gebhart/patrepeval huggingface dataset:
Identification of activating region (AR) of <i>Escherichia coli</i> LysR‐type transcription factor CysB and CysB contact site on RNA polymerase alpha subunit at the <i>cysP</i> promoter (2004)

CysB is a LysR-type transcriptional regulator (LTTR) controlling the expression of numerous genes involved in bacterial sulphur assimilation via cysteine biosynthesis. Our previous mutational analysis of CysB identified several residues within the N-terminal domain crucial for DNA-binding function. Here, we focus on the functional significance of CysB residues localized in the turn between the alpha2 and alpha3 helices forming an N-terminal helix-turn-helix motif. On the basis of the characteristics of alanine-substituted mutants, we propose that CysB residues Y27, T28 and S29, lying in this turn region, comprise an 'activating region' (AR) that is crucial for positive control of the cysP promoter, but not for DNA binding and inducer response activities of CysB. Using a library of alanine substitutions in the C-terminal domain of the RNAP alpha subunit (alpha-CTD), we identify several residues in alpha-CTD that are important for CysB-dependent transcription from the cysP promoter. After probing potential protein-protein contacts in vivo with a LexA-based two-hybrid system, we propose that the '273 determinant' on alpha-CTD, including residues K271 and E273, represents a target for interaction with CysB at the cysP promoter.
Effect of Antifungal Drugs on Cytochrome P450 (CYP) 2C9, CYP2C19, and CYP3A4 Activities in Human Liver Microsomes (2005)

The effects of five antifungal drugs, fluconazole, itraconazole, micafungin, miconazole, and voriconazole, on cytochrome P450 (CYP) 2C9-mediated tolbutamide hydroxylation, CYP2C19-mediated S-mephenytoin 4'-hydroxylation, and CYP3A4-mediated nifedipine oxidation activities in human liver microsomes were compared. In addition, the effects of preincubation were estimated to investigate the mechanism-based inhibition. The IC50 value against tolbutamide hydroxylation was the lowest for miconazole (2.0 microM), followed by voriconazole (8.4 microM) and fluconazole (30.3 microM). Similarly, the IC50 value against S-mephenytoin 4'-hydroxylation was the lowest for miconazole (0.33 microM), followed by voriconazole (8.7 microM) and fluconazole (12.3 microM). On the other hand, micafungin at a concentration of 10 or 25 microM neither inhibited nor stimulated tolbutamide hydroxylation and S-mephenytoin 4'-hydroxylation, and the IC50 values for itraconazole against these were greater than 10 microM. These results suggest that miconazole is the strongest inhibitor of CYP2C9 and CYP2C19, followed by voriconazole and fluconazole, whereas micafungin would not cause clinically significant interactions with other drugs that are metabolized by CYP2C9 or CYP2C19 via the inhibition of metabolism. The IC50 value of voriconazole against nifedipine oxidation was comparable with that of fluconazole and micafungin and higher than that of itraconazole and miconazole. The stimulation of the inhibition of CYP2C9-, CYP2C19-, or CYP3A4-mediated reactions by 15-min preincubation was not observed for any of the antifungal drugs, suggesting that these drugs are not mechanism-based inhibitors.
Interactive image-based exploded view diagrams (2004)

diagram using our system. These three frames show the user interactively expanding a portion of the object to examine it in more detail (right). We present a system for creating interactive exploded view diagrams using 2D images as input. This imagebased approach enables us to directly support arbitrary rendering styles, eliminates the need for building 3D models, and allows us to leverage the abundance of existing static diagrams of complex objects. We have developed a set of semi-automatic authoring tools for quickly creating layered diagrams that allow the user to specify how the parts of an object expand, collapse, and occlude one another. We also present a viewing system that lets users dynamically filter the information presented in the diagram by directly expanding and collapsing the exploded view and searching for individual parts. Our results demonstrate that a simple 2.5D diagram representation is powerful enough to enable a useful set of interactions and that, with the right authoring tools, effective interactive diagrams in this format can be created from existing static illustrations with a small amount of effort. Key words: Interactive diagrams, Image-based rendering, Exploded views
Low-complexity, near-lossless coding of depth maps from kinect-like depth cameras (2011)

