gebhart/patrepeval huggingface dataset:
Data from Combination Olaparib and Temozolomide in Relapsed Small-Cell Lung Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;Small-cell lung cancer (SCLC) is an aggressive malignancy in which inhibitors of PARP have modest single-agent activity. We performed a phase I/II trial of combination olaparib tablets and temozolomide (OT) in patients with previously treated SCLC. We established a recommended phase II dose of olaparib 200 mg orally twice daily with temozolomide 75 mg/m&lt;sup&gt;2&lt;/sup&gt; daily, both on days 1 to 7 of a 21-day cycle, and expanded to a total of 50 patients. The confirmed overall response rate was 41.7% (20/48 evaluable); median progression-free survival was 4.2 months [95% confidence interval (CI), 2.8–5.7]; and median overall survival was 8.5 months (95% CI, 5.1–11.3). Patient-derived xenografts (PDX) from trial patients recapitulated clinical OT responses, enabling a 32-PDX coclinical trial. This revealed a correlation between low basal expression of inflammatory-response genes and cross-resistance to both OT and standard first-line chemotherapy (etoposide/platinum). These results demonstrate a promising new therapeutic strategy in SCLC and uncover a molecular signature of those tumors most likely to respond.&lt;/p&gt;Significance:&lt;p&gt;We demonstrate substantial clinical activity of combination olaparib/temozolomide in relapsed SCLC, revealing a promising new therapeutic strategy for this highly recalcitrant malignancy. Through an integrated coclinical trial in PDXs, we then identify a molecular signature predictive of response to OT, and describe the common molecular features of cross-resistant SCLC.&lt;/p&gt;&lt;p&gt;&lt;i&gt;See related commentary by Pacheco and Byers, p. 1340&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;&lt;i&gt;This article is highlighted in the In This Issue feature, p. 1325&lt;/i&gt;&lt;/p&gt;&lt;/div&gt;
MicroRNA-184 Regulates Corneal Lymphangiogenesis (2015)

These novel findings indicate that mir-184 is involved critically in LG and potentially could be used as an inhibitor of the process. Further investigation holds the promise for divulging new therapies for LG disorders, which occur inside and outside the eye.
Spatiotemporal evolution of cavitation dynamics exhibited by flowing microbubbles during ultrasound exposure (2012)

Ultrasound and microbubble-based therapies utilize cavitation to generate bioeffects, yet cavitation dynamics during individual pulses and across consecutive pulses remain poorly understood under physiologically relevant flow conditions. SonoVue(®) microbubbles were made to flow (fluid velocity: 10-40 mm/s) through a vessel in a tissue-mimicking material and were exposed to ultrasound [frequency: 0.5 MHz, peak-rarefactional pressure (PRP): 150-1200 kPa, pulse length: 1-100,000 cycles, pulse repetition frequency (PRF): 1-50 Hz, number of pulses: 10-250]. Radiated emissions were captured on a linear array, and passive acoustic mapping was used to spatiotemporally resolve cavitation events. At low PRPs, stable cavitation was maintained throughout several pulses, thus generating a steady rise in energy with low upstream spatial bias within the focal volume. At high PRPs, inertial cavitation was concentrated in the first 6.3 ± 1.3 ms of a pulse, followed by an energy reduction and high upstream bias. Multiple pulses at PRFs below a flow-dependent critical rate (PRF(crit)) produced predictable and consistent cavitation dynamics. Above the PRF(crit), energy generated was unpredictable and spatially biased. In conclusion, key parameters in microbubble-seeded flow conditions were matched with specific types, magnitudes, distributions, and durations of cavitation; this may help in understanding empirically observed in vivo phenomena and guide future pulse sequence designs.
Blade Dynamic Stall Vortex Kinematics for a Horizontal Axis Wind Turbine in Yawed Conditions* (2001)

