gebhart/patrepeval huggingface dataset:
The Importance of PK–PD (2023)

ADVERTISEMENT RETURN TO ISSUEEditorialNEXTThe Importance of PK–PDJames C. Barrow*James C. BarrowMore by James C. Barrowhttps://orcid.org/0000-0001-5115-9300 and Craig W. LindsleyCraig W. LindsleyMore by Craig W. Lindsleyhttps://orcid.org/0000-0003-0168-1445Cite this: J. Med. Chem. 2023, 66, 7, 4273–4274Publication Date (Web):March 29, 2023Publication History Received22 March 2023Published online29 March 2023Published inissue 13 April 2023https://doi.org/10.1021/acs.jmedchem.3c00514Copyright © 2023 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views21326Altmetric-Citations-LEARN 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 (817 KB) Get e-AlertsSUBJECTS:Central nervous system,Drug discovery,Medicinal chemistry,Metabolism,Pharmaceuticals Get e-Alerts
[Prevalence of stomalgy and its causes in people of different age]. (2018)

On the basis of analysis of primary medical records of 9 158 (3 329 males and 5 829 females) patients of average, elderly and old age of outpatient clinics the prevalence of pain and paresthesys of the oral mucosa and tongue was studied. Profile of outpatient medical institutions, where people suffering from painful phenomena and paresthesys of the oral mucosa pass examination and treatment was defined. The causal factors that play a role in the origin and development of this disease in patients of older age groups were established.
Asthma Is More Severe in Older Adults (2015)

Overall, the impact of age and asthma duration on risk for asthma severity in men and women is greatest over times of 18-45 years of age; age has a greater effect than asthma duration on risk of severe asthma.
Microbial Polysaccharides and Polyesters (2007)

The use of green plants as industrial factories will potentially become an important component of “green chemistry” efforts. Realization of this technology will likely require metabolic engineering of multi-step pathways and significant use of plant primary metabolites.– Slater, S., et al. (1999). Metabolic engineering of Arabidopsis and Brassica for poly(3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer production. Nature Biotechnology, 17, 1011–1016.
Evolution of Design Methodologies for Next Generation of Reactor Pressure Vessels and Extensive Role of Thermal-Hydraulic Numerical Tools (2005)

The thermal-hydraulic design of the first pressurized water reactors was mainly based on an experimental approach, with a large series of tests on the main equipment [control rod guide tubes, reactor pressure vessel (RPV) plenums, etc.] to check performance.Development of computational fluid dynamics codes and computers now allows for complex simulations of hydraulics phenomena. Provided adequate qualification, these numerical tools are an efficient means to determine hydraulics in the given design and to perform sensitivities for optimization of new designs. Experiments always play their role, first for qualification and then for validation at the last stage of the design. The design of the European Pressurized Water Reactor (EPR), jointly developed by Framatome ANP, Electricité de France (EDF), and the German utilities, is based on both hydraulics calculations and experiments handled in a complementary approach.This paper describes the collective effort launched by Framatome ANP and EDF on hydraulics calculations for the RPV of the EPR. It concerns three-dimensional calculations of RPV inlets, including the cold legs, the RPV downcomer and lower plenum, and the RPV upper plenum up to and including the hot legs. It covers normal operating conditions but also accidental conditions such as pressurized thermal shock in a small-break loss-of-coolant accident. Those hydraulics studies have provided much useful information for the mechanical design of RPV internals.
How to make a multiprocessor computer that correctly executes multiprocess programs (2019)

Many large sequential computers execute operations in a different order than is specified by the program. A correct execution is achieved if the results produced are the same as would be produced by executing the program steps in order. For a multiprocessor computer, such a correct execution by each processor does not guarantee the correct execution of the entire program. Additional conditions are given which do guarantee that a computer correctly executes multiprocess programs.
Theory for Electromigration Failure in Cu Conductors (2006)

