gebhart/patrepeval huggingface dataset:
Genome-Wide Screening Identifies Six Genes That Are Associated with Susceptibility to Escherichia coli Microcin PDI (2015)

The microcin PDI inhibits a diverse group of pathogenic Escherichia coli strains. Coculture of a single-gene knockout library (BW25113; n=3,985 mutants) against a microcin PDI-producing strain (E. coli 25) identified six mutants that were not susceptible (ΔatpA, ΔatpF, ΔdsbA, ΔdsbB, ΔompF, and ΔompR). Complementation of these genes restored susceptibility in all cases, and the loss of susceptibility was confirmed through independent gene knockouts in E. coli O157:H7 Sakai. Heterologous expression of E. coli ompF conferred susceptibility to Salmonella enterica and Yersinia enterocolitica strains that are normally unaffected by microcin PDI. The expression of chimeric OmpF and site-directed mutagenesis revealed that the K47G48N49 region within the first extracellular loop of E. coli OmpF is a putative binding site for microcin PDI. OmpR is a transcriptional regulator for ompF, and consequently loss of susceptibility by the ΔompR strain most likely is related to this function. Deletion of AtpA and AtpF, as well as AtpE and AtpH (missed in the original library screen), resulted in the loss of susceptibility to microcin PDI and the loss of ATP synthase function. Coculture of a susceptible strain in the presence of an ATP synthase inhibitor resulted in a loss of susceptibility, confirming that a functional ATP synthase complex is required for microcin PDI activity. In trans expression of ompF in the ΔdsbA and ΔdsbB strains did not restore a susceptible phenotype, indicating that these proteins are probably involved with the formation of disulfide bonds for OmpF or microcin PDI.
Effects of Enhanced Striatal Dopamine Turnover In Vivo on Glutathione Oxidation (1994)

In Parkinson's disease (PD), a compensatory increase in dopamine (DA) turnover occurs in the remaining nigrostriatal dopaminergic neurons, resulting in greater exposure of each neuron to hydrogen peroxide (H2O2) derived from oxidative deamination of DA. The formation of oxyradicals from H2O2 is regarded as a mechanism that could contribute to the progression of PD, and incubation of rat striatal synaptosomes with levodopa (LD) results in an increase in oxidized glutathione (GSSG), indicative of oxidant stress. The present study was undertaken to determine whether striatal GSSG levels increase in response to administration of LD in vivo. Acute and repeated (3-week) treatment of normal rats with LD at doses of up to 100 mg/kg did not increase striatal GSSG despite marked increase in DA turnover. These results suggest that intact striatum may possess increased defense capacity against oxidant stress generated by increased DA turnover as compared with isolated synaptosomes.
Severe factor X deficiency due to a homozygous mutation (Cys364Arg) that disrupts a disulphide bond in the catalytic domain (2006)

Severe factor X deficiency (<0.01 IU mL(-1)) is a rare disorder producing a major bleeding tendency including umbilical cord, joint and intracranial haemorrhage. We present the first case of a child homozygous for a g.1177T > C missense alteration, predicted to disrupt the catalytic domain, and resulting in severe FX deficiency. The child suffered intracranial haemorrhage and now receives regular prophylaxis with a prothrombin complex concentrate. Our experience and a review of the literature suggest that optimal frequency of dosing is likely to be two or three times weekly and that the risk of thrombosis is very small.
Optical studies of the crystallization of trans 1,4‐polybutadiene in stretched networks (1975)

Abstract The stress‐induced crystallization of trans 1,4‐polybutadiene was studied by observing changes in birefringence, stress, x‐ray diffraction, and low angle light scattering during the course of crystallization. From these data, the degree of crystallinity was determined as a function of time, temperature, and elongation. Data were fitted to the Avrami equation, leading to an exponent of the order of unity. Light‐scattering patterns suggested the simultaneous existence of two stretched forms: a rod‐like structure oriented preferentially parallel to the stretching direction and a deformed spherulitelike growth with its greatest extension perpendicular to the stretching direction.
Facile Method for the Preparation of Triarylsulfonium Bromides Using Grignard Reagents and Chlorotrimethylsilane as an Activator (2004)

