gebhart/patrepeval huggingface dataset:
PLA2G7, caloric restriction and cardiovascular aging (2022)

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Temporally oversampled CMOS X-ray photon counting sensor for low dose fluoroscopy (2017)

We present an x-ray quanta image sensor (XQIS) utilizing temporal oversampling and CMOS image sensor technology. The output of the XQIS is a binary bit frame with each bit representing the presence or absence of a detected x-ray photon. The bit frames are read out at very high rate (>1000fps) and a series or bit values are combined to form pixel values using digital frame integration. A system model analyzing the design parameter is presented and the component designs are evaluated in simulation.
CLK-dependent exon recognition and conjoined gene formation revealed with a novel small molecule inhibitor (2017)

CDC-like kinase phosphorylation of serine/arginine-rich proteins is central to RNA splicing reactions. Yet, the genomic network of CDC-like kinase-dependent RNA processing events remains poorly defined. Here, we explore the connectivity of genomic CDC-like kinase splicing functions by applying graduated, short-exposure, pharmacological CDC-like kinase inhibition using a novel small molecule (T3) with very high potency, selectivity, and cell-based stability. Using RNA-Seq, we define CDC-like kinase-responsive alternative splicing events, the large majority of which monotonically increase or decrease with increasing CDC-like kinase inhibition. We show that distinct RNA-binding motifs are associated with T3 response in skipped exons. Unexpectedly, we observe dose-dependent conjoined gene transcription, which is associated with motif enrichment in the last and second exons of upstream and downstream partners, respectively. siRNA knockdown of CLK2-associated genes significantly increases conjoined gene formation. Collectively, our results reveal an unexpected role for CDC-like kinase in conjoined gene formation, via regulation of 3'-end processing and associated splicing factors.The phosphorylation of serine/arginine-rich proteins by CDC-like kinase is a central regulatory mechanism for RNA splicing reactions. Here, the authors synthesize a novel small molecule CLK inhibitor and map CLK-responsive alternative splicing events and discover an effect on conjoined gene transcription.
Thieno[3,2‐b]thiophene Flanked Isoindigo Polymers for High Performance Ambipolar OFET Applications (2014)

The synthesis of a new thieno[3,2‐ b ]thiophene isoindigo (iITT) based monomer unit, and its subsequent incorporation into a series of alternating copolymers is reported. Copolymerisation with benzothiadiazole, bithiophene and thiophene comonomer units by palladium catalysed cross coupling gives three new narrow band gap semiconducting polymers for OFET applications. Extending the fused nature of the isoindigo core serves to further enhance molecular orbital overlap along the polymer backbones and facilitate good charge transport characteristics thus demonstrating the potential of extending the fused ring system that is attached to the isoindigo core. When used as the semiconducting channel in top‐gate/bottom‐contact OFET devices, good ambipolar properties are observed, with hole and electron mobilities up to 0.4 cm 2 /Vs and 0.7 cm 2 /Vs respectively. The three new polymers show good stability, with high temperature annealing showing an increase in the crystallinity of the polymers which corresponds directly to charge carrier mobility improvement as shown by X‐ray diffraction, atomic force microscopy and photothermal deflection spectroscopy.
Modeling and comparison of machine and converter losses for PWM and PAM in high-speed drives (2012)

The interaction of the machine and the converter is becoming increasingly important, especially for high-speed drives, mainly due to the effect of the converter modulation on the machine losses. The allocation of the losses to different components of the drive system needs to be known in order to choose the ideal machine and modulation match. In this paper, individual models are introduced for calculating the rotor, copper, core and inverter losses, taking the modulation type into account. These models are developed considering two typical high-speed permanent-magnet synchronous motor topologies (slotted and slotless machines) driven by PulseAmplitude-Modulation (PAM) and Pulse-Width-Modulation (PWM) converters. The models are applied to two off-the-shelf machines and a converter operating both with PAM and PWM. The test bench used to experimentally verify the models is also described and the model results are compared to the measurements. The results show that PAM produces a higher overall efficiency for the high-speed machines considered in this work. However, PWM can be used to move the losses from the rotor to the converter at the expense of decreasing the overall drive efficiency. The possible benefits of these results are discussed.
In vitro Cytotoxicity of Bisphenol A in Monocytes Cell Line (2015)

