gebhart/patrepeval huggingface dataset:
Analysis of Naturalistic Driving Study Data: Safer Glances, Driver Inattention, and Crash Risk (2014)

This work was sponsored by the second Strategic Highway Research Program (SHRP 2), which is administered by the Transportation Research Board of the National Academies. This project was managed by Ken Campbell, Chief Program Officer for SHRP 2 Safety , and Jim Hedlund, SHRP 2 Safety Coordinator . The research reported on herein was performed by the main contractor SAFER Vehicle and Traffic Safety Centre at Chalmers, Gothenburg, Sweden. SAFER is a joint research unit where 25 partners from the Swedish automotive industry, academia and authorities cooperate to make a center of excellence within the field of vehicle and traffic safety (see www.chalmers.se/safer ). The host and legal entity SAFER is Chalmers University of Technology. Principle Investigator Tr ent Victor is Adjunct Professor at Chalmers and worked on the project as borrowed personnel to Chalmers but his main employer is Volvo Cars. The other authors of this report are Co - PI Marco Dozza, Jonas Bargman, and Christian - Nils Boda of Chalmers Universi ty of Technology (as a SAFER partner) ; Johan Engstrom and Gustav Markkula of Volvo Group Trucks Technology (as a SAFER partner) ; John D. Lee of University of Wisconsin - Madison (as a consultant to SAFER); and Carol Flannagan of University of Michigan Transp ortation Research Institute (UMTRI) (as a consultant to SAFER). The authors acknowledge the contributions to this research from Ines Heinig, Vera Lisovskaja, Olle Nerman, Holger Rootzen, Dmitrii Zholud, Helena Gellerman , Leyla Vujic, Martin Rensfeldt, Stefan Venbrant, Akhil Krishnan, Bharat Mohan Redrouthu, Daniel Nilsson of Chalmers; Mikael Ljung - Aust of Volvo Cars; Erwin Boer; Christer Ahlstrom and Omar Bagdadi of VTI.
An update on targeted gene repair in mammalian cells: methods and mechanisms (2011)

Transfer of full-length genes including regulatory elements has been the preferred gene therapy strategy for clinical applications. However, with significant drawbacks emerging, targeted gene alteration (TGA) has recently become a promising alternative to this method. By means of TGA, endogenous DNA repair pathways of the cell are activated leading to specific genetic correction of single-base mutations in the genome. This strategy can be implemented using single-stranded oligodeoxyribonucleotides (ssODNs), small DNA fragments (SDFs), triplex-forming oligonucleotides (TFOs), adeno-associated virus vectors (AAVs) and zinc-finger nucleases (ZFNs). Despite difficulties in the use of TGA, including lack of knowledge on the repair mechanisms stimulated by the individual methods, the field holds great promise for the future. The objective of this review is to summarize and evaluate the different methods that exist within this particular area of human gene therapy research.
Safety and Antitumor Activity of Anti–PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer (2015)

This study, to our knowledge, is the first to explore the effects of nivolumab against ovarian cancer. The encouraging safety and clinical efficacy of nivolumab in patients with platinum-resistant ovarian cancer indicate the merit of additional large-scale investigations (UMIN Clinical Trials Registry UMIN000005714).
Cache management in a tightly coupled fault tolerant multiprocessor (2002)

Some aspects of a fault-tolerant tightly coupled multiprocessor architecture are presented. The originality of this architecture resides in the use of a stable transactional memory shared by all processors. To ensure fault tolerance, each update of a memory block is included into an atomic transaction managed by the stable transactional memory. All the blocks that are part of a transaction are written back atomically into stable transaction memory. This work focuses on a protocol which ensures the atomic update of blocks into stable transactional memory when they have been modified by several caches. The results of various simulations that were conducted in order to evaluate the potential performance of the proposed architecture are also presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Individual differences in two emotion regulation processes: Implications for affect, relationships, and well-being. (2003)

