gebhart/patrepeval huggingface dataset:
Characterization and protective activity of a monoclonal antibody against a capsular epitope shared by Streptococcus suis serotypes 1, 2 and 1/2 (1997)

A monoclonal antibody (mAb Z3) was produced using BALB/c mice immunized with whole cells of Streptococcus suis serotype 2 reference strain S735. Screening by dot-ELISA showed that mAb Z3, of isotype IgG2b, reacted only with reference strains and field isolates of S. suis serotypes 1, 2 and 1/2. The recognized epitope was demonstrated to be polysaccharide in nature by periodate oxidation, and located in the capsule, since mAb Z3 reacted with purified capsular material by immunoblotting and was able to stabilize the capsule as shown by electron microscopy. Further characterization indicated that mAb Z3 may react specifically with the sialic acid moiety of the capsule, a common constituent of the polysaccharidic capsular material of the three capsular types, since sialidase-treated cells did not react with mAb Z3 in immunoblotting or indirect ELISA. Purified mAb Z3 was shown to significantly increase the rate of phagocytosis of S. suis cells by porcine monocytes and to activate the clearance of bacteria from the circulation in experimentally infected mice. However, mAb Z3 only offered partial protection to mice challenged with a minimal lethal dose. Thus, even though the capsule of S. suis seems to be an important virulence factor, the epitope recognized by mAb Z3 does not appear to be involved in complete protection against infection.
Development of sorafenib and other molecularly targeted agents in hepatocellular carcinoma (2007)

It is well appreciated that hepatocellular carcinoma (HCC) represents one of the most challenging malignancies of worldwide importance. In fact, HCC is the fifth most common cancer and the third most common cause of cancer-related death globally. The incidence rates for HCC in the U.S. and Western Europe have been rising. Unresectable or metastatic HCC carries a poor prognosis, and systemic therapy with cytotoxic agents provides marginal benefit. Because of the poor track record of systemic therapy in HCC, there has been a sense of nihilism for this disease in the oncology community for decades. However, with the arrival of newly developed, molecularly targeted agents and the success of some of these agents in other traditionally challenging cancers, such as renal cell carcinoma, there has been renewed interest in developing novel systemic therapy in HCC. At the recent Annual Meeting of the American Society of Clinical Oncology, results of a phase 3, randomized, placebo-controlled trial were presented in which sorafenib demonstrated improved survival in patients with advanced HCC. This landmark study represents the first agent that has demonstrated an improved overall survival benefit in this disease and sets the new standard for first-line treatment of advanced HCC. For this review, the author concisely summarized the current status of molecularly targeted agents that are under clinical development in advanced HCC.
Inter-species DNA polymerase delta chimeras are functional in Saccharomyces cerevisiae. (1995)

The catalytic subunits of DNA polymerase delta of Schizosaccharomyces pombe and Saccharomyces cerevisiae share over 50% identity. The capability of S. pombe DNA polymerase delta to complement two thermosensitive mutants of S. cerevisiae was studied in vivo and it was determined that complementation was allele dependent. However, DNA polymerase delta from S. pombe did not restore growth of a S. cerevisiae strain containing a disrupted chromosomal copy of the POL3 gene that encodes DNA polymerase delta. To identify the regions of DNA polymerase delta responsible for species-specific interactions, we constructed different chimeras with S. cerevisiae and S. pombe DNA polymerase delta genes. The growth of a S. cerevisiae strain with a disrupted chromosomal POL3 gene was studied after transformation with plasmids expressing different chimeras. A 1254-bp region located in the 3' region of the S. cerevisiae POL3 gene is responsible for species-specific functions.
Effect of Rb and Ta Doping on the Ionic Conductivity and Stability of the Garnet Li7+2x–y(La3–xRbx)(Zr2–yTay)O12 (0 ≤ x ≤ 0.375, 0 ≤ y ≤ 1) Superionic Conductor: A First Principles Investigation (2013)

