gebhart/patrepeval huggingface dataset:
Direct in vivo gene transfer into the coronary and peripheral vasculatures of the intact dog. (1991)

Gene therapy approaches have been suggested for the treatment of cardiovascular disease. Recently, direct transfer of the gene encoding beta-galactosidase into peripheral arteries of the pig has been demonstrated. To determine whether this approach is applicable to other arterial beds and to other species, we first evaluated the use of beta-galactosidase as a marker protein in the canine model. We demonstrate that variable but substantial endogenous beta-galactosidase-like activity is induced by manipulation of canine peripheral arteries, which precludes the use of this marker protein in evaluating the efficiency of gene transfer in this model. A marker gene encoding firefly luciferase was then evaluated, and background luciferase activity was found to be low in the dog even after arterial manipulation. Using the luciferase gene, we then demonstrated lipid-mediated gene transfer directly into both coronary and peripheral arteries of the intact dog. These results indicate the feasibility of in vivo gene transfer into coronary arteries and demonstrate the use of the luciferase marker protein in quantifying recombinant protein expression following gene transfer in canine models. This simple and effective method for direct in vivo gene transfer into coronary and peripheral arteries may be applicable to the localized production of therapeutically important proteins for the treatment of cardiovascular diseases.
An Asymmetric Diels–Alder Reaction Catalyzed by Chiral Phosphate Magnesium Complexes: Highly Enantioselective Synthesis of Chiral Spirooxindoles (2013)

Mild Magic: A mild, enantioselective Diels-Alder reaction, catalyzed by a chiral magnesium phosphate species, has been developed for the synthesis of various chiral spirooxindoles. Molecular sieves were found to have a considerable effect when used as additives in this reaction.
Simple and efficient CRISPR/Cas9‐mediated targeted mutagenesis in Xenopus tropicalis (2013)

We have assessed the efficacy of the recently developed CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated) system for genome modification in the amphibian Xenopus tropicalis. As a model experiment, targeted mutations of the tyrosinase gene were verified, showing the expected albinism phenotype in injected embryos. We further tested this technology by interrupting the six3 gene, which is required for proper eye and brain formation. Expected eye and brain phenotypes were observed when inducing mutations in the six3 coding regions, as well as when deleting the gene promoter by dual targeting. We describe here a standardized protocol for genome editing using this system. This simple and fast method to edit the genome provides a powerful new reverse genetics tool for Xenopus researchers.
Characterization of a (2R,3R)-2,3-Butanediol Dehydrogenase as theSaccharomyces cerevisiae YAL060W Gene Product (2000)

The completion of the Saccharomyces cerevisiae genome project in 1996 showed that almost 60% of the potential open reading frames of the genome had no experimentally determined function. Using a conserved sequence motif present in the zinc-containing medium-chain alcohol dehydrogenases, we found several potential alcohol dehydrogenase genes with no defined function. One of these, YAL060W, was overexpressed using a multicopy inducible vector, and its protein product was purified to homogeneity. The enzyme was found to be a homodimer that, in the presence of NAD(+), but not of NADP, could catalyze the stereospecific oxidation of (2R,3R)-2, 3-butanediol (K(m) = 14 mm, k(cat) = 78,000 min(-)(1)) and meso-butanediol (K(m) = 65 mm, k(cat) = 46,000 min(-)(1)) to (3R)-acetoin and (3S)-acetoin, respectively. It was unable, however, to further oxidize these acetoins to diacetyl. In the presence of NADH, it could catalyze the stereospecific reduction of racemic acetoin ((3R/3S)- acetoin; K(m) = 4.5 mm, k(cat) = 98,000 min(-)(1)) to (2R,3R)-2,3-butanediol and meso-butanediol, respectively. The substrate stereospecificity was determined by analysis of products by gas-liquid chromatography. The YAL060W gene product can therefore be classified as an NAD-dependent (2R,3R)-2,3-butanediol dehydrogenase (BDH). S. cerevisiae could grow on 2,3-butanediol as the sole carbon and energy source. Under these conditions, a 3. 5-fold increase in (2R,3R)-2,3-butanediol dehydrogenase activity was observed in the total cell extracts. The isoelectric focusing pattern of the induced enzyme coincided with that of the pure BDH (pI 6.9). The disruption of the YAL060W gene was not lethal for the yeast under laboratory conditions. The disrupted strain could also grow on 2,3-butanediol, although attaining a lesser cell density than the wild-type strain. Taking into consideration the substrate specificity of the YAL060W gene product, we propose the name of BDH for this gene. The corresponding enzyme is the first eukaryotic (2R, 3R)-2,3-butanediol dehydrogenase characterized of the medium-chain dehydrogenase/reductase family.
The Long Term Effects of Percutaneous Transluminal Angioplasty for Treating Patients with Renovascular Hypertension: Case Studies (1986)