Viability, necrosis and apoptosis of monocytes are strongly and positively correlated with BPA concentration. A direct contact of such compound with biological components of blood may lead to high levels of cytotoxicity, and require us to evaluate additional factors while judging the bio-incompatibility of BPA.
Acoustic Performance of an Installed Real-Time Three-Dimensional Audio System (2011)

The Exterior Effects Room (EER), located at the NASA Langley Research Center, is a facility built for psychoacoustic studies of aircraft community noise. Recently, the EER was significantly upgraded to allow for simulation of aircraft flyovers in a three-dimensional audio and visual environment. The upgrade included installation of 27 satellite and 4 subwoofer loudspeakers that are driven by a real-time audio server. The audio server employs an implementation of the Vector Base Amplitude Panning (VBAP) method to position virtual sources at arbitrary azimuth and elevation angles in the EER. Real-time application of filters, time delays, and gains are required to compensate for installation effects, including those associated with the irregular room geometry, colorization due to varying loudspeaker installations, and crossover filtering. The authors previously showed [J. Acoust. Soc. Am., 127, 1969 (2010)] that color compensation and crossover filtering could be achieved for satellite and subwoofer loudspeakers. However, the resulting FIR filters were too long (32,768 taps) to implement in real-time. The focus of this work is on development of reduced-length surrogate IIR filters and on measurement of the acoustic performance of the installed real-time system.
Optimization of Xenon Biosensors for Detection of Protein Interactions (2005)

Hyperpolarized 129Xe NMR can detect the presence of specific low-concentration biomolecular analytes by means of the xenon biosensor, which consists of a water-soluble, targeted cryptophane-A cage that encapsulates xenon. In this work we use the prototypical biotinylated xenon biosensor to determine the relationship between the molecular composition of the xenon biosensor and the characteristics of protein-bound resonances. The effects of diastereomer overlap, dipole-dipole coupling, chemical shift anisotropy, xenon exchange, and biosensor conformational exchange on protein-bound biosensor signal were assessed. It was found that optimal protein-bound biosensor signal can be obtained by minimizing the number of biosensor diastereomers and using a flexible linker of appropriate length. Both the linewidth and sensitivity of chemical shift to protein binding of the xenon biosensor were found to be inversely proportional to linker length.
Human Monoclonal Antibodies against Anthrax Lethal Factor and Protective Antigen Act Independently To Protect againstBacillus anthracisInfection and Enhance Endogenous Immunity to Anthrax (2007)

The unpredictable nature of bioterrorism and the absence of real-time detection systems have highlighted the need for an efficient postexposure therapy for Bacillus anthracis infection. One approach is passive immunization through the administration of antibodies that mitigate the biological action of anthrax toxin. We isolated and characterized two protective fully human monoclonal antibodies with specificity for protective antigen (PA) and lethal factor (LF). These antibodies, designated IQNPA (anti-PA) and IQNLF (anti-LF), were developed as hybridomas from individuals immunized with licensed anthrax vaccine. The effective concentration of IQNPA that neutralized 50% of the toxin in anthrax toxin neutralization assays was 0.3 nM, while 0.1 nM IQNLF neutralized the same amount of toxin. When combined, the antibodies had additive neutralization efficacy. IQNPA binds to domain IV of PA containing the host cell receptor binding site, while IQNLF recognizes domain I containing the PA binding region in LF. A single 180-mug dose of either antibody given to A/J mice 2.5 h before challenge conferred 100% protection against a lethal intraperitoneal spore challenge with 24 50% lethal doses [LD50s] of B. anthracis Sterne and against rechallenge on day 20 with a more aggressive challenge dose of 41 LD50s. Mice treated with either antibody and infected with B. anthracis Sterne developed detectable murine anti-PA and anti-LF immunoglobulin G antibody responses by day 17 that were dependent on which antibody the mice had received. Based on these results, IQNPA and IQNLF act independently during prophylactic anthrax treatment and do not interfere with the establishment of endogenous immunity.
How Energy-Efficient Can a Wireless Communication System Become? (2018)

