gebhart/patrepeval huggingface dataset:
Antimicrobial Peptides: Diversity, Mechanism of Action and Strategies to Improve the Activity and Biocompatibility In Vivo (2018)

Antibiotic resistance is projected as one of the greatest threats to human health in the future and hence alternatives are being explored to combat resistance. Antimicrobial peptides (AMPs) have shown great promise, because use of AMPs leads bacteria to develop no or low resistance. In this review, we discuss the diversity, history and the various mechanisms of action of AMPs. Although many AMPs have reached clinical trials, to date not many have been approved by the US Food and Drug Administration (FDA) due to issues with toxicity, protease cleavage and short half-life. Some of the recent strategies developed to improve the activity and biocompatibility of AMPs, such as chemical modifications and the use of delivery systems, are also reviewed in this article.
改革的经济学——评 A.阿甘别吉扬著《改革——双重的挑战》一书 (1990)

苏联改革的出发点:发展后的停滞苏联的官方统计认为,苏联的“国民收入”概念与西方的纯社会产品概念不好相比,因为今天西方纯社会产品的绝大部分是由劳务组成的,而按照马克思主义的思想(错误的理解),劳务只能理解为“非生产性的”。阿甘别吉扬明确表示,他对这样论述问题并不满意。随着苏联经济的发展,劳务也在不断增长,但苏联经济的纯社会产品却增长太少。作者在他著作的第一章(标题为“改革的挑战”)中,认为有必要指出,官方的统计数字或多或少是不可信的,必须用“现实的价格指数”来修改那些有名无实的统计数字。从官方的统计数字得出,国民收入增长率从1966—1970年的约每年8%下降到
Isolation of PEBP2 alpha B cDNA representing the mouse homolog of human acute myeloid leukemia gene, AML1. (1993)

Breakpoints of the t(8;21) chromosome translocation in acute myeloid leukemia are clustered within the human gene, AML1, located on chromosome 21 [Miyoshi, H., Shimizu, K., Maseki, N., Kaneko, Y. & Ohki, M. (1991). Proc. Natl. Acad. Sci. USA, 88, 10431-10434]. The product of AML1 has a region about 130 amino acids long that is highly homologous to the Drosophila segmentation gene runt (runt homology region). The cDNA isolated from mouse fibroblasts encoding the alpha-subunit of polyomavirus enhancer binding protein 2 (PEBP2/PEA2) revealed that it also has a runt homology region (E. Ogawa et al., submitted). In this study, a different cDNA clone presumed to represent the mouse homolog of human AML1 (PEBP2 alpha B) was isolated from a cDNA library derived from B cells. The deduced amino acid sequence of PEBP2 alpha B is 99% identical to that of AML1 for the first 241 residues, including the runt homology region, though their sequences diverge thereafter. On the other hand, PEBP2 alpha B and PEBP2 alpha share only 92% and 82% homologies at the amino acid and nucleotide levels respectively, even for the runt homology region, indicating that these proteins are encoded by distinct genes. While PEBP2 alpha is highly expressed in T-cell lines but not in most of the B-cell lines and functions as an activator of T-cell-specific genes, PEBP2 alpha B is expressed in both types of cells. A possible functional relationship between PEBP2 alpha and PEBP2 alpha B is discussed in relation to leukemogenic potential of AML1.
Differential effects of palmitate and palmitoleate on insulin action and glucose utilization in rat L6 skeletal muscle cells (2006)

An increase in circulating levels of specific NEFAs (non-esterified fatty acids) has been implicated in the pathogenesis of insulin resistance and impaired glucose disposal in skeletal muscle. In particular, elevation of SFAs (saturated fatty acids), such as palmitate, has been correlated with reduced insulin sensitivity, whereas an increase in certain MUFAs and PUFAs (mono- and poly-unsaturated fatty acids respectively) has been suggested to improve glycaemic control, although the underlying mechanisms remain unclear. In the present study, we compare the effects of palmitoleate (a MUFA) and palmitate (a SFA) on insulin action and glucose utilization in rat L6 skeletal muscle cells. Basal glucose uptake was enhanced approx. 2-fold following treatment of cells with palmitoleate. The MUFA-induced increase in glucose transport led to an associated rise in glucose oxidation and glycogen synthesis, which could not be attributed to activation of signalling proteins normally modulated by stimuli such as insulin, nutrients or cell stress. Moreover, although the MUFA-induced increase in glucose uptake was slow in onset, it was not dependent upon protein synthesis, but did, nevertheless, involve an increase in the plasma membrane abundance of GLUT1 and GLUT4. In contrast, palmitate caused a substantial reduction in insulin signalling and insulin-stimulated glucose transport, but was unable to antagonize the increase in transport elicited by palmitoleate. Our findings indicate that SFAs and MUFAs exert distinct effects upon insulin signalling and glucose uptake in L6 muscle cells and suggest that a diet enriched with MUFAs may facilitate uptake and utilization of glucose in normal and insulin-resistant skeletal muscle.
Antigenic structures of proteins. Their determination has revealed important aspects of immune recognition and generated strategies for synthetic mimicking of protein binding sites (1984)

