gebhart/patrepeval huggingface dataset:
T-cell activation in autoimmune and inflammatory diseases (1998)

Recent progress in experimental models and human genetic linkage studies have provided new insight into the pathogenesis of autoimmunity. Both antigen-specific and antigen-nonspecific signals are crucial in the development of autoimmune disease. Interestingly, several of the single gene loci that have been identified as potential causes of autoimmune disease encode molecules that regulate antigen-nonspecific modulation of immunity. The focus of this review is the role of the opposing signals transduced by the CD28 and cytotoxic T-lymphocyte antigen-4 receptors that bind the B7 costimulatory ligands. Recent studies suggest that CD28 signals activate T cells, whereas cytotoxic T-lymphocyte antigen-4 signals deactivate T cells. importantly, both signals contribute to the induction of autoimmunity and offer novel targets for future therapeutic strategies to treat autoimmune disease.
Combination treatment with Grb7 peptide and Doxorubicin or Trastuzumab (Herceptin) results in cooperative cell growth inhibition in breast cancer cells (2007)

Grb7 has potential importance in the progression of cancer. We have previously identified a novel peptide that binds to the SH2 domain of Grb7 and inhibits its association with several different receptor tyrosine kinases. We have synthesised the Grb7 peptide, G7-18NATE, with two different cell penetrating peptides, Penetratin and Tat. In this study, we have shown that both Penetratin- and Tat-conjugated G7-18NATE peptides are able to inhibit the proliferation of SK-BR-3, ZR-75-30, MDA-MB-361 and MDA-MB-231 breast cancer cells. There was no significant effects on breast cancer MCF-7cells, non-malignant MCF 10A or 3T3 cells. In addition, there was no significant inhibition of proliferation by Penetratin or Tat alone or by their conjugates with arbitrary peptide sequence in any of the cell lines tested. We determined the EC50 of G7-18NATE-P peptide for SK-BR-3 cell proliferation to be 7.663 x 10(-6) M. Co-treatment of G7-18NATE-P peptide plus Doxorubicin in SK-BR-3 breast cancer cells resulted in an additional inhibition of proliferation, resulting in 56 and 84% decreases in the Doxorubicin EC50 value in the presence of 5 x 10(-6) and 1.0 x 10(-5) M G7-18NATE-P peptide, respectively. Importantly, the co-treatment with Doxorubicin and the delivery peptide did not change the Doxorubicin EC50. Since Grb7 associates with ErbB2, we assessed whether the peptide inhibitor would have a combined effect with a molecule that targets ErbB2, Herceptin. Co-treatment of Herceptin plus 1.0 x 10(-5) M G7-18NATE-P peptide in SK-BR-3 cells resulted in a 46% decrease in the Herceptin EC50 value and no decrease following the co-treatment with Herceptin and penetratin alone. This Grb7 peptide has potential to be developed as a therapeutic agent alone, in combination with traditional chemotherapy, or in combination with other targeting molecules.
A P450‐centric view of plant evolution (2011)

Being by far the largest family of enzymes to support plant metabolism, the cytochrome P450s (CYPs) constitute an excellent reporter of metabolism architecture and evolution. The huge superfamily of CYPs found in angiosperms is built on the successful evolution of 11 ancestral genes, with very different fates and progenies. Essential functions in the production of structural components (membrane sterols), light harvesting (carotenoids) or hormone biosynthesis kept some of them under purifying selection, limiting duplication and sub/neofunctionalization. One group (the CYP71 clan) after an early trigger to diversification, has kept growing, producing bursts of gene duplications at an accelerated rate. The CYP71 clan now represents more than half of all CYPs in higher plants. Such bursts of gene duplication are likely to contribute to adaptation to specific niches and to speciation. They also occur, although with lower frequency, in gene families under purifying selection. The CYP complement (CYPomes) of rice and the model grass weed Brachypodium distachyon have been compared to view evolution in a narrower time window. The results show that evolution of new functions in plant metabolism is a very long-term process. Comparative analysis of the plant CYPomes provides information on the successive steps required for the evolution of land plants, and points to several cases of convergent evolution in plant metabolism. It constitutes a very useful tool for spotting essential functions in plant metabolism and to guide investigations on gene function.
Photodegradation dynamics of pure microcystin variants with illumination of fixed wavelength UV-lights (2004)

