gebhart/patrepeval huggingface dataset:
Prevention of in-stent restenosis via reduction of thrombo-inflammatory reactions with recombinant P-selectin glycoprotein ligand-1 (2004)

The binding of leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) to platelet P-selectin is central to post-angioplasty restenosis. Although intracoronary stents limit the mechanical component of restenosis, they cause marked thrombo-inflammation and neointimal proliferation leading to greater late luminal loss. We sought to demonstrate that P-selectin antagonism, using recombinant PSGL-1 (rPSGL-Ig), is effective in reducing platelet-leukocyte reactions and in-stent restenosis in double-injured porcine coronary arteries. Two weeks after initial injury by angioplasty to the coronary arteries, stents were implanted at the injury-induced lesion site, 15 min after an i.v. bolus administration of a vehicle or rPSGL-Ig (1 mg/kg). Four weeks later, adhesion of (51)Cr-platelets and (111)In-neutrophils and histomorphometric analyses were performed. In-stent residual lumen was almost 3 fold larger in rPSGL-Ig-treated arteries (3.1 +/- 0.4 mm(2)) as compared to control (1.1 +/- 0.2 mm(2)), which correspond to 64% vascular stenosis in control with no change in rPSGL-Ig animals. For a similar injury score, in-stent neointima was significantly reduced by 30 to 40% in the rPSGL-Ig group and quantitative coronary angiography showed a significant 35% reduction in late lumen loss. These effects of rPSGL-Ig were associated with a respective 70% and 53% reduction in platelet and neutrophil adhesion. In conclusion, pretreatment with rPSGL-Ig reduces thrombo-inflammatory responses, neointimal proliferation, and in-stent restenosis. P-selectin antagonism offers a promising therapy to improve clinical outcomes of coronary stenting.
Construction of N‐Glycan Microarrays by Using Modular Synthesis and On‐Chip Nanoscale Enzymatic Glycosylation (2010)

An effective chemoenzymatic strategy is reported that has allowed the construction, for the first time, of a focused microarray of synthetic N-glycans. Based on modular approaches, a variety of N-glycan core structures have been chemically synthesized and covalently immobilized on a glass surface. The printed structures were then enzymatically diversified by the action of three different glycosyltransferases in nanodroplets placed on top of individual spots of the microarray by a printing robot. Conversion was followed by lectin binding specific for the terminal sugars. This enzymatic extension of surface-bound ligands in nanodroplets reduces the amount of precious glycosyltransferases needed by seven orders of magnitude relative to reactions carried out in the solution phase. Moreover, only those ligands that have been shown to be substrates to a specific glycosyltransferase can be individually chosen for elongation on the array. The methodology described here, combining focused modular synthesis and nanoscale on-chip enzymatic elongation, could open the way for the much needed rapid construction of large synthetic glycan arrays.
Polymeric Biomaterials for Medical Implants and Devices (2016)

In this review article, we focus on the various types of materials used in biomedical implantable devices, including the polymeric materials used as substrates and for the packaging of such devices. Polymeric materials are used because of the ease of fabrication, flexibility, and their biocompatible nature as well as their wide range of mechanical, electrical, chemical, and thermal behaviors when combined with different materials as composites. Biocompatible and biostable polymers are extensively used to package implanted devices, with the main criteria that include gas permeability and water permeability of the packaging polymer to protect the electronic circuit of the device from moisture and ions inside the human body. Polymeric materials must also have considerable tensile strength and should be able to contain the device over the envisioned lifetime of the implant. For substrates, structural properties and, at times, electrical properties would be of greater concern. Section 1 gives an introduction of some medical devices and implants along with the material requirements and properties needed. Different synthetic polymeric materials such as polyvinylidene fluoride, polyethylene, polypropylene, polydimethylsiloxane, parylene, polyamide, polytetrafluoroethylene, poly(methyl methacrylate), polyimide, and polyurethane have been examined, and liquid crystalline polymers and nanocomposites have been evaluated as biomaterials that are suitable for biomedical packaging (section 2). A summary and glimpse of the future trend in this area has also been given (section 3). Materials and information used in this manuscript are adapted from papers published between 2010 and 2015 representing the most updated information available on each material.
Lifestyle Risk Factors and New-Onset Diabetes Mellitus in Older Adults (2009)