Percutaneous transluminal angioplasty was performed on 10 patients with unilateral renovascular hypertension (7 with atheromatous and 3 with fibromuscular stenoses) who were then followed for an average of 42 months (range, 24 to 67 months). Dilation of the stenosis was initially successful in all patients except one who had severe atheromatous stenosis. Among patients with atheromatous disease, normotension was attained for 40, 25 and 24 months in 3 patients given no antihypertensive medication and for 67 and 55 months in 2 patients given only nicardipine. The remaining one patient had a recurrent stenosis 3 months after angioplasty. All patients with fibromuscular dysplasia have been normotensive without any hypotensive medication for more than 4 years. Plasma renin activity declined within one week after angioplasty and remained unchanged thereafter in all patients except the one case suffering from a recurrent stenosis. Renal blood flow and glomerular filtration rate remained increased after angioplasty. These results suggest that hypertension can be controlled and renal dysfunction in patients with renal artery stenosis caused by atheroma or fibromuscular dysplasia improved for long periods by percutaneous transluminal angioplasty. The antihypertensive effect obtained by this procedure was more valuable for the patients with fibromuscular dysplasia than in those with atheromatous disease.
Oxidized Redox State of Glutathione in the Endoplasmic Reticulum (1992)

The redox state of the endoplasmic reticulum (ER) was measured with the peptide N-Acetyl-Asn-Tyr-Thr-Cys-NH2. The peptide diffused across cellular membranes; some became glycosylated and thus trapped within the secretory pathway, and its cysteine residue underwent reversible thiol-disulfide exchanges with the surrounding redox buffer. Glycosylated peptides from cells were disulfide-linked to glutathione, indicating that glutathione is the major redox buffer in the secretory pathway. The redox state of the secretory pathway was more oxidative than that of the cytosol; the ratio of reduced glutathione to the disulfide form (GSH/GSSG) within the secretory pathway ranged from 1:1 to 3:1, whereas the overall cellular GSH/GSSG ratio ranged from 30:1 to 100:1. Cytosolic glutathione was also transported into the lumen of microsomes in a cell-free system. Although how the ER maintains an oxidative environment is not known, these results suggest that the demonstrated preferential transport of GSSG compared to GSH into the ER lumen may contribute to this redox compartmentation.
Stress focusing for controlled fracture in microelectromechanical systems (2007)

This letter describes a strategy for controlling fracture in microelectromechanical systems (MEMSs) based on the control of corner sharpness. Studies of model MEMS structures with round (radius of approximately microns), intermediate, and sharp (&amp;lt;10nm) corners demonstrate the effects of corner sharpness on the concentration of applied stress. Finite-element analysis reveals that stress distributions intensify and localize as sharpness increases, and transfer printing experiments demonstrate the influence of stress concentration on breakability.
Biolistic transformation of prokaryotes: factors that affect biolistic transformation of very small cells (1992)

Five bacterial species were transformed using particle gun-technology. No pretreatment of cells was necessary. Physical conditions (helium pressure, target cell distance and gap distance) and biological conditions (cell growth phase, osmoticum concentration, and cell density) were optimized for biolistic transformation of Escherichia coli and these conditions were then used to successfully transform Agrobacterium tumefaciens, Erwinia amylovora, Erwinia stewartii and Pseudomonas syringae pv. syringae. Transformation rates for E. coli were 10(4) per plate per 0.8 micrograms DNA. Although transformation rates for the other species were low (less than 10(2) per plate per 0.8 micrograms DNA), successful transformation without optimization for each species tested suggests wide utility of biolistic transformation of prokaryotes. E. coli has proven to be a useful model system to determine the effects of relative humidity, particle size and particle coating on efficiency of biolistic transformation.
Fibroblast growth factor signaling in embryonic and cancer stem cells (2006)

