gebhart/patrepeval huggingface dataset:
Conformational analysis of azaproline and other turn inducers (2006)

We previously investigated the conformation of several different peptidomimetics and their propensity for reverse turns, for example, Ala-Pro-Pro-Ala and Ala-D-Pro-Pro-Ala and the impact of N-methylation and N-hydroxylation [1,2]. Boussard et al. [3] studied recently azaprolines (AzPro) with the -carbon replaced by a nitrogen as -turn inducers. They concluded that both AzaPro and N-methylazaalanine (MeAzAla) induced -turns in a mixture of and DMSO-d6 that may stabilize peptide conformation differently than in water. To investigate these Aza peptides in water, we have used the AMBER* force field as implemented in MacroModel. The N-N bond parameterization in MacroModel was confirmed with 6-31G* ab initio calculations. We have studied both Ala-Pro-AzPro-Ala (1) and Ala-Ala-AzPro-Ala (2) peptides with conformational searches [4] and MC/MD [5] simulations in water as implicitly represented by the GB/SA solvation model [6].
Abstract 4134: Reversal of adenosine-mediated immune suppression by CB-708, an orally bioavailable and potent small molecule inhibitor of CD73 (2019)

Abstract Introduction: High adenosine (ADO) in the tumor microenvironment suppresses the immune response against cancer cells by inhibiting immune effector functions and promoting the development of immunosuppressive cells. Extracellular ADO can be generated from ATP released by cells undergoing stress or death through the combined actions of the ecto-nucleotidases CD39 (ATP to AMP) and CD73 (AMP to ADO). Inhibition of ADO production via CD73 is a promising therapeutic approach for the treatment of cancer. Methods: The potency of CB-708 was evaluated against recombinant CD73 and CD73-expressing cells using a malachite green assay. Selectivity against related ecto-nucleotidases was also assessed. Inhibition of CD73 in plasma was measured using LC/MS to assess conversion of 15N5-AMP into 15N5-ADO. The ability to reverse AMP-mediated immune suppression of human CD8+ T cells was determined by adding exogenous AMP during T cell activation. T cell proliferation was assayed by flow cytometry and cytokine levels were measured by ELISA. The EG7 syngeneic tumor model was used to assess the therapeutic effect of CB-708. Results: CB-708 is an orally bioavailable small molecule inhibitor that can potently inhibit both soluble human CD73 (IC50 = 170 pM) and cell-bound human CD73 (IC50 = 210 pM), but does not inhibit human CD39 (IC50&amp;gt;10 µM), ENTPD2 (IC50&amp;gt;10 µM), nor ENTPD3 (IC50&amp;gt;10 µM). CB-708 retained high potency in the presence of plasma and reversed AMP-mediated suppression of human CD8+ T cell proliferation and production of IFNγ (EC50 = 4.5 nM) and granzyme B (EC50 = 5.6 nM) in vitro. Orally administered CB-708 had dose-dependent single-agent tumor growth inhibition in the EG7 mouse syngeneic tumor model and that was associated with pharmacodynamic inhibition of plasma CD73. Enhanced tumor growth inhibition was observed when anti-PD-L1 was combined with a highly related analog of CB-708 in the EG7 model. Conclusion: CB-708 is an orally bioavailable and highly potent small molecule inhibitor of CD73. CB-708 reverses the immunosuppressive effects of AMP-derived ADO in vitro and in vivo and leads to anti-tumor activity as a monotherapy. CB-708 is expected to enter clinical development in 2019. Citation Format: Clarissa C. Lee, Deepthi Bhupathi, Roland J. Billedeau, Jason Chen, Lijing Chen, Ethan D. Emberley, Matthew I. Gross, Tony Huang, Weiqun Li, Yong Ma, Andrew L. Mackinnon, Amani Makkouk, Gisele M. Marguier, Silinda Neou, Francesco Parlati, Natalija Sotirovska, Timothy F. Stanton, Susanne M. Steggerda, Jing Zhang, Winter Zhang, Jim Li. Reversal of adenosine-mediated immune suppression by CB-708, an orally bioavailable and potent small molecule inhibitor of CD73 [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 4134.
Hybrid silicon modulators (2009)

