gebhart/patrepeval huggingface dataset:
The Nck SH2/SH3 adaptor protein: a regulator of multiple intracellular signal transduction events (1998)

The process generally termed signal transduction involves the coordinated relay of information from extracellular cues to intracellular effectors, subsequently leading to a specified cellular response. The formation of multimeric protein complexes is a critical step in the activation of most intracellular signal transduction cascades. In many cases, these processes are initiated by a family of molecules consisting of protein association motifs known as src homology 2 and 3 (SH2 and SH3) domains. This review focuses on a group of proteins within this family that lack intrinsic enzymatic functions and consist almost entirely of SH2 and SH3 domains. Termed "adaptors," these proteins serve to physically bridge activated cell surface receptors to various intracellular signal transduction pathways. Here, I briefly summarize current knowledge concerning the various adaptor proteins and place a particular emphasis on Nck. Various data are discussed which collectively support a role for Nck in the regulation of multiple intracellular signaling events.
NF-B-Inducing Kinase Increases Renal Tubule Epithelial Inflammation Associated with Diabetes (2011)

The impact of increased NF-κB-inducing kinase (NIK), a key component of the NF-κB activation pathways, on diabetes-induced renal inflammation remains unknown. We overexpressed NIK wild type (NIKwt) or kinase-dead dominant negative mutants (NIKdn) in HK-2 cells and demonstrated that RelB and p52, but not RelA, abundance and DNA binding increased in nuclei of NIKwt but not NIKdn overexpressed cells, and this corresponded with increases in multiple proinflammatory cytokines. Since TRAF3 negatively regulates NIK expression, we silenced TRAF3 by >50%; this increased nuclear levels of p52 and RelB, and transcript levels of proinflammatory cytokines and transcription factors. In HK-2 cells and mouse primary proximal tubule epithelial cells treated with methylglyoxal-modified albumin, multiple proinflammatory cytokines and NIK were increased in association with increased nuclear RelB and p52. These observations indicate that NIK regulates proinflammatory responses of renal proximal tubular epithelial cells via mechanisms involving TRAF3 and suggest a role for NF-κB noncanonical pathway activation in modulating diabetes-induced inflammation in renal tubular epithelium.
Persistent membrane translocation of protein kinase C alpha during 12-0-tetradecanoylphorbol-13-acetate-induced apoptosis of LNCaP human prostate cancer cells. (1996)

Others have reported that the phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA), an activator and down-regulator of most protein kinase C (PKC) isozymes, can induce apoptotic cell death of androgen-sensitive LNCaP but not androgen-insensitive PC-3 or DU 145 human prostate cancer cells. As a first step toward uncovering the mechanism by which TPA induces apoptosis of LNCaP cells, we quantified expression of PKC isozyme mRNAs in unmodified and TPA-resistant LNCaP cells and in naturally TPA-resistant PC-3, PC-3M, and DU 145 cells. All of the cell lines and normal prostate expressed RNAs for PKC alpha, delta, epsilon, eta, and mu; only DU 145 cells and normal prostate expressed PKC beta and theta RNAs, and none expressed PKC gamma. The amount of PKC alpha RNA and protein was 6- to 38-fold lower, and PKC mu RNA was 4.5- to 16.5-fold higher in unmodified and TPA-resistant LNCaP cells than in the androgen-independent cells. We examined the effects of TPA on PKC alpha and mu mRNA levels and on membrane translocation of PKC alpha. Incubation with TPA for 6 h or more induced 95% inhibition of cell growth, a transient 12-fold increase and 5-fold decrease in PKC alpha and mu mRNA levels, respectively, and prolonged translocation of PKC alpha to non-nuclear membranes in unmodified LNCaP cells and in TPA-resistant LNCaP cells from which TPA had been removed for 10 days. TPA-resistant LNCaP cells in the continuous presence of TPA, or 24 h after removal of TPA, had down-regulated PKC alpha and remained resistant to re-addition of TPA. These data demonstrate a strong correlation of the presence and absence of membrane PKC alpha with apoptosis and resistance to apoptosis, respectively.
A greatly improved procedure for ruthenium tetroxide catalyzed oxidations of organic compounds (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA greatly improved procedure for ruthenium tetroxide catalyzed oxidations of organic compoundsPer H. J. Carlsen, Tsutomu Katsuki, Victor S. Martin, and K. Barry SharplessCite this: J. Org. Chem. 1981, 46, 19, 3936–3938Publication Date (Print):September 1, 1981Publication History Published online1 May 2002Published inissue 1 September 1981https://pubs.acs.org/doi/10.1021/jo00332a045https://doi.org/10.1021/jo00332a045research-articleACS PublicationsRequest reuse permissionsArticle Views17252Altmetric-Citations1602LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Improvement in Glucose Tolerance and Insulin Resistance in Obese Subjects Treated with Troglitazone (1994)