Cancer stem cells are cancer cells that originate from the transformation of normal stem cells. The most important property of any stem cell is the ability to self-renew. Through this property, there are striking parallels between normal stem cells and cancer stem cells. Both cell types share various markers of "stemness". In particular, normal stem cells and cancer stem cells utilize similar molecular mechanisms to drive self-renewal, and similar signaling pathways may induce their differentiation. The fibroblast growth factor 2 (FGF-2) pathway is one of the most significant regulators of human embryonic stem cell (hESC) self-renewal and cancer cell tumorigenesis. Here we summarize recent data on the effects of FGF-2 and its receptors on hESCs and leukemic stem/progenitor cells. Also, we discuss the similarities of these findings with stem cell renewal and differentiation phenotypes.
A new type of thin film magnetoresistive magnetometer--An analysis of circuit principles (1984)

There have been investigated various modes of biasing and feeding of the Permalloy thin film sensors used in magneto-resistive magnetometers. These magnetometers may be used for relatively simple measurements of direct and alternating flux density in the range 100nT-10mT. The introduction of alternating bias field in the direct flux density measurements helps to reduce the temperature zero drift of a magnetometer.
Regulation of Dendritic Cell Migration to the Draining Lymph Node (2003)

Antigen-pulsed dendritic cells (DCs) are used as natural adjuvants for vaccination, but the factors that influence the efficacy of this treatment are poorly understood. We investigated the parameters that affect the migration of subcutaneously injected mouse-mature DCs to the draining lymph node. We found that the efficiency of DC migration varied with the number of injected DCs and that CCR7+/+ DCs migrating to the draining lymph node, but not CCR7-/- DCs that failed to do so, efficiently induced a rapid increase in lymph node cellularity, which was observed before the onset of T cell proliferation. We also report that DC migration could be increased up to 10-fold by preinjection of inflammatory cytokines that increased the expression of the CCR7 ligand CCL21 in lymphatic endothelial cells. The magnitude and quality of CD4+ T cell response was proportional to the number of antigen-carrying DCs that reached the lymph node and could be boosted up to 40-fold by preinjection of tumor necrosis factor that conditioned the tissue for increased DC migration. These results indicate that DC number and tissue inflammation are critical parameters for DC-based vaccination.
Titration of protein transport activity by incremental changes in signal peptide hydrophobicity (1993)

A systematic series of mutants has been generated which provides a means for titrating the dependence of protein transport activity on signal peptide hydrophobicity. These mutants involve replacement of the hydrophobic core segment of the Escherichia coli alkaline phosphatase signal peptide while maintaining the natural amino- and carboxyl-terminal segments and the overall length. The new core regions vary in composition from 10:0 to 0:10 in the ratio of alanine to leucine residues. Thus, a nonfunctional polyalanine-containing signal peptide is titrated with the more hydrophobic residue, leucine. Using precursor processing to quantify transport activity, we observe a clear, nonlinear dependence on hydrophobicity. At ratios of alanine to leucine of less than or equal to 8:2, the signal peptide is essentially nonfunctional; at ratios greater than or equal to 3:7, the signal peptide functions efficiently. The midpoint is between alanine to leucine ratios of 6:4 and 5:5. Signal peptides with hydrophobicity just below the midpoint show substantial, additional precursor processing over time while the others do not. The data are consistent with a simple model involving a two-state equilibrium between the untransported and transported species and a change in the delta G of -0.85 kcal/mol for every alanine to leucine conversion.
CD38 ligation induces discrete cytokine mRNA expression in human cultured lymphocytes (1995)

