gebhart/patrepeval huggingface dataset:
Strand Bias in Targeted Gene Repair Is Influenced by Transcriptional Activity (2002)

Modified single-stranded DNA oligonucleotides can direct nucleotide exchange in Saccharomyces cerevisiae. Point and frameshift mutations are corrected in a reaction catalyzed by cellular enzymes involved in various DNA repair processes. The present model centers on the annealing of the vector to one strand of the helix, followed by the correction of the designated base. The choice of which strand to target is a reaction parameter that can be controlled, so here we investigate the properties of strand bias in targeted gene repair. An in vivo system has been established in which a plasmid containing an actively transcribed, but mutated, hygromycin-enhanced green fluorescent protein fusion gene is targeted for repair and upon conversion will confer hygromycin resistance on the cell. Overall transcriptional activity has a positive influence on the reaction, elevating the frequency. If the targeting vector is synthesized so that it directs nucleotide repair on the nontranscribed strand, the level of gene repair is higher than if the template strand is targeted. We provide data showing that the targeting vector can be displaced from the template strand by an active T7 phage RNA polymerase. The strand bias is not influenced by which strand serves as the leading or lagging strand during DNA synthesis. These results may provide an explanation for the enhancement of gene repair observed when the non-template strand is targeted.
Personal area network using human body properties (2007)

Abstract:- The paper deals with the possibility of data transfer, using a human body as a transfer channel. A physically separated transmitter and receiver are located in clothes on various parts of the human body. The individual parts that perform data communication between each other are referred to as Personal Area Network- PAN. This paper includes starting requirements on data communication through the human body and also actual parameters taken on the human body in the function of the transfer channel. The end of the paper describes construction of a vibration alarm device that was assembled and verified. Although this paper concentrates predominantly on military applications, the operation principle of data transfer over the human body that was used here can be directly implemented to purely civil usage. Key-Words:- Unattended ground sensor, personal area network, human body communication 1
The shape of fiber tapers (1992)

A model for the shape of optical fiber tapers, formed by stretching a fiber in a heat source of varying length, is presented. Simple assumptions avoid any need for the techniques of fluid mechanics. It is found that any decreasing shape of taper can be produced. The procedure for calculating the hot-zone length variation required to produce a given shape of taper is described, and is used to indicate how an optical adiabatic taper can be made. A traveling burner tapering system is capable of realizing the model's prediction, and a complete practical procedure for the formation of fiber tapers with any reasonable shape is thus presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Evolutionary Morphing (2006)

We introduce a technique to visualize the gradual evolutionary change of the shapes of living things as a morph between known three-dimensional shapes. Given geometric computer models of anatomical shapes for some collection of specimens - here the skulls of the some of the extant members of a family of monkeys - an evolutionary tree for the group implies a hypothesis about the way in which the shape changed through time. We use a statistical model which expresses the value of some continuous variable at an internal point in the tree as a weighted average of the values at the leaves. The framework of geometric morphometrics can then be used to define a shape-space, based on the correspondences of landmark points on the surfaces, within which these weighted averages can be realized as actual surfaces. Our software provides tools for performing and visualizing such an analysis in three dimensions. Beginning with laser range scans of crania, we use our landmark editor to interactively place landmark points on the surface. We use these to compute a "tree-morph" that smoothly interpolates the shapes across the tree. Each intermediate shape in the morph is a linear combination of all of the input surfaces. We create a surface model for an intermediate shape by warping all the input meshes towards the correct shape and then blending them together. To do the blending, we compute a weighted average of their associated trivariate distance functions and then extract a surface from the resulting function. We implement this idea using the squared distance function, rather than the usual signed distance function, in a novel way.
Direct Atom-Efficient Esterification between Carboxylic Acids and Alcohols Catalyzed by Amphoteric, Water-Tolerant TiO(acac)2 (2005)

A diverse array of oxometallic species were examined as catalysts for a test direct condensation of benzoic acid and 2-phenylethanol in 1:1 stoichiometry. Besides group IVB MOCl2-xH2O and TiOX2-xH2O, group VB VOCl2-xTHF and group IVB TiO(acac)2 were found to be the most efficient and water-tolerant catalysts for the test reaction. The new neutral catalytic protocol with the optimal TiO(acac)2 tolerates many stereo/electronic structural variations in both (di)acid (1 degree -3 degrees alkyl and aryl) and (di)alcohol (1 degree, 2 degrees alkyl, and aryl) components with high chemoselectivity.
Site-specific Recombination and Its Role in the Life Cycle of Bacteriophage P1 (1981)