Studies in this laboratory have resulted in the delineation and synthetic verification of several complete protein antigenic structures that are recognized by antibodies. More recently, for the first time, the full profiles of the sites that are recognized by T cells have been localized and confirmed by synthesis for two proteins, myoglobin and lysozyme. These have thus far constituted the only complete antigenic structures to be determined. The availability of these antigenic structures has enabled us to investigate in detail the molecular and cellular parameters responsible for immune recognition, responses to, and control and regulation of these responses to protein antigens at the molecular and submolecular levels. Moreover, these investigations have afforded general strategies for the synthetic mimicking of not only antigenic sites, but also protein binding sites involved in other biological activities.
An efficient parallel transparent BIST method for multiple embedded memory buffers (2002)

In this paper, we propose a new transparent built-in self-test (TBIST) method to test multiple embedded memory arrays with various sizes in parallel. First, a new transparent test interface is designed to perform testing in the normal mode and to cope with nested interrupts in a realtime manner. The circular scan test interface facilitates the processes of both test pattern generation and signature analysis. By tolerating redundant read/write/shift operations, we develop a new march algorithm called TRSMarch to achieve the goals of low hardware overhead, short test time, and high fault coverage.
Chronic in Vivo Function of a New Ventricular Assist Device: The Extracorporeal Pulsatile Assist Device (Epad) (1993)

An extracorporeal pulsatile assist device (EPAD) is a valveless, single-chambered, pneumatically-actuated blood pump composed of a graft conduit, connecting ring, bladder, and blowmolded housing. This allows a simple and quick surgical procedure and is easily actuated with a conventional intraaortic balloon pumping console if desired. To evaluate in vivo pump functions, the EPAD was tested in calves as a left ventricular assist device for 6-24 days. The EPAD was well synchronized to the natural heart beat up to 130 bpm in the counterpulsation mode with mild systemic heparinization (active clotting time: 200-250 seconds). Heart rate, coronary flow and cardiac output were not significantly changed by on-off testing. However, the pump showed promising diastolic augmentation (10.8% increase in the diastolic pressure time index) in these chronic animal experiments.
Synthesis and Characterization of a New Substrate of Photinus pyralis Luciferase: 4-Methyl-D-luciferin (1990)

A derivative of luciferin, 4-methyl-D-luciferin, was synthesized in low yield, and characterized by its ultraviolet and fluorescence spectra. The spectra of luciferin and its derivative are very similar. 4-Methyl-D-luciferin is a substrate of Photinus pyralis luciferase, and it causes light emission in luminometric assays.
Functional Gene Screening System Identified TRPV4 as a Regulator of Chondrogenic Differentiation (2007)

Sox9 is a transcription factor that is essential for chondrocyte differentiation and chondrocyte-specific gene expression. However, the precise mechanism of Sox9 activation during chondrogenesis is not fully understood. To investigate this mechanism, we performed functional gene screening to identify genes that activate SOX9-dependent transcription, using full-length cDNA libraries generated from a murine chondrogenic cell line, ATDC5. Screening revealed that TRPV4 (transient receptor potential vanilloid 4), a cation channel molecule, significantly elevates SOX9-dependent reporter activity. Microarray and quantitative real time PCR analyses demonstrated that during chondrogenesis in ATDC5 and C3H10T1/2 (a murine mesenchymal stem cell line), the expression pattern of TRPV4 was similar to the expression patterns of chondrogenic marker genes, such as type II collagen and aggrecan. Activation of TRPV4 by a pharmacological activator induced SOX9-dependent reporter activity, and this effect was abolished by the addition of the TRPV antagonist ruthenium red or by using a small interfering RNA for TRPV4. The SOX9-dependent reporter activity due to TRPV4 activation was abrogated by both EGTA and a calmodulin inhibitor, suggesting that the Ca2+/calmodulin signal is essential in this process. Furthermore, activation of TRPV4 in concert with insulin activity in ATDC5 cells or in concert with bone morphogenetic protein-2 in C3H10T1/2 cells promoted synthesis of sulfated glycosaminoglycan, but activation of TRPV4 had no effect alone. We showed that activation of TRPV4 increased the steady-state levels of SOX9 mRNA and protein and SOX6 mRNA. Taken together, our results suggest that TRPV4 regulates the SOX9 pathway and contributes to the process of chondrogenesis.
Molecular analysis of Japanese patients with Rett syndrome: Identification of five novel mutations and genotype-phenotype correlation Communicated by Mark H. Paalman Online Citation: Human Mutation, Mutation in Brief #443 (2001) Online http://journals.wiley.com/1059-7794/pdf/mutation/443.pdf (2001)

