gebhart/patrepeval huggingface dataset:
Drugging the PI3 Kinome: From Chemical Tools to Drugs in the Clinic (2010)

The phosphatidylinositide 3-kinase (PI3K) pathway is very commonly activated in a wide range of human cancers and is a major driving force in oncogenesis. One of the class I lipid kinase members of the PI3K family, p110alpha, is probably the most commonly mutated kinase in the human genome. Alongside genetic, molecular biological, and biochemical studies, chemical inhibitors have been extremely helpful tools in understanding the role of PI3K enzymes in signal transduction and downstream physiological and pathological processes, and also in validating PI3Ks as therapeutic targets. Although they have been valuable in the past, the early and still frequently employed inhibitors, wortmannin and LY294002, have significant limitations as chemical tools. Here, we discuss the case history of the discovery and properties of an increasingly used chemical probe, the pan-class I PI3K and mammalian target of rapamycin (mTOR) inhibitor PI-103 (a pyridofuropyrimidine), and its very recent evolution into the thienopyrimidine drug GDC-0941, which exhibits excellent oral anticancer activity in preclinical models and is now undergoing phase I clinical trials in cancer patients. We also illustrate the impact of structural biology on the design of PI3K inhibitors and on the interpretation of their effects. The challenges and outlook for drugging the PI3 kinome are discussed in the more general context of the role of structural biology and chemical biology in innovative drug discovery.
Fabrication and Microstructuring of Hexagonally Ordered Two-Dimensional Nanopore Arrays in Anodic Alumina (1999)

Hexagonally ordered nanopore arrays in anodic alumina with high aspect ratios (see Fig.) have been produced using a self-organization process. The pore arrays are straight and parallel, and of polycrystalline structure. The distance between pores can be controlled by adjusting the electrolyte and the applied voltage. The arrays could find application as photonic crystals.
Ester Hydrogenation Catalyzed by CNN-Pincer Complexes of Ruthenium (2016)

Ruthenium complexes supported by two new CNN-pincer ligands were synthesized. Both were tested as catalysts for the hydrogenation of esters under mild conditions (105 °C, 6 bar H2). A striking dependence on ligand structure was observed, as a dimethylamino-substituted ligand gave a nearly inactive catalyst, while a diethylamino-substituted variant gave up to 980 catalytic turnovers for the hydrogenation of benzyl benzoate. This system catalyzes the hydrogenation of various substrates including ethyl, benzyl, and hexyl esters, but is surprisingly unreactive toward methyl esters. Experiments demonstrate that base-catalyzed transesterification is rapid under the reaction conditions and that methyl esters are effectively hydrogenated when benzyl alcohol is added to the reaction mixture. The reverse reaction, dehydrogenation of primary alcohols to give esters, was tested as well; up to 920 catalytic turnovers were observed for the dehydrogenation of 1-hexanol to hexyl hexanoate.
Data Analysis: the Questionnaire (1996)

The aim of this chapter is to enable you to handle data efficiently and to 'tell a story' with the data that has been produced. It deals primarily with survey information which can be counted and measured, summarised in terms of averages and percentages and displayed in graphs and tables. The level of statistical knowledge covered here is quite basic, with the emphasis on describing variables and comparing the characteristics and experiences of different groups. For those unfamiliar with the language of statistics, suggestions for further reading are included at the end of this chapter.
Error propagation in two-sensor three-dimensional position estimation (2001)

The accuracy of 3D position estimation using two angles-only sensors (such as passive optical imagers) is investigated. Beginning with the basic multisensor triangulation equations used to estimate a 3D target position, error propagation equations are derived by taking the appropriate partial derivatives with respect to various measurement errors. Next the concept of Gaussian measurement error is introduced and used to relate the standard deviation of various measurement errors to the standard deviation of the target 3D position estimate. Plots of the various error propagation coefficients are generated. These analytical results are verified using a Monte Carlo statistical approach. The result is a set of equations and graphs useful for designing a two-sensor system to meet a required accuracy specification.
Optofluidic Intracavity Spectroscopy of Canine Lymphoma and Lymphocytes (2008)

Multiple transverse mode, intracavity spectra of canine lymphoma cells in a passive Fabry–Pérot cavity are distinct from single-mode spectra of normal lymphocytes. Two-dimensional effective-index modal calculations provide insight into the nuclear size versus refractive index relationship and clarify the impact of lateral optical confinement on modal shift.
Heat Transfer Coefficient, Pressure Gradient, and Flow Patterns of R1234yf Evaporating in Microchannel Tube (2021)