In this work, we investigated the effect of Rb and Ta doping on the ionic conductivity and stability of the garnet Li7+2x–y(La3–xRbx)(Zr2–yTay)O12 (0 ≤ x ≤ 0.375, 0 ≤ y ≤ 1) superionic conductor using first principles calculations. Our results indicate that doping does not greatly alter the topology of the migration pathway, but instead acts primarily to change the lithium concentration. The structure with the lowest activation energy and highest room temperature conductivity is Li6.75La3Zr1.75Ta0.25O12 (Ea = 19 meV, σ300K = 1 × 10–2 S cm–1). All Ta-doped structures have significantly higher ionic conductivity than the undoped cubic Li7La3Zr2O12 (c-LLZO, Ea = 24 meV, σ300K = 2 × 10–3 S cm–1). The Rb-doped structure with composition Li7.25La2.875Rb0.125Zr2O12 has a lower activation energy than c-LLZO, but further Rb doping leads to a dramatic decrease in performance. We also examined the effect of changing the lattice parameter at fixed lithium concentration and found that a decrease in the lattice parameter leads to a rapid decline in Li+ conductivity, whereas an expanded lattice offers only marginal improvement. This result suggests that doping with larger cations will not provide a significant enhancement in performance. Our results find higher conductivity and lower activation energy than is typically reported in the experimental literature, which suggests that there is room for improving the total conductivity in these promising materials.
Disease sequence from mutant rhodopsin allele to rod and cone photoreceptor degeneration in man (1998)

Mutations in the gene encoding rhodopsin, the visual pigment in rod photoreceptors, lead to retinal degeneration in species from Drosophila to man. The pathogenic sequence from rod cell-specific mutation to degeneration of rods and cones remains unclear. To understand the disease process in man, we studied heterozygotes with 18 different rhodopsin gene mutations by using noninvasive tests of rod and cone function and retinal histopathology. Two classes of disease expression were found, and there was allele-specificity. Class A mutants lead to severely abnormal rod function across the retina early in life; topography of residual cone function parallels cone cell density. Class B mutants are compatible with normal rods in adult life in some retinal regions or throughout the retina, and there is a slow stereotypical disease sequence. Disease manifests as a loss of rod photoreceptor outer segments, not singly but in microscopic patches that coalesce into larger irregular areas of degeneration. Cone outer segment function remains normal until >75% of rod outer segments are lost. The topography of cone loss coincides with that of rod loss. Most class B mutants show an inferior-nasal to superior-temporal retinal gradient of disease vulnerability associated with visual cycle abnormalities. Class A mutant alleles behave as if cytotoxic; class B mutants can be relatively innocuous and epigenetic factors may play a major role in the retinal degeneration.
The Reactions of Grignard Reagents with Transition Metal Halides: Coupling, Disproportionation, and Exchange with Olefins (1971)

Abstract The reactions of transition metal halides (Mn, Fe, Co, Ni, Pd, Cu, and Ag) with the low-molecular-weight alkyl Grignard reagents in tetrahydrofuran and diethyl ether, especially in the presence of styrene were reinvestigated. An alkyl transition metal species formed in situ by metathesis decomposed to a dialkyl (oxidative dimerization) or to an alkene and an alkane (oxidative disproportionation). Silver(I) and copper(II) were particularly effective in oxidative dimerization of primary alkyl groups. Alkyl groups which contain no β-hydrogen were also coupled by iron, cobalt, nickel, palladium, and copper(I) halides with varying degrees of efficiency. Oxidative disproportionation was generally the more common route to decomposition for alkyl groups which have β-hydrogens. It seemed to proceed directly via a bimolecular interaction of alkylmetals or indirectly by elimination of a hydrido-metal species. If the latter added to an alkene reversibly, exchange was observed between Grignard reagent and alkene. Styrene was reduced to ethylbenzene during the reaction both in tetrahydrofuran and in diethyl ether in varying yield with transition metal halide and Grignard reagent. In addition to alkyl exchange, dehydrogenation of the ethereal solvent by active (reduced) metal species complicated the stoichiometry of decomposition as measured by the value of the empirical parameter, Q,(R). The selection of transition metal in addition to the temperature, solvent and triphenylphosphine was effective variables in promoting the efficiency of the exchange process.
Heat shock proteins in chronic kidney disease (2010)