Five studies tested two general hypotheses: Individuals differ in their use of emotion regulation strategies such as reappraisal and suppression, and these individual differences have implications for affect, well-being, and social relationships. Study 1 presents new measures of the habitual use of reappraisal and suppression. Study 2 examines convergent and discriminant validity. Study 3 shows that reappraisers experience and express greater positive emotion and lesser negative emotion, whereas suppressors experience and express lesser positive emotion, yet experience greater negative emotion. Study 4 indicates that using reappraisal is associated with better interpersonal functioning, whereas using suppression is associated with worse interpersonal functioning. Study 5 shows that using reappraisal is related positively to well-being, whereas using suppression is related negatively.
Purification and Physical Characterization of Tyrosyl Ribonucleic Acid Synthetases from Escherichia coli and Bacillus subtilis* (1966)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPurification and Physical Characterization of Tyrosyl Ribonucleic Acid Synthetases from Escherichia coli and Bacillus subtilis*Richard Calendar and Paul BergCite this: Biochemistry 1966, 5, 5, 1681–1690Publication Date (Print):May 1, 1966Publication History Published online1 May 2002Published inissue 1 May 1966https://doi.org/10.1021/bi00869a033RIGHTS & PERMISSIONSArticle Views317Altmetric-Citations177LEARN 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 InReddit PDF (3 MB) Get e-Alerts Get e-Alerts
3 x 3 all-fiber routing switch (1997)

An all-fiber acoustooptic switch has been constructed from a 3×3 null fused coupler. The maximum drive power required is 4 mW, the switching time is 100 μs and the insertion loss is less than 0.5 dB and has a cross talk of 20 dB. The switch shares the advantages of an earlier 2×2 switch but with more fiber ports, and should permit the design of compound routing arrays with fewer switching elements per channel.
Fc epsilon receptor I-associated lyn-dependent phosphorylation of Fc gamma receptor IIB during negative regulation of mast cell activation. (1998)

Fc gamma RIIB are low-affinity receptors for IgG whose intracytoplasmic domain contains an immunoreceptor tyrosine-based inhibition motif (ITIM). Fc gamma RIIB inhibit cell activation triggered by receptors that signal via immunoreceptor tyrosine-based activation motifs. This inhibition requires ITIM tyrosyl phosphorylation and is correlated with the binding of SH2 domain-containing phosphatases that may mediate the inhibitory signal. In the present work, we investigated the mechanism of Fc gamma RIIB phosphorylation and its consequences in mast cells. We demonstrate that the phosphorylation of Fc gamma RIIB requires coaggregation with Fc epsilon RI and that, once phosphorylated, Fc gamma RIIB selectively recruit the inositol polyphosphate 5 phosphatase SHIP, in vivo. In vitro, however, the phosphorylated Fc gamma RIIB ITIM binds not only SHIP, but also the two protein tyrosine phosphatases, SHP-1 and SHP-2. We show that the coaggregation of Fc gamma RIIB with Fc epsilon RI does not prevent Fc epsilon RI-mediated activation of lyn and syk. Both kinases can phosphorylate Fc gamma RIIB in vitro. However, when coaggregated with Fc epsilon RI, Fc gamma RIIB was in vivo phosphorylated in syk-deficient mast cells, but not in lyn-deficient mast cells. When Fc epsilon RI are coaggregated with Fc gamma RIIB by immune complexes, Fc epsilon RI-associated lyn may thus phosphorylate Fc gamma RIIB. By this mechanism, Fc epsilon RI initiate ITIM-dependent inhibition of intracellular propagation of their own signals.
Application of 2,6-Diphenylpyridine as a Tridentate [C∧N∧C] Dianionic Ligand in Organogold(III) Chemistry. Structural and Spectroscopic Properties of Mono- and Binuclear Transmetalated Gold(III) Complexes (1998)

The synthesis of a series of mono- and binuclear cyclometalated gold(III) complexes containing the tridentate C∧N∧C ligand (HC∧N∧CH = 2,6-diphenylpyridine) was developed using K[AuCl4] and the organomercury(II) compound Hg(C∧N∧CH)Cl as precursors. The molecular structures of [Au(C∧N∧C)(Spy-2)] (Spy-2 = 2-mercaptopyridine), [Au(C∧N∧C)PPh3]ClO4, [Au2(C∧N∧C)2(μ-dppm)](ClO4)2, and [Au2(C∧N∧C)2(μ-dppe)](ClO4)2 have been determined by X-ray crystallography. In the crystal lattice of [Au2(C∧N∧C)2(μ-dppm)](ClO4)2 and [Au2(C∧N∧C)2(μ-dppe)](ClO4)2, interplanar separations of 3.4 Å are observed between the intramolecular [Au(C∧N∧C)] moieties, which imply the presence of weak π−π interactions. The torsion angle between the two [Au(C∧N∧C)] units in the former is 8.7°, while a larger angle (34.2°) is observed in the latter. In the absorption spectra, the binuclear complexes show a red shift for the absorption band in the near-visible region compared to the mononuclear analogues. This is attributed to π−π interactions between the intramolecular C∧N∧C ligands in solution. The new complexes are emissive at low temperatures (77 K) in acetonitrile.
Phase I study of two different schedules of bortezomib (BORT) and pemetrexed (PEM) in advanced solid tumors (2006)