Even later in life, combined lifestyle factors are associated with a markedly lower incidence of new-onset diabetes mellitus.
Nucleotide and deduced amino acid sequences of the lacR, lacABCD, and lacFE genes encoding the repressor, tagatose 6-phosphate gene cluster, and sugar-specific phosphotransferase system components of the lactose operon of Streptococcus mutans (1992)

The complete nucleotide sequences of lacRABCDF and partial nucleotide sequence of lacE from the lactose operon of Streptococcus mutans are presented. Comparison of the streptococcal lac determinants with those of Staphylococcus aureus and Lactococcus lactis indicate exceptional protein and nucleotide identity. The deduced polypeptides also demonstrate significant, but lower, sequence similarity with the corresponding lactose proteins of Lactobacillus casei. Additionally, LacR has sequence homology with the repressor (DeoR) of the Escherichia coli deoxyribonucleotide operon, while LacC is similar to phosphokinases (FruK and PfkB) from E. coli. The primary translation products of the lacRABCDFE genes are polypeptides of 251 (M(r) 28,713), 142 (M(r) 15,610), 171 (M(r) 18,950), 310 (M(r) 33,368), 325 (M(r) 36,495), 104 (M(r) 11,401), and 123 (NH2-terminal) amino acids, respectively. As inferred from their direct homology to the staphylococcal lac genes, these determinants would encode the repressor of the streptococcal lactose operon (LacR), galactose-6-phosphate isomerase (LacA and LacB), tagatose-6-phosphate kinase (LacC), tagatose-1,6-bisphosphate aldolase (LacD), and the sugar-specific components enzyme III-lactose (LacF) and enzyme II-lactose (LacE) of the S. mutans phosphoenolpyruvate-dependent phosphotransferase system. The nucleotide sequence encompassing the S. mutans lac promoter appears to contain repeat elements analogous to those of S. aureus, suggesting that repression and catabolite repression of the lactose operons may be similar in these organisms.
Three-dimensional bioprinting of thick vascularized tissues (2016)

Significance Current tissue manufacturing methods fail to recapitulate the geometry, complexity, and longevity of human tissues. We report a multimaterial 3D bioprinting method that enables the creation of thick human tissues (&gt;1 cm) replete with an engineered extracellular matrix, embedded vasculature, and multiple cell types. These 3D vascularized tissues can be actively perfused with growth factors for long durations (&gt;6 wk) to promote differentiation of human mesenchymal stem cells toward an osteogenic lineage in situ. The ability to construct and perfuse 3D tissues that integrate parenchyma, stroma, and endothelium is a foundational step toward creating human tissues for ex vivo and in vivo applications.
The Transcriptional Regulatory Protein, YB-1, Promotes Single-stranded Regions in the DRA Promoter (1995)

YB-1 is a member of a newly defined family of DNA- and RNA-binding proteins, the Y box factors. These proteins have been shown to affect gene expression at both the transcriptional and translational levels. Recently, we showed that YB-1 represses interferon-gamma-induced transcription of class II human major histocompatibility (MHC) genes (1). Studies in this report characterize the DNA binding properties of purified, recombinant YB-1 on the MHC class II DRA promoter. The generation of YB-1-specific antibodies further permitted an analysis of the DNA binding properties of endogenous YB-1. YB-1 specifically binds single-stranded templates of the DRA promoter with greater affinity than double-stranded templates. The single-stranded DNA binding sites of YB-1 were mapped to the X box, whereas the double-stranded binding sites were mapped to the Y box of the DRA promoter, by methylation interference analysis. Most significantly, YB-1 can induce or stabilize single-stranded regions in the X and Y elements of the DRA promoter, as revealed by mung bean nuclease analysis. In concert with the findings that YB-1 represses DRA transcription, this study of YB-1 binding properties suggests a model of repression in which YB-1 binding results in single-stranded regions within the promoter, thus preventing loading and/or function of other DRA-specific transactivating factors.
Depletion of CD25+ regulatory cells uncovers immune responses to shared murine tumor rejection antigens (2002)