Troglitazone decreases insulin resistance and improves glucose tolerance in obese subjects with either impaired or normal glucose tolerance. The ability of troglitazone to reduce insulin resistance could be useful in preventing NIDDM:
High Quality Ultra-thin TiOJSi3N4 Gate Dielectric for Giga Scale MOS Technology (1998)

This paper presents the study of physical and electrical properties of ultra-thin (2.0-3.0 nm EOT) Ti02/Si3N4 stack gate dielectrics for future giga scale MOS technology. Both layers of the dielectric stack are deposited by the Jet Vapor Deposition (JVD) process. Our experimental data indicate that the leakage current in the Ti02/Si3N4 stack is substantially (several decades) lower than that in single oxide layer of the same equivalent oxide thickness (EOT). These films also exhibit excellent interface quality, dielectric reliability, and MOSFET transistor performance comparable to that of thermal oxide.
Abstract 2439: Cross-linker evaluation in the design of antibody-SN-38 conjugates for cancer therapy (2010)

Abstract Antibody (MAb) conjugates of the potent topoisomerase I inhibitor, SN-38, prepared using the bifunctional derivative, ‘CL2-SN-38’ (maleimido-[x]-Phe-Lys-PABOCO-20-O-SN-38), were previously shown to produce significant and selective therapeutic efficacies of human tumor xenografts in nude mice. With a view to examining alternative linkers for possible improvement, we prepared a variant, namely maleimido-[x]-Lys-PABOCO-20-O-SN-38 (‘CL2A-SN-38’), and two other derivatives with cross-linker attachment at the 10-position of SN-38 instead of the 20-position: maleimido-[x]-Phe-Lys-N(Me)-(CH2)2-N(Me)-CO-10-O-SN-38 (‘CL2D-SN-38’) and maleimido-[x]-Phe-Lys-PABOCO-N(Me)-(CH2)2-N(Me)-CO-10-O-SN-38 (‘CL2E-SN-38’). In these, PAB is p-aminobenzyl moiety and ‘x’ contains a short PEG group to increase solubility. Conjugates of the humanized anti-CEACAM5 MAb, hMN-14 (labetuzumab), were prepared by reacting the maleimide-appended SN-38 derivatives with mildly reduced hMN-14. The SN-38/MAb molar substitutions were in the range of 5.9 to 6.3. In vitro studies showed a similarity in the stabilities, in mouse serum, of CL2 and CL2A-based linkers, but an order of magnitude greater stability for conjugates with linker at the 10-position; however, CL2D-SN-38 linker was inert to dipeptide cleavage by cathepsin B at the lysosomal pH of ∼ 5. The latter finding was also reflected in the loss of cytotoxicity due to hMN-14-CL2D-SN-38 conjugate in the LS174T colon cancer cell line in vitro. All conjugates were also evaluated in an exploratory preclinical therapy experiment in nude mice with aggressive s.c. LS174T human colon cancer xenografts. Conjugates were administered i.p. in groups of tumor-bearing animals (n = 10) at a schedule of 0.39 mg/kg of SN-38 equivalent twice weekly × 2 weeks. Untreated animals received saline. Mean tumor volumes (cm3) of animals in various treatment groups, on day 18, were: 0.073 ± 0.035 for the hMN-14-CL2-SN-38 positive control group; 0.055 ± 0.032 for the hMN-14-CL2A-SN-38 group; 0.518 ± 0.239 for the hMN-14-CL2D-SN-38 group; 0.490 ± 0.224 for the hMN-14-CL2E-SN-38 group; and 1.09 ± 0.88 for the untreated group. Median survival times (days) were 54.5, 55, 30, 25, and 26.5 for these groups, respectively. These results showed that a cleavable peptide was not necessary in the SN-38 conjugate design, as hMN-14-CL2A-SN-38 was equivalent to hMN-14-CL2-SN-38 in efficacy, and that hMN-14-CL2E-SN-38 was surprisingly much less efficacious than the CL2 and CL2A-based conjugates despite its higher relative stability. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2439.
Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples (2009)

