gebhart/patrepeval huggingface dataset:
Ablation of Sphingosine Kinase-2 Inhibits Tumor Cell Proliferation and Migration (2011)

Sphingosine kinases (SK) regulate the balance between proapoptotic ceramides and mitogenic sphingosine-1-phosphate (S1P); however, the functions of the two isoenzymes (SK1 and SK2) in tumor cells are not well defined. Therefore, RNA interference was used to assess the individual roles of SK1 and SK2 in tumor cell sphingolipid metabolism, proliferation, and migration/invasion. Treatment of A498, Caki-1, or MDA-MB-231 cells with siRNAs specific for SK1 or SK2 effectively suppressed the expression of the target mRNA and protein. Ablation of SK1 did not affect mRNA or protein levels of SK2 and reduced intracellular levels of S1P while elevating ceramide levels. In contrast, ablation of SK2 elevated mRNA, protein, and activity levels of SK1 and increased cellular S1P levels. Interestingly, cell proliferation and migration/invasion were suppressed more by SK2-selective ablation than by SK1-selective ablation, showing that the increased S1P does not rescue these phenotypes. Similarly, exogenous S1P did not rescue the cells from the antiproliferative or antimigratory effects of the siRNAs. Consistent with these results, differential effects of SK1- and SK2-selective siRNAs on signaling proteins, including p53, p21, ERK1, ERK2, FAK, and VCAM1, indicate that SK1 and SK2 have only partially overlapping functions in tumor cells. Overall, these data indicate that loss of SK2 has stronger anticancer effects than does suppression of SK1. Consequently, selective inhibitors of SK2 may provide optimal targeting of this pathway in cancer chemotherapy.
Separation and Analysis of Peptides and Proteins (1997)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTSeparation and Analysis of Peptides and ProteinsAndreas F. R. Hühmer, Gabi I. Aced, Melissa D. Perkins, R. Neslihan Gürsoy, D. S. Seetharama Jois, Cynthia Larive, Teruna J. Siahaan, and Christian SchöneichView Author Information Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047 Cite this: Anal. Chem. 1997, 69, 12, 29–58Publication Date (Web):June 15, 1997Publication History Published online15 June 1997Published inissue 1 June 1997https://pubs.acs.org/doi/10.1021/a1970003shttps://doi.org/10.1021/a1970003sreview-articleACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views1460Altmetric-Citations32LEARN 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 SUBJECTS:Chromatography,Mass spectrometry,Monomers,Peptides and proteins,Purification Get e-Alerts
Indian hedgehog signals independently of PTHrP to promote chondrocyte hypertrophy (2008)

Chondrocyte hypertrophy is an essential process required for endochondral bone formation. Proper regulation of chondrocyte hypertrophy is also required in postnatal cartilage homeostasis. Indian hedgehog (Ihh) and PTHrP signaling play crucial roles in regulating the onset of chondrocyte hypertrophy by forming a negative feedback loop, in which Ihh signaling regulates chondrocyte hypertrophy by controlling PTHrP expression. To understand whether there is a PTHrP-independent role of Ihh signaling in regulating chondrocyte hypertrophy, we have both activated and inactivated Ihh signaling in the absence of PTHrP during endochondral skeletal development. We found that upregulating Ihh signaling in the developing cartilage by treating PTHrP(-/-) limb explants with sonic hedgehog (Shh) protein in vitro, or overexpressing Ihh in the cartilage of PTHrP(-/-) embryos or inactivating patched 1 (Ptch1), a negative regulator of hedgehog (Hh) signaling, accelerated chondrocyte hypertrophy in the PTHrP(-/-) embryos. Conversely, when Hh signaling was blocked by cyclopamine or by removing Smoothened (Smo), a positive regulator of Hh signaling, chondrocyte hypertrophy was delayed in the PTHrP(-/-) embryo. Furthermore, we show that upregulated Hh signaling in the postnatal cartilage led to accelerated chondrocyte hypertrophy during secondary ossification, which in turn caused reduction of joint cartilage. Our results revealed a novel role of Ihh signaling in promoting chondrocyte hypertrophy independently of PTHrP, which is particularly important in postnatal cartilage development and homeostasis. In addition, we found that bone morphogenetic protein (Bmp) and Wnt/beta-catenin signaling in the cartilage may both mediate the effect of upregulated Ihh signaling in promoting chondrocyte hypertrophy.
Small circular microstrip antenna with dual-frequencyoperation (1997)