17051 Background: BORT(PS-341) is a small molecule proteasome inhibitor while PEM, a multi-targeted antifolate, inhibits multiple enzymes involved in purine/pyrimidine formation. Both are approved anti-cancer agents. We examined the safety and tolerability of two different schedules of BORT and PEM in patients with advanced solid tumors. Methods: Two dose escalation trials (Arm A and Arm B) were conducted simultaneously. PEM was given every 21 days in both arms (500–600 mg/m 2 IV). Arm A: BORT was given D1,4,8 &amp;11 (0.7–1.3 mg/m 2 ). Arm B: BORT was given D1 &amp; 8 (1.0–1.6 mg/m 2 ). All patients received vitamin B12, folic acid and decadron. Dose limiting toxicity (DLT) was defined as: grade (GR) 4 platelets (plts) (≤25K); GR 3 plts (25K-49,999K) with bleeding, requirement for transfusion, or lasting &gt; 7 days; febrile neutropenia; GR3 ANC (ANC ≤1.0 × 10 9 ) with documented infection, or any ≥ GR3 non-heme toxicity. Results: 18 patients have been treated on 3 of the 4 planned dose levels. Tumor types included lung (12), prostate (2), breast (1), thymus (1), head &amp; neck (1) and adenoid cystic carcinoma (1). Pt. characteristics: Median age 65 years; Sex M/F = 7/11; Performance Status ≤1/2 = 18/0. There have been no DLTs in either arm (Dose level 3-Arm A: PEM 500 mg/m 2 , BORT 1.3 mg/m 2 ; Arm B:PEM 500 mg/m 2 , BORT 1.6 mg/m 2 ). Most common GR3/4 toxicities were: neutropenia 27% and lymphopenia 11%. Of 17 evaluable patients: 1 had partial response, 11 had stable disease, 5 had progressive disease. Mean number of cycles: 4. Arm A had more doses held during the first cycle than Arm B (6 doses held vs. 1 dose held). Accrual to the final dose level in both arms is ongoing. Conclusions: 1) PEM in combination with BORT is feasible and tolerable. 2) Thus far, there are no differences in toxicity between the arms. 3) A randomized, multi-institutional phase II study will examine the efficacy of these two schedules in patients with NSCLC. No significant financial relationships to disclose.
Inhibitory mode of N-phenyl-4-pyrazolo[1,5-b] pyridazin-3-ylpyrimidin-2-amine series derivatives against GSK-3: molecular docking and 3D-QSAR analyses (2005)

Glycogen synthase kinase 3 (GSK-3) inhibition is an important research topic because of its wide range of associated health implications. The interaction mode of a series of N-phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine compounds with human GSK-3 has been studied using molecular docking and 3D-QSAR approaches. In the 3D-QSAR studies, the molecular alignment and conformation determination are so important that they affect the success of a model. Flexible docking (AutoDock3.0.5) was used for the determination of 'active' conformation and molecular alignment. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used to develop 3D-QSAR models of 80 N-phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine compounds. The r(2) values were 0.870 and 0.861 for CoMFA and CoMSIA models, respectively. The predictive ability of these models was validated by 10 compounds of the test set. Mapping these models back to the topology of the active site of GSK-3 led to a better understanding of the vital N-phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amines-GSK-3 interactions. The results demonstrate that combination of ligand-based and receptor-based modeling is a powerful approach to build 3D-QSAR models. The interaction mode from this study may be helpful for the design of a novel inhibitor and guide the selection of candidate sites for further experimental studies on site-directed mutagenesis.
Utilization of a Novel Rib Spreader for Minimally Invasive Lung Transplantation (2014)

