gebhart/patrepeval huggingface dataset:
Large-Scale Validation of Mixed-Solvent Simulations to Assess Hotspots at Protein–Protein Interaction Interfaces (2018)

The ability to target protein-protein interactions (PPIs) with small molecule inhibitors offers great promise in expanding the druggable target space and addressing a broad range of untreated diseases. However, due to their nature and function of interacting with protein partners, PPI interfaces tend to extend over large surfaces without the typical pockets of enzymes and receptors. These features present unique challenges for small molecule inhibitor design. As such, determining whether a particular PPI of interest could be pursued with a small molecule discovery strategy requires an understanding of the characteristics of the PPI interface and whether it has hotspots that can be leveraged by small molecules to achieve desired potency. Here, we assess the ability of mixed-solvent molecular dynamic (MSMD) simulations to detect hotspots at PPI interfaces. MSMD simulations using three cosolvents (acetonitrile, isopropanol, and pyrimidine) were performed on a large test set of 21 PPI targets that have been experimentally validated by small molecule inhibitors. We compare MSMD, which includes explicit solvent and full protein flexibility, to a simpler approach that does not include dynamics or explicit solvent (SiteMap) and find that MSMD simulations reveal additional information about the characteristics of these targets and the ability for small molecules to inhibit the PPI interface. In the few cases were MSMD simulations did not detect hotspots, we explore the shortcomings of this technique and propose future improvements. Finally, using Interleukin-2 as an example, we highlight the advantage of the MSMD approach for detecting transient cryptic druggable pockets that exists at PPI interfaces.
Title: Through Silicon Via (TSV) technology creates electro-optical interfaces (2012)

Through Silicon Via (TSV) technology is emerging as an essential method for stacking and interconnecting semiconductor chips. Much has been reported about the interconnecting and stacking of devices, such as, memory-on-memory and memory-on-logic devices. TSV fabrication is a micro-machining process for silicon. As such it can also be utilized to etch and form structures other than vias. One such structure is an electro-optical interposer using TSVs and fiberoptic channels. The performance of this structure has been tested to over 10 Gb/sec.
Effect of YM155, a potent survivin suppressant, on the antitumor effect of rituximab in diffuse large B-cell lymphoma (DLBCL) xenograft models: FLT-/FDG-PET imaging studies. (2010)

8087 Background: YM155 is a novel small-molecule survivin suppressant, and is currently under development for the treatment of non- Hodgkin's lymphoma in a phase II clinical trial. Therapy monitoring by non-invasive PET (positron emission tomography) imaging study allow a straightforward translation from preclinical to clinical research. The aim of this study was to evaluate the utility of the PET tracers, FLT(3'-deoxy-3'-[18F]fluorothymidine) and FDG(2-[18F]fluoro-2-deoxy-D-glucose) to monitor tumor response to YM155 in combination with rituximab (RTX) treatment in diffuse large B cell lymphoma (DLBCL) xenograft model. Methods: YM155 (0.5 mg/kg/day) was administered on day 0 (D0) as a 7-day continuous subcutaneous infusion, and RTX (50 mg/kg/day) was administered by intravenous bolus injection on D0 and D+2 in mice (N=4) with the human derived DLBCL xenograft, WSU-DLCL- 2. FLT/FDG uptake was evaluated using a small-animal PET scan, Inveon (Siemens), on D0 (before treatment), D+3, +7, and +14 / on D0 and D+3 after treatment, respectively. At each time point, excised tumors from other mice (N=4) were evaluated for histopathology with proliferative activity (Ki-67 index). Results: YM155 in combination with RTX (combo) resulted in significant (P <.05) regression of tumor size compared to the RTX monotherapy group without loss of body weight. PET imaging data showed tumor uptake of FLT/FDG significantly decreased in the YM155 alone (-17%/-18%) and combo (-50%/-42%) groups on D+3 compared to baseline (D0) in contrast to the RTX alone (+72%/+12%) or saline (+126%/+48%) groups where uptake increased, respectively. In addition, significant (P <.05) decrease of the Ki-67 positive cells in the tumor compared to the RTX alone group could be observed on D+3. Conclusions: YM155 may increase anti-tumor activity of RTX for the treatment of DLBCL. FLT-PET as a cell proliferation imaging, FDG-PET imaging reflecting glucose metabolism and Ki-67 index, respectively may be a useful biomarker of this combination therapy. No significant financial relationships to disclose.
Hydrogen in layered iron arsenides: Indirect electron doping to induce superconductivity (2011)

