gebhart/patrepeval huggingface dataset:
Hyperactivation of MAPK Induces Loss of ERα Expression in Breast Cancer Cells (2001)

ERalpha-negative breast tumors tend to overexpress growth factor receptors such as epidermal growth factor receptor or c-erbB-2. Raf-1 is a key intermediate in the signal transduction pathways of these receptors. High levels of constitutive Raf kinase (Deltaraf) activity imparts ERalpha- positive MCF-7 breast cancer cells with the ability to grow in the absence of estrogen. Deltaraf transfectants maintained in estrogen-depleted media showed greatly diminished responses to 17beta-estradiol or the pure antiestrogen ICI 182,780. Western blotting, ligand binding, and immunohistochemistry assays revealed a loss of ERalpha protein expression, and ribonuclease protection assays indicated that this correlated with loss of ERalpha message. In examining the basal expression of estrogen-induced genes in the stable transfectants or in transient cotransfection assays with an estrogen-response element- reporter construct and Deltaraf or constitutively active MAPK kinase (DeltaMEK), no ligand- independent activation of ERalpha was observed. Transient expression of Deltaraf and double-label immunostaining showed ERalpha was lost in those cells that transiently expressed Deltaraf. Abrogation of Raf signaling via treatment with the MEK inhibitors PD 098059 or U0126 resulted in reexpression of ERalpha. Similar studies performed with MCF-7 cells overexpressing epidermal growth factor receptor or c-erbB-2 confirmed that hyperactivation of MAPK resulted in down-regulation of ERalpha that was reversible by MEK inhibition or transfection with dominant negative ERK1 and ERK2 constructs. These data suggest that the hyperactivation of MAPK in epidermal growth factor receptor- or c-erbB-2-overexpressing breast cancer cells is directly responsible for generation of an ERalpha-negative phenotype and, more importantly, that this process may be abrogated by inhibiting these pathways, thus restoring ERalpha expression.
Dynamic closed-loop system for focus tracking using a spatial light modulator and a deformable membrane mirror (2006)

A dynamic closed-loop method for focus tracking using a spatial light modulator and a deformable membrane mirror within a confocal microscope is described. We report that it is possible to track defocus over a distance of up to 80 microm with an RMS precision of 57 nm. For demonstration purposes we concentrate on defocus, although in principle the method applies to any wavefront shape or aberration that can be successfully reproduced by the deformable membrane mirror and spatial light modulator, for example, spherical aberration.
Close Approximation of Two Platelet Factor 4 Tetramers by Charge Neutralization Forms the Antigens Recognized by HIT Antibodies (2006)

HIT antigens are formed when charge neutralization by polyanion allows positively charged PF4 tetramers to undergo close approximation. Whereas such a model could explain why all 3 polyanions form antibodies with similar specificities, the striking differences in the relative size and amount of complexes formed likely correspond to the observed differences in immunogenicity (UFH>LMWH approximately fondaparinux) and clinically relevant cross-reactivity (UFH>LMWH>>fondaparinux).
P2‐039: Novel tau fragments are present in human CSF (2012)

CSF Aβ42, Tau and p181Tau are widely accepted diagnostic biomarkers of Alzheimer's disease (AD). Results from numerous studies demonstrate that CSF Tau levels are ∼2X higher in mild-to-moderate AD compared to age-matched controls. In addition, this increase in CSF Tau is detected prior to the onset of clinical symptoms, and thus is predictive of the conversion from predementia (MCI) to clinical disease. Despite the importance as a diagnostic biomarker, the molecular nature of Tau present in CSF is not known. We have employed CSF denaturation coupled with reverse-phase HPLC in order to enrich and concentrate Tau and to further characterize the CSF Tau profile. Individual fractions from pooled AD and control CSF samples were analyzed by SDS-PAGE/Western blot (WB) using various anti-Tau antibodies or by using in-house, research-grade Tau ELISAs. Multiple fragments of Tau, with apparent MW sizes ranging from ∼15 kD to 40 kD, were identified by WB using an antibody that recognizes the mid-domain of Tau, but not an isotype control IgG. A subset of these bands was recognized using an antibody specific for the N-terminal of Tau. In contrast, relatively low levels of C-terminal-containing fragments were detected as demonstrated using a C-terminal specific antibody. Tau ELISA results confirmed the WB data and demonstrated that differences in Tau levels between AD and control CSF are more prominent in specific fractions, corresponding to certain apparent molecular weight Tau fragments. Our results demonstrate the existence of multiple Tau fragments in CSF and suggest that a subset of these fragments are increased in AD CSF. These particular Tau fragments may have utility as disease and/or pharmacodynamic biomarkers.
Synthesis of Glycopolymers for Microarray Applications via Ligation of Reducing Sugars to a Poly(acryloyl hydrazide) Scaffold (2010)

