gebhart/patrepeval huggingface dataset:
Vaccination with cytokines in autoimmune diseases (2008)

Most autoimmune diseases have an unknown etiology, but all involve cytokines cascade in their development. At the present time, several cytokines have been identified as major targets in various autoimmune diseases, involving the development of monoclonal antibodies (MAbs) against those cytokines. Even if MAbs are indeed efficient, the passive immunotherapies also present some disadvantages and are expensive. To counter this, several strategies have been developed, including active immunotherapy, based on the vaccination principle. The aim of such a strategy is to induce a B cell response and to obtain autoantibodies able to neutralize the interaction of the self-cytokine with its receptor. To that purpose, cytokines (entire or peptide) are either coupled with a protein-carrier or virus-like particle, or modified with foreign Th cell epitopes. DNA vaccination can also be used with cytokine sequences. This review focuses on the different vaccination strategies with cytokines (including Tumor Necrosis Factor (TNF)alpha, Interleukin-1beta (IL-1beta), IL-17) in different autoimmune diseases in preclinical studies; the benefit/risk ratio of such a strategy and the present development of clinical trials in some autoimmune diseases are also discussed.
Audotory intensity discrimination with bursts of reproducible noise (1975)

Auditory−intensity discrimination was investigated using gated bursts of reproducible noise. Weber fractions were determined at a number of energy levels with stimuli that differed in intensity, duration, and bandwidth. Weber’s law was approximated in all cases. In addition, discriminability was found to be somewhat dependent on burst duration and relatively independent of noise bandwidth; threshold signal−to−noise ratios improved when duration was increased from 10 to 100 msec, but not when bandwidth was increased from 500 to 5000 Hz. The data were compared with the results of a second experiment in which the stimuli were random—rather than pseudorandom—noises. Finally, the results of both experiments were compared with predictions about intensity discrimination derived from two theoretical models: (1) a Poisson−counting mechanism and (2) an energy detector incorporating additive internal noise. Subject Classification: 65.35, 65.58.
A comparison of four cathepsins (B, L, N and S) with collagenolytic activity from rabbit spleen (1988)

We have separated four cathepsins (B, L, N and S) from rabbit spleen. They are all collagen-degrading cysteine proteinases, with Mr values of 25,250, 23,500, 34,000 and 30,000 for cathepsin B, L, N and S respectively. Cathepsins B, N and S have isoelectric points of 5.4, 6.2 and 6.8 respectively, whereas cathepsin L exhibited multiple charge forms in the range 5.0-5.7. A comparison of their specific activity against a variety of protein and synthetic substrates shows many differences. These differences can be visually illustrated through isoelectric focusing and detection of enzymic activity with protein and synthetic-substrate overlays. By using an enzyme-linked immunosorbent assay based on the binding to chicken cystatin and detection with polyclonal and monoclonal antibodies to native cathepsins B and L, no cross-reactivity of the four native enzymes was observed. Studies on the co-operative or synergistic effect in degrading collagen indicated that, of the different combinations tested, only the combination of cathepsin B and N exhibited enhanced collagenolysis.
Learning Local Feature Descriptors Using Convex Optimisation (2014)

The objective of this work is to learn descriptors suitable for the sparse feature detectors used in viewpoint invariant matching. We make a number of novel contributions towards this goal. First, it is shown that learning the pooling regions for the descriptor can be formulated as a convex optimisation problem selecting the regions using sparsity. Second, it is shown that descriptor dimensionality reduction can also be formulated as a convex optimisation problem, using Mahalanobis matrix nuclear norm regularisation. Both formulations are based on discriminative large margin learning constraints. As the third contribution, we evaluate the performance of the compressed descriptors, obtained from the learnt real-valued descriptors by binarisation. Finally, we propose an extension of our learning formulations to a weakly supervised case, which allows us to learn the descriptors from unannotated image collections. It is demonstrated that the new learning methods improve over the state of the art in descriptor learning on the annotated local patches data set of Brown et al. and unannotated photo collections of Philbin et al.
Cooperative Regulation of Mcl-1 by Janus Kinase/STAT and Phosphatidylinositol 3-Kinase Contribute to Granulocyte-Macrophage Colony-Stimulating Factor-Delayed Apoptosis in Human Neutrophils (2001)

