gebhart/patrepeval huggingface dataset:
Pharmacokinetics, Safety, Tolerability, and Pharmacodynamics of Alicapistat, a Selective Inhibitor of Human Calpains 1 and 2 for the Treatment of Alzheimer Disease: An Overview of Phase 1 Studies (2018)

Alicapistat is an orally active selective inhibitor of calpain 1 and 2 whose overactivation has been linked to Alzheimer disease (AD). Three studies were conducted in healthy subjects (18-55 years), 1 in healthy elderly subjects (≥65 years), and 1 in patients with mild to moderate AD. Four studies assessed pharmacokinetics, 1 study in healthy subjects assessed pharmacodynamics (sleep parameters, particularly rapid eye movement [REM], as a measure of central nervous system [CNS] penetration and activity), and all studies assessed safety. Participants received single doses or multiple twice-daily doses of alicapistat for up to 14 days. Maximum alicapistat plasma concentrations were reached in 2 to 5 hours; half-life was 7 to 12 hours postdose. Alicapistat exposure was dose proportional in the alicapistat 50- to 1000-mg dose range. Exposure of the alicapistat R,S diastereomer was approximately 2-fold greater than exposure of the R,R diastereomer in healthy young and elderly subjects and patients with AD. Alicapistat at 400- or 800-mg twice-daily doses had no effect on REM sleep parameters, whereas the active control, donepezil at 10 mg twice daily, affected sleep parameters. Across all trials, the incidence of treatment-emergent adverse events was similar in the placebo and alicapistat groups. There were no clinically significant changes in vital signs and laboratory measurements. The lack of an effect of alicapistat on sleep suggests that concentrations in the CNS were inadequate or that preclinical studies do not predict alicapistat effects in humans.
Coexistence of Grain‐Boundaries‐Assisted Bipolar and Threshold Resistive Switching in Multilayer Hexagonal Boron Nitride (2017)

The use of 2D materials to improve the capabilities of electronic devices is a promising strategy that has recently gained much interest in both academia and industry. However, while the research in 2D metallic and semiconducting materials is well established, detailed knowledge and applications of 2D insulators are still scarce. In this paper, the presence of resistive switching (RS) in multilayer hexagonal boron nitride ( h ‐BN) is studied using different electrode materials, and a family of h ‐BN‐based resistive random access memories with tunable capabilities is engineered. The devices show the coexistence of forming free bipolar and threshold‐type RS with low operation voltages down to 0.4 V, high current on/off ratio up to 10 6 , and long retention times above 10 h, as well as low variability. The RS is driven by the grain boundaries (GBs) in the polycrystalline h ‐BN stack, which allow the penetration of metallic ions from adjacent electrodes. This reaction can be boosted by the generation of B vacancies, which are more abundant at the GBs. To the best of our knowledge, h ‐BN is the first 2D material showing the coexistence of bipolar and threshold RS, which may open the door to additional functionalities and applications.
Urolithiasis, Endourology and Laparoscopy (2007)

No AccessJournal of UrologyAdult urology1 Oct 2007Urolithiasis, Endourology and Laparoscopy Ralph ClaymanM.D. Ralph ClaymanRalph Clayman More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2007.06.023AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Urolithiasis, Endourology and Laparoscopy." The Journal of Urology, 178(4), pp. 1436–1437 © 2007 by American Urological AssociationFiguresReferencesRelatedDetails Volume 178Issue 4October 2007Page: 1436-1437 Advertisement Copyright & Permissions© 2007 by American Urological AssociationMetricsAuthor Information Ralph Clayman More articles by this author Expand All Advertisement PDF DownloadLoading ...
Regulation of Iron Transport inStreptococcus pneumoniaeby RitR, an Orphan Response Regulator (2004)

