gebhart/patrepeval huggingface dataset:
A MARGINAL REGRESSION MODELLING FRAMEWORK FOR EVALUATING MEDICAL DIAGNOSTIC TESTS (1997)

Technological advances continue to develop for early detection of disease. Research studies are required to define the statistical properties of such screening or diagnostic tests. However, statistical methodology currently used to evaluate diagnostic tests is limited. We propose the use of marginal regression models with robust sandwich variance estimators to make inference about the sensitivity and specificity of diagnostic tests. This method is more flexible than standard methods in that it allows comparison of sensitivity between two or more tests even if all tests are not carried out on all subjects, it can accommodate correlated data, and the effect of covariates can be evaluated. This last feature is important since it allows researchers to understand the effects on sensitivity and specificity of various environmental and patient characteristics. If such factors are under the control of the clinician, it provides the opportunity to modify the diagnostic testing program to maximize sensitivity and/or specificity. We show that the marginal regression modelling methods generalize standard statistical methods. In particular, when we compare two screening tests and we test each subject with both screens, the method corresponds to McNemar's test. We describe data from an ongoing audiology screening study and we analyse a simulated version of the data to illustrate the methodology. We also analyse data from a longitudinal study of PCR as a diagnostic test for cytomegalovirus.
Combating Protein Misfolding and Aggregation by Intracellular Antibodies (2008)

Conformational or misfolding diseases are a large class of devastating human disorders associated with protein misfolding and aggregation. Most conformational diseases are caused by a combination of genetic and environmental factors, suggesting that spontaneous events can destabilize the protein involved in the pathology or impair the clearance mechanisms of misfolded aggregates. Aging is one of the risk factors associa-ted to these events, and the clinical relevance of conformational disorders is growing dramatically, as they begin to reach epidemic proportions due to increases in mean lifespan. Currently, there are no effective strategies to slow or prevent these diseases. Intrabodies are promising therapeutic agents for the treatment of misfolding diseases, because of their virtually infinite ability to specifically recognize the different conformations of a protein, including pathological isoforms, and because they can be targeted to the potential sites of aggregation (both intra- and extracellular sites). These molecules can work as neutralizing agents against amylo-idogenic proteins by preventing their aggregation, and/or as molecular shunters of intracellular traffic by re-routing the protein from its potential aggregation site. The fast-developing field of recombinant antibody technology provides intrabodies with enhanced binding specificity and stability, together with lower immunogenicity, for use in a clinical setting. This review provides an update on the applications of intrabodies in misfolding diseases, with particular emphasis on an evaluation of their multiple and feasible modes of action.
Cell Proliferation in Bronchial Epithelium and Submucosal Glands of Cystic Fibrosis Patients (1995)