Rack-and-pinion-type stainless steel rib spreader was innovated by Truffier in 1914, which was modified by Finochietto to have fenestrated blades and a hand-cranked lever to both separate the arms in a staged fashion and lock them in place at each stop. Its Burford-Finochietto variants with replaceable blades are ubiquitous in open thoracic surgery. Fehling Surgical Instrument, Inc (Acworth, GA) introduced a modified rib spreader-an assembly of movable and adjustable blades, a mobile bridge and spreader arms, which owing to its adaptation of thoracotomy incision provides an optimum exposure without injuring the ribs. The spreader is indispensible in lung transplantation surgery performed especially through minimally invasive (bilateral limited anterolateral thoracotomies with intact sternum) approach.
Synthetic reactions by complex catalysts. XXXI. Novel and versatile method of heterocycle synthesis (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthetic reactions by complex catalysts. XXXI. Novel and versatile method of heterocycle synthesisYoshihiko. Ito, Yoshinori. Inubushi, Michio. Zenbayashi, Shimpei. Tomita, and Takeo. SaegusaCite this: J. Am. Chem. Soc. 1973, 95, 13, 4447–4448Publication Date (Print):June 27, 1973Publication History Published online1 May 2002Published inissue 27 June 1973https://doi.org/10.1021/ja00794a065RIGHTS & PERMISSIONSArticle Views297Altmetric-Citations39LEARN 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 InReddit PDF (240 KB) Get e-Alerts Get e-Alerts
Virus-specific cytotoxic T-lymphocyte activity elicited by coimmunization with human immunodeficiency virus type 1 genes regulated by the bacteriophage T7 promoter and T7 RNA polymerase protein (1997)

Cytotoxic T lymphocyte (CTL) activity was assessed in mice immunized with DNA plasmids containing the human immunodeficiency virus type 1 (HIV-1) gp120 envelope (pTMIgp120) or p55gag (pTMIgag) gene regulated by the bacteriophage T7 promoter. Immunization with either plasmid resulted in CTL activity against class I major histocompatibility complex-restricted viral epitopes when coadministered with a recombinant vaccinia virus expressing the T7 RNA polymerase protein (T7 RNAP) but not a control vaccinia virus. Recombinant vaccinia-T7 RNAP virus (VTF7-3) could be replaced with a noninfectious source of T7 RNAP. A three-component vaccine consisting of pTMIgag, a recombinant subunit T7 RNAP protein, and a plasmid (pT7T7) encoding T7 RNAP under the control of its own promoter induced gag-specific CTL activity. Intramuscular immunization with the pTMIgag plasmid delivered with either the T7 RNAP protein or pT7T7 plasmid alone also induced HIV-1-specific CTL. Thus, there is adventitious expression of the pT7T7 plasmid in vivo, and enough T7 RNAP is produced to result in production of p24gag protein from the pTMIgag plasmid. The results demonstrate that regulated expression of genes in vivo is possible with this T7-based expression system, and may be useful in vaccine settings where short-term cytoplasmic expression of protein in antigen presenting cells is desired.
Cellular mechanisms underlying cutaneous pressure-induced vasodilation: in vivo involvement of potassium channels (2005)

In the skin of humans and rodents, local pressure induces localized cutaneous vasodilation, which may be protective against pressure-induced microvascular dysfunction and lesion formation. Once activated by the local pressure application, capsaicin-sensitive nerve fibers release neuropeptides that act on the endothelium to synthesize and release nitric oxide (NO) and prostaglandins, leading to the development of the cutaneous pressure-induced vasodilation (PIV). The present study was undertaken to test in vivo the hypothesis that PIV is mediated or modulated by differential activation of K+ channels in anesthetized rats using pharmacological methods. Local pressure was applied at 11.1 Pa/s. Endothelium-independent and -dependent vasodilation were tested using iontophoretic delivery of sodium nitroprusside (SNP) and acetylcholine (ACh), respectively, and was correlated with PIV response. PIV was reduced after systemic administration of tetraethylammonium (a nonspecific K+ channel blocker), iberiotoxin [a specific large-conductance Ca2+-activated K+ (BKCa) channel blocker], and glibenclamide [a specific ATP-sensitive K+ (KATP) channel blocker], whereas PIV was unchanged by apamin (a specific small-conductance Ca2+-activated K+ channel blocker) and 4-aminopyridine (a specific voltage-sensitive K+ channel blocker). The responses to SNP and ACh were reduced by iberiotoxin but were unchanged by glibenclamide. We conclude that the cellular mechanism of PIV in skin involves BKCa and KATP channels. We suggest that the opening of BKCa and KATP channels contributes to the hyperpolarization of vascular smooth muscle cells to produce PIV development mainly via the NO and prostaglandin pathways, respectively.
Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells (2013)