The data traffic in wireless networks is steadily growing. The long-term trend follows Cooper's law, where the traffic is doubled every two-and-a-half year, and it will likely continue for decades to come. The data transmission is tightly connected with the energy consumption in the power amplifiers, transceiver hardware, and baseband processing. The relation is captured by the energy efficiency metric, measured in bit/Joule, which describes how much energy is consumed per correctly received information bit. While the data rate is fundamentally limited by the channel capacity, there is currently no clear understanding of how energy-efficient a communication system can become. Current research papers typically present values on the order of 10 Mbit/Joule, while previous network generations seem to operate at energy efficiencies on the order of 10 kbit/Joule. Is this roughly as energy-efficient future systems (5G and beyond) can become, or are we still far from the physical limits? These questions are answered in this paper. We analyze a different cases representing potential future deployment and hardware characteristics.
Reply (2008)

*Department of Ophthalmology; Osaka University Medical School; Suita, Osaka, Japan; †Tennessee Retina; Nashville, Tennessee
Movie S1 from The Second-Generation Exportin-1 Inhibitor KPT-8602 Demonstrates Potent Activity against Acute Lymphoblastic Leukemia (2023)

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ChemInform Abstract: anti‐Human Immunodeficiency Virus Type‐1 (HIV‐1) and anti‐Hepatitis B Virus (HBV) Activities of (2,3‐Dideoxy‐2‐fluoro‐β‐L‐threo‐ pentofuranosyl)nucleosides. (1995)

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.
Mutational screens highlight glycosylation as a modulator of colony-stimulating factor 3 receptor (CSF3R) activity (2023)

The colony-stimulating factor 3 receptor (CSF3R) controls the growth of neutrophils, the most abundant type of white blood cell. In healthy neutrophils, signaling is dependent on CSF3R binding to its ligand, CSF3. A single amino acid mutation in CSF3R, T618I, instead allows for constitutive, ligand-independent cell growth and leads to a rare type of cancer called chronic neutrophilic leukemia. However, the disease mechanism is not well understood. Here, we investigated why this threonine to isoleucine substitution is the predominant mutation in chronic neutrophilic leukemia and how it leads to uncontrolled neutrophil growth. Using protein domain mapping, we demonstrated that the single CSF3R domain containing residue 618 is sufficient for ligand-independent activity. We then applied an unbiased mutational screening strategy focused on this domain and found that activating mutations are enriched at sites normally occupied by asparagine, threonine, and serine residues-the three amino acids which are commonly glycosylated. We confirmed glycosylation at multiple CSF3R residues by mass spectrometry, including the presence of GalNAc and Gal-GalNAc glycans at WT threonine 618. Using the same approach applied to other cell surface receptors, we identified an activating mutation, S489F, in the interleukin-31 receptor alpha chain. Combined, these results suggest a role for glycosylated hotspot residues in regulating receptor signaling, mutation of which can lead to ligand-independent, uncontrolled activity and human disease.
Vaccines and global health: In search of a sustainable model for vaccine development and delivery (2019)

Most vaccines for diseases in low- and middle-income countries fail to be developed because of weak or absent market incentives. Conquering diseases such as tuberculosis, HIV, malaria, and Ebola, as well as illnesses caused by multidrug-resistant pathogens, requires considerable investment and a new sustainable model of vaccine development involving close collaborations between public and private sectors.
Aberrant Promoter Methylation Profiles of Tumor Suppressor Genes in Hepatocellular Carcinoma (2003)

