gebhart/patrepeval huggingface dataset:
MAGUK-Controlled Ubiquitination of CARMA1 Modulates Lymphocyte NF-κB Activity (2009)

The adaptor protein CARMA1 is required for antigen receptor-triggered activation of IKK and JNK in lymphocytes. Once activated, the events that subsequently turn off the CARMA1 signalosome are unknown. In this study, we found that antigen receptor-activated CARMA1 underwent lysine 48 (K48) polyubiquitination and proteasome-dependent degradation. The MAGUK region of CARMA1 was an essential player in this event; the SH3 and GUK domains contained the main ubiquitin acceptor sites, and deletion of a Hook domain (an important structure for maintaining inactive MAGUK proteins) between SH3 and GUK was sufficient to induce constitutive ubiquitination of CARMA1. A similar deletion promoted the ubiquitination of PSD-95 and Dlgh1, suggesting that a conserved mechanism may control the turnover of other MAGUK family protein complexes. Functionally, we demonstrated that elimination of MAGUK ubiquitination sites in CARMA1 resulted in elevated basal and inducible NF-kappaB and JNK activation as a result of defective K48 ubiquitination and increased persistence of this ubiquitination-deficient CARMA1 protein in activated lymphocytes. The coordination of degradation with the full activation of the CARMA1 molecule likely provides an intrinsic feedback control mechanism to balance lymphocyte activation upon antigenic stimulation.
Structural Characterization of Mycobacterium abscessus Phosphopantetheine Adenylyl Transferase Ligand Interactions: Implications for Fragment-Based Drug Design (2022)

Anti-microbial resistance is a rising global healthcare concern that needs urgent attention as growing number of infections become difficult to treat with the currently available antibiotics. This is particularly true for mycobacterial infections like tuberculosis and leprosy and those with emerging opportunistic pathogens such as <i>Mycobacterium abscessus</i>, where multi-drug resistance leads to increased healthcare cost and mortality. <i>M. abscessus</i> is a highly drug-resistant non-tuberculous <i>mycobacterium</i> which causes life-threatening infections in people with chronic lung conditions such as cystic fibrosis. In this study, we explore <i>M. abscessus</i> phosphopantetheine adenylyl transferase (PPAT), an enzyme involved in the biosynthesis of Coenzyme A, as a target for the development of new antibiotics. We provide structural insights into substrate and feedback inhibitor binding modes of <i>M. abscessus</i> PPAT, thereby setting the basis for further chemical exploration of the enzyme. We then utilize a multi-dimensional fragment screening approach involving biophysical and structural analysis, followed by evaluation of compounds from a previous fragment-based drug discovery campaign against <i>M. tuberculosis</i> PPAT ortholog. This allowed the identification of an early-stage lead molecule exhibiting low micro molar affinity against <i>M. abscessus</i> PPAT (K<sub>d</sub> 3.2 ± 0.8 µM) and potential new ways to design inhibitors against this enzyme. The resulting crystal structures reveal striking conformational changes and closure of solvent channel of <i>M. abscessus</i> PPAT hexamer providing novel strategies of inhibition. The study thus validates the ligandability of <i>M. abscessus</i> PPAT as an antibiotic target and identifies crucial starting points for structure-guided drug discovery against this bacterium.
Temperature dependent electronic band structure of wurtzite GaAs nanowires (2017)

It has recently become possible to grow GaAs in the wurtzite crystal phase. This ability allows interesting tests of band-structure theory. Wurtzite GaAs has two closely spaced direct conduction bands as well as three nondegenerate valence bands. The energies of the band edges are not well known, in particular not as a function of temperature. In order to improve the accuracy we have studied the temperature dependence of the conduction band minimum as well as of the second valence band maximum using resonant Raman scattering (of up to 3LO Raman lines). We find that the temperature dependence of the bandgap in wurtzite GaAs is very similar to that in zinc blende GaAs. Our results show that they have the same band gaps not only at 7 K but also at room temperature to within 5 meV. This is in some discrepancy with previous work. We find that the energy difference between the first two Γ<sub>9V</sub> and Γ<sub>7V</sub> valence bands is constant, around 100 meV, over the investigated temperature range, 7 K to 300 K. Due to a fortuitous spacing of the energy bands we find a very unexpected and strong quadruple resonance in the resonant Raman scattering.
Open Surgery Assisted by the Neuronavigator, a Stereotactic, Articulated, Sensitive Arm (1991)

