gebhart/patrepeval huggingface dataset:
Regulatory functional territory of PLK-1 and their substrates beyond mitosis (2017)

Polo-like kinase 1 (PLK-1) is a well-known (Ser/Thr) mitotic protein kinase and is considered as a proto-oncogene. As hyper-activation of PLK-1 is broadly associated with poor prognosis and cancer progression, it is one of the most extensively studied mitotic kinases. During mitosis, PLK-1 regulates various cell cycle events, such as spindle pole maturation, chromosome segregation and cytokinesis. However, studies have demonstrated that the role of PLK-1 is not only restricted to mitosis, but PLK-1 can also regulate other vital events beyond mitosis, including transcription, translation, ciliogenesis, checkpoint adaptation and recovery, apoptosis, chromosomes dynamics etc. Recent reviews have tried to define the regulatory role of PLK-1 during mitosis progression and tumorigenesis, but its' functional role beyond mitosis is still largely unexplored. PLK-1 can regulate the activity of many proteins that work outside of its conventional territory. The dysregulation of these proteins can cause diseases such as Alzheimer's disease, tumorigenesis etc. and may also lead to drug resistance. Thus, in this review, we discussed the versatile role of PLK-1 and tried to collect data to validate its' functional role in cell cycle regulation apart from mitosis.
DNA damage, cellular senescence and organismal ageing: causal or correlative? (2007)

Cellular senescence has long been used as a cellular model for understanding mechanisms underlying the ageing process. Compelling evidence obtained in recent years demonstrate that DNA damage is a common mediator for both replicative senescence, which is triggered by telomere shortening, and premature cellular senescence induced by various stressors such as oncogenic stress and oxidative stress. Extensive observations suggest that DNA damage accumulates with age and that this may be due to an increase in production of reactive oxygen species (ROS) and a decline in DNA repair capacity with age. Mutation or disrupted expression of genes that increase DNA damage often result in premature ageing. In contrast, interventions that enhance resistance to oxidative stress and attenuate DNA damage contribute towards longevity. This evidence suggests that genomic instability plays a causative role in the ageing process. However, conflicting findings exist which indicate that ROS production and oxidative damage levels of macromolecules including DNA do not always correlate with lifespan in model animals. Here we review the recent advances in addressing the role of DNA damage in cellular senescence and organismal ageing.
N-(2-hydroxypropyl)methacrylamide–amphotericin B (HPMA–AmB) copolymer conjugates as antileishmanial agents (2008)

Leishmaniasis is a major health problem in many parts of the world, caused by various species of Leishmania. Amastigotes are the clinically relevant form of the parasite in the human host and reside in the parasitophorous vacuole within macrophages. Polymer-drug conjugates have been used for lysosomotropic drug delivery and have already shown potential in anticancer and antileishmanial chemotherapy. We synthesised N-(2-hydroxypropyl)methacrylamide-amphotericin B (HPMA-AmB) copolymer conjugates in which the AmB was attached to the polymer through a degradable GlyPheLeuGly linker. Antileishmanial activity was assessed in vitro against intracellular amastigotes in host macrophages [murine peritoneal exudate macrophages (PEMs), murine bone marrow-derived macrophages (BMMs) and differentiated THP-1 cells]. The most potent copolymers had 50% effective concentration (EC(50)) values of 0.03 microg/mL AmB equivalent against Leishmania donovani amastigotes in PEMs and BMMs and an EC(50) of 0.57 microg/mL AmB equivalent against L. donovani in THP-1 cells. This activity was comparable with free AmB (EC(50)=0.03-0.07 microg/mL against L. donovani in PEMs and BMMs and 0.24-0.42 microg/mL against amastigotes in THP-1 cells) and Fungizone (EC(50)=0.04-0.07 microg/mL against amastigotes in PEMs). Conjugates also showed potent in vivo activity with ca. 50% inhibition of parasite burden at 1mg/kg body weight.
The Presentation (2008)

<sc>When</sc> Albert found himself alone with Monte Cristo, ‘M. le Comte,’ said he, ‘allow me to commence my duties by showing you a specimen of a bachelor’s apartment. You, who are accustomed to the palaces of Italy, can amuse yourself by calculating in how...
Effects of Mutations in GrlA of Topoisomerase IV from Staphylococcus aureus on Quinolone and Coumarin Activity (1998)

