gebhart/patrepeval huggingface dataset:
The Major Attenuating Mutations of the Respiratory Syncytial Virus Vaccine Candidate <i>cpts</i> 530/1009 Specify Temperature-Sensitive Defects in Transcription and Replication and a Non-Temperature-Sensitive Alteration in mRNA Termination (1999)

The live-attenuated respiratory syncytial virus vaccine candidate cpts530/1009 was previously shown to contain two separate amino acid changes in the L protein, mutations 530 and 1009 (Phe-521-->Leu and Met-1169-->Val, respectively, according to the amino acid sequence of the L protein). Each mutation independently specifies temperature-sensitive (ts) and attenuation phenotypes. In this study, we examined the effects of these mutations on transcription and RNA replication, using complete infectious recombinant virus as well as a plasmid-based minireplicon system, the latter under conditions in which effects on replication and transcription are uncoupled. In comparison with recombinant wild-type virus, the 530 and 1009 viruses were partially restricted at 37 degrees C for RNA replication, mRNA synthesis, and virus growth. The 1009 virus was partially restricted for RNA synthesis and virus growth even at 32 degrees C, which suggested that the 1009 mutation has a non-ts component in addition to the ts component. Interestingly, the synthesis of polycistronic readthrough mRNAs was elevated 1.6- to 3.8-fold for the 1009 virus, and this defect was non-ts. Studies with the minigenome system showed that the 530 and 1009 mutations each directly affect both replication and transcription, that the effect on replication was marginally greater than on transcription for the 530 mutation, and that the increase in readthrough mRNA associated with the 1009 mutation also was observed with the minigenome system.
Lithium-ion supercapacitors for pulsed power applications (2011)

A new class of supercapacitors has the potential to supplement or replace mechanical flywheels for energy storage and pulsed energy in some high power applications. These Lithium Ion Capacitors have three times the gravimetric energy density, and five times the volumetric energy density of standard electric double layer supercapacitors. In this work, we utilize two experimental test bench systems; one constructed with a motor/generator/flywheel combination, and the other with a purely solid-state solution using Lithium Ion Capacitors. This is done to facilitate a comparison that demonstrates the potential of this new device for solid-state energy storage. Of particular interest is the fact that Li-ion capacitors, as an energy storage component, offer gravimetric energy density (50-60 J/g) comparable to state-of-the-art flywheels, thus making them a possible replacement as the energy-storage media in some applications utilizing flywheel technology as the most cost effective solution. Also discussed are other unique capabilities of Li-ion capacitors, including long lifetime, high reliability, zero maintenance, and very low energy leakage, which allow energy storage for many years without power input.
Lysis of staphylococcal mastitis pathogens by bacteriophage phi11 endolysin (2006)

The Staphylococcus aureus bacteriophage phi11 endolysin has two peptidoglycan hydrolase domains (endopeptidase and amidase) and an SH3b cell wall-binding domain. In turbidity reduction assays, the purified protein can lyse untreated staphylococcal mastitis pathogens, Staphylococcus aureus and coagulase-negative staphylococci (Staphylococcus chronogenes, Staphylococcus epidermidis, Staphylococcus hyicus, Staphylococcus simulans, Staphylococcus warneri and Staphylococcus xylosus), making it a strong candidate protein antimicrobial. This lytic activity is maintained at the pH (6.7), and the "free" calcium concentration (3 mM) of milk. Truncated endolysin-derived proteins containing only the endopeptidase domain also lyse staphylococci in the absence of the SH3b-binding domain.
Design, Synthesis, and Biological Evaluation of a Second Generation of Pyrazolo[4,3-<i>e</i>]-1,2,4-triazolo[1,5-<i>c</i>]pyrimidines as Potent and Selective A<sub>2A</sub> Adenosine Receptor Antagonists (1998)