Integrative gene therapy typically requires dividing cells. This requirement has been perceived as an impediment for gene transfer to mature, uninjured airways where proliferation rates are very low. In diseases such as cystic fibrosis (CF) that may be candidates for integrative gene therapy, airway cell turnover is not known but may be increased as a result of chronic inflammation. To determine if cells in airway surface epithelium and submucosal glands of CF patients proliferate at an increased rate, paraffin sections of bronchial segments removed from CF patients (n = 6) at the time of lung transplantation or rapid autopsy and from non-CF patients (n = 4) undergoing lung resection or transplantation were immunostained with PC10, a monoclonal antibody to proliferating cell nuclear antigen (PCNA), a marker of proliferating cells. The PCNA index (percentage of nuclei immunostaining for PCNA) in CF bronchial surface epithelium was 17.0 +/- 4.6% (mean +/- SEM), substantially greater than in non-CF airways (less than 0.2%). Within submucosal glands, PCNA-positive cells were more prevalent in the collecting ducts of CF patients than in those of normal subjects, but only rare mucous or serous cells were PCNA positive. These studies show that airway epithelial cell proliferation rates can be very high in inflamed CF airways. This prevalence of proliferating cells suggests that CF airway epithelium and submucosal gland ducts may be amenable to gene transfer using vectors, such as retroviruses, that require cell replication for stable integrative expression. Further studies are needed to evaluate cell proliferation in CF airways with less extensive airway injury.
Effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on neutrophil kinetics and function in normal human volunteers (1998)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) (250 microg/m2) was administered subcutaneously to 7 normal volunteers for up to 14 days to study its effects on neutrophil kinetics and function. With treatment, blood neutrophil counts rose gradually to peak at 3 1/2 times baseline by day 14. At day 5 marrow mitotic cells were increased and post-mitotic cells decreased, and the transit time through the post-mitotic marrow pool accelerated (normal = 6.4 days, GM-CSF = 3.9 days; P < 0.01). Treatment had little effect on the blood neutrophil half-life (normal = 9.6 +/- 1.3 hours; GM-CSF = 13.1 +/- 2.4 hours, P > 0.05); or the neutrophil turnover rate (normal = 78.5 +/- 11.9 x 10(7)/cells/kg/day, GM-CSF = 91.4 +/- 19.8 x 10(7)/cells/kg/day, P > 0.05). GM-CSF reduced the number of neutrophils migrating to skin chambers (normal = 104 +/- 25.0 x 10(6)/cells, GM-CSF = 48.6 +/- 16.0 x 10(6)/cells; P < 0.05). Treatment increased expression of CD11b/CD18 but not Fcgamma receptors (CD16, CD32, CD64). Treatment also stimulated the in vitro neutrophil respiratory burst in response to a variety of agonists, and this enhancement persisted for the duration of treatment. All subjects experienced local and systemic adverse effects and developed eosinophilia. This study indicates that GM-CSF at a dose of 250 microg/m2 causes neutrophilia chiefly by accelerating delivery of neutrophils from the marrow to the blood and by decreasing migration from the blood to the tissues, with only a modest effect on neutrophil production and blood half-life.
Cardiomyocyte-Specific Transforming Growth Factor β Suppression Blocks Neutrophil Infiltration, Augments Multiple Cytoprotective Cascades, and Reduces Early Mortality After Myocardial Infarction (2014)

These data reveal a novel role of myocyte TGFβ signaling as a potent regulator of protective cardiokine and neutrophil-mediated infarct remodeling.
Semi-supervised hashing for scalable image retrieval (2010)

Large scale image search has recently attracted considerable attention due to easy availability of huge amounts of data. Several hashing methods have been proposed to allow approximate but highly efficient search. Unsupervised hashing methods show good performance with metric distances but, in image search, semantic similarity is usually given in terms of labeled pairs of images. There exist supervised hashing methods that can handle such semantic similarity but they are prone to overfitting when labeled data is small or noisy. Moreover, these methods are usually very slow to train. In this work, we propose a semi-supervised hashing method that is formulated as minimizing empirical error on the labeled data while maximizing variance and independence of hash bits over the labeled and unlabeled data. The proposed method can handle both metric as well as semantic similarity. The experimental results on two large datasets (up to one million samples) demonstrate its superior performance over state-of-the-art supervised and unsupervised methods.
Miniature dual mode microstrip filters (2002)

A new generation of planar dual mode filters is introduced which offers significant size, weight, and cost advantages over previous designs. All currently used elliptic function, self-equalized, etc. filter designs can be implemented in microstrip using this new concept. The proposed filter structures are ideally suited for implementation using high-temperature superconductors. Basic dual mode resonator and filter structures are discussed, and experimental data for proof-of-concept filters implemented using both normal and superconducting microstrip are presented. Superconducting realizations of this class of filters may be used to replace bulkier, heavier filters currently used for satellite communications.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Transplantable stem cells: home to specific niches (2004)

Overall, recent advancements in our understanding of hematopoietic stem cell biology and, in particular, the interaction of hematopoietic stem cells with the hematopoietic microenvironment paves the way for expanded use in regenerative medicine.
Pathophysiologic Studies of Experimental Chronic Pancreatitis in Rats Induced by Injection of Zein-Oleic Acid-Linoleic Acid Solution into the Pancreatic Duct (1998)