Abstract This paper presents the heat transfer coefficient, pressure gradient, and flow pattern of R1234yf in a microchannel tube. Both heat transfer coefficient and pressure gradient are presented against real saturation pressure, while flow pattern captures at the exit of data points are presented in the same plot. The experiment was conducted on a 24-port microchannel tube with an average hydraulic diameter of 0.643 mm. The experiment covers mass flux from 100 to 200 kg m−2s−1, heat flux from 0 to 6 kW m−2, vapor quality from 0 to 1, and inlet saturation temperature from 10 to 30 °C. Comparing the correlations to the HTC measurements at very low quality (about 0.1), Gorenflo, D., and Kenning, D. (2010, Pool Boiling, in: VDI Heat Atlas, 2nd ed, Springer, pp. 757–788) agree with the results. As vapor quality increases, pressure gradient increases. The adiabatic pressure gradient is a strong function of mass flux and saturation pressure (temperature). Flow patterns of R1234yf are also affected by mass flux and saturation pressure. The heat transfer coefficient is a strong function of mass flux and heat flux. The saturation temperature has a smaller effect on HTC in the condition range (10 – 30 °C). Under the test range, the accelerating pressure drop is insignificant compared to friction. Comparing to the results, Mishima, K., and Hibiki, T. (1996, “Some Characteristics of Air-Water Two-Phase Flow in Small Diameter Vertical Tubes,” Int. J. Multiph. Flow, 22(4), pp. 703–712) and Muller-Steinhagen, H., and Heck, K. (1986, “A Simple Friction Pressure Drop Correlation for Two-Phase Flow in Pipes,” Accessed March 1, 2018)., 20, pp. 297–308.) have small mean absolute error (MAE) to predict local pressure gradient. For the heat transfer coefficient, Sun, L., and Mishima, K. (2009, “An Evaluation of Prediction Methods for Saturated Flow Boiling Heat Transfer in Mini-Channels,” Int. J. Heat Mass Transf, 52(23–24), pp. 5323–5329) and Gungor, K. E., and Winterton, R. H. S. (1986, “A General Correlation for Flow Boiling in Tubes and Annuli,” Int. J. Heat Mass Transf, 29(3), pp. 351–358) have an MAE less than 30%.
The price elasticity of quantity, and of quality, for tobacco products (2019)

We use household survey data to estimate the price elasticity of quantity, and of quality, for tobacco products. In our data, commonly used estimation methods suggest an own-price elasticity of demand of about -1. These methods add together responses on the quantity margin and the quality margin. Just one third of the response to price is from quantity and two thirds is from quality. The simulated effect of higher excise taxes is to reduce overall quantity by just one third of what is predicted if the quality response is ignored. Higher taxes also shift demand to lower quality tobacco products.
Nonrandom Chromosomal Imbalances in Esophageal Squamous Cell Carcinoma Cell Lines: Possible Involvement of the ATF3 and CENPF Genes in the 1q32 Amplicon (2000)

Using comparative genomic hybridization (CGH), we investigated copy number aberrations in 29 esophageal squamous cell carcinoma (ESC) cell lines. All lines displayed numerous chromosome imbalances. The most frequent losses were observed on chromosome 18q (65.5%), Xp (48. 3%), 3p (44.8%), 4q (44.8%), 8p (41.4%), 11q23 - 25 (34.5%) and 4p (27.6%), whereas the most common copy number gains were noted at 8q (86.2%), 3q (82.8%), 5p (69%), 7p (69%), 20q (65.5%), 9q (55.2%), 11q (55.2%), 1q (48.3%), Xq (44.8%) and 18p (37.9%). High-level gains (HLGs) were detected at 3q26 (9 cases), 8q23 (6 cases), 5p14 - 15 (6 cases), 18p11.2 - 11.3 (6 cases), 3q27 - 28 (5 cases), 5p13 (3 cases), 7p14 - 15 (3 cases), 20q12 - 13 (3 cases), 11q13 (3 cases), 14q21 (2 cases), 20p11.2 (2 cases), 13q32 (2 case), and 1q32 (1 case). Among them, HLGs of 1q32 have been reported in other types of cancer, including glioblastoma and breast cancers. We successfully narrowed down the smallest common amplicon involving 1q-gain to the genomic segment between D1S414 and D1S2860 by fluorescence in situ hybridization (FISH). Southern and northern blot analysis clearly demonstrated that ATF3, human activating transcription factor-3 and CENPF, centromere protein F, mapped within this region, were significantly amplified and over-expressed in 1q32 amplicon.
Unveiling Electronic Transitions in Three Novel Chiral Azo-Compounds Using Linear and Nonlinear Circular Dichroism: A Theoretical−Experimental Study (2011)

