gebhart/patrepeval huggingface dataset:
Predictive utility of progesterone receptor (PR) and multigene expression in identifying benefit from adjuvant doxorubicin plus cyclophosphamide (AC) or docetaxel (AT) in intergroup trial E2197 (2008)

557 Background: Although E2197 showed no difference in recurrence or overall survival, an exploratory analysis suggested differential benefit for AC in PR-pos disease and AT in PR-neg disease (Proc ASCO 2005, abstr 512) when PR was determined in local labs. We evaluated the predictive utility of PR protein expression by IHC in a central lab and quantitative RNA expression by RT-PCR for 371 genes (including the 21-gene recurrence score [RS]) in a representative sample of 734 patients who received at least 3–4 treatment cycles. Methods: Individual gene by treatment interactions were tested in Cox models for relapse-free interval (RFI). Permutation methods were used to control the false discovery proportion at <10%. Supervised principal components (SPC) was used to combine genes into an interaction predictor, which was evaluated via cross-validation (CV). Results: PR Analysis. There was a weak benefit for AT in PR-neg (AT vs AC hazard ratio [RR]=0.75; p=0.06) and AC in PR-pos disease (RR=1.37; p=0.05) by central IHC (Allred score > 2 positive) but not when genomic PR was evaluated by RT-PCR (> 5.5 units positive). RS and New Genes. There was little evidence that gene expression identified AT vs. AC benefit in the hormone receptor (HR)-neg, or HR-pos, RS < 18 subsets. In contrast, there were many genes that strongly predicted differential AT vs AC benefit in the HR-pos, RS > 18 subset; SPC analyses of a multigene model suggest a significant effect (CV continuous interaction permutation p=0.03), with the AT vs. AC RR in the highest and lowest third of the SPC values estimated in CV to be 0.23 and 2.48. Oncotype DX RS did not predict differential AC vs AT benefit in HR-pos disease. Conclusions: PR protein expression may identify a potentially clinically relevant association for differential taxane benefit, but requires validation in other datasets. A genomic classifier predicting differential benefit was identified in HR-pos tumors with a RS > 18, and if externally validated, might be useful in defining differential benefit in patients with HR-pos disease. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genomic Health, sanofi-aventis Genomic Health Institute, GlaxoSmithKline, sanofi-aventis Genomic Health Genomic Health Institute, GlaxoSmithKline, sanofi-aventis sanofi-aventis
Effects of "duration" of reperfusate administration versus reperfusate "dose" on regional functional, biochemical, and histochemical recovery. (1986)

This study tests the hypothesis that improved myocardial salvage following regional ischemia occurs when attention is directed toward the duration of blood cardioplegic reperfusion rather than the reperfusate "dose". Pilot studies after global ischemia established the postischemic oxygen use pattern consistent with normal and impaired recovery; the best recovery occurred when postischemic muscle consumed oxygen in excess of basal demands. Experimental studies were then performed on 22 dogs undergoing 2 hours of left anterior descending coronary occlusion. Nine dogs received normal blood reperfusion, with the heart allowed to remain in the beating, working state. In 13 dogs, cardiac O2 demands were kept low during reperfusion by delivering a dose of 150 to 250 mumol/L Ca2++ aspartate-glutamate-enriched blood cardioplegic solution containing 250 to 350 micrograms/kg body weight diltiazem during total vented bypass. This same reperfusate dose with diltiazem was given over 10 minutes in five dogs and over 20 minutes in eight others. Persistent systolic bulging (ultrasonic crystals) of -27% (p less than 0.05) of systolic shortening followed normal blood reperfusion without bypass. During blood cardioplegic reperfusion, regional O2 uptake exceeded basal demands by 24 ml/100 gm/min at 10 minutes (p less than 0.05) and did not return to baseline until 20 minutes had elapsed. Hearts reperfused with blood cardioplegia for 20 minutes had better recovery of systolic shortening (58% versus 30%, p less than 0.05), less edema (79.8% versus 80.9% water content, p less than 0.05), and less triphenyltetrazolium chloride nonstaining (12% versus 21%, p less than 0.05) than those reperfused for 10 minutes with the same solution containing the same diltiazem dose. Continuing blood cardioplegic reperfusion until myocardial oxygen uptake reaches control levels enhances regional functional recovery after acute coronary occlusion. These results indicate that attention should be directed toward the duration of reperfusion, as well as the "dose" of cardioplegic reperfusate.
Design, analysis, and fabrication of a tri-axial cable system (2003)