An experimental model of chronic pancreatitis was induced by a retrograde injection of a viscous solution consisting of zein-oleic acid-linoleic acid (0.05 ml/100 g body weight) into the rat pancreatic duct. Histologic and biochemical changes were investigated over a period of 6 months after induction of this model. The treated rats gained weight, but pancreatic weight decreased with time. Histologically, the widening of acinar lumen and cellular vacuolization occurred within 24 h at the parenchyma neighboring the small ducts filled with the injected solution. Degenerative parenchyma, interstitial edema, and inflammatory cell infiltration were pronounced 1 week later. Thereafter, duct-like tubular complex formation progressed, and the exocrine tissue exhibited marked atrophy of the gland with irregular fibrosis and fat replacement over a period of 6 months. Pancreatic contents of protein, amylase, DNA, and RNA markedly decreased, as did pancreatic weight, whereas hydroxyproline content increased. Oral administration of camostat did not affect pancreatic weight and contents of enzyme in this model. Urinary para-aminobenzoic acid (PABA) excretion in the BT-PABA test decreased to 54% at 6 weeks and 22% at 6 months. Although three quarters of pancreatic immunoreactive insulin (IRI) content was lost after 6 months, overt diabetes did not occur. The results suggest that an obstructive mechanism in the small ducts plays an important role in the genesis and development of chronic pancreatitis.
Robust road sign detection and recognition from image sequences (2005)

This paper describes a method for detecting and recognizing road signs in grey-level images acquired by a single camera mounted on a moving vehicle. An extensive experimentation has shown that the method is robust against low-level noise corrupting edge detection and contour following, and works for images of cluttered urban streets as well as country roads and highways. A further improvement on the detection and recognition scheme has been obtained by means of a Kalman-filter-based temporal integration of the extracted information. The proposed approach can be very helpful for the development of a system for driving assistance.
Reaction of Quinoxaline Derivatives with Nucleophilic Reagents (1983)

Abstract 2-Chloro-3-methylquinoxaline reacts with aromatic amines in basic medium forming 2-arylamino-3-methylquinoxalines, also it reacts with mercaptoacetic acid. The 3-methyl-2(1H)-quinoxalinone condenses with aromatic aldehydes forming the corresponding 3-(substituted styryl)-2(1H)-quinoxalinones which add bromine in acetic acid to yield the corresponding dibromo derivatives which react with morpholine, sodium methoxide, and piperidine to give the corresponding compounds. 3-Methyl-2(1H)-quinoxalinone undergoes side-chain bromination to yield 3-bromomethyl-2(1H)-quinoxalinone, which reacts with aromatic amines, sodium salt of saccharine, potassium phthalimide··· 3-Methyl-2(1H)-quinoxalinone with P2S5 gave 3-methyl-2(1H)-quinoxalinethione which reacts with 2-aminoethanol, dimethyl sulfate, and halo acids.
Preferential activity of Tie2 promoter in arteriolar endothelium (2005)

The tyrosine kinase Tie2/Tek (the receptor for angiopoietins) is considered one of the most reliable markers of the endothelial phenotype, across organisms, organs, and developmental stages. However, endothelium is intrinsically heterogeneous in origin, composition and function, presenting an arteriolar/venular asymmetry. In this regard, the expression of Tie2 along the vascular tree, although thought to be homogenous, has not been systematically investigated. Therefore we questioned whether the activity of Tie2 promoter is uniform in the microvascular endothelium. To this end, we analyzed in situ the expression of the markers beta-galactosidase [LacZ(Tie2)] and green fluorescent protein (GFP) [GFP(Tie2)], placed under the Tie2 promoter in transgenic mice, in whole mount tissue samples, which allow the simultaneous evaluation of its relative distribution in various microvascular compartments. In the mesenteries of LacZ(Tie2) and GFP(Tie2) mice, we found that the activity of Tie2 promoter is asymmetrically distributed, being much stronger in arteries and arterioles than on the venular side of the vascular tree. This observation was replicated in the diaphragm of LacZ(Tie2) mice. The capillaries presented a mosaic pattern of Tie2 promoter activity. Stimulation of angiogenesis either by wounding, or by intraperitoneal injection of Vascular Endothelial Growth Factor (VEGF), revealed that the arteriolar/venular asymmetry is established at endothelial cellular level early during new capillary formation, even before the starting of the microvascular blood flow. In conclusion, a strong Tie2 promoter activity qualifies as a novel marker of the arteriolar phenotype in microvascular endothelium.
Expression of transcripts for CSF-1 and for the "macrophage" and "epithelial" isoforms of the CSF-1R transcripts in human ovarian carcinomas. (1994)

