gebhart/patrepeval huggingface dataset:
A Farnesyltransferase Inhibitor Induces Tumor Regression in Transgenic Mice Harboring Multiple Oncogenic Mutations by Mediating Alterations in Both Cell Cycle Control and Apoptosis (1998)

The farnesyltransferase inhibitor L-744,832 selectively blocks the transformed phenotype of cultured cells expressing a mutated H-ras gene and induces dramatic regression of mammary and salivary carcinomas in mouse mammary tumor virus (MMTV)-v-Ha-ras transgenic mice. To better understand how the farnesyltransferase inhibitors might be used in the treatment of human tumors, we have further explored the mechanisms by which L-744,832 induces tumor regression in a variety of transgenic mouse tumor models. We assessed whether L-744,832 induces apoptosis or alterations in cell cycle distribution and found that the tumor regression in MMTV-v-Ha-ras mice could be attributed entirely to elevation of apoptosis levels. In contrast, treatment with doxorubicin, which induces apoptosis in many tumor types, had a minimal effect on apoptosis in these tumors and resulted in a less dramatic tumor response. To determine whether functional p53 is required for L-744,832-induced apoptosis and the resultant tumor regression, MMTV-v-Ha-ras mice were interbred with p53(-/-) mice. Tumors in ras/p53(-/-) mice treated with L-744,832 regressed as efficiently as MMTV-v-Ha-ras tumors, although this response was found to be mediated by both the induction of apoptosis and an increase in G1 with a corresponding decrease in the S-phase fraction. MMTV-v-Ha-ras mice were also interbred with MMTV-c-myc mice to determine whether ras/myc tumors, which possess high levels of spontaneous apoptosis, have the potential to regress through a further increase in apoptosis levels. The ras/myc tumors were found to respond nearly as efficiently to L-744,832 treatment as the MMTV-v-Ha-ras tumors, although no induction of apoptosis was observed. Rather, the tumor regression in the ras/myc mice was found to be mediated by a large reduction in the S-phase fraction. In contrast, treatment of transgenic mice harboring an activated MMTV-c-neu gene did not result in tumor regression. These results demonstrate that a farnesyltransferase inhibitor can induce regression of v-Ha-ras-bearing tumors by multiple mechanisms, including the activation of a suppressed apoptotic pathway, which is largely p53 independent, or by cell cycle alterations, depending upon the presence of various other oncogenic genetic alterations.
The Speech-Language Interface in the Spoken Language Translator (1994)

The Spoken Language Translator is a prototype for practically useful systems capable of translating continuous spoken language within restricted domains. The prototype system translates air travel (ATIS) queries from spoken English to spoken Swedish and to French. It is constructed, with as few modifications as possible, from existing pieces of speech and language processing software. The speech recognizer and language understander are connected by a fairly conventional pipelined N-best interface. This paper focuses on the ways in which the language processor makes intelligent use of the sentence hypotheses delivered by the recognizer. These ways include (1) producing modified hypotheses to reflect the possible presence of repairs in the uttered word sequence; (2) fast parsing with a version of the grammar automatically specialized to the more frequent constructions in the training corpus; and (3) allowing syntactic and semantic factors to interact with acoustic ones in the choice of a meaning structure for translation, so that the acoustically preferred hypothesis is not always selected even if it is within linguistic coverage.
A novel design of targeted endocrine and cytokine therapy for breast cancer. (2002)