A model for electromigration failure is proposed where the criterion for damage is not classical nucleation forming a void, but is a delamination at an interface. In addition, the anisotropy in the elastic constants of Cu metal is responsible for a bimodal failure distribution recognizing that the driving force for mass transport depends on the hydrostatic stress whereas the failure criterion depends on a normal stress. The agreement with published data is reasonably good.
Optical trapping and propulsion of red blood cells on waveguide surfaces (2010)

We have studied optical trapping and propulsion of red blood cells in the evanescent field of optical waveguides. Cell propulsion is found to be highly dependent on the biological medium and serum proteins the cells are submerged in. Waveguides made of tantalum pentoxide are shown to be efficient for cell propulsion. An optical propulsion velocity of up to 6 µm/s on a waveguide with a width of ~6 µm is reported. Stable optical trapping and propulsion of cells during transverse flow is also reported.
Detection of Glottal Closure Instants from Speech Signals: a Quantitative Review (2019)

The pseudo-periodicity of voiced speech can be exploited in several speech processing applications. This requires however that the precise locations of the Glottal Closure Instants (GCIs) are available. The focus of this paper is the evaluation of automatic methods for the detection of GCIs directly from the speech waveform. Five state-of-the-art GCI detection algorithms are compared using six different databases with contemporaneous electroglottographic recordings as ground truth, and containing many hours of speech by multiple speakers. The five techniques compared are the Hilbert Envelope-based detection (HE), the Zero Frequency Resonator-based method (ZFR), the Dynamic Programming Phase Slope Algorithm (DYPSA), the Speech Event Detection using the Residual Excitation And a Mean-based Signal (SEDREAMS) and the Yet Another GCI Algorithm (YAGA). The efficacy of these methods is first evaluated on clean speech, both in terms of reliabililty and accuracy. Their robustness to additive noise and to reverberation is also assessed. A further contribution of the paper is the evaluation of their performance on a concrete application of speech processing: the causal-anticausal decomposition of speech. It is shown that for clean speech, SEDREAMS and YAGA are the best performing techniques, both in terms of identification rate and accuracy. ZFR and SEDREAMS also show a superior robustness to additive noise and reverberation.
CONCENTRATED CUPRIC CHLORIDE SOLUTIONS: POSSIBILITIES OFFERED IN COPPER PRODUCTION (2007)

This study presents the advantages of chloride med ia as a leaching media for sulfide minerals. The advantage in using cupric chloride so lution as a leaching media is its ability to form complexes, which increases the redox potential and thus the oxidative power of the solution remarkably. The thermodynamics of the solution are discussed and the prevailing species suggested. Cuprous ion can be suggested to be present mostly as (CuCl 3)
Community Assessment of the Predictability of Cancer Protein and Phosphoprotein Levels from Genomics and Transcriptomics (2020)

Cancer is driven by genomic alterations, but the processes causing this disease are largely performed by proteins. However, proteins are harder and more expensive to measure than genes and transcripts. To catalyze developments of methods to infer protein levels from other omics measurements, we leveraged crowdsourcing via the NCI-CPTAC DREAM proteogenomic challenge. We asked for methods to predict protein and phosphorylation levels from genomic and transcriptomic data in cancer patients. The best performance was achieved by an ensemble of models, including as predictors transcript level of the corresponding genes, interaction between genes, conservation across tumor types, and phosphosite proximity for phosphorylation prediction. Proteins from metabolic pathways and complexes were the best and worst predicted, respectively. The performance of even the best-performing model was modest, suggesting that many proteins are strongly regulated through translational control and degradation. Our results set a reference for the limitations of computational inference in proteogenomics. A record of this paper's transparent peer review process is included in the Supplemental Information.
CLUES: Few-Shot Learning Evaluation in Natural Language Understanding (2021)

