gebhart/patrepeval huggingface dataset:
Vascular Endothelial Growth Factor Is Expressed in Multiple Sclerosis Plaques and Can Induce Inflammatory Lesions in Experimental Allergic Encephalomyelitis Rats (2002)

The active lesions in multiple sclerosis (MS) are characterized by blood-brain-barrier (BBB) breakdown, upregulation of adhesion molecules on capillary endothelial cells, and perivascular inflammation, suggesting that altered vessel permeability and activated endothelial cells are involved in the pathogenesis of the disease. Vascular endothelial growth factor (VEGF) mediates multiple aspects of blood vessel physiology, including regulation of growth, permeability, and inflammation. To investigate a possible relationship between VEGF expression and CNS autoimmune disease, we examined VEGF expression in MS plaques compared to normal white matter by immunohistochemistry and in situ hybridization. VEGF expression was consistently upregulated in both acute and chronic MS plaques. We also examined VEGF expression during the course of experimental allergic encephalomyelitis (EAE) in rats. VEGF-positive cells with astrocytic morphology increased in the spinal cord during the development of EAE and were found in association with inflammatory cells. Furthermore, intracerebral infusion of VEGF in animals previously immunized with myelin basic protein induced an inflammatory response in the brain, whereas infusion of vehicle, or infusion of VEGF in naive animals, did not. These results suggest that overexpression of VEGF may exacerbate the inflammatory response in autoimmune diseases of the CNS by inducing focal BBB breakdown and migration of inflammatory cells into the lesions.
Cloning and characterization of the segment polarity gene cubitus interruptus Dominant of Drosophila. (1990)

The segment polarity mutation, cubitus interruptus Dominant (ciD), of Drosophila melanogaster causes defects in the posterior half of every embryonic segment. We cloned sequences from the ciD region on the proximal fourth chromosome by "tagging" the gene with the transposable element P. Genetic and molecular evidence indicates that the P-element insertions, which all occurred within the same restriction fragment, are in 5'-regulatory regions of the ciD gene within 3 kb of the first exon of its transcript. The putative ciD transcript was identified on the basis of its absence in homozygous ciD embryos. Its spatial pattern of expression during development is unusual in that, unlike most other segmentation genes, it exhibits uniform expression throughout cellular blastoderm and gastrulation and does not resolve into a periodic pattern until the end of the fast phase of germ-band elongation when it is present in 15 broad segmentally repeating stripes along the anterior-posterior axis of the embryo. Registration of the ciD stripes of expression relative to the stripes of other segment polarity genes shows that ciD is expressed in the anterior three-quarters of every segment. This registration does not correlate with the pattern defects observed in ciD mutants. Sequence analysis indicates that the protein encoded by the ciD transcript contains a domain of five tandem amino acid repeats that have sequence similarity to the zinc-finger repeats of the Xenopus transcription factor TFIIIA and that share the highest degree of identity with the human zinc-finger protein GLI, which has been found to be amplified in several human glioblastomas.
Immunologic aspects of human thyroid cancer.Humoral and cell-mediated immunity, and a trial of immunotherapy (1975)

Immunologic studies were performed on 16 patients with thyroid cancer. Circulating leukocyte counts increased, parallel to development of the terminal stage of disease, but total lymphocytes decreased. Serum immunoglobulin and complement were high, even though almost all patients showed negative antithyroid antibodies. Delayed skin hypersensitivity to bacterial and viral antigens and lymphocyte responsivity to PHA were not impaired at the initial stage of disease, but were impaired in terminal illness. Cell-mediated immunity (CMI) to tumor antigens(s) was measured using the assays of lymphotoxin, migration inhibition factor, and peripheral leukocyte migration inhibition. A few patients showed significant response to tumor antigen, but not to homogenates of Graves' thyroid gland. Active immunotherapy was applied to three patients. Two patients, who were in the terminal stage of illness, could not develop generalized CMI; immunization did not alter the patients' rapid downhill course. One patient developed in vitro evidence of CMI against cancer tissue antigens, associated with decrease in tumor size. Four months after immunization, CMI was impaired in autologous plasma culture, but not in cultures in allogenic normal plasma.
Von Willebrand Factor Expression in a Shiga Toxin-mediated Primate Model of Hemolytic Uremic Syndrome (2002)