Photolysis of microcystins by UV irradiation and the effects of different environmental factors on efficiency of UV degradation were studied. The results indicated that the rates of the photolytical degradation reactions of microcystin-LR and RR-follow pseudo-first-order kinetic process. The results also showed that the concentrations of two microcystin variants decreased significantly by UV-C Irradiation; the wavelength and intensitiy of UV irradiation are two very important factors affecting the rate of degradation; temperature and pH value could also affect the half life of degradation rates. When irradiated by weaker UV-Iight, isomerization could be detected in the course of photolytical degradation. The concentrations of two isomers transformed from microcystin-LR reached its maximum at the third minute and decreased with the time afterwards. To simulate photolysis of microcystins in the field water body, microcystins with low concentration were used. It was found that UV-C illumination was capable of decomposing over 95% of microcystins within 40 min. In the presence of humic substances the photodecomposition slowed down to a certain extent. These results are valuable in using UV irradiation for elimination microcystins from raw water.
On Network-level Clusters for Spam Detection. (2010)

IP-based blacklist is an effective way to filter spam emails. However, building and maintaining individual IP addresses in the blacklist is difficult, as new mali-cious hosts continuously appear and their IP addresses may also change over time. To mitigate this problem, researchers have proposed to replace individual IP ad-dresses in the blacklist with IP clusters, e.g., BGP clus-ters. In this paper, we closely examine the accuracy of IP-cluster-based approaches to understand their effec-tiveness and fundamental limitations. Based on such understanding, we propose and implement a new clus-tering approach that considers both network origin and DNS information, and incorporate it with SpamAssas-sin, a popular spam filtering system widely used today. Applying our approach to a 7-month email trace col-lected at a large university department, we can reduce the false negative rate by 50 % compared with directly applying various public IP-based blacklists without in-creasing the false positive rate. Furthermore, using hon-eypot email accounts and real user accounts, we show that our approach can capture 30 %- 50 % of the spam emails that slip through SpamAssassin today. 1
Antibodies to Envelope Glycoprotein of Dengue Virus during the Natural Course of Infection Are Predominantly Cross-Reactive and Recognize Epitopes Containing Highly Conserved Residues at the Fusion Loop of Domain II (2008)

The antibody response to the envelope (E) glycoprotein of dengue virus (DENV) is known to play a critical role in both protection from and enhancement of disease, especially after primary infection. However, the relative amounts of homologous and heterologous anti-E antibodies and their epitopes remain unclear. In this study, we examined the antibody responses to E protein as well as to precursor membrane (PrM), capsid, and nonstructural protein 1 (NS1) of four serotypes of DENV by Western blot analysis of DENV serotype 2-infected patients with different disease severity and immune status during an outbreak in southern Taiwan in 2002. Based on the early-convalescent-phase sera tested, the rates of antibody responses to PrM and NS1 proteins were significantly higher in patients with secondary infection than in those with primary infection. A blocking experiment and neutralization assay showed that more than 90% of anti-E antibodies after primary infection were cross-reactive and nonneutralizing against heterologous serotypes and that only a minor proportion were type specific, which may account for the type-specific neutralization activity. Moreover, the E-binding activity in sera of 10 patients with primary infection was greatly reduced by amino acid replacements of three fusion loop residues, tryptophan at position 101, leucine at position 107, and phenylalanine at position 108, but not by replacements of those outside the fusion loop of domain II, suggesting that the predominantly cross-reactive anti-E antibodies recognized epitopes involving the highly conserved residues at the fusion loop of domain II. These findings have implications for our understanding of the pathogenesis of dengue and for the future design of subunit vaccine against DENV as well.
Butyrate infusions in the ovine fetus delay the biologic clock for globin gene switching. (1988)

