gebhart/patrepeval huggingface dataset:
Use of convolutional neural networks for semantic image segmentation across different computing systems (2020)

The advent of powerful computing platforms coupled with deep learning architectures have resulted in novel approaches to tackle many traditional computer vision problems in order to automate the interpretation of large and complex geospatial data. Such tasks are particularly important as data are widely available and UAS are increasingly being used.
Significance of hydrophobic S4-P4 interactions in subtilisin 309 from Bacillus lentus (1993)

The subtilisins have an extended substrate binding cleft comprising at least 8 subsites. Two pockets at the S1 and S4 sites are particularly conspicuous, and the interactions between substrate and these two pockets are very important for the substrate specificity. Phe residues have mutationally been introduced at one of positions 102, 128, 130, and 132 of the subtilisin Savinase from Bacillus lentus to investigate the effects of introducing bulky groups along the rim of the S4 binding pocket. It is shown that the marked P4 preference of wild-type Savinase for aromatic groups is eliminated by the Gly102-->Phe and Ser128-->Phe mutations, indicating that bulky groups at positions 102 and 128 block the S4 binding site. In contrast, the activity toward hydrophilic P4 residues is not nearly as affected by these mutations, suggesting that the binding mode of the P4 side chain is dependent on its properties. Introduction of a bulky -CH2-S-CH2-CH2-pyridyl group at position 128, by mutational incorporation of Cys followed by chemical modification with 2-vinylpyridine, has essentially the same effect. The Ser130-->Phe mutation hardly affects the activity of the enzyme while the Ser-->Phe mutation at position 132 renders the preference for hydrophobic groups in P4 even more pronounced. This mutation furthermore affects the size of the S4 pocket. An analysis of double mutants at positions 132 and 104 suggests that the S4 region is flexible and is adjusted upon binding of substrates.
The usefulness of casein-specific IgE and IgG4 antibodies in cow's milk allergic children (2012)

High levels of casein-sIgE antibodies are strongly associated with milk allergy in children and might be associated with prolonged allergy. Elevated casein-sIgG4 levels in milk-sensitized individuals on normal diet indicate a modified Th2 response. However, the protective role of IgG4 antibodies in milk allergy is unclear.
CT Screening for Lung Cancer: Suspiciousness of Nodules according to Size on Baseline Scans (2004)

In modern CT screening for lung cancer at baseline, detected noncalcified nodules smaller than 5.0 mm in diameter do not justify immediate work-up but only annual repeat screening to determine whether interim growth has occurred.
Experimental Internet Stream Protocol: Version 2 (ST-II) (1990)

This memo defines the Internet Stream Protocol, Version 2 (ST-II), an IP-layer protocol that provides end-to-end guaranteed service across an internet. This specification obsoletes IEN 119 ST - A Proposed Internet Stream Protocol written by Jim Forgie in 1979, the previous specification of ST. ST-II is not compatible with Version 1 of the protocol, but maintains much of the architecture and philosophy of that version. It is intended to fill in some of the areas left unaddressed, to make it easier to implement, and to support a wider range of applications.
Molecular Physiology of the Regulation of Hepatic Gluconeogenesis and Glycolysis (1992)