In this paper, we report on a general synthetic strategy for the assembly of glycopolymers that capitalizes on the intrinsic reactivity of reducing glycans toward hydrazides to form stable cyclic N-glycosides. We developed a poly(acryloyl hydrazide) (PAH) scaffold to which we conjugated a variety of reducing glycans ranging in structure from simple mono- and disaccharides to considerably more complex human milk and blood oligosaccharides. The conjugation proceeds under mild conditions with excellent ligation efficiencies and in a stereoselective manner, providing glycopolymers with pendant glycans accommodated mostly in their cyclic beta-glycosidic form. Utilizing a biotin-terminated PAH scaffold prepared via RAFT polymerization, we quickly assembled a panel of glycopolymers that we microarrayed on streptavidin-coated glass. We then demonstrated that in these microarrays, the glycopolymer ligands bind lectins according to the structures of their pendant glycans. Importantly, glycopolymers containing biologically relevant branched oligosaccharides, such as sialyl Lewis(x), as well as sulfated glycosaminoglycan-like epitopes can be readily prepared using our methodology.
BMP‐1 and the astacin family of metalloproteinases: A potential link between the extracellular matrix, growth factors and pattern formation (1996)

Members of the astacin family of metalloproteinases such as human bone morphogenetic protein 1 (BMP-1) have previously been linked to cell differentiation and pattern formation during development through a proposed role in the activation of latent growth factors of the TGF-beta superfamily. Recent findings indicate that BMP-1 is identical to pro-collagen C-proteinase, which is a metalloproteinase involved in extracellular matrix (ECM) formation. This observation suggests that a functional link may exist between astacin metalloproteinases, growth factors and cell differentiation and pattern formation during development. Taken together, current studies indicate that BMP-1 and possibly other astacin metalloproteinases are multifunctional enzymes that act directly on growth factors and the ECM. In combination, these dual actions would have profound effects on developmental processes.
Exosomes in Tumour Immunity (2009)

Exosomes are nanometre-size vesicles manufactured within late multi-vesicular endosomes and actively secreted into the extracellular environment [...]
Myotonic Dystrophy Mutation: an Unstable CTG Repeat in the 3′ Untranslated region of the Gene (1992)

Myotonic dystrophy (DM) is the most common inherited neuromuscular disease in adults, with a global incidence of 1 in 8000 individuals. DM is an autosomal dominant, multisystemic disorder characterized primarily by myotonia and progressive muscle weakness. Genomic and complementary DNA probes that map to a 10-kilobase Eco RI genomic fragment from human chromosome 19q13.3 have been used to detect a variable length polymorphism in individuals with DM. Increases in the size of the allele in patients with DM are now shown to be due to an increased number of trinucleotide CTG repeats in the 3' untranslated region of a DM candidate gene. An increase in the severity of the disease in successive generations (genetic anticipation) is accompanied by an increase in the number of trinucleotide repeats. Nearly all cases of DM (98 percent or 253 of 258 individuals) displayed expansion of the CTG repeat region. These results suggest that DM is primarily caused by mutations that generate an amplification of a specific CTG repeat.
A review of nutrients and botanicals in the integrative management of cognitive dysfunction. (1999)