Rett syndrome is an X-linked dominant neurodevelopmental disorder that affects females almost exclusively. The recent identification of mutations of the methyl-CpG-binding protein 2 gene (MECP2) in patients with RTT, encouraged us to analyze the gene in 37 Japanese patients divided into classical RTT (14 cases), variant RTT (13 cases), and mentally retarded patients with Rett-like features (10 cases). Mutations in MECP2 were identified from most of the patients with classical and variant RTT (25 of 27 cases). Six reported common mutations were detected in 17 cases, and rare single nucleotide substitutions were found in 3 patients. In addition, one insertion mutation (1189insA) and four deletion mutations including one double deletion mutant (451delG, 100del4, 1124del53 and 881del289 plus 1187del8) were newly identified. In the 10 mentally retarded patients with Rett-like features, however, no mutation was detected in the coding region of MECP2. The finding of MECP2 mutations in 92.5% of patients with RTT indicates that RTT fulfilling the diagnostic criteria are due to genetic alteration. © 2001 Wiley-Liss, Inc.
The Raf Inhibitor BAY 43-9006 (Sorafenib) Induces Caspase-Independent Apoptosis in Melanoma Cells (2006)

Mitogen-activated protein kinase (MAPK) is activated in the majority of melanomas, and its activity is essential for cell survival. In this report, we examined the effects of a novel raf inhibitor BAY 43-9006 on melanoma cell viability and intracellular signaling and found that it induces apoptosis through a caspase-independent mechanism. At concentrations that suppress extracellular signal-regulated kinase (ERK) phosphorylation, BAY 43-9006 dephosphorylates Bad on Ser(75) and Ser(99), activates Bak and Bax, and reduces the mitochondrial transmembrane potential. BAY 43-9006 (sorafenib) down-modulates the levels of Bcl-2 and Bcl-X(L) in a MAPK-independent manner in A2058 and SKMEL5 melanoma cells but not in the more resistant A375 cells. Of the three lines tested, only A375 cells were rescued from BAY 43-9006-induced apoptosis by knocking down Bad. BAY 43-9006 induced poly(ADP-ribose) polymerase cleavage and the mitochondrial release of cytochrome c and SMAC. However, the pan-caspase inhibitor Z-VAD-fmk had only a modest protective effect against the drug, suggesting that BAY 43-9006-induced apoptosis is largely caspase independent. BAY 43-9006 but not the MAP/ERK kinase inhibitors PD98059 or U0126 induced the nuclear translocation of apoptosis-inducing factor (AIF) in A2058 and SKMEL5 cells, and the introduction of a small interfering RNA (siRNA) for AIF partially protected these cells from BAY 43-9006-induced apoptosis. The AIF siRNA had little effect in A375 cells, in which drug-induced AIF release was negligible. These data indicate that in sensitive cell lines, BAY 43-9006-induced apoptosis is independent of Bad dephosphorylation and caspase activation and largely mediated through the nuclear translocation of AIF.
Low power integrated scan-retention mechanism (2002)

This paper presents a methodology for unifying the scan mechanism and data retention in latches which leads to scannable latches with the data retention capability achieved at a very low power overhead during the active mode. A detailed analysis of power and area overhead is presented, with layout examples for various common latch styles. Implications of using different power gating techniques for reducing leakage during sleep mode on the design of retention latches are considered, including well biasing for leakage control and sharing wells between gated logic and retention latch devices.
Tumor necrosis factor inhibits a polymorphonuclear leukocyte-dependent airway edema in guinea pigs (1988)

