gebhart/patrepeval huggingface dataset:
Development of Resistance to 4’-Ethynyl-2-Fluoro-2’-Deoxyadenosine (EFdA) by WT and Nucleoside Reverse Transcriptase Inhibitor Resistant Human Immunodeficiency Virus Type 1 (2020)

4’-ethynyl-2-fluoro-2’-deoxyadenosine (EFdA, MK-8591, islatravir) is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) with exceptional potency against WT and drug-resistant HIV strains. However, HIV resistance to EFdA is not well characterized. We therefore developed resistance to EFdA by serial passages using progressively increasing concentrations of EFdA. The starting virus was either WT or clinically relevant NRTI-resistant viruses K65R, M184V, and D67N/K70R/T215F/K219Q). In all cases, the selected mutations included M184V. Additional mutations in the RT connection domain (R358K and E399K) and one mutation in the RNase H domain (A502V) were noted. Site-specific mutagenesis validated the role for M184V as the primary determinant for resistance to EFdA; none of the connection domain mutations contributed significantly to phenotypic resistance to EFdA. A novel EFdA resistance mutation was also observed in the background of M184V. The A114S/M184V combination of mutations imparted higher resistance to EFdA (~24-fold) than M184V (−8-fold) or A114S (~2-fold) alone. Virus fitness data suggested that A114S affects HIV fitness by itself and in the presence of M184V. This is consistent with biochemical experiments that showed decreases in the enzymatic efficiency (k cat /K m ) of WT RT vs. A114S (2.1-fold) and A114S/M184V/502V (6.5-fold), whereas there was no significant effect of A502V on RT or virus fitness. The observed EFdA resistance of M184V by itself and in combination with A114S combined with the strong published in vitro and in vivo data, confirm that EFdA is an excellent candidate as a potential HIV therapeutic.
Integro-Differential Equation for the Non-Equilibrium Thermal Response of Glass-Forming Materials: Analytical Solutions (2021)

An integro-differential equation describes the non-equilibrium thermal response of glass-forming substances with a dynamic (time-dependent) heat capacity to fast thermal perturbations. We found that this heat transfer problem could be solved analytically for a heat source with an arbitrary time dependence and different geometries. The method can be used to analyze the response to local thermal perturbations in glass-forming materials, as well as temperature fluctuations during subcritical crystal nucleation and decay. The results obtained can be useful for applications and a better understanding of the thermal properties of glass-forming materials, polymers, and nanocomposites.
Dynamic Response of Overhead Transmission Lines With Eccentric Ice Deposits Following Shock Loads (2015)

Two types of ice failure criteria are modified and combined to model the shedding phenomenon of eccentric ice deposits on overhead power transmission lines impacted by shock loads. The criteria are formulated in a user-defined element rupture subroutine, and implemented into nonlinear finite-element (FE) analysis using commercial software. The proposed modeling method is validated by the comparison of results from a physical deicing test on a real-scale 100 m single-span line and those obtained from numerical simulation. The FE model proves to be capable of differentiating eccentric ice from concentric ice deposits and confirms the ice shedding response observed in tests. The improved modeling method can be used for the design and evaluation of transmission lines in cold regions, and for the design and optimization of mechanical deicing devices and methods.
The pathogen-associated <i>iroA</i> gene cluster mediates bacterial evasion of lipocalin 2 (2006)

Numerous bacteria cope with the scarcity of iron in their microenvironment by synthesizing small iron-scavenging molecules known as siderophores. Mammals have evolved countermeasures to block siderophore-mediated iron acquisition as part of their innate immune response. Secreted lipocalin 2 (Lcn2) sequesters the Escherichia coli siderophore enterobactin (Ent), preventing E. coli from acquiring iron and protecting mammals from infection by E. coli. Here, we show that the iroA gene cluster, found in many pathogenic strains of Gram-negative enteric bacteria, including E. coli, Salmonella spp., and Klebsiella pneumoniae, allows bacteria to evade sequestration of Ent by Lcn2. We demonstrate that C-glucosylated derivatives of Ent produced by iroA-encoded enzymes do not bind purified Lcn2, and an iroA-harboring strain of E. coli is insensitive to the growth inhibitory effects of Lcn2 in vitro. Furthermore, we show that mice rapidly succumb to infection by an iroA-harboring strain of E. coli but not its wild-type counterpart, and that this increased virulence depends on evasion of host Lcn2. Our findings indicate that the iroA gene cluster allows bacteria to evade this component of the innate immune system, rejuvenating their Ent-mediated iron-acquisition pathway and playing an important role in their virulence.
Perigraft-reaction after implantation of vascular prostheses. Pathogenesis, clinical picture and treatment. (1988)