Polymorphonuclear neutrophils (PMN) are phagocytic cells constitutively programmed for apoptotic cell death. Exposure to GM-CSF delays apoptosis as measured by annexin-V staining and cell morphological change. We found that STAT5B, STAT1, and STAT3 DNA-binding activity was induced by GM-CSF. We also detected activation of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway after GM-CSF treatment which was inhibited by treatment with the PI 3-kinase inhibitors, wortmannin and LY294002. We investigated whether STAT or PI 3-kinase activity was necessary for the pro-survival response of GM-CSF in PMN. Exposure of PMN to GM-CSF in the presence of either AG-490, antisense STAT3 oligonucleotides, or wortmannin resulted in a partial inhibition of GM-CSF-mediated pro-survival activity. GM-CSF induced a time-dependent increase in the mRNA and protein expression of the anti-apoptotic Bcl-2-family protein, Mcl-1. We examined the hypothesis that Janus kinase/STAT and PI 3-kinase regulation of Mcl-1 contributed to GM-CSF-delayed apoptosis. Using either AG-490 or wortmannin alone, we observed a dose-dependent inhibition of GM-CSF-induced Mcl-1 expression. Using suboptimal doses of AG-490 and wortmannin, we found that both drugs together had an additive effect on delayed apoptosis and Mcl-1 expression. These data suggest that cooperative regulation of Mcl-1 by the Janus kinase/STAT and PI 3-kinase pathways contribute to GM-CSF-delayed apoptosis.
Activation of the classical complement pathway by mannose-binding protein in association with a novel C1s-like serine protease. (1992)

Serum mannose-binding protein (MBP) is a C-type lectin that binds to terminal mannose and N-acetylglucosamine moieties present on surfaces of certain pathogens and activates the classical complement pathway. In the present study, we describe the mechanism underlying the activation triggered by MBP. The human serum MBP fraction was obtained by sequential affinity chromatography on mannan-Sepharose, anti-IgM-Sepharose and anti-MBP-Sepharose in the presence of calcium ions. This fraction contained a C1s-like serine protease as assessed by C4 consumption. The C1s-like serine protease, designated MBP-associated serine protease (MASP), was separated from MBP by rechromatography on anti-MBP-Sepharose in the presence of ethylenediaminetetraacetic acid. MASP exhibited both C4- and C2-consuming activities. The molecular mass of MASP was estimated to be 83 kD with two polypeptides of heavy (66 kD) and light (L) (31 kD) chains linked by disulfide bonds. The serine residue responsible for protease activity is located on the L chain. Reconstitution experiments using MASP and MBP revealed that combination of the two components restores C4- and C2-activating capacity on mannan. Based on analyses of molecular size, antigenicity, and 11 NH2-terminal amino acid sequences of the L chain, we conclude that MASP is a novel protein different from C1r or C1s. Our findings are not in accord with a proposed mechanism by which MBP utilizes the C1r2-C1s2 complex to initiate the classical complement pathway.
Application of Tracers to Monitor Fluid Flow in the Snorre Field: A Field Study (1999)

Abstract This paper discusses the applications of gas and water tracers in the Central Fault Block (CFB) of the Snorre Field in the North Sea. An extensive tracer program was initiated in 1993 to improve the understanding of the flow dynamics in the field. The CFB of Snorre has been produced by WAG injection since 1994. The tracer program has involved 3 injectors and 4 producers. Tracers applied were perfluorinated hydrocarbons (PFCs) and SF6 as gas tracers. As water tracers tritiated water (HTO), chemical SCN− and radioactive S14CN− have been applied in addition to the new tracer 4-fluoro benzoic acid (4-FBA). Results from this integrated tracer study have improved the understanding of fluid flow and WAG injection efficiency in the reservoir. The tracer program will be continued and will also be expanded to other fault blocks.
Cell attachment and viability on micro-arc-oxidation (MAO) microwave/hydrothermal treated titanium surface (2013)

