gebhart/patrepeval huggingface dataset:
REVIEW ARTICLE. MICROSATELLITES AND PCR GENOMIC ANALYSIS (1996)

Microsatellites form a significant proportion of the growing family of repetitive DNA sequences, widely dispersed in the human genome. Due to their ubiquity, PCR (polymerase chain reaction) typability, Mendelian co-dominant inheritance, and extreme polymorphism, microsatellites have assumed an increasingly important role as markers in the genome. Apart from their obvious applications in genome mapping and positional cloning, these markers have been applied in fields as disparate as tumour biology, personal identification, population genetic analysis, and the construction of human evolutionary trees. Microsatellites are associated with human disease, not only as markers of risk but also directly in disease aetiopathogenesis, providing new insights into non-Mendelian inheritance; the replication, repair, and mutation of eukaryotic DNA; the regulation of gene transcription; and protein-protein interactions. These insights have resulted in novel paradigms for oncogenesis and neurological disease.
Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease (1998)

Patients with Alzheimer's disease (AD) have elevations of fasting plasma insulin that are hypothesized to be associated with disrupted brain insulin metabolism. We examined paired fasted plasma and CSF insulin levels in 25 patients with AD and 14 healthy age-matched adults and determined whether insulin levels were related to severity of dementia and apolipoprotein E-epsilon4 homozygosity, a known genetic risk factor for AD. The AD patients had lower CSF insulin, higher plasma insulin, and a reduced CSF-to-plasma insulin ratio when compared with healthy adults. The differences were greater for patients with more advanced AD. Patients who were not apolipoprotein E-epsilon4 homozygotes had higher plasma insulin levels and reduced CSF-to-plasma ratios, whereas epsilon4 homozygotes with AD had normal values. Both plasma and CSF insulin levels are abnormal in AD, and there are metabolic differences among apolipoprotein E genotypes.
Micelle structure in a deep eutectic solvent: a small-angle scattering study (2016)

In recent years many studies into green solvents have been undertaken and deep eutectic solvents (DES) have emerged as sustainable and green alternatives to conventional solvents since they may be formed from cheap non-toxic organic precursors. In this study we examine amphiphile behaviour in these novel media to test our understanding of amphiphile self-assembly within environments that have an intermediate polarity between polar and non-polar extremes. We have built on our recently published results to present a more detailed structural characterisation of micelles of sodium dodecylsulfate (SDS) within the eutectic mixture of choline chloride and urea. Here we show that SDS adopts an unusual cylindrical aggregate morphology, unlike that seen in water and other polar solvents. A new morphology transition to shorter aggregates was found with increasing concentration. The self-assembly of SDS was also investigated in the presence of water; which promotes the formation of shorter aggregates.
Battery Energy Storage Another Option for Load-Frequency-Control and Instantaneous Reserve (1986)

Energy storage plants utilizing batteries and thyristor power converters can be operated like pumped hydro storage units. Under the conditions actually prevailing in Europe, load leveling operation of such plants is not economical. Nevertheless, a battery energy storage plant promises both operational and economical advantages for load-frequency-control and instantaneous reserve operation. Queries according to this unconventional operation of batteries have been settled in a test facility in Berlin (West). After two years of test operation a decision was made to build up a full-scale demonstration plant, which will be commissioned in early 1987.
One billion word benchmark for measuring progress in statistical language modeling (2014)

We propose a new benchmark corpus to be used for measuring progress in statistical language modeling. With almost one billion words of training data, we hope this benchmark will be useful to quickly evaluate novel language modeling techniques, and to compare their contribution when combined with other advanced techniques. We show performance of several well-known types of language models, with the best results achieved with a recurrent neural network based language model. The baseline unpruned Kneser-Ney 5-gram model achieves perplexity 67.6; a combination of techniques leads to 35% reduction in perplexity, or 10% reduction in cross-entropy (bits), over that baseline. The benchmark is available as a code.google.com project; besides the scripts needed to rebuild the training/held-out data, it also makes available log-probability values for each word in each of ten held-out data sets, for each of the baseline n-gram models.
Phosphoinositide-dependent Kinase-2 Is a Distinct Protein Kinase Enriched in a Novel Cytoskeletal Fraction Associated with Adipocyte Plasma Membranes (2003)

