gebhart/patrepeval huggingface dataset:
Cytokines Induce an Early Steroid Resistance in Airway Smooth Muscle Cells (2007)

We have previously shown that long-term treatment of airway smooth muscle (ASM) cells with a combination of TNF-alpha and IFN-gamma impaired steroid anti-inflammatory action through the up-regulation of glucocorticoid receptor beta isoform (GRbeta) (Mol Pharmacol 2006;69:588-596). We here found that steroid actions could also be suppressed by short-term exposure of ASM cells to TNF-alpha and IFN-gamma (6 h) as shown by the abrogated glucocorticoid responsive element (GRE)-dependent gene transcription; surprisingly, neither GRalpha nuclear translocation nor GRbeta expression was affected by cytokine mixture. The earlier induction of CD38, a molecule recently involved in asthma, seen with TNF-alpha and IFN-gamma combination but not with cytokine alone, was also completely insensitive to steroid pretreatment. Chromatin-immunoprecipitation (IP) and siRNA strategies revealed not only increased binding of interferon regulatory factor 1 (IRF-1) transcription factor to CD38 promoter, but also its implication in regulating CD38 gene transcription. Interestingly, the capacity of fluticasone to completely inhibit TNF-alpha-induced IRF-1 expression, IRF-1 DNA binding, and transactivation activities was completely lost in cells exposed to TNF-alpha and IFN-gamma in combination. This early steroid dysfunction seen with cytokine combination could be reproduced by enhancing IRF-1 cellular levels using constitutively active IRF-1, which dose-dependently inhibited GRE-dependent gene transcription. Consistently, reducing IRF-1 cellular levels using siRNA approach significantly restored steroid transactivation activities. Collectively, our findings demonstrate for the first time that IRF-1 is a novel alternative GRbeta-independent mechanism mediating steroid dysfunction induced by pro-asthmatic cytokines, in part via the suppression of GRalpha activities.
Executive summary (1900)

Bug Breakfast is a series of hour-long breakfast seminars on communicable diseases that has been delivered by the NSW Department of Health since 1990. Bug Breakfast was first broadcast by videoconference in 1999. Since then, the number of remote sites that regularly seek to be connected by videoconference has continued to increase and currently up to 10 remote sites are linked to each session. The size of the live site audience at North Sydney has also increased to 40-50 participants.
Practical Synthesis of Enantiopure γ‐Amino Alcohols by Rhodium‐Catalyzed Asymmetric Hydrogenation of β‐Secondary‐Amino Ketones (2005)

Another way to antidepressants: A series of β-secondary-amino ketone hydrochlorides (e.g. 1) were hydrogenated with remarkably high enantioselectivities by using a Rh complex containing P-chiral bisphospholane 2. These results establish a short and practical means for the synthesis of enantiopure N-monosubstituted γ-amino alcohols (e.g. 3), which are key intermediates in the synthesis of important antidepressants. (nbd=norbornadiene; TON=turnover number). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2005/z462178_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Perch availability and ground cover: factors that may constitute suitable hunting conditions for pale chanting goshawk families (1997)

We investigated the impact ot perch height and abundance, and the cover lor prey, on the hunting tactics of perch-hunting pale chanting goshawks (Melierax canorus). Although pale chanting goshawks demonstrate a clear preference lor perching on the highest available perches, the availability of perches is of more importance than height because these birds hunt almost exclusively from perches, move regularly between them, and an increased number of perches increases the area of habitat accessible for elfective hunting. In Succulent Karoo, pale chanting goshawks occupied areas where perch density (16 natural and 122 artificial/25 ha) was significantly higher than in unoccupied areas (8 natural and 12 artificial/25 ha). The high proportion of cover formed by natural perches (trees and shrubs; 36%) and the low proportion of open ground (42%) resulted in Closed Spekboomveld being unsuitable lor pale chanting goshawks, relative to the adjacent Open Spekboomveld that supported goshawks by offering a less restricted view of the ground and prey (perch cover 18% and open ground 49%), In Karroid Broken Veld, the combination of perch availability (3 026/25 ha) and open ground (62%) may provide the most suitable conditions for hunting rodent prey near cover or in the open. We suggest that such habitat may also provide a pathway, through fitness benefits gained, in the development of delayed dispersal and cooperative breeding in pale chanting goshawk families.
Prevention of Thecal Angiogenesis, Antral Follicular Growth, and Ovulation in the Primate by Treatment with Vascular Endothelial Growth Factor Trap R1R2 (2002)