The aim of this study is to combine endocrine therapy [human prolactin (hPRL) antagonist, G129R] and immune therapy [interleukin 2 (IL2)] in the design of a fusion protein, G129R-IL2, to treat human breast cancer. This novel approach uses the specific interaction between the G129R and hPRL receptors (PRLRs), thus directly targeting the fusion protein to the malignant breast tissues that have previously been shown to contain high levels of PRLR. The localized bifunctional fusion protein is designed to block signal transduction induced by hPRL as well as to activate T lymphocytes near the tumor site. A bacterial expression system was used to produce G129R-IL2 fusion protein that maintained both G129R and IL2 activities as demonstrated by cell-based assays such as signal transducer(s) and activator(s) of transcription (STAT)5 phosphorylation, breast cancer cell proliferation, and T-cell proliferation. The antitumor activities of G129R-IL2 were demonstrated in vivo using a syngeneic model system with BALB/c mice and EMT6-hPRLR breast cancer cells. After daily injection (i.p.) of G129R-IL2 (100 microg/mouse) for 18 days, the tumor growth in the G129R-IL2-treated group was only one-third the size as compared with that of the control group. The growth rate in the G129R-IL2-treated group is also significantly slower than that of the group treated with G129R alone (200 microg/mouse/day). We hope that this novel bifunctional protein will contribute significantly to human breast cancer therapy.
Action of Some Steroids on the Central Nervous System of the Mouse. I. Synthetic Methods (1965)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAction of Some Steroids on the Central Nervous System of the Mouse. I. Synthetic MethodsJ. D. Cocker, J. Elks, P. J. May, F. A. Nice, G. H. Phillipps, and W. F. WallCite this: J. Med. Chem. 1965, 8, 4, 417–425Publication Date (Print):July 1, 1965Publication History Published online1 May 2002Published inissue 1 July 1965https://pubs.acs.org/doi/10.1021/jm00328a003https://doi.org/10.1021/jm00328a003research-articleACS PublicationsRequest reuse permissionsArticle Views228Altmetric-Citations14LEARN 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
Mapping of neutralization epitopes on infectious pancreatic necrosis viruses (1995)

We have characterized and mapped variable and conserved neutralization epitopes of serogroup A strains of aquatic birnaviruses. Epitope mapping using monoclonal antibodies (MAbs) and Escherichia coli-expressed deletion fragments of VP2 of the N1 strain of infectious pancreatic necrosis virus (IPNV) demonstrated that two variable epitopes, H8 and B9, depend on the variable region between amino acid 204-330. A conserved neutralization epitope, F2, was shown to depend on the same region as epitopes H8 and B9 but was additionally dependent on amino acids between 153-203. The neutralization epitopes H8, B9 and F2 were also shown to overlap by a competitive binding assay. One conserved neutralization epitope, AS-1, was not exposed on any of the recombinant VP2 deletion fragments and was therefore not possible to map. However, the MAbs AS1 and F2 were partly competitive indicating that these epitopes are overlapping. All neutralization epitopes were independent of a conserved non-neutralization epitope, E4. Our results demonstrate that the central third of VP2 contains several partly overlapping neutralization epitopes, both variable and conserved among serogroup A strains of IPNV.
Multiple approaches to data‐mining of proteomic data based on statistical and pattern classification methods (2003)

The data-mining challenge presented is composed of two fundamental problems. Problem one is the separation of forty-one subjects into two classifications based on the data produced by the mass spectrometry of protein samples from each subject. Problem two is to find the specific differences between protein expression data of two sets of subjects. In each problem, one group of subjects has a disease, while the other group is nondiseased. Each problem was approached with the intent to introduce a new and potentially useful tool to analyze protein expression from mass spectrometry data. A variety of methodologies, both conventional and nonconventional were used in the analysis of these problems. The results presented show both overlap and discrepancies. What is important is the breadth of the techniques and the future direction this analysis will create.
Crystallization behavior of glucomannan (1982)

Abstract Five different glucomannan samples were recrystallized from dilute solution. Depending on the experimental conditions, the crystals obtained could be identified as corresponding to the mannan I (anhydrous precipitate of more or less regular lozenge‐shaped crystals) or mannan II (hydrated gel‐forming pseudo‐fibrillar precipitate). High‐molecular‐weight material, low temperature of crystallization, or a polar crystallization medium favored the mannan II polymorph, whereas a low‐molecular weight, a high temperature of crystallization, and a crystallization medium of low polarity yielded the mannan I polymorph. Since the base‐plane unit‐cell dimensions are fairly constant with respect to variation of glucose, it is likely that isomorphous replacement of mannose by glucose occurs in glucomannan crystallization; the data also indicate that perfection of the glucomannan crystals was reduced in specimens having a high glucose:mannose ratio. The oriented crystallization of glucomannan on cellulose microfibrils was also studied under conditions where the mannan I polymorph was obtained. This gave shish‐kebab structures that were characterized.
Physiological increments in epinephrine stimulate metabolic rate in humans (1987)