Horizontal axis wind turbines routinely suffer significant time varying aerodynamic loads that adversely impact structures, mechanical components, and power production. As lighter and more flexible wind turbines are designed to reduce overall cost of energy, greater accuracy and reliability will become even more crucial in future aerodynamics models. However, to render calculations tractable, current modeling approaches admit various approximations that can degrade model predictive accuracy. To help understand the impact of these modeling approximations and improve future models, the current effort seeks to document and comprehend the vortex kinematics for three-dimensional, unsteady, vortex dominated flows occurring on horizontal axis wind turbine blades during non-zero yaw conditions. To experimentally characterize these flows, the National Renewable Energy Laboratory Unsteady Aerodynamics Experiment turbine was erected in the NASA Ames 80 ft×120 ft wind tunnel. Then, under strictly-controlled inflow conditions, turbine blade surface pressures and local inflow velocities were acquired at multiple radial locations. Surface pressure histories and normal force records were used to characterize dynamic stall vortex kinematics and normal forces. Stall vortices occupied approximately two-thirds of the aerodynamically active blade span and persisted for nearly one-fourth of the blade rotation cycle. Stall vortex convection varied dramatically along the blade radius, yielding pronounced dynamic stall vortex deformation. Analysis of these data revealed systematic alterations to vortex kinematics due to changes in test section speed, yaw error, and blade span location.
Compensated silicon crystals by metallurgy route (2010)

Abstract The alumothermic reduction of silica from silicate slag was studied for obtaining a silicon‐containing alloy (SCA). A synthetic slag (SS) with composition close to that of phosphorous industry waste (PIW) is used. SS consists of more than 90% silicon dioxide, calcium oxide and less than l0% of other element's oxides. SCA was upgraded by acid leaching up to pure silicon of a fine powder structure. Compensated poly‐ and mono‐crystalline silicon, with resistivity from 0.6 (bottom of crystal) to 4 (top of crystal) Ohm · cm, was grown by Czochralski method using this powder. (© 2011 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
[Significance and possibilities of cytostatic treatment of malignant tumors: testing the effects of cytostatics]. (2000)

The authors present an account on the initiation of a study concerned with the administration of cytostatics according to the sensitivity of the tumour cells. To assess the sensitivity the MTT test was used. The method is described in the paper. Four groups of tumours were examined by the MTT test: breast cancer, carcinoma of the colon and rectum, of the lungs and oesophagus + stomach. Six cytostatics were tested: 5-fluorouracil, cisplatinum, daunorubucin, paclitaxel, vincristine, and vepeside. Evaluation of the sensitivity of different tumours was based on the median of TCS50. The results of the MTT test were not used so far in the therapeutic protocol in all patients where the examination was made, as in solid tumours, contrary to haemo-blastomas, usually common empirically tested protocols are used. The authors reflect whether individually administered cytostatics according to the MTT test can improve the prognosis of patients with malignant diseases. They assume that long-term follow-up of the patients may provide favourable results in particular because more and more effective cytostatics are becoming available.
Die Reaktion der Phenolderivate mit Sulfoxiden. IV (einschlieBlich der von Sulfiden und Wasserstoffperoxid ausgehenden Reaktion). Die Synthese von 4-Thiosubstituierten-1, 2-Naphthochinonderivaten (1968)

Die Reaktion des a-Naphthols mit Dialkylsulfoxid bzw. Methylarylsulfoxid bei Gegenwart der Mischung von Perchlorsaure und Phosphoroxychlorid fuhrte leicht zu Dialkyl-4-oxynaphthylsulfoniumperchlorat (I-IV) sowie Methyl-aryl-4-oxynaphthylsulfoniumperchlorat (V-VII). Auch durch Eintropfen der gerechneten Menge Hydroperoxid ins Reaktionsgemisch in Gegenwart der Mischung von Perchlorsaure und Phosphoroxychlorid ging die Reaktion mit Dialkylsulfid bzw. Methylarylsulfid statt Sulfoxid glatt fort, und dabei wurden gewunschte Sulfoniumsalze (I-VII) leicht mit guter Ausbeute erhalten. Durch Oxydation der von den Sulfoniumsalzen (I-VII) abgeleiteten 4-Alkylthio-oder 4-Arylthio-naphthole (XI-XVII) mit Kaliumnitrosodisulfonat wurden 4-Alkylthio-oder 4-Arylthio-naphthochinone (XVIII-XXIV) am zweckmaBigsten erhalten.
Characterization of Protein Glycosylation in Francisellatularensis subsp. holarctica (2012)