Utilizing the high stability of calcium and rare-earth hydrides, CaFeAsF${}_{1\ensuremath{-}x}$H${}_{x}$ ($x$ $=$ 0.0--1.0) and SmFeAsO${}_{1\ensuremath{-}x}$H${}_{x}$ ($x$ $=$ 0.0--0.47) have been synthesized using high pressure to form hydrogen-substituted 1111-type iron-arsenide superconductors. Neutron diffraction and density functional calculations have demonstrated that the hydrogens are incorporated as H${}^{\ensuremath{-}}$ ions occupying F${}^{\ensuremath{-}}$ sites in the blocking layer of CaFeAsF. The resulting CaFeAsF${}_{1\ensuremath{-}x}$H${}_{x}$ is nonsuperconducting, whereas, SmFeAsO${}_{1\ensuremath{-}x}$H${}_{x}$ is a superconductor, with an optimal ${T}_{\mathrm{c}}$ $=$ 55 K at $x$ \ensuremath{\sim} 0.2. It was found that up to 40% of the O${}^{2\ensuremath{-}}$ ions can be replaced by H${}^{\ensuremath{-}}$ ions, with electrons being supplied into the FeAs layer to maintain neutrality (O${}^{2\ensuremath{-}}$ $=$ H${}^{\ensuremath{-}}$ $+$ ${e}^{\ensuremath{-}}$). When $x$ exceeded 0.2, ${T}_{\mathrm{c}}$ was reduced corresponding to an electron overdoped region.
Polymorphism of LMP2, TAP1, LMP7 and TAP2 in Brazilian Amerindians and Caucasoids: implications for the evolution of allelic and haplotypic diversity (2000)

In the class II region of the major histocompatibility complex (MHC), four genes implicated in processing of MHC class I-presented antigens have been described. Two of these (TAP1 and TAP2) code for endoplasmic reticulum membrane transporter proteins and the other two (LMP2 and LMP7) for proteasome subunits. These genes are polymorphic, although much less so than classical MHC class I and II genes. There is controversy concerning the possible functional implications of this variation. Population genetics is one of the means of investigating the evolutionary and functional significance of genetic polymorphisms; however, few populations have been analysed with respect to TAP and LMP diversity. We present here the polymorphism of TAP1, TAP2, LMP2 and LMP7 genes in the Kaingang and Guarani Amerindian tribes, and in the Caucasoid population of the Brazilian State of Paraná. Allele frequencies found in the Caucasoids were close to those described for similar populations. Amerindians had a somewhat more restricted polymorphism, and allele and haplotype frequencies differed greatly between the two tribes. Overall linkage disequilibrium (LD) between the four genes was low in the Caucasoids, but high in the Amerindians, for which significant LD was seen for all informative pairs of loci. Comparing results of this and previous studies we observed that, whenever significant LD occurs in non-Amerindians, it tends to be similar in the different ethnic groups. While this might be interpreted as evidence of co-evolution of genes in the TAP-LMP region, the high haplotypic diversity in all populations and low LD in non-Amerindians indicate absence of co-evolution of the different genes. Distributions of allele and genotype frequencies are consistent with the hypothesis of selective neutrality. We conclude that genetic polymorphism of the human TAP and LMP genes and haplotypes is of little, if any, functional significance.
Collision Cross Sections of Proteins and Their Complexes: A Calibration Framework and Database for Gas-Phase Structural Biology (2010)

Collision cross sections in both helium and nitrogen gases were measured directly using a drift cell with RF ion confinement inserted within a quadrupole/ion mobility/time-of-flight hybrid mass spectrometer (Waters Synapt HDMS, Manchester, U.K.). Collision cross sections for a large set of denatured peptide, denatured protein, native-like protein, and native-like protein complex ions are reported here, forming a database of collision cross sections that spans over 2 orders of magnitude. The average effective density of the native-like ions is 0.6 g cm(-3), which is significantly lower than that for the solvent-excluded regions of proteins and suggests that these ions can retain significant memory of their solution-phase structures rather than collapse to globular structures. Because the measurements are acquired using an instrument that mimics the geometry of the commercial Synapt HDMS instrument, this database enables the determination of highly accurate collision cross sections from traveling-wave ion mobility data through the use of calibration standards with similar masses and mobilities. Errors in traveling-wave collision cross sections determined for native-like protein complexes calibrated using other native-like protein complexes are significantly less than those calibrated using denatured proteins. This database indicates that collision cross sections in both helium and nitrogen gases can be well-correlated for larger biomolecular ions, but non-correlated differences for smaller ions can be more significant. These results enable the generation of more accurate three-dimensional models of protein and other biomolecular complexes using gas-phase structural biology techniques.
Aggressive leukemia driven by MLL-AF9 (2016)

