gebhart/patrepeval huggingface dataset:
Tyrosine hydroxylase: human isoforms, structure and regulation in physiology and pathology. (1995)

TH is a tetrahydrobiopterin-requiring, iron-containing monooxygenase. It catalyses the conversion of L-tyrosine to L-dopa, which is the first, rate-limiting step in the biosynthesis of catecholamines (dopamine, noradrenaline and adrenaline), the central and sympathetic neurotransmitters and adrenomedullary hormones. The cofactor of TH is tetrahydrobiopterin, which is synthesized from GTP in three steps. The TH gene consists of 14 exons only in humans and 13 exons in animals. Human TH exists in four isoforms (hTH1-4) that are produced by alternative mRNA splicing from a single gene. A single mRNA and protein corresponding to hTH1 exists in non-primates. Monkey TH exists in two isoforms, corresponding to hTH1 and hTH2. TH activity is regulated in the short term by feedback inhibition of catecholamines in competition with tetrahydrobiopterin, and by activation and deactivation due to phosphorylation and dephosphorylation, mainly at Ser-19 and Ser-40 of hTH1. The multiple TH isoforms in humans and monkeys have additional phosphorylation, resulting in more subtle regulation. In long-term regulation under stress conditions, TH protein is induced. CRE and AP1 in the 5' flanking region of the TH gene may be the main functional elements for TH gene expression. TH may be closely related to the pathogenesis of neurological diseases, such as dystonia and Parkinson's disease, psychiatric diseases, such as affective disorders and schizophrenia, as well as cardiovascular diseases. The TH gene may prove useful in gene therapy to compensate for decreased levels of catecholamines in neurological diseases, for example, for supplementation of dopamine in Parkinson's disease.
www.computorcompanion.com (2006)

Defeating the hacker. A non-technical guide to IT security Robert Schifreen Palgrave Willey ISBN 978-0-470-02555-0 £18.99 Score: 9/10 Beginning Ajax with ASP.NET Wallace McClure, Scott Cate, Paul Glavich, Craig Shoemaker Wrox ISBN 978-0-471-78544-6 £25.99 Score: 9/10 Risk Management for IT Projects Bennet Lientz, Lee Larssen Butterworth-Heinemann ISBN 978-0-12-370534-1 £29.99 Score: 10/10
Antibiotic research in the age of omics: from expression profiles to interspecies communication (2011)

The 'age of omics' has revolutionized our way of studying microbial physiology by introducing global analysis tools such as comparative genomics and global expression techniques including DNA microarrays (transcriptomics) and two-dimensional protein gel electrophoresis (proteomics). From the very beginning, such approaches have also been incorporated into the portfolio of antibiotic research. Genome mining has been used to explore the hidden biosynthetic potential in sequenced bacterial chromosomes, but also to search for novel antibiotic targets. Moreover, numerous studies investigating changes in expression patterns in response to antibiotic presence at the level of both the transcriptome and proteome have been performed over the years, which have helped us gain a deeper understanding of antimicrobial action. This review will focus on the impact that applying global expression studies has had on antibiotic research in the last decade. Signatures of differential gene expression in response to antibiotics have led to a deeper understanding of bacterial resistance mechanisms as well as stress response networks. They have also helped to predict the mechanism of action of novel antimicrobial compounds or to identify potential antibiotic-specific biosensors. Moreover, such studies have revealed novel inhibitory mechanisms of seemingly well-known drugs that might be useful for the development of co-drugs for antibiotic therapy and have identified the potential role of antibiotics as mediators of intercellular communication.
Cassie-State Wetting Investigated by Means of a Hole-to-Pillar Density Gradient (2010)

The superhydrophobicity of rough surfaces owes its existence to heterogeneous wetting. To investigate this phenomenon, density gradients of randomly placed holes and pillars have been fabricated by means of photolithography. On such surfaces, drops can be observed in the Cassie state over the full range of f(1) (fraction of the drop's footprint area in contact with the solid). The gradient was produced with four different surface chemistries: native PDMS (polydimethylsiloxane), perfluorosilanized PDMS, epoxy, and CH(3)-terminated thiols on gold. It was found that f(1) is the key parameter influencing the static water contact angle. Advancing and receding contact angles at any given position on the gradient are sensitive to the type of surface feature--hole or pillar--that is prevalent. In addition, roll-off angles have been measured and found to be influenced not only by the drop weight but also by suction events, edge pinning, and f(1).
Insulin-like and insulin-inhibitory effects of monoclonal antibodies for different epitopes on the human insulin receptor (1987)