The switch from fetal to adult hemoglobin expression is regulated in many mammalian species by a developmental clock-like mechanism and determined by the gestational age of the fetus. Prolonging fetal globin gene expression is of considerable interest for therapeutic potential in diseases caused by abnormal beta-globin genes. Butyric acid, which is found in increased plasma concentrations in infants of diabetic mothers who have delayed globin gene switching, was infused into catheterized fetal lambs in utero during the time of the normal globin gene switch period. The globin gene switch was significantly delayed in three of four butyrate-treated fetuses compared with controls and was entirely prevented in one fetus in whom the infusion was begun before the globin switch was under way. These data provide a model for investigating and arresting the biologic clock of hemoglobin switching.
Strategies for stabilising tetanus toxoid towards the development of a single-dose tetanus vaccine. (1996)

The stability of tetanus toxoid (TT) has been investigated for the purpose of enhancing its immunogenicity when encapsulated in TT-polylactide-co-glycolide (PLGA) microspheres. In this paper we describe our simulations of various potential inactivating events during microsphere processing and release of the antigen. These include: i) processing aqueous TT solutions in the presence of organic solvents, ii) exposing lyophilized TT to moisture, and iii) incubating vaccine with the degrading PLGA. At 37 degrees C, TT began to aggregate in solution a few hours after the addition of either methylene chloride or ethyl acetate to form a single oil-water interface. Similarly, exposure of the lyophilized vaccine to elevated humidity caused the antigen to lose solubility. Previous analysis of moisture-induced aggregates has revealed that formaldehyde, which is stored in labile linkages in the vaccine following its detoxification, is the precursor to the reactive species in the principal aggregation pathway [1]. Methods to inhibit this mechanism, such as blocking nucleophilic amino groups of TT with succinic anhydride, were verified. Succinylation of TT resulted in the incorporation of 10-fold greater antigenically active vaccine in PLGA microspheres relative to the unmodified TT following processing by double-emulsion/solvent evaporation with ethyl acetate, strongly suggesting the formaldehyde-mediated aggregation pathway also occurs during the deleterious conditions of microsphere processing. Incubation of solutions of TT in the presence of excess blank (unloaded) poly (D,L) lactide (mol. wt. 2000) microspheres led to a dramatic reduction in pH (approximately 3.2 units after one day at 45 degrees C) and simultaneous precipitation of TT. Stabilisation in the presence of the degrading polymer is likely to be the final obstacle before controlled-release preparations can be formulated to release antigenically active TT over extended time periods. Hence, mechanistic analyses as described here may be crucial for the development of effective single-dose vaccines.
Murine mucopolysaccharidosis type VII. Characterization of a mouse with beta-glucuronidase deficiency. (1989)

We have characterized a new mutant mouse that has virtually no beta-glucuronidase activity. This biochemical defect causes a murine lysosomal storage disease that has many interesting similarities to human mucopolysaccharidosis type VII (MPS VII; Sly syndrome; beta-glucuronidase deficiency). Genetic analysis showed that the mutation is inherited as an autosomal recessive that maps to the beta-glucuronidase gene complex, [Gus], on the distal end of chromosome 5. Although there is a greater than 200-fold reduction in the beta-glucuronidase mRNA concentration in mutant tissues, Southern blot analysis failed to detect any abnormalities in the structural gene, Gus-sb, or in 17 kb of 5' flanking and 4 kb of 3' flanking sequences. Surprisingly, a sensitive S1 nuclease assay indicated that the relative level of kidney gusmps mRNA responded normally to androgen induction by increasing approximately 11-fold. Analysis of this mutant mouse may offer valuable information on the pathogenesis of human MPS VII and provide a useful system in which to study bone marrow transplantation and gene transfer methods of therapy.
Mannan‐Binding Lectin Recognizes Structures on Ischaemic Reperfused Mouse Kidneys and is Implicated in Tissue Injury (2005)