This study was designed to investigate the effects of inhibition of thecal angiogenesis on follicular development in the marmoset monkey (Callithrix jacchus). To inhibit vascular endothelial growth factor (VEGF), a soluble combined truncated form of the fms-like tyrosine kinase (Flt) and kinase insert domain-containing receptor (KDR) receptor fused to IgG (VEGF Trap R1R2) was administered for 10 d during the follicular phase of the cycle. Changes in angiogenesis and follicular cell proliferation were quantified using immunocytochemistry for bromodeoxyuridine to obtain a proliferation index, CD31 to visualize endothelial cell area, and dual staining to distinguish thecal endothelial cell proliferation. The effects of the treatment on follicular development were assessed by morphometric analyses by measuring follicle diameter, thecal thickness, and a proliferation index for granulosa cells. Follicular atresia was detected and quantified using the terminal deoxynucleotidyltransferase-UTP nick end labeling method. Effects on gene expression of VEGF and its receptors, Flt and KDR, were studied by in situ hybridization. VEGF Trap R1R2 treatment resulted in a significant decrease in thecal proliferation and endothelial cell area, demonstrating the suppression of thecal angiogenesis. The absence of a normal thecal vasculature was associated with a significantly reduced thecal thickness. Antral follicular development was severely compromised, as indicated by decreased granulosa cell proliferation, decreased follicular diameter, and lack of development of ovulatory follicles. Furthermore, the rate of atresia was significantly increased. VEGF expression in granulosa and thecal cells increased after treatment, whereas Flt and KDR expressions in thecal endothelial cells were markedly decreased. These results show that VEGF Trap treatment is associated with the suppression of follicular angiogenesis, which results in the inhibition of antral follicular development and ovulation.
Betaine supplementation is less effective than methionine restriction in correcting phenotypes of CBS deficient mice (2015)

Cystathionine beta synthase (CBS) deficiency is a recessive inborn error of metabolism characterized by elevated serum total homocysteine (tHcy). Betaine supplementation, which can lower tHcy by stimulating homocysteine remethylation to methionine, is often given to CBS deficient patients in combination with other treatments such as methionine restriction and supplemental B-vitamins. However, the effectiveness of betaine supplementation by itself in the treatment of CBS deficiency has not been well explored. Here, we have examined the effect of a betaine supplemented diet on the Tg-I278T Cbs (-/-) mouse model of CBS deficiency and compared its effectiveness to our previously published data using a methionine restricted diet. Tg-I278T Cbs (-/-) mice on betaine, from the time of weaning until for 240 days of age, had a 40 % decrease in mean tHcy level and a 137 % increase in serum methionine levels. Betaine-treated Tg-I278T Cbs (-/-) mice also exhibited increased levels of betaine-dependent homocysteine methyl transferase (BHMT), increased levels of the lipogenic enzyme stearoyl-coenzyme A desaturase (SCD-1), and increased lipid droplet accumulation in the liver. Betaine supplementation largely reversed the hair loss phenotype in Tg-I278T Cbs (-/-) animals, but was far less effective than methionine restriction in reversing the weight-loss, fat-loss, and osteoporosis phenotypes. Surprisingly, betaine supplementation had several negative effects in control Tg-I278T Cbs (+/-) mice including decreased weight gain, lean mass, and bone mineral density. Our findings indicate that while betaine supplementation does have some beneficial effects, it is not as effective as methionine restriction for reversing the phenotypes associated with severe CBS deficiency in mice.
HMG-1 REDISCOVERED AS A CYTOKINE (2001)

High-mobility group-1 (HMG-1), an abundant, highly conserved cellular protein, is widely known as a nuclear DNA-binding protein that stabilizes nucleosome formation, facilitates gene transcription, and regulates the activity of steroid hormone receptors. We discovered that HMG-1 is a late mediator of delayed endotoxin lethality. When released by activated monocytes, it participates in the development of lethality and it activates downstream cytokine release. This review covers the general features of HMG-1 and its newly appreciated role as a cytokine.
3-D seismic refraction for deep exploration targets (1999)

According to Milton Dobrin’s classic text, the first seismic technique used in petroleum exploration was refraction (1923 in Mexico). During the following seven years, fan-shooting refraction methods led to the discovery of large volumes of oil trapped by salt domes on the Gulf Coast.
Stem and progenitor cells for liver repopulation: can we standardise the process from bench to bedside? (2008)

There has been recent progress in the isolation and characterisation of stem/progenitor cells that may differentiate towards the hepatic lineage. This has raised expectations that therapy of genetic or acquired liver disease might be possible by transplanting stem/progenitor cells or their liver-committed progeny. However, it is currently impossible to determine from the many documented studies which of the stem/progenitor cell populations are the best for therapy of a given disease. This is largely because of the great variability in methods used to characterise cells and their differentiation ability, variability in transplantation models and inconsistent methods to determine the effect of cell grafting in vivo. This manuscript represents a first proposal, created by a group of investigators ranging from basic biologists to clinical hepatologists. It aims to define standardised methods to assess stem/progenitor cells or their hepatic lineage-committed progeny that could be used for cell therapy in liver disease. Furthermore standardisation is suggested both for preclinical animal models to evaluate the ability of such cells to repopulate the liver functionally, and for the ongoing clinical trials using mature hepatocytes. Only when these measures have been put in place will the promise of stem/progenitor-derived hepatocyte-based therapies become reality.
Accessing and Processing Real-Time GPS Corrections for Precise Point Positioning … Some User Considerations (2005)

