gebhart/patrepeval huggingface dataset:
Discovery of Begacestat, a Notch-1-Sparing γ-Secretase Inhibitor for the Treatment of Alzheimer’s Disease (2008)

SAR on HTS hits 1 and 2 led to the potent, Notch-1-sparing GSI 9, which lowered brain Abeta in Tg2576 mice at 100 mg/kg po. Converting the metabolically labile methyl groups in 9 to trifluoromethyl groups afforded the more stable analogue 10, which had improved in vivo potency. Further side chain modification afforded the potent Notch-1-sparing GSI begacestat (5), which was selected for development for the treatment of Alzheimer's disease.
Phospho Sugars; Novel Preparation and Their Glycosyl Compounds (1989)

Treatment of 1-phenyl-2-,and -3-phospholene 1-oxides with N-bromosuccinimide affords 4-bromo-1-phenyl-2-phospholene 1-oxide. Substitution of the bromide with acetate, followed by stereoselective oxidation with osmium tetroxide and peracetylation with acetic anhydride/pyridine affords phospho sugar derivatives of tetrafuranose. Furthermore, N-, O-, and S-glycosyl compounds of phospho sugars can be prepared from 3-methyl-1-phenyl-2-phospholenc 1-oxide by bromination and nucleophilic substitution reactions. This is a novel and excellent route to prepare phospho sugar derivatives.
Ion Selectivity of Lysenin Channels (2015)

Ion channels in living systems show a pronounced selectivity for transported ions. This key feature is used by living cells to create and maintain electrochemical gradients that participate in multiple physiological functions. Our work focuses on measuring permeability of lysenin channels from anions and cations. Our experiments are comprised of an electrophysiology setup that includes lysenin channels inserted into planar bilayer lipid membranes. The solutions bathing the membrane are wired to an Axopatch 200B electrophysiology amplifier through Ag/AgCl electrodes. The transmembrane voltages, measured for asymmetrical ionic conditions, have been estimated from the intercept of I-V plots. The experimental values of the transmembrane voltages have been fitted with the Goldman-Hodgkin-Katz equation and indicated that lysenin channels discriminate between anions and cations. Our research showed that owing to the ionic selectivity, it is possible to produce transmembrane voltages in the physiological range (up to +/-100mV). Measurements of the transmembrane voltages at different ionic compositions suggest that lysenin channels also possess supplementary selectivity for cations only.
Nanostructured graphene/Fe3O4 incorporated polyaniline as a high performance shield against electromagnetic pollution (2013)

The development of high-performance shielding materials against electromagnetic pollution requires mobile charge carriers and magnetic dipoles. Herein, we meet the challenge by building a three-dimensional (3D) nanostructure consisting of chemically modified graphene/Fe3O4(GF) incorporated polyaniline. Intercalated GF was synthesized by the in situ generation of Fe3O4 nanoparticles in a graphene oxide suspension followed by hydrazine reduction, and further in situ polymerization with aniline to form a polyaniline composite. Spectroscopic analysis demonstrates that the presence of GF hybrid structures facilitates strong polarization due to the formation of a solid-state charge-transfer complex between graphene and polyaniline. This provides proper impedance matching and higher dipole interaction, which leads to the high microwave absorption properties. The higher dielectric loss (ε'' = 30) and magnetic loss (μ'' = 0.2) contribute to the microwave absorption value of 26 dB (>99.7% attenuation), which was found to depend on the concentration of GF in the polyaniline matrix. Moreover, the interactions between Fe3O4, graphene and polyaniline are responsible for superior material characteristics, such as excellent environmental (chemical and thermal) degradation stability and good electric conductivity (as high as 260 S m(-1)).
L-shaped piezoelectric motor-Part I: Design and experimental analysis (2012)