RitR (formerly RR489) is an orphan two-component signal transduction response regulator in Streptococcus pneumoniae that has been shown to be required for lung pathogenicity. In the present study, by using the rough strain R800, inactivation of the orphan response regulator gene ritR by allele replacement reduced pathogenicity in a cyclophosphamide-treated mouse lung model but not in a thigh model, suggesting a role for RitR in regulation of tissue-specific virulence factors. Analysis of changes in genome-wide transcript mRNA levels associated with the inactivation of ritR compared to wild-type cells was performed by the use of high-density DNA microarrays. Genes with a change in transcript abundance associated with inactivation of ritR included piuB, encoding an Fe permease subunit, and piuA, encoding an Fe carrier-binding protein. In addition, a dpr ortholog, encoding an H(2)O(2) resistance protein that has been shown to reduce synthesis of reactive oxygen intermediates, was activated in the wild-type (ritR(+)) strain. Microarray experiments suggested that RitR represses Fe uptake in vitro by negatively regulating the Piu hemin-iron transport system. Footprinting experiments confirmed site-specific DNA-binding activity for RitR and identified three binding sites that partly overlap the +1 site for transcription initiation upstream of piuB. Transcripts belonging to other gene categories found to be differentially expressed in our array studies include those associated with (i) H(2)O(2) resistance, (ii) repair of DNA damage, (iii) sugar transport and capsule biosynthesis, and (iv) two-component signal transduction elements. These observations suggest that RitR is an important response regulator whose primary role is to maintain iron homeostasis in S. pneumoniae. The name ritR (repressor of iron transport) for the orphan response regulator gene, rr489, is proposed.
Nový český stafylokok, Staphylococcus simiae (2005)

V taxonomickem casopise International Journal of Systematic and
Evolutionary Microbiology byly popsany vlastnosti noveho
ceskeho zastupce rodu Staphylococcus, který byl pojmenovan S.
simiae. Vsech jeho 8 dosavadnich izolatů bylo zachyceno z
rektalnich výtěrů z nemocných, resp. zdravých jihoamerických
opic kotul veverovitý. Fenotypove vlastnosti noveho druhu jsou
nejbližsi k druhu S. piscifermentans, podle genotypizace je S.
simiae nejbližsi druhu S. aureus.
Alterations in sperm long RNA contribute to the epigenetic inheritance of the effects of postnatal trauma (2018)

Abstract Psychiatric diseases have a strong heritable component known to not be restricted to DNA sequence-based genetic inheritance alone but to also involve epigenetic factors in germ cells 1,2 . Initial evidence suggested that sperm RNA is causally linked 2,3 to the transmission of symptoms induced by traumatic experiences. Here we show that alterations in long RNA in sperm contribute to the inheritance of specific trauma symptoms. Injection of long RNA fraction from sperm of males exposed to postnatal trauma recapitulates the effects on food intake, glucose response to insulin and risk-taking in adulthood whereas the small RNA fraction alters body weight and behavioral despair. Alterations in long RNA are maintained after fertilization, suggesting a direct link between sperm and embryo RNA.
A Pilot Pre and Post 4 Week Intervention Evaluating the Effect of a Proprietary, Powdered, Plant Based Food on Micronutrient Status, Dietary Intake, and Markers of Health in a Healthy Adult Population (2022)

Although energy intake decreased during the intervention period, the adherence to recommended micronutrient intake, as quantified by the dietary Total Adherence Score, significantly increased which tallies with the preservation or improvement of micronutrient status. This study potentially demonstrates that consuming only Huel for 4 weeks does not negatively affect micronutrient status.
Enhancing transesterification reactions by using pervaporation (2012)

Pervaporation was used to enhance transesterification reactions of methyl acetate and n-butanol to yield n-butyl acetate and methanol. This reaction was heterogeneously catalyzed by a strongly acidic ion-exchange resin (Amberlyst 15). Several commercial membrane types were used to establish their grade of application at different concentrations of the binary mixture methanol/n-butyl acetate. Self-made membranes were used to improve the performance of the separation. Comparison in terms of permeability and selectivity of methanol showed the potential of pervaporation for organic-organic separations. The mass transfer through the membrane was discussed to elucidate the separation mechanism on a microscopic level.
Accuracy of Transthoracic Echocardiography in Assessing Retro-aortic Rim prior to Device Closure of Atrial Septal Defects (2014)