Herein, we report on the experimental and theoretically study of the linear absorption, electronic circular dichroism (ECD) spectra, as well as the two-photon absorption circular-linear dichroism measurements of three different chiral azo derivatives in dimethylsulfoxide solution. Using potential energy surfaces and frontier orbital analysis, we established the most stable conformation for each molecule and elucidated their different electronic transitions. Our theoretical calculations allowed us to unambiguously identify the spectral position of such transitions and correlate them with the spectral profiles observed in the two-photon absorption spectra. To further elucidate the characteristics of the main electronic transitions in terms of spectral shape and position, we carried out measurements of the polarization dependent two-photon absorption cross sections and determined the two-photon circular-linear dichroism spectra of these azo dyes.
The adsorption of prothrombin to phosphatidylserine multilayers quantitated by ellipsometry. (1983)

We investigated by means of an automated ellipsometer the adsorption of prothrombin from a buffer solution by multilayers of 14:0/14:0- and 18:1/18:1-phosphatidylserine (PS) stacked on chromium slides. In this instrument thickness and refractive index of the adsorbed phospholipid and proteins are monitored continuously. Two equations are derived to relate the mass of stacked phospholipids and the mass of protein adsorbed to the thickness and refractive index. These equations are based upon the Lorentz-Lorenz relation among the molar refractivities, refractive indices, and the densities of binary mixtures. Experimental validation of these equations is performed by measuring stacked multilayers of known mass of phosphatidylserine and the adsorption of [125I] albumin and [3H]prothrombin on these multilayers. Using these equations we measured the dissociation constants Kd and the number of binding sites nb of prothrombin. Values of Kd = 0.15 x 10(-8) M and nb = 122 molecules of PS/molecule of prothrombin were observed for di C14:0 PS and values of Kd = 0.45 x 10(-8) M and nb = 54 molecules of PS/molecule of prothrombin for di C18:1 PS. These data compare well to data obtained by other methods available in the literature.
Clustered DNA Double-Strand Breaks: Biological Effects and Relevance to Cancer Radiotherapy (2020)

Cells manage to survive, thrive, and divide with high accuracy despite the constant threat of DNA damage. Cells have evolved with several systems that efficiently repair spontaneous, isolated DNA lesions with a high degree of accuracy. Ionizing radiation and a few radiomimetic chemicals can produce clustered DNA damage comprising complex arrangements of single-strand damage and DNA double-strand breaks (DSBs). There is substantial evidence that clustered DNA damage is more mutagenic and cytotoxic than isolated damage. Radiation-induced clustered DNA damage has proven difficult to study because the spectrum of induced lesions is very complex, and lesions are randomly distributed throughout the genome. Nonetheless, it is fairly well-established that radiation-induced clustered DNA damage, including non-DSB and DSB clustered lesions, are poorly repaired or fail to repair, accounting for the greater mutagenic and cytotoxic effects of clustered lesions compared to isolated lesions. High linear energy transfer (LET) charged particle radiation is more cytotoxic per unit dose than low LET radiation because high LET radiation produces more clustered DNA damage. Studies with I-SceI nuclease demonstrate that nuclease-induced DSB clusters are also cytotoxic, indicating that this cytotoxicity is independent of radiogenic lesions, including single-strand lesions and chemically "dirty" DSB ends. The poor repair of clustered DSBs at least in part reflects inhibition of canonical NHEJ by short DNA fragments. This shifts repair toward HR and perhaps alternative NHEJ, and can result in chromothripsis-mediated genome instability or cell death. These principals are important for cancer treatment by low and high LET radiation.
Automatic control of aircraft and missiles (1965)

Longitudinal Dynamics. Longitudinal Autopilots. Lateral Dynamics. Lateral Autopilots. Inertial Cross-Coupling. Self-Adaptive Autopilots. Missile Control Systems. Guidance Systems. Integrated Flight/Fire Control System. Multivariable Control Systems. Structural Flexibility. Application of Statistical Design Principles. Pilot Modeling. Appendices. Index.
Millimeter-wave signal properties resulting from electrooptical upconversion (2001)