New A2A adenosine receptor antagonists in the series of pyrazolo[4, 3-e]-1,2,4-triazolo[1,5-c]pyrimidines, bearing oxygenated substituents on the phenylalkyl chains on the 7-position, have been synthesized. The compounds were tested in binding and functional assays to evaluate affinity, potency, and selectivity for rat A2A compared to rat A1 and human A3 receptor subtypes. The most interesting compounds (5d,e,h) were tested also in binding to human A1 and A2A adenosine receptors. They showed very good affinity (Ki = 0.94 nM for compound 5h) and interesting selectivity with respect to both rA1 and hA3 (compound 5h: rA1/rA2A = 787, hA3/rA2A > 10 000). These important findings make this new series of compounds the first really selective for A2A adenosine receptors. Thermodynamic parameters were evaluated; all the tested compounds displayed an enthalpy-driven binding as expected for antagonists. Moreover, compound 5h showed a negative entropy value. The highly negative enthalpic and entropic contributions could mean that 5h fits very well in the binding site where, probably, an electrostatic interaction is present associated to a scarce solvent reorganization around the receptor binding site. These compounds deserve to be further developed to assess their potential for treatment of neurodegenerative disorders such as Parkinson's disease.
Discovery and <i>in vitro</i> biosynthesis of haloduracin, a two-component lantibiotic (2006)

Lantibiotics are ribosomally synthesized peptides that undergo posttranslational modifications to their mature, antimicrobial form. They are characterized by the unique amino acids lanthionine and methyllanthionine, introduced by means of dehydration of Ser/Thr residues followed by reaction of the resulting dehydro amino acids with cysteines to form thioether linkages. Two-component lantibiotics use two peptides that are each posttranslationally modified to yield two functionally distinct products that act in synergy to provide bactericidal activity. By using genetic data instead of isolation, a two-component lantibiotic, haloduracin, was identified in the genome of the Gram-positive alkaliphilic bacterium Bacillus halodurans C-125. We show that heterologously expressed and purified precursor peptides HalA1 and HalA2 are processed by the purified modification enzymes HalM1 and HalM2 in an in vitro reconstitution of the biosynthesis of a two-component lantibiotic. The activity of each HalM enzyme is substrate-specific, and the assay products exhibit antimicrobial activity after removal of their leader sequences at an engineered Factor Xa cleavage site, indicating that correct thioether formation has occurred. Haloduracin's biological activity depends on the presence of both modified peptides. The structures of the two mature haloduracin peptides Halalpha and Halbeta were investigated, indicating that they have similarities as well as some distinct differences compared with other two-component lantibiotics.
Single‐Crystalline LaB<sub>6</sub> Nanowires. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Learning Thematic Similarity Metric from Article Sections Using Triplet Networks (2018)

Liat Ein Dor, Yosi Mass, Alon Halfon, Elad Venezian, Ilya Shnayderman, Ranit Aharonov, Noam Slonim. Proceedings of the 56th Annual Meeting of the Association for Computational Linguistics (Volume 2: Short Papers). 2018.
Conversion of Sox17 into a Pluripotency Reprogramming Factor by Reengineering Its Association with Oct4 on DNA (2011)

Very few proteins are capable to induce pluripotent stem (iPS) cells and their biochemical uniqueness remains unexplained. For example, Sox2 cooperates with other transcription factors to generate iPS cells, but Sox17, despite binding to similar DNA sequences, cannot. Here, we show that Sox2 and Sox17 exhibit inverse heterodimerization preferences with Oct4 on the canonical versus a newly identified compressed sox/oct motif. We can swap the cooperativity profiles of Sox2 and Sox17 by exchanging single amino acids at the Oct4 interaction interface resulting in Sox2KE and Sox17EK proteins. The reengineered Sox17EK now promotes reprogramming of somatic cells to iPS, whereas Sox2KE has lost this potential. Consistently, when Sox2KE is overexpressed in embryonic stem cells it forces endoderm differentiation similar to wild-type Sox17. Together, we demonstrate that strategic point mutations that facilitate Sox/Oct4 dimer formation on variant DNA motifs lead to a dramatic swap of the bioactivities of Sox2 and Sox17.
An engineered transforming growth factor β (TGF-β) monomer that functions as a dominant negative to block TGF-β signaling (2017)