Hepatocellular carcinoma (HCC) is one of the most fatal human malignancies, but the molecular mechanisms of hepatocarcinogenesis remain unclear. Although p53 mutations are frequently observed in Asian HCC, it is not a common event in Western HCC. Recent studies suggest that tumor suppressor genes (TSGs) can also be silenced through epigenetic disruption, such as promoter CpG island methylation, during carcinogenesis. To further understand the molecular mechanism of hepatocarcinogenesis, we have investigated the promoter methylation status of nine TSGs (SOCS-1, GSTP, APC, E-cadherin, RAR-beta, p14, p15, p16, and p73) in 51 cases of HCC using methylation-specific polymerase chain reaction. We found that 82% of HCCs had methylation of at least one TSG promoter. The most frequently methylated TSGs in HCC were: SOCS-1 (65%), GSTP (54%), APC (53%), E-cadherin (49%), and p15 (49%). Methylation of SOCS-1, GSTP, APC, E-cadherin, and p15 was more frequent in HCC than in nontumor liver (P < 0.05). Methylation of SOCS-1, GSTP, and p15 was also significantly more frequent in HCC than cirrhotic liver (P < 0.05). Although methylation of one or two genes could be seen in both nontumor and cirrhotic livers, 53% of the HCC cases had three or more TSG promoters methylated, in comparison to 0% in nontumor liver and 13% in cirrhosis (P = 0.001). Methylation of SOCS-1, APC, and p15 was more frequently seen in hepatitis C virus-positive HCC than hepatitis C virus/hepatitis B virus-negative HCC. Our data suggest that promoter hypermethylation of TSGs is a common event in HCC and may play an important role in hepatocarcinogenesis.
ChemInform Abstract: Reactivity of 3,3′‐Methylenebis(5‐phenyl)oxazolidine with Urea, Thiourea and Cyanamide. An Alternative Mechanism for the α‐ Ureidoalkylation of 2‐Amino‐1‐phenylethanol. (1995)

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.
Network Design and Architectures for Highly Dynamic Next-Generation IP-Over-Optical Long Distance Networks (2009)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> The DARPA CORONET project seeks to develop the target network architectures and technologies needed to build next-generation long-distance IP-over-Optical-Layer (IP/OL) networks. These next-generation networks are expected to scale 10–100 times larger than today's largest commercial IP/OL network. Furthermore, DARPA has established advanced objectives for very rapid provisioning of new IP or private line connections, very rapid restoration against up to three simultaneous network failures, and future dynamic “wavelength” services ranging from speeds of 40–800 Gigabits per second. Besides these ambitious goals, the CORONET project seeks to establish a commercially-viable network architecture that supports both commercial and government services. In this paper, we describe the CORONET program requirements, and present our initial architectures and analysis of the early phases of this long-term project. We propose a novel <emphasis emphasistype="boldital">2-Phase Fast Reroute</emphasis> restoration method that achieves 50–100 ms restoration in the IP-Layer in a cost-effective manner, and a commercially viable OL restoration method that can meet the rapid CORONET requirements. We also estimate the magnitude of the extra capacity needed to provide dynamic wavelength services compared to that of static services, and show that the extra capacity to restore a small percentage of high priority traffic against multiple failures requires a small amount of extra capacity compared to that of single failures. </para>
MaizeGDB becomes 'sequence-centric' (2009)

MaizeGDB is the maize research community's central repository for genetic and genomic information about the crop plant and research model Zea mays ssp. mays. The MaizeGDB team endeavors to meet research needs as they evolve based on researcher feedback and guidance. Recent work has focused on better integrating existing data with sequence information as it becomes available for the B73, Mo17 and Palomero Toluqueño genomes. Major endeavors along these lines include the implementation of a genome browser to graphically represent genome sequences; implementation of POPcorn, a portal ancillary to MaizeGDB that offers access to independent maize projects and will allow BLAST similarity searches of participating projects' data sets from a single point; and a joint MaizeGDB/PlantGDB project to involve the maize community in genome annotation. In addition to summarizing recent achievements and future plans, this article also discusses specific examples of community involvement in setting priorities and design aspects of MaizeGDB, which should be of interest to other database and resource providers seeking to better engage their users. MaizeGDB is accessible online at http://www.maizegdb.org.Database URL:http://www.maizegdb.org.
The R345W mutation in EFEMP1 is pathogenic and causes AMD-like deposits in mice (2007)