Heat shock proteins (HSP) form a heterogenous, evolutionarily conserved group of molecules with high sequence homology. They mainly act as intracellular chaperones, protecting the protein structure and folding under stress conditions. The extracellular HSP, released in the course of damage or necrosis, play a pivotal role in the innate and adaptive immune responses. They also take part in many pathological processes. The aim of this review is to update the recent developments in the field of HSP in chronic kidney disease (CKD), in regard to three different aspects. The first is the assessment of the role of HSP, either positive or deleterious, in the pathogenesis of CKD and the possibilities to influence its progression. The second is the impact of dialysis, being a potentially modifiable stressor, on HSP and the attempt to assess the value of these proteins as the biocompatibility markers. The last area is that of kidney transplantation and the potential role of HSP in the induction of the immune tolerance in kidney recipients.
Evaluation of a new polyacrolein microsphere (acrobead) protein A column: an in vitro study using the blood of patients with immune thrombocytopenia or malignancies (1992)

The present study describes the use of a new polyacrolein microsphere (acrobead) protein A column. This method enables immunomodulation by the perfusion of whole blood. The efficacy of the column and its adverse effects following perfusion of blood of patients with immune thrombocytopenic purpura (ITP) or malignancies were investigated. Concurrent experiments in which blood was perfused through an acrobead lactoglobulin column were carried out. Cellular blood components were mildly affected during the procedure. A moderate decrease in platelet number, to a nadir of 90 x 10(3) per microL (90 x 10(9)/L), was documented. During the hemoperfusion of ITP patients' blood, plasma hemoglobin reached levels of 25 to 40 mg per dL, a level similar to that found in banked blood during storage. Plasma tumor necrosis factor level, which serves as an indicator of monocytic activation, increased after 90 minutes of hemoperfusion. IgG and immune complexes were removed. The specific activities (removal of mg Ig/mL bead) of acrobead protein A columns, using blood from patients with ITP or malignancies, were 4.9 and 4.5 mg IgG per mL of bead, respectively. The diminution of platelet-specific IgG in the plasma of patients with ITP was documented as well. There was no activation of the fibrinolytic system as examined by D-dimers. The use of this new technique, which incorporates the method of direct hemoperfusion, is suggested for future clinical studies.
Optimal Control Theory for Infinite Dimensional Systems (1995)

Infinite dimensional systems can be used to describe many phenomena in the real world. As is well known, heat conduction, properties of elastic plastic material, fluid dynamics, diffusion-reaction pro
Microbiome analysis of dairy cows fed pasture or total mixed ration diets (2011)

Understanding rumen microbial ecology is essential for the development of feed systems designed to improve livestock productivity, health and for methane mitigation strategies from cattle. Although rumen microbial communities have been studied previously, few studies have applied next-generation sequencing technologies to that ecosystem. The aim of this study was to characterize changes in microbial community structure arising from feeding dairy cows two widely used diets: pasture and total mixed ration (TMR). Bacterial, archaeal and protozoal communities were characterized by terminal restriction fragment length polymorphism of the amplified SSU rRNA gene and statistical analysis showed that bacterial and archaeal communities were significantly affected by diet, whereas no effect was observed for the protozoal community. Deep amplicon sequencing of the 16S rRNA gene revealed significant differences in the bacterial communities between the diets and between rumen solid and liquid content. At the family level, some important groups of rumen bacteria were clearly associated with specific diets, including the higher abundance of the Fibrobacteraceae in TMR solid samples and members of the propionate-producing Veillonelaceae in pasture samples. This study will be relevant to the study of rumen microbial ecology and livestock feed management.
Clinical implications of cellular biologic advances in periodontal regeneration. (1994)