Most recent progress in natural language understanding (NLU) has been driven,
in part, by benchmarks such as GLUE, SuperGLUE, SQuAD, etc. In fact, many NLU
models have now matched or exceeded human-level performance on many tasks in
these benchmarks. Most of these benchmarks, however, give models access to
relatively large amounts of labeled data for training. As such, the models are
provided far more data than required by humans to achieve strong performance.
That has motivated a line of work that focuses on improving few-shot learning
performance of NLU models. However, there is a lack of standardized evaluation
benchmarks for few-shot NLU resulting in different experimental settings in
different papers. To help accelerate this line of work, we introduce CLUES
(Constrained Language Understanding Evaluation Standard), a benchmark for
evaluating the few-shot learning capabilities of NLU models. We demonstrate
that while recent models reach human performance when they have access to large
amounts of labeled data, there is a huge gap in performance in the few-shot
setting for most tasks. We also demonstrate differences between alternative
model families and adaptation techniques in the few shot setting. Finally, we
discuss several principles and choices in designing the experimental settings
for evaluating the true few-shot learning performance and suggest a unified
standardized approach to few-shot learning evaluation. We aim to encourage
research on NLU models that can generalize to new tasks with a small number of
examples. Code and data for CLUES are available at
https://github.com/microsoft/CLUES.
Hexahydrido(pentamethylcyclopentadienyl)rhenium,[(C5Me5)ReH6] (1986)

Das neuartige metallorganische Polyhydrid 2, formal ein ReVII -Derivat, entsteht überraschend bei der Umsetzung des Rev -Komplexes 1 mit LiAlH4 und anschließender vorsichtiger Methanolyse. 2 hat bei Raumtemperatur in Lösung eine fluktuierende Struktur; bei tiefen Temperaturen liegt eine starre, pentagonal-bipyramidale Geometrie vor.
Mechanism of action of porphobilinogen deaminase: ordered addition of the four porphobilinogen molecules in the formation of preuroporphyrinogen (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMechanism of action of porphobilinogen deaminase: ordered addition of the four porphobilinogen molecules in the formation of preuroporphyrinogenJ. S. Seehra and P. M. JordanCite this: J. Am. Chem. Soc. 1980, 102, 22, 6841–6846Publication Date (Print):October 15, 1980Publication History Published online1 May 2002Published inissue 15 October 1980https://pubs.acs.org/doi/10.1021/ja00542a030https://doi.org/10.1021/ja00542a030research-articleACS PublicationsRequest reuse permissionsArticle Views91Altmetric-Citations13LEARN 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-Alertsclose Get e-Alerts
Activation and Oligomerization of Aspartylglucosaminidase (1998)

