gebhart/patrepeval huggingface dataset:
Kinetic analysis of Escherichia coli RNase H using DNA-RNA-DNA/DNA substrates. (1990)

The kinetic properties of Escherichia coli ribonuclease H (RNase H) were investigated using oligonucleotide substrates that consist of a short stretch of RNA, flanked on either side by DNA (DNA-RNA-DNA). In the presence of a complementary DNA strand, RNase H cleavage is restricted to the short ribonucleotide stretch of the DNA/RNA heteroduplex. The DNA-RNA-DNA substrate utilized for kinetic studies: (formula; see text) is cleaved at a single site (decreases) in the presence of a complementary DNA strand, to generate (dT)7-(rA)2-OH and p-(rA)2-(dT)9. Anion exchange high performance liquid chromatography was used to separate and quantitate the cleavage products. Under these conditions, RNase H-specific and nonspecific degradation products could be resolved. Kinetic parameters were measured under conditions of 100% hybrid formation (1.2-1.5 molar excess of complementary DNA, T much less than Tm). A linear double reciprocal plot was obtained, yielding a Km of 4.2 microM and a turnover number of 7.1 cleavages per s per RNase H monomer. The kinetic properties of substrate analogs containing varying lengths of RNA (n = 3-5) and 2'-O-methyl modifications were also investigated. Maximal turnover was observed with DNA-RNA-DNA substrates containing a minimum of four RNA residues. Kcat for the rA3 derivative was decreased by more than 100-fold. The Km appeared to decrease with the size of the internal RNA stretch (n = 3-5). No significant difference in turnover number of Km was observed when the flanking DNA was replaced with 2'-O-methyl RNA, suggesting that RNase H does not interact with this region of the heteroduplex.
Exon 3 of the α folate receptor gene contains a 5′ splice site which confers enhanced ovarian carcinoma specific expression (2001)

The human folate receptor (FR) is overexpressed in ovarian carcinoma. FR transcripts are heterogeneous due to the use of two promoters, P1 and P4, and alternative splicing of exon 3. RNase protection assay and RT-PCR revealed higher levels of the transcripts that include exon 3 in lines and specimens from ovarian carcinoma. A P1-chloramphenicol acetyltransferase (CAT) construct containing exon 3 demonstrated efficient reporter expression only in ovarian carcinoma. 5' and 3' deleted variants of the P1-CAT construct were analyzed by RT-PCR of the exogenous transcripts and reporter activity. A 5' splice site and 35 bp downstream intronic region of exon 3 appeared to regulate enhanced FR expression in ovarian carcinoma.
Novel genetic variants in miR-191 gene and familial ovarian cancer (2010)

Our findings suggest that there are novel genetic variants in miRNA genes, and those certain genetic variants in miRNA genes can affect the expression of mature miRNAs and, consequently, might alter the regulation of TSGs or oncogenes. Additionally, the variant might be potentially associated with the development of familial ovarian cancer.
Improvements in quality of life and disease-related symptoms in phase I trials of the selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in non-small cell lung cancer and other solid tumors. (2003)

QoL (FACT-L) questionnaires were used successfully in the Phase I clinical trials of ZD1839. They appeared to be a sensitive tool to monitor clinical changes for the five tumor types in these trials and showed that ZD1839 has the potential to improve patients' QoL.
Polylaminin, a polymeric form of laminin, promotes regeneration after spinal cord injury (2010)