Our results demonstrate the clinical feasibility of high-throughput mutation profiling to query a large panel of "actionable" cancer gene mutations. In the future, this type of approach may be incorporated into both cancer epidemiologic studies and clinical decision making to specify the use of many targeted anticancer agents.
Public Auditing for Big Data Storage in Cloud Computing -- A Survey (2013)

Data integrity is an important factor to ensure in almost any data and computation related context. It serves not only as one of the qualities of service, but also an important part of data security and privacy. With the proliferation of cloud computing and the increasing needs in big data analytics, verification of data integrity becomes increasingly important, especially on outsourced data. Therefore, research topics related to data integrity verification have attracted tremendous research interest. Among all the metrics, efficiency and security are two of the most concerned measurements. In this paper, we provide an analysis on authenticator-based efficient data integrity verification. we will analyze and provide a survey on the main aspects of this research problem, summarize the research motivations, methodologies as well as main achievements of several of the representative approaches, then try to bring forth a blueprint for possible future developments.
An experimental time-sharing system (1962)

It is the purpose of this paper to discuss briefly the need for time-sharing, some of the implementation problems, an experimental timesharing system which has been developed for the contemporary IBM 7090, and finally a scheduling algorithm of one of us (FJC) that illustrates some of the techniques which may be employed to enhance and be analyzed for the performance limits of such a time-sharing system.
The dephosphorylation of insulin and epidermal growth factor receptors. Role of endosome-associated phosphotyrosine phosphatase(s). (1992)

The autophosphorylation, from [gamma-32P]ATP, of insulin and epidermal growth factor receptors in rat liver endosomes peaked at 2-5 min and declined thereafter. When autophosphorylation from either [gamma-32P]ATP or unlabeled ATP was stopped after 5 min by adding excess EDTA +/- ATP, the phosphotyrosine (PY) content of each receptor decreased at 37 degrees C with a t 1/2 of 1.6 min. This was equally so whether the PY content of 32P-labeled receptors was analyzed by autoradiography of KOH-treated gels or by Western blotting with PY antibodies of immunoprecipitated receptors. The dephosphorylation reaction was strictly dependent on the presence of sulfhydryl, was unaffected by the addition of rat liver cytosol, and was temperature-dependent. The phosphotyrosine phosphatase(s) (PTPase(s)) appeared to be tightly anchored to the endosomal membrane, since the dephosphorylation reaction was unaffected by sodium carbonate and 0.6 M KCl treatments. However, treatment with Triton X-100 abolished dephosphorylation, implying an intimate association between the PTPase(s) and its substrate in an intact membrane environment. The powerful insulinomimetic agent pervanadate was the most potent inhibitor (50% inhibition at 1 microM). Increasing the dose of injected ligand augmented the rate of insulin and decreased that of EGF receptor dephosphorylation, respectively. Immunoblotting with specific antibodies failed to identify PTPase 1B or T-cell PTPase in ENs, whereas positive signals were seen in plasma membrane. These studies indicate that the phosphorylation state of receptor tyrosine kinases is dynamically regulated, with dephosphorylation, by closely associated PTPase(s), playing an important role.
Functional Roles of Nasal Nitric Oxide in Nasal Patency and Mucociliary Function (2002)