A number of active elements have been demonstrated using the hybrid silicon evanescent platform, including lasers, amplifiers, and detectors.In this letter, two types of hybrid silicon modulators, fulfilling the building blocks in optical communication on this platform, are presented.A hybrid silicon electroabsorption modulator, suitable for high speed interconnects, with 10-dB extinction ratio at -5 V and 16-GHz modulation bandwidth is demonstrated.In addition, a hybrid silicon Mach-Zehnder modulator utilizing carrier depletion in multiple quantum wells is proved with 2 V•mm voltage-length product, 150-nm optical bandwidth, and a large signal modulation up to 10 Gb/s.
P16-13. A greater breadth of HIV-1-specific T cell responses detected using mosaic peptides compare to consensus peptides (2009)

Background The accurate identification of HIV-1-specific T cell responses is important for determining the relationship between immune responses and viral control. Overlapping peptides were synthesized to span gag and nef core 'mosaic' proteins. Mosaic proteins were assembled from fragments of natural sequence using an optimized computational biology method (W. Fischer et al., Nature Medicine, 2007). These proteins resemble natural proteins and were designed to maximize the coverage of potential T cell epitopes. Whilst recent studies have shown that mosaic proteins are highly immunogenic in mice models (W.P. Kong et al., J Virol, 2009), it remains unknown whether mosaics when compared with consensus peptide sets will detect a greater breadth of T cell responses in natural HIV-1 infection.
Switching characteristics and maximum repetitive frequency of InGaAsP/InP bistable injection lasers (1988)

Switching characteristics of nonuniformly pumped InGaAsP/InP buried-heterostructure bistable lasers are investigated both experimentally and theoretically. The automatic turn-on phenomenon, which is a random process, was observed. For repetitive operation, turn-on delay time and the necessary duration of the switch-off pulse practically limited the maximum repetitive frequency. For switch-on, triggering the saturable absorption region is more effective. For reducing the minimum switch-off pulse width, either higher doping of reverse biasing at the absorption region is recommended. The tradeoff of OFF pulse width with threshold current, and stable operation are discussed. With some improvements in device parameters, bistable operation at a repetitive frequency over 1 GHz is expected.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Perceptually Grounded Word Meaning Acquisition: A Computational Model (2010)

We present a computational model for the incremental acquisition of word meanings.Inspired by Complementary Learning Systems theory the model comprises different components which are specifically tailored to satisfy the contradictory needs of (1) rapid memorization of word-scene associations and ( 2) statistical feature extraction to reveal word meanings.Both components are recurrently coupled to achieve a memory consolidation.This process reflects itself in a gradual transfer of the knowledge about a word's meaning into the extracted features.Thereby, the internal representation of a word becomes more efficient and robust.We present simulation results for a visual scene description task in which words describing the relations between objects have been trained.This includes relations in size, color, and position.The results demonstrate our model's capability to acquire word meanings from few training exemplars.We further show that the model correctly extracts word meaning-relevant features and therefore perceptually grounds the words.
Magnetic Bearings. Super-Hybrid Magnetic Suspensions for Interferometric Scanners. (1997)

NASA maintains the Geosynchronous Operational Environmental Satellite(GOES)fleet for observing severe weather and anomalous atmospheric behavior such as the greenhouse effect. A critical instrument flown on these satellites is the Fourier Transform Infrared(FTIR)interferometer used for atmospheric element detection. An integral part of the FTIR interferometer is the scanning mechanism, which must position a mirror with a high degree of accuracy along its optical axis. Traditional means of controlling the position of this mirror have used flexure-based designs, "porch swing" linkages, or other mechanical actuators. As an alternative mechanism, we have developed a magnetic bearing-based scanner. This scanner uses what we call a super-hybrid magnetic circuit, in which permanent magnets bias both the magnetic bearings and a voice coil actuator. Two designs incorporating this super-hybrid magnetic bearing configuration are presented herein, along with experimental results for the first design. In addition to their use in FTIR interferometers, these magnetic bearing designs may have applications in coordinate measuring machines, lithographic steppers, and other precision motion control devices.
Research note : Maternally-controlled ovule abortion results from cosuppression of dihydroflavonol-4-reductase or flavonoid-3′,5′-hydroxylase genes in Petunia hybrida (2002)