Secretory, membrane, and lysosomal proteins undergo covalent modifications and acquire their secondary and tertiary structure in the lumen of the endoplasmic reticulum (ER). In order to pass the ER quality control system and become transported to their final destinations, many of them are also assembled into oligomers. We have recently determined the three-dimensional structure of lysosomal aspartylglucosaminidase (AGA), which belongs to a newly discovered family of homologous amidohydrolases, the N-terminal nucleophile hydrolases. Members of this protein family are activated from an inactive precursor molecule by an autocatalytic proteolytic processing event whose exact mechanism has not been thoroughly determined. Here we have characterized in more detail the initial events in the ER required for the formation of active AGA enzyme using transient expression of polypeptides carrying targeted amino acid substitutions. We show that His124 at an interface between two heterodimers of AGA is crucial for the thermodynamically stable oligomeric structure of AGA. Furthermore, the side chain of Thr206 is essential both for the proteolytic activation and enzymatic activity of AGA. Finally, the proper geometry of the residues His204-Asp205 seems to be crucial for the activation of AGA precursor polypeptides. We propose here a reaction mechanism for the activation of AGA which could be valid for homologous enzymes as well.
Data from Immunization against HIF-1α Inhibits the Growth of Basal Mammary Tumors and Targets Mammary Stem Cells <i>In Vivo</i> (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Triple-negative breast cancer (TNBC) represents a cancer stem cell–enriched phenotype. Hypoxia-inducible factor-1α (HIF-1α) induces the expression of proteins associated with stemness and is highly upregulated in TNBC. We questioned whether HIF-1α was immunogenic and whether vaccination targeting HIF-1α would impact the growth of basal-like mammary tumors in transgenic mice.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; We evaluated HIF-1α–specific IgG in sera from controls and patients with breast cancer. Class II epitopes derived from the HIF-1α protein sequence were validated by ELISPOT. To assess therapeutic efficacy, we immunized Tg-MMTVneu and C3(1)Tag mice with HIF-1α Th1-inducing peptides. Stem cells were isolated via magnetic bead separation. Levels of HIF-1α and stem cells in the tumor were quantitated by Western blotting and flow cytometry.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; The magnitude (&lt;i&gt;P&lt;/i&gt; &lt; 0.001) and incidence (&lt;i&gt;P&lt;/i&gt; &lt; 0.001) of HIF-1α–specific IgG were elevated in TNBC patients compared with controls. Both breast cancer patients and donors showed evidence of HIF-1α–specific Th1 and Th2 immunity. Three HIF-1α–specific Th1 class II restricted epitopes that were highly homologous between species elicited type I immunity in mice. After HIF-1α vaccination, mammary tumor growth was significantly inhibited in only C3(1)Tag (basal-like/stem cell&lt;sup&gt;high&lt;/sup&gt;; &lt;i&gt;P&lt;/i&gt; &lt; 0.001) not TgMMTV-neu (luminal/neu/stem cell&lt;sup&gt;low&lt;/sup&gt;; &lt;i&gt;P&lt;/i&gt; = 0.859) murine models. Vaccination increased type I T cells in the tumor (&lt;i&gt;P&lt;/i&gt; = 0.001) and decreased cells expressing the stem cell marker, Sca-1, compared with controls (&lt;i&gt;P&lt;/i&gt; = 0.004).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; An HIF-1α vaccine may be uniquely effective in limiting tumor growth in TNBC. Inhibiting outgrowth of breast cancer stem cells via active immunization in the adjuvant setting may impact disease recurrence. &lt;i&gt;Clin Cancer Res; 23(13); 3396–404. ©2016 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
An Isolated Quasi-Resonant Multiphase Single-Stage Topology for 48-V VRM Applications (2017)

In order to increase the efficiency of modern microprocessors power supplies used in data centers, the 48-V dc distribution bus is gaining growing attention. For such applications, voltage regulation modules (VRMs) are currently obtained using two-stage conversion systems with an intermediate 12-V dc bus. This paper presents an innovative single-stage approach for the 48-V VRM based on a quasi-resonant constant on-time (COT) operation. The proposed topology inherently integrates the multiphase approach, providing fast phase shedding and flat high-efficiency curves even at light load conditions. This is a unique advantage, usually not available in the two-stage approach, that is very important in server architectures, where high efficiency is required even at light load conditions. The paper analyses the circuit topology, and proposes a control architecture for fast transient response, including the current sharing capabilities, and a solution for implementing the integrated magnetics. The digital controller has been implemented in 0.16-μ m lithography together with a digital pulse-width-modulation with a 195 ps resolution, and a 40 MS/s, 7-bit ADC. Experimental results show an efficiency of 93.1% for a 250 A, 1.8 V VRM, and of 93.2% for a 102 A, 1.2-V double data rate (DDR) power supply.
Rücktitelbild: An n‐Type Conjugated Oligoelectrolyte Mimics Transmembrane Electron Transport Proteins for Enhanced Microbial Electrosynthesis (Angew. Chem. 33/2023) (2023)