Although it is known that the immune system can mount responses to a variety of tumors it is clear that most tumors exhibit weak or even undetectable immunogenicity. Recent findings suggest that the lack of tumor immunogenicity is partly due to a population of cells called CD4+ CD25+ regulatory T cells since depletion of these cells in mice can result in tumor rejection. These cells have also been shown to inhibit the development of organ-specific autoimmune diseases suggesting that they inhibit immune responses to tissue-specific self-antigens. Such immune responses may also mediate tumor rejection. Alternatively, immune responses in mice depleted of regulatory cells may target tumor antigens that are not tissue-specific, but which are shared by tumors of diverse origins. In experiments performed to discriminate between these possibilities we found, using the murine colorectal tumor CT26, that tumor immunity stimulated in the absence of regulatory cells is not restricted to tumors of colorectal origin, but is effective against tumors of different histological types such as B cell lymphomas and a renal cell carcinoma. By comparing this to CT26-induced immunity through the use of adjuvant we show that the generation of cross-reactive tumor immunity is a specific manifestation of CD25+ regulatory cell depletion. The generation of CD4+ T cells capable of mediating tumor rejection is another important feature of tumor immunity induced in the absence of CD25+ cells.
Betamethasone modulation of sphingomyelin hydrolysis up-regulates CTP:cholinephosphate cytidylyltransferase activity in adult rat lung (1996)

Glucocorticoids appear to play an integral role in stimulating surfactant synthesis by activating the rate-regulatory enzyme for phosphatidylcholine synthesis, CTP:cholinephosphate cytidylyltransferase (CT). The activity of liver CT, in vitro, has been shown to be inhibited by the sphingomyelin hydrolysis product, sphingosine. In order to investigate the mechanisms by which glucocorticoids alter CT activity, in vivo, we administered betamethasone (1 mg/kg intraperitoneally) sequentially to adult male rats for 5 days. Betamethasone increased CT activity 2-fold relative to control in whole lung. The hormone also increased membrane-bound activity, but did not affect cytosolic enzyme activity. Betamethasone modestly increased CT mRNA as determined by the reverse-transcription PCR and Southern analysis of PCR products, but did not alter the levels of immunoreactive enzyme in lung membranes as demonstrated by Western blotting. The hormone did, however, produce a nearly 3-fold increase in membrane-associated sphingomyelin, and co-ordinately a substantial decrease in the levels of sphingosine in lung membranes. Sphingosine, but not sphinganine, was a competitive, reversible inhibitor of lung CT with respect to the enzyme activator, phosphatidylglycerol. Betamethasone decreased the activities of the sphingomyelin hydrolases: acid sphingomyelinase by 33% and of alkaline ceramidase by 21%. The hormone also inhibited the generation of sphingosine from lysosphingomyelin in lung membranes. There was no significant effect of the hormone on serine palmitoyltransferase activity, the first committed enzyme for sphingolipid biosynthesis. Further, administration of L-cycloserine, an inhibitor of sphingosine formation, was shown to stimulate CT activity by 74% and increase disaturated phosphatidylcholine in alveolar lavage by 52% relative to control. These observations suggest that glucocorticoids up-regulate surfactant synthesis at the level of a key regulatory enzyme by significantly altering the availability of inhibitory metabolites resulting from sphingomyelin hydrolysis.
A hyperspectral imaging system for in vivo optical diagnostics (2004)

This paper details the basic principles and instrumental systems as well as applications of hyperspectral imaging system in the biomedical field. The development of an HSI system that combines recent advances in several photonic technologies, including an AOTF, a 2-D CCD detector, and imaging fiber optics. The integration of these technologies leads to a versatile and powerful imaging system that can rapidly record spectral images of samples. This imaging system could find useful applications in medical diagnostics applications where rapid in vivo detection of complex samples is required. The HSI technique has the potential for in site optical diagnosis on tissue and it can be use for guidance of surgical intervention and treatment. The optical diagnostic approaches may either be an imaging modality or a spectroscopic modality. The spectroscopic diagnostics may also provide real-time assessment of tissue response to therapy.
A hop towards running humanoid biped (2004)