Depth cameras are gaining interest rapidly in the market as depth plus RGB is being used for a variety of applications ranging from foreground/background segmentation, face tracking, activity detection, and free viewpoint video rendering. In this paper, we present a low-complexity, near-lossless codec for coding depth maps. This coding requires no buffering of video frames, is table-less, can encode or decode a frame in close to 5ms with little code optimization, and provides between 7:1 to 16:1 compression ratio for near-lossless coding of 16-bit depth maps generated by the Kinect camera.
Maternal cell traffic bounds for immune modulation: tracking maternal H‐2 alleles in spleens of baby mice by DNA fingerprinting (2002)

We have previously reported that the immunization of pregnant mice with T-dependent antigens successfully induced suppression of the antigen-specific plaque-forming cell (PFC) response to the relevant antigens in the offspring. This suppression was not caused by the administered antigens, the antibodies produced by the pregnant mother, or lactational transfer, but was dependent on the presence of the intact maternal T cells. It was major histocompatibility complex (MHC)-restricted manner tolerance, which continued for at least one-sixth of the murine life. Traditionally, the placenta acts as a natural barrier, not allowing the cells to pass through. However, the results presented strongly suggested that maternal T cells pass through the placenta and subsequently induce tolerance. In this present study, we attempted to substantiate the presence of maternal cells in the fetal circulation through the use of molecular techniques. We found that a highly polymorphic microsatellite sequence within the class II Eb gene of the H-2 complex is useful for the molecular detection of various H-2 alleles. DNA polymorphic analysis was used for tracking maternal H-2 alleles in the spleens of baby mice. The main procedure involved polymerase chain reaction amplification and restriction fragment length polymorphism analysis of the DNA sequence encompassing the H-2-specific microsatellite from the genomic DNA of baby mice. The results indicated that maternal T cells of immunized pregnant mice cross the placenta into the fetus, eventually inducing antigen-specific immunological tolerance in the offspring.
Early Detection of High Cholesterol Levels in Young Adults (2000)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Anti-neuropilin 1 antibody Fab′ fragment conjugated liposomal docetaxel for active targeting of tumours (2014)

Neuropilin-1, a transmembrane receptor entailed in wide range of human tumour cell lines and diverse neoplasms, mediates the effects of VEGF and Semaphorins during the processes of cellular proliferation, survival and migration. In view of this, we had developed and evaluated in vitro and in vivo efficacy of anti-neuropilin-1 immunoliposomes against neuropilin-1 receptor expressing tumours. The PEGylated liposomes loaded with docetaxel were prepared using thin film hydration method. Functionalised PEGylated liposomes were prepared using post-insertion technique. Anti-neuropilin-1 immunoliposomes were prepared by covalently conjugating Fab' fragments of neuropilin-1 antibody to functionalised PEGylated liposomes via thioether linkage. In vivo evaluation of Taxotere and liposomal formulations was performed using intradermal tumour model to demonstrate anti-angiogenic and tumour regression ability. The modified Fab' fragments and immunoliposomes were found to be immunoreactive against A549 cells. Further, docetaxel loaded PEGylated liposomes and PEGylated immunoliposomes demonstrated higher in vitro cytotoxicity than Taxotere formulation at the same drug concentration and exposure time. The live imaging showed distinctive cellular uptake of functional immunoliposomes. Further, significant decrease in micro-blood vessel density and tumour volumes was observed using bio-engineered liposomes. The results clearly highlight the need to seek neuropilin-1 as one of the prime targets in developing an anti-angiogenic therapy.
Open architecture environment for control engineering education (1995)