Dementias and other severe cognitive dysfunction states pose a daunting challenge to existing medical management strategies. An integrative, early intervention approach seems warranted. Whereas, allopathic treatment options are highly limited, nutritional and botanical therapies are available which have proven degrees of efficacy and generally favorable benefit-to-risk profiles. This review covers five such therapies: phosphatidylserine (PS), acetyl-l-carnitine (ALC), vinpocetine, Ginkgo biloba extract (GbE), and Bacopa monniera (Bacopa). PS is a phospholipid enriched in the brain, validated through double-blind trials for improving memory, learning, concentration, word recall, and mood in middle-aged and elderly subjects with dementia or age-related cognitive decline. PS has an excellent benefit-to-risk profile. ALC is an energizer and metabolic cofactor which also benefits various cognitive functions in the middle-aged and elderly, but with a slightly less favorable benefit-to-risk profile. Vinpocetine, found in the lesser periwinkle Vinca minor, is an excellent vasodilator and cerebral metabolic enhancer with proven benefits for vascular-based cognitive dysfunction. Two meta-analyses of GbE demonstrate the best preparations offer limited benefits for vascular insufficiencies and even more limited benefits for Alzheimer's, while "commodity" GbE products offer little benefit, if any at all. GbE (and probably also vinpocetine) is incompatible with blood-thinning drugs. Bacopa is an Ayurvedic botanical with apparent anti-anxiety, anti-fatigue, and memory-strengthening effects. These five substances offer interesting contributions to a personalized approach for restoring cognitive function, perhaps eventually in conjunction with the judicious application of growth factors.
Functional neuroimaging by using an implantable CMOS multimodal device in a freely-moving mouse (2011)

We have developed implantable complementary metal oxide semiconductor (CMOS) multimodal devices to observe various neural activities in the brain. The devices, biomedical photonic large scale integration (BpLSI), have an image sensing array, light emitting diodes (LEDs), and an absorbing filter to enable a real-time fluorescence imaging. Additionally, BpLSI can equip with electrodes, a cannula, and an optical fiber for various applications. Here, we report three applications of BpLSI for freely-moving mice to visualize serine-protease activities in the hippocampus, to monitor kinetic alterations of dopaminergic-fibers in the striatum, and to obtain physiological responses with broad scope in the visual cortex.
Linkage and linkage disequilibrium in chromosome band 1p36 in American Chaldeans with inflammatory bowel disease (2000)

The idiopathic inflammatory bowel diseases (IBDs), consisting of Crohn's disease and ulcerative colitis, are complex genetic disorders involving chronic inflammation of the intestines. Multiple genetic loci have been implicated through genome-wide searches, but refinement of localization sufficient to undertake positional cloning efforts has been problematic. This difficulty can be obviated through identification of ancestrally shared regions in genetic isolates, such as the Chaldean population, a Roman Catholic group from Iraq. We analyzed four multiply affected American Chaldean families with inflammatory bowel disease not known to be related. We observed evidence for linkage and linkage disequilibrium in precisely the same region of chromosome band 1p36 reported previously in an outbred population. Maximal evidence for linkage was observed near D1S1597 by multipoint analysis (MLOD = 3.01, P = 6.1 x 10(-5)). A shared haplotype (D1S507 to D1S1628) was observed over 27 cM between two families. There was homozygous sharing of a 5 cM portion of that haplotype in one family and over a <1 cM region in the second family. Homozygous sharing of this haplotype near D1S2697 and D1S3669 was observed in one individual in a third multiply affected family, with heterozygous sharing in a fourth family. Linkage in outbred families as well as in this genetic isolate indicates that a pathophysiologically crucial IBD susceptibility gene is located in 1p36. These findings provide a unique opportunity to refine the localization and identify a major susceptibility gene for a complex genetic disorder.
Stromal cells from human long-term marrow cultures are mesenchymal cells that differentiate following a vascular smooth muscle differentiation pathway (1993)