By using a single shorting pin and a single probe feed, the dual-frequency operation of the circular microstrip antenna is demonstrated. This dual-frequency design can result in a much reduced antenna size and provide a tunable frequency ratio of ~2.55 – 3.83 for the two operating frequencies. Typical experimental results are presented.
Mimicking Human Camera Operators (2015)

Filming team sports is challenging because there are many points of interest which are constantly changing. Unlike previous automatic broadcasting solutions, we propose a data-driven approach for determining where a robotic pan-tilt-zoom (PTZ) camera should look. Without using any pre-defined heuristics, we learn the relationship between player locations and corresponding camera configurations by crafting features which can be derived from noisy player tracking data, and employ a new calibration algorithm to estimate the pan-tilt-zoom configuration of a human operated broadcast camera at each video frame. Using this data, we train a regress or to predict the appropriate pan angle for new noisy input tracking data. We demonstrate our system on a high school basketball game. Our experiments show how our data-driven planning approach achieves superior performance to a state-of-the-art algorithm and does indeed mimic a human operator.
Detection of human sapovirus by real‐time reverse transcription‐polymerase chain reaction (2006)

Sapovirus (SaV) is an agent of gastroenteritis for humans and swine, and is divided into five distinct genogroups (GI-GV) based on its capsid gene sequences. Typical methods of SaV detection include electron microscopy (EM), enzyme-linked immunosorbent assay (ELISA), and reverse transcription-polymerase chain reaction (RT-PCR). A novel TaqMan-based real-time RT-PCR assay was developed that is sensitive and has the ability to detect the broad range of genetically diverse human SaV strains. A nucleotide alignment of 10 full-length SaV genome sequences was subjected to similarity plot analysis, which indicated that the most conserved site was the polymerase-capsid junction in open reading frame 1 (ORF1). Based on multiple alignments of the 27 available sequences encoding this junction, we designed sets of primers and TaqMan MGB probes that detect human SaV GI, GII, GIV, and GV sequences in a single tube. The reactivity was confirmed with SaV GI, GII, GIV, and GV control plasmids, and the efficiency ranged from 2.5 x 10(7) to 2.5 x 10(1) copies per tube. Analysis using clinical stool specimens revealed that the present system was capable of detecting SaV GI, GII, GIV, and GV sequences, and no cross-reactivity was observed against other enteric viruses, including norovirus (NoV), rotavirus, astrovirus, and adenovirus. This is the first real-time RT-PCR system that could detect all genogroups of human sapoviruses.
Relative Enzymatic Activity, Protein Stability, and Tissue Distribution of Human Steroid-Metabolizing UGT2B Subfamily Members (2001)

Androgens and estrogens play major roles in cell differentiation, cell growth, and peptide secretion in steroid target tissues.In addition to the binding of these hormones to their receptors, formation and metabolism are important in the action of steroids.Metabolism of the potent steroid hormones includes glucuronidation, a major pathway of steroid elimination in liver and several steroid target tissues.Glucuronidation is catalyzed by UDP-glucuronosyltransferases (UGTs), which transfer the polar moiety from UDP-glucuronic acid to a wide variety of endogenous compounds, including steroid hormones.The UGT superfamily of enzymes is subdivided into two families, UGT1 and UGT2, on the basis of sequence homology.To date, six UGT2B proteins have been isolated, namely UGT2B4, UGT2B7, UGT2B10, UGT2B11, UGT2B15, and UGT2B17, all of which have been demonstrated to be active on steroid molecules, except for UGT2B10 and UGT2B11, for which no substrate was found.The relative activity of these enzymes on steroidal compounds remains unknown due to variable levels of UGT2B expression in different in vitro cell line models and various conditions of the enzymatic assays.Comparison of the glucuronidation rates of these enzymes requires a unique system for UGT2B protein expression, protein normalization, and enzymatic assays.In this study we have stably expressed UGT2B4, UGT2B7, UGT2B15, and UGT2B17 in the HK293 cell line, which is devoid of steroid UGT activity; characterized their kinetic properties relative to
Intracerebral grafting of neuronal cell suspensions. VI. Survival and growth of intrahippocampal implants of septal cell suspensions. (1983)