This report is based on 18 perigraft reactions in 2237 implanted vascular prostheses (1970-1985). The incidence of this complication is 6.8-9.5/1000 both for Dacron-double-velour and expanded PTFE-prostheses. The clinical picture is characterized by localized or extended fluid accumulation around the artificial graft (perigraft cysts or "swimming prosthesis"). Including 271 reports from the literature, 75% of vascular prostheses in extraanatomical positions were affected. The time interval between vascular substitution and clinical manifestation is on average 23.5 months. The pathogenesis of this aseptic late complication is still unclear. Several disposing factors are under discussion: (a) physico-chemical irritation of the surrounding tissue by the fabric itself (release of monomers, emulgators etc.), (b) mechanical trauma (continuous movement of the graft in the tissue bed, i.e. insufficient tissue fixation resulting in gaps and exudation of fluid round the prosthesis), (c) latent or manifest renal insufficiency. The partial or total removal of the affected prosthesis and its substitution by another type of vascular prosthesis offers the best chance of definitive cure. Repeated puncture of perigraft cysts produces frequent recurrencies and the danger of secondary infections. Therefore only an exchange of the graft can be recommended.
Cell-free synthesis and segregation of beta 2-microglobulin. (1979)

beta2-Microglobulin has been synthesized in vitro by using a rabbit reticulocyte lysate system and mRNA from the mouse tumor cell line EL4. The molecule is synthesized as a precursor with an NH2-terminal extension of 19 amino acids: Ser-X-Ser-Val-X-Leu-Val-Phe-Leu-Val-Leu-Val-Ser-Leu-X-Gly-Leu-Tyr-X. The processing and segregation of this peripheral membrane protein are directly comparable to those of secretory proteins and integral membrane proteins: addition of dog pancreas microsomal membranes during translation caused conversion to the processed chain, but addition of membranes after synthesis did not; only the processed chain sedimented with the membrane vesicles and was protected from proteolysis by the vesicles; and processing of nascent beta 2-microglobulin was blocked by competitive inhibitors that prevent processing and segregation of secretory and integral membrane proteins. These results suggest that the signal sequences of secretory proteins, integral membrane proteins, and peripheral membrane proteins have a common function and a common receptor on the cytoplasmic face of dog pancreas microsomal membranes. This system also provides a means for studying in vitro the expression and function of the major histocompatibility antigens that are associated with beta 2-microglobulin on cell surfaces.
Forearm orientation guidance with a vibrotactile feedback bracelet: On the directionality of tactile motor communication (2008)

User-teacher interaction during the learning and the execution of motor tasks requires the employment of various sensory channels, of which the tactile is one of the most natural and effective. In this paper we present a wearable robotic teacher for predefined motor tasks, consisting of a localization system and a wearable stimulation unit. This unit embeds four vibrotactile stimulators which are activated in order to provide the user with a feedback about the movement direction of the forearm in the cartesian space. Stimulators were chosen in order to maximize tactile sensitivity and spatial resolution. Tactile interface performances in guiding 2 DOF forearm movements were comparatively evaluated with two different sensory modalities: visual and visuotactile, by using a Virtual Reality (VR) rendering of the motor task. The comparison among sensory modalities was based on two movement indexes ad hoc defined: positioning accuracy and directionality of motor communication. The experimental tests have shown that the system described hereafter is a valuable tool for human motor motion guidance, allowing a successful and useful weighting of concurrent sensory inputs without providing relevant sensory interferences. Compared to visually-guided trajectories, positioning accuracy was improved in visuotactile-guided trajectories. The comparative analysis of the directionality index in all sensory modalities suggests that increasing the number of stimulators could improve the directionality of tactile motor communication.
On the influence of using a zwitterionic coformer for cocrystallization: structural focus on naproxen–proline cocrystals (2013)

Four original cocrystal structures incorporating a zwitterionic amino acid, prolinium, and a therapeutical agent from profen pharmaceutical family, naproxen, are highlighted and characterized in this study. Powder X-ray diffraction and differential scanning calorimetry permits the observation of the formation of the new structures, obtained by liquid-assisted grinding with methanol. Single-crystal X-ray diffraction gives us a precise outlook of the crystalline network, and allows us to accurately determine the main structural supramolecular synthon: column-like motifs, formed by prolinium entities, around whom the pharmaceutical coformer is organized. From comparison with the CSD, a similar structural pattern emerged in several other structures incorporating prolinium moieties, but not in the case of cocrystals incorporating naproxen and other non-zwitterionic coformers. This result leads us to the conclusion that zwitterionic compounds, such as amino acids, can force a pharmaceutical coformer to structure itself following a known common motif guided only by the zwitterionic entity; a very challenging aspect to take into account when developing new solid forms of therapeutical agents.
Uso de la estimulación cerebral no invasiva en los trastornos psiquiátricos de la infancia: nuevas oportunidades y retos diagnósticos y terapéuticos (2011)

