gebhart/patrepeval huggingface dataset:
Insulin-degrading Enzyme Modulates the Natriuretic Peptide-mediated Signaling Response (2010)

Natriuretic peptides (NPs) are cyclic vasoactive peptide hormones with high therapeutic potential. Three distinct NPs (ANP, BNP, and CNP) can selectively activate natriuretic peptide receptors, NPR-A and NPR-B, raising the cyclic GMP (cGMP) levels. Insulin-degrading enzyme (IDE) was found to rapidly cleave ANP, but the functional consequences of such cleavages in the cellular environment and the molecular mechanism of recognition and cleavage remain unknown. Here, we show that reducing expression levels of IDE profoundly alters the response of NPR-A and NPR-B to the stimulation of ANP, BNP, and CNP in cultured cells. IDE rapidly cleaves ANP and CNP, thus inactivating their ability to raise intracellular cGMP. Conversely, reduced IDE expression enhances the stimulation of NPR-A and NPR-B by ANP and CNP, respectively. Instead of proteolytic inactivation, IDE cleavage can lead to hyperactivation of BNP toward NPR-A. Conversely, decreasing IDE expression reduces BNP-mediated signaling. Additionally, the cleavages of ANP and BNP by IDE render them active with NPR-B and a reduction of IDE expression diminishes the ability of ANP and BNP to stimulate NPR-B. Our kinetic and crystallographic analyses offer the molecular basis for the selective degradation of NPs and their variants by IDE. Furthermore, our studies reveal how IDE utilizes its catalytic chamber and exosite to engulf and bind up to two NPs leading to biased stochastic, non-sequential cleavages and the ability of IDE to switch its substrate selectivity. Thus, the evolutionarily conserved IDE may play a key role in modulating and reshaping the strength and duration of NP-mediated signaling.
Detection of viral DNA and RNA by in situ hybridization. (1986)

Using cloned restriction endonuclease fragments of Herpes simplex virus (HSV), human papillomavirus (HPV), and cytomegalovirus (CMV) DNA as probes, viral DNA and RNA sequences have been detected in human tissues. The probes were labeled either with a radioactive isotope, for subsequent detection by autoradiography, or with biotin. This latter technique has been successfully used to visualize HPV DNA in tissues that have been fixed in formalin and embedded in paraffin, and is therefore of value in retrospective studies of histological specimens. HPV DNA was detected under non-stringent conditions (Tm = -42 degrees C) with heterologous probes in plantar and common warts, laryngeal papillomas, and anogenital condylomas. The specific type of HPV was established using stringent hybridization conditions (Tm = - 17 degrees C). Results from these and from malignant tissues show the distribution and localization of HSV and HPV RNA and DNA sequences in malignancies of squamous cell origin in the anogenital region. Both HSV and HPV DNA sequences have occasionally been detected in the same tumor, providing a further impetus to test the hypothesis that an initiator-promoter relationship might involve these common human viruses in the development of some tumors.
Interaction of IL-2Rβ and γ c Chains with Jak1 and Jak3: Implications for XSCID and XCID (1994)

Interleukin-2 (IL-2) signaling requires the dimerization of the IL-2 receptor beta.(IL-2R beta) and common gamma (gamma c) chains. Mutations of gamma c can result in X-linked severe combined immunodeficiency (XSCID). IL-2, IL-4, IL-7 (whose receptors are known to contain gamma c), and IL-9 (whose receptor is shown here to contain gamma c) induced the tyrosine phosphorylation and activation of the Janus family tyrosine kinases Jak1 and Jak3. Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively; IL-2 induced Jak3-IL-2R beta and increased Jak3-gamma c associations. Truncations of gamma c, and a gamma c, point mutation causing moderate X-linked combined immunodeficiency (XCID), decreased gamma c-Jak3 association. Thus, gamma c mutations in at least some XSCID and XCID patients prevent normal Jak3 activation, suggesting that mutations of Jak3 may result in an XSCID-like phenotype.
Safety of an Intravitreal Injection of Triamcinolone (2004)