Triarylsulfonium bromides were synthesized by the reaction of diaryl sulfoxides with aryl Grignard reagents in the presence of TMSCl followed by treatment with HBr aqueous solution. Triarylsulfonium bromides bearing three identical substituents on sulfur atom were synthesized by the treatment of dimethyl sulfite or thionyl chloride with 5 equivalents of Grignard reagent in the presence of TMSCl.
A unified approach to route planning for shared mobility (2018)

There has been a dramatic growth of shared mobility applications such as ride-sharing, food delivery and crowdsourced parcel delivery. Shared mobility refers to transportation services that are shared among users, where a central issue is route planning . Given a set of workers and requests, route planning finds for each worker a route, i.e. , a sequence of locations to pick up and drop off passengers/parcels that arrive from time to time, with different optimization objectives. Previous studies lack practicability due to their conflicted objectives and inefficiency in inserting a new request into a route, a basic operation called insertion . In this paper, we present a unified formulation of route planning called URPSM. It has a well-defined parameterized objective function which eliminates the contradicted objectives in previous studies and enables flexible multi-objective route planning for shared mobility. We prove the problem is NP-hard and there is no polynomial-time algorithm with constant competitive ratio for the URPSM problem and its variants. In response, we devise an effective and efficient solution to address the URPSM problem approximately. We design a novel dynamic programming (DP) algorithm to accelerate the insertion operation from cubic or quadric time in previous work to only linear time. On basis of the DP algorithm, we propose a greedy based solution to the URPSM problem. Experimental results on real datasets show that our solution outperforms the state-of-the-arts by 1.2 to 12.8 times in effectiveness, and also runs 2.6 to 20.7 times faster.
YEAST TRANSCRIPTIONAL REGULATORY MECHANISMS (1995)

Transcriptional regulation directly influences many biological phenomena such as cell growth, response to environmental change, development of multicellular organisms, and disease. Transcriptional regulatory mechanisms are fundamentally similar in eukaryotic organisms (93). Components of the basic RNA polymerase II (Pol II) machinery are highly conserved and, in some cases, functionally interchangeable. Transcription factors with similar structures and DNA-binding specificities are found throughout the eukaryotic kingdom, and acidic activation domains stimulate transcription across a wide range of species. Complex promoters with multiple protein binding sites are typical in all eukaryotic organisms, and efficient transcription generally requires the combinatorial and synergistic action of activator proteins that function at long and variable distances from the mRNA initiation site. Molecular mechanisms of eukaryotic transcriptional regulation have been elucidated from the studies that involve a wide variety of genes, promoters, proteins, organisms, and experimental approaches. This review focuses on transcriptional regulatory mechanisms in the baker's yeast Saccharomyces cerevisiae. Studies in yeast have emphasized powerful genetic approaches that are not available in other eukaryotic organisms. As a consequence, yeast is particularly amenable for analyzing transcriptional regulatory mechanisms in vivo under true physiological conditions. Furthermore, classical and molecular yeast genetics has permitted the discovery and functional characterization of transcriptional regulatory proteins that were not identified in biochemical studies. Thus, genetic analysis in yeast has often generated information complementary to that obtained from biochemical studies of transcription in vitro, and it has provided unique insights into mechanisms of eukaryotic transcriptional regulation.
ChemInform Abstract: GENERAL PROCEDURE FOR THE SYNTHESIS OF MONO‐N‐ACYLATED 1,6‐DIAMINOHEXANES (1978)

Abstract Hexamethylendiamin (I) liefert das Carbo‐tert.‐butoxy‐Derivat (Ib) neben Bis‐Substitutionsprodukten, die glatt abgetrennt werden können.
Service-Oriented Computing and Cloud Computing: Challenges and Opportunities (2010)

Service-oriented computing and cloud computing have a reciprocal relationship - one provides computing of services and the other provides services of computing. Although service-oriented computing in cloud computing environments presents a new set of research challenges, the authors believe the combination also provides potentially transformative opportunities.
Detecting malware samples with similar image sets (2014)