Transgenes designed to overexpress anthocyanin genes An6 (encoding dihydroflavonol-4-reductase) or Hf1 (encoding flavonoid-3',5'-hydroxylase) in Petunia hybrida L. produced flower colour phenotypes similar to those caused by sense cosuppression of chalcone synthase (Chs) genes. However, unlike Chs, sense cosuppression of An6 and Hf1 resulted in female infertility in transgenotes exhibiting complete phenotypic suppression of anthocyanins. Female sterility appeared to be due to embryo abortion, with discolouration of ovules first appearing about 4 d post-fertilization, followed by gradual collapse of the ovule. Pollen from cosuppressed, female-sterile transgenotes placed on wild-type stigmas produced normal seed set, indicating that sterility of cosuppressed plants was maternally controlled. We suggest an hypothesis that cosuppression of An6 and Hf1 leads to accumulation of dihydroflavonols in the seed coat, a maternal tissue, and that this accumulation inhibits embryo growth, either directly or indirectly. In this hypothesis, direct inhibition of embryo growth would require that dihydroflavonols diffuse from the seed coat into the embryo and act there, whereas indirect inhibition would require that dihydroflavonols interfere with some capacity of the seed coat to promote embryo growth.
Development of a Hydrophobically Modified Water-Soluble Polymer as a Selective Bullhead System for Water-Production Problems (2003)

Abstract For many years, bullhead systems have received a great deal of attention from the oil and gas industry. Because of the completion techniques used in many wells, protecting the hydrocarbon interval effectively during a water control treatment is not always practical or cost-effective. Bullhead systems offer the option of a treatment without zonal isolation and are designed to decrease water production with little or no decrease in oil or gas production. This paper describes the laboratory development of a new polymer that shows promise as a bullhead system. The material falls into the class of hydrophobically modified water-soluble polymers; that is, a water-soluble polymer into which water-insoluble moieties have been introduced. The unique associative and adsorptive properties of this class of polymers are well documented, but they have not been commercially exploited to a great extent in oil field applications. These materials offer improvements over the hydrophilic polymers traditionally used for permeability modifications. For example, hydrophobic modification appears to improve cleanup of the polymer that penetrates an oil saturated core, resulting in less risk of damage to oil permeability. Hydrophobic modification, depending on the structural features, also increases reduction to water flow in comparison to the unmodified polymer. This paper includes a general description of hydrophobically modified polymers and their properties, as well as detailed descriptions of the development and laboratory testing of the new system.
Interfacial oxygen and nitrogen induced dipole formation and vacancy passivation for increased effective work functions in TiN/HfO2 gate stacks (2010)

Effective work function (EWF) changes of TiN/HfO2 annealed at low temperatures in different ambient environments are correlated with the atomic concentration of oxygen in the TiN near the metal/dielectric interface. EWF increases of 550 meV are achieved with anneals that incorporate oxygen throughout the TiN with [O]=2.8×1021 cm−3 near the TiN/HfO2 interface. However, further increasing the oxygen concentration via more aggressive anneals results in a relative decrease of the EWF and increase in electrical thickness. First-principles calculations indicate the exchange of O and N atoms near the TiN/HfO2 interface cause the formation of dipoles that increase the EWF.
High Expression and Persistent Activation of STAT1, 3 and 5 Predicts Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) Resistance in Cutaneous T-Cell Lymphoma Cells. (2006)