Intravenously administered endotoxin inhibits the polymorphonuclear leukocyte (PMN)-dependent airway edema produced in guinea pigs exposed to toluene diisocyanate (TDI). Tumor necrosis factor (TNF) is produced in vivo by peripheral blood monocytes and tissue macrophages stimulated with endotoxin and has been shown to activate PMN's and vascular endothelial cells. To determine whether the inhibition of airway edema is mediated by TNF, guinea pigs were treated with intravenous saline or 75,000 U/kg recombinant human TNF 1.5 h before exposure to air or 3 ppm TDI for 1 h. Animals were then injected intravenously with 50 mg/kg Evans blue dye as a marker of protein extravasation. Saline-treated animals exposed to TDI had a significant increase in tracheal Evans blue dye extravasation (85 +/- 6.5 micrograms dye/g trachea, mean +/- SE) compared with saline-treated animals exposed to air (31.3 +/- 2.5, P less than 0.001). The tracheal extravasation of Evans blue dye was significantly inhibited (P less than 0.05) in TDI-exposed animals treated with TNF (64.7 +/- 7.5). Neither heat-inactivated TNF (104.9 +/- 9.5) nor TNF neutralized with a monoclonal antibody against TNF (99.7 +/- 17.9) inhibited TDI-induced airway edema. In addition, treatment with 15,000 U/kg (99.9 +/- 21.3) or 150,000 U/kg (103.2 +/- 17.6) interleukin 1, a monokine also produced in response to endotoxin, did not prevent airway edema. These results suggest that TNF released in response to endotoxin mediates endotoxin's inhibition of a PMN-dependent airway edema.
Single-Dose Pharmacokinetics and Metabolism of [ 14 C]Remofovir in Rats and Cynomolgus Monkeys (2005)

Single-dose pharmacokinetics and metabolism of [(14)C]remofovir was studied in rats and monkeys following intravenous (i.v.) and oral administration (30 mg/kg of body weight). Oral absorption and bioavailability were 29.7 and 5.42% in rats and 65.6 and 19.4% in monkeys, respectively. Following i.v. administration, the elimination half-life for remofovir was 0.7 h in both rats and monkeys. Total body clearance was 5.85 liters/h/kg in rats and 2.60 liters/h/kg in monkeys; apparent volume of distribution was 5.99 liters/kg in rats and 2.70 liters/kg in monkeys. Following oral administration, remofovir was extensively converted to 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and other metabolites in both species. In rats, excretion of total radioactivity in urine accounted for 61.8% of the i.v. dose and 12.9% of the oral dose, while in monkeys it accounted for 43.3% of the i.v. dose and 34.9% of the oral dose. Following i.v. dosing of [(14)C]remofovir, fecal excretion of radioactivity accounted for 37.5% of the dose in rats and 17.4% of the dose in monkeys, indicating significant biliary excretion of the drug in animals. PMEA and metabolite A were the major urinary metabolites in both species after i.v. and oral administration of remofovir.
Simultaneous Elevation of the Levels of Circulating Monocyte Chemoattractant Protein-1 and Tissue Factor in Acute Coronary Syndromes (1998)

The levels of circulating monocyte chemoattractant protein-1 (MCP-1) and tissue factor (TF) were examined on admission in 46 consecutive patients with acute coronary syndromes (ACS) and 30 patients with stable exertional angina (SEA). The plasma levels of both MCP-1 and TF were higher in the ACS patients than in the SEA patients (MCP-1: p<0.001; TF: p<0.001). Only the circulating TF level related to the number of diseased vessels. A positive correlation between plasma MCP-1 and TF levels was found (r=0.476, p<0.001). These results suggest that circulating MCP-1 plays an important role in the pathogenesis and/or development of ACS.
The Distribution of Estrogen Receptor-β mRNA in Forebrain Regions of the Estrogen Receptor-α Knockout Mouse (1997)

Neurons in the hypothalamus of estrogen receptor alpha-knockout (ER alphaKO) mice have been shown to concentrate radiolabeled estrogen and estrogen treatment regulates the expression of progesterone receptor mRNA. The purpose of the present study was to utilize in situ hybridization histochemistry to determine the anatomical distribution of ER beta mRNA in ER alphaKO mouse forebrain. The results of these studies revealed an extensive distribution of ER beta mRNA in the hypothalamic regions including medial preoptic area, suprachiasmatic nucleus, paraventricular nucleus, dorsomedial nucleus, medial tuberal nucleus, and the premammillary nuclei. Additional labeled perikarya were also detected in the glomerular layer of the olfactory bulb; tenia tecta; anterior septum; bed nucleus of the stria terminalis; medial, basolateral and cortical nuclei of the amygdala; cerebral and entorhinal cortex; the septohippocampal nucleus; Ammon's horn of the hippocampus and the dorsal raphe. The results of these in situ hybridization histochemical studies have provided novel information about the distribution of ER beta mRNA in the ER alphaKO mouse forebrain. In addition, these morphological data provides evidence that estrogen may exert its actions in the ER alphaKO mouse brain via ER beta and thereby maintain organizational and activational effects.
On Being Muonged (2001)