Markedly elevated plasma epinephrine is known to increase metabolic rate (MR), but such levels of epinephrine are encountered infrequently in normal free-living subjects. We studied whether epinephrine levels common in usual daily activities can affect MR and thus possibly regulate caloric expenditure. To aid definition of a MR threshold, we first measured the hourly and daily variation in MR within individuals by measuring the MR of four individuals by indirect calorimetry for 6 h on six separate occasions without any intervention. We found that hour-to-hour variation (2.0 +/- 0.9%) and the day-to-day variation (2.7 +/- 0.9%) were low, thus allowing confident detection of small increments in metabolic rate during epinephrine infusion. To define a threshold for epinephrine's effect to increase MR, we studied five normal-weight postabsorptive young men on four separate occasions. During the 1st h of each 5-h study period, saline was infused intravenously. Then, during the subsequent 4 h, subjects received intravenous infusion of saline or epinephrine at 0.1, 0.5, and 1.0 microgram/min (randomized). A significant increase in MR (3.6 +/- 1.0% SE) was measured with the lowest epinephrine infusion rate (venous plasma concentration, 94 +/- 32 pg/ml). The increases in MR correlated (r = 0.85, P less than 0.001) with increases in plasma epinephrine. The threshold concentration (upper 95% confidence limit) of epinephrine to affect MR was 90 pg/ml, a concentration frequently occurring in daily life. Thus epinephrine may play an important role in weight maintenance by affecting energy expenditure.
Immunologic and Clinical Outcomes of a Randomized Phase II Trial of Two Multipeptide Vaccines for Melanoma in the Adjuvant Setting (2007)

These data support continued investigation of complex multipeptide vaccines for melanoma.
Kaposi's sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells (2005)

MicroRNAs (miRNAs) are an endogenously encoded class of small RNAs that have been proposed to function as key posttranscriptional regulators of gene expression in a range of eukaryotic species, including humans. The small size of miRNA precursors makes them potentially ideal for use by viruses as inhibitors of host cell defense pathways. Here, we demonstrate that the pathogenic human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) encodes an array of 11 distinct miRNAs, all of which are expressed at readily detectable levels in latently KSHV infected cells. Individual KSHV miRNAs were expressed at up to 2,200 copies per cell. The KSHV miRNAs are expressed from what appears to be a single genetic locus that largely coincides with an approximately 4-kb noncoding sequence located between the KSHV v-cyclin and K12/Kaposin genes, both of which are also expressed in latently infected cells. Computer analysis of potential mRNA targets for these viral miRNAs identified a number of interesting candidate genes, including several mRNAs previously shown to be down-regulated in KSHV-infected cells. We hypothesize that these viral miRNAs play a critical role in the establishment and/or maintenance of KSHV latent infection in vivo and, hence, in KSHV-induced oncogenesis.
Cytidinediphosphocholine (CDP-choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly (2005)

There was some evidence that CDP-choline has a positive effect on memory and behaviour in at least the short to medium term. The evidence of benefit from global impression was stronger, but is still limited by the duration of the studies. Further research with CDP-choline should focus on longer term studies in subjects who have been diagnosed with currently accepted standardised criteria, especially Vascular Mild Cognitive Impairment (VaMCI) or vascular dementia.
A cell‐based Dkk1 binding assay reveals roles for extracellular domains of LRP5 in Dkk1 interaction and highlights differences between wild‐type and the high bone mass mutant LRP5(G171V) (2009)