The purpose of this study was twofold: (i) to clarify whether it is possible to change the amount of nasal nitric oxide (NO) artificially; and (ii) to confirm that the artificially altered nasal NO has biological properties such as vasodilatation and mucociliary function. We measured nasal NO and nasal airway resistance (NAR) in healthy subjects before and after topical administration of sodium nitroprusside (SNP), an NO donor. We also measured nasal NO and saccharin transport time after administration of SNP or L-N(G)-nitroarginine methylester (L-NAME), a NO synthase inhibitor. In addition, we examined the effect of SNP and L-NAME on nasal NO and saccharin transport time after pretreatment with flutropium bromide (FB), an anticholinergic agent. Administration of SNP elicited increases in nasal NO and NAR in a dose-dependent manner. Nasal NO decreased significantly after topical administration of L-NAME. Saccharin transport time, an indicator of mucociliary function, was shortened after topical administration of SNP and prolonged after administration of L-NAME. Moreover, these phenomena were observed even after pretreatment with FB. These results suggest that artificially altered nasal NO may affect NAR and mucociliary function.
Effects of a phosphodiesterase IV inhibitor rolipram on microsphere embolism‐induced defects in memory function and cerebral cyclic AMP signal transduction system in rats (2002)

The effects of treatment with rolipram, a specific phosphodiesterase IV inhibitor, on learning and memory function and on the cyclic AMP/PKA/CREB signal transduction system were examined in rats with microsphere embolism (ME)-induced cerebral ischaemia. Sustained cerebral ischaemia was induced by the injection of 900 microspheres (48 microm in diameter) into the right hemisphere of the rat brain. The animals were treated once daily with 3 mg kg(-1) rolipram i.p. from 6 h after the onset of the operation for consecutive 10 days. Microsphere-embolized rats showed prolongation of the escape latency in the water maze task starting from day 7 after the operation and lasting for 3 consecutive days. Treatment with rolipram reduced the escape latency. ME decreased the cyclic AMP content, cytosolic PKA Cbeta level, and nuclear PKA Calpha and Cbeta levels, as well as reduced the pCREB level and the DNA-binding activity of CREB in the cerebral cortex and hippocampus on day 10 after the operation. These alterations were attenuated by treatment with rolipram. These results suggest that ME-induced failure in learning and memory function may be mediated by dysfunction of the cyclic AMP/PKA/CREB signal transduction system, that rolipram may ameliorate ME-induced impairment of learning and memory function, and that the drug effect may be partly attributed to activation of the cyclic AMP/PKA/CREB signal transduction system.
Genetic variability in the regulatory region of presenilin 1 associated with risk for Alzheimer's disease and variable expression (2000)

Mutations in the presenilin 1 ( PSEN1 ) gene have been implicated in 18-50% of autosomal dominant cases with early-onset Alzheimer's disease (EOAD). Also, PSEN1 has been suggested as a potential risk gene in late-onset AD cases. We recently showed genetic association in a population-based study of EOAD, pointing to the 5' regulatory region of PSEN1. In this study we systematically screened 3.5 kb of the PSEN1 upstream region and found four novel polymorphisms. Genetic analysis confirmed association of two polymorphisms with increased risk for EOAD. In addition, we detected two different mutations in EOAD cases at-280 and-2818 relative to the transcription initiation site in exon 1A of PSEN1. Analysis of the mutant and wild-type-280 variants using luciferase reporter gene expression in transiently transfected neuroblastoma cells showed a 30% decrease in transcriptional activity for the mutant-280G PSEN1 promoter variant compared with the wild-type variant-280C. Our data suggest that the increased risk for EOAD associated with PSEN1 may result from genetic variations in the regulatory region leading to altered expression levels of the PSEN1 protein.
Mortality amongst multiple trauma patients admitted to an intensive therapy unit (1984)