We recently showed that cellular origin impacts the aggressiveness and the phenotype of acute myeloid leukemia (AML). Direct induction of the MLL-AF9 fusion in various hematopoietic compartments <i>in vivo</i> using a doxycycline (DOX) regulated mouse model (iMLL-AF9) led to an invasive chemoresistant AML expressing several genes known to be involved in epithelial to mesenchymal transition (EMT) in solid cancers. Many of these genes play important roles in migration and invasion and are significantly associated with poor overall survival in AML patients.
A subjective experiment for 3D-mesh segmentation evaluation (2010)

Abstract—In this paper we present a subjective quality as-sessment experiment for 3D-mesh segmentation. For this end, we carefully designed a protocol with respect to several factors namely the rendering conditions, the possible interactions, the rating range, and the number of human subjects. To carry out the subjective experiment, more than 40 human observers have rated a set of 250 segmentation results issued from various algorithms. The obtained Mean Opinion Scores, which represent the human subjects ’ point of view toward the quality of each segmentation, have then been used to evaluate both the quality of automatic segmentation algorithms and the quality of similarity metrics used in recent mesh segmentation benchmarking systems. I.
Distal Junctional Kyphosis of Adolescent Idiopathic Thoracic Curves Following Anterior or Posterior Instrumented Fusion: Incidence, Risk Factors, and Prevention (2006)

It appears that both posterior and anterior instrumentation for thoracic curves must include the junctional level to prevent postoperative DJK when postoperative DJK is present. The presence of increased kyphosis after surgery in the T10-L2 region seen in both anterior and posterior groups that had postoperative DJK develop constitutes a "risk factor" for the development of DJK.
Synthesis of a Selective Estrogen Receptor Degrader via a Stereospecific Elimination Approach (2018)

An efficient synthesis of a selective estrogen receptor degrader, GDC-0810, bearing a challenging stereodefined (E)-tetrasubstituted all-carbon olefin core, is reported. The described synthetic route involves a highly diastereoselective addition of an arylmagnesium reagent 3a to ketone 4, yielding the key tertiary alcohol 2a in >99:1 dr. The corresponding tert-butyl carbonate derivative was identified among other leaving groups to provide the desired olefin geometry in a 98:2 E/Z ratio via a concerted elimination. A four-step telescoped process was then developed starting from the tertiary alcohol 2a to produce GDC-0810 API as a pyrrolidine salt in 70% yield.
Going to the wire: The next generation financial risk management platform (2013)

Presents a collection of slides covering the following topics: financial risk management platform; CME Group; exchange sector; financial industry; FPGA dataflow engines; multiscale dataflow computer; dataflow box programming; trading strategies; financial gateway platform; and MaxCompiler.
Evaluation of Mutational Load (ML) in Microdissection Target of Dysplastic and Non-Dysplastic Barrettʼs Esophagus (2012)