Understanding the regulation of hepatic glucose metabolism had its foundation in the elucidation of several pathways, but recent advances have come from the application of molecular genetics. Five years ago little was known about the primary structure of the key regulatory enzymes. Since then, the primary sequence of liver GK, 6-PF-1-K, Fru-1,6-P2ase, PK, PEPCK, and 6-PF-2-K/Fru-2,6-P2ase have been derived from cDNA sequences and/or determined by direct protein sequencing. This has provided new insights into the molecular mechanisms of catalysis and the regulation of these enzymes by covalent modification. Isolation of the cDNAs for these enzymes also has allowed for the quantitation of specific mRNAs and permitted analysis of hormonal control of specific gene expression. The genes for these enzymes have been isolated and sequenced, and their promoter regions are being identified and characterized. Hormone response elements have been delineated in several of the promoters. The promoter regions for 6-PF-2-K/Fru-2,6-P2ase and Fru-1,6-P2ase have also been identified, and future research will focus on the elucidation of the mechanisms whereby hormones regulate the expression of these genes. A number of generalizations can be made about the regulation of gene expression of glycolytic/gluconeogenic enzymes. First, there is coordinate hormonal regulation of gene expression and these effects are consonant with their physiologic actions. Insulin induces the mRNAs that encode glycolytic enzymes and represses the mRNAs that encode gluconeogenic enzymes; cAMP has opposite effects. Both can increase or decrease transcription. Whereas insulin and cAMP affect all of these mRNAs, glucocorticoids appear to have a more restricted action. Second, transcriptional and posttranscriptional regulatory mechanisms are involved. The synthesis of all of the mRNAs discussed is regulated by hormones. Relatively little is known about how mRNA stability is regulated in general, but it is clear that PEPCK mRNA is stabilized by agents that increase the rate of transcription of the gene. Under appropriate metabolic signals this dual control of mRNA synthesis and stability provides for a long-term increase in PEPCK mRNA and protein. Studies with PK mRNA are less direct, but suggest a similar dual mechanism. It will be interesting to see whether multilevel regulation is restricted to these two mRNAs, both of which are involved in the same substrate cycle, or whether the stability of other mRNAs involved in hepatic glucose metabolism is also affected. Third, glucose appears to be important in the regulation of these hepatic genes.(ABSTRACT TRUNCATED AT 400 WORDS)
Homing to solid cancers: a vascular checkpoint in adoptive cell therapy using CAR T-cells (2016)

The success of adoptive T-cell therapies for the treatment of cancer patients depends on transferred T-lymphocytes finding and infiltrating cancerous tissues. For intravenously transferred T-cells, this means leaving the bloodstream (extravasation) from tumour blood vessels. In inflamed tissues, a key event in extravasation is the capture, rolling and arrest of T-cells inside blood vessels which precedes transmigration across the vessel wall and entry into tissues. This depends on co-ordinated signalling of selectins, integrins and chemokine receptors on T-cells by their respective ligands which are up-regulated on inflamed blood vessels. Clinical data and experimental studies in mice suggest that tumour blood vessels are anergic to inflammatory stimuli and the recruitment of cytotoxic CD8(+)T-lymphocytes is not very efficient. Interestingly, and somewhat counter-intuitively, anti-angiogenic therapy can promote CD8(+)T-cell infiltration of tumours and increase the efficacy of adoptive CD8(+)T-cell therapy. Rather than inhibit tumour angiogenesis, anti-angiogenic therapy 'normalizes' (matures) tumour blood vessels by promoting pericyte recruitment, increasing tumour blood vessel perfusion and sensitizing tumour blood vessels to inflammatory stimuli. A number of different approaches are currently being explored to increase recruitment by manipulating the expression of homing-associated molecules on T-cells and tumour blood vessels. Future studies should address whether these approaches improve the efficacy of adoptive T-cell therapies for solid, vascularized cancers in patients.
A learning approach to personalized information filtering (1994)

A personalized information filtering system must specialize to current interests of the user and adapt as they change over time. It must also explore newer domains for potentially interesting information. A learning approach to building personalized information filtering systems is proposed. The system is designed as a collection of information filtering interface agents. Interface Agents are intelligent and autonomous computer programs which learn users&amp;apos; preferences and act on their behalf --- electronic personal assistants that automate tasks for the user. This thesis presents the basic framework for personalized information filtering agents, and describes an implementation, &amp;quot;Newt&amp;quot;, built using the framework. Newt uses a keyword based filtering algorithm. The learning mechanisms used are relevance feedback and the genetic algorithm. The user interface is friendly and accessible to both naive as well as power users. Experimental results indicate that Newt can be personalized to serve ...
Bendamustine (Treanda) Displays a Distinct Pattern of Cytotoxicity and Unique Mechanistic Features Compared with Other Alkylating Agents (2008)

These results suggest that bendamustine possesses mechanistic features that differentiate it from other alkylating agents and may contribute to its distinct clinical efficacy profile.
Panning phage antibody libraries on cells: isolation of human Fab fragments against ovarian carcinoma using guided selection. (1998)