: FTH_0069 is a previously uncharacterized strongly
immunoreactive protein that has been proposed to be a novel
virulence factor in Francisella tularensis. Here, the glycan
structure modifying two C-terminal peptides of FTH_0069 was
identified utilizing high resolution, high mass accuracy mass
spectrometry, combined with in-source CID tandem MS
experiments. The glycan observed at m/z 1156 was determined to
be a hexasaccharide, consisting of two hexoses, three
N-acetylhexosamines, and an unknown monosaccharide containing a
phosphate group. The monosaccharide sequence of the glycan is
tentatively proposed as X-P-HexNAc-HexNAc-Hex-Hex-HexNAc, where
X denotes the unknown monosaccharide. The glycan is identical
to that of DsbA glycoprotein, as well as to one of the multiple
glycan structures modifying the type IV pilin PilA, suggesting
a common biosynthetic pathway for the protein
modification.Here, we demonstrate that the glycosylation of
FTH_0069, DsbA, and PilA was affected in an isogenic mutant
with a disrupted wbtDEF gene cluster encoding O-antigen
synthesis and in a mutant with a deleted pglA gene encoding
pilin oligosaccharyltransferase PglA. Based on our findings, we
propose that PglA is involved in both pilin and general F.
tularensis protein glycosylation, and we further suggest an
inter-relationship between the O-antigen and the glycan
synthesis in the early steps in their biosynthetic pathways.
Joint Factor Analysis Versus Eigenchannels in Speaker Recognition (2007)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> We compare two approaches to the problem of session variability in Gaussian mixture model (GMM)-based speaker verification, eigenchannels, and joint factor analysis, on the National Institute of Standards and Technology (NIST) 2005 speaker recognition evaluation data. We show how the two approaches can be implemented using essentially the same software at all stages except for the enrollment of target speakers. We demonstrate the effectiveness of zt-norm score normalization and a new decision criterion for speaker recognition which can handle large numbers of t-norm speakers and large numbers of speaker factors at little computational cost. We found that factor analysis was far more effective than eigenchannel modeling. The best result we obtained was a detection cost of 0.016 on the core condition (all trials) of the evaluation. </para>
Influence of alloying additions on grain boundary cohesion of transition metals: First-principles determination and its phenomenological extension (2001)

The toughness and ductility of ultrahigh-strength alloys is often limited by intergranular embrittlement, particularly under conditions of unfavorable environmental interactions such as hydrogen embrittlement and stress corrosion cracking. Here we investigated the mechanism by which the segregated substitutional additions cause intergranular embrittlement. An electronic level phenomenological theory is proposed to predict unambiguously the effect of a substitutional alloying addition on grain boundary cohesion of metallic alloys, based on first-principles full-potential linearized augmented plane-wave method (FLAPW) calculations on the strengthening and embrittling effects of the metals Mo and Pd on the Fe grain boundary cohesion. With the bulk properties of substitutional alloying addition A and the matrix element M as inputs, the strengthening or embrittling effect of A at the grain boundary of M can be predicted without carrying out first-principles calculations once the atomic structure of the corresponding clean grain boundary is determined. Predictions of the embrittlement potency of a large number of metals, including the $3d,$ $4d,$ and $5d$ transition metals, are presented for the Fe $\ensuremath{\Sigma}3$ (111) and the Ni $\ensuremath{\Sigma}5$ (210) grain boundaries. Rigorous FLAPW calculations on the effect of Co, Ru, W, and Re on the Fe $\ensuremath{\Sigma}3$ (111) grain boundary and Ca on the Ni $\ensuremath{\Sigma}5$ (210) grain boundary cohesion confirm the predictions of our model. This model is expected to be applicable to other high-angle boundaries in general and instructive in the quantum design of ultrahigh-strength alloys with resistance to intergranular fracture.
Optimisation methods for ranking functions with multiple parameters (2006)

Optimising the parameters of ranking functions with respect to standard IR rank-dependent cost functions has eluded satisfactory analytical treatment. We build on recent advances in alternative differentiable pairwise cost functions, and show that these techniques can be successfully applied to tuning the parameters of an existing family of IR scoring functions (BM25), in the sense that we cannot do better using sensible search heuristics that directly optimize the rank-based cost function NDCG. We also demonstrate how the size of training set affects the number of parameters we can hope to tune this way.
Synthesis and Photochemistry of Ru(II) Complexes Containing Phenanthroline-Based Ligands with Fused Pyrrole Rings (2002)

Hydrolysis of 1,10-phenanthrolinopyrrole ethyl ester leads to the acid derivative which is unstable at room-temperature releasing CO(2) and forming 1,10-phenanthrolinopyrrole (php). The ligand reacts with ruthenium(II) to form a series of complexes of the general formula [Ru(php)(n)(bpy)(3-n)](2+), where bpy = 2,2'-bipyridine and n = 1-3. The photochemical properties reveal that the complexes have longer-lived excited states than the standard complex, [Ru(bpy)(3)](2+). Their emission lifetimes range from 9.04 micros (n = 1) to 35.5 micros (n = 3) at 77 K compared to 7.57 micros for the standard. Similarly, at room-temperature, emission lifetimes range from 1.20 micros (n = 1) to 1.70 micros (n = 3) relative to the standard (0.56 micros). The emission quantum yields also have higher values than the standard [Ru(bpy)(3)](2+) under similar conditions. The temperature-dependent studies for the complexes establish the distribution among the radiative, nonradiative, and (3)MLCT to (3)d-d decay channels and are in agreement with the energy gap law.
Persistence of IgG, IgM, and IgE antibodies in human trichinosis. (1992)