Despite a significant adverse event profile, intravitreal triamcinolone is generally well tolerated by the human eye as long as patients are carefully followed up by their surgeon and treated appropriately, when necessary.
A point mutation in the alpha-actinin-4 gene generates an antigenic peptide recognized by autologous cytolytic T lymphocytes on a human lung carcinoma. (2001)

We have identified an antigen recognized on a human large cell carcinoma by an autologous tumor-specific CTL clone that was derived from mononuclear cells infiltrating the primary tumor. The antigenic peptide is presented by HLA-A2 molecules and is encoded by the alpha-actinin-4 gene, which is expressed ubiquitously. In the tumor cells, a point mutation generates an amino-acid change that is essential for recognition by the CTLS: The mutation was not found in alpha-actinin-4 cDNA sequences from about 50 lung carcinoma cell lines, suggesting that it is unique to this patient. Although he did not receive chemotherapy or radiotherapy, the patient has been without evidence of tumor since the resection of the primary lesion in 1996. Using tetramers of soluble HLA-A2 molecules loaded with the mutated antigenic peptide, anti-alpha-actinin-4 CTLs could be derived from blood samples collected from the patient in 1998 and 2000. It is possible that these CTLs, recognizing a truly tumor-specific antigen, play a role in the clinical evolution of this lung cancer patient.
A reduced-complexity PTS scheme for peak-to-average power ratio reduction in OFDM systems (2008)

In this paper a reduced-complexity partial transmit sequences (PTS) approach is proposed for the reduction of peak-to-average power ratio (PAPR) in OFDM systems. In the PTS scheme, we need several IFFTs (inverse fast Fourier transforms) to compute the partial transmit sequences. There are two main contributions in the paper. Firstly, we propose to partition the input symbols into disjoint subblocks in an interleaving manner. In this way, we can significantly reduce the complexity by sharing the arithmetic in the IFFT computations. Secondly, we show that in the new partition scheme, the number of rotation factors can be reduced by one without affecting the PAPR reduction ability. As a result, the search time for the optimal rotation factor can be reduced by 75%. Simulation results show that the PAPR of the proposed method is only slightly worse than the original PTS scheme but it has a much lower complexity.
Vision-based state estimation for autonomous rotorcraft MAVs in complex environments (2013)

In this paper, we consider the development of a rotorcraft micro aerial vehicle (MAV) system capable of vision-based state estimation in complex environments. We pursue a systems solution for the hardware and software to enable autonomous flight with a small rotorcraft in complex indoor and outdoor environments using only onboard vision and inertial sensors. As rotorcrafts frequently operate in hover or nearhover conditions, we propose a vision-based state estimation approach that does not drift when the vehicle remains stationary. The vision-based estimation approach combines the advantages of monocular vision (range, faster processing) with that of stereo vision (availability of scale and depth information), while overcoming several disadvantages of both. Specifically, our system relies on fisheye camera images at 25 Hz and imagery from a second camera at a much lower frequency for metric scale initialization and failure recovery. This estimate is fused with IMU information to yield state estimates at 100 Hz for feedback control. We show indoor experimental results with performance benchmarking and illustrate the autonomous operation of the system in challenging indoor and outdoor environments.
Benzodiazepine gastrin and brain cholecystokinin receptor ligands; L-365,260 (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBenzodiazepine gastrin and brain cholecystokinin receptor ligands; L-365,260Mark G. Bock, Robert M. DiPardo, Ben E. Evans, Kenneth E. Rittle, Willie L. Whitter, Daniel F. Veber, Paul S. Anderson, and Roger M. FreidingerCite this: J. Med. Chem. 1989, 32, 1, 13–16Publication Date (Print):January 1, 1989Publication History Published online1 May 2002Published inissue 1 January 1989https://pubs.acs.org/doi/10.1021/jm00121a004https://doi.org/10.1021/jm00121a004research-articleACS PublicationsRequest reuse permissionsArticle Views306Altmetric-Citations295LEARN 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
Protein tyrosine phosphatase 1B undergoes mitosis-specific phosphorylation on serine. (1993)