Levels of CSF-1 and CSF-1 receptor (CSF-1R) (fms) transcripts were quantified by Northern and dot blotting in total RNA extracts from 68 human ovarian carcinomas and positive and negative controls. Overall, very high levels of CSF-1 and CSF-1R transcripts were found in 11 and 21% of ovarian carcinoma specimens, respectively. When probes specific for CSF-1R exon1 were employed, which hybridize with the "epithelial" but not with the "hematopoietic" isoforms of the CSF-1R transcripts, the results suggested that both isoforms of the CSF-1R transcript were present in the tumor specimens. When levels of CSF-1 and CSF-1R were compared, a positive correlation was observed. Taken together, these results confirm prior observations of high levels of CSF-1 and CSF-1R in ovarian carcinoma specimens and that the latter include both "epithelial" and "macrophage" CSF-1R transcript isoforms, as might be expected for specimens composed of malignant epithelial cells and stromal macrophages.
Simulation and the Monte Carlo Method (2016)

Simulation and the Monte Carlo Method, Third Edition reflects the latest developments in the field and presents a fully updated and comprehensive account of the major topics that have emerged in Monte Carlo simulation since the publication of the classic First Edition over more than a quarter of a century ago. While maintaining its accessible and intuitive approach, this revised edition features a wealth of up-to-date information that facilitates a deeper understanding of problem solving across a wide array of subject areas, such as engineering, statistics, computer science, mathematics, and the physical and life sciences. The book begins with a modernized introduction that addresses the basic concepts of probability, Markov processes, and convex optimization. Subsequent chapters discuss the dramatic changes that have occurred in the field of the Monte Carlo method, with coverage of many modern topics including: Markov Chain Monte Carlo, variance reduction techniques such as the transform likelihood ratio method and the screening method, the score function method for sensitivity analysis, the stochastic approximation method and the stochastic counter-part method for Monte Carlo optimization, the cross-entropy method to rare events estimation and combinatorial optimization, and application of Monte Carlo techniques for counting problems, with an emphasis on the parametric minimum cross-entropy method. New to this edition are two chapters on the classic splitting method, which is used widely by the simulation community, and stochastic enumeration. Cross-entropy (CE) programs are written in Matlab.
Genetic risk for metabolic syndrome: examination of candidate gene polymorphisms related to lipid metabolism in Japanese people (2007)

APOA5, LDLR, CYP3A4 and C1QTNF5 are susceptibility loci for metabolic syndrome in Japanese people. Genotypes for these polymorphisms may prove informative for prediction of genetic risk for metabolic syndrome.
A new method for isolation of cardiac myocytes by percutaneous endomyocardial biopsy (1996)