Monoclonal antibodies previously shown to react with five distinct epitopes on the human insulin receptor were tested for their metabolic effects on isolated human adipocytes. Two antibodies which reacted with receptor alpha-subunit and completely inhibited 125I-insulin binding mimicked the actions of insulin to stimulate lipogenesis from [14C]glucose and to inhibit catecholamine-induced lipolysis. On a molar basis, these antibodies were comparable in potency with insulin itself. Two other antibodies which decreased insulin binding only slightly or not at all also mimicked these metabolic effects of insulin. One of these antibodies reacted with receptor beta-subunit. In contrast, a further antibody which reacted with alpha-subunit and inhibited insulin binding did not affect basal lipogenesis or catecholamine-induced lipolysis, but was able to antagonize the effects of insulin on these processes. The same antibody antagonized the insulin-like effect of another antibody with which it competed in binding to insulin receptor, but not the effect of an antibody which bound independently to the receptor. It is concluded that binding of ligand at or close to the insulin-binding site is neither necessary nor sufficient to trigger insulin-like metabolic effects, which may rather depend on some general property of antibodies, such as their ability to cross-link and aggregate receptor molecules.
A Portable Kernel-Mode Resource Manager On Windows 2000 Platforms (2007)

The radical technological improvements, the low cost and the popularity of Intel processors are leading the major multiprocessor system integrators to design and build the new parallel systems based on Intel microprocessors, which are interweaved historically with the Windows operating system. In this paper, we present the development of a kernel-mode device driver that performs efficient scheduling of parallel applications on the Windows 2000 operating system. This environment can easily be used as a platform for developing and evaluating scheduling policies on multiprocessors systems running Windows 2000. We review and evaluate the basic primitives and mechanisms in kernel-mode, which we used in our implementation, introducing our own solutions wherever is necessary. Our results demonstrate significant performance improvements and scalability enhancements over the native Windows 2000 scheduler, indicating the integration of such a subsystem in the Windows kernel. Keywords: threads, ...
Diversity of RET proto-oncogene mutations in familial and sporadic Hirschsprung disease (1995)

Hirschsprung disease (HSCR) is a common congenital malformation (1 in 5,000 live births) due to the absence of autonomic ganglia in the terminal hindgut, and resulting in intestinal obstruction in neonates. Recently, a dominant gene for familial HSCR has been mapped to chromosome sub-band 10q11.2 and the disease has been ascribed to mutations in a tyrosine kinase receptor gene mapping to this region, the RET proto-oncogene. Studying the 20 exons of the RET gene by a combination of denaturating gradient gel electrophoresis and single strand conformation polymorphism in a large series of HSCR patients (45 sporadic cases and 35 familial forms), we found mutations of the RET gene in 50% of familial HSCR, regardless of the length of the aganglionic segment. The mean penetrance of the mutant allele in familial HSCR was significantly higher in males (72%) than in females (51%). Most interestingly, mutations at the RET locus accounted for at least 1/3 of sporadic HSCR in our series. These mutations were scattered along the length of the gene. Finally, among the mutations identified in sporadic cases (16/45), seven proved to be de novo mutations suggesting that new mutations at the RET locus significantly contribute to sporadic HSCR. Taken together, the low penetrance of the mutant gene, the lack of genotype-phenotype correlation, the sex-dependent effect of RET mutations and the variable clinical expression of the disease support the existence of one or more modifier genes in familial HSCR.
Metabolomics as a Novel Approach for Early Diagnosis of Pediatric Septic Shock and its Mortality (2013)

Our results indicate that nuclear magnetic resonance metabolite profiling might serve as a promising approach for the diagnosis and prediction of mortality in septic shock in a pediatric population and that quantitative metabolomics methods can be applied in the clinical evaluations of pediatric septic shock.
Bone Anatomy and Rotational Alignment in Total Knee Arthroplasty (2002)

The purpose of the current study was to investigate the bone anatomy in determining the rotational alignment in total knee arthroplasty using computed tomography. Axial images of 109 knees in 83 patients with varus osteoarthritis who had total knee arthroplasty were analyzed. On the images of the distal femur and the proximal tibia, a baseline for the anteroposterior axis of each component was drawn based on the epicondylar axis for the femur and the medial (1/3) of the tibial tuberosity for the tibia. The angle between these two lines was analyzed as the rotational mismatch between the components when they were aligned to the anatomic landmarks of each bone. Fifty-four knees (49.5%) had an angle of 5 degrees or greater and 13 knees (11.9%) had an angle of 10 degrees or greater. There was a tendency to align the tibial component in external rotation relative to the femoral component. The results indicated that the landmarks of each bone were the intrinsic cause of the rotational mismatch in knees with varus osteoarthritis. Surgeons doing total knee arthroplasties should be aware of this and check the rotational mismatch between the components. When it is present, the tibial component should be realigned to match the femoral component rotation to minimize problems caused by the mismatch.
The Business Object Management System (1994)