Novel diagnostic and therapeutic approaches based on noninvasive brain stimulation offer some promise in the field of childhood psychiatric disorders. There are two primary methods of noninvasive brain stimulation currently available: transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Both noninvasive neuromodulation techniques appear to rely on modulating brain plasticity and thus open new hopes in the treatment of brain circuit and plasticity disorders. Since many childhood psychiatric disorders involve disturbances in the timing or mechanisms of plasticity within frontostriatal circuits, and the developing brain shows a greater capacity of brain plasticity, noninvasive brain stimulation might induce greater benefits in this population than in adults. Although the utilization of TMS and tDCS remains limited in children, there is enough evidence for their rational, safe use in this population. In this paper, we review the principles of noninvasive brain stimulation and the diagnostic and therapeutic applications in child-hood psychiatric disorders in order to inform its development into safe and reliable diagnostic and effective therapeutic approaches in pediatric psychiatry.
Proteolytic targeting of Rab29 by an effector protein distinguishes the intracellular compartments of human-adapted and broad-host <i>Salmonella</i> (2011)

Unlike broad-host Salmonella serovars, which cause self-limiting disease, Salmonella enterica serovar Typhi can infect only humans causing typhoid fever, a life-threatening systemic disease. The molecular bases for these differences are presently unknown. Here we show that the GTPase Rab29 (Rab7L1) distinguishes the intracellular vacuole of human-adapted and broad-host Salmonella serovars. A screen to identify host factors required for the export of typhoid toxin, which is exclusively encoded by the human-specific Salmonella enterica serovars Typhi (S. Typhi) and Paratyphi (S. Paratyphi) identified Rab29. We found that Rab29 is recruited to the S. Typhi-containing vacuole but not to vacuoles containing broad-host Salmonella. We observed that in cells infected with broad-host Salmonella Rab29 is specifically cleaved by the proteolytic activity of GtgE, a unique type III secretion effector protein that is absent from S. Typhi. An S. Typhi strain engineered to express GtgE and therefore able to cleave Rab29 exhibited increased intracellular replication in human macrophages. These findings indicate significant differences in the intracellular biology of human-adapted and broad-host Salmonella and show how subtle differences in the assortment of effector proteins encoded by highly related pathogens can have a major impact in their biology.
ChemInform Abstract: Photochemical Reactions. Part 145. Carbonyl vs. Epoxyketone Photochemistry: Photolysis of 1,2;3,4‐Diepoxy‐2,6,6‐trimethyl‐1‐cyclohexyl Methyl Ketone. (1985)

Abstract Die Photolyse der Titelverbindung (IV), die ausgehend von dem Carbinol (Ib) [zugänglich aus Safranal (Ia) mit Methyl‐Li] über die angegebenen Stufen synthetisiert wird, liefert die Produkte (Va)‐(Vc) + (VI)‐(VIII), deren Bildungsmechanismen eingehend diskutiert werden.
Learning from Multiple Sources (2007)

We consider the problem of learning accurate models from multiple sources of “nearby” data. Given distinct samples from multiple data sources and estimates of the dissimilarities between these sources, we provide a general theory of which samples should be used to learn models for each source. This theory is applicable in a broad decision-theoretic learning framework, and yields results for classification and regression generally, and for density estimation within the exponential family. A key component of our approach is the development of approximate triangle inequalities for expected loss, which may be of independent interest.
Immunocytochemical evidence for co-expression of Type III IP3receptor with signaling components of bitter taste transduction (2001)

IP3R3 is the dominant form of the IP3 receptor expressed in taste cells and our data suggest it plays an important role in bitter taste transduction.
Quantitative TIRF Microscopy for Counting Protein Copy Numbers in Isolated Sub-cellular Structures (2009)

Extended abstract of a paper presented at Microscopy and Microanalysis 2009 in Richmond, Virginia, USA, July 26 – July 30, 2009
A novel dopamine receptor D2 antagonist (ONC206) potentiates the effects of olaparib in endometrial cancer (2023)