Regeneration of spinal cord injury (SCI) is a major topic of biomedical research. Laminin is an extracellular matrix protein implicated in neural development and regeneration, but despite that, there are no reports of exogenous laminin contributing to improve the outcome of experimental SCI. Here we investigated whether a biomimetic polymer of laminin assembled on pH acidification, henceforth called polylaminin, could be used to treat SCI in rats. Acute local injection of polylaminin, but not of nonpolymerized laminin, improved motor function after thoracic compression, partial or complete transection. In the latter case, the BBB score for open field locomotion 8 wk after lesion increased from 4.2 ± 0.48 to 8.8 ± 1.14 in animals treated with polylaminin of human origin. Accordingly, neurons retrogradely labeled from the sublesion stump were detected in the spinal cord and brain stem, indicating regrowth of short and long fibers across a complete transection. Polylaminin also played an unsuspected anti-inflammatory role, which underlies the early onset of its positive effects on locomotion from the first week after treatment. The beneficial effects of polylaminin were not observed in animals treated with the nonpolymerized protein or vehicle only. We propose that polylaminin is a promising therapeutic agent to treat human SCI.
Fragmentation of cell-free fetal DNA in plasma and urine of pregnant women (2005)

Cell-free fetal DNA in maternal plasma is stable under cryopreservation at -20 degrees C for at least 4 years. Approximately, 60% of fetal DNA in maternal plasma was fragmented to <100-bp long, and fetal DNA in urine was further fragmented. Maternal urine may be usable for detection of fetal DNA, although smaller target size is more important for PCR amplification of fetal DNA in urine than in the analysis of plasma from pregnant women.
Total Dose Intravenous Infusion of Iron Dextran for Iron-Deficiency Anemia in Children With Inflammatory Bowel Disease (2002)

Total dose intravenous infusion of iron dextran, when appropriately used, is a safe and potentially efficacious treatment for children with inflammatory bowel disease and iron deficiency anemia who are unresponsive to or noncompliant with oral iron therapy.
A 45‐bp proximal region containing AACA and GCN4 motif is sufficient to confer endosperm‐specific expression of the rice storage protein glutelin gene,GluA‐3 (1996)

A 45-bp proximal region of the rice glutelin promoter (-104/-60) containing two putative cis-elements, the AACA motif and GCN4 motifs, was fused to a truncated CaMV 35S promoter (-90/+9; -90 delta 35S)/GUS. The 45-bp fragment specifically enhanced the promoter activity in endosperm tissue of transformed tobacco. A substitution mutation of the GCN4 motif reduced the promoter activity, whereas mutation of the AACA motif increased the activity in the embryo as well as in the endosperm. These results suggest that the GCN4 motif generally enhances the promoter activity but that the combination of the two motifs confers the endosperm specificity. Furthermore, the function of the two motifs was dependent on the orientation and/or distance from a G-box element in -90 delta 35S, suggesting that synergistic interaction between the factors that recognize those motifs and the G-box element is important for transcriptional regulation.
Accelerometer Use in Physical Activity: Best Practices and Research Recommendations (2005)

Researchers are increasingly interested in the potential of accelerometers to improve our ability to measure and understand the health impacts of physical activity. Although accelerometers have been available commercially for more than 25 yr, broad consensus about how to use these tools has not been established. At a scientific conference in December 2004, a number of scientists were invited to present papers, serve as reactors or moderators to papers, present posters of original research, or serve as members of an audience knowledgeable about the use of accelerometers. During 2 1/2 d, information about best practices of accelerometer use was presented and suggestions for future research were made. From the collective experience of papers presented and discussions held, five areas of accelerometer use were described. This paper summarizes the best practices and future research needs from those five areas: monitor selection, quality, and dependability; monitor use protocols; monitor calibration; analysis of accelerometer data; and integration with other data sources. Suggestions for reporting standards for journal articles also are presented.
Transient plane source techniques for thermal conductivity and thermal diffusivity measurements of solid materials (1991)

The general theory of the transient plane source (TPS) technique is outlined in some details with approximations for the two experimental arrangements that may be referred to as ‘‘hot square’’ and ‘‘hot disk.’’ Experimental arrangements and measurements on two materials, Cecorite 130P and Corning 9606 Pyroceram, using a hot disk configuration, are reported and assessed.
The Pseudomonas syringae Hrp regulation and secretion system controls the production and secretion of multiple extracellular proteins (1996)