Human CD38 is a surface glycoprotein expressed by different immuno-competent cells such as immature and activated lymphocytes, plasma cells and natural killer cells. It has recently been reported that the CD38 molecule exerts adenosine diphosphate ribosyl cyclase activity and is associated with distinct transmembrane signaling molecules. This study reports that ligation of CD38 by specific monoclonal antibodies (mAb) induces multiple cytokine mRNA expression in cultured peripheral blood mononuclear cells (PBMC). The mRNA for tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-12 were always detected, whereas interferon-gamma and IL-10 mRNA expression were seen in most, but not all PBMC cultures. Low levels of IL-2, IL-4 and IL-5 mRNA were also found. The key observation of this work is that CD38 ligation in PBMC induces a large spectrum of cytokines, many of which overlap with those induced via CD3 activation. The main differences between CD38 and CD3 activation are the low to undetectable levels of IL-2 mRNA, and the sustained IL-1 beta and IL-6 mRNA accumulation found in PBMC cultures following treatment with anti-CD38 mAb. Furthermore, PBMC proliferation was not found to be a prerequisite for CD38-mediated cytokine induction. Together, these results suggest that human CD38 activates a signaling pathway which leads to the induction of a discrete array of cytokines, and that this pathway only partially overlaps with that controlled by T cell receptor CD3.
A titanium-nickel shape-memory alloy actuated micropump (2002)

The shape memory alloy (SMA) titanium-nickel (TiNi) is used in thin film form as the basis of actuation for a reciprocating micropump. A novel configuration comprising two complementary TiNi actuators is used to perform cyclic motion by utilizing the shape memory effect (SME). Check valves are fabricated from polyimide to ensure unidirectional flow through the pump chamber. The pump is driven by an electrical drive signal, which is passed directly through the TiNi thin films, causing a Joule heating-induced phase transformation and initiating the SME. Cyclic motion is achieved by heating the actuators out of phase. The pump was tested with filtered DI water and attained a pump rate of 50 /spl mu/L/min.
Quasiparticle self-consistentGWcalculations for PbS, PbSe, and PbTe: Band structure and pressure coefficients (2010)

The electronic band structures of PbS, PbSe, and PbTe in the rocksalt structure are calculated with the quasiparticle self-consistent GW (QSGW) approach with spin-orbit coupling included. The semiconducting gaps and their deformation potentials as well as the effective masses are obtained. The GW approximation provides a correct description of the electronic structure around the gap, in contrast to the local-density approximation, which leads to inverted gaps in the lead chalcogenides. The QSGW calculations are in good quantitative agreement with experimental values of the gaps and masses. At moderate hole doping a complex filamental Fermi-surface structure develops with ensuing large density of states. The pressure-induced gap closure leads to linear (Dirac-type) band dispersions around the L point.
Interaction of IGF-Binding Protein-Related Protein 1 with a Novel Protein, Neuroendocrine Differentiation Factor, Results in Neuroendocrine Differentiation of Prostate Cancer Cells (2001)

Neuroendocrine cells have been implicated in many cancers, including small cell lung, cervical, breast, and prostate carcinomas. The increase in neuroendocrine cell number in prostate cancer has been reported to correlate with poor prognosis, progressive tumors, and androgen insensitivity. The mechanisms involved in this differentiation remain unknown. IGF-binding protein-related protein 1 is a member of the IGF-binding protein superfamily and has recently been shown to exhibit differentiation and tumor suppression activity in prostate cancer cell lines stably overexpressing IGF-binding protein-related protein 1. From a yeast two-hybrid screen, a novel IGF-binding protein-related protein 1-interacting protein was identified. Immunocytochemical techniques indicate that this protein, 25.1, and intracellular IGF-binding protein-related protein 1 colocalize in the nucleus. When 25.1 is transiently expressed in a stable prostate cancer cell line overexpressing IGF-binding protein-related protein 1, cells assume a neuritic-like morphology with long dendritic-like processes and express the neuroendocrine markers chromogranin A and neuron-specific enolase. We propose that 25.1 (neuroendocrine differentiation factor) together with IGF-binding protein-related protein 1 can induce neuroendocrine cell differentiation in prostate cancer cells.
Bone regeneration by implantation of purified, culture‐expanded human mesenchymal stem cells (1998)