This paper argues that use of the term Muong to designate an ethnic minority in Vietnam began in the early twentieth century as a product of French colonial efforts to apply modern social scientific description to form knowledge of upland peoples adjacent to and linguistically related to Vietnamese speakers in the lowlands. Subsequently, Vietnamese speakers adopted this usage to designate a national minority. A local text from the turn of the century is used to suggest an alternative way of viewing these peoples based on pre-French experience.
Novel Adenoviruses in Wild Primates: a High Level of Genetic Diversity and Evidence of Zoonotic Transmissions (2011)

Adenoviruses (AdVs) broadly infect vertebrate hosts, including a variety of nonhuman primates (NHPs). In the present study, we identified AdVs in NHPs living in their natural habitats, and through the combination of phylogenetic analyses and information on the habitats and epidemiological settings, we detected possible horizontal transmission events between NHPs and humans. Wild NHPs were analyzed with a pan-primate AdV-specific PCR using a degenerate nested primer set that targets the highly conserved adenovirus DNA polymerase gene. A plethora of novel AdV sequences were identified, representing at least 45 distinct AdVs. From the AdV-positive individuals, 29 nearly complete hexon genes were amplified and, based on phylogenetic analysis, tentatively allocated to all known human AdV species (Human adenovirus A to Human adenovirus G [HAdV-A to -G]) as well as to the only simian AdV species (Simian adenovirus A [SAdV-A]). Interestingly, five of the AdVs detected in great apes grouped into the HAdV-A, HAdV-D, HAdV-F, or SAdV-A clade. Furthermore, we report the first detection of AdVs in New World monkeys, clustering at the base of the primate AdV evolutionary tree. Most notably, six chimpanzee AdVs of species HAdV-A to HAdV-F revealed a remarkably close relationship to human AdVs, possibly indicating recent interspecies transmission events.
Law and Religion, by Russell Sandberg. Cambridge: Cambridge University Press, 2011, 216pp (including index) (£19.99 paperback). ISBN: 978-0-521-17718-4. (2012)

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Power: a first-class architectural design constraint (2001)

Power is a design constraint not only for portable computers and mobile communication devices but also for high-end systems, and the design process should not subordinate it to performance.
Plasma-Enhanced Atomic Layer Deposition of Tantalum Nitrides Using Hydrogen Radicals as a Reducing Agent (2001)

Plasma-enhanced atomic layer deposition (PEALD) of tantalum nitride (Ta-N) thin films at a deposition temperature of 260°C using hydrogen radicals as a reducing agent for tertbutylimidotris(diethylamido)tantalum is described. The PEALD yielded superior Ta-N films with an electric resistivity of 400 μΩ cm and no aging effect under exposure to air. The film density was higher than that of Ta-N films formed by typical ALD, in which is used instead of hydrogen radicals. In addition, the as-deposited films were not amorphous, but rather polycrystalline structures of cubic TaN. The density and crystallinity of the films increased with the pulse time of hydrogen plasma. The films were Ta-rich in composition and contain around 15 atom % of carbon impurity. © 2001 The Electrochemical Society. All rights reserved.
Topoisomerase II is a structural component of mitotic chromosome scaffolds. (1985)

We have obtained a polyclonal antibody that recognizes a major polypeptide component of chicken mitotic chromosome scaffolds. This polypeptide migrates in SDS PAGE with Mr 170,000. Indirect immunofluorescence and subcellular fractionation experiments confirm that it is present in both mitotic chromosomes and interphase nuclei. Two lines of evidence suggest that this protein is DNA topoisomerase II, an abundant nuclear enzyme that controls DNA topological states: anti-scaffold antibody inhibits the strand-passing activity of DNA topoisomerase II; and both anti-scaffold antibody and an independent antibody raised against purified bovine topoisomerase II recognize identical partial proteolysis fragments of the 170,000-mol-wt scaffold protein in immunoblots. Our results suggest that topoisomerase II may be an enzyme that is also a structural protein of interphase nuclei and mitotic chromosomes.