The display of repertoires of human antibody (Ab) fragments on filamentous phages and selection by binding of the phage to antigen (Ag) have provided a ready means of deriving human Ab against purified Ag. However, it has been more difficult to obtain phage Ab against an individual Ag of a complex mixture, such as cell surface Ag. Using the technique of "guided selection," we generated human Ab against the high-affinity folate-binding protein (FBP), a cell surface Ag that is overexpressed in many human ovarian carcinomas. The guiding Ab template was provided by the light chain of mouse monoclonal Ab Mov19 (K[aff], 10[8] M[-1]) directed against FBP; this was paired with repertoires of human heavy chains displayed on phages, and the hybrid Ab fragments were selected by binding to an ovarian carcinoma cell line (OVCAR3). The selected human heavy chains were then paired with repertoires of human light chains. Further panning led to the isolation of a human Fab fragment, C4, with a binding affinity of 0.2 x 10(8) M(-1). This was highly specific for FBP, as demonstrated by ELISA and flow cytometry data and by immunoprecipitation of the relevant molecule from the cell surface of ovarian carcinoma cells. Moreover, C4 targeted the same or a closely related epitope of the Ag, as did the template rodent monoclonal Ab Mov19. These results suggest the usefulness of guided selection as a simple means to deriving human Ab against cell surface Ag for which a rodent Ab is available.
The Tuberin-Hamartin Complex Negatively Regulates β-Catenin Signaling Activity (2003)

Tuberous sclerosis complex (TSC) is characterized by the formation of hamartomas in multiple organs resulting from mutations in the TSC1 or TSC2 gene. Their protein products, hamartin and tuberin, respectively, form a functional complex that affects cell growth, differentiation, and proliferation. Several lines of evidence, including renal tumors derived from TSC2+/- animals, suggest that the loss or inhibition of tuberin is associated with up-regulation of cyclin D1. As cyclin D1 can be regulated through the canonical Wnt/beta-catenin signaling pathway, we hypothesize that the cell proliferative effects of hamartin and tuberin are partly mediated through beta-catenin. In this study, total beta-catenin protein levels were found to be elevated in the TSC2-related renal tumors. Ectopic expression of hamartin and wild-type tuberin, but not mutant tuberin, reduced beta-catenin steady-state levels and its half-life. The TSC1-TSC2 complex also inhibited Wnt-1 stimulated Tcf/LEF luciferase reporter activity. This inhibition was eliminated by constitutively active beta-catenin but not by Disheveled, suggesting that hamartin and tuberin function at the level of the beta-catenin degradation complex. Indeed, hamartin and tuberin co-immunoprecipitated with glycogen synthase kinase 3 beta and Axin, components of this complex in a Wnt-1-dependent manner. Our data suggest that hamartin and tuberin negatively regulate beta-catenin stability and activity by participating in the beta-catenin degradation complex.
Investigation of acoustic waves in thin plates of lithium niobate and lithium tantalate (2001)

The general properties of fundamental antisymmetric A0, symmetric S0, and shear horizontal SH0 acoustic waves propagating in thin piezoelectric plates have been theoretically investigated on samples of lithium niobate (LiNbO3) and lithium tantalate (LiTaO3). The results obtained will be useful for a proper development of various physical, chemical, and biological sensors and devices for signal processing based on plate acoustic waves.
Two-dimensional silicon oxidation experiments and theory (1985)

The effect of stress on the growth rate in 2-D Si oxidation has been clearly observed and characterized. It will be quantitatively demonstrated that the oxidation of curved Si surfaces is retarded by the stress associated with the nonplanar viscous deformation of the oxide, and that the retardation is more severe on concave structures than on convex structures. This result is based on an unique experimental approach in which extensive data was collected on the oxidation of cylindrical silicon structures of controlled radii of curvature. A theoretical model is developed based on the premise that the viscous stress normal to the Si surface is responsible for the retarded oxide growth, and that the stress in the bulk of the oxide is responsible for the difference between concave and convex structures.
Fetal RhD genotyping from maternal plasma (1999)