Organ damage as a consequence of ischaemia and reperfusion (I/R) is a major clinical problem in an acute renal failure and transplantation. Ligands on surfaces of endothelial cells that are exposed due to the ischaemia may be recognized by pattern recognition molecules such as mannan-binding lectin (MBL), inducing complement activation. We examined the contribution of the MBL complement pathway in a bilateral renal I/R model (45 min of ischaemia followed by 24 h of reperfusion), using transgenic mice deficient in MBL-A and MBL-C [MBL double knockout (MBL DKO)] and in wildtype (WT) mice. Kidney damages, which were evaluated by levels of blood urea nitrogen (BUN) and creatinine, showed that MBL DKO mice were significantly protected compared with WT mice. MBL DKO mice, reconstituted with recombinant human MBL, showed a dose-dependent severity of kidney injury increasing to a comparable level to WT mice. Acute tubular necrosis was evident in WT mice but not in MBL DKO mice after I/R, confirming renal damages in WT mice. MBL ligands in kidneys were observed to be present after I/R but not in sham-operated mice. C3a (desArg) levels in MBL DKO mice were decreased after I/R compared with that in WT mice, indicating less complement activation that was correlated with less C3 deposition in the kidneys of MBL DKO mice. Our data implicate a role of MBL in I/R-induced kidney injury.
Immunotherapeutic Potential of Oncolytic Vaccinia Virus (2014)

The concept of oncolytic viral therapy was based on the hypothesis that engineering tumor-selectivity into the replication potential of viruses would permit direct destruction of tumor cells as a result of viral-mediated lysis, resulting in amplification of the therapy exclusively within the tumor environment. The immune response raised by the virus was not only considered to be necessary for the safety of the approach, but also something of a hindrance to optimal therapeutic activity and repeat dosing. However, the pre-clinical and subsequent clinical success of several oncolytic viruses expressing selected cytokines has demonstrated the potential for harnessing the immune response as an additional and beneficial mechanism of therapeutic activity within the platform. Over the last few years, a variety of novel approaches have been incorporated to try to enhance this immunotherapeutic activity. Several innovative and subtle approaches have moved far beyond the expression of a single cytokine transgene, with the hope of optimizing anti-tumor immunity while having minimal detrimental impact on viral oncolytic activity.
Calculation of Fluctuations in Boundary Layers of Nanowire Field-Effect Biosensors (2010)

Fluctuations in the biofunctionalized boundary layers of nanowire field-effect biosensors are investigated by using the stochastic linearized Poisson-Boltzmann equation. The noise and fluctuations considered here are due to the Brownian motion of the biomolecules in the boundary layer, i.e., the various orientations of the molecules with respect to the surface are associated with their probabilities. The probabilities of the orientations are calculated using their free energy. The fluctuations in the charge distribution give rise to fluctuations in the electrostatic potential and hence in the current through the semiconductor transducer of the sensor, both of which are calculated. A homogenization result for the variance and covariance of the electrostatic potential is presented. In the numerical simulations, a cross section of a silicon nanowire on a flat surface including electrode and back-gate contacts is considered. The biofunctionalized boundary layer contains single-stranded or double-stranded DNA oligomers, and varying values of the surface charge, of the oligomer length, and of the electrolyte ionic strength are investigated.
Technology for sub-50nm DRAM and NAND flash manufacturing (2006)

This paper discusses whether memory technologies can continue advances beyond sub-50nm node especially for DRAM and NAND flash memories. First, the barriers to shrink technology are addressed for DRAM and NAND flash memories, depending on their inherent operation principles. Then, details of technology solutions are introduced and its manufacturability is examined. Beyond 30nm node, It is expected that 3-dimensional transistor scheme is needed for both logic and memory array in addition to the development of new materials and structural technologies
Circulating Breast Tumor Cells Exhibit Dynamic Changes in Epithelial and Mesenchymal Composition (2013)

Epithelial-mesenchymal transition (EMT) of adherent epithelial cells to a migratory mesenchymal state has been implicated in tumor metastasis in preclinical models. To investigate its role in human cancer, we characterized EMT in circulating tumor cells (CTCs) from breast cancer patients. Rare primary tumor cells simultaneously expressed mesenchymal and epithelial markers, but mesenchymal cells were highly enriched in CTCs. Serial CTC monitoring in 11 patients suggested an association of mesenchymal CTCs with disease progression. In an index patient, reversible shifts between these cell fates accompanied each cycle of response to therapy and disease progression. Mesenchymal CTCs occurred as both single cells and multicellular clusters, expressing known EMT regulators, including transforming growth factor (TGF)-β pathway components and the FOXC1 transcription factor. These data support a role for EMT in the blood-borne dissemination of human breast cancer.
Induction of Cross-Reactive Antibodies to Novel H7N9 Influenza Virus by Recombinant Newcastle Disease Virus Expressing a North American Lineage H7 Subtype Hemagglutinin (2013)

