in the bone microenvironment. Several growth factor signaling pathways, secreted micro RNAs (miRNAs) and exosomes are functional mediators of tumor-stromal interactions in bone metastasis. We developed a functional genomic approach to systemically identified molecular pathways utilized by breast cancer cells to engage the bone stroma in order to generate osteolytic bone metastasis. We showed that elevated expression of vascular cell adhesion molecule 1 (VCAM1) in disseminated breast tumor cells mediates the recruitment of pre-osteoclasts and promotes their differentiation to mature osteoclasts during the bone metastasis formation. Transforming growth factor β (TGF-β) is released from bone matrix upon bone destruction, and signals to breast cancer to further enhance their malignancy in developing bone metastasis. We furthered identified Jagged1 as a TGF-β target genes in tumor cells that engaged bone stromal cells through the activation of Notch signaling to provide a positive feedback to promote tumor growth and to activate osteoclast differentiation. Substantially change in miRNA expression was observed in osteoclasts during their differentiation and maturation, which can be exploited as circulating biomarkers of emerging bone metastasis and therapeutic targets for the treatment of bone metastasis. Further research in this direction may lead to improved diagnosis and treatment strategies for bone metastasis.
Regulation of herpes simplex virus γ134.5 expression and oncolysis of diffuse liver metastases by Myb34.5 (2002)

Myb34.5 is a herpes simplex virus 1 (HSV-1) mutant deleted in the gene for ribonucleotide reductase (ICP6). It also carries a version of γ134.5 (a viral gene product that promotes the dephosphorylation of eIF-2α) that is under control of the E2F-responsive cellular B-myb promoter, rather than of its endogenous promoter. Myb34.5 replication in tumor cells results in their destruction (oncolysis). γ134.5 expression by HSV-1 subverts an important cell defense mechanism against viral replication by preventing shutoff of protein synthesis after viral infection. Infection of colon carcinoma cells with Myb34.5 results in greater eIF-2α dephosphorylation and viral replication compared with infection with HSV-1 mutants completely defective in γ134.5 expression. In contrast, infection of normal hepatocytes with Myb34.5 results in low levels of eIF-2α dephosphorylation and viral replication that are similar to those observed with HSV-1 mutants completely defective in γ134.5 and ICP6. When administered intravascularly into mice with diffuse liver metastases, Myb34.5 has greater antineoplastic activity than HSV-1 mutants with completely defective γ134.5 expression and more restricted biodistribution compared with HSV-1 mutants with wild-type γ134.5 expression. Myb34.5 displays reduced virulence and toxicity compared to HSV-1 mutants with wild-type γ134.5 expression. Portal venous administration of Myb34.5 significantly reduces liver tumor burden in and prolongs the life of mice with diffuse liver metastases. Preexisting Ab’s to HSV-1 do not reduce the antitumor efficacy of Myb34.5 in vivo.
Ghrelin stimulates interleukin‐8 gene expression through protein kinase C‐mediated NF‐κB pathway in human colonic epithelial cells (2005)

Ghrelin, a newly identified gastric peptide, is known for its potent activity in growth hormone (GH) release and appetite. Although ghrelin is involved in several other responses such as stress and intestinal motility, its potential role in intestinal inflammation is not clear. Here, we show that expression of ghrelin and its receptor mRNA is significantly increased during acute experimental colitis in mice injected intracolonically with trinitrobenzene sulfate (TNBS). We found by PCR that ghrelin receptor mRNA is expressed in non-transformed human colonic epithelial NCM460 cells. Exposure of NCM460 cells stably transfected with ghrelin receptor mRNA to ghrelin, increased IkappaBalpha phosphorylation and its subsequent degradation. In addition, ghrelin stimulated NF-kappaB-binding activity and NF-kappaB p65 subunit phosphorylation, and induced IL-8 promoter activity and IL-8 protein secretion. Furthermore, our data show that ghrelin-induced IkappaBalpha and p65 phosphorylation was markedly reduced by pharmacological inhibitors of intracellular calcium mobilization (BAPTA/AM) and protein kinase C (GF 109203X). Pretreatment with BAPTA/AM or GF109203X also significantly attenuated ghrelin-induced IL-8 production. Together, our results strongly suggest that ghrelin may be a proinflammatory peptide in the colon. Ghrelin may participate in the pathophysiology of colonic inflammation by inducing PKC-dependent NF-kappaB activation and IL-8 production at the colonocyte level.
H3K9 methyltransferase G9a and the related molecule GLP (2011)

The discovery of Suv39h1, the first SET domain-containing histone lysine methyltransferase (HKMT), was reported in 2000. Since then, research on histone methylation has progressed rapidly. Among the identified HKMTs in mammals, G9a and GLP are the primary enzymes for mono- and dimethylation at Lys 9 of histone H3 (H3K9me1 and H3K9me2), and exist predominantly as a G9a-GLP heteromeric complex that appears to be a functional H3K9 methyltransferase in vivo. Recently, many important studies have reported that G9a and GLP play critical roles in various biological processes. The physiological relevance of G9a/GLP-mediated epigenetic gene regulation is discussed.
Avian Influenza A (H5N1) in 10 Patients in Vietnam (2004)

Influenza A (H5N1) infection, characterized by fever, respiratory symptoms, and lymphopenia, carries a high risk of death. Although in all 10 cases the infection appears to have been acquired directly from infected poultry, the potential exists for genetic reassortment with human influenzaviruses and the evolution of human-to-human transmission. Containment of influenza A (H5N1) in poultry throughout Asia is therefore urgently required.
CCR5-Reactive Antibodies in Seronegative Partners of HIV-Seropositive Individuals Down-Modulate Surface CCR5 In Vivo and Neutralize the Infectivity of R5 Strains of HIV-1 In Vitro (2000)