TTE is a sensitive and specific screening test for deficient retro-aortic rim across a range of patient ages and sizes.
Anomalous exciton lifetime by an electromagnetic coupling of self-assembled quantum dots (2007)

We report on the experimental observation of a hitherto ignored long-range electromagnetic coupling between self-assembled quantum dots. A 12 times enhancement of the quantum dot exciton lifetime is observed by means of time-resolved differential reflection spectroscopy. The enhancement is explained by utilizing and extending the local field effects as developed in \emph{Phys. Rev. B \textbf{64},125326 (2001)}. The electromagnetic coupling of the quantum dots results in a collective polarizability, and is observed as a suppression of the emission rate. Our results reveal that the coupling is established over a distance exceeding 490 nm. Moreover, the mutual coupling strength is optically tuned by varying the pump excitation density and enables us to optically tune the exciton lifetime.
Lecture 12. Entropy and The Second Law. (2012)

UCI Chem 131C Thermodynamics and Chemical Dynamics (Spring 2012) Lec 12. Thermodynamics and Chemical Dynamics -- Entropy and The Second Law -- Instructor: Reginald Penner, Ph.D. Description: In Chemistry 131C, students will study how to calculate macroscopic chemical properties of systems. This course will build on the microscopic understanding (Chemical Physics) to reinforce and expand your understanding of the basic thermo-chemistry concepts from General Chemistry (Physical Chemistry.) We then go on to study how chemical reaction rates are measured and calculated from molecular properties. Topics covered include: Energy, entropy, and the thermodynamic potentials; Chemical equilibrium; and Chemical kinetics. Index of Topics 0:04:00 Energy Is Conserved for an Isolated System... 0:06:51 Entropy 0:15:53 Carnot Cycle 0:24:18 Efficiency 0:27:52 Data on an Adiabat 0:33:50 Temperature-Entropy Diagram 0:34:48 S is a State Function
Production of a specific polyclonal antibody against the rat β thyroid receptor, using synthetic peptide as antigen (1991)

We have developed a polyclonal antibody to a synthetic peptide corresponding to the deduced amino acid residues 67-80 of the amino terminal sequence of the rat thyroid receptor beta cDNA. Immunopositive sera were identified by radioimmunoassay and purified by affinity chromatography. The antibody specifically immunoprecipitated the labelled thyroid receptor beta synthetized in vitro but not the rat thyroid receptor alpha. Furthermore, 38% of the L-T3 binding capacity of the rat liver nuclear receptor were immunoabsorbed by this antibody. By immunocytochemistry, this antibody stained specifically the nuclei of hepatocytes while no staining was observed in the rat testis. This study presents a specific polyclonal antibody against the thyroid receptor beta. This antibody will be of a great help in determining the role of the beta receptors in the mechanism of action of thyroid hormone.
Kinetic Isotopic Effect Studies of Iron–Nitrogen–Carbon Electrocatalysts for Oxygen Reduction Reaction (2019)

The kinetic isotopic effect (KIE) of oxygen reduction reaction (ORR) was studied via the investigation of both Koutecky−Levich and Tafel methods on atomically dispersed iron-containing, a.k.a. iron−nitrogen−carbon (Fe−N−C) electrocatalyst. This type of catalyst has been under intensive development for use as a platinum-group-metal-free cathode catalyst in polymer electrolyte membrane fuel cells. The KIE value derived from the Tafel method (the slopes of the semilogarithmic representation of the polarization data) is effectively 1, indicating that for this Fe–N–C electrocatalyst, the rate-determining step (RDS), i.e., first electron charge transfer, is independent of the proton/deuteron ratio (H⁺/D⁺). This finding suggests that the RDS of the Fe–N–C catalysts is not the main factor limiting its performance. Thus, through careful optimization of structure and morphology resulting in overcoming other limitations, Fe–N–C catalysts could, in principle, successfully compete with Pt-based ORR electrocatalysts. In contrast, the KIE value derived from the Koutecky–Levich method, based on the analysis of linear sweep voltammetry in the diffusion-limited region of polarization response at varied convective conditions (electrode rotating speeds), is approximately 2, thus implying that in mass-transport-controlled region of ORR, the mechanism and, hence, the RDS are H⁺-dependent. This behavior, combined with the understanding that Fe–N–C display multiple active sites, suggests a more complex and more limited mechanism of ORR for the sites involved in hydrogen peroxide production and further reduction, a.k.a. “parallel” or peroxide pathway. The catalysts exhibiting this hydrogen peroxide production (bifunctional or 2 × 2 e–) pathway will be intermittently inferior in ORR due to the concerted proton/electron charge-transfer process as RDS.
Hydrocarbon bio-jet fuel from bioconversion of poplar biomass: techno-economic assessment (2016)