Encouraged by the positive test results of a /spl sim/1.5-m long prototype tri-axial cable, the Southwire Company/Oak Ridge National Laboratory (ORNL) team has conceived, designed, and built a 5-m tri-axial cable with three-phase terminations. The three concentric superconducting phases are made of BSCCO-2223 high-temperature superconducting (HTS) tapes, separated by layers of cold-dielectric (CD) tape. A copper braid is added as the grounding shield. The completed tri-axial cable is enclosed in a flexible cryostat. Cooling of the cable and terminations is achieved by liquid nitrogen flowing through the annulus between the cable and the cryostat. A challenging analysis and design problem was development and implementation of an insulator material between the concentric phases with high enough thermal conductivity to meet temperature gradient requirements and acceptable mechanical performance (strength and contraction on cool down). The resulting three-phase, CD cable and termination design is nearly as compact as the single-phase, co-axial design developed previously by Southwire/ORNL and represents the highest cable current density achievable in an electric alternating-current power cable.
Clinical assessment of wounds and antimicrobial susceptibility profiles of aerobic bacterial isolates in dogs at two surgeries in Harare (2016)

A study was conducted at two veterinary surgeries to investigate the common aerobic bacteria associated with dog bite wounds in dogs, and to determine their antimicrobial susceptibilities. From each wound, two swabs were collected for bacterial culture and cytology. A total of 50 wounds from 50 dogs were examined, with 78% (39/50) lacerations classified as; contaminated (52%) and infected (26%) while 22% (11/50) were puncture wounds classified as; contaminated (18%) and infected (4%). All the wounds yielded 91 different isolates with 61.5% and 38.5% Gram-positive and Gram negative bacteria, respectively. Staphylococcus aureus (22.0%), Staphylococcus pseuintermedius (17.6%), Streptococcus spp. (12.1%) and Klebsiella spp. 9.9% were predominant. None of the isolates were resistant to ciprofloxacin, with low resistance to gentamicin, kanamycin and amikacin. For S. aureus and S. pseudintermedius , multiple drug resistance to ampicillin/cloxacillin and cotrimoxazole was dominant. Thus, it is prudent to carry out antimicrobial susceptibility testing prior to antimicrobial treatment. Keywords: Dog bite wounds, aerobic bacteria, antimicrobial susceptibility, multi-drug resistance
Relationship between Serum Renin Concentration, Renal Renin Content, and Juxtaglomerular Apparatus in Hypertensive Patients (1969)

On a variety of 30 hypertensive patients and 3 controls, relationship between serum renin concentration, renal renin content, and juxtaglomerular apparatus (JGA) was studied. A highly significant correlation was found between serum renin concentration and renal renin content. The correlations between serum renin concentration and juxtaglomerular granulation index (JGI), and between renal renin content and JGI were also significant. The correlation coefficients, however, were significantly lower than that between serum renin and renal renin. Several factors including staining techniques may be related to this difference. From these results, it is concluded that renin levels are related to the changes in the JGA on a variety of hypertensive patients, although these relations are still problematic in a few cases.
Estudio de los parámetros de transferencia de calor y de degradación del núcleo de un reactor PWR. Ajuste del modelo utilizado (2005)

Esta memoria incluye una descripción de un modelo de planta de Ascó II, llevado a cabo enel marco de un Proyecto Final de Carrera. Este modelo fue realizado utilizando el código decálculo RELAP/SCDAP a partir de un modelo de planta en desarrollo continuo en la Secciónde Ingeniería Nuclear, y de un modelo detallado de vasija incorporado al resto del modelo deplanta.Posteriormente, se simulará el funcionamiento en régimen estacionario, a potencia de 2686MW y se contrastarán los valores obtenidos con los valores reales de planta para la validacióndel modelo.Ajustado el modelo, se procederá al estudio de dos escenarios accidentales de LOCA (“LossOf Coolant Accident”). En concreto, se simulará, en primer lugar, una pérdida importante derefrigerante en uno de los lazos del circuito primario de la central nuclear en el caso de queactúen normalmente los sistemas de inyección de seguridad. Posteriormente, se considerará lamisma rotura, postulando un fallo del sistema de inyección de alta presión y un retardo deunos 15 min del sistema de inyección de baja presión. Estos cálculos se harán con elpropósito de analizar los fenómenos de intercambio de calor (calor producido por oxidación,calor transferido por convección y radiación, conducción térmica en las barras decombustible, efecto del calentamiento sobre los materiales, etc).Finalmente, se procurará evaluar el aporte de la utilización del código SCDAP para el estudiode tales escenarios de transitorios de planta.
Tracking heavy water (D <sub>2</sub> O) incorporation for identifying and sorting active microbial cells (2014)