We have investigated the regulation of protein tyrosine phosphatase 1B (PTP1B) through the cell cycle of HeLa cells. PTP1B from HeLa cells arrested in mitosis migrated more slowly during sodium dodecyl sulfate-polyacrylamide gel electrophoresis than did PTP1B from unsynchronized HeLa cells. To explore whether this mobility shift was caused by phosphorylation, PTP1B was immunoprecipitated from 32Pi-labeled unsynchronized and mitotic HeLa cells. PTP1B from mitotic cells incorporated significantly more 32Pi than did PTP1B from unsynchronized cells. Alkaline phosphatase treatment of mitotic HeLa cell lysates resulted in the conversion of PTP1B to its more rapidly migrating form, confirming that the mobility shift was a result of the mitotic phosphorylation. Phosphoamino acid analysis of PTP1B from mitotic cells revealed that PTP1B became phosphorylated on serine. Dephosphorylation of PTP1B occurred following the release of cells from nocodazole synchronization and was independent of new protein synthesis. This dephosphorylation was inhibited by okadaic acid, a potent inhibitor of types 1 and 2A serine/threonine phosphatases. The mitotic phosphorylation had no apparent effect on the activity of PTP1B as measured in in vitro phosphatase assays using 32P-labeled Raytide as substrate. p34cdc2 appears not to be the mitotic PTP1B kinase, as mapping experiments showed that this enzyme phosphorylated PTP1B on a site different from that on which it was phosphorylated in vivo. These observations suggest that PTP1B may be differentially regulated through the cell cycle.
BAITS FOR AGGREGATING LARGE NUMBERS OF SUBTERRANEAN TERMITES (1981)

Abstract Artificial baits consisting of wetted toilet rolls packed in steel drums with detachable lids, and with several small holes in the base of each drum to allow the entry of subterranean termites, were buried to about a quarter of their depth in the soil. These baits proved effective in attracting large numbers of non‐mound building termites in the area, namely Heterotermes ferox (Froggatt), Coptotermes frenchi Hill and C. acinaciformis (Froggatt) (Isoptera: Rhinotermitidae).
Regulation of iron metabolism through GDF15 and hepcidin in pyruvate kinase deficiency (2008)

Iron absorption is inadequately increased in patients with chronic haemolytic anaemia, which is commonly complicated by iron overload. Growth differentiation factor 15 (GDF15) has been identified as a bone marrow-derived factor that abrogates hepcidin-mediated protection from iron overload under conditions of increased erythropoiesis. Increased concentrations of GDF15 have been reported in beta-thalassaemia patients and GDF15 has been found to suppress hepcidin expression in vitro. To further study the interdependencies of iron metabolism and erythropoiesis in vivo, the concentrations of hepcidin and GDF15 were determined in sera from 22 patients with pyruvate kinase deficiency (PKD) and 21 healthy control subjects. In PKD patients, serum hepcidin levels were 13-fold lower than in controls (2.0 ng/ml vs. 26.2 ng/ml) and GDF15 was significantly higher (859 pg/ml vs. 528 pg/ml). Serum hepcidin concentrations correlated positively with haemoglobin and negatively with serum GDF15. These results suggest that GDF15 contributes to low hepcidin expression and iron loading in PKD.
Two Potent Nuclear Localization Signals in the Gut-enriched Krüppel-like Factor Define a Subfamily of Closely Related Krüppel Proteins (1997)