von Willebrand Factor (vWF) is stored and released from activated or damaged endothelial cells and platelets, and its multimers have considerable prothrombotic properties. To investigate the role of vWF in the pathogenesis of post-diarrheal (D+) hemolytic uremic syndrome (HUS), we used a baboon model to study vWF expression following the intravenous administration of 100 ng/kg of Shiga toxin 1 (Stx 1), given either as a single dose, or as four divided doses, with and without lipopolysaccharide (LPS). vWF antigen was measured in plasma and urine obtained at 0, 12, 24, 36, 48, and 60 h by enzyme-linked immunosorbent assay (ELISA), and immunohistochemical expression of vWF in renal tissue obtained at autopsy was quantified by image analysis. Animals that received the single dose of Stx 1, or the four divided doses of Stx 1 plus LPS uniformly developed HUS, but those that received divided doses of Stx 1 without LPS, or LPS alone did not. Plasma vWF levels rose significantly in animals that received LPS, with or without Stx 1; but not in those that received Stx 1 alone. Urine vWF levels were generally undetectable. vWF expression was greater in renal tissue of animals that developed HUS than in those that did not, and was seen in both glomeruli, and, especially, peritubular capillaries. Since HUS developed in animals that did not experience a rise in plasma vWF levels, it does not appear that LPS-mediated systemic vWF release is essential to the pathogenesis of HUS in our model. The renal tissue findings, however, suggest a role for Stx-mediated intrarenal vWF release in the acute nephropathy of D+ HUS.
Boolean matching for complex PLBs in LUT-based FPGAs with application to architecture evaluation (1998)

In this paper, we developed Boolean matching techniques for complex programmable logic blocks (PLBs) in LUT-based FPGAs. A complex PLB can not only be used as a K-input LUT, but also can implement some wide functions of more than K variables. We apply previous and develop new functional decomposition methods to match wide functions to PLBs. We can determine exactly whether a given wide function can be implemented with a XC4000 CLB or other three PLB architectures (including the XC5200 CLB). We evaluate functional capabilities of the four PLB architectures on implementing wide functions in MCNC benchmarks. Experiments show that the XC4000 CLB can be used to implement up to 98% of 6-cuts and 88% of 7-cuts in MCNC benchmarks, while two of the other three PLB architectures have a smaller cost in terms of logic capability per silicon area. Our results are useful for designing future logic unit architectures in LUT based FPGAs.
In Vitro Synergism of Colistin and N-acetylcysteine against Stenotrophomonas maltophilia (2019)

<i>Stenotrophomonas maltophilia</i> is an emerging global opportunistic pathogen, responsible for a wide range of human infections, including respiratory tract infections. Intrinsic multidrug resistance and propensity to form biofilms make <i>S. maltophilia</i> infections recalcitrant to treatment. Colistin is among the second-line options in case of difficult-to-treat <i>S. maltophilia</i> infections, with the advantage of being also administrable by nebulization. We investigated the potential synergism of colistin in combination with N-acetylcysteine (NAC) (a mucolytic agent with antioxidant and anti-inflammatory properties) against <i>S. maltophilia</i> grown in planktonic phase and biofilm. Eighteen <i>S. maltophilia</i> clinical isolates (comprising three isolates from cystic fibrosis (CF) and two trimethoprim-sulfamethoxazole (SXT)-resistant strains) were included. Checkerboard assays showed a synergism of colistin/NAC combinations against the strains with colistin Minimum Inhibitory Concentration (MIC) >2 µg/mL (<i>n</i> = 13), suggesting that NAC could antagonize the mechanisms involved in colistin resistance. Nonetheless, time-kill assays revealed that NAC might potentiate colistin activity also in case of lower colistin MICs. A dose-dependent potentiation of colistin activity by NAC was also clearly observed against <i>S. maltophilia</i> biofilms, also at sub-MIC concentrations. Colistin/NAC combinations, at concentrations likely achievable by topical administration, might represent a valid option for the treatment of <i>S. maltophilia</i> respiratory infections and should be examined further.
A bisected pupil for studying single-molecule orientational dynamics and its application to three-dimensional super-resolution microscopy (2014)