Age-related macular degeneration (AMD) is the most common cause of vision loss in developed countries. A defining characteristic of this disorder is the accumulation of material between Bruch's membrane and the retinal pigment epithelium (RPE), first as microscopic basal deposits and later as clinically evident drusen. The pathogenesis of these deposits remains to be defined. Biochemical and genetic studies have suggested that inflammation and complement activation may play roles in AMD. Several lines of evidence also suggest that alterations to the extracellular matrix (ECM) of the RPE and choroid contribute to the development of AMD. The inherited macular degeneration Doyne honeycomb retinal dystrophy/Malattia Leventinese is thought to be caused by an R345W mutation in the EFEMP1 gene (also called fibulin-3). The pathogenicity of this mutation has been questioned because all individuals identified to date with the R345W mutation have shared a common haplotype. We investigated the pathogenicity of this mutation in families with early-onset macular degeneration and by generating Efemp1-R345W knockin mice. Genetic studies show that one of the identified families with the R345W mutation has a novel haplotype. The mutant Efemp1-R345W mice develop deposits of material between Bruch's membrane and the RPE, which resemble basal deposits in patients with AMD. These basal deposits contain Efemp1 and Timp3, an Efemp1 interacting protein. Evidence of complement activation was detected in the RPE and Bruch's membrane of the mutant mice. These results confirm that the R345W mutation in EFEMP1 is pathogenic. Further, they suggest that alterations in the ECM may stimulate complement activation, demonstrating a potential connection between these two etiologic factors in macular degeneration.
Dendrimers incorporating benzenesulfonamide moieties strongly inhibit carbonic anhydrase isoforms I–XIV (2015)

As extension of our previous study herein we report a comprehensive investigation of poly(amidoamine) (PAMAM) dendrimers as modulators of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I-XIV. Interestingly inhibitory activity was observed for the non-functionalized dendrimers against the hCA I, VII, IX, XII and XIV isoforms, whereas activation properties were reported only for the cytosolic abundant hCA II. Highly efficient inhibitory action against many isoforms having medicinal chemistry applications, such as hCA II, V, VII, IX, XII and XIV, was observed for the PAMAM functionalized counterparts bearing 4, 8, 16 and 32 benzenesulfonamide moieties. Possible applications of dendrimer-CA inhibitors as therapeutic/diagnostic agents are envisaged.
Learning Data-Driven Patient Risk Stratification Models for Clostridium difficile (2014)

Automated risk stratification of patients based on the contents of their EMRs can be used to accurately identify a high-risk population of patients. The proposed method holds promise for enabling the selective allocation of interventions aimed at reducing the rate of CDI.
Considerations in developing successful, population‐based molecular screening and prevention of lung cancer (2000)

The current mortality rate for lung cancer exceeds 85%, as it has for the last 3 decades. This statistic reflects the utility of the major diagnostic tool that has been used during this period to diagnose lung cancer: the chest X-ray. The overwhelming majority of new cases of lung cancer that are detected with chest X-rays involve individuals who already have regional or distant metastatic disease. Because the systemic treatment of this disease has not improved greatly, patients with metastatic disease rarely are cured. This article reviews the issues involved with the development of sputum-based cellular diagnostics for early stage lung cancer. The biomarker, heterogeneous nuclear ribonucleoprotein A2/B1, is the lead marker for this approach. It has been used in several studies in independent cohorts that have suggested that its overexpression in bronchial epithelial cells is associated highly with the development of lung cancer. This marker is detectable 1 year or more prior to the detection of lung cancer by chest X-ray. Finding this early airway-confined phase of lung cancer may allow for the evolution of new management approaches for very early stage lung cancer. Research activities, such aerosolized chemoprevention, are discussed. Cancer 2000;89:2465–7. © 2000 American Cancer Society.