Abstract The hydroxamic acid vorinostat (SAHA) is an HDAC inhibitor that induces differentiation, growth arrest and/or apoptosis of malignant cells both in vitro and in vivo, and is currently being tested in the clinic for a variety of indications. In particular, vorinostat has demonstrated an overall response rate of approximately 30% in advanced cutaneous T-cell lymphoma (CTCL). The purpose of this study was to identify biomarkers that predict response to vorinostat in CTCL using preclinical model systems based upon gene expression profiling and pathogenesis of lymphoma. Herein we report the results of our evaluation of the STAT (signal transducer and activator of transcription) signaling pathway. The relative level of mRNA and protein expression as well as activation status of several members of this family have been evaluated in lymphoid cell lines with diverse vorinostat sensitivity (proliferation/viability IC50 range: 0.3–14 mM). Among them, the more responsive CTCL cells lines HH and HUT102 exhibited an IC50 ≃ 0.8 mM. These cells underwent apoptosis in response to vorinostat as assessed by TUNEL assay, in contrast to Hut78 and MJ cells (IC50 &amp;gt; 2 mM) that did not show signs of DNA fragmentation upon incubation in vorinostat-containing media for 48 h. Our results indicate that in lymphoma cell lines elevated protein levels and persistent activation of STAT1, 3 and 5 correlate with resistance to vorinostat. Immunofluorescence microscopy studies revealed that STAT proteins preferentially localize to the nuclear compartment in cells with impaired vorinostat response, consistent with the expected distribution for this group of transcription factors in the active state. Simultaneous treatment with a pan-JAK inhibitor (JAK inhibitor I; Calbiochem) resulted in an additive antiproliferative effect consistent with a survival, antiapoptotic role for STAT proteins in the response to vorinostat treatment. Immunohistochemical analysis of STAT1 in skin biopsies isolated from CTCL patients (N = 49) enrolled in the vorinostat Phase IIb clinical trial showed that malignant T cells were positively stained in approximately half of the samples (21 positively stained; 25 negatively stained; 3 poor quality specimens), and in those cases a relationship between nuclear accumulation of STAT1 and lack of response to treatment exists (p=0.007&amp;lt;0.05; Fisher’s exact test). In conclusion, our results suggest that deregulation of STAT signaling plays a role in resistance to vorinostat in CTCL and strategies that block this pathway may improve response to vorinostat.
Alkylidene hydride complexes of tantalum and the polymerization of ethylene by diiodotris(trimethylphosphine)hydroneopentylidenetantalum [Ta(CHCMe3)(H)(PMe3)3I2] (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAlkylidene hydride complexes of tantalum and the polymerization of ethylene by diiodotris(trimethylphosphine)hydroneopentylidenetantalum [Ta(CHCMe3)(H)(PMe3)3I2]H. W. Turner, R. R. Schrock, J. D. Fellmann, and S. J. HolmesCite this: J. Am. Chem. Soc. 1983, 105, 15, 4942–4950Publication Date (Print):July 1, 1983Publication History Published online1 May 2002Published inissue 1 July 1983https://pubs.acs.org/doi/10.1021/ja00353a017https://doi.org/10.1021/ja00353a017research-articleACS PublicationsRequest reuse permissionsArticle Views330Altmetric-Citations72LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Delayed and Prolonged Local Brain Hypothermia Combined with Decompressive Craniectomy: A Novel Therapeutic Strategy That Modulates Glial Dynamics (2014)

Hypothermia is considered a useful intervention for limiting pathophysiological changes after brain injury. Local hypothermia is a relatively safe and convenient intervention that circumvents many of the complications associated with systemic hypothermia. However, successful hypothermia treatment requires careful consideration of several factors including its practicality, feasibility, and associated risks. Here, we review the protective effects-and the cellular mechanisms that underlie them-of delayed and prolonged local hypothermia in rodent and canine brain injury models. The data show that the protective effects of therapeutic hypothermia, which mainly result from the modulation of inflammatory glial dynamics, are limited. We argue that decompressive craniectomy can be used to overcome the limitations of local brain hypothermia without causing histological abnormalities or other detrimental effects to the cooled area. Therefore, delayed and prolonged local brain hypothermia at the site of craniectomy is a promising intervention that may prove effective in the clinical setting.
Mixed Warm and Cold Autoimmune Hemolytic Anemia With Concomitant Immune Thrombocytopenia Following Recent SARS-CoV-2 Infection and Ongoing Rhinovirus Infection (2023)