Exposure to HIV does not necessarily result in infection. Because primary HIV infection is associated with CCR5-tropic HIV variants (R5), CCR5-specific Abs in the sera of HIV-seronegative, HIV-exposed individuals (ESN) might be associated with protection against infection. We analyzed sera from ESN, their HIV-infected sexual partners (HIV+), and healthy controls (USN) searching for CCR5-specific Abs, studying whether incubation of PBMC with sera could prevent macrophage inflammatory protein 1 beta (Mip1 beta) (natural ligand of CCR5) binding to CCR5. Results showed that Mip1 beta binding to CCR5 was not modified by sera of either 40 HIV+ or 45 USN but was greatly reduced by sera of 6/48 ESN. Binding inhibition was due to Abs reactive with CCR5. The CCR5-specific Abs neutralized the infectivity of primary HIV isolates obtained from the corresponding HIV+ partners and of R5-primary HIV strains, but not that of CXCR4-tropic or amphitropic HIV strains. Immunoadsorption on CCR5-transfected, but not on CXCR4-transfected, cells removed CCR5-specific and virus-neutralizing Abs. Epitope mapping on purified CCR5-specific Abs showed that these Abs recognize a conformational epitope in the first cysteine loop of CCR5 (aa 89-102). Affinity-purified anti-CCR5-peptide neutralized the infectivity of R5 strains of HIV-1. Anti-CCR5 Abs inhibited Mip1beta-induced chemotaxis of PBMC from healthy donors. PBMC from two ESN (with anti-CCR5 Abs) were CCR5-negative and could not be stimulated by Mip1beta in chemotaxis assays. These results contribute to clarifying the phenomenon of immunologic resistance to HIV and may have implications for the development of a protective vaccine.
Development of an animal brain tumor model and its response to therapy with 1,3-bis(2-chloroethyl)-1-nitrosourea. (1973)

Summary A chemically induced rat glioma, carried in cell culture, was transplanted to the brain of CDF rats. The tumor thrived in cell culture, producing a typical malignant astrocytoma when implanted in rat brain. Survival of tumor-bearing rats varied in different experimental groups, but the range of survival within each experimental group was within acceptable limits. The rat glioma in cell culture grew progressively through three phases, namely, exponential, stationary, and a variable phase, limited by space and medium. The cell-cycle time of the glioma in vivo was 20 hr, the growth fraction was 0.35 to 0.46, the observed doubling time was 72 hr, and the cell-loss factor was 0.42. These data, along with the chronology of the cell-cycle phases, enhance the usefulness of this system as a model for brain tumor chemotherapy. 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) significantly increased the survival time of rats bearing intracerebral gliomas. A dose of BCNU approximating 40% of the 10% lethal dose, when given 9 and 16 days after tumor implantation, produced an increased life-span of 38%. A dose of BCNU equivalent to 80% of the 10% lethal dose given on Days 9 and 16 produced an increased life-span of 84%. When BCNU was withheld until the 16th and 23rd days, a significant increase in survival time was still evident. The advantages of this animal model for brain tumor chemotherapy are that (a) the transplanted tumor is of glial origin, (b) the tumor take of the model has been 100%, (c) the mean survival of animals is approximately 30 days, permitting the start of a treatment schedule after the tumor has grown to significant size, and (d) the rat is suitable for various routes of therapy.
Neocortical Seizure Termination by Focal Cooling: Temperature Dependence and Automated Seizure Detection (2002)

Cooling terminates neocortical seizures when applied very close to the epileptogenic focus. The threshold for seizure termination (24 degrees C) may be lower than the threshold for termination of normal cortical activity, suggesting that this technique will not dissociate the anticonvulsant effect of cooling from the disruption of normal behavior. However, when coupled with automatic seizure detection, focal cooling remains an attractive option for development as a treatment for focal epilepsy.
Interleukin-1 receptor antagonist as a biomarker for bronchiolitis obliterans syndrome in lung transplant recipients (2002)

These findings suggest that elevated levels of IL-1Ra may be attenuating IL-1 bioactivity during the pathogenesis of BOS and creating a local environment that favors fibroproliferation and matrix deposition.
Gonococcal and meningococcal pathogenesis as defined by human cell, cell culture, and organ culture assays (1989)

Human cells, cell cultures, and organ cultures have been extremely useful for studying the events that occur when gonococci and meningococci encounter human mucosal surfaces. The specificity and selectivity of these events for human cells are striking and correlate with the adaptation of these pathogens for survival on human mucous membranes. To colonize these sites, meningococci and gonococci have developed mechanisms to damage local host defenses such as the mucociliary blanket, to attach to epithelial cells, and to invade these cells. Attachment to epithelial cells mediated by pili, and to some types of cells mediated by PIIs, serves to anchor the organism close to sources of nutrition and allows multiplication. Intracellular invasion, possibly initiated by the major porin protein, may provide additional nutritional support and protection from host defenses. Mucosal invasion may also result in access of gonococci and meningococci to the bloodstream, leading to dissemination.
Reduction in ohmic loss of small microstrip antennas using multiple copper layers (2006)

In this paper, the simulation results of multi-layered miniaturized microstrip antennas were presented. The gain was increased and the method shows a great promise for directivity enhancement of the small antennas, by reducing the resistive losses in stacked multiple thin copper layers. Using the available microfabrication laboratory, multi-layered compact antennas are now being fabricated, and the test results were presented during the symposium. Silicon, or other dielectric, can be used as laminating material, instead of the air gap, in the practical fabrication process