The grlA genes of Staphylococcus aureus ISP794 (wild type), MT5224c4 (grlA [Phe-80]), MT5224c2 (grlA [Pro-116]), and MT111 (grlA [Glu-116]) were cloned in pSK950, a shuttle vector, and introduced into S. aureus strains derived from strain RN4220. The mutations at position 116 of GrlA (Ala-->Pro or Glu) caused an increase in the level of fluoroquinolone resistance and a decrease in the level of coumarin susceptibility, whereas the mutation at position 80 (Ser-->Phe) caused only an increase in the level of fluoroquinolone resistance. In multicopy alleles, both types of mutations were codominant for fluoroquinolone resistance, and mutations at position 116 were also codominant for coumarin resistance.
Calcium Chloride and Adrenaline as Bronchial Dilators Compared by Sequential Analysis (1954)

A case of cantharidin poisoning in which death occurred is described and clinical aspects of this condition are briefly discussed.
Requirement of aggregation propensity of Alzheimer amyloid peptides for neuronal cell surface binding (2007)

Taken together, our findings reveal that amyloid peptide aggregation propensity is an essential determinant of neuronal cell surface association. We anticipate that our approach, involving Abeta imaging in live cells, will be highly useful for evaluating the efficacy of therapeutic drugs that prevent toxic Abeta association with neuronal cells.
Pentostam® (sodium stibogluconate); a 50-year personal reminiscence (1995)

Journal Article Pentostam® (sodium stibogluconate); a 50-year personal reminiscence Get access L.G. Goodwin L.G. Goodwin Shepperlands Farm, Park Lane, Finchampstead, Berkshire, RG404QF, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 89, Issue 3, May-June 1995, Pages 339–341, https://doi.org/10.1016/0035-9203(95)90572-3 Published: 01 June 1995 Article history Received: 12 December 1994 Accepted: 04 January 1995 Published: 01 June 1995
Correlation Between DNase I Hypersensitive Site Distribution and Gene Expression in HeLa S3 Cells (2012)

Mapping DNase I hypersensitive sites (DHSs) within nuclear chromatin is a traditional and powerful method of identifying genetic regulatory elements. DHSs have been mapped by capturing the ends of long DNase I-cut fragments (>100,000 bp), or 100-1200 bp DNase I-double cleavage fragments (also called double-hit fragments). But next generation sequencing requires a DNA library containing DNA fragments of 100-500 bp. Therefore, we used short DNA fragments released by DNase I digestion to generate DNA libraries for next generation sequencing. The short segments are 100-300 bp and can be directly cloned and used for high-throughput sequencing. We identified 83,897 DHSs in 2,343,479 tags across the human genome. Our results indicate that the DHSs identified by this DHS assay are consistent with those identified by longer fragments in previous studies. We also found: (1) the distribution of DHSs in promoter and other gene regions of similarly expressed genes differs among different chromosomes; (2) silenced genes had a more open chromatin structure than previously thought; (3) DHSs in 3'untranslated regions (3'UTRs) are negatively correlated with level of gene expression.
Cognitive effects of GABAergic antiepileptic drugs (2011)

Many patients undergoing long-term treatment of epilepsy complain of memory disorders, which entail worse quality of life. The risk factors generating memory disorders include: morphological brain damage, the duration and course of epileptic seizures (conscience disorders), the time of diagnosis (the risk is greater if epileptic seizures start early in life), drug resistance, the presence of interseizure changes in the EEG in the form of sharp-wave discharges or sharp spike-wave/ slow spike-wave complexes and improper pharmacotherapy (exceeding the admissible concentration of drugs in blood serum, polytherapy). GABAergic neurotransmission of older antiepileptic drugs (barbiturates, benzodiazepines) makes them particularly prone to produce modest, but statistically significant disruption of cognitive processes. This explains the search for new antiepileptic drugs that will improve, or at least not impair, cognitive functions. The improvement of cognitive functions by new generation antiepileptic drugs results, among others, from their non-GABAergic mechanisms: they influence the ion channels and glutaminergic transmission.
Measuring Friedreich ataxia: Interrater reliability of a neurologic rating scale (2005)

