gebhart/patrepeval huggingface dataset:
Treatment of Alzheimerʼs Disease with Sabeluzole (1997)

Sabeluzole, a new benzothiazole derivative, has been shown to be neurobiologically active preclinically and clinically appears to exert beneficial effects on memory. In this study, sabeluzole (5 or 10 mg twice daily vs. placebo) was investigated in patients with probable Alzheimer's disease over 1 year, with assessments of cognitive performance and structural changes. Cognitive performance was measured using the Alzheimer's Disease Assessment Scale periodically during treatment. Potential structural correlates in the frontal horn, caudate, third ventricle and hippocampal regions were examined by obtaining computerized tomographic (CT) images before and after treatment. Patients receiving sabeluzole evidenced greater stability than did placebo-treated patients in some cognitive measures. CT measures showed no significant changes from baseline, but some weak associations were found between relative preservation of cognitive function and smaller structural declines in the third ventricle and hippocampus. Cognitive outcome measures suggest that sabeluzole may have potential in slowing the cognitive deterioration of Alzheimer's disease. Furthermore, the method used to explore potential benefits on a morphologic level, although negative in this study, could yet have potential.
Transcriptional modulation of human IL-6 gene expression by verapamil. (1990)

Calcium channel-blocking agents interfere with the initial increase of cytosolic calcium that follows mitogenic stimulation of T lymphocytes. In cultures of mitogen-stimulated PBMC, verapamil also blocked T cell accumulation of cytoplasmic IL-2-encoding mRNA. In sharp contrast, the addition of verapamil to PHA and PMA-stimulated PBMC augmented the mitogen-stimulated increases in nuclear transcription of IL-6-encoding mRNA, steady state levels of IL-6 encoding mRNA, and release of IL-6 bioactivity. These experiments indicated that an increased IL-6 transcriptional rate rather than stabilization of transcripts accounted for the increased cytoplasmic IL-6 mRNA levels and subsequent expression of IL-6 bioactivity. These effects were not produced by nicardipine, another potent calcium channel blocker, or EGTA. We suggest that a non-calcium-dependent, IL-6 regulatory factor, absent or inactive in verapamil-treated cultures, inhibits IL-6 gene activation in mitogen-stimulated PBMC. Failure to express this inhibitory factor would result in IL-6 gene superinduction at a transcriptional level.
Thymidine Phosphorylase and Fluoropyrimidines Efficacy: A Jekyl and Hyde Story (2004)

Thymidine phosphorylase (TP) is markedly upregulated in many solid tumors such as colorectal, breast and kidney cancers. Because TP is identical to platelet-derived endothelial cell growth factor, this enzyme is believed to have angiogenic properties, although the precise mechanisms through which it promotes neoangiogenesis are still not fully elucidated. TP is involved as well in the tumoral activation of widely prescribed pyrimidine-derived antimetabolites such as 5-FU, 5'-dFUR and newly marketed capecitabine, and, in this respect, has been presented as a determinant to fluoropyrimidine efficacy in various in vitro and in vivo models. This dual and apparently contradictory role that TP plays yields inconsistent results in the study of relationships between this enzyme expression and clinical outcome in patients treated with fluoropyrimidine analogs. Some studies have shown that high tumoral TP expression was associated indeed with poor clinical response and tumor aggressiveness. Conversely, other reports demonstrated that tumoral TP could be considered as a good response factor in patients exposed to fluoropyrimidine drugs. TP exhibits then its more favorable profile, probably in converting 5-FU to active metabolites responsible for its efficacy as antitumor agent. As a result, TP-targeting as a rationale for anticancer therapy remains unclear. TP inhibitors are being synthesized as an attempt to fight neoangiogenesis, whereas promising new strategies such as taxotere/capecitabine or radiotherapy/fluoropyrimidines associations aim at nothing but boosting TP activity to optimize drug activation in tumors. Such a discrepancy illustrates the complexity of understanding and predicting the exact role of TP in the clinical outcome of patients exposed to fluoropyrimidines, a group of major drugs extensively used in oncology.
From Diagnosing the Dilemma to Divining a Cure: Post-Crisis Regulation of Financial Markets (2010)