The Business Object Management System (BOMS) is a distributed resource manager that generalizes and extends the concepts of shared corporate information to include not only data that are structured such that the data can be held in relational tables but also generalized, complex business information objects. BOMS allows enterprises to store, manage, and query the totality of their documents, business transaction records, images, etc., in a uniform and consistent way. With this system, businesses can make more effective use of information that has in the past been inaccessible to thorough and systematic queries and that could not be integrated effectively into existing or new business processes. BOMS is targeted toward very large collections of information objects (on the order of a billion objects, equivalent to terabytes of data) and allows enterprises to unlock information treasures that would otherwise remain hidden in collections of that size. BOMS is influenced by theoretical concepts, such as object-orientation and hypermedia, but relies on proven relational database and transaction processing concepts. BOMS has been implemented with DATABASE 2™ (DB2®) and Customer Information Control System/Enterprise Systems Architecture (CICS/ESA™) and has been in productive use since 1991.
A new algorithm for image noise reduction using mathematical morphology (1995)

Morphological openings and closings are useful for the smoothing of gray-scale images. However, their use for image noise reduction is limited by their tendency to remove important, thin features from an image along with the noise. The paper presents a description and analysis of a new morphological image cleaning algorithm (MIC) that preserves thin features while removing noise. MIC is useful for gray-scale images corrupted by dense, low-amplitude, random, or patterned noise. Such noise is typical of scanned or still-video images. MIC differs from previous morphological noise filters in that it manipulates residual images-the differences between the original image and morphologically smoothed versions. It calculates residuals on a number of different scales via a morphological size distribution. It discards regions in the various residuals that it judges to contain noise. MIC creates a cleaned image by recombining the processed residual images with a smoothed version. The paper describes the MIC algorithm in detail, discusses the effects of parametric variations, presents the results of a noise analysis and shows a number of examples of its use, including the removal of scanner noise. It also demonstrates that MIC significantly improves the JPEG compression of a gray-scale image.
MYC Activation Is a Hallmark of Cancer Initiation and Maintenance (2014)

The MYC proto-oncogene has been implicated in the pathogenesis of most types of human tumors. MYC activation alone in many normal cells is restrained from causing tumorigenesis through multiple genetic and epigenetically controlled checkpoint mechanisms, including proliferative arrest, apoptosis, and cellular senescence. When pathologically activated in a permissive epigenetic and/or genetic context, MYC bypasses these mechanisms, enforcing many of the "hallmark" features of cancer, including relentless tumor growth associated with DNA replication and transcription, cellular proliferation and growth, protein synthesis, and altered cellular metabolism. MYC mandates tumor cell fate, by inducing stemness and blocking cellular senescence and differentiation. Additionally, MYC orchestrates changes in the tumor microenvironment, including the activation of angiogenesis and suppression of the host immune response. Provocatively, brief or even partial suppression of MYC back to its physiological levels of activation can result in the restoration of intrinsic checkpoint mechanisms, resulting in acute and sustained tumor regression, associated with tumor cells undergoing proliferative arrest, differentiation, senescence, and apoptosis, as well as remodeling of the tumor microenvironment, recruitment of an immune response, and shutdown of angiogenesis. Hence, tumors appear to be "addicted" to MYC because of both tumor cell-intrinsic, cell-autonomous and host-dependent, immune cell-dependent mechanisms. Both the trajectory and persistence of many human cancers require sustained MYC activation. Multiscale mathematical modeling may be useful to predict when tumors will be addicted to MYC. MYC is a hallmark molecular feature of both the initiation and maintenance of tumorigenesis.
Identification of a Second Human Subtilisin-Like Protease Gene in the fes/fps Region of Chromosome 15 (1991)

A cDNA encoding a novel human subtilisin-like protease was identified by a polymerase chain reaction (PCR) methodology. PCR primers were designed to be specific for the subfamily of eukaryotic subtilisin-like proteases with specificity for paried basic amino acid residue processing motifs. The gene encoding this protease, designated PACE4, also encoded a smaller subtilisin-related polypeptide derived by alternate mRNA splicing. The deduced PACE4 protein sequence contained a number of interesting features not present in other family members, including an extended signal peptide region, and a relatively large carboxyl-terminal cysteine-rich region with no obvious membrane anchor sequence. As with the fur gene product, the tissue distribution of PACE4 was widespread, with comparatively higher levels in the liver. An additional relationship to the fur gene product was shown by chromosomal localization studies. The close proximity of the fur and PACE4 genes on chromosome 15 suggests that these genes probably evolved from a common ancestor by gene duplication.
Mastering Delphi 4 (1998)