A variety of bacteriophages, including λ, P2, P22, and Mu, encode site-specific recombination systems. The need for these systems is clear because the normal prophage DNA of these viruses is integrated into the bacterial chromosome. Integration occurs at specific sites within the phage DNA, and in the cases of λ, P2, and P22 also within the bacterial chromosome. In contrast, the prophage DNA of bacteriophage P1 is an autonomous plasmid. Consequently, the need for and the role of a P1 site-specific recombination system are not at all obvious. Despite this, the following observations suggest that P1 encodes such a system. First, the viral DNA of P1, like that of phages P22 and T4, is terminally redundant and cyclically permuted (Ikeda and Tomizawa 1969). Thus, one could expect that the genetic map of P1, like those of P22 and T4, would be circular; in fact, it is linear (Scott 1968; Walker...
Respiratory epithelial cells require Toll-like receptor 4 for induction of Human β-defensin 2 by Lipopolysaccharide (2005)

This data defines an additional role for TLR4 in the host defense in the lung.
Successive Decoding for Finite State Markov Modelled Flat Fading Channels (2006)

This paper proposes novel successive decoding paradigm for fading channels, K independent codewords of different rates and lengths are interleaved at the transmitter according to a pattern, and successively decoded at the receiver. This enables progressively better channel estimates for the receiver, at a minimal cost of pilot symbols. At each decoding stage, channel estimation and decoding are performed separately. or iteratively if the residual channel correlation within a codeword can be exploited. The flexible interleaver pattern, after some level of optimization, achieves near-capacity system performance with only a small number of codewords K, as demonstrated numerically by a finite state Markov modelled flat fading channel
Heart and skeletal muscle inflammation in Atlantic salmon, Salmo salar L.: a new infectious disease (2004)

Heart and skeletal muscle inflammation (HSMI) is a disease syndrome of unknown aetiology first observed in farmed Atlantic salmon, Salmo salar, in 1999. In the present study we have demonstrated for the first time that HSMI is an infectious disease. It was induced in Atlantic salmon post-smolts after injection with tissue homogenate from farmed Atlantic salmon previously diagnosed with HSMI. The lesions were also induced in cohabitating salmon given a corresponding injection without tissue homogenate. Six weeks post-challenge the fish that had been injected with tissue homogenate developed a serious epicarditis and myocarditis with mononuclear cell infiltrations in compact and spongy layers of the heart. Similar lesions were found in cohabitants after 10 weeks. The lesions were consistent with samples from field outbreaks of HSMI. No lesions were found in control fish. A viral aetiology is strongly suggested, as no difference in disease induction between an inoculum containing antibiotics and a non-treated inoculum was found. Further investigations are required in order to make conclusions regarding the cause and pathogenesis of HSMI.
Role of Ceramide in Cellular Senescence (1995)

Recently the sphingomyelin cycle, involving the hydrolysis of membrane sphingomyelin by an activated sphingomyelinase to generate ceramide, has emerged as a key pathway in cell differentiation and apoptosis in leukemic and other cell types. Here we investigate a role for this pathway in the senescence of WI-38 human diploid fibroblasts (HDF). We found that endogenous levels of ceramide increased considerably (4-fold) and specifically (compared with other lipids) as cells entered the senescent phase. Investigation of the mechanism of increased ceramide led to the discovery that neutral sphingomyelinase activity is elevated 8-10 fold in senescent cells. There were no changes in sphingomyelinase activity or ceramide levels as HDF entered quiescence following serum withdrawal or contact inhibition. Thus, the activation of the sphingomyelinase/ceramide pathway in HDF is due to senescence and supports the hypotheses that senescence represents a distinct program of cell development that can be differentiated from quiescence. Additional studies disclosed the ability of ceramide to induce a senescent phenotype. Thus, when exogenous ceramide (15 microM) was administered to young WI-38 HDF, it produced endogenous levels comparable to those observed in senescent cells (as determined by metabolic labeling studies). Ceramide concentrations of 10-15 microM inhibited the growth of young HDF and induced a senescent phenotype by its ability to inhibit DNA synthesis and mitogenesis. These concentrations of ceramide also induced retinoblastoma dephosphorylation and inhibited serum-induced AP-1 activation in young HDF, thus recapitulating basic biochemical and molecular changes of senescence. Sphingomyelinase and ceramide may thus be implicated as mediators of cellular senescence.
Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 ( USF2 ) knockout mice (2001)