The recent financial crisis highlights gaps in the regulation of financial markets. This Essay introduces the contributions of some of the participants in the 2009 Seton Hall Law Review Symposium exploring the future of financial markets regulation. Their contributions examine causes of the recent crisis, mechanisms that may address these concerns, and unexplored concerns that impact effective regulation of financial markets. ∗ Associate Professor of Law, Seton Hall University School of Law. J.D. University of Michigan Law School; B.S. Georgetown University. I would like to thank Erika Lopes for her excellent research assistance in the preparation of this Essay and the Editors of the Seton Hall Law Review for their editorial assistance. JOHNSON_FINAL_11.12.DOCX (DO NOT DELETE) 11/16/2010 1:36 PM 1300 SETON HALL LAW REVIEW [Vol. 40:1299
Heterochrony in Hybrid Macaques (2008)

Hybridization among phenotypically distinct phylogenetic species is ubiquitous within the order Primates, particularly cercopithecine monkeys. In primates, hybridization (and its effects on the adult phenotype) has been a topic of considerable research in biological anthropology because of its implications for interpreting the fossil record (e.g., Jolly 2001, Ackermann et al. 2006, Jolly et al. 1997). The effect of hybridization on the primate phenotype, especially growth and development, however, is not well understood and has received little attention in the literature. In this report, we examine the effects of hybridization on heterochronic growth processes and growth allometry (Table 1) using a published dataset on a sample of hybrid macaques and their parental match of Indian origin (Macaca mulatta mulatta). We focus on heterochrony because small changes in developmental timing and growth rates caused by hybrid heterosis can substantially affect the hybrid adult phenotype.
Evaluation of two X chromosomal candidate genes for Rett syndrome: Glutamate dehydrogenase-2 (GLUD2) and rab GDP-dissociation inhibitor (GDI1) (1998)

The most likely cause of the Rett syndrome (RTT) is an X-linked dominant mutation lethal in hemizygous males. Previous exclusion mapping studies have identified putative regions for the RTT gene on the X chromosome. In the present study, we evaluated two candidate genes, glutamate dehydrogenase-2 (GLUD2) and rab GDP-dissociation inhibitor (GDI1/XAP-4), chosen because of their expression patterns and functions in the central nervous system and their location in the nonexcluded region of Xq. The intronless gene GLUD2, located in Xq25 and expressed in neuronal and testicular tissues, is involved in the metabolism of glutamate, a neurotransmitter reported to be elevated in the spinal fluid of RTT individuals. The GLUD2 gene was screened for mutations by Southern hybridization and by direct sequencing of polymerase chain reaction (PCR) products. The GDI1 gene in Xq28, also known as RABGDIA or XAP-4, encodes a human GDI that is expressed predominantly in neuronal and sensory tissues. All 11 exons and splice junctions of the GDI1 gene were PCR-amplified and sequenced directly or screened by single-strand conformation analysis. No mutation in either of these two genes was found in 22 RTT patients. Therefore, GLUD2 and GDI1 can be excluded as candidate genes for this syndrome.
PZ Calibration Using Critically Refracted Waves (2002)

A-08 PZ CALIBRATION USING CRITICALLY REFRACTED WAVES Abstract In marine multi-component seismic data the vertical geophone recordings must be calibrated against the pressure recordings to account for differences such as coupling and impulse responses of the measuring devices. One known way of doing this is by applying the equation of motion and minimizing the downgoing energy in a window containing only primary reflections (Schalkwijk et al. 1999). Picking such a window may be difficult if we have a long source signature or when operating in shallow water. In this paper we utilize the same calibration approach based on a window
Extending a Parser to Distant Domains Using a Few Dozen Partially Annotated Examples (2018)