Microbial communities are essential to the function of virtually all ecosystems and eukaryotes, including humans. However, it is still a major challenge to identify microbial cells active under natural conditions in complex systems. In this study, we developed a new method to identify and sort active microbes on the single-cell level in complex samples using stable isotope probing with heavy water (D2O) combined with Raman microspectroscopy. Incorporation of D2O-derived D into the biomass of autotrophic and heterotrophic bacteria and archaea could be unambiguously detected via C-D signature peaks in single-cell Raman spectra, and the obtained labeling pattern was confirmed by nanoscale-resolution secondary ion MS. In fast-growing Escherichia coli cells, label detection was already possible after 20 min. For functional analyses of microbial communities, the detection of D incorporation from D2O in individual microbial cells via Raman microspectroscopy can be directly combined with FISH for the identification of active microbes. Applying this approach to mouse cecal microbiota revealed that the host-compound foragers Akkermansia muciniphila and Bacteroides acidifaciens exhibited distinctive response patterns to amendments of mucin and sugars. By Raman-based cell sorting of active (deuterated) cells with optical tweezers and subsequent multiple displacement amplification and DNA sequencing, novel cecal microbes stimulated by mucin and/or glucosamine were identified, demonstrating the potential of the nondestructive D2O-Raman approach for targeted sorting of microbial cells with defined functional properties for single-cell genomics.
Wnt Signaling in Neural Development (2014)

The importance of Wnt signaling in nervous system formation has been recognized since the initial characterization of a vertebrate Wnt homolog. Analysis of the expression and function of Wnt pathway components has continued to support a critical role in the formation of neuronal and glial cell populations throughout the central nervous system (CNS) and peripheral nervous system (PNS). The CNS arises from ectoderm in all triploblastic animals, and differentiates from nonneural ectoderm as a result of extracellular signals, through a process called neural induction. Wnt pathway antagonists are specifically expressed in the anterior neuroectoderm, creating a gradient of Wnt/β-catenin activity that patterns the anterior– posterior axis of the brain and spinal cord. The first observable expression of Wnt ligands within the CNS occurs in organizer regions, which often are found at boundaries between major subdivisions of the brain.
Abstract 3811: Robust anti-tumor activity through targeting integrin α5β1 and eliciting ADCC with a dual functional monoclonal antibody PF-04605412 (2010)

Abstract Integrin α5β1 and its ligand fibronectin are significantly and coordinately over-expressed in tumor associated blood vessels and cancer cells. These molecules have been reported to mediate angiogenesis, tumor survival and metastasis. α5β1 has also been implicated as a poor prognostic marker in a number of human tumor types including NSCLC and ovarian carcinoma. Thus, α5β1 is a potential target for cancer therapy. Accumulating evidence suggests an important role of innate immune effector cells in tumor killing via antibody dependent cellular cytotoxicity (ADCC). Taking advantage of both of these mechanisms, we generated an α5 integrin-specific neutralizing monoclonal antibody (mAb, PF-04605412) with high affinity for Fcγ receptors. In vitro, PF-04605412 potently inhibited α5β1-mediated intracellular signaling, cell adhesion, migration, endothelial cell tubulogenesis, and induced apoptosis of endothelial and tumor cells. Compared to a wild type IgG1 of identical antigen specificity (wt IgG1), PF-04605412 induced a significantly greater tumor and endothelial cell cytotoxicity. ADCC activity correlated with the abundance of NK cells within PBMCs of human donors, but was independent of donor FcγRIIIa polymorphism. In in vivo studies using human xenograft, immuno-xenograft and syngeneic tumor models, PF-04605412 (and an anti-murine α5 surrogate mAb) displayed robust and dose-dependent anti-angiogenesis and anti-tumor efficacy including tumor growth delay, regression and metastasis inhibition, all of which were superior to effects observed with an IgG2 or wt IgG1 of identical antigen specificity. Western blotting and immunohistochemistry analysis of tumor samples showed that anti-tumor efficacy was associated with reduction of total and phosphorylated focal adhesion kinase and positively correlated with α5 expression, infiltrating macrophages, markers of effector cell activity, and apoptosis. Furthermore, depletion of host macrophages abrogated anti-tumor efficacy, indicating a critical contribution of ADCC/phagocytosis to the anti-tumor activity of PF-04605412. The PK-PD relationship, efficacy of PF-04605412 in combination with anti-angiogenic and tumor targeting agents will also be reported. The distinct dual mechanism of action and robust anti-tumor efficacy of PF-04605412 supports the clinical development of this agent for the treatment of human cancers. Short Title: Dual functional mAb PF-04605412 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3811.
Optimal Risk Sharing with Limited Liability (2012)