Measuring the severity of neurologic dysfunction in patients with inherited ataxias, including Friedreich ataxia (FA), is difficult because of the variable rate of progression, the variable age at onset and the variety of neural systems that may be affected. The authors discuss the problems related to rating scales in the ataxias, report a neurologic rating scale for FA, and demonstrate acceptable interrater reliability of the instrument.
Metropolitan-area networks (1990)

Metropolitan-area networks (MAN), which fill the gap between local area networks (LANs) and wide-area networks (WANs), are discussed. MANs were originally oriented toward data, but now often carry voice and video traffic as well. Supplying more bandwidth than LANs, they support two-way communication over a shared medium such as an optical-fiber cable, and may offer point-to-point high-speed circuits or packet-switched communication. The two most favored topologies, double-star and double-ring, are described and emerging MAN protocols are examined.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Intramyocellular Lipid and Insulin Resistance (2003)

Insulin resistance plays an important role in the pathogenesis of human type 2 diabetes. In humans, a negative correlation between insulin sensitivity and intramyocellular lipid (IMCL) content has been shown; thus, IMCL becomes a marker for insulin resistance. Recently, magnetic resonance spectroscopy (MRS) has been established as a dependable method for selective detection and quantification of IMCL in humans. To validate the interrelation between insulin sensitivity and IMCL in an animal model of type 2 diabetes, we established volume selective (1)H-MRS at 7 Tesla to noninvasively assess IMCL in the rat. In male obese Zucker Diabetic Fatty rats and their lean littermates, IMCL levels were determined repeatedly over 4 months, and insulin sensitivity was measured by the euglycemic-hyperinsulinemic clamp method at 6-7 and at 22-24 weeks of age. A distinct relation between IMCL and insulin sensitivity was demonstrated as well as age dependence for both parameters. Rosiglitazone treatment caused a clear reduction of IMCL and hepatic fat despite increased body weight, and a marked improvement of insulin sensitivity. Thus, the insulin sensitizing properties of rosiglitazone were consistent with a redistribution of lipids from nonadipocytic (skeletal muscle, liver) back into fat tissue.
Solid-Phase Peptide Synthesis. III. An Improved Synthesis of Bradykinin* (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleSolid-Phase Peptide Synthesis. III. An Improved Synthesis of Bradykinin*R. B. MerrifieldCite this: Biochemistry 1964, 3, 9, 1385–1390Publication Date (Print):September 1, 1964Publication History Published online1 May 2002Published inissue 1 September 1964https://pubs.acs.org/doi/10.1021/bi00897a032https://doi.org/10.1021/bi00897a032research-articleACS PublicationsRequest reuse permissionsArticle Views2808Altmetric-Citations458LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Rapamycin and Interleukin-10 Treatment Induces T Regulatory Type 1 Cells That Mediate Antigen-Specific Transplantation Tolerance (2006)

Islet transplantation is a cure for type 1 diabetes, but its potential is limited by the need for constant immunosuppression. One solution to this problem is the induction of transplantation tolerance mediated by T regulatory cells. T regulatory type 1 (Tr1) cells are characterized by their production of high levels of interleukin (IL)-10, which is crucial for their differentiation and suppressive function. We investigated the effects of IL-10 administered in combination with rapamycin on the induction of Tr1 cells that could mediate a state of tolerance in diabetic mice after pancreatic islet transplantation. The efficacy of this treatment was compared with IL-10 alone and standard immunosuppression. Stable long-term tolerance that was not reversible by alloantigen rechallenge was achieved only in mice treated with rapamycin plus IL-10. Tr1 cells that produced high levels of IL-10 and suppressed T-cell proliferation were isolated from splenocytes of rapamycin plus IL-10–treated mice after treatment withdrawal. In rapamycin plus IL-10–treated mice, endogenous IL-10 mediated an active state of tolerance, as was observed when the blockade of IL-10 activity rapidly induced graft rejection >100 days after transplantation. CD4+ T-cells from rapamycin plus IL-10–treated mice transferred antigen-specific tolerance in mice that received new transplants. Thus rapamycin plus IL-10 not only prevented allograft rejection but also induced Tr1 cells that mediated stable antigen-specific, long-term tolerance in vivo.
CD4 T cells inhibit in vivo the CD8‐mediated immune response against murine colon carcinoma cells transduced with interleukin‐12 genes (1995)