Aiming for a humanoid robot of the next generation, we have been developing a biped which can jump and run. This paper introduces biped robot HRP-2LR and its hopping with both legs as our first attempt towards running. Using a dynamic model of HRP-2LR, hopping patterns are pre-calculated so that it follows the desired profiles of the total linear and angular momentum. For this purpose we used resolved momentum control. Adding small modifications to negotiate the difference between the model and the real hardware, we successfully realized a steady hopping motion of 0.06 [s] flight phase and 0.5 [s] support phase. A hopping with forward velocity of 15 [mm/s] was also realized. Finally, a running pattern of 0.06 [s] flight and 03 [s] support phase was tested. HRP-2LR could successfully run with average speed of 0.16 [m/s].
A new symbol time estimator for orthogonal frequency division multiplexing systems (2004)

We propose a new symbol time estimator utilizing a specifically designed pilot symbol for orthogonal frequency division multiplexing systems. The proposed estimator consists of two stages of estimation (coarse-to-fine). In the stage of coarse estimation, the redundant information contained within the cyclic prefix is used for rough symbol time estimation. In the stage of fine estimation, the merit of the designed pilot symbol structure is utilized to generate a fine symbol time estimate. Computer simulation results show that, although the new estimator has a slightly larger variance than a recently described method by H. Minn et al. (see IEEE Commun. Lett., vol.4, p.242-4, 2000) for additive white Gaussian noise channels, it has a significantly smaller variance and a smaller bias (i.e., the mean of the estimation error) for intersymbol interference channels. The new method also involves less computational complexity than previous related approaches.
An Automated, Column-Switching HPLC Method for Analyzing Active and Excipient Materials in Both Cream and Ointment Formulations (1985)

We developed a microprocessor-controlled, tandem reverse-phase HPLC method for analyzing both cream and ointment formulations. Analytes included: a developmental corticosteroid in both cream and ointment formulations; a developmental naphthohydroquinone diester in the ointment; and benzyl alcohol, a cream excipient material. Sample preparation consisted simply of dissolving cream or ointment in 30:60 tetrahydrofuran:isopropanol, centrifuging to sediment undissolved residue, and directly injecting onto the HPLC column. With automated switching valves operating in a front-cutting mode, analytes plus internal standard were directed from the reverse-phase precolumn to a 30-cm reverse-phase analytical column while retained excipient materials were backflushed to waste. For comparison, we also analyzed the corticosteroid cream and ointment formulations by reverse-phase HPLC with conventional liquid-liquid partition sample preparation procedures. In all cases, method performance was satisfactory as evidenced by: sample recovery, response linearity, precision, stability specificity, peak tailing factors, peak assymetries, peak resolution, and theoretical plate counts. Compared with liquidated extraction techniques, the reported column-switching methods reduced required sample preparation times by a factor of nearly 3.
An amino-terminal domain of the hepatitis C virus NS3 protease is essential for interaction with NS4A (1995)

Hepatitis C virus (HCV) genomic RNA is translated into a large polyprotein that is processed into structural and nonstructural proteins. Processing at the N termini of several nonstructural proteins requires sequences contained in both NS3 and NS4A. NS3 contains a serine protease, whereas the function of NS4A in proteolysis is yet to be determined. By using the vaccinia virus-T7 hybrid expression system to transiently express HCV polypeptides in HeLa cells, we studied the effect of several N-terminal and C-terminal deletions of HCV NS3 on the processing activity at all the downstream cleavage sites. In this way, we have delineated the minimal domain of NS3 required for the serine protease activity associated with this protein. In addition, we demonstrate the formation of a stable complex between NS3 and NS4A: analysis of the deletion mutants reveals a region at the N terminus of NS3 that is necessary for both complex formation and modulation of the proteolytic activity by NS4A but not for the NS4A-independent serine protease activity of NS3.
A Comparative Model: Reaction Time Performance in Sleep‐Disordered Breathing Versus Alcohol‐Impaired Controls (1999)