By recombining subcellular components of 3T3-L1 adipocytes in a test tube, early insulin signaling events dependent on phosphatidylinositol 3-kinase (PI 3-kinase) were successfully reconstituted, up to and including the phosphorylation of glycogen synthase kinase-3 by the serine/threonine kinase, Akt (Murata, H., Hresko, R.C., and Mueckler, M. (2003) J. Biol. Chem. 278, 21607-21614). Utilizing the advantages provided by a cell-free methodology, we characterized phosphoinositide-dependent kinase 2 (PDK2), the putative kinase responsible for phosphorylating Akt on Ser-473. Immunodepleting cytosolic PDK1 from an in vitro reaction containing plasma membrane and cytosol markedly inhibited insulin-stimulated phosphorylation of Akt at the PDK1 site (Thr-308) but had no effect on phosphorylation at the PDK2 site (Ser-473). In contrast, PDK2 activity was found to be highly enriched in a novel cytoskeletal subcellular fraction associated with plasma membranes. Akt isoforms 1-3 and a kinase-dead Akt1 (K179A) mutant were phosphorylated in a phosphatidylinositol 3,4,5-trisphosphate-dependent manner at Ser-473 in an in vitro reaction containing this novel adipocyte subcellular fraction. Our data indicate that this PDK2 activity is the result of a kinase distinct from PDK1 and is not due to autophosphorylation or transphosphorylation of Akt.
Immunotherapy with antibodies to the EGF receptor (1994)

A series of rat monoclonal antibodies (MAbs) has been generated against the extracellular domain of the receptor for EGF which block the binding of EGF and TGF alpha to the receptor and inhibit the growth in vitro of a range of carcinoma cell lines that over-express the receptor for EGF. Some of these antibodies were able also to induce the complete regression of xenografts of EGFR-over-expressing tumours when treatment was started, either at the time of tumour inoculation or later when the tumours were established. The most effective of these antibodies was ICR62, which was also able to activate host immune effector functions. We conclude that antibodies which block growth-factor-ligand interaction can have a profound influence on the proliferative capacity of tumour cells in vivo and may have useful clinical application.
Microbial fuel cell cathodes: from bottleneck to prime opportunity? (2008)

Microbial fuel cells that can generate energy out of wastewaters are close to pilot scale testing. As such, MFC technology is complementary to methane generation due to the possibility to rapidly convert organic acids, polish effluents and work at low substrate concentrations. The main bottleneck perceived at the moment is the cathodic electron transfer. A variety of catalysts has been investigated for the direct transfer of electrons from the cathode to oxygen in the air. Overlooked in this context were bacteria. Bacteria could indeed be worthwhile to replace chemical catalysts. Moreover, their versatility enables us to not only target at oxygen, but also at nitrous oxides and contaminants as possible drivers of electricity generation, nutrient removal and bioremediation. This paper addresses several recent developments in MFC cathode research, and demonstrates that energy generation is but an aspect of this versatile technology.
Salts of Therapeutic Agents: Chemical, Physicochemical, and Biological Considerations (2018)

The physicochemical and biological properties of active pharmaceutical ingredients (APIs) are greatly affected by their salt forms. The choice of a particular salt formulation is based on numerous factors such as API chemistry, intended dosage form, pharmacokinetics, and pharmacodynamics. The appropriate salt can improve the overall therapeutic and pharmaceutical effects of an API. However, the incorrect salt form can have the opposite effect, and can be quite detrimental for overall drug development. This review summarizes several criteria for choosing the appropriate salt forms, along with the effects of salt forms on the pharmaceutical properties of APIs. In addition to a comprehensive review of the selection criteria, this review also gives a brief historic perspective of the salt selection processes.
Redirecting αβT cells against cancer cells by transfer of a broadly tumor-reactive γδT-cell receptor (2011)