Retroviral-mediated cytokine gene transfer into tumor cells is a highly effective way of inducing tumor inhibition and immunity. We analyzed the tumorigenicity of C-26 murine colon carcinoma cells transduced with genes encoding the two subunits of murine interleukin-12 (IL-12) in a polycistronic retroviral vector and selected for resistance to G418 and for IL-12 production (30-80 pg/ml). BALB/c mice injected s.c., i.v. and intrasplenically with C-26/IL-12 cells from three different IL-12-producing clones showed delayed tumor onset as compared with mice injected with control NeoR-transduced or parental tumor cells. Although C-26/IL-12 tumor-bearing mice eventually died of lung metastasis, their survival time was twice as long as that of mice injected with control cells. In experiments with mice selectively depleted of natural killer (NK) cells before tumor cell injection, the time of tumor onset and survival of mice injected with C-26/IL-12 s.c. and i.v., respectively, was reduced. CD8+ T cell depletion had no effect on latency or survival, whereas removal of CD4+ T cells led to C-26/IL-12 tumor regression in about 40% of mice. Histological and immunocytochemical characterization of leukocytes infiltrating C-26/IL-12 tumors showed only slight infiltration with few T cells in non-depleted mice but abundant infiltration by CD8+ T cells and asialo-GM1+ NK cells in tumors of mice depleted of CD4+ T cells. The lack of CD8+ T cell infiltration is not due to a CD4-mediated suppression of their activation because irradiated C-26/IL-12 cells primed for the induction of a strong cytotoxic T lymphocyte response against C-26 parental cells and induced CD8+ effector cells that protected against C-26/IL-12 in a Winn assay. Rather, the results suggest that, although C-26/IL-12 cells injected in vivo stimulate both NK and CD8+ T cells, tumor infiltration by the latter is inhibited by CD4+ T cells.
A 3D structural model of memapsin 2 protease generated from theoretical study. (2001)

The 3D-structure model from our study is informative to guide future molecular biology study about M2 and drug design based on database searching.
Morphology of nylon 6/polypropylene blends compatibilized with maleated polypropylene (1995)

Abstract Transmission electron microscopy (TEM) was used to examine the morphology of blends of nylon 6 and polypropylene (PP) containing various maleated polypropylenes (PP‐g‐MA). The size of the dispersed polypropylene particles decreases as the content of maleic anhydride in the PP‐g‐MA increases for binary blends of nylon 6 and the maleated polypropylenes. Ternary blends of nylon 6, PP, and PP‐g‐MA show morphologies that depend on the content of maleic anhydride of the PP‐g‐MA and on the miscibility of PP and PP‐g‐MA. Blends where PP and PP‐g‐MA are immiscible show a bimodal distribution of particle sizes. Miscibility of the PP and PP‐g‐MA was determined by TEM using a special staining technique. Experimental observations of miscibility were further corroborated by thermodynamic calculations. The morphology of the ternary blends was also found to be dependent on the ratio of PP/PP‐g‐MA. By changing this ratio it was possible to induce drastic changes of morphology, going from a continuous nylon 6 phase to a continuous PP phase at a fixed composition. The mechanical properties of these blends were found to be dependent on their morphology. ©1995 John Wiley &amp; Sons, Inc.
An advanced platform for development and evaluation of grid interconnection systems using hardware-in-the-loop (2013)

The recently highlighted vulnerabilities, environmental effects, and critically aging status of the North American Electric Power System (EPS) are fueling a shift towards a power system paradigm that more fully leverages Distributed Resources (DRs). In order to support and accelerate DR grid integration, methods to rapidly evaluate DRs against existing grid interconnection standards and assess advanced DRs integrated in complex EPS scenarios are needed. This thesis develops a novel solution for rapid evaluation of DR grid interconnection standard conformance that uses a real-time simulator and a single graphical user interface to automate the time-consuming process required for the many repeated conformance tests of IEEE Std 1547.1™. A method for evaluating advanced DR grid integration scenarios using Power Hardware-in-the-Loop (PHIL) is presented. The results from a novel demonstration of a DR grid integration scenario using both PHIL-based and hardware-only approaches are presented, establishing the utility and validity of the PHIL method.
Identification of Minimal p53 Promoter Region Regulated by MALAT1 in Human Lung Adenocarcinoma Cells (2018)