A unique biorefinery is explored to produce a hydrocarbon biofuel with a high yield from bone dry wood of 330 L t<sup>-1</sup>. This yield is achieved chiefly due to the use of acetogenic bacteria that do not produce carbon dioxide as a co-product during fermentation. Capital investment is significant in the biorefinery in part because hydrogen is required to produce a fully de-oxygenated fuel. Minimum selling price to achieve reasonable returns on investment is sensitive to capital financing options because of high capital costs. Various strategies, such as producing alternative, intermediate products, are investigated with the intent to reduce risk in building the proposed facility. It appears that producing and selling these intermediates may be more profitable than converting all the biomass into aviation fuel. With variability in historical petroleum prices and environmental subsidies, a high internal rate of return would be required to attract investors.
Attosecond Spectroscopy of Band-gap Dynamics (2015)

The ability to transfer electrons from valence to conduction band states in a semiconductor is the basis of modern electronics. Here, attosecond spectroscopy is used to resolve this process in real-time. The excitation of electrons across the band-gap of silicon by few-cycle laser pulses is found to induce lasting modifications of the XUV absorbance spectrum in steps synchronized with the laser electric field oscillations, indicative of light-field induced electron tunneling [1]. In contrast, in SiO<inf>2</inf>, a dielectric with 9 eV band-gap, similar excitation pulses are found to cause a transient field-induced polarizability without lasting population transfer [2].
Perpendicular Interlaced Magnetic Recording (2019)

Perpendicular magnetic recording is the current generation hard disk drive technology, which enables the continued and significant growth of large storage systems in data centers. There are currently two common architectures for the layout of tracks in perpendicular hard disk drives: conventional magnetic recording (CMR) and shingled magnetic recording (SMR). In CMR, any track can be written at any time and neighboring tracks do not intentionally overlap. In SMR, the tracks are written sequentially in bands with the tracks intentionally overlapped like shingles on a roof. In this article, interlaced magnetic recording (IMR) architecture is applied with a perpendicular magnetic recording system. With Perpendicular Interlaced Magentic Recording (PIMR), we observed 2%–3% increase in areal density for single writer PIMR and 7%–20% increase in areal density for two writer PIMR over CMR whereas with SMR, we observed 19% increase in areal density over CMR.
Optimal usage of available wiring resources in diffractive–reflective optoelectronic multichip modules (1998)

Advances in VLSI and optoelectronic multichip module technologiesare enabling the construction of ultracompact massively parallelprocessing systems. The technological parameters that define thewirability and delay characteristics of these technologies have asignificant impact on the system architecture. An analytical modelis presented that allows the design space exploration of theinterconnection networks associated with multinode chips packaged on asingle multichip module substrate. Possible system designs areevaluated for a two-level interconnect with separate k-aryn-cube networks for interchip and intrachipcommunication. The impact of several architectural andtechnological parameters on the optimal network implementation (based on average no-load latency) is analyzed.
35 Novel statistical methods to unlock the clinical potential of liquid biopsy sampling (2023)