Pseudomonas syringae pv. tomato DC3000 produces seven to eight major extracellular proteins (EXPs) in a minimal medium inducing hrp genes. Using a polyclonal antibody against DC3000 EXPs, we have determined that the production and secretion of five EXPs (EXP-60, EXP-45, EXP-43, EXP-22, and EXP-10) are under the control of the Hrp regulation and secretion system.
Cross-reactive dengue human monoclonal antibody prevents severe pathologies and death from Zika virus infections (2017)

Zika virus (ZIKV) infections have been linked with neurological complications and congenital Zika syndrome. Given the high level of homology between ZIKV and the related flavivirus dengue virus (DENV), we investigated the level of cross-reactivity with ZIKV using a panel of DENV human mAbs. A majority of the mAbs showed binding to ZIKV virions, with several exhibiting neutralizing capacities against ZIKV in vitro. Three of the best ZIKV-neutralizing mAbs were found to recognize diverse epitopes on the envelope (E) glycoprotein: the highly conserved fusion-loop peptide, a conformation-specific epitope on the E monomer, and a quaternary epitope on the virion surface. The most potent ZIKV-neutralizing mAb (SIgN-3C) was assessed in 2 type I interferon receptor-deficient (IFNAR-/-) mouse models of ZIKV infection. Treatment of adult nonpregnant mice with SIgN-3C rescued mice from virus-induced weight loss and mortality. The SIgN-3C variant with Leu-to-Ala mutations in the Fc region (SIgN-3C-LALA) did not induce antibody-dependent enhancement (ADE) in vitro but provided similar levels of protection in vivo. In pregnant ZIKV-infected IFNAR-/- mice, treatment with SIgN-3C or SIgN-3C-LALA significantly reduced viral load in the fetal organs and placenta and abrogated virus-induced fetal growth retardation. Therefore, SIgN-3C-LALA holds promise as a ZIKV prophylactic and therapeutic agent.
Nicotinamide mononucleotide synthetase is the key enzyme for an alternative route of NAD biosynthesis in Francisella tularensis (2009)

Enzymes involved in the last 2 steps of nicotinamide adenine dinucleotide (NAD) cofactor biosynthesis, which catalyze the adenylylation of the nicotinic acid mononucleotide (NaMN) precursor to nicotinic acid dinucleotide (NaAD) followed by its amidation to NAD, constitute promising drug targets for the development of new antibiotics. These enzymes, NaMN adenylyltransferase (gene nadD) and NAD synthetase (gene nadE), respectively, are indispensable and conserved in nearly all bacterial pathogens. However, a comparative genome analysis of Francisella tularensis allowed us to predict the existence of an alternative route of NAD synthesis in this category A priority pathogen, the causative agent of tularaemia. In this route, the amidation of NaMN to nicotinamide mononucleotide (NMN) occurs before the adenylylation reaction, which converts this alternative intermediate to the NAD cofactor. The first step is catalyzed by NMN synthetase, which was identified and characterized in this study. A crystal structure of this enzyme, a divergent member of the NadE family, was solved at 1.9-A resolution in complex with reaction products, providing a rationale for its unusual substrate preference for NaMN over NaAD. The second step is performed by NMN adenylyltransferase of the NadM family. Here, we report validation of the predicted route (NaMN --> NMN --> NAD) in F. tularensis including mathematical modeling, in vitro reconstitution, and in vivo metabolite analysis in comparison with a canonical route (NaMN --> NaAD --> NAD) of NAD biosynthesis as represented by another deadly bacterial pathogen, Bacillus anthracis.
Reading between the Lanes: Road Layout Reconstruction from Partially Segmented Scenes (2018)