The MALAT1 long noncoding RNA is strongly linked to cancer progression. Here we report a MALAT1 function in repressing the promoter of <i>p53 (TP53)</i> tumor suppressor gene. <i>p21</i> and <i>FAS</i>, well-known p53 targets, were upregulated by MALAT1 knockdown in A549 human lung adenocarcinoma cells. We found that these upregulations were mediated by transcriptional activation of p53 through MALAT1 depletion. In addition, we identified a minimal MALAT1-responsive region in the P1 promoter of <i>p53</i> gene. Flow cytometry analysis revealed that MALAT1-depleted cells exhibited G1 cell cycle arrest. These results suggest that MALAT1 affects the expression of p53 target genes through repressing <i>p53</i> promoter activity, leading to influence the cell cycle progression.
DNA microarray analysis of vitamin D-induced gene expression in a human colon carcinoma cell line (2004)

The full extent to which 1,25-dihydroxyvitamin D(3) affects gene expression in human intestinal epithelial cells is unknown. We used oligonucleotide arrays to catalog vitamin D-induced changes in gene expression in Caco-2 cells, a human colon carcinoma cell line. Five paired sets of Caco-2 cell cultures were subjected to either control conditions or 1,25-dihydroxyvitamin D (10(-7) mol/l x 24 h), and RNA was analyzed on an Affymetrix cDNA array containing 12,625 human sequences. Only 13 sequences representing 12 distinct genes exhibited statistically significant changes in expression of twofold or greater and were also called as "present" or "marginal" by the array-reading software in all five experiments. Genes regulated by 1,25-dihydroxyvitamin D included two previously known genes (25-hydroxyvitamin D-24-hydroxylase and amphiregulin) and 10 genes (sorcin, Gem, adaptin-gamma, TIG1, CEACAM6, carbonic anhydrase XII, junB, ceruloplasmin, and two unidentified sequences) that were novel. We tested and independently confirmed the effect of 1,25-dihydroxyvitamin D on 11 of these genes by RT-PCR. Increased protein expression was tested and confirmed in two of the novel 1,25-dihydroxyvitamin D-regulated genes, ceruloplasmin and sorcin. The known function of these genes suggests that many of them could be involved in the antiproliferative effects of 1,25-dihydroxyvitamin D3.
A General Method for the Synthesis of 2‘-O-Cyanoethylated Oligoribonucleotides Having Promising Hybridization Affinity for DNA and RNA and Enhanced Nuclease Resistance (2005)

[reaction: see text] An effective method for the synthesis of 2'-O-cyanoethylated oligoribonucleotides as a new class of 2'-O-modified RNAs was developed. The reaction of appropriately protected ribonucleoside derivatives with acrylonitrile in t-BuOH in the presence of Cs2CO3 gave 2'-O-cyanoethylated ribonucleoside derivatives in excellent yields, which were converted by a successive selective deprotection/protection strategy to 2'-O-cyanoethylated 5'-O-dimethoxytritylribonucleoside 3'-phosphoramidite derivatives in high yields. Fully 2'-O-cyanoethylated oligoribonucleotides, (Uce)12 and (GceAceCceUce)3, were successfully synthesized in the phosphoramidite approach by use of the phosphoramidite building blocks. It was also found that oligoribonucleotides having a 2'-O-cyanoethylated ribonucleoside (Uce, Cce, Ace, or Gce) could be obtained by the selective removal of the TBDMS group from fully protected oligoribonucleotide intermediates without loss of the cyanoethyl group by use of NEt3 x 3HF as a desilylating reagent. The detailed T(m) experiments revealed that oligoribonucleotides containing 2'-O-cyanoethylated ribonucleosides have higher hybridization affinity for both DNA and RNA than the corresponding unmodified and 2'-O-methylated oligoribonucleotides. In addition, introduction of a cyanoethyl group into the 2'-position of RNA resulted in significant increase of nuclease resistance toward snake venom and bovine spleen phosphodiesterases compared with that of the methyl group.