Natural Resources Canada makes its GPS Corrections (GPS·C) available in real-time through the Canada-wide Differential GPS Service. These corrections have also recently become available over the Internet using prototype UDP and TCP servers. The latter uses the NTRIP model of data transfer to allow, in part, for the creation of Virtual Reference Stations and the production of RTCM-SC104 local-area corrections for Differential GPS. In addition, both servers provide high-precision wide-area corrections in a modified RTCA-SC159 format to provide the necessary precision to eventually realize real-time Precise Point Positioning (PPP) to the subdecimetre level. Obtaining the highest possible accuracy from GPS corrections requires an awareness of the clock reference, or datum, to which they refer. The pseudorange measurements selected for the correction computation determine the clock reference for those corrections. The GPS·C corrections are currently referenced to the C/A (C1) and P2´ (C1+P2-P1) pseudorange observables and users must match these to achieve the best possible accuracy. Failure to do so can degrade positioning precision by up to a factor of three or more.
Absorption and hot electron production by high intensity femtosecond uv-laser pulses in solid targets (1996)

The interaction of femtosecond ${\mathrm{KrF}}^{\mathrm{*}}$-laser pulses with plasmas of various solid target materials has been studied up to intensities exceeding ${10}^{18}$ W/${\mathrm{cm}}^{2}$. Absorption measurements were performed for p- ands-polarized laser light and as a function of the laser intensity and the angle of incidence. They reveal substantial absorption up to 70% even at intensities in excess of ${10}^{18}$W/${\mathrm{cm}}^{2}$. The results have also been compared to simulations of the absorption at high intensities and, in particular, the peaking of the absorption for large angles of incidence (70\ifmmode^\circ\else\textdegree\fi{}--80\ifmmode^\circ\else\textdegree\fi{}) appears to be consistent with the anomalous skin effect as an important contribution to the total laser pulse absorption. X-ray spectra were measured in the keV range (i.e., between 6.5 and 8.4 \AA{}) and in the soft-x-ray region (i.e., between 25 and 400 \AA{}). The electron density and temperature of the plasma has been estimated by comparison of the experimental spectra with spectral simulations. A systematic study of the hot electrons produced by 248-nm light is presented. Targets consisting of an Al layer on a Si substrate have been used to determine the hot electron yield and the corresponding energy. The K-\ensuremath{\alpha} line emission produced by the hot electrons has been observed as a function of the Al-layer thickness. The measurements have been compared to simulations. The estimated hot electron temperature \ensuremath{\sim}8 keV is considerably lower than that deduced from experiments using lasers of longer wavelength and comparable intensities. Scaling indicates that 0.25-\ensuremath{\mu}m lasers can simultaneously fulfill the requirements for both intensity and hot electron temperature for the ``fast ignitor.'' \textcopyright{} 1996 The American Physical Society.
N-Desmethyl Derivatives of Deoxybouvardin and RA-VII: Synthesis and Evaluation (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTN-Desmethyl Derivatives of Deoxybouvardin and RA-VII: Synthesis and EvaluationDale L. Boger and Jiacheng ZhouCite this: J. Am. Chem. Soc. 1995, 117, 28, 7364–7378Publication Date (Print):July 1, 1995Publication History Published online1 May 2002Published inissue 1 July 1995https://pubs.acs.org/doi/10.1021/ja00133a010https://doi.org/10.1021/ja00133a010research-articleACS PublicationsRequest reuse permissionsArticle Views319Altmetric-Citations30LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Generation and detection of high-speed pulses of mid-infrared radiation with intersubband semiconductor lasers and detectors (2000)

Semiconductor lasers and detectors based on intersubband electron transitions are used to generate and measure high-speed pulses of mid-infrared radiation. In particular, we use a commercial comb generator to gain-switch a state-of-the-art 8-μm quantum cascade laser mounted in a high-speed package. The output pulses of this device are then detected with a small-area quantum-well infrared photodetector, also packaged for high-speed operation. Pulse widths shorter than 90 ps are directly measured with this system. Accounting for the finite response time of the detection electronics, a deconvolved duration of approximately 45 ps is extrapolated.
A general method ofin vitropreparation and specific mutagenesis of DNA fragments: study of protein and DNA interactions (1988)