Mixed-type autoimmune hemolytic anemia (AIHA) is a term used to describe hemolysis occurring in the context of both warm and cold reactive autoantibodies to red blood cells. Immune thrombocytopenia (ITP) is an acquired form of thrombocytopenia potentially complicated by hemorrhage due to autoantibodies reactive with platelets and megakaryocytes. Diagnosis of ITP requires exclusion of other known causes of thrombocytopenia. AIHA and ITP may be primary disorders or associated with lymphoproliferative, autoimmune, or viral infections. Here, we report a rare case of simultaneous mixed-type autoimmune hemolytic anemia with immune thrombocytopenia following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection treated with Paxlovid followed by Rhinovirus infection.
Schwann Cell Mitochondrial Metabolism Supports Long-Term Axonal Survival and Peripheral Nerve Function (2011)

Mitochondrial dysfunction is a common cause of peripheral neuropathies. While the role of neuron and axonal mitochondria in peripheral nerve disease is well appreciated, whether Schwann cell (SC) mitochondrial deficits contribute to peripheral neuropathies is unclear. Here, we examine how SC mitochondrial dysfunction affects axonal survival and contributes to the decline of peripheral nerve function by generating mice with SC-specific mitochondrial deficits. These mice (Tfam-SCKOs) were produced through the tissue-specific deletion of the mitochondrial transcription factor A gene (Tfam), which is essential for mitochondrial DNA (mtDNA) transcription and maintenance. Tfam-SCKOs were viable, but as they aged, they developed a progressive peripheral neuropathy characterized by nerve conduction abnormalities as well as extensive muscle denervation. Morphological examination of Tfam-SCKO nerves revealed early preferential loss of small unmyelinated fibers followed by prominent demyelination and degeneration of larger-caliber axons. Tfam-SCKOs displayed sensory and motor deficits consistent with this pathology. Remarkably, the severe mtDNA depletion and respiratory chain abnormalities in Tfam-SCKO mice did not affect SC proliferation or survival. Mitochondrial function in SCs is therefore essential for maintenance of axonal survival and normal peripheral nerve function, suggesting that SC mitochondrial dysfunction contributes to human peripheral neuropathies.
Vaccination of Rhesus Macaques with the Anthrax Vaccine Adsorbed Vaccine Produces a Serum Antibody Response That Effectively Neutralizes Receptor-Bound Protective AntigenIn Vitro (2010)

Anthrax toxin (ATx) is composed of the binary exotoxins lethal toxin (LTx) and edema toxin (ETx). They have separate effector proteins (edema factor and lethal factor) but have the same binding protein, protective antigen (PA). PA is the primary immunogen in the current licensed vaccine anthrax vaccine adsorbed (AVA [BioThrax]). AVA confers protective immunity by stimulating production of ATx-neutralizing antibodies, which could block the intoxication process at several steps (binding of PA to the target cell surface, furin cleavage, toxin complex formation, and binding/translocation of ATx into the cell). To evaluate ATx neutralization by anti-AVA antibodies, we developed two low-temperature LTx neutralization activity (TNA) assays that distinguish antibody blocking before and after binding of PA to target cells (noncomplexed [NC] and receptor-bound [RB] TNA assays). These assays were used to investigate anti-PA antibody responses in AVA-vaccinated rhesus macaques (Macaca mulatta) that survived an aerosol challenge with Bacillus anthracis Ames spores. Results showed that macaque anti-AVA sera neutralized LTx in vitro, even when PA was prebound to cells. Neutralization titers in surviving versus nonsurviving animals and between prechallenge and postchallenge activities were highly correlated. These data demonstrate that AVA stimulates a myriad of antibodies that recognize multiple neutralizing epitopes and confirm that change, loss, or occlusion of epitopes after PA is processed from PA83 to PA63 at the cell surface does not significantly affect in vitro neutralizing efficacy. Furthermore, these data support the idea that the full-length PA83 monomer is an appropriate immunogen for inclusion in next-generation anthrax vaccines.