The prenatal diagnosis of fetal rhesus D (RhD) status is useful for the management of RhD-negative women with partners heterozygous for the RHD gene. Conventional methods for prenatal fetal RhD status determination involve invasive procedures such as fetal blood sampling and amniocentesis. The recent demonstration of the existence of cell-free fetal DNA in maternal plasma and serum opens up the possibility of determining fetal RhD status by analysis of maternal plasma or serum DNA. This possibility has recently been realized by three independent groups of investigators. This development represents an important step towards the routine application of noninvasive fetal blood group diagnosis in sensitized pregnancies and may become a model for developing safer noninvasive prenatal tests for other single-gene disorders.
Identification of a Receptor Mediating Absorption of Dietary Cholesterol in the Intestine (1998)

Here we show that scavenger receptor class B type I is present in the small-intestine brush border membrane where it facilitates the uptake of dietary cholesterol from either bile salt micelles or phospholipid vesicles. This receptor can also function as a port for several additional classes of lipids, including cholesteryl esters, triacylglycerols, and phospholipids. It is the first receptor demonstrated to be involved in the absorption of dietary lipids in the intestine. In liver and steroidogenic tissues, the physiological ligand of this receptor is high-density lipoprotein. We show that binding of high-density lipoprotein and apolipoprotein A-I to the brush border membrane-resident receptor inhibits uptake of cholesterol (sterol) into the brush border membrane from lipid donor particles. This finding lends further support to the conclusion that scavenger receptor BI catalyzes intestinal cholesterol uptake. Our findings suggest new therapeutic approaches for limiting the absorption of dietary cholesterol and reducing hypercholesterolemia and the risk of atherosclerosis.
Induced Pluripotent Stem Cell Models of Progranulin-Deficient Frontotemporal Dementia Uncover Specific Reversible Neuronal Defects (2012)

The pathogenic mechanisms of frontotemporal dementia (FTD) remain poorly understood. Here we generated multiple induced pluripotent stem cell lines from a control subject, a patient with sporadic FTD, and an FTD patient with a novel heterozygous GRN mutation (progranulin [PGRN] S116X). In neurons and microglia differentiated from PGRN S116X induced pluripotent stem cells, the levels of intracellular and secreted PGRN were reduced, establishing patient-specific cellular models of PGRN haploinsufficiency. Through a systematic screen of inducers of cellular stress, we found that PGRN S116X neurons, but not sporadic FTD neurons, exhibited increased sensitivity to staurosporine and other kinase inhibitors. Moreover, the serine/threonine kinase S6K2, a component of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways, was specifically downregulated in PGRN S116X neurons. Both increased sensitivity to kinase inhibitors and reduced S6K2 were rescued by PGRN expression. Our findings identify cell-autonomous, reversible defects in patient neurons with PGRN deficiency, and provide a compelling model for studying PGRN-dependent pathogenic mechanisms and testing potential therapies.
The Combination of a Novel Selective Estrogen Receptor Modulator with an Estrogen Protects the Mammary Gland and Uterus in a Rodent Model: The Future of Postmenopausal Women’s Health? (2003)

The Women's Health Initiative Study and other reports have created major uncertainty among postmenopausal women and physicians concerning hormone replacement therapy. We have thus investigated the possibility of replacing the progestin in hormone replacement therapy by a novel selective estrogen receptor (ER) modulator having potent and pure antiestrogenic activity in the mammary gland and uterus. As measured by changes in histology and Cdc47 labeling in the rat model, the present study shows that the stimulatory effect of estradiol in the mammary gland and uterus is efficiently blocked by simultaneous administration of the novel selective ER modulator EM-652, but bone mineral density is preserved and serum cholesterol is decreased. After the administration of 14C-labeled EM-652, we observed that there is no detectable radioactivity in the brain. Moreover, ER alpha immunoreactivity remained constant in the hypothalamus after EM-652 treatment, whereas ER alpha became almost undetectable in the mammary gland and uterus. The present data show the poor or absent access of EM-652 to the brain, whereas the effects of estrogens are efficiently neutralized in the mammary gland and uterus. Such data support the exciting possibility of a novel approach that could meet most of the needs of women's health at menopause, namely control of hot flushes and prevention of breast, uterine, and ovarian cancer as well as osteoporosis and potentially helping brain function and preventing Alzheimer's disease with no identifiable risk or negative effect.
Lower-Stretch Spanning Trees (2004)