The survival and growth of intrahippocampal septal suspension grafts were investigated by acetylcholine esterase (AChE) histochemistry in animals with lesions of the intrinsic septohippocampal cholinergic pathways. AChE was demonstrable in the grafts after the first postoperative week, and AChE-positive fibres were seen to extend into the host hippocampus by 3 weeks. Rapid fibre outgrowth occurred between 3 weeks and 3 months after grafting, and continued at a slower rate thereafter. By 6 months a fairly complete reinnervation of the initially denervated hippocampus was achieved in most specimens, and this persisted at 14 months, the longest postoperative time analysed. A comparison between the development of the AChE-positive neurones in the suspension grafts with that seen during ontogeny in situ suggested that the grafted neurones lagged behind normal development by at least 1 week. Similar to our previous observations on septal grafts implanted as solid tissue pieces, the pattern of the newly-formed AChE-positive innervation in the host hippocampal formation, established from the septal suspension grafts, was remarkably similar to that of the normal AChE-positive septal innervation. This pattern became established as soon as the graft-derived fibres first grew in, suggesting that the ingrowing axons extended and ramified preferentially into those hippocampal subfields which normally receive an AChE-positive innervation from the septal-diagonal band area.
Comparison of different miR-21 inhibitor chemistries in a cardiac disease model (2011)

We would like to comment on a recent study that analyzed the role of microRNA-21 (miR-21) in a mouse model of cardiac disease (1). Using miR-21–deficient mice and novel, very short, 8-nucleotide anti–miR-21 oligonucleotides, the authors failed to detect any modulation of pressure overload-induced myocardial hypertrophy and fibrosis and concluded that miR-21 plays no role in cardiac disease. In contrast, we and others reported that inhibition of miR-21 with highly specific, 22- and 15-nucleotide-long anti–miR-21 oligonucleotides effectively inhibits myocardial and pulmonary fibrosis (2, 3). While genetic deletion of a target may lead to compensation during development and is often different from pharmacological inhibition of this target in the adult organism, the discrepancy between the therapeutic trials using long versus short 8-mer oligonucleo­tides is striking. We therefore carried out a direct head-to-head comparison of three different oligonucleotide chemistries (Figure ​(Figure1A)1A) in the same model of pressure overload-induced cardiac hypertrophy (transaortic constriction [TAC]). The two 22-mer oligonucleotides were complementary to the full-length miR-21, while the 8-mer was complementary to nucleotides 2 to 9 of miR-21, locked nucleic acid modified (LNA modified), and identical to the oligonucleotide used in the report by Patrick et al. (Figure ​(Figure1A). 1A). 



Figure 1

Comparison of different miR-21 oligonucleotide inhibitors.
Characterization of the Polypeptide Composition of Human Factor VIII:C and the Nucleotide Sequence and Expression of the Human Kidney cDNA (1985)

Human coagulation factor VIII:C has been purified approximately 5000-fold from commercial preparations with an average activity yield of 35%. Proteins of 92 kD and 77-80 kD enriched during purification are precipitated by a human serum polyclonal antibody which inhibits factor VIII:C activity. Evidence suggests that these polypeptides are linked by a calcium ion bridge. Partial amino acid sequence information from these proteins has been obtained from the intact polypeptides and from products of digestion with thrombin, endoproteinase lysC, or trypsin after citraconylation. An oligonucleotide probe designed from one of the amino acid sequences was used to isolate a partial genomic clone from a human 4X chromosome library in bacteriophage lambda. The genomic segment was used to isolate two cDNA molecules encompassing the entire human kidney factor VIII:C mRNA. Biologically active factor VIII:C has been produced in a mammalian cell line utilizing a complete cDNA construction.
Spatial and temporal diversity in genomic instability processes defines lung cancer evolution (2014)