Specific, end-labeled DNA fragments can be simply and rapidly prepared using the polymerase chain reaction (PCR). Such fragments are suitable for use in DNase I protection footprint assays, chemical sequencing reactions, and for the production and analysis of paused RNA polymerase transcription complexes. Moreover, a general means of introducing a specific mutation at any position along the length of such PCR-generated fragments is described. These procedures, which can circumvent the need for large-scale phage or plasmid growths, preparative gel-electrophoresis and the screening of molecular clones, can facilitate the rapid study of sequence-specific interactions of proteins and DNA. A rapid means of removing excess oligonucleotide primers from completed PCRs is also described.
High reflectivity 1.55 μm (Al)GaSb/AlSb Bragg mirror grown by molecular beam epitaxy (1994)

We report the molecular beam epitaxy growth of (Al)GaSb/AlSb Bragg mirrors around the 1.55 μm wavelength region. Mirrors with 97% reflectivity have been achieved by using 10 pairs of (Al)GaSb (1048 Å) and AlSb (1207 Å) quarter wavelength layers. This demonstrates the capability of the antimonide system to obtain efficient Bragg mirrors grown on GaAs substrates.
Overview of the H.264/AVC video coding standard (2003)

H.264/AVC is newest video coding standard of the ITU-T Video Coding Experts Group and the ISO/IEC Moving Picture Experts Group. The main goals of the H.264/AVC standardization effort have been enhanced compression performance and provision of a "network-friendly" video representation addressing "conversational" (video telephony) and "nonconversational" (storage, broadcast, or streaming) applications. H.264/AVC has achieved a significant improvement in rate-distortion efficiency relative to existing standards. This article provides an overview of the technical features of H.264/AVC, describes profiles and applications for the standard, and outlines the history of the standardization process.
Peroxisome Proliferator-activated Receptor γ Coactivator 1β (PGC-1β), A Novel PGC-1-related Transcription Coactivator Associated with Host Cell Factor (2002)

Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) plays a critical role in regulating multiple aspects of energy metabolism, including adaptive thermogenesis, mitochondrial biogenesis, and fatty acid beta-oxidation. Recently, this coactivator of nuclear receptors/transcription factors has been shown to control hepatic gluconeogenesis, an important component of the pathogenesis of both type-1 and type-2 diabetes. We described here the cloning of a novel bona fide homologue of PGC-1, PGC-1beta (PGC-1 was renamed as PGC-1alpha), first identified through searches of new data base entries. Despite the fact that PGC-1alpha and -1beta share similar tissue distributions with highest levels of expression in brown fat and heart, their mRNAs are differentially regulated in the brown adipose tissue upon cold exposure and during brown fat cell differentiation. Like PGC-1alpha, PGC-1beta mRNA levels are increased significantly in the liver during fasting, suggesting a possible role for this factor in the regulation of hepatic gluconeogenesis and/or fatty acid oxidation. Consistent with this, PGC-1beta was shown to physically interact and potently coactivate hepatic nuclear factor 4 and peroxisome proliferator-activated receptor alpha, nuclear receptors that are essential for hepatic adaptation to fasting. Finally, using sequence comparisons between PGC-1alpha and -1beta, we have identified a conserved amino acid motif that serves as a docking site for host cell factor, a cellular protein implicated in cell cycle regulation and viral infection. HCF is shown to bind to both PGC-1alpha and -1beta and augment their transcriptional activity.
Well‐Defined, Reversible Boronate Crosslinked Nanocarriers for Targeted Drug Delivery in Response to Acidic pH Values and cis ‐Diols (2012)

Demand and deliver: Micelles reversibly crosslinked by boronate esters (see scheme) show in vitro and in vivo stability, and thus minimize premature drug release under physiological conditions. After reaching the tumor sites, drug (stars in scheme) release is activated by cleavage of the boronate esters by the acidic conditions around the tumor or in the target cells, or by the administration of mannitol. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Chemical Modification of Proteins at Cysteine: Opportunities in Chemistry and Biology (2009)

Chemical modification of proteins is a rapidly expanding area in chemical biology. Selective installation of biochemical probes has led to a better understanding of natural protein modification and macromolecular function. In other cases such chemical alterations have changed the protein function entirely. Additionally, tethering therapeutic cargo to proteins has proven invaluable in campaigns against disease. For controlled, selective access to such modified proteins, a unique chemical handle is required. Cysteine, with its unique reactivity, has long been used for such modifications. Cysteine has enjoyed widespread use in selective protein modification, yet new applications and even new reactions continue to emerge. This Focus Review highlights the enduring utility of cysteine in protein modification with special focus on recent innovations in chemistry and biology associated with such modifications.