We prove that every weighted graph contains a spanning tree subgraph of average stretch O((log n log log n)^2). Moreover, we show how to construct such a tree in time O(m log^2 n).
Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. (1989)

In national samples of 9921 10 year olds and 3259 adults in Britain systolic blood pressure was inversely related to birth weight. The association was independent of gestational age and may therefore be attributed to reduced fetal growth. This suggests that the intrauterine environment influences blood pressure during adult life. It is further evidence that the geographical differences in average blood pressure and mortality from cardiovascular disease in Britain partly reflect past differences in the intrauterine environment. Within England and Wales 10 year olds living in areas with high cardiovascular mortality were shorter and had higher resting pulse rates than those living in other areas. Their mothers were also shorter and had higher diastolic blood pressures. This suggests that there are persisting geographical differences in the childhood environment that predispose to differences in cardiovascular mortality.
Construction and characterization of an active factor VIII variant lacking the central one-third of the molecule (1986)

The primary structure of factor VIII consists of 2332 amino acids that exhibit 3 distinct structural domains, including a triplicated region (A domains), a unique region of 909 amino acids (B domain), and a carboxy-terminal duplicated region (C domains), that are arranged in the order A1-A2-B-A3-C1-C2. The B domain (residues 741-1648) of factor VIII is lost when factor VIII is activated by thrombin, which proteolytically processes factor VIII to active subunits of Mr 50,000 (domain A1), 43,000 (domain A2), and 73,000 (domains A3-C1-C2). To determine if the B domain is required for factor VIII coagulant activity, a variant was constructed by using recombinant DNA techniques in which residues 797-1562 were eliminated. This shortened the B domain from 909 to 142 amino acids. This variant factor VIIIdes-797-1652 was expressed in mammalian cells and was found to be functional. The factor VIIIdes-797-1562 protein was purified and shown to be processed by thrombin in the same manner as full-length factor VIII. The factor VIIIdes-797-1562 variant also bound to von Willebrand factor (vWF) immobilized on Sepharose. These results indicate that most of the highly glycosylated B domain of factor VIII is not required for the expression of factor VIII coagulant activity and its interaction with vWF.
Pathogenic Human Viruses in Coastal Waters (2003)

This review addresses both historical and recent investigations into viral contamination of marine waters. With the relatively recent emergence of molecular biology-based assays, a number of investigations have shown that pathogenic viruses are prevalent in marine waters being impacted by sewage. Research has shown that this group of fecal-oral viral pathogens (enteroviruses, hepatitis A viruses, Norwalk viruses, reoviruses, adenoviruses, rotaviruses, etc.) can cause a broad range of asymptomatic to severe gastrointestinal, respiratory, and eye, nose, ear, and skin infections in people exposed through recreational use of the water. The viruses and the nucleic acid signature survive for an extended period in the marine environment. One of the primary concerns of public health officials is the relationship between the presence of pathogens and the recreational risk to human health in polluted marine environments. While a number of studies have attempted to address this issue, the relationship is still poorly understood. A contributing factor to our lack of progress in the field has been the lack of sensitive methods to detect the broad range of both bacterial and viral pathogens. The application of new and advanced molecular methods will continue to contribute to our current state of knowledge in this emerging and important field.
Multithreading decoupled architectures for complexity-effective general purpose computing (2001)

Decoupled architectures have not traditionally been used in the context of general purpose computing because of their inability to tolerate control-intensive code that exists across a wide range of applications. This work investigates the possibility of using multithreading to overcome the loss of decoupling dependencies that represent the cause of this main limitation in decoupled architectures. A proposal for a multithreaded decoupled control/access/execute architecture is presented as a platform for achieving high performance on general purpose workloads. It is argued that such a decoupled architecture is more complexity-effective and scalable than comparable superscalar processors, which incorporate enormous amounts of complexity for modest performance gains.