Spatial and temporal dissection of the genomic changes occurring during the evolution of human non-small cell lung cancer (NSCLC) may help elucidate the basis for its dismal prognosis. We sequenced 25 spatially distinct regions from seven operable NSCLCs and found evidence of branched evolution, with driver mutations arising before and after subclonal diversification. There was pronounced intratumor heterogeneity in copy number alterations, translocations, and mutations associated with APOBEC cytidine deaminase activity. Despite maintained carcinogen exposure, tumors from smokers showed a relative decrease in smoking-related mutations over time, accompanied by an increase in APOBEC-associated mutations. In tumors from former smokers, genome-doubling occurred within a smoking-signature context before subclonal diversification, which suggested that a long period of tumor latency had preceded clinical detection. The regionally separated driver mutations, coupled with the relentless and heterogeneous nature of the genome instability processes, are likely to confound treatment success in NSCLC.
Scalable Data Partitioning Techniques for Parallel Sliding Window Processing over Data Streams (2011)

This paper proposes new techniques for e ciently parallelizing sliding window processing over data streams on a shared-nothing cluster of commodity hardware. Data streams are first partitioned on the fly via a continuous split stage that takes the query semantics into account in a way that respects the natural chunking (windowing) of the stream by the query. The split does not scale well enough when there is high degree of overlap across the windows. To remedy this problem, we propose two alternative partitioning strategies based on batching and pane-based processing, respectively. Lastly, we provide a continuous merge stage at the end that combines the results on the fly while meeting QoS requirements on ordered delivery. We implemented these techniques as part of the Borealis distributed stream processing system, and conducted experiments that show the scalability of our techniques based on the Linear Road Benchmark.
Suppression and acceleration of autoimmune diabetes by neutralization of endogenous interleukin-12 in NOD mice. (2000)

A corpus of evidence suggests that T-helper type 1 (Th1)-dependent cellular immunity plays a pivotal role in the pathogenesis of autoimmune diabetes. This study was intended to find ways to prevent the development of NOD diabetes using a neutralizing anti-interleukin (IL)-12 antibody (C17.8) that inhibits Thl cell differentiation. When C17.8 was administered from 5 to 30 weeks of age, NOD mice exhibited suppression of both insulitis and diabetes. However, when C17.8 administration ceased at 15 weeks of age, 8 of 13 recipients showed diabetes at 30 weeks of age. These results suggest that IL-12 plays an important role not only in the development of effector cells but also in their activation. In contrast, when C17.8 was injected into 2-week-old female NOD mice for 6 consecutive days, all 16 recipients showed diabetes at 30 weeks of age, whereas 12 of 20 control mice became diabetic. This result suggests that depletion of endogenous IL-12 at a young age results in the enhancement of diabetes. Flow cytometric analysis indicated that activated memory T-cells were present in higher numbers after C17.8 treatment. Transfer of spleen cells from 15-week-old C17.8-treated NOD mice to NOD-scid mice resulted in an earlier onset and a higher incidence of diabetes. Furthermore, administration of C17.8 to 2-week-old NOD mice also resulted in a much earlier onset of diabetes. These results suggest that short-term treatment with anti-IL-12 antibody prohibits IL-2 production at a young age, which may influence the expansion and apoptosis of pathogenic T-cells, resulting in the acceleration of autoimmune diabetes.
Proliferation of smooth muscle cells at sites distant from vascular injury. (1990)