Signaling between endothelial cells, endothelial progenitor cells, and stromal cells is crucial for the establishment and maintenance of vascular integrity and involves exosomes, among other signaling pathways. Exosomes are important mediators of intercellular communication in immune signaling, tumor survival, stress responses, and angiogenesis. The ability of exosomes to incorporate and transfer messenger RNAs (mRNAs) encoding for "acquired" proteins or micro RNAs (miRNAs) repressing "resident" mRNA translation suggests that they can influence the physiological behavior of recipient cells. We demonstrate that miR-214, an miRNA that controls endothelial cell function and angiogenesis, plays a dominant role in exosome-mediated signaling between endothelial cells. Endothelial cell-derived exosomes stimulated migration and angiogenesis in recipient cells, whereas exosomes from miR-214-depleted endothelial cells failed to stimulate these processes. Exosomes containing miR-214 repressed the expression of ataxia telangiectasia mutated in recipient cells, thereby preventing senescence and allowing blood vessel formation. Concordantly, specific reduction of miR-214 content in exosome-producing endothelial cells abolishes the angiogenesis stimulatory function of the resulting exosomes. Collectively, our data indicate that endothelial cells release miR-214-containing exosomes to stimulate angiogenesis through the silencing of ataxia telangiectasia mutated in neighboring target cells.
Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)-γ Inhibitor (IPI-549) as an Immuno-Oncology Clinical Candidate (2016)

Optimization of isoquinolinone PI3K inhibitors led to the discovery of a potent inhibitor of PI3K-γ (26 or IPI-549) with >100-fold selectivity over other lipid and protein kinases. IPI-549 demonstrates favorable pharmacokinetic properties and robust inhibition of PI3K-γ mediated neutrophil migration in vivo and is currently in Phase 1 clinical evaluation in subjects with advanced solid tumors.
Frequency of formation of chimeric molecules as a consequence of PCR coamplification of 16S rRNA genes from mixed bacterial genomes (1997)

PCR is routinely used in amplification and cloning of rRNA genes from environmental DNA samples for studies of microbial community structure and identification of novel organisms. There have been concerns about generation of chimeric sequences as a consequence of PCR coamplification of highly conserved genes, because such sequences may lead to reports of nonexistent organisms. To quantify the frequency of chimeric molecule formation, mixed genomic DNAs from eight actinomycete species whose 16S rRNA sequences had been determined were used for PCR coamplification of 16S rRNA genes. A large number of cloned 16S ribosomal DNAs were examined by sequence analysis, and chimeric molecules were identified by multiple-sequence alignment with reference species. Here, we report that the level of occurrence of chimeric sequences after 30 cycles of PCR amplification was 32%. We also show that PCR-induced chimeras were formed between different rRNA gene copies from the same organism. Because of the wide use of PCR for direct isolation of 16S rRNA sequences from environmental DNA to assess microbial diversity, the extent of chimeric molecule formation deserves serious attention.
The Role of Orphan Nuclear Receptors in the Regulation of Cholesterol Homeostasis (2000)

Cholesterol balance is maintained by a series of regulatory pathways that control the acquisition of cholesterol from endogenous and exogenous sources and the elimination of cholesterol, facilitated by its conversion to bile acids. Over the past decade, investigators have discovered that a family of membrane-bound transcription factors, sterol regulatory element-binding proteins (SREBPs), mediate the end-product repression of key enzymes of cholesterol biosynthesis. Recently orphan members of another family of transcription factors, the nuclear hormone receptors, have been found to regulate key pathways in bile acid metabolism, thereby controlling cholesterol elimination. The study of these orphan nuclear receptors suggests their potential as targets for new drug therapies.