This paper proposes a method for identifying and visualizing similarity relationships between malware samples based on their embedded graphical assets (such as desktop icons and button skins). We argue that analyzing such relationships has practical merit for a number of reasons. For example, we find that malware desktop icons are often used to trick users into running malware programs, so identifying groups of related malware samples based on these visual features can highlight themes in the social engineering tactics of today's malware authors. Also, when malware samples share rare images, these image sharing relationships may indicate that the samples were generated or deployed by the same adversaries.
Datawave: a single-chip multiprocessor for video applications (1991)

A fine-grained MIMD (multiple-instruction, multiple-data) array processor for video applications that combines submicron technology, parallel processing, and dataflow programming is presented. The Datawave processor is used as the building block of this cellular, data-driven system architecture. The processor executes statically scheduled dataflow programs, and self-timed hardware mechanisms handle the asynchronous dataflows automatically and transparently. The architecture is discussed first at the array level and then at the cell level. It is shown how Datawave implements a four-tap finite impulse response filer and a real-time image codec. Program development tools for Datawave are discussed, and the chip itself is briefly described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Specific inhibition of hepatitis B viral gene expression in vitro by targeted antisense oligonucleotides. (1992)

A 21-mer oligodeoxynucleotide complementary to the polyadenylation signal for human hepatitis B virus (HBV) was complexed to a soluble DNA-carrier system that is targetable to hepatocytes via asialoglycoprotein receptors present on those cells. A cell line, HepG2 (2.2.15) that possesses asialoglycoprotein receptors and is permanently transfected with hepatitis B virus (ayw subtype) was exposed to complexed antisense DNA or controls. In the presence of complexed antisense DNA, the concentration of hepatitis B surface antigen in medium was 80% lower than controls after 24 h. Furthermore, during the next 6 days, there was no significant increase in surface antigen concentration in the presence of complexed antisense DNA. The inhibition could be effectively blocked by competition with an excess of free asialoglycoprotein. Total protein synthesis remained unchanged by exposure to complexed antisense sequences under identical conditions. In addition, HBV DNA in the medium and cell layers after 24-h exposure to complexed antisense sequences was 80% lower than in controls. The data indicate that antisense oligonucleotides complexed by a soluble DNA-carrier system can be targeted to cells via asialoglycoprotein receptors resulting in specific inhibition of hepatitis B viral gene expression and replication.
IPv6 integration and coexistence strategies for next-generation networks (2004)

IPv6 has been designed, among other things, to provide an expanded address space to satisfy the future networking requirements. In this article, we analyze and discuss important aspects of IPv6 deployment scenarios, and propose the system architecture coexisting and integrating with IPv4/MPLS networks. We investigate on various IPv6 deployment strategies along with network design examples, comparing these techniques. Then the IPv6 deployment in service provider environments is proposed.
Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2 (1996)

There is evidence that treatment with an antibody to tumor necrosis factor alpha (TNF alpha) improves an animal model of multiple sclerosis (MS) and is beneficial in two systemic inflammatory disease in humans, but there are no reports about anti-TNF treatment of MS. Therefore, we treated two rapidly progressive MS patients with intravenous infusions of a humanized mouse monoclonal anti-TNF antibody (cA2) in an open-label phase I safety trial and monitored their clinical status, gadolinium-enhanced brain magnetic resonance imaging (MRI), and peripheral blood and cerebrospinal fluid (CSF) immunologic status. We did not notice any clinically significant neurologic changes in either patient. The number of gadolinium-enhancing lesions increased transiently after each treatment in both patients. CSF leukocyte counts and IgG index increased after each treatment. The transient increase in the number of gadolinium-enhancing lesions that followed each infusion of cA2 together with the increase in cells and immunoglobulin in the CSF of each patient suggest that the treatment caused immune activation and an increase in disease activity. These results suggest that further use of cA2 in MS is not warranted and that studies of other agents that antagonize TNF alpha should be carried out with frequent monitoring of gadolinium-enhanced MRIs.
Mitochondrial Changes in Ageing Caenorhabditis elegans – What Do We Learn from Superoxide Dismutase Knockouts? (2011)