This paper proposes an L-shaped piezoelectric motor consisting of two piezoelectric bimorphs of different lengths arranged perpendicularly to each other. The coupling of the bending vibration mode of the bimorphs results in an elliptical motion at the tip. A detailed finite element model was developed to optimize the dimensions of bimorph to achieve an effective coupling at the resonance frequency of 246 Hz. The motor was characterized by developing rotational and linear stages. The linear stage was tested with different friction contact surfaces and the maximum velocity was measured to be 12 mm/s. The rotational stage was used to obtain additional performance characteristics from the motor: maximum velocity of 120 rad/s, mechanical torque of 4.7 × 10-(5) N·m, and efficiency of 8.55%.
Secure data communication and cryptography based on DNA based message encoding (2014)

Secure data communication is the most important and essential issue in the area of message transmission over the networks. Cryptography provides the way of making secure message for confidential message transfer. Cryptography is the process of transforming the sender's message to a secret format called cipher text that only intended receiver will get understand the meaning of the secret message. There are various cryptographic or DNA based encoding algorithms have been proposed in order to make secret message for communication. But all these proposed DNA based encryption algorithms are not secure enough to provide better security as compared with the today's security requirement. In this paper, we have proposed a technique of encryption that will enhance the message security. In this proposed algorithm, a new method of DNA based encryption with a strong key of 256 bit is used. Along with this big size key various other encoding tools are used as key in the encoding process of the message like random series of DNA bases, modified DNA bases coding. Moreover a new method of round key selection is also given in this paper to provide better security in the message. The cipher text contains the extra bit of information as similar with the DNA strands that will provide better and enhanced security against intruder's attack.
Big bang theory of stem-like T cells confirmed (2014)

In this issue of Blood , Stemberger et al show that the progeny of a single CD62Lhi cell can provide protection against bacterial challenge and that ultra-low doses of cytomegalovirus (CMV)-specific CD8+ T cells can expand greatly in humans.[1][1]

![Figure][2] 

Current model of CD8+ T-cell
Mass-spectrometry analysis of genetic markers of S. pneumoniae resistance to β-lactam antibiotics (2010)

Beta-lactam antibiotics remain the drugs of choice for treatment of S. pneumoniae infections in spite of growing level of resistance. The formation of S. pneumoniae resistance to these drugs is mediated by modifications of the penicillin-binding proteins (PBPs), the targets of the antibiotic action. A new approach to detection of mutations in PBP1A, 2B and 2X genes based on minisequencing reaction followed by MALDI-ToF (Matrix-Assisted Laser Desorption/Ionization Time of Flight) mass spectrometry was developed in this study. The evaluation of these mutations prevalence in clinical S. pneumoniae isolates (n = 194) with different susceptibility level to beta-lactam antibiotics was performed. Twenty-four different combinations of mutations in PBPs (genotypes) were detected. All isolates susceptible to penicillin (n = 49, MIC > or = 0.06 > or = gamma/ml) carried no mutations in all analyzed loci. For 145 S. pneumoniae isolates with reduced susceptibility to penicillin (MIC > 0.06 > or = gamma/ml) the mutations in PBPs were detected in 133 (91.7 %) cases that testify to high diagnostic sensitivity of such approach. The isolates with MIC > or = 4 > or = gamma/ml (n = 20) carried multiple mutations in all analyzed genes that confirms cumulative effects of penicillin resistance formation. However, it was not possible to associate observed mutations in PBPs genes with decrease of susceptibility to cefotaxime that allows suggesting the entire difference in molecular mechanisms of formation of resistance to penicillins and cephalosporins. The offered method of S. pneumoniae genotyping is suitable for susceptibility testing to penicillin of individual isolates and for molecular monitoring of the resistance determinants in population.
Radar-based Retrievals of Cloud Properties in the Arctic and New Results from SHEBA (2001)

Clouds play a crucial role in the radiative balance of the Earth’s surface, particularly in the Arctic where they participate in various feedback mechanisms with the underlying surface that consists of a complex mixture of snow, sea-ice, and open water. Our current understanding of clouds, and especially their representation in climate models, is limited. Longer term
Model-Driven Management a of Construction Carbon Footprint: Case Study (2016)