Purpose: Management of Barrett's esophagus (BE) is challenging due to 1) inter-observer variability in histologic classification and 2) lack of adequate risk-stratification of patients with intestinal metaplasia (IM) by histopathology. Previous work [1] indicates that determining mutational load (ML), a measure of genomic instability, in BE may help differentiate patients with more advanced or progressive disease, with High ML correlating to high grade dysplasia and a small subset (4%) of intestinal metaplasia [1]. Methods: We examined biopsy specimens from 59 patients with BE. Patients were 30 to 88 years of age (mean 60 years), with 47 males and 12 females. Mean BE segment length was 2.8 cm. We microdissected multiple targets (n=146) from biopsy slides and tested them for loss of heterozygosity (LOH) and/or microsatellite instability (MSI) in a panel of 17 microsatellite markers targeting known tumor suppressor genes. The presence or absence of LOH and the proportion of cells affected by LOH were quantitatively determined, with high clonality mutations representing >75% of cells, and low clonality representing 50%-75%. We estimated ML using numbers of low and high clonality mutations and the number of loci affected by MSI. Individual targets were then independently diagnosed histologically by 3 pathologists blinded to molecular findings. Results: Increased ML correlated with increasing severity of disease according to consensus diagnosis (Table 1), (p<0.0001). There was consensus diagnosis in 130/146 targets (3-way in 82 targets and 2-way in 48). Concordance of diagnosis was higher for histologic diagnosis of the whole slide than for individual targets (kappa = 0.5 for whole slide vs 0.3 for individual targets). Of 110 targets with IM-only, 35 (27%) had No ML (no mutations), 70% had Low ML (0<ML<=2), and (3) 3% had High ML (ML>2). These percentages were similar to previously reported results [1]. 2 of 4 targets histologically diagnosed as HGD/CIS had High ML, and 2 had Low ML. Notably, several cases with HGD/CIS consensus diagnosis had lower grades of disease described in their original pathology report.Table: Mutational Load (ML) correlation with disease severityConclusion: Severity of histologic diagnosis in BE correlates with ML. A subset of IM with no histologic features of dysplasia had High ML, which correlates with high grade dysplasia [1]. Determining ML may assist in risk-stratification to determine which patients should be treated more aggressively and which should have surveillance.
Engineering Microbial Metabolism For Chemical Synthesis: Reviews And Perspectives (2017)

"Microbial metabolism refers to how microbes obtain energy and nutrients needed to live and reproduce. Its uses in chemical synthesis are multiple, and, when engineered, can provide reliable and reproducible reactions for application in industrial or biogeochemical processes. This book provides expert reviews and perspectives on how to engineer microbial metabolism for chemical synthesis. Major metabolic pathways or networks in microbial systems, including glycolysis, citric acid and photosynthesis, are briefly summarized. Following this, the metabolic engineering efforts of extending these pathways and networks for the biosynthesis of various chemicals are reviewed with the emphasis on the biochemical reactions and engineering strategies. The potential of these pathways for further metabolic engineering are also discussed. From graduate to professional level, cellular metabolism and metabolic engineering applications are introduced to the readers gradually and systematically, making it perfect for students, researchers and practitioners of chemistry, biochemistry and metabolic engineering."--
ChemInform Abstract: A New Regio‐Defined Synthesis of PMEA. (1998)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Precise analysis of the timing performance of Cherenkov-radiator-integrated MCP-PMTs: analytical deconvolution of MCP direct interactions (2020)

In order to achieve the ultimate goal of reducing coincidence time resolution (CTR) to 10 ps, thus enabling reconstruction-less positron emission tomography, a Cherenkov-radiator-integrated microchannel plate photomultiplier tube (CRI) reaching CTR of sub-50 ps full width at half maximum (FWHM) has been developed. However, a histogram of time differences between a pair of the CRIs shows undesirable side peaks, which are caused by gamma rays directly interacting with the micro channel plates (MCPs). Such direct interaction events are detrimental to the timing performance of the CRI. In this paper, we demonstrate an analytical method of deconvolving MCP direct interaction events from the timing histogram. Considering the information of the main and the two side peaks, the timing uncertainty caused by the MCP direct interaction events is deconvolved and the CTR of the CRI is analytically investigated. Consequently, the CTR is improved from 41.7 to 40.5 ps FWHM by the deconvolution. It means that a mixture of the Cherenkov radiator events and the MCP direct interaction events contribute to the CTR by a factor of 10 ps. The timing performance of the MCP direct interaction events are also evaluated. The CTR between the two MCPs is found to be 66.2 ps FWHM. This indicates that a photocathode-free radiation detector with high timing performance is possible. Elimination of the photocathode from the detector would make detector construction easier and more robust.
Chemical and thermal properties of VO2 mechanochemically derived from V2O5 by co-milling with paraffin wax (2018)

