gebhart/patrepeval huggingface dataset:
Improved Precursor Characterization for Data-Dependent Mass Spectrometry (2017)

Modern ion trap mass spectrometers are capable of collecting up to 60 tandem MS (MS/MS) scans per second, in theory providing acquisition speeds that can sample every eluting peptide precursor presented to the MS system. In practice, however, the precursor sampling capacity enabled by these ultrafast acquisition rates is often underutilized due to a host of reasons (e.g., long injection times and wide analyzer mass ranges). One often overlooked reason for this underutilization is that the instrument exhausts all the peptide features it identifies as suitable for MS/MS fragmentation. Highly abundant features can prevent annotation of lower abundance precursor ions that occupy similar mass-to-charge (m/z) space, which ultimately inhibits the acquisition of an MS/MS event. Here, we present an advanced peak determination (APD) algorithm that uses an iterative approach to annotate densely populated m/z regions to increase the number of peptides sampled during data-dependent LC-MS/MS analyses. The APD algorithm enables nearly full utilization of the sampling capacity of a quadrupole-Orbitrap-linear ion trap MS system, which yields up to a 40% increase in unique peptide identifications from whole cell HeLa lysates (approximately 53 000 in a 90 min LC-MS/MS analysis). The APD algorithm maintains improved peptide and protein identifications across several modes of proteomic data acquisition, including varying gradient lengths, different degrees of prefractionation, peptides derived from multiple proteases, and phosphoproteomic analyses. Additionally, the use of APD increases the number of peptides characterized per protein, providing improved protein quantification. In all, the APD algorithm increases the number of detectable peptide features, which maximizes utilization of the high MS/MS capacities and significantly improves sampling depth and identifications in proteomic experiments.
Development of semiconductor detectors for fast neutron radiography. (2000)

No abstract prepared.
Rat and human liver cytochrome P-450 isoform metabolism of ecteinascidin 743 does not predict gender-dependent toxicity in humans. (2002)

Ecteinascidin 743 (ET743, NSC648766) is a marine natural product with potent in vivo activity in human xenograft models. Hepatotoxicity was the most prominent toxicity in preclinical studies and was greater in female rats than in male rats. To assess the potential implications for human toxicities, the in vitro metabolism of ET743 was characterized using rat and human preparations. NADPH-dependent ET743 metabolism was greater with male rat liver microsomal preparations than with preparations from female rats and was induced by pretreatment of rats with phenobarbital and dexamethasone but not by pretreatment with 3-methylcholanthrene. Rat and human microsomal metabolism of ET743 was reduced in the presence of chemical CYP3A inhibitors or antirat CYP3A2 antiserum and to a much lesser extent by CYP2E, CYP2C, and CYP2A inhibitors. In human liver panel studies, ET743 disappearance was highly correlated with CYP3A activities and to a lesser extent with CYP2C activities. ET743 was metabolized by a number of cDNA-expressed rat P-450 isoforms, including male-predominant CYP2A2 and CYP3A2. ET743 was metabolized by cDNA-expressed human CYP3A4 and to a much lesser extent by CYP2C9, CYP2D6, and CYP2E1 preparations. Three oxidative metabolites were detected in cDNA-expressed isoform incubations, including the N-demethylated metabolite ET729 and two additional products characterized by laser capture-mass spectrometry analyses. The plasma pharmacokinetics and biliary excretion of ET743 were characterized in rats. There were no gender-dependent differences in half-life or total body clearance values. Although very modest, the biliary excretion of ET743 in male rats (0.48%) was greater than in female rats (0.28%). In contrast, the biliary excretion of the cytotoxic N-demethylated metabolite ET729 was 5-fold greater in the female rat (1.05% of dose) than in the male rat (0.19% of dose). Biliary excretion of ET729 may contribute to the hepatic toxicity in rats. These data are consistent with a major role for CYP3A isoforms in ET743 rat and human metabolism. Although there are conflicting data in the literature, expression of CYP3A isoforms in human tissues and elimination of CYP3A substrates have not been shown to vary substantially by gender. There are no indications that the other CYP isoforms implicated in ET743 metabolism are expressed differently in males and females. Thus, although it is not possible to rule out gender differences in ET743 human toxicities, our data do not predict major gender-dependent differences in the toxicity of ET743 based on metabolism.
ChemInform Abstract: Highly Fluorinated Phosphonium Ionic Liquids: Novel Media for the Generation of Superhydrophobic Coatings. (2009)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 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.
Scatter/trues detection efficiency compensation in scatter correction of PET emission data (2008)