A phase mask design that we term a "bisected pupil" (BSP) provides several advantages for single-molecule optical imaging. When using the BSP with a dual-polarization optical Fourier processing system, both the position and dipole orientation of individual fluorescent molecules may be measured from a single camera image. In the context of single-molecule super-resolution microscopy, this technique permits one to diagnose, and subsequently to remove imaging artifacts resulting from orientation-induced localization errors. If the molecules labeling a structure are rotationally mobile, thus mitigating dipole orientation errors, this technique enables super-resolution imaging in three dimensions. We present simulations and experimental verification.
Gateway compatible vectors for analysis of gene function in the zebrafish (2007)

The recent establishment of recombination-based cloning systems has greatly facilitated the analysis of gene function by allowing rapid and high-efficiency generation of plasmid constructs. However, the use of such an approach in zebrafish requires the availability of recombination-compatible plasmids that are appropriate for functional studies in zebrafish embryos. In this work, we describe the construction and validation of Gateway compatible vectors based on commonly used zebrafish plasmids. We have generated pCS-based plasmids that allow rapid generation of both N-terminal and C-terminal fusion proteins, and we demonstrate that mRNA synthesized from these plasmids encodes functional native or fusion proteins in injected zebrafish embryos. In parallel, we have established similar Gateway plasmids containing Tol2 cis elements that promote efficient integration into the zebrafish genome and allow expression of native or fusion proteins in a tissue-specific manner in the zebrafish embryo. Finally, we demonstrate the use of this system to rapidly identify tissue-specific cis elements to aid the establishment of blood vessel-specific transgenic constructs. Taken together, this work provides an important platform for the rapid functional analyses of open reading frames in zebrafish embryos.
A novel hetero-material gate (HMG) MOSFET for deep-submicron ULSI technology (1998)

A novel hetero-material gate MOSFET intended for integration into the existing deep-submicron silicon technology is proposed and simulated. It is shown that by adding a layer of material with a larger workfunction to the source side of the gate, short-channel effects can be greatly suppressed without degrading the driving ability. The threshold voltage roll-off can be compensated and tuned by controlling the length of this second gate. The new structure has great potential in breaking the barrier of deep-suhmicron MOSFET's scaling beyond 0.1 /spl mu/m technologies.
Subcellular Distribution of Thyroxine 5′-Deiodinase in the Rat Kidney: A Plasma Membrane Location* (1978)

The enzymatic activity in rat kidney homogenates mediating the conversion of T4 to T3 has been previously shown to be particulate. The subcellular organelle responsible for T4 5′-deiodination, however, has not been identified. Enzymatic activity was assessed with outer ring 125I-labeled L-T4 as the substrate and the iodothyronines were separated by descending paper chromatography. Comparison of the distribution of T4 5′-deiodinase activity with that of established enzyme markers of subcellular organelles demonstrated: 1) T4 5′-deiodinase activity paralleled that of plasma membrane enzyme markers in subcellular fractions prepared by differential centrifugation, with 80% of the T4 5′-deiodinase and (Na+/K+)-ATPase equally distributed in the crude nuclear and microsomal fractions; 2) the smooth microsomal fraction, known to be contaminated with plasma membrane in ki ney tissue preparations, contained the bulk of the T4 5′-deiodinase activity and plasma membrane marker enzymes found in the microsomal fraction; and 3) purified plasma membrane showed enrichment of T4 5′-deiodinase comparable to that of the known plasma membrane enzyme (Na+/K+)-ATPase. These data suggest that T4 5′-deiodinase in kidney tissue is an enzyme of the plasmalemma.
The 65nm tunneling field effect transistor (TFET) 0.68μm/sup 2/ 6T memory cell and multi-V/sub th/ device (2005)