Abstract A new computed tomographic-stereotactic device that translates the operating point onto preoperative computed tomographic (CT) images, the Neuronavigator, has been developed. We have applied this system to various neurosurgical procedures to examine its usefulness. The system consists of a 6-joint sensing arm and a 16-bit personal computer. It projects the location of the arm tip onto a corresponding CT slice with a cursor that guides the surgeon toward the intracranial target during open surgery. The system also projects the location of the tip onto angiograms, and when used in conjunction with echography or a transcranial Doppler (TCD) flow meter, the surgeon's ability to navigate is enhanced. Sixty-eight patients underwent operation with the Neuronavigator. The navigation system worked as the core of a multimodal three-dimensional data base that proved to be useful during surgery. The maximum detection error was 2.5 mm, which was considered sufficient for open microsurgery. It also proved useful in designing the position of a craniotomy, in targeting deep-seated mass lesions, and in tracing the tumor edge, which had been identified on a CT scan. When the angiogram was combined with the navigator, it became easy to identify key vessels within a small operating field. The system was also combined with a TCD flow meter. This combination makes it possible to translate the measuring point of the TCD directly into CT coordinates, improving the precision of location of the TCD probe. The Neuronavigator combines various diagnostic images into one database and effectively guides the surgeon during surgery.
Improved mobile 70 MeV race-track microtron design (2002)

To increase the reliability, simplify the tuning, and boost the efficiency of our 70 MeV mobile race-track microtron design we use a narrow rectangular asymmetric accelerating structure, rare-earth permanent end magnets, wiggler-like vertical focusing lenses on the return paths, and a beam buncher preceding the linac. We present here beam dynamics simulation results and construction details.
Suppressing detrimental phase transitions via tungsten doping of LiNiO2 cathode for next-generation lithium-ion batteries (2019)

W doping alleviates the structural stress associated with the repetitive phase transition, markedly improving cycling performance.
Comment concerning the Hypothesis: Origins of globular structure in proteins by Vladimir Tolstoguzov (1999)

I read with interest the paper but am somewhat frustrated as it seems difficult to repeat a part of the reported data. Indeed, the author seems to have forgotten to describe the material he used. As an example I want to quote the ‘so-called’ protein casein. Its origin is not specified: cow, sheep, goat? or another? Was the sample a commercial one? In that case the origin and the impurities must be specified. Was the sample a purified one? Purified by which method? Or has the author used the aggregate alpha+beta+kappa caseins, or only one of the latter constituents? All this must be explained. Similar remarks can be made for other proteins mentioned in the paper. A last remark: one-half of the references are to works by the author himself (14 out of 28): this should be avoided and does not seem necessary.
Dermatologic toxicities of 3,517 solid tumor patients on phase I clinical trials of the National Institutes of Health Cancer Therapy Evaluation Program (CTEP). (2015)

2546 Background: Dermatologic adverse events (AEs) can be key determinants of overall drug tolerability, and the maximum tolerated and recommended phase II doses of therapy on phase I trials. We present the largest dedicated analysis of dermatologic AEs on phase I trials to date. Methods: Data from a prospectively maintained database of solid tumor patients (pts) enrolled onto CTEP-sponsored phase I trials from 2000 to 2010 was analyzed. Cumulative incidence, site, type, and timing of drug-related dermatologic AEs were described and compared between pts who received molecularly targeted agents (MTAs), cytotoxic therapy, or a combination of both. Results: 3,517 solid tumor pts and 6,165 unique drug-related dermatologic AEs were analyzed: 1,545 pts on MTA only trials, 671 on cytotoxic only trials, and 1,392 on combination MTA and cytotoxic trials. Percent grade 1, 2, 3, and 4 dermatologic drug-related AEs were 75.5%, 22.6%, 1.9% and < 0.1%, respectively. Most common drug-related dermatologic AEs were alopecia (23%) and maculopapular rash (21%). Of 1,270 pts with drug-related dermatologic AEs, timing of worst drug-related toxicity was: 743 pts (cycle 1), 303 (cycle 2), and 224 (cycle 3 or later). While cumulative incidence of ≥ grade 3 drug-related dermatologic AEs increased to 2.4% by cycle 6, it was only 1.6% at the end of cycle 1. Cumulative incidence of drug-related dermatologic AEs was highest in pts with MTA only therapy, and significantly differed by dose level (p < 0.001). In pts who received MTA only therapy, drug-related dermatologic toxicity was most common for combination kinase inhibitor-containing therapy (p < 0.001). Conclusions: A substantial proportion of drug-related dermatologic AEs occurs after the traditional DLT monitoring period. Future phase I trial designs should account for delayed toxicities to avoid defining intolerable doses of study therapy.
Model-Matching-Control of a Redundantly Actuated Steer-by-Wire-System (2020)