The purpose of this study is to investigate the cell attachment and viability on the micro-arc oxidization (MAO) microwave/hydrothermal treated titanium surfaces. The MAO samples were microwave irradiated in vessels containing 50 mL of double-distilled water for 30 minutes (MWDD). The immersion solution consisted of 0.05 mM calcium hydroxide and 0.03 mM ammonium dihydrogen phosphate (MWCP), and same solution with the pH value adjusted to 9.6 (MWCP9.6) were compared. The hydrothermal (HT) samples were conducted under DD water at 250°C for 3 hr. The cell viability (WST assay) results show that there was no significant different on the cell viability at 4 hrs. After cultured for 1 day, the cell viability of MG63 cells on the samples from high to low is HT = MWDD = MWCP > MWCP9.6 > MAO. No significant different was found on the cell number between groups. However, the percentages of spreading cells to total adherent cells are higher on the MWDD, MWCP, and MWCP9.6 groups (75.7%, 69.9%, 69.4%, respectively), when compare to MAO and HT groups (48.4% and 41.5%). These results demonstrate that increased cell spreading on a MW groups with submicro-to- nano scale calcium phosphates on titania produced by microwave/hydrothermal process.
Belatacept: from rational design to clinical application (2011)

Gradually improved immunosuppression has contributed significantly to the progress achieved in transplantation medicine so far. Nevertheless, current drug regimens are associated with late graft loss--in particular as a result of immunologic damage or drug toxicity--and substantial morbidity. Recently, the costimulation blocker belatacept (marketed under the name Nulojix®) has been approved for immunosuppression in renal transplantation. Belatacept (a mutated version of CTLA4Ig) is a fusion protein rationally designed to block CD28, a critical activating receptor on T cells, by binding and saturating its ligands B7-1 and B7-2. In phase II and III trials, belatacept was compared with cyclosporine (in combination with basiliximab, MMF, and steroids). Advantages observed with belatacept include superior graft function, preservation of renal structure and improved cardiovascular risk profile. Concerns associated with belatacept are a higher frequency of cellular rejection episodes and more post-transplant lymphoproliferative disorder (PTLD) cases especially in EBV seronegative patients, who should be excluded from belatacept-based regimens. Thus, after almost three decades of calcineurin inhibitors as mainstay of immunosuppression, belatacept offers a potential alternative. In this article, we will provide an overview of belatacept's preclinical development and will discuss the available evidence from clinical trials.
Expression of the Novel T Cell Activation Molecule hpH4 in HIV-Infected Patients: Correlation with Disease Status (2000)

We have described hpH4, a surface glycoprotein selectively expressed by activated T cells and mature thymocytes and displaying weak lateral association with CD4. The hpH4 expression pattern and biochemical features, together with analysis of its tryptic digest by peptide mass searching using MALDI-MS, suggested that it is a novel molecule. The aim of this work was to evaluate the peripheral blood T cell expression of hpH4 in HIV-infected patients and the interplay between HIV gp120 and hpH4, since both molecules interact with CD4. hpH4 expression during HIV-1 infection was evaluated by assessing 55 patients at various disease stages and following up 3 patients with primary infection and 3 patients with AIDS. hpH4 expression displayed a peak in the early phase of primary infection, dropped to control levels in the asymptomatic phase, and was newly expressed, at low levels, as AIDS developed. The expression kinetics were different than those shown by HLA-DR, CD25, and CD38. The most striking findings were the transient hpH4 expression peak displayed in the earliest stage, which was unique for hpH4. Incubation of T cells from normal donors with HIV gp120 induced transient hpH4 expression in resting CD4+ T cells and potentiated the hpH4 lateral association with CD4 in activated T cells. Moreover, hpH4 triggering inhibited gp120-induced death of CD4+ cells. Therefore, H4 expression may be a response to avoid apoptosis induced by HIV products.
Mapping and sequencing of a gene from myxoma virus that is related to those encoding epidermal growth factor and transforming growth factor alpha (1987)