The gut-enriched Krüppel-like factor (GKLF) is a newly identified transcription factor that contains three C2H2 Krüppel-type zinc fingers. Previous immunocytochemical studies indicate that GKLF is exclusively localized to the nucleus. To identify the nuclear localization signal (NLS) within GKLF, cDNA constructs with various deletions in the coding region of GKLF were generated and analyzed by indirect immunofluorescence in transfected COS-1 cells. In addition, constructs fusing regions representing putative NLSs of GKLF to green fluorescent protein (GFP) were generated and examined by fluorescence microscopy in similarly transfected cells. The results indicate that GKLF contains two potent, independent NLSs: one within the zinc fingers and the other in a cluster of basic amino acids (called 5' basic region) immediately preceding the first zinc finger. In comparison, putative NLSs within the zinc fingers and the 5' basic region of a related Krüppel protein, zif268/Egr-1, are relatively less efficient in their ability to translocate GFP into the nucleus. A search in the protein sequence data base revealed that despite the existence of numerous Krüppel proteins, only two, the lung Krüppel-like factor (LKLF) and the erythroid Krüppel-like factor (EKLF), exhibit similar NLSs to those of GKLF. These findings indicate that GKLF, LKLF, and EKLF are members of a subfamily of closely related Krüppel proteins.
Role of cdk4, p16<sup>INK4</sup>, and Rb Expression in the Prognosis of Bronchioloalveolar Carcinomas (2005)

The results suggest a role of the cdk4/p16(INK4) pathway in the prognosis of BACs. Further studies are warranted to clarify whether a low p16(INK4)/cdk4 ratio may identify tumors that are destined to behave unfavorably.
WW6: an embryonic stem cell line with an inert genetic marker that can be traced in chimeras. (1995)

Mutant mice produced by gene targeting in embryonic stem (ES) cells often have a complex or embryonic lethal phenotype. In these cases, it would be helpful to identify tissues and cell types first affected in mutant embryos by following the contribution to chimeras of ES cells homozygous for the mutant allele. Although a number of strategies for following ES cell development in vivo have been reported, each has limitations that preclude its general application. In this paper, we describe ES cell lines that can be tracked to every nucleated cell type in chimeras at all developmental stages. These lines were derived from blastocysts of mice that carry an 11-Mb beta-globin transgene on chromosome 3. The transgene is readily detected by DNA in situ hybridization, providing an inert, nuclear-localized marker whose presence is not affected by transcriptional or translational controls. The "WW" series of ES lines possess the essential features of previously described ES lines, including giving rise to a preponderance of male chimeras, all of which have to date exhibited germ-line transmission. In addition, clones selected for single or double targeting events form strong chimeras, demonstrating the feasibility of using WW6 cells to identify phenotypes associated with the creation of a null mutant.
Compartmentalization of algal bioluminescence: autofluorescence of bioluminescent particles in the dinoflagellate Gonyaulax as studied with image-intensified video microscopy and flow cytometry. (1985)

Compartmentalization of specialized functions to discrete locales is a fundamental theme of eucaryotic organization in cells. We report here that bioluminescence of the dinoflagellate alga Gonyaulax originates in vivo from discrete subcellular loci that are intrinsically fluorescent. We demonstrate this localization by comparing the loci of fluorescence and bioluminescence as visualized by image-intensified video microscopy. These fluorescent particles appeared to be the same as the previously described in vitro "scintillons." We attribute the endogenous fluorescence to that of the bioluminescence substrate, luciferin, because (a) the fluorescence excitation and emission characteristics are comparable, (b) the autofluorescence is lost after exhaustive stimulation of bioluminescence, and (c) the fluorescence of discharged particles in vitro can be restored by adding luciferin. The fluorescence in vivo exhibits a standard property of circadian (daily) rhythmicity: under constant environmental conditions, the intensity of the particle fluorescence fluctuates cyclically (it is maximal during the night phase and is low during the day). Thus, luciferin is localized within the cell at discrete loci from which the bioluminescence emanates; the cellular quantity of luciferin is rhythmically modulated by the circadian clock.
Advances in information retrieval(ACM 82 Panel Session) (1982)

In conventional information retrieval Boolean combinations of index terms are used to formulate the users' information request. Boolean queries are difficult to generate and the retrieved items are not presented to the user in any useful order. A new flexible retrieval system is described which makes it possible to relax the strict conditions of Boolean query logic thereby retrieving useful items that are rejected in a conventional retrieval situation. The query structure inherent in the Boolean system is preserved, while at the same time weighted terms may be incorporated into both queries and stored documents; the retrieved output can also be ranked in strict similarity order with the user queries. A conventional retrieval system can be modified to make use of the flexible metric system. Laboratory tests indicate that the extended system produces better retrieval output than conventional Boolean or vector processing systems.
Tomographic measurement of local cerebral glucose metabolic rate in humans with (F‐18)2‐fluoro‐2‐deoxy‐D‐glucose: Validation of method (1979)