In human long-term marrow cultures connective tissue-forming stromal cells are an essential cellular component of the adherent layer where granulomonocytic progenitors are generated from week 2 onward. We have previously found that most stromal cells in confluent cultures were stained by monoclonal antibodies directed against smooth muscle-specific actin isoforms. The present study was carried out to evaluate the time course of alpha-SM-positive stromal cells and to search for other cytoskeletal proteins specific for smooth muscle cells. It was found that the expression of alpha-SM in stromal cells was time dependent. Most of the adherent spindle-shaped, vimentin-positive stromal cells observed during the first 2 weeks of culture were alpha-SM negative. On the contrary, from week 3 to week 7, most interdigitated stromal cells contained stress fibers whose backbone was made of alpha-SM-positive microfilaments. In addition, in confluent cultures, other proteins specific for smooth muscle were detected: metavinculin, h-caldesmon, smooth muscle myosin heavy chains, and calponin. This study confirms the similarity between stromal cells and smooth muscle cells. Moreover, our results reveal that cells in vivo with the phenotype closest to that of stromal cells are immature fetal smooth muscle cells and subendothelial intimal smooth muscle cells; a cell subset with limited development following birth but extensively recruited in atherosclerotic lesions. Stromal cells very probably derive from mesenchymal cells that differentiate along this distinctive vascular smooth muscle cell pathway. In humans, this differentiation seems crucial for the maintenance of granulomonopoiesis. These in vitro studies were completed by examination of trephine bone marrow biopsies from adults without hematologic abnormalities. These studies revealed the presence of alpha-SM-positive cells at diverse locations: vascular smooth muscle cells in the media of arteries and arterioles, pericytes lining capillaries, myoid cells lining sinuses at the abluminal side of endothelial cells or found within the hematopoietic logettes, and endosteal cells lining bone trabeculae. More or less mature cells of the granulocytic series were in intimate contact with the thin cytoplasmic extensions of myoid cells. Myoid cells may be the in vivo counterpart of stromal cells with the above-described vascular smooth muscle phenotype.
Minocycline for acne vulgaris: efficacy and safety (2003)

Minocycline is likely to be an effective treatment for moderate acne vulgaris, but this review found no reliable RCT evidence to justify its continued use first-line, especially given the price differential and the concerns that still remain about its safety. Its efficacy relative to other acne therapies could not be reliably determined due to the poor methodological quality of the trials and lack of consistent choice of outcome measures. Similarly the relative risk of adverse drug reactions could not be ascertained reliably and no recommendations can be made concerning the appropriate dose that should be used. It is hoped that this review will highlight the inadequacy of acne trials in general and encourage improvements in methodological quality and standards of reporting.
Why Is Spatial Stereoresolution So Low? (2004)

Spatial stereoresolution (the finest detectable modulation of binocular disparity) is much poorer than luminance resolution (finest detectable luminance variation). In a series of psychophysical experiments, we examined four factors that could cause low stereoresolution: (1) the sampling properties of the stimulus, (2) the disparity gradient limit, (3) low-pass spatial filtering by mechanisms early in the visual process, and (4) the method by which binocular matches are computed. Our experimental results reveal the contributions of the first three factors. A theoretical analysis of binocular matching by interocular correlation reveals the contribution of the fourth: the highest attainable stereoresolution may be limited by (1) the smallest useful correlation window in the visual system, and (2) a matching process that estimates the disparity of image patches and assumes that disparity is constant across the patch. Both properties are observed in disparity-selective neurons in area V1 of the primate (Nienborg et al., 2004).
Transmit SENSE (2002)

The idea of using parallel imaging to shorten the acquisition time by the simultaneous use of multiple receive coils can be adapted for the parallel transmission of a spatially-selective multidimensional RF pulse. As in data acquisition, a multidimensional RF pulse follows a certain k-space trajectory. Shortening this trajectory shortens the pulse duration. The use of multiple transmit coils, each with its own time-dependent waveform and spatial sensitivity, can compensate for the missing parts of the excitation k-space. This results in a maintained spatial definition of the pulse profile, while its duration is reduced. This work introduces the concept of parallel transmission with arbitrarily shaped transmit coils (termed "Transmit SENSE"). Results of numerical studies demonstrate the theoretical feasibility of the approach. The experimental proof of principle is provided on a commercial MR scanner. The lack of multiple independent transmit channels was addressed by combining the excitation patterns from two separate subexperiments with different transmit setups. Shortening multidimensional RF pulses could be an interesting means of making 3D RF pulses feasible even for fast T(2)(*) relaxing species or strong main field inhomogeneities. Other applications might benefit from the ability of Transmit SENSE to improve the spatial resolution of the pulse profile while maintaining the transmit duration.
Allocating scarce resources in real-time to reduce heart failure readmissions: a prospective, controlled study (2013)