From the Publisher:
Introducing programmers to all of Delphi 4's new features and techniques, this reference explores secrets of the environment, the programming language, the custom components, and Windows 95 programming in general.
Performance of the 3-D sidewall flash EPROM cell (2002)

We report on the performance of a promising new 3-D sidewall flash EPROM cell that has been implemented in a novel memory array. The 3-D flash EPROM is a vertical stacked gate cell with both floating and control gates surrounding a silicon pillar. The cell size is within 10% of the square of the minimum pitch and can be scaled without encountering punchthrough or isolation constraints. The cell has fast write and erase speeds and is suitable for 5V only operation. Read current is 3/spl times/ that of an equivalent generation conventional NOR-type cell.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Correlation between Plasma DNA and Tumor Status in an Animal Model (2014)

Overcoming metastasis is one of the most important issues with lung cancer. Since metastasis arises through complex steps, a suitable animal model is indispensable for investigation of metastasis. To establish an animal model reflecting human metastatic lung cancers, we used NOD/SCID/Jak3null (NOJ) mice, which exhibit deficiencies in NK cell activity, macrophage and dendritic cell function, and complement activation, as well as T and B cell deficiencies. After screening twenty human lung cancer cell lines through expression patterns of E-cadherin and vimentin according to epithelial mesenchymal transition features, an H1975 cell line carrying EGFR mutations, L858R and T790M, was selected for investigation. Inoculation of the cells into the dorsal flanks caused systemic metastases after one month in lymph nodes, liver, lung, and peritoneum, suggesting that metastases occurred both lymphogenically and hematogenously. We confirmed the existence of H1975 cells in metastatic lesions by detection of T790M and L858R using the mutation-biased PCR and quenching probe (MBP-QP) system previously established in our laboratory. In addition, tumor-derived plasma DNA could be detected using the MBP-QP method. The amount of tumor-derived DNA was associated with tumor volume, whereas an unrelated large amount of tumor-derived DNA was circulating in the presence of metastasis. We present a novel animal model with systemic metastasis with human lung cancer cells. The amount of tumor derived DNA would be related with tumor volume and tumor progression such as metastasis.
Membrane-anchored and soluble forms of betaglycan, a polymorphic proteoglycan that binds transforming growth factor-beta. (1989)

Transforming growth factors beta 1 and beta 2 bind with high affinity to the core protein of a 250-350-kD cell surface proteoglycan. This proteoglycan (formerly referred to as the type III TGF-beta receptor) coexists in many cells with the receptor implicated in TGF-beta signal transduction (type I TGF-beta receptor), but its function is not known. We report here that soluble TGF-beta-binding proteoglycans are released by several cell types into the culture media, and can be found in serum and extracellular matrices. As has been shown for the membrane-bound form, the soluble proteoglycans have a heterogeneous core protein of 100-120 kD that carries chondroitin sulfate and/or heparan sulfate glycosaminoglycan chains and a small amount of N-linked carbohydrate. The membrane-bound form of this proteoglycan is hydrophobic and associates with liposomes, whereas the soluble forms lack a membrane anchor and do not associate with liposomes. Differences in the electrophoretic migration of the soluble and membrane forms of this proteoglycan suggest additional structural differences in their core proteins and glycosaminoglycan chains. These soluble and membrane-bound proteoglycans, for which we propose the name "betaglycans," might play distinct roles in pericellular retention, delivery, or clearance of activated TGF-beta.
ChemInform Abstract: Substituted 3,4‐Pyridynes: Clean Cycloadditions. (2000)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Pharmacokinetics of phenoxodiol, a novel isoflavone, following intravenous administration to patients with advanced cancer (2011)

Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12610000334000.
A fast program for maximum likelihood-based inference of large phylogenetic trees (2004)

The computation of large phylogenetic trees with maximum likelihood is computationally intensive. In previous work we have introduced and implemented algorithmic optimizations in PAxML. The program shows run time improvements > 25% over parallel fastDNAml yielding exactly the same results. This paper is focusing on computations of large phylogenetic trees (> 100 organisms) with maximum likelihood. We propose a novel, partially randomized algorithm and new parsimony-based rearrangement heuristics, which are implemented in a sequential and parallel program called RAxML.We provide experimental results for real biological data containing 101 up to 1000 sequences and simulated data containing 150 to 500 sequences, which show run time improvements of factor 8 up to 31 over PAxML yielding equally good trees in terms of likelihood values and RF distance rates at the same time. Finally, we compare the performance of the sequential version of RAxML with a greater variety of available ML codes such as fastDNAml, AxML and MrBayes. RAxML is a freely available open source program.