The integration of dynamic models from the various branches of control system engineering into laboratory settings is a familiar means of providing real experience to students. The main objective of this paper is to introduce the concept of open architecture application in educational control laboratories and to discuss the advantages of this approach. The presentation is based on the examples of open architecture demonstration tools developed in the Control Laboratory of the Institute of Automatics in Krakow. The application of these tools to a commercial digital servo trainer is also described. In contrast with other approaches the environment includes commercial analysis and simulation tools popular with control engineers.
Repeat instability and motor incoordination in mice with a targeted expanded CAG repeat in the Sca1 locus (2000)

To elucidate the pathophysiology of spinocerebellar ataxia type 1 (SCA1) and to evaluate repeat length instability in the context of the mouse Sca1 gene, we generated knock-in mice by inserting an expanded tract of 78 CAG repeats into the mouse Sca1 locus. Mice heterozygous for the CAG expansion show intergenerational repeat instability (+2 to -6) at a much higher frequency in maternal transmission than in paternal transmission. The majority of changes transmitted through the female germline were small contractions, as in humans, whereas small expansions occurred more frequently in paternal transmission. The frequency of intergenerational changes was age dependent for both paternal and maternal transmissions. Mice homozygous for mutant ataxin-1 on a C57BL/6J-129/SvEv mixed background performed significantly less well on the rotating rod than did wild-type littermates at 9 months of age, although they were not ataxic by cage behavior. Histological examination of brain tissue from mutant mice up to 18 months of age revealed none of the neuropathological changes observed in other transgenic models overexpressing expanded polyglutamine tracts. These data suggest that, even with 78 glutamines, prolonged exposure to mutant ataxin-1 at endogenous levels is necessary to produce a neurological phenotype reminiscent of human SCA1. Pathogenesis is thus a function of polyglutamine length, protein levels and duration of neuronal exposure to the mutant protein.
Allosteric Modulation Bypasses the Requirement for ATP Hydrolysis in Regenerating Low Affinity Transition State Conformation of Human P-glycoprotein (2006)

ATP-dependent drug transport by human P-glycoprotein (Pgp, ABCB1) involves a coordinated communication between its drug-binding site (substrate site) and the nucleotide binding/hydrolysis domain (ATP sites). It has been demonstrated that the two ATP sites of Pgp play distinct roles within a single catalytic turnover; whereas ATP binding or/and hydrolysis by one drives substrate translocation and dissociation, the hydrolytic activity of the other resets the transporter for the subsequent cycle (Sauna, Z. E., and Ambudkar, S. V. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 2515-2520; Sauna, Z. E., and Ambudkar, S. V. (2001) J. Biol. Chem. 276, 11653-11661). Trapping of ADP (or 8-azido-ADP) and vanadate (ADP.Vi or 8-azido-ADP.Vi) at the catalytic site, following nucleotide hydrolysis, markedly reduces the affinity of Pgp for its transport substrate [125I]iodoarylazidoprazosin ([125I]IAAP), resulting in dissociation of the latter. Regeneration of the [125I]IAAP site requires an additional round of nucleotide hydrolysis. In this study, we demonstrate that certain thioxanthene-based allosteric modulators, such as cis-(Z)-flupentixol and its closely related analogs, induce regeneration of [125I]IAAP binding to vanadate-trapped (or fluoroaluminate-trapped) Pgp without any further nucleotide hydrolysis. Regeneration was facilitated by dissociation of the trapped nucleotide and vanadate. Once regenerated, the substrate site remains accessible to [125I]IAAP even after removal of the modulator from the medium, suggesting a modulator-induced relaxation of a constrained transition state conformation. Consistent with this, limited trypsin digestion of vanadate-trapped Pgp shows protection by cis-(Z)-flupentixol of two Pgp fragments (approximately 60 kDa) recognizable by a polyclonal antiserum specific for the NH2-terminal half. No regeneration was observed in the Pgp mutant F983A that is impaired in modulation by flupentixols, indicating involvement of the allosteric modulator site in the phenomenon. In summary, the data demonstrate that in the nucleotide-trapped low affinity state of Pgp, the allosteric site remains accessible and responsive to modulation by flupentixol (and its closely related analogs), which can reset the high affinity state for [125I]IAAP binding without any further nucleotide hydrolysis.
Breast Milk Pharmacokinetics of Efavirenz and Breastfed Infants' Exposure in Genetically Defined Subgroups of Mother-Infant Pairs: An Observational Study (2015)