Bone marrow contains a population of rare progenitor cells capable of differentiating into bone, cartilage, tendon, and other connective tissues. These cells, referred to as mesenchymal stem cells, can be purified and culture-expanded from animals and humans and have been shown to regenerate functional tissue when delivered to the site of musculoskeletal defects in experimental animals. To test the ability of purified human mesenchymal stem cells to heal a clinically significant bone defect, mesenchymal stem cells isolated from normal human bone marrow were culture-expanded, loaded onto a ceramic carrier, and implanted into critical-sized segmental defects in the femurs of adult athymic rats. For comparison, cell-free ceramics were implanted in the contralateral limb. The animals were euthanized at 4, 8, or 12 weeks, and healing bone defects were compared by high-resolution radiography, immunohistochemistry, quantitative histomorphometry, and biomechanical testing. In mesenchymal stem cell-loaded samples, radiographic and histologic evidence of new bone was apparent by 8 weeks and histomorphometry demonstrated increasing bone formation through 12 weeks. Biomechanical evaluation confirmed that femurs implanted with mesenchymal stem cell-loaded ceramics were significantly stronger than those that received cell-free ceramics. These studies demonstrate that human mesenchymal stem cells can regenerate bone in a clinically significant osseous defect and may therefore provide an alternative to autogenous bone grafts.
Chromosome abnormalities in non‐small cell lung cancer pleural effusions: Cytogenetic indicators of disease subgroups (1993)

A cytogenetic study of pleural effusions (PE) containing metastatic or invasive tumor cells from 11 patients with non-small cell lung cancer (NSCLC) (3 squamous cell carcinomas [SQC] and 8 adenocarcinomas [ADC] including 1 giant cell variant) was performed to identify non-random chromosome abnormalities. Numerical abnormalities seen in > or = 30% of cases included gain of chromosomes 7 and 20, and loss of chromosomes 4, 9, 10, 13, 15, 16, 18, 19, 21, and 22. The most frequent structural abnormality involved rearrangement in 1p with breakpoints clustering at 1p10-p13. Other recurrent breakpoint regions, seen in > or = 30% of cases, occurred in chromosome region 3p10-p21, 3q11-q25, 6p11-p25, 6q13-q23, 7q11-q36, 9q32-q34, 11p11-p13, 11q13-q24, 13p/14p and/or 15p, 17p and 19p, with, in particular, apparent loss of 6q21-q27, 3p21-p26, 7q21-q22, 9p22-p24 (shortest regions of common overlap) and 17p. There was also recurrent gain of 1q23-q44, 8q13-q24, and 11q13-q23. These abnormalities were not restricted to a particular histological subtype, with the exception of +8 and a breakpoint in 9q32-q34, which were seen only in ADC. The 9q32-q34 breakpoint observed in 4 ADC PE (including 1 giant cell variant) represents a new observation in NSCLC. These findings, when compared to those reported for primary NSCLC indicate cytogenetic differences between the two which may be associated with pleural invasion of NSCLC.
Critical role of MCP-1 in the pathogenesis of experimental colitis in the context of immune and enterochromaffin cells (2006)

Mucosal changes in inflammatory bowel disease (IBD) are characterized by ulcerative lesions accompanied by a prominent infiltrate of inflammatory cells including lymphocytes, macrophages, and neutrophils and alterations in 5-hydroxytryptamine (5-HT)-producing enterochromaffin (EC) cells. Mechanisms involved in recruiting and activating these cells are thought to involve a complex interplay of inflammatory mediators. Studies in clinical and experimental IBD have shown the upregulation of various chemokines including monocyte chemoattractant protein (MCP)-1 in mucosal tissues. However, precise information on the roles of this chemokine or the mechanisms by which it takes part in the pathogenesis of IBD are not clear. In this study, we investigated the role of MCP-1 in the development of hapten-induced experimental colitis in mice deficient in MCP-1. Our results showed a significant reduction in the severity of colitis both macroscopically and histologically along with a decrease in mortality in MCP-1-deficient mice compared with wild-type control mice. This was correlated with a downregulation of myeloperoxidase activity, IL-1beta, IL-12p40, and IFN-gamma production, and infiltration of CD3+ T cells and macrophages in the colonic mucosa. In addition, we observed significantly lower numbers of 5-HT-expressing EC cells in the colon of MCP-1-deficient mice compared with those in wild-type mice after dinitrobenzenesulfonic acid. These results provide evidence for a critical role of MCP-1 in the development of colonic inflammation in this model in the context of immune and enteric endocrine cells.