In positron emission tomography (PET), a detector’s response to scattered radiation may be different from its response to unscattered (true coincidence) photons. This difference should be accounted for during normalization and scatter correction. We show that only a knowledge of the ratio of the scatter to trues efficiencies is necessary, however. We describe a new technique for measuring the scatter/trues detection efficiency ratio, and a procedure for applying this compensation during the scatter correction of PET emission data. We present some initial results, confirmed by simulations, indicating that the scatter/trues efficiencies may vary by up to 20% for a Siemens BrainPET MR insert in the vicinity of block gaps near the center of the transaxial field of view. These variations could result in ±5% variations in scatter corrected images if left uncompensated.
Methanol to olefins: State of the art and perspectives (2002)

Natural gas is an attractive feedstock on account of its vast reserves worldwide. World gas reserves have continued to increase as a result of the discovery of new gas fields and increasing conservation methods used in the recovery of associated gas from crude oil production. While processes are not yet available for the direct conversion of natural gas to olefins, its conversion to methanol is well established, with the trend being toward the construction of ever larger methanol plants, presently being built for up to 5,000 metric tons per day (MTD) and soon possibly for up to 10,000 MTD. The availability of low cost methanol provides a very attractive economic incentive to selectively convert it to ethene and propene and further to downstream derivatives such as polyethene, polypropene and PVC through the gas-to-olefins (GTO) and gas-to-polymers (GTP) concepts. The UOP/Hydro MTO process has been jointly developed by UOP and Norsk Hydro for the selective production of ethene and propene from either crude or refined methanol. The catalyst used in the process is based on a silicoaluminophosphate, SAPO-34. The technology has been extensively demonstrated in a demo plant by Norsk Hydro. The MTO process converts methanol to ethene and propene at close to 80% carbon selectivity in a fluidized bed reactor. The carbon selectivity approaches 90% if butenes are also accounted for as part of the product slate. There is considerable flexibility in the operation of an MTO unit. Typically, the C{sub 2}{sup =}/C{sub 3}{sup =} ratio can be modified within a range from about 0.75 to 1.5 by adjusting the operating severity, with higher temperatures leading to higher C{sub 2}{sup =}/C{sub 3}{sup =} ratios. The UOP/Hydro MTO process is a major step forward compared to earlier MTO technologies. For gas monetization GTO is more economical than GTL (fuels) and LNG, and MTO competes well with naphtha crackers for light olefin production. GTO/MTO introduces through the use of cheap natural gas a new feedstock which is less sensitive to oil price and offers an ethene/propene flexibility that can meet the increased future need for propene. (orig.)
Identification of serine 205 as a site of phosphorylation on Pax3 in proliferating but not differentiating primary myoblasts (2008)

Pax3, a member of the paired class homeodomain family of transcription factors, is essential for early skeletal muscle development. Previously, others and we have shown that the stability of Pax3 is regulated on a post-translational level. Evidence in the literature and from our laboratory suggests that phosphorylation, a common form of regulation, may play a role. However, at present, the sites of Pax3 phosphorylation are not known. We demonstrate here the first evidence that Pax3 exists as a phosphoprotein in proliferating mouse primary myoblasts. Using an in vitro kinase assay, deletion, and point mutant analysis, we conclusively identify Ser205 as a site of phosphorylation. The phosphorylation of Ser205 on endogenously expressed Pax3 was confirmed in vivo using antibodies specific for phosphorylation at Ser205. Finally, we demonstrate for the first time that the phosphorylation status of endogenous Pax3 changes rapidly upon the induction of myogenic differentiation. The presence of phosphorylation in a region of Pax3 important for mediating protein-protein interactions, and the fact that phosphorylation is lost upon induction of differentiation, allow for speculation on the biological relevance of phosphorylation.
Multicolor detection of fluorescent droplets on a cell phone using time domain encoded optofluidics (2017)