Myxoma virus, a Leporipoxvirus and agent of myxomatosis, was shown to possess a gene with the potential to encode an epidermal growth factorlike factor. Its relationship to other members of this family, including the poxvirus growth factors from Shope fibroma virus and vaccinia virus, was analyzed. Alignment of DNA sequences and related open reading frames of myxoma virus and Shope fibroma virus indicated colinearity of genes between these poxviruses.
Orange Persistent Luminescence and Photodarkening Related to Paramagnetic Defects of Nondoped CaO-Ga2O3-GeO2 Glass (2019)

Orange persistent luminescence and photodarkening phenomena were observed after ultraviolet (UV) excitation in calcium-gallium-germanate (CGG) glass with a composition of 3CaO-1Ga2O3-3GeO2 prepared by a melt-quenching method. The CGG glass was characterized by using X-ray diffraction, differential scanning calorimetry, and Raman scattering analyses. Also, the optical and electronic properties of the CGG glass were investigated. Based on the electron paramagnetic resonance (EPR) spectra, it is found that new defects, NBOHC (nonbridging oxygen hole center) and E’(Ge) (unpaired electron at Ge ion bonding three oxygen), were created after UV excitation. From the good agreement between the time dependence of the photodarkening absorption intensity and EPR intensity of the NBOHC, the origin of the photodarkening phenomenon is found to be caused by NBOHC. Also, from the relationship between the time dependence of persistent luminescence intensity and the time-derivative EPR intensities of NBOHC and E’(Ge) centers, the persistent luminescence is found to be caused by the recombination process between these two different defects.
New wind in the sails: improving the agronomic value of crop plants through RNAi‐mediated gene silencing (2014)

RNA interference (RNAi) has emerged as a powerful genetic tool for scientific research over the past several years. It has been utilized not only in fundamental research for the assessment of gene function, but also in various fields of applied research, such as human and veterinary medicine and agriculture. In plants, RNAi strategies have the potential to allow manipulation of various aspects of food quality and nutritional content. In addition, the demonstration that agricultural pests, such as insects and nematodes, can be killed by exogenously supplied RNAi targeting their essential genes has raised the possibility that plant predation can be controlled by lethal RNAi signals generated in planta. Indeed, recent evidence argues that this strategy, called host-induced gene silencing (HIGS), is effective against sucking insects and nematodes; it also has been shown to compromise the growth and development of pathogenic fungi, as well as bacteria and viruses, on their plant hosts. Here, we review recent studies that reveal the enormous potential RNAi strategies hold not only for improving the nutritive value and safety of the food supply, but also for providing an environmentally friendly mechanism for plant protection.
Fighting Iron Deficiency Anemia with Iron-Rich Rice (2002)

This rice, with higher iron content, rich in phytase and cysteine-peptide has a great potential to substantially improve iron nutrition in those populations where iron deficiency is so widely spread.
Cloning and expression of a transferrin-binding protein from Actinobacillus pleuropneumoniae (1992)

An expression library was constructed from Actinobacillus pleuropneumoniae serotype 7. Escherichia coli transformants expressing recombinant proteins were identified by immunoscreening with porcine convalescent serum. One transformant expressing a 60-kDa protein (60K protein) in aggregated form was identified. Serum raised against the recombinant protein recognized a polypeptide with an indistinguishable electrophoretic mobility in the A. pleuropneumoniae wild type after iron-restricted growth only. The recombinant protein bound transferrin after blotting onto nitrocellulose. Using a competitive enzyme-linked immunosorbent assay (ELISA), the specificity of this binding for the amino-terminal half of iron-saturated porcine transferrin was established. Also, the 60K wild-type protein bound hemin as assessed by hemin-agarose chromatography. Hemin could inhibit transferrin binding of the recombinant protein in the competitive ELISA, whereas hemoglobin and synthetic iron chelators failed to do so. Southern blot analysis of several other A. pleuropneumoniae strains indicated that highly homologous sequence is present in eight of eight isolates of serotype 7 and in some isolates of serotypes 2, 3, and 4.
Downregulated Kynurenine 3-Monooxygenase Gene Expression and Enzyme Activity in Schizophrenia and Genetic Association With Schizophrenia Endophenotypes (2011)