Major limitations of currently investigated αβT cells redirected against cancer by transfer of tumor-specific αβTCR arise from their low affinity, MHC restriction, and risk to mediate self-reactivity after pairing with endogenous α or βTCR chains. Therefore, the ability of a defined γ9δ2TCR to redirect αβT cells selectively against tumor cells was tested and its molecular interaction with a variety of targets investigated. Functional analysis revealed that a γ9δ2TCR efficiently reprograms both CD4(+) and CD8(+) αβT cells against a broad panel of cancer cells while ignoring normal cells, and substantially reduces but does not completely abrogate alloreactivity. γ9δ2TCR-transduced αβT cells reduced colony formation of progenitor cells of primary acute myeloid leukemia blasts and inhibited leukemia growth in a humanized mouse model. Thereby, metabolites of a dysregulated mevalonate pathway are targeted and the additional application of widely used biphosphonates is crucial for in vivo efficacy most likely because of its modulating effect on cytokine secretion of γ9δ2TCR-transduced αβT cells. Expression of NKG2D ligands and F1-ATPase contributed to the activity of γ9δ2TCR-transduced αβT cells but were not mandatory. In summary, γ9δ2 TCRs are an attractive alternative to broadly redirect αβT cells against cancer cells with both an improved efficacy and safety profile compared with currently used αβTCRs.
Semiconductor-metal hybrid structures: novel perspective for read heads (2004)

Recently, it was shown that semiconductor-metal hybrid structures can exhibit a very large magnetoresistance effect, the so-called extraordinary magnetoresistance (EMR) effect. This led to the perspective of using EMR devices in magnetic-field sensors and ultrafast read heads. Based on the finite element method, we study the EMR and optimize the effect with respect to material parameters and geometry. As the important design rule we find that the width-to-length ratio of a rectangular device should be below 0.042. This holds for a broad regime of mobility /spl mu/ in the semiconductor and specific contact resistance /spl rho//sub c/ between the semiconductor and the metal.
Evidence for Separate Involvement of Different μ-Opioid Receptor Subtypes in Itch and Analgesia Induced by Supraspinal Action of Opioids (2008)

The common adverse effect of centrally-injected mu-opioid receptor (mu-OR) agonists is pruritus. This study was conducted using mice to examine whether different subtypes of mu-OR would be responsible for pruritus and analgesia. Intracisternal injections of morphine and morphine-6beta-glucronide (M6G), but not M3G, produced an antinociceptive effect. Morphine, but neither M6G nor M3G, induced facial scratching, a pruritus-related response. Facial scratching following morphine was not affected by the mu(1)-OR antagonist naloxonazine at doses that inhibited the antinociceptive effects. The results suggest that different subtype and/or splice variants of mu-OR are separately involved in pruritus and antinociception of opioids.
Prevention of immunotoxin-induced immunogenicity by coadministration with CTLA4Ig enhances antitumor efficacy (1997)

Immunotoxins have shown promise as antitumor agents in clinical trials. However, they have not become part of standard cancer therapy because of factors that include their inherent immunogenicity, which limits the duration of therapy. To address this issue, we evaluated in preclinical models the concomitant use of the immunosuppressive agent CTLA4Ig and BR96 sFv-PE40, a single-chain immunotoxin that binds to carcinoma cells expressing Le(y). Cotreatment with CTLA4Ig, an inhibitor of the CD28/CTLA4-CD80/CD86 costimulation pathway, blocked the production of Abs against BR96 sFv-PE40 in immunocompetent rodents and dogs. It also blocked hypersensitivity reactions in rats carrying colon carcinoma allografts during a second course of BR96 sFv-PE40 therapy, and the cotreatment with CTLA4Ig resulted in enhanced antitumor activity. Cotreatment with CTLA4Ig also prevented hypersensitivity reactions induced by repeat dosing of BR96 sFv-PE40 (q3dx5) in dogs. The production of anti-BR96-sFv-PE40 Abs was decreased in CTLA4Ig-cotreated rodents and dogs resulting in increased plasma levels of BR96 sFv-PE40 relative to non-CTLA4Ig-cotreated animals. These data show that cotreatment of immunotoxins with CTLA4Ig, by inhibiting the production of anti-immunotoxin Abs, can extend the duration of BR96 sFv-PE40 therapy to give greater exposure, reduced toxicities, and increased efficacy.
A Decade of Bioorthogonal Chemistry (2011)