Tracer techniques and quantitative autoradiographic and tissue counting models for measurement of metabolic rates were combined with positron computed tomography (PCT) and (F-18)2-fluoro-2-deoxy-D-glucose (FDG) for the measurement of local cerebral metabolic rate for glucose (LCMRGlc) in humans. A three-compartment model, which incorporates hydrolysis of FDG-6-PO4 to FDG, was developed for the measure of kinetic constants and calculation of LCMRGlc. Our model is an extension of that developed by Sokoloff et al. Although small, hydrolysis of FDG-6-PO4 was found to be significant. A PCT system, the ECAT, was used to determine the rate constants, lumped constant, and stability of the model in human beings. The data indicate that cerebral FDG-6-PO4 in humans increases for about 90 minutes, plateaus, and then slowly decreases. After 10 minutes, cerebral blood FDG activity levels were found to be a minor fraction of tissue activity. Precursor pool turnover rate, distribution volumes, and red blood cell-plasma concentration ratios were determined. Reproducibility (precision) of LCMRGlc measurements (approximate 2 cm2 regions) was +/- 5.5% over a 5-hour period. The replacement of arterial blood sampling with venous sampling was validated.
Integrative analysis of 111 reference human epigenomes (2015)

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.
The causative organisms of septicaemia and their epidemiology (1990)

During the 20 years, 1969-88, nearly 4000 episodes of septicaemia were studied prospectively at St. Thomas' Hospital. Forty percent were community-acquired and 60% hospital-acquired. Overall the commonest isolate was Escherichia coli (22%). In community-acquired bacteraemias, Esch. coli, Streptococcus pneumoniae and Staphylococcus aureus accounted for almost 60% of episodes, and the commonest foci of infection were the urinary tract (Esch. coli) and the respiratory tract (Str. pneumoniae). Esch. coli was particularly common in diabetic patients and Str. pneumoniae in alcoholics. In hospital-acquired septicaemia, Esch. coli and Staph. aureus accounted for 40% of episodes, but a further 30% were caused by enterobacteria other than Esch. coli, and Pseudomonas aeruginosa. The commonest foci of infection were the urinary tract, often with catheterization or instrumentation, and intravascular access sites, from which episodes of septicaemia were increasingly caused by coagulase-negative staphylococci.
Polymorphisms of STK15 (Aurora-A) gene and lung cancer risk in Caucasians (2006)

STK15/Aurora-A is a centrosome-localized serine/threonine kinase that functions primarily in centrosome maturation and mitotic spindle assembly. In a large lung cancer case-control study of 1401 cases and 1397 controls including three ethnic groups, we examined the associations between two non-synonymous SNPs (Phe31Ile and Val57Ile) of the STK15 gene and lung cancer risk. There were statistically significant differences in the distribution of the genotypes (P<0.0001) and haplotypes (P<0.0001) by ethnicity for the Phe31Ile, but not the Val57Ile variant. Caucasians with the homozygous variant Phe31Ile genotype (Ile/Ile) were at a significantly reduced risk for lung cancer [odds ratio (OR)=0.63, 95% confidence interval (CI)=0.41-0.96]. The variant allele of Val57Ile was not associated with lung cancer risk overall. However, men with the homozygous variant genotype (Ile/Ile) had a reduced lung cancer risk as compared with men with the wild-type genotype (Val/Val) (OR=0.42, 95% CI=0.19-0.94). When we performed joint analysis of these two polymorphisms, compared with the reference group (TT+GG, 40.99% of controls), homozygous Ile31 allele/wild-type Val57 allele (AA+GG) carriers (5.45% of controls) exhibited a reduced lung cancer risk (OR=0.78, 95% CI=0.63-0.97). This is the first epidemiological study to report significant associations between STK15 polymorphisms and lung cancer risk.