We solve the general problem of optimal risk sharing among a finite number of agents with limited liability. We show that the optimal allocation is characterized by endogenously determined ranks assigned to the participating agents and a hierarchical structure of risk sharing, where all agents take on risks only above the agent-specific thresholds determined by their ranks. When all agents have CARA utilities, linear risk sharing is optimal between two adjacent thresholds. We use our general characterization of optimal risk sharing with limited liability to solve the problem of optimal insurance design with multiple insurers. We show that the optimal thresholds, or deductibles, can be efficiently calculated through the fixed point of a contraction mapping. We then use this contraction mapping technique to derive a number of comparative statics results for optimal insurance design and its dependence on microeconomic characteristics.
How Programmers Read Regular Code: A Controlled Experiment Using Eye Tracking (2015)

Regular code, which includes repetitions of the same basic pattern, has been shown to have an effect on code comprehension: a regular function can be just as easy to comprehend as an irregular one with the same functionality, despite being longer and including more control constructs. It has been speculated that this effect is due to leveraging the understanding of the first instances to ease the understanding of repeated instances of the pattern. To verify and quantify this effect, we use eye tracking to measure the time and effort spent reading and understanding regular code. The results are that time and effort invested in the initial code segments are indeed much larger than those spent on the later ones, and the decay in effort can be modeled by an exponential or cubic model. This shows that syntactic code complexity metrics (such as LOC and MCC) need to be made context-sensitive, e.g. By giving reduced weight to repeated segments according to their place in the sequence.
Solubilization of Receptors for Thyrotropin-Releasing Hormone from GH<sub>4</sub>C<sub>1</sub>Rat Pituitary Cells: Demonstration of Guanyl Nucleotide Sensitivity (1987)

TRH receptors have been solubilized from GH4C1 cells using the plant glycoside digitonin. Solubilized receptors retain the principal binding characteristics exhibited by the TRH receptor in intact pituitary cells and their membranes. The binding of the methylhistidyl derivative of TRH [( 3H]MeTRH) attained equilibrium within 2-3 h at 4 C, and it was reversible, dissociating with a t1/2 of 7 h. Analysis of [3H]MeTRH binding to soluble receptors at 4 C yielded a dissociation constant (Kd) of 3.8 nM and a total binding capacity (Bmax) of 3.9 pmol/mg protein. Peptides known to interact with non-TRH receptors on GH cells failed to interfere with the binding of [3H]MeTRH, indicating that the TRH binding was specific. Chlordiazepoxide, a competitive antagonist for TRH action in GH cells, inhibited TRH binding to soluble receptors with an IC50 of 11 microM. When [3H]MeTRH was bound to membranes and the membrane proteins were then solubilized, we found enhanced dissociation of the prebound [3H]MeTRH from its solubilized receptor by guanyl nucleotides. Maximal enhancement of [3H]MeTRH dissociation by 10 microM GTP gamma S occurred within about 45 min at 22 C. GTP gamma S, GTP, GDP beta S, and GDP were all effectors of [3H]MeTRH dissociation, exhibiting EC50s in the range of 14-450 nM. The rank order of potency of the tested nucleotides was GTP gamma S greater than GTP congruent to GDP beta S greater than GDP much greater than ATP gamma S greater than GMP. We conclude that TRH receptors have been solubilized from GH cells with digitonin and retain the binding characteristics of TRH receptors in intact pituitary cells. Furthermore, prebinding [3H]MeTRH to GH4C1 cell membranes results in the solubilization of a complex in which the TRH receptor is linked functionally to a GTP binding protein.
Combinatorial library designs for quantifying thin film adhesion via the edge delamination test (2010)