Steer-by-Wire (sbw) systems gain new importance with regard to autonomous driving since a permanently rotating steering wheel is undesired in such a vehicle. In addition, redundancies in the vehicle steering system must be provided for autonomous vehicles, which have been seen as an obstacle for sbw-systems until now. In this article, a control concept for redundantly actuated sbw-systems is presented. For this purpose, the mechanical model of a redundantly actuated sbw is described, in which the actuators of the steering are elastically connected to each other. Also a linear model of a conventional hydraulic power steering (hps) is derived as reference model, to describe the desired dynamic behavior of the controlled system. A dynamic model-matching controller based on norm minimization is designed to match the dynamics of the sbw-system to the dynamics of the hps-model. Finally, the characteristics of the controlled system are analysed. The controlled system matches the reference system in the relevant frequency range and shows the desired behavior on the test bed.
The Emergency Informatics Transition Course: A Flexible, Online Course in Health Informatics for Emergency Medicine Clinicians and Trainees (2009)

Increasing emphasis on health information technology (HIT) as a mechanism to control costs and increase quality in health care is accelerating the diffusion of more advanced health information systems into emergency medicine. This has created an increased demand for informatics‐trained emergency physicians to provide clinical input. In response to this need we partnered with the American College of Emergency Physicians (ACEP) to adapt an existing informatics educational program to emergency medicine. The American Medical Informatics Association (AMIA) 10X10 program is an effort to provide formal informatics training to 10,000 clinicians by 2010. Our first AMIA‐ACEP 10X10 Emergency Informatics Transition Course matriculated 37 emergency physicians this fall. This 12 week online course is an adaption of the Oregon Health &amp; Science University (OHSU) introductory informatics 10X10 course where students complete weekly assignments and participate in online discussions. At the end of the course they meet face‐to‐face at the ACEP Scientific Assembly where they present their projects and discuss common themes. The online design of the course proved adaptable for a widely varied enrollment. The first class contained students from the United States and four other countries, both large urban and small rural hospitals, and both new and experienced clinicians. Extensive input from the students will assist us in further refining this annual course to better meet the needs of emergency clinicians. We will demonstrate the design of this course, which we believe offers interested residents and fellows in emergency medicine a flexible opportunity to advance their informatics training.
Pharmacogenetic tests for antipsychotic medications: clinical implications and considerations (2016)

Optimizing antipsychotic pharmacotherapy is often challenging due to significant variability in effectiveness and tolerability. Genetic factors influencing pharmacokinetics and pharmacodynamics may contribute to some of this variability. Research studies have characterized these pharmacogenetic relationships, and some genetic markers are now available as clinical tests. These advances in pharmacogenetics research and test availability have great potential to improve clinical outcomes and quality of life in psychiatric patients. For clinicians considering using pharmacogenetics, it is important to understand the clinical implications and also the limitations of markers included in currently available tests. This review focuses on pharmacokinetic and pharmacodynamic gene variants that are currently available in commercial genetic testing panels. Associations of these variants with clinical efficacy and adverse effects, as well as other clinical implications, in antipsychotic pharmacotherapy are discussed.
Big Metadata, Smart Metadata, and Metadata Capital: Toward Greater Synergy Between Data Science and Metadata (2017)

Abstract Purpose The purpose of the paper is to provide a framework for addressing the disconnect between metadata and data science. Data science cannot progress without metadata research. This paper takes steps toward advancing the synergy between metadata and data science, and identifies pathways for developing a more cohesive metadata research agenda in data science. Design/methodology/approach This paper identifies factors that challenge metadata research in the digital ecosystem, defines metadata and data science, and presents the concepts big metadata , smart metadata , and metadata capital as part of a metadata lingua franca connecting to data science. Findings The “utilitarian nature” and “historical and traditional views” of metadata are identified as two intersecting factors that have inhibited metadata research. Big metadata, smart metadata, and metadata capital are presented as part of a metadata lingua franca to help frame research in the data science research space. Research limitations There are additional, intersecting factors to consider that likely inhibit metadata research, and other significant metadata concepts to explore. Practical implications The immediate contribution of this work is that it may elicit response, critique, revision, or, more significantly, motivate research. The work presented can encourage more researchers to consider the significance of metadata as a research worthy topic within data science and the larger digital ecosystem. Originality/value Although metadata research has not kept pace with other data science topics, there is little attention directed to this problem. This is surprising, given that metadata is essential for data science endeavors. This examination synthesizes original and prior scholarship to provide new grounding for metadata research in data science.
Production of alpha-aminophosphonates (2019)

The production of alpha-aminophosphonate compounds was carried out by homogeneous catalysis using acetic acid, aldehydes, benzyl carbamate and trimethylphosphite or triphenylphosphite. This synthesis process provided alpha-aminophosphonates 2a-f in chemical yields of 50-60%.
An improved objective for cell placement (2002)