We previously reported the disruption of the murine gene encoding the transcription factor USF2 and its consequences on glucose-dependent gene regulation in the liver. We report here a peculiar phenotype of Usf2(-/-) mice that progressively develop multivisceral iron overload; plasma iron overcomes transferrin binding capacity, and nontransferrin-bound iron accumulates in various tissues including pancreas and heart. In contrast, the splenic iron content is strikingly lower in knockout animals than in controls. To identify genes that may account for the abnormalities of iron homeostasis in Usf2(-/-) mice, we used suppressive subtractive hybridization between livers from Usf2(-/-) and wild-type mice. We isolated a cDNA encoding a peptide, hepcidin (also referred to as LEAP-1, for liver-expressed antimicrobial peptide), that was very recently purified from human blood ultrafiltrate and from urine as a disulfide-bonded peptide exhibiting antimicrobial activity. Accumulation of iron in the liver has been recently reported to up-regulate hepcidin expression, whereas our data clearly show that a complete defect in hepcidin expression is responsible for progressive tissue iron overload. The striking similarity of the alterations in iron metabolism between HFE knockout mice, a murine model of hereditary hemochromatosis, and the Usf2(-/-) hepcidin-deficient mice suggests that hepcidin may function in the same regulatory pathway as HFE. We propose that hepcidin acts as a signaling molecule that is required in conjunction with HFE to regulate both intestinal iron absorption and iron storage in macrophages.
In vitro and in vivo evaluation of a whole blood platelet‐sparing leukoreduction filtration system (2010)

All WBPSF-derived transfusion products met or exceeded in vitro and in vivo FDA guidelines. This filtration system is suitable for routine blood center or hospital use in the production of LR AS-5 RBCs, CPD PLTs, and CPD plasma.
A Review of Progress in Clinical Photodynamic Therapy (2005)

Photodynamic therapy (PDT) has received increased attention since the regulatory approvals have been granted to several photosensitizing drugs and light applicators worldwide. Much progress has been seen in basic sciences and clinical photodynamics in recent years. This review will focus on new developments of clinical investigation and discuss the usefulness of various forms of PDT techniques for curative or palliative treatment of malignant and non-malignant diseases.
Dynamics of Glucose Consumption in Yeast (1997)

When a continuously grown yeast culture was allowed to rest at the low dilution rate for an extended time period and was then challenged by increasing the dilution rate, applied as a step function, an overshoot of the concentration of residual glucose occurred reproducibly. A structural extension of the bottleneck model describing another intracellular bottleneck in glucose consumption allowed to predict such overshoots quantitatively. The model assumes that an intracellular enzymatic pool increases in response to a challenge by excess substrate supply, and experimentally, the relaxation time was determined to be on the order of 1 h. When the culture is reset to more limiting conditions, the enzymatic pool shrinks with a relaxation time determined by the reciprocal of the current specific growth rate. Generalized, microbial populations do memorize their (recent) history by adapting their metabolic outfit.
Neuropilin-1 Suppresses Tumorigenic Properties in a Human Pancreatic Adenocarcinoma Cell Line Lacking Neuropilin-1 Coreceptors (2005)