This paper applies, extends, and verifies a model-driven framework for managing carbon footprint of a construction project using a case study approach. Current construction management practice lacks methods to track carbon footprint of the construction phase since the application of life cycle assessment (LCA) methods has remained primarily limited to design and operation phases of a project. In addition, the current methods heavily rely on user inputs on materials and the state of planned-vs.-actual work-in-progress. The presented framework addresses existing inefficiencies by leveraging 4D building information models (BIM) in conjunction with LCA tools to benchmark carbon footprint during pre-construction phases and monitor it during the construction phase. The management framework—built on earned value management concepts—offers metrics to assess and communicate deviations between benchmarked and actual carbon footprint, and facilitates root-cause assessments to minimize performance deviations, and excessive carbon footprints. As a full proof-of-concept, an extended case study is conducted on a real-world project. The application of the proposed management framework as a mechanism for increased environmental product data in the supply chain, establishing policies requiring adherence to a carbon footprint budget during project tendering, and incentivizing reductions in carbon footprint through a cap-and-trade scheme are discussed in detail.
The Toeplitz matrix $e^{- \kappa |i-j|}$ and its application to a layered electron gas (2020)

We present an explicit solution of the eigen-spectrum Toeplitz matrix $C_{ij}= e^{- \kappa |i-j|}$ with $0\leq i,j \leq N$ and apply it to find analytically the plasma modes of a layered assembly of 2-dimensional electron gas. The solution is found by elementary means that bypass the Wiener-Hopf technique usually used for this class of problems. It rests on the observation that the inverse of $C_{ij}$ is effectively a nearest neighbor hopping model with a specific onsite energies which can in turn be diagonalized easily. Extensions to a combination of a Toeplitz and Hankel matrix, and to a generalization of $C_{ij}$, are discussed at the end of the paper.
Embryo implantation and GnRH antagonists (2000)

When gonadotrophin-releasing hormone (GnRH) was discovered, the agonist and antagonist of GnRH were developed to control the release of FSH and LH by the gonadotrophs. More than 10 years of research were needed to develop a GnRH antagonist free of histamine release. Recent studies have shown that these GnRH antagonists are effective in preventing a rise in LH during ovarian stimulation in IVF. However, a decrease in ongoing pregnancies seems to suggest that implantation rates per transferred embryo are reduced in GnRH antagonist-stimulated cycles. In my opinion, these data highlight an area less well known to clinicians: the role of the GnRH antagonist at the cellular level in extrapituitary tissues. There are sufficient data in the literature suggesting that GnRH antagonist is an inhibitor of the cell cycle by decreasing the synthesis of growth factors. Given that, for folliculogenesis, blastomere formation and endometrium development, mitosis is everything; the interaction between the GnRH antagonist and the GnRH receptor (present in all these cells and tissues) may compromise the mitotic programme of these cells. This is the Rubicon for the GnRH antagonist: to demonstrate irrevocably that, at the minimal doses necessary to suppress LH release, it does not affect processes such as implantation, embryo development and folliculogenesis.
Atmospheric-pressure argon afterglows as a detector for gas chromatography (1983)

Ames has been involved in developing an atmospheric pressure, active nitrogen (APAN) afterglow as an excitation source for analytical emission spectroscopy and as an element-specific, multielemental gas chromatography detector. The same type of discharges and afterglows can be produced from both helium and argon. The argon afterglow has been evaluated as an element-selective detector for gas chromatography by monitoring atomic spectral lines arising from S, P, C, N, Cl, Br, and I containing species. Limits of detection have ranged from 0.08 ng for P to 50 ng for Br.
Measurements of mechanical properties of microfabricated thin films (2002)