An enzyme-linked immunosorbent assay (ELISA) was used to detect serum IgG, IgM, and IgE antibodies against Trichinella spirals s. str. following an outbreak of human trichinosis in 1989 in Chiang Rai Province, Thailand, for two years and seven months in order to observe diagnostic sensitivity of ELISA as well as the persistence of antibodies. It was found that the sensitivity of IgG-ELISA, as determined from biopsy-positive cases, reached 100% on the 50th day of infection. For IgM-ELISA, peak sensitivity was 93.33% at the 57th and IgE-ELISA 100% at the 85th day of infection. Two years and seven months after infection, the diagnostic sensitivity of IgG-ELISA was 88.24%, and that of IgE-ELISA was 47.06%, while the sensitivity of IgM-ELISA was only 11.76%. It was suggested from the data that IgM-ELISA is a helpful indicator of infection within three years. Other two groups of trichinosis cases, i.e., high-titer and seroconversion cases, were also studied. Antibody response curves were constructed from mean ELISA values from each group. It was revealed that all curves were similar in shape, independent of the group studied. The only exception was IgG-antibody response in the high-titer group, which showed the highest antibody level at the first collection of blood samples, i.e., 23 days after infection.
Atypical Oxidation Reaction by Thionyl Chloride: Easy Two‐Step Synthesis of N‐Alkyl‐1,4‐dithiines (2006)

Abstract Easy two‐step synthesis of a series of dithiines was performed from succinic anhydride via cyclization of the corresponding 4‐(alkylamino)‐4‐oxobutanoic acids (succinamic acids). The reaction, carried out in polar aprotic solvents, gave 4,8‐dithiine‐indacene‐1,3,5,7‐tetraones (diimides 3) via 3,7‐bis‐4,8‐dithia‐indacene‐1,5‐diones (diisoimides 2), which could be isolated. Surprisingly, in this reaction, thionyl chloride appeared as an oxidant, and this process seemed to be useful for the syntheses of S‐containing heterocyclic compounds such as 1,4‐dithiins. A mechanistic pathway was considered.
Targeting CARM1 in ovarian cancer with EZH2 and PARP inhibitors (2020)

Coactivator-associated arginine methyltransferase 1 (<i>CARM1</i>)-expressing high-grade serous ovarian cancers are characterized by poor prognosis and limited therapeutic options. Here we discuss a novel therapeutic strategy to target CARM1-expressing ovarian cancer based on a combination of poly (ADP-ribose) polymerase (PARP) and enhancer of zeste homology 2 (EZH2) inhibitors.
Formation of cis-diamminedichloroplatinum(II) 1,2-intrastrand cross-links on DNA is flanking-sequence independent (2000)

Mapping of cis-diamminedichloroplatinum(II) (cis-DDP, cisplatin) DNA adducts over >3000 nucleotides was carried out using a replication blockage assay. The sites of inhibition of modified T4 DNA polymerase, also referred to as stop sites, were analyzed to determine the effects of local sequence context on the distribution of intrastrand cisplatin cross-links. In a 3120 base fragment from replicative form M13mp18 DNA containing 24.6% guanine, 25.5% thymine, 26.9% adenine and 23.0% cytosine, 166 individual stop sites were observed at a bound platinum/nucleotide ratio of 1-2 per thousand. The majority of stop sites (90%) occurred at G(n>2) sequences and the remainder were located at sites containing an AG dinucleotide. For all of the GG sites present in the mapped sequences, including those with Gn(>)2, 89% blocked replication, whereas for the AG sites only 17% blocked replication. These blockage sites were independent of flanking nucleotides in a sequence of N(1)G*G*N(2) where N(1), N(2) = A, C, G, T and G*G* indicates a 1,2-intrastrand platinum cross-link. The absence of long-range sequence dependence was confirmed by monitoring the reaction of cisplatin with a plasmid containing an 800 bp insert of the human telomere repeat sequence (TTAGGG)(n). Platination reactions monitored at several formal platinum/nucleotide ratios or as a function of time reveal that the telomere insert was not preferentially damaged by cisplatin. Both replication blockage and telomere-insert plasmid platination experiments indicate that cisplatin 1,2-intrastrand adducts do not form preferentially at G-rich sequences in vitro.
Gene cloning and expression of thePseudomonas aeruginosaperiplasmic phosphate-binding protein (1988)