ADVERTISEMENT RETURN TO ISSUEEditorialNEXTA Decade of Bioorthogonal ChemistryCarolyn R. BertozziView Author Information University of California, BerkeleyCite this: Acc. Chem. Res. 2011, 44, 9, 651–653Publication Date (Web):September 20, 2011Publication History Published online20 September 2011Published inissue 20 September 2011https://pubs.acs.org/doi/10.1021/ar200193fhttps://doi.org/10.1021/ar200193feditorialACS PublicationsCopyright © 2011 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views16993Altmetric-Citations225LEARN 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 PDF (563 KB) Get e-AlertscloseSUBJECTS:Addition reactions,Chemical biology,Chemical reactions,Functional groups,Peptides and proteins Get e-Alerts
Acyl coenzyme A:cholesterol acyl transferase in macrophages utilizes a cellular pool of cholesterol oxidase-accessible cholesterol as substrate. (1988)

Cholesterol esterification by acyl CoA:cholesterol acyl transferase (ACAT) in macrophages is a key process in atheroma foam cell formation. However, the process of cholesterol substrate delivery to ACAT is not well defined. In this study, J774 macrophages, which form foam cells with native low density lipoprotein (LDL), were labeled with [3H]cholesterol-containing liposomes. Most (80-90%) of the cholesterol label could be converted by cholesterol oxidase to cholestenone, suggesting plasma membrane localization; only 0.6% of the label was in cholesteryl ester (CE). In cells chased for 6 h in medium lacking LDL, the distribution of label was essentially unchanged, whereas in cells chased with LDL, 28% of the label was incorporated into CE concomitant with a decrease in cholestenone label to 50%. [3H]Cholesterol-labeled mouse peritoneal macrophages incubated with acetyl-LDL, and both J774 and mouse peritoneal macrophages incubated with 25-hydroxy-cholesterol, also showed a shift of label from cholestenone to CE. Similar results were found when cellular cholesterol was biosynthetically labeled with [3H]mevalonate. The percentage of cholesterol substrate for ACAT in LDL-treated J774 macrophages which originates from endogenous cellular pools (versus that originating from LDL itself) is approximately 50%. We conclude that upon activation of ACAT in macrophages, there is a novel process whereby a cholesterol oxidase-accessible pool of cellular cholesterol, presumably plasma membrane cholesterol, is translocated to ACAT in the endoplasmic reticulum.
Clones of Serogroup B Neisseria meningitidis Causing Systemic Disease in the Netherlands, 1958-1986 (1990)

Serogroup B isolates of Neisseria meningitidis recovered from 278 patients with systemic disease in the Netherlands between 1958 and 1986 were analyzed with respect to serotype and multilocus enzyme genotype. Of the isolates, 28% wereserotype 2b and 53% were neither serotypeable nor serosubtypeable. There were 145 distinct multilocus genotypes (electrophoretic types, ETs), with up to 31 isolates belonging to the same ET. Temporal changes in the genotypic composition of meningococcal populations in the Netherlands were demonstrated by the recent occurrence of disease caused by three clone lineages, I, III, and VI, that were not found before 1975. The epidemic of 1966–1967 and the hyperendemic wave of 1972 were caused, in large part, by two closely related but distinct clones of serotype 2b isolates, ET-ll and ET-17, respectively. Deviations in male-to-female ratio and age distribution of patients were observed for disease caused by isolates of individual clone lineages.
Fault management in IP-over-WDM networks: WDM protection versus IP restoration (2002)