We have demonstrated a combinatorial thin film library design for investigating the adhesion between film and substrate as measured by the edge delamination test. This library design allows rapid screening of critical parameters that control thin film reliability and bond strength in films and coatings. Specifically, our library design was aimed at quantifying the effect of film thickness and composition on the interfacial integrity between the film and underlying substrate by applying thermal stress. To create the combinatorial library, a single specimen was fabricated having a thickness gradient of an epoxy film on glass or silicon substrates. After sectioning the film into individual squares, a temperature gradient was applied orthogonal to the thickness gradient to induce debonding events where the adhesion is below a critical value. In addition, another combinatorial library was carried out using the epoxy films with concentration gradient and constant thickness, and applying a constant temperature. The combined results clearly demonstrate that our combinatorial library design and approach provide a large parameter space for accurately and reproducibly mapping the interfacial integrity and bond strength of film/substrate systems.
Suggestive evidence for the two-neutrino double-β decay of<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:mmultiscripts><mml:mrow><mml:mi mathvariant="normal">Ge</mml:mi></mml:mrow><mml:mprescripts/><mml:mrow/><mml:mrow><mml:mn>76</mml:mn></mml:mrow><mml:mrow/><mml:mrow/></mml:mmultiscripts></mml:mrow></mml:math> (1990)

A dramatic reduction in background was achieved in the latest Pacific Northwest Laboratory--University of South Carolina germanium detectors. Two 1.05-kg natural-isotopic-abundance detectors were operated for 1.92 kg yr. The residual spectrum, after straightforward corrections, has a significant region resembling the theoretical spectrum of the two-neutrino \ensuremath{\beta}\ensuremath{\beta} decay of $^{76}\mathrm{Ge}$. A fit to the data yields ${\mathit{T}}_{1/2}^{2\ensuremath{\nu}}$${(}^{76}$Ge)=(1.${1}_{\mathrm{\ensuremath{-}}0.3}^{+0.6}$)\ifmmode\times\else\texttimes\fi{}${10}^{21}$ yr at the 95% C.L., which agrees with shell-model predictions.
Distribution of Plasmodium vivax pvdhfr and pvdhps alleles and their association with sulfadoxine–pyrimethamine treatment outcomes in Indonesia (2015)

With proper malaria diagnosis, SP may still be used as a rational anti-malarial drug either as a single prescription or in combination with artemisinin.
Comparative OHD-RIKES Study of the Low-Frequency (0–250 cm<sup>–1</sup>) Vibrational Dynamics of Dibenzyl- and Monobenzyl-Substituted Imidazolium Ionic Liquids and Benzene/Dimethylimidazolium Mixtures (2015)

The low-frequency (0–450 cm–1) Kerr spectra of 1-benzyl-3-methylimidazolium bis[(trifluoromethane)sulfonyl]amide ([BnzC1im][NTf2]) and 1,3-dibenzylimidazolium bis[(trifluoromethane)sulfonyl]amide ([(Bnz)2im][NTf2]) and 2:1 and 1:1 mixtures of benzene in 1,3-dimethylimidazolium bis[(trifluoromethane)sulfonyl]amide ([C1C1im][NTf2]) were measured by the use of optical heterodyne-detected Raman-induced Kerr effect spectroscopy (OHD-RIKES). Surprisingly, the line-shape of the intermolecular part of the height-normalized Kerr spectrum is the same for both the 1:1 and 2:1 C6H6/[C1C1im][NTf2] mixtures, which may be a signature of the local liquid structure being characterized by π-stacked benzene–cation complexes. The intermolecular part of the Kerr spectrum of [BnzC1im][NTf2] is lower in intensity, higher in frequency, and broader than that of the 1:1 C6H6/[C1C1im][NTf2] mixture. Similarly, the intermolecular part of the Kerr spectrum of [(Bnz)2im][NTf2] is lower in intensity, higher in frequency, and broader than that of the 2:1 C6H6/[C1C1im][NTf2] mixture. These results are explained in terms of the increased restriction of the intermolecular motion of benzene in going from being free in the mixtures to being tethered to the imidazolium ring in the benzyl-substituted ionic liquids.