One of the most popular damage accumulation theories of ageing is the mitochondrial free radical theory of ageing (mFRTA). The mFRTA proposes that ageing is due to the accumulation of unrepaired oxidative damage, in particular damage to mitochondrial DNA (mtDNA). Within the mFRTA, the "vicious cycle" theory further proposes that reactive oxygen species (ROS) promote mtDNA mutations, which then lead to a further increase in ROS production. Recently, data have been published on Caenorhabditis elegans mutants deficient in one or both forms of mitochondrial superoxide dismutase (SOD). Surprisingly, even double mutants, lacking both mitochondrial forms of SOD, show no reduction in lifespan. This has been interpreted as evidence against the mFRTA because it is assumed that these mutants suffer from significantly elevated oxidative damage to their mitochondria. Here, using a novel mtDNA damage assay in conjunction with related, well established damage and metabolic markers, we first investigate the age-dependent mitochondrial decline in a cohort of ageing wild-type nematodes, in particular testing the plausibility of the "vicious cycle" theory. We then apply the methods and insights gained from this investigation to a mutant strain for C. elegans that lacks both forms of mitochondrial SOD. While we show a clear age-dependent, linear increase in oxidative damage in WT nematodes, we find no evidence for autocatalytic damage amplification as proposed by the "vicious cycle" theory. Comparing the SOD mutants with wild-type animals, we further show that oxidative damage levels in the mtDNA of SOD mutants are not significantly different from those in wild-type animals, i.e. even the total loss of mitochondrial SOD did not significantly increase oxidative damage to mtDNA. Possible reasons for this unexpected result and some implications for the mFRTA are discussed.
Met Receptor Contributes to Trastuzumab Resistance of Her2-Overexpressing Breast Cancer Cells (2008)

Her2 is overexpressed in 20% to 30% of breast tumors and correlates with reduced disease-free and overall patient survival. Trastuzumab, a humanized monoclonal antibody directed against Her2, represents the first Her2-targeted therapy, which decreases the risk of relapse and prolongs patient survival. Resistance to trastuzumab, both inherent and treatment-acquired, represents a significant barrier to the effective treatment of Her2 (+) breast cancer. The Met receptor tyrosine kinase is aberrantly expressed in breast cancer and predicts poor patient prognosis. In this study, we find that Met is frequently expressed in Her2-overexpressing breast cancer cells, as well as Her2 (+) breast cancer. Importantly, Met contributes to trastuzumab resistance, as inhibition of Met sensitizes cells to trastuzumab-mediated growth inhibition, whereas Met activation protects cells against trastuzumab by abrogating p27 induction. Remarkably, Her2-overexpressing breast cancer cells rapidly up-regulate Met expression after trastuzumab treatment, promoting their own resistance. Our study suggests that a subset of Her2 (+) patients may benefit from combined inhibition of Her2 and Met.
Bioavailability of low-dose vs high-dose 6-mercaptopurine (1988)

The bioavailability of oral 6-mercaptopurine (6MP) at standard doses is very low, largely as a result of extensive first-pass metabolism by xanthine oxidase. Fewer than one third of patients achieve 6MP plasma concentrations known to be cytocidal in vitro (greater than 1 mumol/L). Studies in vitro have suggested that first-pass metabolism can be saturated at higher doses of 6MP. To determine whether saturation occurs in vivo at clinically used doses and whether bioavailability can be enhanced by increasing the dose, the bioavailability of different doses of 6MP was studied first in rhesus monkeys and then in children with acute lymphoblastic leukemia in remission. In monkeys a higher dose of 6MP resulted in enhanced bioavailability, whereas in patients the mean relative bioavailability at the higher dose was significantly less. However, all patients achieved cytocidal (greater than 1 to 10 mumol/L) plasma concentrations at the higher dose without manifesting significant clinical toxicity. Therefore cytocidal levels of 6MP can be achieved in patients with oral 6MP without the risk of unexpectedly high levels caused by saturation of first-pass metabolism.
Thyrotropin-releasing hormone (TRH) precursor processing (1989)