We revisit domain adaptation for parsers in the neural era. First we show that recent advances in word representations greatly diminish the need for domain adaptation when the target domain is syntactically similar to the source domain. As evidence, we train a parser on the Wall Street Journal alone that achieves over 90% F 1 on the Brown corpus. For more syntactically distant domains, we provide a simple way to adapt a parser using only dozens of partial annotations. For instance, we increase the percentage of error-free geometry-domain parses in a held-out set from 45% to 73% using approximately five dozen training examples. In the process, we demonstrate a new state-of-the-art single model result on the Wall Street Journal test set of 94.3%. This is an absolute increase of 1.7% over the previous state-of-the-art of 92.6%.
Electrochemical deposition as a unique solution processing method for insoluble organic optoelectronic materials (2014)

Electrochemical deposition enables films of low-solubility organic molecules by a solution process, without needing high vacuum or solubilising side chains.
Three-dimensional photonic crystals and their applications (2003)

We report our new approach to develop the complete three-dimensional photonic crystal and the future prospects. Our photonic crystal is constructed with GaAs (or InP) stripes stacked by a wafer-fusion technique to form an asymmetric face-centered cubic (A-FCC) structure. The stacked four layers correspond to the one-period of the A-FCC structure. The band structure has a complete photonic band gap for all wave vectors. Moreover, since the crystal is constructed with a III-V semiconductor, which is widely utilized for optoelectronic devices, by the wafer-bonding technique it is possible to introduce arbitrary defect states and light-emitters and to form an electronically active interface. Thus, once the 3D photonic crystal is realized, it will open a door for various applications including an active quantum device such as zero-threshold laser.
Generalized adaptive procedure for psychometric measurement (2008)

A new Bayesian adaptive psychometric method based on the theory of optimal experiments is introduced and evaluated in simulations over a set of possible observers. The method is flexible enough to be adapted to a wide range of psychophysical experiments (blocks of constant stimuli, n-AFC, yes/no, and discrimination paradigms) and allows specification of many types of assumptions. The four parameters of standard psychometric functions can be estimated in real-time (scales easily to more parameters). An important novelty is the possibility to adjust the desired accuracy of the parameters of interest by weights. Dynamic termination criteria can significantly improve efficiency compared to a fixed number of trials. Yes/no designs turned out to be more efficient than n-AFC in most circumstances. When using blocks of constant stimuli the performance was comparable to single stimuli placement while being more robust to certain experimental phenomena. Simulations showed that the method is at least as efficient and much more flexible than established methods.
Serodiagnosis of Louse-Borne Relapsing Fever with Glycerophosphodiester Phosphodiesterase (GlpQ) from <i>Borrelia recurrentis</i> (2000)

Human louse-borne relapsing fever occurs in sporadic outbreaks in central and eastern Africa that are characterized by significant morbidity and mortality. Isolates of the causative agent, Borrelia recurrentis, were obtained from the blood of four patients during a recent epidemic of the disease in southern Sudan. The glpQ gene, encoding glycerophosphodiester phosphodiesterase, from these isolates was sequenced and compared with the glpQ sequences obtained from other relapsing-fever spirochetes. Previously we showed that GlpQ of Borrelia hermsii is an immunogenic protein with utility as a serological test antigen for discriminating tick-borne relapsing fever from Lyme disease. In the present work, we cloned and expressed the glpQ gene from B. recurrentis and used recombinant GlpQ in serological tests. Acute- and convalescent-phase serum samples obtained from 42 patients with louse-borne relapsing fever were tested with an indirect immunofluorescence assay (IFA) and an enzyme-linked immunosorbent assay (ELISA) that used whole cells of B. recurrentis and with immunoblotting to whole-cell lysates of the spirochete and Escherichia coli producing recombinant GlpQ. The geometric mean titers of the acute- and convalescent-phase serum samples measured by IFA were 1:83 and 1:575, respectively. The immunoblot analysis identified a high level of reactivity and seroconversion to GlpQ, and the assay was more sensitive than the whole-cell IFA and ELISA using purified, recombinant histidine-tagged GlpQ. Serum antibodies to GlpQ and other antigens persisted for 27 years in one patient. We conclude that assessment of anti-GlpQ antibodies will allow serological confirmation of louse-borne relapsing fever and determination of disease prevalence.
Rational Approaches to Improving Selectivity in Drug Design (2012)