Mechanical properties of titanium thin films of 0.5 /spl mu/m thickness, microfabricated by magnetron sputtering, were measured by using a novel tensile machine. These thin films are difficult to handle because they are markedly fragile, so the thin film specimens were fabricated by using semiconductor manufacturing technology in silicon frames to protect them. The test section of these specimens was 300 /spl mu/m in width and 1.4 mm in length. By gripping the thin film specimen with a new device using a micrometer, it could be mounted on the tensile machine easily. The stress-strain diagrams of thin films were measured continuously in the atmosphere at room temperature. Tensile tests were conducted on specimens of 1.0 to 1.4 mm gauge length in order to examine the effect of gauge length on the measurements of mechanical properties. Measurements of Young's modulus, tensile strength and breaking elongation were independent of gauge length for our range of measurements. The experimental results indicated that the titanium thin films had a smaller breaking elongation although they had a larger tensile strength than bulk pure titanium.
The Cell : molecular approach (2004)

This book provides a solid conceptual framework and an introduction to the experimental nature of contemporary research.
Relationships of Polymorphisms for Growth Hormone and Growth Hormone Receptor Genes with Milk Production Traits for Italian Holstein-Friesian Bulls (1996)

Allelic variation in the structural or regulatory sequences of growth hormone and its receptor genes might directly or indirectly affect milk traits. This possibility prompted us to investigate the eventual relationships of restriction fragment length polymorphisms at the locus of bovine growth hormone (using TagI and MspI restriction enzymes) and its receptor (using TaqI restriction enzyme) to PTA of milk production traits of bulls. Ninety-one Italian Holstein-Friesian bulls were used in this experiment, and data were analyzed with a fixed linear model. The restriction fragment length polymorphisms at the growth hormone locus did not affect the milk traits studied. Six restriction enzyme TaqI bands of 7.1, 6.2, 5.7, 5.4, 4.2, and 3.3 kb with nine patterns were observed after hybridization by a cDNA probe containing the coding sequences for the intracellular C-terminal part of the receptor. The effect of this polymorphism on PTA for milk protein percentage was highly significant and was favorable for the rare (6.6%) 5.7- and 5.4-kb pattern. Our results indicate that further study is needed to explain the DNA polymorphism and to obtain more definite conclusions about effects on milk traits.
Shape‐shifting proteins with a potential link to drug side effects (2010)

Human porphobilinogen synthase (huPBGS, EC 4.2.1.24) exists as an equilibrium of high activity octamers, low activity hexamers, and alternate dimer configurations that dictate the stoichiometry and architecture of further assembly. Reduced huPBGS activity factors in the disease states lead poisoning and ALAD porphyria, the latter of which involves hexamer‐favoring huPBGS variants. The Jaffe lab has established that small molecules can allosterically inhibit huPBGS activity by stabilizing the hexamer and putatively potentiate disease states. Two such inhibitors were identified by in silico docking to a hexamer‐specific surface cavity of huPBGS. The compounds were confirmed to inhibit wild‐type huPBGS activity by stabilizing the hexamer in vitro, and showed increased potency against two porphyria‐associated variants. One of the compounds is a structural analog to two amebicidal drugs, which have porphyria‐like side effects, and were found to stabilize the huPBGS hexamer in vitro. If the drugs can inhibit huPBGS by inducing hexamer formation in vivo, this would constitute an unprecedented explanation for a drug side effect. It is possible that other known drugs, toxins, or environmental contaminants could have a hexamer‐stabilizing inhibitory effect on huPBGS. An ongoing screen of ~1500 compounds approved for pharmaceutical use has so far revealed 6 compounds that stabilize the huPBGS hexamer in vitro.
Identification of the PLA2G6 c.1579G>A Missense Mutation in Papillon Dog Neuroaxonal Dystrophy Using Whole Exome Sequencing Analysis (2017)

Whole exome sequencing (WES) has become a common tool for identifying genetic causes of human inherited disorders, and it has also recently been applied to canine genome research. We conducted WES analysis of neuroaxonal dystrophy (NAD), a neurodegenerative disease that sporadically occurs worldwide in Papillon dogs. The disease is considered an autosomal recessive monogenic disease, which is histopathologically characterized by severe axonal swelling, known as "spheroids," throughout the nervous system. By sequencing all eleven DNA samples from one NAD-affected Papillon dog and her parents, two unrelated NAD-affected Papillon dogs, and six unaffected control Papillon dogs, we identified 10 candidate mutations. Among them, three candidates were determined to be "deleterious" by in silico pathogenesis evaluation. By subsequent massive screening by TaqMan genotyping analysis, only the PLA2G6 c.1579G>A mutation had an association with the presence or absence of the disease, suggesting that it may be a causal mutation of canine NAD. As a human homologue of this gene is a causative gene for infantile neuroaxonal dystrophy, this canine phenotype may serve as a good animal model for human disease. The results of this study also indicate that WES analysis is a powerful tool for exploring canine hereditary diseases, especially in rare monogenic hereditary diseases.
Contribution a la formulation generale d'un probleme de synthese de mecanismes et resolution (1999)