Poly ADP-ribose polymerase (PARP) inhibitors are effective therapies for cancer patients with homologous recombination (HR) deficient tumors. The imipridone ONC206 is an orally bioavailable dopamine receptor D2 antagonist and mitochondrial protease ClpP agonist that has anti-tumorigenic effects in endometrial cancer via induction of apoptosis, activation of the integrated stress response and modulation of PI3K/AKT signaling. Both PARP inhibitors and imipridones are being evaluated in endometrial cancer clinical trials but have yet to be explored in combination. In this manuscript, we evaluated the effects of the PARP inhibitor olaparib in combination with ONC206 in human endometrioid endometrial cancer cell lines and in a genetically engineered mouse model of endometrial cancer. Our results showed that simultaneous exposure of endometrial cancer cells to olaparib and ONC206 resulted in synergistic anti-proliferative effects and increased cellular stress and apoptosis in both cell lines, compared to either drug alone. The combination treatment also decreased expression of the anti-apoptotic protein Bcl-2 and reduced phosphorylation of AKT and S6, with greater effects compared to either drug alone. In the transgenic model of endometrial cancer, the combination of olaparib and ONC206 resulted in a more significant reduction in tumor weight in obese and lean mice compared to ONC206 alone or olaparib alone, together with a considerably decreased Ki-67 and enhanced H2AX expression in obese and lean mice. These results suggest that this novel dual therapy may be worthy of further exploration in clinical trials.
Combinatorial studies of silicon-based alloy negatives for lithium-ion batteries. (2005)

Si-based materials are promising candidates to replace graphite as the negative electrode in Li-ion batteries. Si and Si-based materials are attractive because they can reversibly alloy with large amounts of Li. This leads to batteries with higher energy density when compared to cells made with graphite negative electrodes.
ChemInform Abstract: Water‐Promoted One‐Pot Vinylogous Mannich‐Type Reaction of Trimethylsilyloxyfuran. (2012)

Abstract The formation of imines from aldehydes and amines generates water which promotes the one‐pot Mannich reaction of trimethylsilyloxyfuran under neat conditions.
Reaction of Phenyllithium with Poly(dichlorophosphazene) (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReaction of Phenyllithium with Poly(dichlorophosphazene)H. R. Allcock and C. Ting-Wah ChuCite this: Macromolecules 1979, 12, 4, 551–555Publication Date (Print):July 1, 1979Publication History Published online1 May 2002Published inissue 1 July 1979https://doi.org/10.1021/ma60070a003RIGHTS & PERMISSIONSArticle Views126Altmetric-Citations29LEARN 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 InReddit PDF (668 KB) Get e-Alerts Get e-Alerts
Abstract 3469: Photodynamic diagnosis (PDD) and therapy (PDT) with dendrimer porphyrin micelle (2012)

Abstract [Background and purpose] We previously reported that the efficacy of photodynamic therapy (PDT) with dendrimer phthalocyanine-loaded micelles (DPc/m). However, monitoring of this photosensitizer by the clue of fluorescence is quite difficult because of the low intrinsic fluorescence originating from phthalocyanine, thus other fluorescence dye such as Alexa is required for the monitoring. For resolving this problem, we developed a novel micelle-based photosensitizer loading dendrimer porphyrin (DP). The DP-loaded micelles (DP/m) intensely emit fluorescence from porphyrin without an additional fluorescence labeling. The aim of this study was to verify practical effectiveness of DP/m by comparing that of DP on PDD and PDT. [Materials and Methods] For in vitro cytotoxicity tests, rat bladder carcinoma cells (AY-27) were incubated with DP/m for 4 h and were exposed to laser light (635 nm, 100 J/cm2). One day after PDT, cell viability was measured by WST-8 assay. Distribution of DP/m in cellular organelles was investigated using fluorescence markers of cellular organelles by a confocal laser scanning microscope. In addition, we examined in vivo fluorescence imaging using an orthotopic bladder tumor model established by inoculating AY27 cells in female Fischer F344 rats via transurethral catheterization. Four hours after intravenous administration of DP/m, the bladders were extracted and fluorescence image was obtained of bladder. [Results] DP and DP/m without light irradiation were basically non-toxic (low dark toxicity), showing cell viability being &amp;gt; 85% at the concentration up to 17 μM. However, photoirradiated DP and DP/m induced the high level of cytotoxicity: survival rate was less than 5%. PDT using DP/m showed an approximately 15 times of cytotoxicity when compared with PDT using DP. The results suggested that DP/m highly accumulate in cancer cells and can provide a significant photodynamic effect leading to cell damage. Confocal laser scanning microscopic studies showed that DP/m exhibited preferential accumulation in lysosomes through endocytosis and retention in the cells. When DP/m were injected (i.v.) into the bladder tumor animal models, fluorescence from the DP/m were clearly visualized in accordance with tumor distribution. We detected fluorescence even when a size of tumor was less than 1 mm, thus enabling optical imaging with excellent contrast between tumor and surrounding normal tissue. A study of PDT in vivo is now carried out. [Conclusion] We developed dendrimer porphyrin-loaded micelles (DP/m), which were effective for both PDD and PDT. An excellent detection of tumor was achieved owing to the intense fluorescence of DP/m and highly accumulation in tumors. The preferable DP/m uptake in tumors resulted in effective phototoxicity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3469. doi:1538-7445.AM2012-3469