This paper describes the combined effects of laser chirp, electrooptical mixing, dispersive fiber transmission, and photodetection on the nonlinear signal properties of the electrooptically generated millimeter-wave signal (60 GHz). Analytical expressions describing the complex currents of fundamental and higher order products are provided for the case of single-tone modulation as well as for two-tone modulation, respectively. Examples will be considered including the nonlinear amplitude response (output power at millimeter-wave range versus input power at IF), the nonlinear phase response (relative output phase at millimeter-wave range versus input power at IF), the input related 1-dB gain compression condition, the amplitude response of third- and fifth-order intermodulation products, as well as the input related intercept points for the latter signals. The model developed performed well, even under moderate to large signal conditions, and very good agreement has been achieved between theory and experiment.
The Volatilome in Metabolomics (2018)

This chapter is intended to provide a broad vision of what are volatile organic compounds (VOCs), the reasons of their interest in biological matrices, and their use in the study of the VOCs produced by all living organisms, the volatilomics. We provide a list of the last review for the period 2016–2017, focusing on biomedical applications as well as sampling techniques and state-of-the-art scientific instrumentation used for those applications. We specially focus on human volatilomics and its use with metabolomics techniques, and their relation with systems biology and precision medicine. Finally, as volatilomics generates large and diverse sets of analytical data, it has significant challenges, mainly in standardization and metadata reporting, which are described in detail.
Model-based phase-shaping for SPM-compensation in mJ-pulse-energy fiber CPA-systems (2010)

Based on an analytical model for the impact of SPM on stretched ultrashort pulses, the influence of SPM is experimentally controlled in a fiber-based CPA-system. Nearly transform-limited pulses with energies as high as 1 mJ are produced at a B-integral as high as 8 rad. The value of the B-integral is measured by the phase-compensation method. The technique neither relies on complex phase-measurements nor on time-consuming optimization routines.
Local production of human IL-6 promotes insulitis but retards the onset of insulin-dependent diabetes mellitus in non-obese diabetic mice (1994)

Journal Article Local production of human IL-6 promotes insulitis but retards the onset of insulin-dependent diabetes mellitus in non-obese diabetic mice Get access Bruno F. DiCosmo, Bruno F. DiCosmo 1Pulmonary and Critical Care Section, Department of Internal Medicine2Department of Immunobiology Search for other works by this author on: Oxford Academic PubMed Google Scholar Dominic Picarella, Dominic Picarella 2Department of Immunobiology Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard A. Flavell Richard A. Flavell 2Department of Immunobiology3Howard Hughes Medical InstituteYale University School of Medicine, New Haven, CT 06510, USA Correspondence to: R. A. Ravell, Department of Immunobiology, Yale School of Medicine, 310 Cedar Street, New Haven, CT 06510, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar International Immunology, Volume 6, Issue 12, December 1994, Pages 1829–1837, https://doi.org/10.1093/intimm/6.12.1829 Published: 01 December 1994 Article history Received: 09 May 1994 Accepted: 03 August 1994 Published: 01 December 1994
Catecholamine Synthesizing Enzyme Activity in Brainstem Areas from Victims of Sudden Infant Death Syndrome (1987)

In order to investigate whether central catecholaminergic neurons are altered in sudden infant death syndrome (SIDS), the activities of dopamine-beta-hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT) were determined in nine brainstem areas from 19 victims of totally unexplained SIDS (tSIDS), 9 victims of partially unexplained SIDS (pSIDS) and 8 control infants. The distinction between tSIDS and pSIDS was made according to the results of the autopsy. They were totally negative for the tSIDS victims, while minor pathological alterations were found in pSIDS victims. In both tSIDS and pSIDS victims, the PNMT activity was significantly decreased in the medullary C2m and C21 areas and in the nucleus medullae oblongatae centralis. In the C21 area only DBH activity was decreased. Further, in the nucleus ambiguus PNMT activity was decreased in tSIDS, while DBH was lowered in pSIDS victims. No significant modifications were found in the areas from the dorso-lateral pons (locus coeruleus, Kolliker Fuse and parabrachialis nuclei). Thus, in the two groups of SIDS victims the capacity to synthesize adrenaline was decreased in some medullary areas. It is considered that these biochemical alterations are related to the abnormal central respiratory and arousal control, which is thought to be present in SIDS.
Characterization of dermal type I collagen of C3H mouse at different stages of the hair cycle (1999)