A novel mechanochemical reduction process of V<sub>2</sub>O<sub>5</sub> to VO<sub>2</sub> was established by milling with paraffin wax (PW, average molecular weight 254-646), serving as a reductant. The reduction progressed with increasing milling time and mass ratio V<sub>2</sub>O<sub>5</sub> : PW (MRVP). The mechanochemically derived VO<sub>2</sub> became phase pure after milling for 3 h with an MRVP of 30 : 1 and exhibited a reversible polymorphic transformation between tetragonal and monoclinic phases at around 53-60 °C and 67-79 °C during heating and cooling, respectively. The latent heat was above 20 J g<sup>-1</sup> in both processes, being superior to those of commercial VO<sub>2</sub>. Doping of starting V<sub>2</sub>O<sub>5</sub> with Cr, Mo or W at 1 at% in the form of oxide did not increase the latent heat. This is another difference from the conventionally prepared doped VO<sub>2</sub>. These anomalous heat storage properties of mechanochemically derived VO<sub>2</sub> were discussed mainly on the basis of X-ray photoelectron spectroscopy V<sub>2p3/2</sub> peaks combined with ion etching. The observed relatively high heat storage capacity of undoped VO<sub>2</sub> is primarily ascribed to the abundance of V<sup>4+</sup> ionic states introduced during milling with PW, which were stabilized with simultaneously introduced structural degradation throughout the entire particles. The possible role of a remaining small amount of PW was also discussed.
Painless Electrodiagnostic Current Perception Threshold and Pain Tolerance Threshold Values in CRPS Subjects and Healthy Controls: A Multicenter Study (2001)

Abstract: The purpose of this study is to evaluate both painless and painful sensory transmission in patients with Complex Regional Pain Syndrome (CRPS) using the automated electrodiagnostic sensory Nerve Conduction Threshold (sNCT) test. This test generates reliable, painless Current Perception Threshold (CPT) and atraumatic Pain Tolerance Threshold (PTT) measures. Standardized CPT and PTT measures using constant alternating current sinusoid waveform stimulus at 3 different frequencies 5 Hz, 250 Hz, and 2 kHz (Neurometer® CPT/C Neurotron, Inc. Baltimore, MD) were obtained from CRPS subjects at a distal phalange of the affected extremity and at an ipsilateral asymptomatic control site. Matched sites were tested on healthy subjects. Detection sensitivities for an abnormal PTT and CPT test were calculated based on specificity of 90% as determined from data obtained from healthy controls. A Spearman rank correlation was used to test for a significant association between presence of allodynia and an abnormal PTT or CPT at any frequency tested. Thirty‐six CRPS subjects and 57 healthy controls were tested. The highest detection sensitivity of the PTT test from symptomatic test sites was 63% for the finger and 71% for the toe. PTT abnormalities were also detected, to a lesser degree, at the asymptomatic control site (41% finger control site, 16% toe control site). The highest CPT detection sensitivity at the symptomatic site was 37% for the finger site and 53% for the toe site. CPT abnormalities were also detected at the asymptomatic control site (29% finger control site, 37% toe control site). Eighty‐six percent of the CRPS subjects had either a PTT or CPT abnormality at any frequency at the symptomatic site. There was a significant correlation between presence of allodynia and presence of an abnormal CPT and PTT, respectively ( P &lt; .01). The correlation coefficient was lower for CPT than for PTT, ie, 0.34 versus 0.6 for the finger and 0.48 versus 0.67 for the toe, respectively. In studied CRPS patients an abnormal PTT was detected with higher sensitivity than an abnormal CPT. Assessing PTT may become a useful electrodiagnostic quantitative sensory test for diagnosing and following the course of neuropathic pain conditions.
Optimal field measurement design for radio environment mapping (2013)

White spaces are locally or temporally available frequencies that are principally reserved for primary use such as TV broadcasting. The currently prevalent view to the utilization of such spectrum resources is that white space devices must query a geolocation database to obtain information about available frequencies and related maximum transmission powers. A geolocation database is fundamentally based on field strength estimates of the primary service obtained using radio propagation models. However, field strength estimates for geographically extensive broadcast networks are typically computed for spatial resolutions of hundreds of square meters. Therefore, even with the most sophisticated propagation models currently available, the predicted values always contain errors due to the limited geographical information. To overcome such deficiency, we propose a geostatistical approach for estimating the radio environment based on universal kriging interpolation. In addition, we optimize the locations of field measurements using spatial simulated annealing, and show that it improves significantly local field strength estimates. Index Terms-radio