The transforming growth factor β isoforms, TGF-β1, -β2, and -β3, are small secreted homodimeric signaling proteins with essential roles in regulating the adaptive immune system and maintaining the extracellular matrix. However, dysregulation of the TGF-β pathway is responsible for promoting the progression of several human diseases, including cancer and fibrosis. Despite the known importance of TGF-βs in promoting disease progression, no inhibitors have been approved for use in humans. Herein, we describe an engineered TGF-β monomer, lacking the heel helix, a structural motif essential for binding the TGF-β type I receptor (TβRI) but dispensable for binding the other receptor required for TGF-β signaling, the TGF-β type II receptor (TβRII), as an alternative therapeutic modality for blocking TGF-β signaling in humans. As shown through binding studies and crystallography, the engineered monomer retained the same overall structure of native TGF-β monomers and bound TβRII in an identical manner. Cell-based luciferase assays showed that the engineered monomer functioned as a dominant negative to inhibit TGF-β signaling with a <i>K<sub>i</sub></i> of 20-70 nm Investigation of the mechanism showed that the high affinity of the engineered monomer for TβRII, coupled with its reduced ability to non-covalently dimerize and its inability to bind and recruit TβRI, enabled it to bind endogenous TβRII but prevented it from binding and recruiting TβRI to form a signaling complex. Such engineered monomers provide a new avenue to probe and manipulate TGF-β signaling and may inform similar modifications of other TGF-β family members.
Adaptive optical zoom (2004)

In order to optically vary the magnification of an imaging system, continuous mechanical zoom lenses require multiple optical elements and use fine mechanical motion to precisely adjust the separations between individual or groups of lenses. By incorporating active elements, such as liquid crystal spatial light modulators or deformable mirrors, into the optical design, we can eliminate the need to change the spacing between lenses and create an imaging system with variable optical magnification that has no macroscopic moving parts.
Modeling network traffic on a global network-centric system with artificial neural networks (2007)

This dissertation proposes a new methodology for modeling and predicting network traffic. It features an adaptive architecture based on artificial neural networks and is especially suited for large-scale, global, network-centric systems. Accurate characterization and prediction of network traffic is essential for network resource sizing and real-time network traffic management. As networks continue to increase in size and complexity, the task has become increasingly difficult and current methodology is not sufficiently adaptable or scaleable. Current methods model network traffic with express mathematical equations which are not easily maintained or adjusted. The accuracy of these models is based on detailed characterization of the traffic stream which is measured at points along the network where the data is often subject to constant variation and rapid evolution. The main contribution of this dissertation is development of a methodology that allows utilization of artificial neural networks with increased capability for adaptation and scalability. Application on an operating global, broadband network, the Connexion by Boeing ® network, was evaluated to establish feasibility. A simulation model was constructed and testing was conducted with operational scenarios to demonstrate applicability on the case study network and to evaluate improvements in accuracy over existing methods.
Inverse Normalization Method for Cross-Sectional Imaging and Velocimetry of Two-Phase Flows Based on Electrical Capacitance Tomography (2018)

Proper normalization of the measured capacitance data is a prerequisite in electrical capacitance tomography (ECT). Conventional methods, such as parallel and series normalization, assume a higher permittivity perturbation in a homogeneous (lower) permittivity background. Although this is applicable to a number of cases, some two-phase flows are better modeled instead as a lower permittivity perturbation in a homogeneous (higher) permittivity background. A different normalization method is proposed for such cases, which provides similar image quality as conventional but is particularly beneficial for velocimetry applications based on sensitivity gradient of the ECT sensor. Simulation and experimental results are provided to illustrate the advantages for the proposed normalization technique.
PMON165 Favorable Liver Safety Profile of the Selective Glucocorticoid Receptor Modulator Relacorilant in Healthy and Hepatically Impaired Adults and in Patients with Cushing Syndrome (2022)