Dkk1 is a secreted antagonist of the LRP5-mediated Wnt signaling pathway that plays a pivotal role in bone biology. Because there are no well-documented LRP5-based assays of Dkk1 binding, we developed a cell-based assay of Dkk1/LRP5 binding using radioactive (125)I-Dkk1. In contrast to LRP6, transfection of LRP5 alone into 293A cells resulted in a low level of specific binding that was unsuitable for routine assay. However, co-transfection of LRP5 with the chaperone protein MesD (which itself does not bind Dkk1) or Kremen-2 (a known Dkk1 receptor), or both, resulted in a marked enhancement of specific binding that was sufficient for evaluation of Dkk1 antagonists. LRP5 fragments comprising the third and fourth beta-propellers plus the ligand binding domain, or the first beta-propeller, each inhibited Dkk1 binding, with mean IC(50)s of 10 and 196 nM, respectively. The extracellular domain of Kremen-2 ("soluble Kremen") was a weaker antagonist (mean IC(50) 806 nM). We also found that cells transfected with a high bone mass mutation LRP5(G171V) had a subtly reduced level of Dkk1 binding, compared to wild type LRP5-transfected cells, and no enhancement of binding by MesD. We conclude that (1) LRP5-transfected cells do not offer a suitable cell-based Dkk1 binding assay, unless co-transfected with either MesD, Kremen-2, or both; (2) soluble fragments of LRP5 containing either the third and fourth beta-propellers plus the ligand binding domain, or the first beta-propeller, antagonize Dkk1 binding; and (3) a high bone mass mutant LRP5(G171V), has subtly reduced Dkk1 binding, and, in contrast to LRP5, no enhancement of binding with MesD.
The Importance of the Time Interval Between Insulin Injection and Breakfast in Determining Postprandial Glycaemic Control—A Comparison Between Human and Porcine Insulin (1988)

This study assessed the effect of the time interval between insulin injection and breakfast in determining subsequent postprandial glycaemic control and also whether this differed between highly purified porcine insulin and human insulin (crb) in six diabetic patients (age range 24-36 years, duration of diabetes greater than 10 years) usually treated with twice daily Actrapid MC and Monotard MC and with stable insulin requirements and diabetic control. On separate mornings each patient was given, after an overnight fast, their usual dose of either Actrapid MC and Monotard MC or Humulin S and Humulin Zn injected 5, 20, or 40 min before a standard breakfast. The postprandial glycaemic profile was not significantly different at any of the three time intervals with Actrapid MC and Monotard MC. However, with the human insulin the profile was significantly better at the 40 min interval than at the 5 min interval (p less than 0.05) and this was also better than any of the profiles with the porcine insulin, there being a significant difference between the two types of insulin (p less than 0.05). These findings suggest that the time interval between insulin injection and breakfast may be more important with human insulin than with porcine insulin.
Scoping Review of the Zika Virus Literature (2016)

The global primary literature on Zika virus (ZIKV) (n = 233 studies and reports, up to March 1, 2016) has been compiled using a scoping review methodology to systematically identify and characterise the literature underpinning this broad topic using methods that are documented, updateable and reproducible. Our results indicate that more than half the primary literature on ZIKV has been published since 2011. The articles mainly covered three topic categories: epidemiology of ZIKV (surveillance and outbreak investigations) 56.6% (132/233), pathogenesis of ZIKV (case symptoms/ outcomes and diagnosis) 38.2% (89/233) and ZIKV studies (molecular characterisation and in vitro evaluation of the virus) 18.5% (43/233). There has been little reported in the primary literature on ZIKV vectors (12/233), surveillance for ZIKV (13/233), diagnostic tests (12/233) and transmission (10/233). Three papers reported on ZIKV prevention/control strategies, one investigated knowledge and attitudes of health professionals and two vector mapping studies were reported. The majority of studies used observational study designs, 89.7% (209/233), of which 62/233 were case studies or case series, while fewer (24/233) used experimental study designs. Several knowledge gaps were identified by this review with respect to ZIKV epidemiology, the importance of potential non-human primates and other hosts in the transmission cycle, the burden of disease in humans, and complications related to human infection with ZIKV. Historically there has been little research on ZIKV; however, given its current spread through Australasia and the Americas, research resources are now being allocated to close many of the knowledge gaps identified in this scoping review. Future updates of this project will probably demonstrate enhanced evidence and understanding of ZIKV and its impact on public health.
Anomaly detection (2009)