The tunneling field effect transistor (TFET) is fabricated using a 65nm standard CMOS process flow. The short-narrow TFET offers an on-current of 550/spl mu/A//spl mu/m which is comparable to the reference MOSFET device. Due to the integrated substrate/well contact the effective area of the TFET is smaller compared to the corresponding MOSFET. Thus, the size of a system-on-a-chip design is reduced by more than 5%. The quantum-mechanical TFET is able to extend the epoch of the CMOS technology by showing reduced short channel effects and smaller leakage currents. A multi-threshold TFET device is proposed which does not need additional implantation steps. A 0.68/spl mu/m/sup 2/ 6 transistor memory cell is fabricated using TFETs and MOSFETs showing the compatibility of MOSFET and TFET and a decrease of the memory array area of approximately 3%.
The Sialyltransferase “Sialylmotif” Participates in Binding the Donor Substrate CMP-NeuAc (1995)

All members of the sialyltransferase gene family cloned to date contain a conserved region, the "sialylmotif," consisting of 48-49 amino acids in the center of the coding sequence. To investigate the function of this motif, mutant constructs of the Gal beta 1,4GlcNAc alpha 2,6-sialyltransferase were designed by site-directed mutagenesis, replacing 11 individual conserved amino acids with alanine. Each of the mutants was expressed in COS-1 cells, and eight of these retained sialyltransferase activity, allowing comparison of their enzymatic properties with that of the wild type enzyme. Kinetic analysis showed that six of eight mutants had a 3-12-fold higher Km for the donor substrate CMP-NeuAc relative to the wild type enzyme, while the Km values for the acceptor substrate were within 0.5-1.2-fold of the wild type for all eight mutants evaluated. The Ki of the donor substrate analog CDP was also evaluated for the recombinant sialyltransferase with the Val to Ala mutation at residue 220, which produced a 6-fold increase in Km of CMP-NeuAc. A corresponding increase in Ki of 3.4-fold was observed for CDP, indicating a decreased affinity for the cytidine nucleotide. Taken together, these results suggest that the conserved sialylmotif in the sialyltransferase gene family participates in the binding of the common donor substrate, CMP-NeuAc.
A comparative analysis of three different techniques for the detection of breast cancer cells in bone marrow (1991)

Three different methods, morphologic, immunocytochemic, and fluorescence activated cell sorter (FC) analysis, were compared with respect to their efficiency in detecting breast cancer cells in bone marrow. In the first series of experiments, the three techniques were compared using bone marrow cells artificially mixed with a known amount of breast cancer cells, whereas in a second series bone marrow from breast cancer patients with bone metastases were used. The following results were obtained: When mixtures of the first series were analyzed, FC analysis detected from 1% to 10% of breast cancer cells in bone marrow (0.2% was a border line value), the morphologic method detected from 0.05% to 10%, and the immunocytochemic method, which was clearly superior, detected breast cancer cells in all mixtures (from 0.00025% to 10%). It was noted that, with both the morphologic and immunocytochemic methods, the percentage of breast cancer cells detected was 2 to 360 times higher than the percentage of added cells, and enrichment was inversely proportional to the percentage of added cells. This result could be a result of different separation of cells during centrifugation due to the different density of breast cancer cells. The superiority of the immunocytochemic method was confirmed in the second series of experiments.
Human Cytomegalovirus Inhibition by Cardiac Glycosides: Evidence for Involvement of the hERG Gene (2012)