Abstract Background Relacorilant is a highly selective glucocorticoid receptor (GR) modulator in development for the treatment of endogenous Cushing syndrome (CS). Unlike the FDA-approved GR antagonist mifepristone, relacorilant lacks affinity for the progesterone and other receptors. In a phase 2 study in patients with CS (NCT02804750, Pivonello et al, 2021), relacorilant provided clinically meaningful changes in a number of cortisol-excess-related comorbidities, including hypertension and hyperglycemia, without undesirable antiprogesterone effects or drug-induced hypokalemia. Currently, 4 clinical studies of relacorilant in patients with CS are ongoing: GRACE (NCT03697109), a phase 3 trial enrolling patients with endogenous CS of all etiologies; GRADIENT (NCT04308590), a phase 3 trial focusing on hypercortisolism due to adrenal adenomas or hyperplasia; a phase 2/3 long-term extension study (NCT03604198); and a phase 1b study in patients with adrenocortical carcinoma associated with glucocorticoid excess (NCT04373265). Here, we report safety results and liver function test (LFT) changes from open-label phase 1 and 2 studies of relacorilant in healthy and hepatically impaired adults and in adult patients with CS. Methods In a special population study, 9 subjects with moderate hepatic impairment (Child-Pugh Class B) and 9 matched controls with normal hepatic function received relacorilant (300 mg QD) for 10 days. In a phase 1 fixed-sequence drug-drug interaction study (NCT03512548), 28 healthy subjects received relacorilant (300 mg QD) for 10 days followed by 10 days of relacorilant (300 mg QD) combined with itraconazole (200 mg QD). Thirty-five patients with CS received relacorilant (100–400 mg QD) for up to 16 weeks in the phase 2 study. Results While relacorilant is eliminated primarily through the hepatic route, no apparent difference in relacorilant pharmacokinetics in subjects with moderate hepatic impairment vs matched controls was observed, with relacorilant exposures (as measured by area under the concentration-time curve [AUC] and maximum concentration [Cmax]) largely overlapping across both groups. In addition, reductions in LFTs were observed in this study. In healthy adults treated with relacorilant followed by relacorilant + itraconazole (an agent with reported liver toxicity), a similar trend toward reduced LFTs was seen throughout the study. In the phase 2 study in patients with CS, reductions in LFTs were also observed, including normalization of LFTs in some patients with abnormal values at baseline. Conclusions These results suggest that relacorilant has a favorable liver safety profile that includes a trend toward improved LFTs in volunteers and patients with normal and abnormal liver function. The findings of the hepatic impairment study support the use of relacorilant without dose adjustment in patients with moderate hepatic impairment. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
A simplified approach to rushes summarization (2008)

In this paper we describe methods for video summarization in the context of the TRECVID 2008 BBC Rushes Summarization task. Color, motion, and audio features are used to segment, filter, and cluster the video. We experiment with varying the segment similarity measure to improve the joint clustering of segments with and without camera motion. Compared to our previous effort for TRECVID 2007 we have reduced the complexity of the summarization process as well as the visual complexity of the summaries themselves. We find our objective (inclusion) performance to be competitive with systems exhibiting similar subjective performance.
Abstract 2677: <i>MSIClass–</i>Identification and classification of microsatellite unstable using cell-free DNA from ultra-low-pass sequencing (2019)

Abstract The acquisition of mismatch repair deficiency is common in many tumor types. A unique subtype of mismatch repair deficient tumors, called tumors with microsatellite instability (MSI), has been recently approved for treatment with PD-1\PD-L1 blockade immunotherapy. Therefore, developing a quick, inexpensive, and easy-to-implement technique for classifying tumors as MSI is of utmost importance. Here, we describe such a method using next-generation sequencing data, and show that it can detect MSI from cell-free DNA (cfDNA), even when there is low fraction of tumor DNA in the cfDNA. We first analyzed the unique mutational features of MSI vs. microsatellite stable (MSS) tumors. Using our SignatureAnalyzer tool, we analyzed the signatures of the different insertions and deletions within microsatellite loci (MS-indels), and found that MSI tumors harbor elevated MS-indels of certain types, which we further validated using whole genome sequencing data from The Cancer Genome Atlas. We next used this information to develop a method (MSIClass) that analyzes the WGS data of a given sample by capturing the features unique to MSI tumors. This method assigns each sample a score based on aggregating information from all MS loci simultaneously; since MSIClass is a sample-based tool, it can call the MSI status of tumor samples that have no patient-matched normal sample. We further demonstrate that MSIClass requires minimal genomic information; indeed, sequencing coverage as low as 0.05x (current sequencing cost of ~$2/sample) is sufficient for accurate classification by MSIClass. Using in silico and in vitro DNA mixing we show that MSIClass can accurately identify MSI cases in very low purity cases, at 0.1% tumor DNA (using 0.5x sequencing coverage). We show that MSIClass, applied on cfDNA, could accurately classify 29 colon cases – 22 MSS and 7 MSI cases, 3 of which are early stage disease and with low tumor content. These results demonstrate that MSIClass is an inexpensive MSI test that can be applied in various cases: bulk sequencing where a matched normal is not available, cases of very low purity tumors, and even using cfDNA from blood in cases a biopsy is not available or possible. Finally, this methodology can be the basis for monitoring minimal residual disease, and potential be used for early detection of MSI tumors. Citation Format: Yosef E. Maruvka, Ruslana Frazer, Jonna Grimsby, Carrie Cibulskis, Viktor Adalsteinsson, Ryan Corcoran, Gad Getz. MSIClass–Identification and classification of microsatellite unstable using cell-free DNA from ultra-low-pass sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2677.
Development of SiC Gas Sensor Systems (2002)