To estimate the wiring area needed by the router to connect a signal net, most placement tools measure one half of the perimeter of the minimum rectangle enclosing all terminals of the net. In the past, this approach is reasonable because the half-perimeter value correlates well with the wiring area. As we are entering the deep-submicron era, the approach is no longer appropriate because the wiring delay must be characterized based on a distributed-RC model, in which not only the wiring area but also the wiring topology affects the wiring delay. In this paper, we show that the half-perimeter metric does not correlate well with the wiring delay under the distributed-RC model. We show that the radius of a net estimates the wiring delay more accurately than the half-perimeter metric does. We expand the acceptance criteria of a simulated annealing based placement tool to include moves that do not improve on the wiring length but do reduce the radius. Over all, for a set of benchmark circuits the critical path delays are improved up to 15%.
Real-time monitoring of landslides (2012)

During the exceptionally wet spring of 2006, thousands of tons of rock crashed onto one of the main highways leading into Yosemite National Park in the mountainous Sierra Nevada of California (fig. These rocks, emanating from the massive Ferguson rockslide perched upslope, buried the highway and encroached into the Merced River. After 92 days, the highway was temporarily rerouted to the opposite side of the river. Nevertheless, geologists and land managers remained concerned-if the entire rock mass slid rapidly and blocked the river, it could cause upstream inundation and, potentially, downstream flooding.
Improving Flow Assurance in Multi-Zone Fracturing Treatments in Hydrocarbon Reservoirs with High Strength Corrodible Tripping Balls (2012)

Abstract Multi point hydraulic fracturing in unconventional hydrocarbon bearing shale reservoirs has been proven to greatly enhance production economics. A major component of these multi point fracturing systems consist of tripping balls used to actuate fracturing sleeves. The sleeves are used to focus fracturing initiation and placement. The tripping balls may experience pressures approaching 10,000psi. Recent technology has allowed as many as 40 individual fracture points. Once the formation has been fractured the tripping balls may hinder production. One potential problem is related to the tripping balls becoming stuck on the fracturing seats. Tripping balls remaining in the lateral can create a choking effect and also lead to problems if wellbore re-entry is required. These risks to production can lead to significant increased costs and potentially lost production. A new high strength corrodible material has been developed and used for tripping balls to alleviate these potential problems in these unconventional reservoirs. This material has yielded a truly intervention-less means of flow assurance. The mechanical properties and corrosion rates of these newly engineered materials have been investigated to determine the downhole performance. The characterization results of these materials will be discussed and compared to other materials currently used for tripping balls. The testing included investigation of the corrosion rates of these materials in brines and acids at various temperatures and pressures. Materials were also functionally tested on multiple ball seat configurations used in the multi-zone fracturing systems.
Estimation and equalization techniques applied to Radio over Fiber System (2015)

In this paper, signal processing techniques applied on the received signal from Radio over Fiber system have been investigated. The structure of the RoF system, starting by the 60 GHz carrier generation using an external modulator, Optical Single Side Band 10 Gb/s QPSK modulation with IQ Dual Parallel Mach Zehnder Modulator, base station, and the electrical coherent receiver is introduced. The performance of the system with attenuation, chromatic dispersion, and frequency offset of the local oscillator at the receiver side is discussed. The frequency domain equalization technique and feedforward carrier recovery algorithm which are used to mitigate the effect of chromatic dispersion on the carrier and the data as well are investigated. Moreover, the proposed solution also covers the frequency offset of the local oscillator at the receiver side. The proposed algorithms are evaluated by simulations run under VPItransmissionMaker environment as well as MATLAB.
The factors of family management affecting asthma control status in school-age children with asthma in China (2021)

This study shows that asthma control status of school-age children in China is related to the parents' views of their child as having a "normal condition" and the parents' satisfaction with the balance between asthma related management and other aspects of family life.
Recent developments in the use or organoboranes in organic synthesis (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRecent developments in the use or organoboranes in organic synthesisG. M. L. Cragg Cite this: J. Chem. Educ. 1969, 46, 12, 794Publication Date (Print):December 1, 1969Publication History Received3 August 2009Published online1 December 1969Published inissue 1 December 1969https://doi.org/10.1021/ed046p794RIGHTS & PERMISSIONSArticle Views177Altmetric-Citations4LEARN 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 (3 MB) Get e-Alerts Get e-Alerts
Estimates of array and pool-construction variance for planning efficient DNA-pooling genome wide association studies (2011)

We conclude that relative to var(e(array)), var(e(construction)) is of less importance in reducing the variance in allele frequency estimation from DNA pools; however, our data suggests that on average it may be more important than previously thought. We have prepared a simple online tool, PoolingPlanner (available at http://www.kchew.ca/PoolingPlanner/), which calculates the effective sample size (ESS) of a DNA pool given a range of replicate array values. ESS can be used in a power calculator to perform pool-adjusted calculations. This allows one to quickly calculate the loss of power associated with a pooling experiment to make an informed decision on whether a pool-based GWAS is worth pursuing.