An EMR-enabled strategy that targeted scarce care transition resources to high-risk HF patients significantly reduced the risk-adjusted odds of readmission.
An overview of nosocomial infections, including the role of the microbiology laboratory. (1993)

An estimated 2 million patients develop nosocomial infections in the United States annually. The increasing number of antimicrobial agent-resistant pathogens and high-risk patients in hospitals are challenges to progress in preventing and controlling these infections. While Escherichia coli and Staphylococcus aureus remain the most common pathogens isolated overall from nosocomial infections, coagulase-negative staphylococci (CoNS), organisms previously considered contaminants in most cultures, are now the predominant pathogens in bloodstream infections. The growing number of antimicrobial agent-resistant organisms is troublesome, particularly vancomycin-resistant CoNS and Enterococcus spp. and Pseudomonas aeruginosa resistant to imipenem. The active involvement and cooperation of the microbiology laboratory are important to the infection control program, particularly in surveillance and the use of laboratory services for epidemiologic purposes. Surveillance is used to identify possible infection problems, monitor infection trends, and assess the quality of care in the hospital. It requires high-quality laboratory data that are timely and easily accessible.
A Classical Arabinogalactan Protein Is Essential for the Initiation of Female Gametogenesis in Arabidopsis (2004)

Classical arabinogalactan proteins (AGPs) are an abundant class of cell surface proteoglycans widely distributed in flowering plants. We have used a combination of enhancer detection tagging and RNA interference (RNAi)-induced posttrancriptional silencing to demonstrate that AGP18, a gene encoding a classical arabinogalactan protein, is essential for female gametogenesis in Arabidopsis thaliana. AGP18 is expressed in cells that spatially and temporally define the sporophytic to gametophytic transition and during early stages of seed development. More than 75% of the T1 transformants resulted in T2 lines showing reduced seed set during at least three consecutive generations but no additional developmental defects. AGP18-silenced T2 lines showed reduced AGP18 transcript levels in female reproductive organs, the presence of 21-bp RNA fragments specific to the AGP18 gene, and the absence of in situ AGP18 mRNA localization in developing ovules. Reciprocal crosses to wild-type plants indicate that the defect is female specific. The genetic and molecular analysis of AGP18-silenced plants containing a single T-DNA RNAi insertion suggests that posttranscriptional silencing of AGP18 is acting both at the sporophytic and gametophytic levels. A cytological analysis of all defective AGP18-RNAi lines, combined with the analysis of molecular markers acting at key stages of female gametogenesis, showed that the functional megaspore fails to enlarge and mitotically divide, indicating that AGP18 is essential to initiate female gametogenesis in Arabidopsis. Our results assign a specific function in plant development to a gene encoding a classical AGP.
Studies on total synthesis of the olivomycins (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStudies on total synthesis of the olivomycinsRobert P. Hatch, Jayant Shringarpure, and Steven M. WeinrebCite this: J. Org. Chem. 1978, 43, 21, 4172–4177Publication Date (Print):October 1, 1978Publication History Published online1 May 2002Published inissue 1 October 1978https://pubs.acs.org/doi/10.1021/jo00415a041https://doi.org/10.1021/jo00415a041research-articleACS PublicationsRequest reuse permissionsArticle Views1163Altmetric-Citations65LEARN 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
Improvement in neurological outcome after administration of atorvastatin following experimental intracerebral hemorrhage in rats (2004)

Analysis of the data in this study indicates that atorvastatin improves neurological recovery after experimental ICH and may do so in part by increasing neuronal plasticity.