Digital droplet assays - in which biological samples are compartmentalized into millions of femtoliter volume droplets and interrogated individually - have generated enormous enthusiasm for their ability to robustly detect nucleic acids and proteins with single molecule sensitivity. A key challenge in the field however has been the cumbersome instrumentation necessary to generate, process, and detect millions of individual droplets. We have demonstrated the miniaturization of droplet diagnostics into a portable platform that can process millions of droplets per second by combining the parallelization of thousands of microfluidic droplet generators onto a single chip and a strategy to rapidly detect droplets using time-domain encoded cell phone imaging. Building on our work in this area, we show that multiple fluorescent dyes can be detected in each individual droplet by encoding the excitation light from multiple LEDs with unique maximum length sequences that are decoded using cloud-based computation. By developing a strategy to carry out multiplexed digital droplet assays in a portable platform at a rate (10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sup> droplets / sec), 1000x faster than conventional approaches on a cell phone based device, we have demonstrated a key step towards translating the sensitivity of digital assays from research laboratories to portable molecular diagnostics.
An 1800 V triple implanted vertical 6H-SiC MOSFET (1999)

6H silicon carbide vertical power MOSFETs with a blocking voltage of 1800 V have been fabricated. Applying a novel processing scheme, n/sup +/ source regions, p-base regions and p-wells have been fabricated by three different ion implantation steps. Our SiC triple ion implanted MOSFETs have a lateral channel and a planar polysilicon gate electrode. The 1800 V blocking voltage of the devices is due to the avalanche breakdown of the reverse diode. The reverse current density is well below 200 /spl mu/A/cm/sup 2/ for drain source voltages up to 90% of the breakdown voltage. The MOSFETs are normally off showing a threshold voltage of 2.7 V. The active area of 0.48 mm/sup 2/ delivers a forward drain current of 0.3 A at Y/sub GS/=10 V and V/sub DS/=8 V. The specific on resistance was determined to 82 m/spl Omega/dcm/sup 2/ at 50 mV drain source voltage and at V/sub GS/=10 V which corresponds to an uppermost acceptable oxide field strength of about 2.7 MV/cm. This specific on resistance is an order of magnitude lower than silicon DMOSFET's of the same blocking capability could offer.
Effects of Aggregation on Blood Sedimentation and Conductivity (2015)

The erythrocyte sedimentation rate (ESR) test has been used for over a century. The Westergren method is routinely used in a variety of clinics. However, the mechanism of erythrocyte sedimentation remains unclear, and the 60 min required for the test seems excessive. We investigated the effects of cell aggregation during blood sedimentation and electrical conductivity at different hematocrits. A sample of blood was drop cast into a small chamber with two planar electrodes placed on the bottom. The measured blood conductivity increased slightly during the first minute and decreased thereafter. We explored various methods of enhancing or retarding the erythrocyte aggregation. Using experimental measurements and theoretical calculations, we show that the initial increase in blood conductivity was indeed caused by aggregation, while the subsequent decrease in conductivity resulted from the deposition of erythrocytes. We present a method for calculating blood conductivity based on effective medium theory. Erythrocytes are modeled as conducting spheroids surrounded by a thin insulating membrane. A digital camera was used to investigate the erythrocyte sedimentation behavior and the distribution of the cell volume fraction in a capillary tube. Experimental observations and theoretical estimations of the settling velocity are provided. We experimentally demonstrate that the disaggregated cells settle much slower than the aggregated cells. We show that our method of measuring the electrical conductivity credibly reflected the ESR. The method was very sensitive to the initial stage of aggregation and sedimentation, while the sedimentation curve for the Westergren ESR test has a very mild slope in the initial time. We tested our method for rapid estimation of the Westergren ESR. We show a correlation between our method of measuring changes in blood conductivity and standard Westergren ESR method. In the future, our method could be examined as a potential means of accelerating ESR tests in clinical practice.
Universal microbial diagnostics using random DNA probes (2016)