Microbial electrosynthesis is a sustainable strategy for electricity-driven chemical production. In their Communication (e202305189), Guillermo C. Bazan et al. designed an n-type redox-active conjugated oligoelectrolyte (COE) that intercalates into cell membranes and mimics the function of endogenous transmembrane electron transport proteins. The incorporation of the COE into electroactive bacteria amplifies current uptake from the electrode, leading to enhanced microbial electrosynthesis.
Analysis of the Causes of the Intensity Enhancement of the Typhoon “Tiange” (2023)

This paper analyzes the causes of the offshore strength enhancement of Typhoon Tiange (No. 1713) from four aspects: high and low layer divergence, vertical wind shear, southwest monsoon transport, offshore sea temperature and weak cold air. The conclusions are as follows: The high-level airflow divergence enhancement and positive vorticity advection in the offshore, strengthen the middle rise movement of the “Tiange”, and the ascending movement enhances the strength of the “Tiange” by strengthening the lower layer convergence; The high offshore sea temperature and sea temperature are changing temperature, which also has a certain effect on the strengthening of “Tiange” in the offshore; The strengthening of the southwest warm and humid airflow provides sufficient water vapor and energy for the development of “Tiange”, which is beneficial to the maintenance of the typhoon warm heart structure; The intrusion of weak cold air, enhanced the radiation cooperation of the lower typhoon disturbance, which is beneficial to the enhancement of “Tiange”.
‘Inverse crown ether’ complexes: extension to potassium through the synthesis of [{[(Me3Si)2N]4K2Mg2(O2)}∞], a peroxo-centred macrocycle linked into infinite chains by intermolecular K⋯CH3(SiMe2) interactions (1999)

The title compound represents the first potassium example of a novel class of amide-supported heterobimetallic macrocycle having a dicationic (N4K2Mg2)2+ octagonal ring framework surrounding a dianionic (O2)2– core.
Lateral IGBT in thin SOI for high voltage, high speed power IC (1998)

A high voltage LIGBT built in ultra-thin silicon-on-insulator (SOI) with a linearly graded doping profile is reported. The highest breakdown voltage of 720 V was measured for an LIGBT built in 0.5 /spl mu/m SOI with a 4 /spl mu/m buried oxide. A forward voltage drop of 6 V at 100 Acm/sup -2/ and a turn-off time of 140 ns have been achieved in the same device. Device forward voltage drop is very sensitive to the SOI thickness due to the recombination of carriers at the two silicon-silicon dioxide interfaces. An SOI thickness of 0.5 /spl mu/m and an n-buffer doped to 10/sup 18/ cm/sup -3/ have been found to be a reasonable trade-off between the breakdown voltage and the forward voltage drop.
Physiological Aspects of Bitterness (2017)

The human sense of taste serves the important function to evaluate the nutritional value of food prior to its ingestion. It retrieves information about the caloric content, the concentration of electrolytes, and the presence of potentially harmful food components. As many toxic food components taste bitter this taste quality is believed to warn us against the ingestion of harmful substances and tightly linked to rejection behavior, at least for strongly bitter tasting food. The detection of the numerous and structurally diverse bitter compounds is facilitated by 25 bitter taste receptors belonging to the TAS2R gene family. In addition to the presence of TAS2Rs in the oral cavity an increasing number of non-gustatory tissues have been reported to express TAS2R genes as well and may hence be involved in defense mechanisms against toxic substances beyond the oral cavity. The present article addresses, after a brief introduction into the anatomy of the gustatory system and the taste-specific signal transduction process, the physiological roles of bitter taste receptors in the gustatory system and beyond.
"Oj, det hade jag aldrig trott om dig. Kan du vara deprimerad?" (2011)

"Oj, det hade jag aldrig trott om dig, kan du vara deprimerad?" är ett examensarbete om varför män tar livet av sig oftare än kvinnor. Två tidigare suicidala män berättar om tiden när de ville ta sina liv. En nära vän till en man som tog sitt liv berättar om de händelser som ledde fram till självmordet och hur vården svek. Forskare och experter ger förklaringar till varför män är överrepresenterade i självmordsstatistiken.