Autonomous vehicles require an accurate and adequate representation of their environment for decision making and planning in real-world driving scenarios. While deep learning methods have come a long way providing accurate semantic segmentation of scenes, they are still limited to pixel-wise outputs and do not naturally support high-level reasoning and planning methods that are required for complex road manoeuvres. In contrast, we introduce a hierarchical, graph-based representation, called scene graph, which is reconstructed from a partial, pixel-wise segmentation of an image, and which can be linked to domain knowledge and AI reasoning techniques. In this work, we use an adapted version of the Earley parser and a learnt probabilistic grammar to generate scene graphs from a set of segmented entities. Scene graphs model the structure of the road using an abstract, logical representation which allows us to link them with background knowledge. As a proof-of-concept we demonstrate how parts of a parsed scene can be inferred and classified beyond labelled examples by using domain knowledge specified in the Highway Code. By generating an interpretable representation of road scenes and linking it to background knowledge, we believe that this approach provides a vital step towards explainable and auditable models for planning and decision making in the context of autonomous driving.
Neurotensin receptors in adeno- and squamous cell carcinoma. (2006)

Since the receptor protein is targeted in vivo, the enhanced protein expression of NTR1 in xenografts could be a useful tool for molecular targeting with radioligands and for further characterization of the carcinogenic process.
Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease (2006)

Supplements combining folic acid and vitamins B6 and B12 did not reduce the risk of major cardiovascular events in patients with vascular disease. (ClinicalTrials.gov number, NCT00106886; Current Controlled Trials number, ISRCTN14017017.).
Total synthesis of (.+-.)-15-deoxyspergualin (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal synthesis of (.+-.)-15-deoxyspergualinRaymond J. Bergeron and James S. McManisCite this: J. Org. Chem. 1987, 52, 9, 1700–1703Publication Date (Print):May 1, 1987Publication History Published online1 May 2002Published inissue 1 May 1987https://pubs.acs.org/doi/10.1021/jo00385a010https://doi.org/10.1021/jo00385a010research-articleACS PublicationsRequest reuse permissionsArticle Views1241Altmetric-Citations100LEARN 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
Cavity size in reaction field theory (1998)

The optimum size of the cavity accommodating a solute in the reaction field theory of solvation is considered by empirical calibration of the results of electronic structure calculations against experiment. To isolate the long range electrostatic free energy contributions treated by reaction field theory from the many other short range contributions not explicitly considered, computational results are compared to experimental determinations of conformational free energy differences in polar solutes having two or more stable or metastable isomers. When the cavity shape is defined by a solute electronic isodensity contour, it is found that the best overall agreement with experiment is obtained with a cavity size corresponding to the 0.001 a.u. contour.
Next generation sequencing of pooled samples reveals new SNRNP200 mutations associated with retinitis pigmentosa (2011)

The gene SNRNP200 is composed of 45 exons and encodes a protein essential for pre-mRNA splicing, the 200 kDa helicase hBrr2. Two mutations in SNRNP200 have recently been associated with autosomal dominant retinitis pigmentosa (adRP), a retinal degenerative disease, in two families from China. In this work we analyzed the entire 35-Kb SNRNP200 genomic region in a cohort of 96 unrelated North American patients with adRP. To complete this large-scale sequencing project, we performed ultra high-throughput sequencing of pooled, untagged PCR products. We then validated the detected DNA changes by Sanger sequencing of individual samples from this cohort and from an additional one of 95 patients. One of the two previously known mutations (p.S1087L) was identified in 3 patients, while 4 new missense changes (p.R681C, p.R681H, p.V683L, p.Y689C) affecting highly conserved codons were identified in 6 unrelated individuals, indicating that the prevalence of SNRNP200-associated adRP is relatively high. We also took advantage of this research to evaluate the pool-and-sequence method, especially with respect to the generation of false positive and negative results. We conclude that, although this strategy can be adopted for rapid discovery of new disease-associated variants, it still requires extensive validation to be used in routine DNA screenings.
Motheaten, an Immunodeficient Mutant of the Mouse: I. Genetics and pathology (1975)