This study investigated the phenomenon that injury at one specific site in blood vessels induces cell replication at distant vascular sites. A polyethylene tube was inserted via the common carotid into rat aortic arch, which caused focal endothelial cell loss and formation of platelet thrombi. In a similar fashion, a polyethylene tube was placed into the lower abdominal aorta via a femoral artery. All animals received 3H-thymidine continuously for 2 weeks, after which time segments of the aorta distant from the polyethylene tubing were processed for autoradiography. These sites showed no loss of endothelium or adherent platelets, and yet the smooth muscle and endothelial cell replications were significantly elevated as compared to control aortas. There was no significant change in blood pressure during these experiments and no increase in smooth muscle cell ploidy. When the polyethylene tubing was left in situ for 2 months, no increased replication of the smooth muscle cells was observed during the last 2 weeks of the experiment, and at this time the aorta adjacent to the tubing was completely re-endothelialized. Finally, the mitogenic activity of plasma from these animals was tested in vitro. At the time of a significant increase of in vivo cell replication (2 weeks), the mitogenic activity of the plasma from animals with the indwelling tubing was similar to that of the control animals. In summary, these data show that injury at one discrete arterial site leads to general cell proliferation in the same vessel, and the data would support the possibility that cell communication initiates this response.
Solid State Electronic Devices and Semiconductors and Electronic Devices (1982)

First Page
Use of repetitive sequences and the polymerase chain reaction technique to classify genetically related Bradyrhizobium japonicum serocluster 123 strains (1993)

We have determined that repetitive (repetitive extragenic palindromic [REP] and enterobacterial repetitive intergenic consensus [ERIC]) sequences used in conjunction with the polymerase chain reaction technique (REP and ERIC PCR) provide an effective means of differentiating between and classifying genetically related Bradyrhizobium japonicum serocluster 123 strains. Analysis of REP and ERIC PCR-generated dendrograms indicated that this technique can effectively differentiate between closely related strains which were indistinguishable by using other classification methods. To maximize the genomic differences detected by REP and ERIC PCR fingerprint patterns, the REP and the ERIC data sets were combined for statistical analyses. REP-plus-ERIC PCR fingerprints were also found to provide a method to differentiate between highly diverse strains of Bradyrhizobium spp., but they did not provide an effective means for classifying these strains because of the relatively low number of REP and ERIC consensus sequences found in some of the bradyrhizobia. Our results also suggest that there is a relationship between nodulation phenotypes and the distribution of REP and ERIC consensus sequences within the genomes of B. japonicum serogroup 123 and 127 strains. Results obtained by restriction fragment length polymorphism hybridization analyses were correlated with the phylogenetic classification of B. japonicum serocluster 123 strains obtained by using REP and ERIC PCR.
Changes in interferon receptors on peripheral blood mononuclear cells from patients with chronic hepatitis B being treated with interferon (1990)

We studied the binding of 125I-labeled human interferon-alpha to peripheral blood mononuclear cells and the activity of 2',5'-oligoadenylate synthetase in peripheral blood mononuclear cells obtained from 21 patients with chronic hepatitis B who were treated with human interferon-alpha or interferon-beta. Fourteen patients were given interferon daily for 4 wk. Interferon receptors per cell decreased to about 50% of baseline but increased to baseline by 2 wk after therapy ended. The activity of 2',5'-oligoadenylate synthetase rose about fivefold during therapy, decreasing to baseline by 1 wk after the end of therapy. The seven other patients were given interferon daily for 2 wk, no interferon for 2 wk and then interferon daily for 2 wk more. During both periods of therapy on this schedule, interferon receptors decreased to about 50% but returned to baseline 1 wk after the interferon was stopped. The activity of 2',5'-oligoadenylate synthetase increased about fivefold during both the first and second periods of therapy and decreased to baseline 1 wk after interferon was stopped. Close negative correlation existed between the number of interferon receptors and the 2',5'-oligoadenylate synthetase activity. The results of interferon therapy could not be predicted by either the numbers of interferon receptors before therapy or by the decrease in this number during therapy.
ChemInform Abstract: SYNTHESIS OF SOME BENZOXAZIN‐4‐ONES, QUINAZOLIN‐4‐ONES AND THE RELATED PRODUCTS (1975)

Abstract Durch Kondensation von 2‐Methyl‐3,1‐benzoxazinon‐(4) mit Aldehyden wurden Styrolderivate, wie z.B. (I), und analog bzw. nach schon beschriebenen Verfahren Chinazolinone, wie (III), dargestellt.