Hair follicles develop or regress in accordance with the hair cycle. In this study, we partially characterized fibrillar type I collagen, the predominant component in the dermis, at two stages of the hair cycle: anagen and telogen. Skin samples were obtained from the backs of two groups of 11-week-old C3H mice: one at anagen stage induced by shaving and the other at telogen stage. The amount of neutral salt-soluble (newly synthesized) collagen obtained from anagen skin was about twofold that from telogen skin, while the level of acid-soluble collagen was not significantly different between the two groups. The degree of lysine hydroxylation of pepsinized type I collagen obtained from anagen skin was significantly higher than that in telogen (5.0% higher in alpha1 chain, and 15.6% higher in alpha2 chain). Proline hydroxylation at the anagen stage was also slightly higher than in the telogen stage. Two major collagen cross-links were found in both groups of skin; dehydro-hydroxylysinonorleucine and dehydro-histidinohydroxymerodesmosine. The concentration of the latter, a complex tetravalent cross-link, was significantly lower in anagen skin when compared with telogen skin (mean +/- SD 0.64 +/- 0. 07 vs. 0.78 +/- 0.06 mol/mol collagen). The former showed no significant difference between the two groups. In addition, a significant amount of lysyl-aldehyde (a cross-link precursor) was found in anagen (0.16 +/- 0.02 mol/mol collagen), while it was 0.12 mol/mol collagen in telogen. These results indicate that the remodelling of collagen is more active in anagen skin than in telogen, and that characteristic post-translational modifications of dermal collagen seen in anagen may play a part in facilitating an environment around hair follicles for their migration and growth.
A systematic review and network meta-analysis of FDA approved treatment options in men with nonmetastatic, castration-resistant prostate cancer (M0CRPC). (2020)

335 Background: Network meta-analysis can provide useful evidence for relative efficacy and toxicity of different treatment options in absence of head-to-head trials. Previously, we reported no difference in efficacy between Apalutamide (APA) and Enzalutamide (ENZA). In this analysis, we provide updated indirect comparisons of all FDA approved agents (APA,ENZA, Darolutamide(DARO) for the treatment of M0CRPC with rapid PSA doubling time. Methods: MEDLINE, EMBASE and Cochrane Library were searched to identify relevant clinical trials. Hazard ratios (HR) and 95% confidence interval (CI) for Metastasis Free Survival (MFS), Overall Survival (OS) and data on grade 3 or higher AEs were abstracted. Bayesian network meta-analysis was conducted using WinBUGS 1.4.3 software (MRC Biostatistics Unit, Cambridge, UK) to perform an indirect comparisons. Risk for bias was assessed using the Cochrane Collaboration’s tool. Results: Three RCTs (SPARTAN, PROSPER and ARAMIS) compared APA, ENZA and DARO respectively in combination with ADT to ADT alone. A total of 4117 patients were included in efficacy analysis (2694 received novel hormonal agents and 1423 received ADT and placebo). There were no statistically significant differences in MFS (HR 0.97, 95% CrI 0.74 - 1.30) between APA and ENZA; however, both APA 0.69 (95% CI 0.52 -0.92) and ENZA 0.71 (95% CrI 0.53, 0.92) significantly improved MFS as compared to DARO. There were no statistically significant differences in OS between these drugs. DARO had fewer grade 3 or higher adverse events of fatigue (HR 0.09, 95% CrI 0.01 – 0.51) compared to ENZA. However other common adverse events such as hypertension, falls, coronary artery disease/myocardial infarction and diarrhea were not significantly different between treatment groups. There was low risk of bias amongst included studies. Conclusions: APNA and ENZA provide significant improved in MFS as compared to DARO in patients with M0CRPC. The drugs have similar toxicity profile except that DARO was associated with lower incidence of fatigue compared to ENZA. Cost effective analysis of these drugs will be reported separately.
Macht Frauenmangel Männer heiratswillig? Das Gesetz von Angebot und Nachfrage auf dem Partnermarkt (2005)

"Was haben sinkende oder steigende Geburtenzahlen mit der Chance zu tun, einen Lebenspartner zu finden? Einiges! Raphael Weiss hat im Rahmen einer Fachprogrammsarbeit theoretische Überlegungen zum Partnerschaftsverhalten am Beispiel der Schweiz empirisch überprüft. Das Ergebnis ist überraschend: Sinkende Frauenzahlen erhöhen die Heiratswahrscheinlichkeit bei Männern." (Autorenreferat)