Infection with human cytomegalovirus (HCMV) continues to be a major threat for pregnant women and the immunocompromised population. Although several anti-HCMV therapies are available, the development of new anti-HCMV agents is highly desired. There is growing interest in identifying compounds that might inhibit HCMV by modulating the cellular milieu. Interest in cardiac glycosides (CG), used in patients with congestive heart failure, has increased because of their established anticancer and their suggested antiviral activities. We report that the several CG--digoxin, digitoxin, and ouabain--are potent inhibitors of HCMV at nM concentrations. HCMV inhibition occurred prior to DNA replication, but following binding to its cellular receptors. The levels of immediate early, early, and late viral proteins and cellular NF-κB were significantly reduced in CG-treated cells. The activity of CG in infected cells correlated with the expression of the potassium channel gene, hERG. CMV infection upregulated hERG, whereas CG significantly downregulated its expression. Infection with mouse CMV upregulated mouse ERG (mERG), but treatment with CG did not inhibit virus replication or mERG transcription. These findings suggest that CG may inhibit HCMV by modulating human cellular targets associated with hERG and that these compounds should be studied for their antiviral activities.
Activation-induced Modification in the CD3 Complex of the γδ T Cell Receptor (2002)

The T cell antigen receptor complexes expressed on alphabeta and gammadelta T cells differ not only in their respective clonotypic heterodimers but also in the subunit composition of their CD3 complexes. The gammadelta T cell receptors (TCRs) expressed on ex vivo gammadelta T cells lack CD3delta, whereas alphabeta TCRs contain CD3delta. While this result correlates with the phenotype of CD3delta(-/-) mice, in which gammadelta T cell development is unaffected, it is inconsistent with the results of previous studies reporting that CD3delta is a component of the gammadelta TCR. Since earlier studies examined the subunit composition of gammadelta TCRs expressed on activated and expanded peripheral gammadelta T cells or gammadelta TCR(+) intestinal intraepithelial lymphocytes, we hypothesized that activation and expansion may lead to changes in the CD3 subunit composition of the gammadelta TCR. Here, we report that activation and expansion do in fact result in the inclusion of a protein, comparable in mass and mobility to CD3delta, in the gammadelta TCR. Further analyses revealed that this protein is not CD3delta, but instead is a differentially glycosylated form of CD3gamma. These results provide further evidence for a major difference in the subunit composition of alphabeta- and gammadelta TCR complexes and raise the possibility that modification of CD3gamma may have important functional consequences in activated gammadelta T cells.
Effects of a Chlorhexidine Gluconate-Containing Mouthwash on the Vitality and Antimicrobial Susceptibility of In Vitro Oral Bacterial Ecosystems (2003)

Oral bacterial microcosms, established using saliva inocula from three individuals, were maintained under a feast-famine regime within constant-depth film fermenters. Steady-state communities were exposed four times daily, postfeeding, to a chlorhexidine (CHX) gluconate-containing mouthwash (CHXM) diluted to 0.06% (wt/vol) antimicrobial content. The microcosms were characterized by heterotrophic plate counts and PCR-denaturing gradient gel electrophoresis (DGGE). CHXM caused significant decreases in both total anaerobe and total aerobe/facultative anaerobe counts (P < 0.05), together with lesser decreases in gram-negative anaerobes. The degree of streptococcal and actinomycete inhibition varied considerably among individuals. DGGE showed that CHXM exposure caused considerable decreases in microbial diversity, including marked reductions in Prevotella sp. and Selenomonas infelix. Pure-culture studies of 10 oral bacteria (eight genera) showed that Actinomyces naeslundii, Veillonella dispar, Prevotella nigrescens, and the streptococci were highly susceptible to CHX, while Lactobacillus rhamnosus, Fusobacterium nucleatum, and Neisseria subflava were the least susceptible. Determination of the MICs of triclosan, CHX, erythromycin, penicillin V, vancomycin, and metronidazole for microcosm isolates, before and after 5 days of CHXM exposure, showed that CHXM exposure altered the distribution of isolates toward those that were less susceptible to CHX (P < 0.05). Changes in susceptibility distributions for the other test agents were not statistically significant. In conclusion, population changes in plaque microcosms following repeated exposure to CHXM represented an inhibition of the most susceptible flora with a clonal expansion of less susceptible species.