We consider an IP-over-WDM network in which network nodes employ optical crossconnects and IP routers. Nodes are connected by fibers to form a mesh topology. Any two IP routers in this network can be connected together by an all-optical wavelength-division multiplexing (WDM) channel, called a lightpath, and the collection of lightpaths that are set up form a virtual topology. In this paper, we concentrate on single fiber failures, since they are the predominant form of failures in optical networks. Since each lightpath is expected to operate at a rate of few gigabits per second, a fiber failure can cause a significant loss of bandwidth and revenue. Thus, the network designer must provide a fault-management technique that combats fiber failures. We consider two fault-management techniques in an IP-over-WDM network: (1) provide protection at the WDM layer (i.e., set up a backup lightpath for every primary lightpath) or (2) provide restoration at the IP layer (i.e., overprovision the network so that after a fiber failure, the network should still be able to carry all the traffic it was carrying before the fiber failure). We formulate these fault-management problems mathematically, develop heuristics to find efficient solutions in typical networks, and analyze their characteristics (e.g., maximum guaranteed network capacity in the event of a fiber failure and the recovery time) relative to each other.
Immunoglobulin G expression in carcinomas and cancer cell lines (2007)

The traditional view that immunoglobulin is produced only by differentiated B lymphocytes has been challenged as immunoglobulin genes have been found to be expressed in nonhematopoietic human cancer cells. However, this phenomenon has not been widely accepted, and knowledge about this newly discovered concept is limited. In this study, we investigated the IgG1 heavy chain (IGHG1) constant region gene and IgG protein expression in 6 cell lines, including epithelial cancer cells, and in tissues from 66 hyperplasias, adenomas, and carcinomas. We also studied the mechanism of IgG production in these cells by examining the expression of RAG1 (recombination activating gene 1), RAG2, and AID (activation-induced cytidine deaminase). In cancer cell lines, mRNA of the IGHG1 constant region and Igamma-Cgamma sterile transcript were detected by nested RT-PCR, and Ig gamma and Ig kappa proteins were detected by immunofluorescence and Western blot. In surgically resected carcinoma tissues, we detected mRNA of the IGHG1 constant region by in situ hybridization, and by laser microdissection-assisted nested RT-PCR. Ig gamma and Ig kappa proteins were detected by immunohistochemistry. The V(D)J recombination of IgH and IgL loci, the Sgamma1/2-Smu switch circle, and the expression of RAG1 and RAG2 were also found in these cancer cell lines. These data suggest that cancer cells are capable of producing IgG. Because of its potential biological and clinical significance, this phenomenon warrants further investigation.
Relation of vascular proliferation to tumor growth. (1976)

Silica formation in a rubber matrix is studied. The hypothesis that the formation proceeds via inverse micelles where the hexylamine present, being a catalyst, also behaves as a surfactant, is made highly plausible. As well-known, the conversion of TEOS into a solid silica particles proceeds via hydrolysis and condensation reactions. These transformations of TEOS comprise consequential substitution of the hydroxyl (-OH) groups with siloxane ones (-OSi), labeled as Q1: one -OSi group; Q2: two -OSi groups; Q3: three -OSi groups; and Q4: four -OSi groups. Here the kinetics of the sol–gel reaction in the rubber matrix was studied as a function of the reaction temperature (40–120 °C) by 1H high-resolution magic-angle spinning (HR-MAS) NMR spectroscopy. Real-time small-angle X-ray scattering (SAXS) measurements of the sol–gel reaction in NR and EPDM rubber matrices were performed in a time scale of 1 s to 60 min with images being acquired every 15 s. The sol–gel reaction in NR and EPDM rubber at 100 °C shows an initial fast increase in particle size that decreases gradually for longer reaction times, eventually reaching a plateau where the particle size does not change anymore. In the NR matrix the initial fast increase in particle size lasts approximately 25 min after which the plateau begins, while for the EPDM the initial phase is approximately 50 min. Moreover quantitative 29Si MAS NMR measurements used for mapping the silicon atoms showed no significant difference in the structure of the silica particles formed after 15 and 60 min reaction time at 100 °C, indicating that a good quality silica with a ratio Q4:Q3 ¿ 2 can be realized in a relatively short reaction time, thereby offering options for future industrial applications such as reactive extrusion processes.