OBJECTIVES/GOALS: Decoding the origins of cell-free DNA (cfDNA) released from dying cells in a liquid biopsy sample (e.g. blood) can provide insight into the dynamic, organism-wide changes reflective of health and disease state. Making cfDNA an ideal target for genomic monitoring of disease-related changes. METHODS/STUDY POPULATION: Methylome-wide sequencing (WGBS) data present unique statistical challenges. To this end, we developed a novel statistical method using an Expectation-Maximization algorithm to decode the cellular origins of cfDNA fragments in liquid biopsies. Our flexible, probabilistic method leverages the co-regulation of neighboring CpG sites on the individual sequencing read to facilitate tissue of origin analysis, as opposed to prior methods that focus on the methylation rate of a single CpG site. We assess the performance of our model in various simulated settings and apply our model to an important clinical example in which we are able to detect early off-target tissue damage from radiation therapy via minimally invasive blood draws. RESULTS/ANTICIPATED RESULTS: We found our model more effective at capturing the range of biologically plausible methylation patterns on cfDNA read fragments compared to prior models that use single CpG sites. We also show our model is robust to high levels of noise inherent with WGBS data. We demonstrate the accuracy of cell-type proportion estimation on in-silico mixed cfDNA samples from real WGBS data. Finally, we use our model in a clinical application. We detect significant (p &lt; 0.05) increases in cellular contributions from lung and cardiac tissue in breast cancer patients (n=15) undergoing radiation therapy compared to baseline. We also detect novel signals of radiation induced toxicity to the liver in right-sided breast cancer patients (n=8) receiving radiation treatment compared to matched left-sided breast cancer patients (n=7). DISCUSSION/SIGNIFICANCE: Here we address an unmet need in developing novel statistical methodologies that can handle the unique complexities of methylated cfDNA obtained from liquid biopsy samples. We also demonstrate the far-ranging clinical utility of serial liquid biopsy sampling to complement and advance standards of clinical care in oncology and other pathologies.
Synthesis and characterization of a novel family of dimeric nickel(II) complexes - bimetallic species separated by a persistent void (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and characterization of a novel family of dimeric nickel(II) complexes - bimetallic species separated by a persistent voidDaryle H. Busch, Gary G. Christoph, L. Lawrence Zimmer, Susan C. Jackels, Joseph J. Grzybowski, Robert C. Callahan, Massaki Kojima, Katherine Anne Holter, Jan Mocak, and Cite this: J. Am. Chem. Soc. 1981, 103, 17, 5107–5114Publication Date (Print):August 1, 1981Publication History Published online1 May 2002Published inissue 1 August 1981https://pubs.acs.org/doi/10.1021/ja00407a027https://doi.org/10.1021/ja00407a027research-articleACS PublicationsRequest reuse permissionsArticle Views96Altmetric-Citations26LEARN 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 InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Ballistic-electron-emission-spectroscopy detection of monolayer thickness fluctuations in a semiconductor heterostructure (1999)

Ballistic-electron-emission spectroscopy (BEES) is used to measure fluctuations in the thickness of buried Ga0.8Al0.2As layers. The device under measurement is a half-electron-wavelength Fabry–Perot filter that has been designed to have two quasibound states. By performing BEES at several different spatial locations and by utilizing the relationship between the thicknesses of the device layers and the location (in energy) of the quasibound states, single-monolayer variations are detected in the thicknesses of both the GaAs quantum well and the surrounding Ga0.8Al0.2As barriers. The lateral resolution is shown to be better than 20 nm.
A hybrid bearing concept for high-speed applications employing aerodynamic gas-bearings and a self-sensing active magnetic damper (2011)

Successful application of ultra high-speed electrical drive systems in industrial products is currently limited by lacking high-speed bearing technologies permitting high reliability and long lifetime. Promising bearing technologies for high rotational speeds are contact-less bearing concepts such as active magnetic bearings or gas bearings. While magnetic bearings usually are major electromechanical systems with substantial complexity, gas bearings allow compact realizations with high load capacity and stiffness; however poor dynamic stability has been limiting their use at high rotational speeds. For a new hybrid bearing concept employing an aerodynamic gas bearing for load support, a small-sized self-sensing active magnetic damper is proposed allowing to effectively counteract the self-excited whirl instability of the gas bearing and therewith enabling high speed operation with a minimum of additional complexity and costs.