Early identification of pathogens is essential for limiting development of therapy-resistant pathogens and mitigating infectious disease outbreaks. Most bacterial detection schemes use target-specific probes to differentiate pathogen species, creating time and cost inefficiencies in identifying newly discovered organisms. We present a novel universal microbial diagnostics (UMD) platform to screen for microbial organisms in an infectious sample, using a small number of random DNA probes that are agnostic to the target DNA sequences. Our platform leverages the theory of sparse signal recovery (compressive sensing) to identify the composition of a microbial sample that potentially contains novel or mutant species. We validated the UMD platform in vitro using five random probes to recover 11 pathogenic bacteria. We further demonstrated in silico that UMD can be generalized to screen for common human pathogens in different taxonomy levels. UMD's unorthodox sensing approach opens the door to more efficient and universal molecular diagnostics.
Positive Modulation of AMPA Receptors Increases Neurotrophin Expression by Hippocampal and Cortical Neurons (2000)

This study investigated whether positive modulators of AMPA-type glutamate receptors influence neurotrophin expression by forebrain neurons. Treatments with the ampakine CX614 markedly and reversibly increased brain-derived neurotrophic factor (BDNF) mRNA and protein levels in cultured rat entorhinal/hippocampal slices. Acute effects of CX614 were dose dependent over the range in which the drug increased synchronous neuronal discharges; threshold concentrations for acute responses had large effects on mRNA content when applied for 3 d. Comparable results were obtained with a second, structurally distinct ampakine CX546. Ampakine-induced upregulation was broadly suppressed by AMPA, but not NMDA, receptor antagonists and by reducing transmitter release. Antagonism of L-type voltage-sensitive calcium channels blocked induction in entorhinal cortex but not hippocampus. Prolonged infusions of suprathreshold ampakine concentrations produced peak BDNF mRNA levels at 12 hr and a return to baseline levels by 48 hr. In contrast, BDNF protein remained elevated throughout a 48 hr incubation with the drug. Nerve growth factor mRNA levels also were increased by ampakines but with a much more rapid return to control levels during chronic administration. Finally, intraperitoneal injections of CX546 increased hippocampal BDNF mRNA levels in aged rats and middle-aged mice. The present results provide evidence of regional differences in mechanisms via which activity regulates neurotrophin expression. Moreover, these data establish that changes in synaptic potency produce sufficient network level physiological effects for inducing neurotrophin genes, indicate that the response becomes refractory during prolonged ampakine exposure, and raise the possibility of using positive AMPA modulators to regulate neurotrophin levels in aged brain.
Eosinophilic esophagitis (2005)

Understanding of eosinophilic esophagitis has evolved to a point at which patients can be appropriately diagnosed and initially treated; however, a paucity of long-term outcome data prevents the creation of uniform recommendations for the clinical care of patients with eosinophilic esophagitis.
Accurate quantitative phase imaging by the transport of intensity equation: a mixed-transfer-function approach (2021)