A new recessive mutation, motheaten (me), is on chromosome 6, 21.9 +/- 4.3 recombination units distal to white (Miwh). Mice homozygous for the new mutation have neutrophilic lesions of the skin beginning as early as day 1, and pneumonitis with many macrophages in the alveoli as early as day 3. They suffer high mortality from birth onward and none has survived longer than 8 weeks. The lymph nodes may be enlarged, but the thymus, Reyer's patches, and lymphatic tissue of the spleen are much reduced in size. Lymph nodes, spleen, and Peyer's patches lack lymphatic nodules. The lymph nodes and spleen contain many plasma cells. There are increased numbers of neutrophils and monocytes in the peripheral blood, and increased numbers of neutrophils in bone marrow at the expense of red cell precursors. Hematopoietic tissue in the spleen is increased and appears more active than normal. Motheaten mice appear to have an immune deficiency beginning very shortly after birth.
Downhole Adjustable Gauge Stabilizer Improves Drilling Efficiency in Directional Wells (1990)

ABSTRACT This paper evaluates the use of a downhole adjustable stabilizer in place of conventional stabilizers through the tangent sections of directional wells. It includes a survey of more than 100 directional wells and illustrates typical applications of the tool. The strategic placement of undergauge and full gauge nearbit and/or first string stabilizers to control hole inclination is now proving unnecessary. A correctly positioned adjustable stabilizer allows changes to be made to the Bottomhole Assembly (BHA) without pulling out of hole. Not only can expensive BHA trips be avoided, but correct utilisation of the an adjustable stabilizer will improve the trajectory of the hole section and minimise doglegs to reduce torque and pipe drag.
A Chimeric Switch-Receptor Targeting PD1 Augments the Efficacy of Second-Generation CAR T Cells in Advanced Solid Tumors (2016)

Chimeric antigen receptor (CAR)-modified adoptive T-cell therapy has been successfully applied to the treatment of hematologic malignancies, but faces many challenges in solid tumors. One major obstacle is the immune-suppressive effects induced in both naturally occurring and genetically modified tumor-infiltrating lymphocytes (TIL) by inhibitory receptors (IR), namely PD1. We hypothesized that interfering with PD1 signaling would augment CAR T-cell activity against solid tumors. To address this possibility, we introduced a genetically engineered switch receptor construct, comprising the truncated extracellular domain of PD1 and the transmembrane and cytoplasmic signaling domains of CD28, into CAR T cells. We tested the effect of this supplement, "PD1CD28," on human CAR T cells targeting aggressive models of human solid tumors expressing relevant tumor antigens. Treatment of mice bearing large, established solid tumors with PD1CD28 CAR T cells led to significant regression in tumor volume due to enhanced CAR TIL infiltrate, decreased susceptibility to tumor-induced hypofunction, and attenuation of IR expression compared with treatments with CAR T cells alone or PD1 antibodies. Taken together, our findings suggest that the application of PD1CD28 to boost CAR T-cell activity is efficacious against solid tumors via a variety of mechanisms, prompting clinical investigation of this potentially promising treatment modality.
Designing structure-based information agents (1994)

This paper presents a new methodology for building special-purpose software agents that capture and ac-cess information in large, heterogeneous, distributed information environments. It allows rapid prototyp-ing of information agents for solving a wide range of retrieval tasks with guarantees on performance. The key idea is to exploit underlying structure at various levels of granularity to build partial models that act as high-level indices with task-specific interpretations. These partial models are constructed using modules called navigators. Information agents are configured by using effective communication protocols to connect structure detectors and navigators. This methodology is applied to the design and implementation of infor-mation agents in two contexts: one for retrieving stock market information from scanned copies of newspapers and another for retrieving technical reports from the Internet. 1
An mRNA Vaccine against SARS-CoV-2 — Preliminary Report (2020)

The mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461).
Daily Oral Ketamine for the Treatment of Depression and Anxiety in Patients Receiving Hospice Care: A 28-Day Open-Label Proof-of-Concept Trial (2013)

Patients who received daily oral ketamine experienced a robust antidepressant and anxiolytic response with few adverse events. The response rate for depression is similar to those found with IV ketamine; however, the time to response is more protracted. The findings of the potential efficacy of oral ketamine for depression and the response of anxiety symptoms are novel. Further investigation with randomized, controlled clinical trials is necessary to firmly establish the efficacy and safety of oral ketamine for the treatment of depression and anxiety in patients receiving hospice care or other subject populations.