Most breastfed infants are exposed to <10% of the weight-adjusted therapeutic pediatric dose, the safety threshold for exposure to maternal drugs from breast milk.
Cardiac Progenitor Cell–Derived Extracellular Vesicles Reduce Infarct Size and Associate with Increased Cardiovascular Cell Proliferation (2018)

Cell transplantation studies have shown that injection of progenitor cells can improve cardiac function after myocardial infarction (MI). Transplantation of human cardiac progenitor cells (hCPCs) results in an increased ejection fraction, but survival and integration are low. Therefore, paracrine factors including extracellular vesicles (EVs) are likely to contribute to the beneficial effects. We investigated the contribution of EVs by transplanting hCPCs with reduced EV secretion. Interestingly, these hCPCs were unable to reduce infarct size post-MI. Moreover, injection of hCPC-EVs did significantly reduce infarct size. Analysis of EV uptake showed cardiomyocytes and endothelial cells primarily positive and a higher Ki67 expression in these cell types. Yes-associated protein (YAP), a proliferation marker associated with Ki67, was also increased in the entire infarcted area. In summary, our data suggest that EV secretion is the driving force behind the short-term beneficial effect of hCPC transplantation on cardiac recovery after MI.
Specificity of a mycoplasma mitogen for lymphocytes from human and various animal hosts (1982)

Spleen lymphocytes from Lewis and Buffalo rats and peripheral blood lymphocytes from 10 human donors exhibited high levels of transformation when exposed to Mycoplasma arthritidis supernatants. In contrast, spleen lymphocytes from rabbits and guinea pigs and peripheral blood lymphocytes from sheep and calves failed to transform when exposed to M. arthritidis supernatants. The lymphocytes from all hosts were transformed in the presence of phytohemagglutinin or concanavalin A or both Serological studies failed to provide evidence that the responding hosts were presensitized against M. arthritidis antigens.
Ion Desorption by Core-Hole Auger Decay (1978)

We present evidence for a fundamentally new mechanism for impact-induced desorption, viz., core-hole Auger decay. We thereby explain why observed thresholds for electron-stimulated desorption (ESD) of positive ions (${\mathrm{O}}^{+}$, O${\mathrm{H}}^{+}$, and ${\mathrm{F}}^{+}$) from certain $d$-band metal oxides (Ti${\mathrm{O}}_{2}$, ${\mathrm{V}}_{2}$${\mathrm{O}}_{5}$, and W${\mathrm{O}}_{3}$) correlate in energy with the ionization potential of the highest-lying atomic core levels. We conclude that electron-stimulated desorption is in many interesting cases an atom-specific, valence-sensitive probe of surfaces.
Small molecule mimics of hydrogenases: hydrides and redox (2008)

This tutorial review is aimed at chemical scientists interested in understanding and exploiting the remarkable catalytic behavior of the hydrogenases. The key structural features are analyzed for the active sites of the two most important hydrogenases. Reactivity is emphasized, focusing on mechanism and catalysis. Through this analysis, gaps are identified in the synthesis of functional replicas of these fascinating and potentially useful enzymes.
AC Electroluminescent Processes in Pr3+-Activated (Ba0.4Ca0.6)TiO3 Diphase Polycrystals (2017)