En synthese de mecanismes, le choix des topologies de mecanismes, i. E. Le choix de la nature des articulations et de leur arrangement, est un probleme difficile. En effet, il pose la question du choix de variables non continues et non numeriques : on ne peut pas comparer deux articulations. Par opposition avec l'etude des parametres de dimension (longueur des corps ou orientation entre les liaisons) et de placement qui sont tres largement abordes dans la litterature, cette question est aujourd'hui peu discutee. Dans nos travaux, nous decrivons une modelisation d'un probleme de synthese de mecanismes sous la forme d'un probleme d'optimisation. Pour cela, nous proposons une formalisation generale des mecanismes et introduisons une nouvelle variable d'optimisation liee a leurs topologies. Puis, nous analysons l'ensemble des taches qu'ils sont susceptibles de realiser. Ces taches sont la manipulation d'objets, la transformation de mouvement, l'accessibilite a un repere, a une surface, a un volume et la parcourabilite de trajectoire. Nous proposons de resoudre notre probleme de synthese de mecanismes a l'aide de methodes d'optimisation stochastiques comme les algorithmes genetiques ou le recuit simule. Enfin, nous presentons deux applications en vue de realiser deux classes de taches qui sont la parcourabilite de trajectoires et l'accessibilite a une surface. Ces exemples sont envisages pour des mecanismes plans seriels et a chaine fermees et pour des mecanismes spatiaux seriels en presence d'obstacles. La validite de la methode est demontree sur des exemples industriels.
ADME Evaluation in Drug Discovery. 6. Can Oral Bioavailability in Humans Be Effectively Predicted by Simple Molecular Property-Based Rules? (2007)

A critically evaluated database of human oral bioavailability for 768 chemical compounds is described in this study (http://modem.ucsd.edu/adme), which provides the scientific community a publicly available and reliable source for developing predictive models of human oral bioavailability. The correlations between several important molecular properties and human oral bioavailability were investigated and compared with an earlier report by analyzing the rat oral bioavailability data (J. Med. Chem. 2002, 45, 2615). We showed that the percentages of compounds meeting the criteria based on molecular properties does not distinguish compounds with poor oral bioavailability from those with acceptable values, which may suggest that no simple rule based on molecular properties can be used as general filters to predict oral bioavailability with high confidence. A data set of intestinal absorption was also examined and compared with that of oral bioavailability. The performance of these rules based on molecular properties in the prediction of intestinal absorption is obviously much better than that of oral bioavailability in term of false positive rate, and, therefore, the applications of the "rule-based" approaches on the prediction of human bioavailability should be very cautious.
Evaluation of a patient prior to second‐look surgery (1991)

The evaluation of a patient with a suspected colorectal malignancy is well defined; however, the preoperative work-up of a patient who is a candidate for second-look surgery is controversial and based less on scientific evidence than on empiric or anecdotal grounds. The preoperative assessment of these patients can be divided into two phases. Phase I consists of a thorough history, physical examination, and routine laboratory tests as the most logical and traditional starting point. Phase II consists of specific tests aimed at evaluating the extent of the recurrence and the resectability of the tumor. Of the various modalities available, the enhanced computerized tomogram is currently the method most likely to provide significant information prior to carcinoembryonic antigen (CEA) -directed second-look surgery. The results of the preoperative evaluation together with a thorough understanding of the natural history of the disease will offer a clear perspective as to the most likely outcome.