Neuropilin-1 (NRP-1) was first described as a coreceptor implicated in neuronal guidance that bound members of the semaphorin/collapsin family. NRP-1 is also expressed in endothelial cells and is believed to promote angiogenesis by acting as a coreceptor with vascular endothelial growth factor (VEGF) receptor 2. Recent studies suggest that NRP-1 can function through both a VEGF-dependent and VEGF-independent fashion. Expression of NRP-1 has been shown in many human tumors, including pancreatic adenocarcinomas. The exact role of NRP-1 in tumor cells is unknown, particularly in cells that lack the NRP-1 coreceptors VEGF receptor 2 and Plexin-A1. To discern the regulatory role(s) of NRP-1 in pancreatic adenocarcinoma that lack these coreceptors, we overexpressed both full-length NRP-1 and a deletion form of NRP-1 that does not interact with semaphorin or VEGF. Overexpression of either isoform reduced several key tumorigenic properties, including anchorage-independent cell growth and migration in vitro, and resulted in reduced tumor incidence and tumor volume in vivo. Conversely, reduction of NRP-1 expression by small interfering RNA targeting led to enhanced tumor growth. Thus, NRP-1 may play distinct growth regulatory roles in different tumor types, and altering NRP-1 expression or function may be a means of influencing the growth of pancreatic cancers.
[The role of protein kinase C in left ventricular relaxation impaired by global ischemia]. (1989)

The role of protein kinase C (C kinase) in the left ventricular relaxation impaired by global ischemia was investigated in anesthetised dogs. Left ventricular global ischemia model was made by coronary blood flow reduction and atrial pacing (100-180 beats/min). By this maneuver, the time constant T and left ventricular end-diastolic pressure (LVEDP) were increased in a pacing-rate dependent manner. Intracoronary infusion of H-7, an inhibitor of C kinase, suppressed the magnitudes of the increments of T and LVEDP, while intracoronary infusion of 12-O-tetradecanoyl-phorbol-13-acetate, an activator of C kinase, enhanced the increases of T and LVEDP caused by ischemia. In non-ischemic group, H-7 did not influenced T and LVEDP. The results indicate that C kinase is activated by myocardial ischemia and enhances impairment of left ventricular relaxation.
Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase. (1996)

The central role of cyclin-dependent kinases (CDKs) in cell cycle regulation makes them a promising target for studying inhibitory molecules that can modify the degree of cell proliferation. The discovery of specific inhibitors of CDKs such as polyhydroxylated flavones has opened the way to investigation and design of antimitotic compounds. A novel flavone, (-)-cis-5,7-dihydroxyphenyl-8-[4-(3-hydroxy-1-methyl)piperidinyl] -4H-1-benzopyran-4-one hydrochloride hemihydrate (L868276), is a potent inhibitor of CDKs. A chlorinated form, flavopiridol, is currently in phase I clinical trials as a drug against breast tumors. We determined the crystal structure of a complex between CDK2 and L868276 at 2.33 angstroms resolution and refined to an Rfactor 20.3%. The aromatic portion of the inhibitor binds to the adenine-binding pocket of CDK2, and the position of the phenyl group of the inhibitor enables the inhibitor to make contacts with the enzyme not observed in the ATP complex structure. The analysis of the position of this phenyl ring not only explains the great differences of kinase inhibition among the flavonoid inhibitors but also explains the specificity of L868276 to inhibit CDK2 and CDC2.
Secreted Versus Membrane-anchored Collagenases (2009)

Fibroblasts degrade type I collagen, the major extracellular protein found in mammals, during events ranging from bulk tissue resorption to invasion through the three-dimensional extracellular matrix. Current evidence suggests that type I collagenolysis is mediated by secreted as well as membrane-anchored members of the matrix metalloproteinase (MMP) gene family. However, the roles played by these multiple and possibly redundant, degradative systems during fibroblast-mediated matrix remodeling is undefined. Herein, we use fibroblasts isolated from Mmp13(-/-), Mmp8(-/-), Mmp2(-/-), Mmp9(-/-), Mmp14(-/-) and Mmp16(-/-) mice to define the functional roles for secreted and membrane-anchored collagenases during collagen-resorptive versus collagen-invasive events. In the presence of a functional plasminogen activator-plasminogen axis, secreted collagenases arm cells with a redundant collagenolytic potential that allows fibroblasts harboring single deficiencies for either MMP-13, MMP-8, MMP-2, or MMP-9 to continue to degrade collagen comparably to wild-type fibroblasts. Likewise, Mmp14(-/-) or Mmp16(-/-) fibroblasts retain near-normal collagenolytic activity in the presence of plasminogen via the mobilization of secreted collagenases, but only Mmp14 (MT1-MMP) plays a required role in the collagenolytic processes that support fibroblast invasive activity. Furthermore, by artificially tethering a secreted collagenase to the surface of Mmp14(-/-) fibroblasts, we demonstrate that localized pericellular collagenolytic activity differentiates the collagen-invasive phenotype from bulk collagen degradation. Hence, whereas secreted collagenases arm fibroblasts with potent matrix-resorptive activity, only MT1-MMP confers the focal collagenolytic activity necessary for supporting the tissue-invasive phenotype.
The use of high-selenium yeast to raise selenium status: how does it measure up? (2004)