Silicon carbide (SiC) based gas sensors have significant potential to address the gas sensing needs of aerospace applications such as emission monitoring, fuel leak detection, and fire detection. However, in order to reach that potential, a range of technical challenges must be overcome. These challenges go beyond the development of the basic sensor itself and include the need for viable enabling technologies to make a complete gas sensor system: electrical contacts, packaging, and transfer of information from the sensor to the outside world. This paper reviews the status at NASA Glenn Research Center of SiC Schottky diode gas sensor development as well as that of enabling technologies supporting SiC gas sensor system implementation. A vision of a complete high temperature microfabricated SiC gas sensor system is proposed. In the long-term, it is believed that improvements in the SiC semiconductor material itself could have a dramatic effect on the performance of SiC gas sensor systems.
Enhanced Serum Proteolysis Resistance of cell-penetrating Peptides (2015)

Small modifications in the peptide sequence result in improvements allowing the selection of better candidates for preclinical studies.
Enzymatic hydrolysis of cellulose and simultaneous fermentation to alcohol (1978)

The simultaneous saccharification of cellulose and fermentation to ethanol, utilizing the cellulase enzymes of T. reesei and the yeast S. cerevisiae, has been shown to give increased rates of hydrolysis when compared to saccharification alone due to removal of competitive inhibition by glucose and cellubiose. The effect of increasing the concentrations of enzyme and substrate resulted in increased yields of ethanol while an increase in the size of the yeast inoculum had little effect on the yield. In addition, experiments indicate no inhibitory effect of the cellulase enzymes due to accumulation of ethanol in the reaction mixture.
Identification of Regions Involved in Enzymatic Stability of Peptide Deformylase of<i>Mycobacterium tuberculosis</i> (2005)

Sequence analysis of peptide deformylase of Mycobacterium tuberculosis revealed the presence of insertions (residues 74 to 85) and an unusually long carboxy-terminal end (residues 182 to 197). Our results with deletion mutants indicated the contribution of these regions in maintaining enzymatic stability. Furthermore, we showed that the region spanning the insertions was responsible for maintaining resistance to oxidizing agents, like H(2)O(2).
Individualized Hear-Through For Acoustic Transparency Using PCA-Based Sound Pressure Estimation At The Eardrum (2022)

The hear-through functionality on hearing devices, which allows hearing equivalent to the open-ear while providing the possibility to modify the sound pressure at the eardrum in a desired manner, has drawn great attention from researchers in recent years. To this end, the output of the device is processed by means of an equalization filter, such that the transfer function between external sound sources and the eardrum is equivalent for the open-ear and the aided condition with the device in the ear. To achieve an ideal performance, the equalization filter design assumes the exact knowledge of all the relevant acoustic transfer functions. A particular challenge is the transfer function between the hearing device receiver and the eardrum, which is difficult to obtain in practice as it requires additional probe-tube measurements. In this work, we address this issue by proposing an individualized hear-through equalization filter design that leverages the measurement of the so-called secondary path to predict the sound pressure at the eardrum using a principle component analysis based estimator. Experimental results using real-ear measured transfer functions confirm that the proposed method achieves a good sound quality compared to the open-ear while outperforming filter designs that do not leverage the proposed estimator.