Our results provide converging lines of evidence implicating reduced KMO activity in the etiopathophysiology of schizophrenia and related neurocognitive deficits.
Multimeric Soluble CD40 Ligand and GITR Ligand as Adjuvants for Human Immunodeficiency Virus DNA Vaccines (2006)

For use in humans, human immunodeficiency virus (HIV) DNA vaccines may need to include immunostimulatory adjuvant molecules. CD40 ligand (CD40L), a member of the tumor necrosis factor (TNF) superfamily (TNFSF), is one candidate adjuvant, but it has been difficult to use because it is normally expressed as a trimeric membrane molecule. Soluble trimeric forms of CD40L have been produced, but in vitro data indicate that multimeric, many-trimer forms of soluble CD40L are more active. This multimerization requirement was evaluated in mice using plasmids that encoded either 1-trimer, 2-trimer, or 4-trimer soluble forms of CD40L. Fusion with the body of Acrp30 was used to produce the 2-trimer form, and fusion with the body of surfactant protein D was used to produce the 4-trimer form. Using plasmids for secreted HIV-1 antigens Gag and Env, soluble CD40L was active as an adjuvant in direct proportion to the valence of the trimers (1 < 2 < 4). These CD40L-augmented DNA vaccines elicited strong CD8(+) T-cell responses but did not elicit significant CD4(+) T-cell or antibody responses. To test the applicability of the multimeric fusion protein approach to other TNFSFs, a 4-trimer construct for the ligand of glucocorticoid-induced TNF family-related receptor (GITR) was also prepared. Multimeric soluble GITR ligand (GITRL) augmented the CD8(+) T-cell, CD4(+) T-cell, and antibody responses to DNA vaccination. In summary, multimeric CD40L and GITRL are new adjuvants for DNA vaccines. Plasmids for expressing multimeric TNFSF fusion proteins permit the rapid testing of TNFSF molecules in vivo.
A multi-focal high-performance vision system (2006)

A novel multi-focal four camera vision system is presented. The dynamic performance reaches velocities and accelerations exceeding far beyond human capabilities. Extreme wide-angle aperture angles to narrow foveated are provided simultaneously and are independently controllable. The vision system is designed in the context of the new development of the successor model of the humanoid robot Johnnie targeting at real-world wide distance range applications. This paper presents the design, kinematic and perception models, and mechatronical integration. The dynamic performance is evaluated in experiments. A novel multi-camera view direction stabilization strategy is presented and experimentally validated
Combined restriction landmark genomic scanning and virtual genome scans identify a novel human homeobox gene, ALX3, that is hypermethylated in neuroblastoma (2002)

Restriction landmark genome scanning (RLGS) allows comparative analysis of several thousand DNA fragments in the genome and provides a means to identify CpG islands that are altered in tumor cells as a result of amplification, deletion, or methylation changes. We have developed a novel informatics tool, designated virtual genome scan (VGS), that makes it possible to predict automatically the sequence of fragments in RLGS patterns by matching to the human genome sequence. A combination of RLGS and VGS was utilized to identify changes of chromosome 1-derived fragments in neuroblastoma. A NotI-EcoRV fragment was found to be absent frequently in neuroblastoma cell line RLGS patterns. Sequence prediction by VGS as well as cloning of the fragment showed that it contained a CpG island that is part of the human orthologue of the hamster homeobox gene Alx3. Expression analysis in a panel of human and mouse tissues showed predominant expression of ALX3 in brain tissue. Methylation-sensitive sequence analysis of the promoter region in neuroblastoma cell lines indicated that methylation of specific sequences correlated with repression of the ALX3 gene. Expression was re-induced after treatment with the methylation inhibitor 5-aza-2'-deoxycytidine. Promoter methylation analysis of ALX3 in primary neuroblastoma tumors, using methylation-sensitive polymerase chain reaction, found preferential ALX3 methylation in advanced-stage tumors. The VGS approach we have implemented in combination with RLGS is useful for the identification of genomic CpG island-related methylation changes or deletions in cancer.