ADVERTISEMENT RETURN TO ISSUEPREVPerspectiveNEXTRational Approaches to Improving Selectivity in Drug DesignDavid J. Huggins*†‡, Woody Sherman*§, and Bruce Tidor*∥⊥#View Author Information† Department of Oncology, Hutchison/MRC Research Centre, University of Cambridge, Hills Road, Cambridge, CB2 0XZ, United Kingdom‡ Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, United Kingdom§ Schrödinger Inc., 120 West 45th Street, New York, New York 10036, United States∥Computer Science and Artificial Intelligence Laboratory, ⊥Department of Biological Engineering, and #Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States*For D.J.H.: phone, +44 1223 763367; fax, +44 1223 763 374; e-mail, [email protected]. For W.S.: phone, +1 212 295 5800; fax, +1 212 295 5801; e-mail, [email protected]. For B.T.: phone, +1 617 253 7258; fax, +1 617 252 1816; e-mail, [email protected]Cite this: J. Med. Chem. 2012, 55, 4, 1424–1444Publication Date (Web):January 12, 2012Publication History Received2 August 2011Published online12 January 2012Published inissue 23 February 2012https://doi.org/10.1021/jm2010332Copyright © 2012 American Chemical SocietyRIGHTS & PERMISSIONSACS AuthorChoiceArticle Views26263Altmetric-Citations174LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (9 MB) Get e-AlertsSUBJECTS:Inhibitors,Peptides and proteins,Selectivity,Receptors,Molecules Get e-Alerts
Comprehensive study of the resistivity of copper wires with lateral dimensions of 100 nm and smaller (2004)

Copper wires were prepared in a silicon oxide matrix using the methods of semiconductor manufacturing and were electrically characterized. The width of the smallest structure was 40 nm and of the largest, 1000 nm; the heights were 50, 155, and 230 nm. Many samples of each size have been measured in order to perform a systematic investigation. The resistivity of the sample was extracted using the temperature coefficient of resistance. A significant increase in the resistivity was found for the small structures (roughly a factor 2 for 50-nm width). A model based on physical parameters was used in the analysis of the electrical data and very good agreement was obtained. The sensitivity of the various model parameters obtained by a best-fit procedure to the experimental data has been investigated. The impact of width and height on the resistivity, the influence of electron scattering at grain boundaries compared to surface scattering, and the impact of grain sizes and impurities will be discussed in detail.
Compact Physical IR-Drop Models for Chip/Package Co-Design of Gigascale Integration (GSI) (2005)

The supply voltage decrease and power density increase of future GSI chips demand accurate models for the IR-drop. Compact physical IR-drop models of on-chip power/ground distribution networks are derived for two generic types of packages. In the early stages of design, these models enable accurate estimates of all required power/ground grid interconnect dimensions and chip pad counts that are needed for power distribution. The models also quantify the tradeoff between on-chip interconnect dimensions and the number of I/O pads required for power distribution and therefore enable rigorous chip/package co-design. Comparison with SPICE simulations show less than 1% and 5% error for the wire-bond package and the flip-chip package, respectively.
Real-time scheduling theory and Ada (1990)

Rate monotonic scheduling theory puts real-time software engineering on a sound analytical footing. The authors review the theory and its implications for Ada.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Recent Advances in the Mitsunobu Reaction: Modified Reagents and the Quest for Chromatography‐Free Separation (2004)

Abstract Recent progress in synthetic approaches to the Mitsunobu reaction are reviewed. Efforts that have focused on the phase‐switching modifications of phosphane, azodicarboxylate, and nucleophilic components are emphasized. An approach to product separation with fluorous compounds is reviewed in detail. Alternative reagents and recently introduced products are cited. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
On partitioning polygons (1985)