Severe human disease caused by the emerging H7N9 influenza virus in China warrants a rapid response. Here, we present a recombinant Newcastle disease virus expressing a North American lineage H7 influenza virus hemagglutinin. Sera from immunized mice were cross-reactive to a broad range of H7 subtype viruses and inhibited hemagglutination by the novel H7 hemagglutinin. Immunized mice were protected against a heterologous H7 subtype challenge, and genetic analysis suggested that cross-protective antibodies recognize conserved antigenic sites.
Oscillation-Based Prebond TSV Test (2013)

Testing the quality of prebond through-silicon vias (TSV) is a vital part of the Known-Good-Die test that is often necessary to retain a high compound yield for 3-D stacked integrated circuits. In this paper, we present a versatile prebond TSV test method applicable before wafer thinning when the deep end of the TSV is inaccessible as buried in the still-thick wafer. Technical merits include: 1) the ability to handle both the resistive open fault and the leakage fault in the same test structure; 2) a capability that allows an user to have a better measure of the severity of the fault; and 3) an all-digital and easy to implement design-for-testability circuit.
Developmental Changes in Cardiomyocytes Differentiated from Human Embryonic Stem Cells: A Molecular and Electrophysiological Approach (2007)

Cardiomyocytes derived from human embryonic stem cells constitute a promising cell source for the regeneration of damaged hearts. The assessment of their in vitro functional properties is mandatory to envisage appropriate cardiac cell-based therapies. In this study, we characterized human embryonic stem cell-derived cardiomyocytes over a 3-month period, using patch-clamp or intracellular recordings to assess their functional maturation and reverse transcriptase-polymerase chain reaction to evaluate the expression of ion channel-encoding subunits. I(to1) and I(K1), the transient outward and inward rectifier potassium currents, were present in cardiomyocytes only, whereas the rapid delayed rectifier potassium current (I(Kr)), pacemaker current (I(f)), and L-type calcium current (I(Ca,L)) could be recorded both in undifferentiated human embryonic stem cells and in cardiomyocytes. Most of the currents underwent developmental maturation in cardiomyocytes, as assessed by modifications in current density (I(to1), I(K1), and I(Ca,L)) and properties (I(f)). Ion-channel mRNAs were always present when the current was recorded. Intracellular recordings in spontaneously beating clusters of cardiomyocytes revealed changes in action potential parameters and in response to pharmacological tools according to time of differentiation. In summary, human embryonic stem cell-derived cardiomyocytes mature over time during in vitro differentiation, approaching an adult phenotype. Disclosure of potential conflicts of interest is found at the end of this article.
MDM: A Program to Compute Fully Informative Genotype Frequencies in Complex Breeding Schemes (2002)

In many genetics studies it is necessary to compute the expected frequencies of at marker loci and/or to infer the at chromosomal locations from the known at markers. This is the case, for example, for quantitative trait loci (QTL) detection, where likelihood ratio tests or multiple regressions are based on the probabilities of the different at a putative QTL location, given the at flanking markers. This is also the case for graphical genotypes (Young and Tanksley 1989), where it is wanted to estimate the genomic composition of the chromosomes (parental origin of the alleles) given the at markers. The calculations performed by most existing programs (e.g., for QTL detection) are based solely on the at the two closest markers flanking the putative position on each side, observed at only one generation. This is sufficient only if the population considered has issued from a single generation of effective recombination (e.g., BC 1 , F 2 ) and if marker are known without ambiguity. If there is ambiguity in marker (e.g., dominance, missing data) or if more than one effective meiosis has taken place (e.g., F 3 , recombinant inbred lines (RILs), advanced backcross generation), then additional markers further from the putative position and/or marker at previous generations may also be informative and could permit more accurate prediction of the genotype at the putative position.