Prepro-thyrotropin-releasing hormone (TRH) contains five TRH progenitor sequences and at least six other potential peptides (Lechan, R. M., Wu, P., Jackson, I. M. D., Wolf, H., Cooperman, S., Mandel, G., and Goodman, R. H. (1986a) Science 231, 159-161). Previous studies using radioimmunoassays developed against discrete regions of prepro-TRH have demonstrated that several of the potential peptides are present in rat brain and pancreas (Wu, P., Lechan, R. M., and Jackson, I. M. D. (1987) Endocrinology 121, 108-115; Wu, P. and Jackson, I. M. D. (1988a) Brain Res. 456, 22-28; Wu, P., and Jackson, I. M. D. (1988b) Regul. Pept. 22, 347-360). However, the low level of peptides present in intact tissues has made isolation of the peptides difficult. CA77 cells, a medullary thyroid carcinoma cell line, also express prepro-TRH and display processing similar to that found in tissues. However, peptide content in this tumor cell line is enhanced only 3-fold compared with normal tissues (Sevarino, K. A., Wu, P., Jackson, I. M. D., Roos, B. A., Mandel, G., and Goodman, R. H. (1988) J. Biol. Chem. 263, 620-623). To achieve higher levels of expression for facilitating peptide sequencing studies and to see if alternate processing of prepro-TRH could be detected in different cell types, we transfected into 3T3, GH4, AtT20, and RIN 5F cells a cDNA vector under control of the cytomegalovirus immediate-early promoter. 3T3 and GH4 cells failed to process prepro-TRH beyond cleavage of the signal sequence. Both AtT20 and RIN 5F cells efficiently cleaved the precursor at dibasic sites to generate mature TRH and the non-TRH peptides previously identified in vivo. Peptide content was up to 30 times greater than in hypothalamic extracts and 10 times greater than in CA77 cells. Secretion experiments with transfected AtT20 cells demonstrated that both mature TRH and the non-TRH peptides were secreted via a regulated secretory pathway similar to that utilized by endogenously synthesized peptides. We isolated several of the non-TRH peptides synthesized by transfected AtT20 cells and characterized these peptides by sequential Edman degradation. These studies identified the signal sequence cleavage site and determined that the non-TRH peptides are generated by cleavage at the dibasic sites flanking the five TRH progenitor sequences. Further, we determined that processing occurs at the Arg51-Arg52 site located in the amino-terminal portion of the precursor, the only dibasic site not flanking a TRH progenitor sequence.
Terbinafine inhibits oral squamous cell carcinoma growth through anti‐cancer cell proliferation and anti‐angiogenesis (2011)

Terbinafine (TB), an oral antifungal agent used in the treatment of superficial mycosis, has been reported to exert an anti-tumor effect in various cancer cells. However, the effect of TB on oral cancer has not been evaluated. Herein we demonstrate that TB (0-60 µM) concentration-dependently decreased cell number in cultured human oral squamous cell carcinoma (OSCC), KB cells. The anti-proliferation effect of TB was also observed in two other OSCC cell lines, SAS and SCC 15. TB (60 µM) was not cytotoxic and its inhibition on KB cell growth was reversible. [(3) H]thymidine incorporation and flow cytometric analyses revealed that TB-inhibited DNA synthesis and induced the G0/G1 cell-cycle arrest. The TB-induced cell-cycle arrest occurred when the cyclin-dependent kinase 2 activity was inhibited just as the protein levels of p21(cip1) and p27(kip1) were increased. The TB-induced G0/G1 cell-cycle arrest was completely blocked when the expressions of p21(cip1) and p27(kip1) were knocked-down together. Taken together, these results suggest that the p21(cip1) - and p27(kip1) -associated signaling pathways might be involved in the TB-induced anti-proliferation in KB cells. In vivo, TB (50 mg/kg, i.p.) significantly inhibited the KB tumor size. In these TB-treated tumors, increases in the levels of p21(cip1) and p27(kip1) protein and decreases in the number of proliferating cell nuclear antigen-positive cells and the microvessel density were observed. These findings demonstrate for the first time that TB might have potential to serve as a therapeutic tool in the treatment of oral cancer.