Selenium-enriched yeast (Se-yeast) is a common form of Se used to supplement the dietary intake of this important trace mineral. However, its availability within the European Union is under threat, owing to concerns expressed by the European Community (EC) Scientific Committee on Food that Se-yeast supplements are poorly characterised and could potentially cause the build up of Se in tissues to toxic levels. The present review examines the validity of these concerns. Diagrams of the biosynthesis and metabolism of Se compounds show which species can be expected to occur in Se-yeast preparations. Se-yeast manufacture is described together with quality-control measures applied by reputable manufacturers. The way in which speciation of Se-yeast is achieved is explained and results on amounts of Se species in various commercial products are tabulated. In all cases described, selenomethionine is the largest single species, accounting for 54-74 % of total Se. Se-yeast is capable of increasing the activity of the selenoenzymes and its bioavailability has been found to be higher than that of inorganic Se sources in all but one study. Intervention studies with Se-yeast have shown the benefit of this form in cancer prevention, on the immune response and on HIV infection. Of about one dozen supplementation studies, none has shown evidence of toxicity even up to an intake level of 800 microg Se/d over a period of years. It is concluded that Se-yeast from reputable manufacturers is adequately characterised, of reproducible quality, and that there is no evidence of toxicity even at levels far above the EC tolerable upper intake level of 300 microg/d.
MEKK1 phosphorylates MEK1 and MEK2 but does not cause activation of mitogen-activated protein kinase. (1995)

A constitutively active fragment of rat MEK kinase 1 (MEKK1) consisting of only its catalytic domain (MEKK-C) expressed in bacteria quantitatively activates recombinant mitogen-activated protein (MAP) kinase/extracellular signal-regulated protein kinase (ERK) kinases 1 and 2 (MEK1 and MEK2) in vitro. Activation of MEK1 by MEKK-C is accompanied by phosphorylation of S218 and S222, which are also phosphorylated by the protein kinases c-Mos and Raf-1. MEKK1 has been implicated in regulation of a parallel but distinct cascade that leads to phosphorylation of N-terminal sites on c-Jun; thus, its role in the MAP kinase pathway has been questioned. However, in addition to its capacity to phosphorylate MEK1 in vitro, MEKK-C interacts with MEK1 in the two-hybrid system, and expression of mouse MEKK1 or MEKK-C in mammalian cells causes constitutive activation of both MEK1 and MEK2. Neither cotransfected nor endogenous ERK2 is highly activated by MEKK1 compared to its stimulation by epidermal growth factor in spite of significant activation of endogenous MEK. Thus, other as yet undefined mechanisms may be involved in determining information flow through the MAP kinase and related pathways.
Constitutive and inducible secretion of platelet-derived growth factor analogs by human leukemic cell lines coexpressing erythroid and megakaryocytic markers. (1987)

We have examined the constitutive and inducible secretion of platelet-derived growth factor (PDGF)-like proteins in a variety of human hemopoietic cell lines. The highest levels of secreted protein were noted in four human erythroleukemia lines which, in addition to erythroid lineage markers, express one or more megakaryocytic lineage markers. Induction of these lines by 12-O-tetradecanoylphorbol-13-acetate enhanced the expression of megakaryocytic markers and increased secretion of PDGF-like proteins several fold. In concert with these changes, there was significant induction of c-sis/PDGF-B messenger RNA (mRNA) expression in all lines, whereas one line showed significant concurrent induction of PDGF-A mRNA expression. Whether PDGF-like secretion is part of the stem cell-like phenotype displayed by these lines or is secondary to their leukemic transformation remains to be determined. Nevertheless, these lines provide new cellular models for studying the expression and function of PDGF analogs in hemopoietic cells.