Anomaly detection is an important problem that has been researched within diverse research areas and application domains. Many anomaly detection techniques have been specifically developed for certain application domains, while others are more generic. This survey tries to provide a structured and comprehensive overview of the research on anomaly detection. We have grouped existing techniques into different categories based on the underlying approach adopted by each technique. For each category we have identified key assumptions, which are used by the techniques to differentiate between normal and anomalous behavior. When applying a given technique to a particular domain, these assumptions can be used as guidelines to assess the effectiveness of the technique in that domain. For each category, we provide a basic anomaly detection technique, and then show how the different existing techniques in that category are variants of the basic technique. This template provides an easier and more succinct understanding of the techniques belonging to each category. Further, for each category, we identify the advantages and disadvantages of the techniques in that category. We also provide a discussion on the computational complexity of the techniques since it is an important issue in real application domains. We hope that this survey will provide a better understanding of the different directions in which research has been done on this topic, and how techniques developed in one area can be applied in domains for which they were not intended to begin with.
Androgen-stimulated DNA synthesis and cytoskeletal changes in fibroblasts by a nontranscriptional receptor action (2003)

In NIH3T3 cells, 0.001 nM of the synthetic androgen R1881 induces and stimulates association of androgen receptor (AR) with Src and phosphatidylinositol 3-kinase (Pl3-kinase), respectively, thereby triggering S-phase entry. 10 nM R1881 stimulates Rac activity and membrane ruffling in the absence of the receptor-Src-PI3-kinase complex assembly. The antiandrogen Casodex and specific inhibitors of Src and PI3-kinase prevent both hormonal effects, DNA synthesis and cytoskeletal changes. Neither low nor high R1881 concentration allows receptor nuclear translocation and receptor-dependent transcriptional activity in fibroblasts, although they harbor the classical murine AR. The very low amount of AR in NIH3T3 cells (7% of that present in LNCaP cells) activates the signaling pathways, but apparently is not sufficient to stimulate gene transcription. This view is supported by the appearance of receptor nuclear translocation as well as receptor-mediated transcriptional activity after overexpression of AR in fibroblasts. In addition, AR-negative Cos cells transiently transfected with a very low amount of hAR cDNA respond to low and high R1881 concentrations with signaling activation. Interestingly, they do not show significant transcriptional activation under the same experimental conditions. Fibroblasts are the first example of cells that respond to steroid hormones with activation of signaling pathways in the absence of endogenous receptor transcriptional activity. The data reported also show that hormone concentration can be crucial in determining the type of cell responsiveness.
Therapeutic Radiopharmaceuticals Targeting Integrin αvβ6 (2018)

The epithelial integrin αvβ6 is expressed by many malignant carcinoma cell types, including pancreatic cancer, and thus represents a promising target for radionuclide therapy. The peptide cyclo(FRGDLAFp(<i>N</i>Me)K) was decorated with different chelators (DOTPI, DOTAGA, and DOTA). The Lu(III) complexes of these conjugates exhibited comparable αvβ6 integrin affinities (IC<sub>50</sub> ranging from 0.3 to 0.8 nM) and good selectivities against other integrins (IC<sub>50</sub> for αvβ8 >43 nM; for α5β1 >238 nM; and for αvβ3, αvβ5, and αIIbβ3 >1000 nM). Although different formal charges of the Lu(III) chelates (ranging from 0 to 4) resulted in strongly varying degrees of hydrophilicity (log <i>D</i> ranging from -3.0 to -4.1), biodistributions in murine H2009 xenografts of the Lu-177-labeled compounds (except the DOTPI derivative) were quite similar and comparable to our previously reported αvβ6 integrin positron emission tomography tracer Ga-68-avebehexin. Hence, combinations of existing Ga-68- and Lu-177-labeled c(FRGDLAFp(<i>N</i>Me)K) derivatives could be utilized for αvβ6 integrin-targeted theranostics, whereas our data nonetheless suggest that further improvement of pharmacokinetics might be necessary to ensure clinical success.