We investigated the properties of alternating current (AC)-driven electroluminescence from (Ba<sub>0.4</sub>Ca<sub>0.6</sub>)TiO₃:Pr<sup>3+</sup> diphase polycrystal-based device. The results of crystal phases and micrographs, and the symmetrical dual emissions in one AC cycle, indicate the spontaneous formation of a dielectric/phosphor/dielectric sandwich microstructure in (Ba<sub>0.4</sub>Ca<sub>0.6</sub>)TiO₃:Pr<sup>3+</sup>. The electroluminescent device emits a red light of 617 nm, which is attributed to the ¹D₂-³H₄ transition of Pr<sup>3+</sup> in the phosphor phase. At a fixed AC frequency, the intensity of electroluminescence exhibits a steep enhancement when applying an increased driving electric field that is beyond a threshold. In a fixed driving electric field, the intensity of electroluminescence shows a rapid rise at low frequencies, but reaches saturation at high frequencies. Based on a double-injection model, we discussed systematically the electroluminescent processes in a whole cycle of AC electric field, which matched well with the experimental data. Our investigation is expected to expand our understanding of such a diphase electroluminescent device, thereby promoting their applications in lighting and displays.
DKSM: Subverting Virtual Machine Introspection for Fun and Profit (2010)

Virtual machine (VM) introspection is a powerful technique for determining the specific aspects of guest VM execution from outside the VM. Unfortunately, existing introspection solutions share a common questionable assumption. This assumption is embodied in the expectation that original kernel data structures are respected by the untrusted guest and thus can be directly used to bridge the well-known semantic gap. In this paper, we assume the perspective of the attacker, and exploit this questionable assumption to subvert VM introspection. In particular, we present an attack called DKSM (Direct Kernel Structure Manipulation), and show that it can effectively foil existing VM introspection solutions into providing false information. By assuming this perspective, we hope to better understand the challenges and opportunities for the development of future reliable VM introspection solutions that are not vulnerable to the proposed attack.
Improved thermal conductivity in microelectronic encapsulants (1991)

Several thermally conductive ceramics in combination with different polymer matrices have been examined. The interdependence of thermal conductivity with other key properties of the polymer composites are discussed. Selection of the filler and the resultant filler content in semiconductor grade molding compound are discussed in view of the practical limitations of composite thermal conductivity. Theoretical predictions of the Nielsen model (1973) are considered. The temperature dependence of composite thermal conductivity has been measured, and the effects of different types of polymer matrices are shown.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Experimental demonstration of low Axial-Ratio Circular Polarization Selective Surface (2013)

The realization of a Circular Polarization Selective Surface (CPSS) exhibiting low Axial Ratio (AR) has been demonstrated experimentally in the X band, showing good agreement with the simulated response. The fabricated CPSS has been characterized using a free-space collimator system recently acquired by ESA. An AR below 1dB, which is comparatively smaller than previous results shown in the literature, has been achieved for more than 20% bandwidth.
<i>In vitro</i> glutaminase regulation and mechanisms of glutamate generation in HIV‐1‐infected macrophage (2009)

Mononuclear phagocyte (MP, macrophages and microglia) dysfunction plays a significant role in the pathogenesis of HIV-1-associated dementia (HAD) through the production and release of soluble neurotoxic factors including glutamate. Glutamate production is greatly increased following HIV-1 infection of cultured MP, a process dependent upon the glutamate-generating enzyme glutaminase. Glutaminase inhibition was previously found to significantly decrease macrophage-mediated neurotoxicity. Potential mechanisms of glutaminase-mediated excitotoxicity including enzyme up-regulation, increased enzyme activity and glutaminase localization were investigated in this report. RNA and protein analysis of HIV-infected human primary macrophage revealed up-regulation of the glutaminase isoform GAC, yet identified no changes in the kidney-type glutaminase isoform over the course of infection. Glutaminase is a mitochondrial protein, but was found to be released into the cytosol and extracellular space following infection. This released enzyme is capable of rapidly converting the abundant extracellular amino acid glutamine into excitotoxic levels of glutamate in an energetically favorable process. These findings support glutaminase as a potential component of the HAD pathogenic process and identify a possible therapeutic avenue for the treatment of neuroinflammatory states such as HAD.