A retrospective review of 428 severely injured patients admitted to an intensive therapy unit between 1969 and 1982 was performed. The patients' primary injuries were assessed using the injury severity score (ISS), and subsequent complications using the complications impact index and sepsis score. Between 1969 and 1980 mortality fluctuated between 19% and 29% but rose to 47% (p less than 0.05) during 1981-82 in spite of an unchanged ISS. The increased mortality was confined to ventilated patients surviving more than 5 days from injury and was associated with multiple organ failure and severe infection. The rapid and sustained increase in mortality could not be explained by any obvious change in severity of injury or referral pattern. The only deliberate change in management related to the combination of analgesic/sedative drugs used in ventilated patients. During 1979 to 1982 mortality was 28% in patients given morphine with or without benzodiazepines and 77% in those given morphine and etomidate (p less than 0.0005). After discontinuation of the latter regimen (May 1983) and resumption of the former analgesic/sedative combination, mortality fell to 25% (p less than 0.005). Possible mechanisms leading to increased mortality include adrenocortical insufficiency or depth of anaesthesia.
KRAS Mutation in Metastatic Pancreatic Ductal Adenocarcinoma: Results of a Multicenter Phase II Study Evaluating Efficacy of Cetuximab plus Gemcitabine/Oxaliplatin (GEMOXCET) in First-Line Therapy (2011)

KRAS mutation in codon 12 may be associated with reduced survival compared to KRAS wild type. The role of KRAS mutations for cetuximab therapy in pancreatic cancer warrants further investigation in larger trials to exclude an epiphenomenon. Furthermore, the development of a rash is indicative of clinical benefit.
Venous oxygen levels during aerobic forearm exercise: An index of impaired oxidative metabolism in mitochondrial myopathy (2001)

A cardinal feature of impaired skeletal muscle oxidative metabolism in mitochondrial myopathies is a limited ability to increase the extraction of O(2) from blood relative to the increase in O(2) delivery by the circulation during exercise. We investigated whether aerobic forearm exercise would result in an abnormal increase in venous effluent O(2) in patients with impaired skeletal muscle oxidative phosphorylation attributable to mitochondrial disease. We monitored the partial pressure of O(2) (PO(2)) in cubital venous blood at rest, during handgrip exercise, and during recovery in 13 patients with mitochondrial myopathy and exercise intolerance and in 13 healthy control and 11 patient control subjects. Resting and recovery venous effluent PO(2) were similar in all subjects, but during exercise venous PO(2) paradoxically rose in mitochondrial myopathy patients from 27.2 +/- 4.0mmHg to 38.2 +/- 13.3mmHg, whereas PO(2) fell from 27.2 +/- 4.2mmHg to 24.2 +/- 2.7mmHg in healthy subjects and from 27.4 +/- 9.5mmHg to 22.2 +/- 5.2mmHg in patient controls. The range of elevated venous PO(2) during forearm exercise in mitochondrial myopathy patients (32 to 82mmHg) correlated closely with the severity of oxidative impairment as assessed during cycle exercise. We conclude that measurement of venous PO(2) during aerobic forearm exercise provides an easily performed screening test that sensitively detects impaired O(2) use and accurately assesses the severity of oxidative impairment in patients with mitochondrial myopathy and exercise intolerance.
Dietary supplementation with spray-dried porcine plasma has prebiotic effects on gut microbiota in mice (2020)

In animal models of inflammation and in farm animals, dietary inclusion of spray-dried porcine plasma (SDP) reduces mucosal inflammation. Here, we study whether these effects could be mediated by changes in the intestinal microbiota and if these changes are similar to those induced by oral antibiotics. Weaned 21-day-old C57BL/6 mice were divided into 3 groups: the CTL group, fed the control diet; the COL group, administered low doses of neomycin and colistin; and the SDP group, supplemented with 8% SDP. After 14 days, analysis of the fecal microbiome showed that the microbiota profiles induced by SDP and the antibiotics were very different, thus, SDP has prebiotic rather than antibiotic effects. At the phylum level, SDP stimulated the presence of Firmicutes, considerably increasing the lactobacilli population. It also enhanced the growth of species involved in regulatory T-lymphocyte homeostasis and restoration of the mucosal barrier, as well as species negatively correlated with expression of pro-inflammatory cytokines. At the mucosal level, expression of toll-like receptors Tlr2, Tlr4 and Tlr9, and mucous-related genes Muc2 and Tff3 with regulatory and barrier stability functions, were increased. SDP also increased expression of Il-10 and Tgf-β, as well as markers of macrophages and dendritic cells eventually promoting an immune-tolerant environment.