The data demonstrate that sleep-disordered subjects in this study (with a mean age of 47 y) with mild to moderate sleep-disordered breathing had worse test reaction time performance parameters than healthy, nonsleepy subjects (with a mean age of 29 y) whose BAC is illegally high for driving a commercial motor vehicle in California. This comparative model points out the potential risks of daytime sleepiness in those with sleep-disordered breathing relative to a culturally accepted standard of impairment.
Simple kinetic relationships and nonspecific competition govern nuclear import rates in vivo (2006)

Many cargoes destined for nuclear import carry nuclear localization signals that are recognized by karyopherins (Kaps). We present methods to quantitate import rates and measure Kap and cargo concentrations in single yeast cells in vivo, providing new insights into import kinetics. By systematically manipulating the amounts, types, and affinities of Kaps and cargos, we show that import rates in vivo are simply governed by the concentrations of Kaps and their cargo and the affinity between them. These rates fit to a straightforward pump-leak model for the import process. Unexpectedly, we deduced that the main limiting factor for import is the poor ability of Kaps and cargos to find each other in the cytoplasm in a background of overwhelming nonspecific competition, rather than other more obvious candidates such as the nuclear pore complex and Ran. It is likely that most of every import round is taken up by Kaps and nuclear localization signals sampling other cytoplasmic proteins as they locate each other in the cytoplasm.
DNA probes on chip surfaces studied by scanning force microscopy using specific binding of colloidal gold (2000)

Single-stranded DNA was covalently bound on chip surfaces using two different silanization procedures. The resulting surfaces were characterized by fluorescence and scanning force microscopy using sequence-complementary DNA molecules with labels. Colloidal gold (30 nm) was used as the topographic label. Scanning force microscopy revealed the individual labels on the surface and their distribution. Steps of silane layers or DNA-modified surfaces prepared using an elastomeric mask provided internal controls for comparison of modified with unmodified surfaces.
IMRT: delivery techniques and quality assurance (2003)

Intensity modulated radiotherapy (IMRT) is a major development in the delivery of radiation therapy that has the potential to improve patient outcome by reducing morbidity or increasing local tumour control. Delivery techniques include those based on purpose built devices and treatment machines together with those utilizing the capabilities of computer controlled multileaf collimators which are more widely available. The complexity of IMRT techniques demands a high level of quality control both in the operation of the equipment and in the delivery of treatment to individual patients. The purpose of this paper is therefore to review the techniques available, concentrating on the use of multileaf collimators, and to consider the necessary quality control requirements for clinical application. It demonstrates that the technology is mature and sufficiently well understood so that IMRT can be safely implemented in the general clinical environment rather than being limited to application in the research environment.
Pretreatment with the probiotic VSL#3 delays transition from inflammation to dysplasia in a rat model of colitis-associated cancer (2011)

Evidence supports involvement of microflora in the transition of chronic inflammation to neoplasia. We investigated the protective efficacy of the probiotic VSL#3 in a model of colitis-associated colorectal cancer. Chronic colitis was induced in Sprague-Dawley rats by administration of trinitrobenzene sulfonic acid (TNBS), followed 6 wk later by systemic reactivation. To induce colitis-associated dysplasia and cancer, the animals received TNBS (intravenously) twice a week for 10 wk. One group received VSL#3 in drinking water from 1 wk before colitis induction until death. The colons were examined for damage and presence of dysplasia or cancer. Samples were analyzed for cell proliferation and apoptosis, vitamin D receptor (VDR) expression, angiogenic factors, and presence of alkaline sphingomyelinase or phosphatase. Microbial community composition was evaluated by terminal restriction fragment-length polymorphism analysis of the bacterial 16S rRNA gene. None of the probiotic-treated animals developed carcinoma, and no high-grade dysplasia was found in either the proximal or mid colon. In contrast, 29% of the animals in the control group developed carcinoma in one or more regions of the colon. VSL#3-treated animals had significantly less damage than the vehicle treated-controls in all areas of the colon, and this correlated with decreased richness and diversity of the mucosally adherent microbiota. Treatment with the probiotic increased the antiangiogenic factor angiostatin, VDR expression, and alkaline sphingomyelinase. We concluded that pretreatment with the probiotic VSL#3 can attenuate various inflammatory-associated parameters, delaying transition to dysplasia and cancer, thus offering its potential therapeutic use in patients with long-standing colitis.