As a well-established deterministic phase retrieval approach, the transport of intensity equation (TIE) is able to recover the quantitative phase of a sample under coherent or partially coherent illumination with its through-focus intensity measurements. Nevertheless, the inherent paraxial approximation limits its validity to low-numerical-aperture imaging and slowly varying objects, precluding its application to high-resolution quantitative phase imaging (QPI). Alternatively, QPI can be achieved by phase deconvolution approaches based on the coherent contrast transfer function or partially coherent weak object transfer function (WOTF) without invoking paraxial approximation. But these methods are generally appropriate for "weakly scattering" samples in which the total phase delay induced by the object should be small. Consequently, high-resolution high-accuracy QPI of "nonweak" phase objects with fine details and large phase excursions remains a great challenge. In this Letter, we propose a mixed-transfer-function (MTF) approach to address the dilemma between measurement accuracy and imaging resolution. By effectively merging the phases reconstructed by TIE and WOTF in the frequency domain, the high-accuracy low-frequency phase "global" profile can be secured, and high-resolution high-frequency features can be well preserved simultaneously. Simulations and experimental results on a microlens array and unstained biological cells demonstrate the effectiveness of MTF.
Rational Design and Synthesis of 2,2‐Bisheterocycle Tandem Derivatives as Non‐Nucleoside Hepatitis B Virus Inhibitors (2008)

Non-nucleoside tandem derivatives: Potent hepatitis B antiviral activity is established for 2,2′-bisthiazole heterocyclic derivatives. The core structure of these compounds differs from those of known non-nucleoside hepatitis B antiviral agents, constituting a new direction in hepatitis B virus drug development.
PMOS-Only Sleep Switch Dual-Threshold Voltage Domino Logic in Sub-65-nm CMOS Technologies (2007)

A circuit technique is proposed in this paper for simultaneously reducing the subthreshold and gate oxide leakage power consumption in domino logic circuits. Only p-channel sleep transistors and a dual-threshold voltage CMOS technology are utilized to place an idle domino logic circuit into a low leakage state. Sleep transistors are added to the dynamic nodes in order to reduce the subthreshold leakage current by strongly turning off all of the high-threshold voltage transistors. Similarly, the sleep switches added to the output nodes suppress the voltages across the gate insulating layers of the transistors in the fan-out gates, thereby minimizing the gate tunneling current. The proposed circuit technique lowers the total leakage power by up to 77% and 97% as compared to the standard dual-threshold voltage domino logic circuits at the high and low die temperatures, respectively. Similarly, a 22% to 44% reduction in the total leakage power is observed as compared to a previously published sleep switch scheme in a 45-nm CMOS technology. The energy overhead of the circuit technique is low, justifying the activation of the proposed sleep scheme by providing a net savings in total energy consumption during short idle periods.
High resolution fast quantitative docking using fourier domain correlation techniques (1997)

A ‘docking’ method based on finite grid forcefield sampling is proposed for fast evaluation of interaction energies between macromolecules and ligands. Forcefield used to calculate interaction energies utilizes a potential energy function composed of a 1/r-dependent electrostatic term and a (6-12) Lennard-Jones term for van der Waals interactions. Fast evaluation makes use of the convolution theorem allowing a point-by-point N-dimensional correlation in direct space to be replaced by a simple multiplication in spatial frequency space. Predictive accuracy was assessed by using seven protein-ligand complexes available from the Brookhaven Data Bank and determined crystallographically to high resolution. Successful prediction of ligand position and determination of ligand–protein interaction enthalpy was dependent on forcefield sampling grid size. Minimum interaction enthalpy calculated for four protein–ligand complexes coincided with crystallographic structures that used sampling grid sizes of 0.25 Å resolution and was independent of ligand starting position and orientation. Successful docking was obtained for the remaining complexes at same grid resolution provided ligand starting positions were not randomized. Sensitivity of the docking algorithm to starting orientation was a consequence of tight fit of respective ligand structures with their protein target sites for these three cases and can be circumvented by using finer rotational sampling grids for the ligand. Boltzmann statistics derived from calculated interaction energies successfully extracted the observed ribonuclease A cytidylic acid complex from a manifold of similar interaction energies. The proposed method was able to reproduce the observed crystallographic complex by using a dynamical description of ligand. © 1997 Wiley-Liss Inc.