Chaselle has shown how to partition any simple polygon P into two polygons, each of total weight not greater than two thirds of the total weight of P, by drawing a diagonal within P. Under the assumption that a triangulation of P is given, we provide a straightforward proof of Chaselles theorem and derive generalizations of the theorem to include polygons with polygonal holes.
Adjacent releases of mantle helium and soil CO<sub>2</sub> from active faults: Observations from the Marmara region of the North Anatolian Fault zone, Turkey (2009)

Volatile releases, in terms of CO 2 efflux and noble gas of mantle origin, are investigated in the Marmara region of the seismically active North Anatolian Fault (NAF) zone. A total of 180 CO 2 efflux measurements (1 to 309 g m −2 d −1 ) were carried out along four transects across the NAF. Spatial variability of surface CO 2 effluxes was higher at faulted sites, relative to comparable background areas. The δ 13 C values of soil CO 2 are −24.0 to −15.6‰ without correlation with CO 2 efflux values, which suggest that CO 2 efflux anomaly is caused by fault‐related biogenic gas flow. Furthermore, 36 gas and water samples from spring sites were investigated for 3 He/ 4 He ratios which resulted in a range from 0.26 R / R A to 4.22 R / R A . Large mantle helium contributions were observed from several sources along the NAF. The high CO 2 efflux sector on the Gaziköy‐Saros fault along the NAF coincides with the area of high mantle helium flux. This shows that fault zones play an important role both in transferring mantle helium to the surface and in causing fault‐related biogenic gas flow.
Both Subunits of ATP-Citrate Lyase from<i>Chlorobium tepidum</i>Contribute to Catalytic Activity (2006)

ATP-citrate lyase (ACL) is an essential enzyme of the reductive tricarboxylic acid (RTCA) pathway of CO(2) assimilation. The RTCA pathway occurs in several groups of autotrophic prokaryotes, including the green sulfur bacteria. ACL catalyzes the coenzyme A (CoA)-dependent and MgATP-dependent cleavage of citrate into oxaloacetate and acetyl-CoA, representing a key step in the RTCA pathway. To characterize this enzyme from the green sulfur bacterium Chlorobium tepidum and determine the role of its two distinct polypeptide chains, recombinant holo-ACL as well as its two individual subunit polypeptides were synthesized in Escherichia coli. The recombinant holoenzyme, prepared from coexpressed large and small ACL genes, and the individual large and small subunit polypeptides, prepared from singly expressed genes, were all purified to homogeneity to high yield. Purified recombinant holo-ACL was isolated at high specific activity, and its k(cat) was comparable to that of previously prepared native C. tepidum ACL. Moreover, the purified recombinant large and small subunit polypeptides were able to reconstitute the holo-ACL in vitro, with activity levels approaching that of recombinant holo-ACL prepared from coexpressed genes. Stoichiometric amounts of each subunit protein were required to maximize the activity and form the most stable structure of reconstituted holo-ACL. These results suggested that this reconstitution system could be used to discern the catalytic role of specific amino acid residues on each subunit. Reconstitution and mutagenesis studies together indicated that residues of each subunit contributed to different aspects of the catalytic mechanism, suggesting that both subunit proteins contribute to the active site of C. tepidum ACL.
Creating Hybrid Genes by Homologous Recombination (2000)

Recombination of homologous genes is a powerful mechanism for generating sequence diversity, and can be applied to protein analysis and directed evolution. In vitro recombination methods such as DNA shuffling are very flexible and can give hybrid genes with multiple crossovers; they have been used extensively to evolve proteins with improved and novel properties. In vivo recombination in both E. coli and yeast is greatly enhanced by double-strand breaks; for E. coli, mutant strains are often necessary to obtain high efficiency. Intra- and inter-molecular recombination in vivo have distinct features; both give hybrids with one or two crossovers, and have been used to study structure-function relationships of many proteins. Recently in vivo recombination has been used to generate diversity for directed evolution, creating a large phage display antibody library. Recombination methods will become increasingly useful in light of the explosion in genomic sequence data and potential for engineered proteins.