The pstS gene, encoding the Pseudomonas aeruginosa phosphate-binding protein, was cloned onto a cosmid vector into Escherichia coli, and localized by subcloning, mapping the insertion site of Tn501 in a P. aeruginosa pstS::Tn501 mutant, and hybridization to an oligonucleotide pool synthesized according to the aminoterminal amino acid sequence of the purified protein. The cloned pstS gene was transferred to P. aeruginosa pstS mutants. The P. aeruoginosa phosphate-binding protein was also expressed and secreted into the periplasm of E. coli pstS mutants.
GPS Spoofing and the Financial Sector (2018)

All global financial exchanges, including the New York Stock Exchange (NYSE) and the Nasdaq, have gone&#13;\ndigital. Large data centers hold the exchanges’ matching engines—the modern-day equivalent of the&#13;\nhistoric trading floor—in racks of interconnected servers. The Department of Homeland Security&#13;\nconsiders these data centers critical national infrastructure. Private security personnel, tall fences, and&#13;\nthe best network security money can buy protect the integrity of the thousands of high-stakes trades&#13;\nexecuted every second within these data centers.
Evolving pharmacology of orphan GPCRs: IUPHAR Commentary (2013)

The award of the 2012 Nobel Prize in Chemistry to Robert Lefkowitz and Brian Kobilka for their work on the structure and function of GPCRs, spanning a period of more than 20 years from the cloning of the human β2 -adrenoceptor to determining the crystal structure of the same protein, has earned both researchers a much deserved place in the pantheon of major scientific discoveries. GPCRs comprise one of the largest families of proteins, controlling many major physiological processes and have been a major focus of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) since its inception in 1987. We report here recent efforts by the British Pharmacological Society and NC-IUPHAR to define the endogenous ligands of 'orphan' GPCRs and to place authoritative and accessible information about these crucial therapeutic targets online.
Effects of an Efflux Mechanism and Ribosomal Mutations on Macrolide Susceptibility of Haemophilus influenzae Clinical Isolates (2003)

This study investigated macrolide resistance mechanisms in clinical Haemophilus influenzae strains with different levels of susceptibility to macrolides. A total of 6,382 isolates were collected during the Alexander Project from 1997 to 2000. For 96.9% of these isolates, the azithromycin MICs were 0.25 to 4 micro g/ml, and these were defined as baseline strains. For 1.8% of the isolates, the azithromycin MICs were lower (<0.25 micro g/ml), and for 1.3% of the isolates, the MICs were higher (>4 micro g/ml). These isolates were defined as hypersusceptible and high-level macrolide-resistant strains, respectively. To identify the mechanisms associated with these three susceptibility patterns, representative strains were studied for the presence of macrolide efflux pumps and for ribosomal alterations. Macrolide efflux was studied by measuring the accumulation of radioactive azithromycin and clarithromycin in the presence or absence of carbonyl cyanide m-chlorophenylhydrazone (CCCP), a protonophore. Treatment with CCCP increased the accumulation of macrolides in baseline as well as high-level resistant strains, demonstrating the presence of an efflux mechanism, but not in the 20 hypersusceptible strains tested. Among the 31 strains studied that showed high-level resistance to both azithromycin and clarithromycin, 28 had ribosomal alterations, 7 had mutations in ribosomal protein L4, 11 had mutations in L22, 2 had mutations in 23S rRNA, 8 had multiple mutations, and 3 had no mutations. From these results, we conclude that the vast majority (>98%) of H. influenzae strains have a macrolide efflux mechanism, with a few of these being hyperresistant (1.3%) due to one or several ribosomal mutations. Occasional hypersusceptible strains (1.8%) were found and had no macrolide resistance mechanisms and appeared to be the only truly macrolide-susceptible variants of H. influenzae.
Mobile MyPlate: A Pilot Study Using Text Messaging to Provide Nutrition Education and Promote Better Dietary Choices in College Students (2014)

Texting repeated messages appears to be an acceptable and effective way to increase nutrition knowledge and promote positive diet-related behaviors in college students.