The objective of this study was to demonstrate the feasibility of isolating viable canine cardiac myocytes from percutaneous right ventricular endomyocardial biopsy specimens. Although histologic data can be obtained from percutaneous endomyocardial biopsies, this approach has not been used as a source of viable cells for evaluating pathological conditions. Study of isolated viable myocytes may provide insight into the electrical, biochemical, and physiologic functions of the heart. Using a standard 8F sheath, a 5F bioptome was introduced via the right femoral vein and advanced to the right ventricle, where 85 biopsies were obtained from 8 mongrel dogs. An average of six biopsy specimens were pooled for processing to provide adequate tissue substrate. This resulted in 14 groups of specimens which were then processed to isolate individual myocytes. Viable myocytes were striated, rod-shaped, and excluded trypan blue dye. Nonviable myocytes were rounded, had no cross-striations, and did stain with trypan blue. Partially-injured myocytes contracted spontaneously and had a region of loss of cross-striations. The average number of viable cells recovered per group of pooled specimens was 1.8 x 10(4) (1.8 x 10(3) cells/mg of tissue). The greatest yield of viable myocytes recovered was 8.0 x 10(4), which represented a viability of 90% by trypan blue dye exclusion and morphological criteria. Percutaneous right ventricular endomyocardial biopsy is a novel method for obtaining viable cardiac myocytes. Its feasibility and utility in humans warrant further investigation.
Biologically Active [14C]Vasopressin (1973)

Biologically active lysine-[glycinamide-14C]vasopressin can be synthesized by enzymatically removing the COOH—terminal glycinamide residue of the hormone and replacing it with the same compound isotopically labeled. After purification by gel filtration followed by paper electrophoresis or ion exchange chromatography, the radioactive hormone has 75 to 95% of the maximal biological activity of pure synthetic hormone. The dose-response curve for activation of adenylate cyclase from rat renal medullas (an index of antidiuretic activity) is identical to that of native hormone. The method has been used to synthesize hormone with a specific radioactivity of 100 mCi per mmole.
Generation of narrowband inversion with broadband laser pulses (1992)

We show experimentally, here for Na vapor, and theoretically that picosecond frequency-swept laser pulses create in multilevel systems an inversion profile that is far narrower than the pulse spectrum. This selectivity persists even when the Rabi frequency is substantially larger than the spacing between pumped and suppressed transitions.
Complex of the herpes simplex virus initiator protein UL9 with DNA as a platform for the design of a new type of antiviral drugs (2010)

The protein binding to the origin of replication of the herpes simplex virus type 1 is DNA helicase encoded by the UL9 gene of the herpes virus. The protein specifically binds to two binding sites in the viral DNA replication origins OriS or OriL. In order to determine the role of the UL9 protein in the initiation of replication and find efficient inhibitors of the UL9 activity, we have synthesized a recombinant UL9 protein expressed in E. coli cells. It was found that the recombinant UL9 protein binds to Boxes I and II in OriS and possesses DNA helicase and ATPase activities. In the complex with a fluorescent analog of ATP, two molecules of the ATP analog bind to one protein dimer molecule. It was also found that the UL9 protein in the dimer form can bind simultaneously to two DNA fragments, each containing specific binding sites for the protein. The interaction of the recombinant UL9 protein with the 63-mer double- and single-stranded oligonucleotides OriS and OriS*, which correspond to the origin of replication of herpes simplex virus, has been investigated. From the titrations of OriS and OriS* with ethidium bromide in the presence and absence of the UL9 protein, the equilibrium affinity constants of the protein binding to OriS and OriS* have been determined. A DNase I footprinting study showed that bis-netropsins exhibit preference for binding to the AT cluster in the origin of replication OriS and inhibit the fluctuation opening of AT base pairs in the AT cluster. The drugs also prevent formation of an intermediate conformation of OriS* that involves a disordered tail at the 3′ end and stable Box I-Box III hairpin to which the UL9 helicase selectively binds. The stabilization by bis-netropsins of the AT-rich hairpin at its 3′ end can inhibit the helicase activity. It was concluded that the antiviral activity of bis-netropsins may be associated with the inhibitory effects of bis-netropsins on these two stages of the reaction catalyzed by helicase UL9.
How ‘green’ are algae farms for biofuel production? (2010)

Microalgae cultures have been investigated as a source of renewable fuels for almost 50 years. The initial concept was to grow algae in municipal wastewaters, harvest the algal biomass and convert ...