It is known that periodontal tissues retain the ability to regenerate; however, current therapies fail in achieving predictable and consistent regeneration. Cell and molecular biology research in periodontal regeneration hold great promise in providing improved understanding of this complex phenomenon and direct us towards new possibilities of future clinical application. This paper reviews both the cells and extracellular matrix of the periodontal ligament in addition to the cell-to-matrix and cell-to-cell interaction involved in periodontal regeneration. Results of recent studies have suggested that periodontal regeneration recapitulates the process of morphogenesis, histogenesis, and cytodifferentiation, as well as cell field migration that occurs during development of the periodontium. A small population of purported periodontal stem cells is believed to be responsible for maintaining homeostasis in the periodontal ligament. This cell, which may have its origin in late periodontal mesenchyme of the dental papilla, is advocated as a tripotential cell capable of differentiating into cementoblast, osteoblast, and periodontal fibroblast. The clinical implication of advances made in cell and molecular biology research in periodontal regeneration may include future use of biomolecules in periodontal regeneration may include future use of biomolecules to improve the regenerative healing process and use of bioactive degradable membrane barriers in guided tissue regeneration as well as seeding of periodontal stem cells into periodontal defects. If the current trend continues, clinicians can look forward to seeing periodontal wound healing being substantially enhanced to achieve predictable periodontal regeneration.
A polynomial time algorithm for generating neural networks for classification problems (2003)

A novel polynomial time algorithm for the construction and training of multilayer perceptrons for classification problems is presented. It uses linear programming models to generate incrementally the hidden layer in a restricted higher-order perceptron. The polynomial time complexity of the method is proven and computational results are provided for some well-known problems. In all cases, very small nets were created compared to those reported previously.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Supervised Classification by Filter Methods and Recursive Feature Elimination Predicts Risk of Radiotherapy-Related Fatigue in Patients with Prostate Cancer (2014)

The results suggest that a novel analytical algorithm that incorporates fold-change differential analysis, LDA, and a k-NN may have applicability in predicting regimen-related toxicity in cancer patients with high reliability, if we take into account these results and the limited amount of data that we had at disposal. It is expected that the accuracy will be improved by increasing data sampling in the learning phase.
Active Site Residues of Cyclophilin A Are Crucial for Its Signaling Activity via CD147 (2002)

Cyclophilin A (CyPA), a ubiquitously distributed intracellular protein, is a peptidylprolyl cis-trans-isomerase and the major target of the potent immunosuppressive drug cyclosporin A. Although expressed predominantly as an intracellular molecule, CyPA is secreted by cells in response to inflammatory stimuli and is a potent neutrophil and eosinophil chemoattractant in vitro and in vivo. The mechanisms underlying CyPA-mediated signaling and chemotaxis are unknown. Here, we identified CD147 as a cell surface receptor for CyPA and demonstrated that CD147 is an essential component in the CyPA-initiated signaling cascade that culminates in ERK activation. Both signaling and chemotactic activities of CyPA depended also on the presence of heparans, which served as primary binding sites for CyPA on target cells. The proline 180 and glycine 181 residues in the extracellular domain of CD147 were critical for signaling and chemotactic activities mediated by CD147. Also crucial were active site residues of CyPA, because rotamase-defective CyPA mutants failed to initiate signaling events. These results establish cyclophilins as natural ligands for CD147 and suggest an unusual, rotamase-dependent mechanism of signaling.
Selective tumor sensitization to taxanes with the mAb-drug conjugate cBR96-doxorubicin (2001)

The chimeric monoclonal antibody cBR96 conjugated to doxorubicin (cBR96-Dox) is selectively internalized by a wide variety of human carcinomas expressing an extended form of Lewis Y antigen (Le(y)). Endocytosis is followed by cleavage and release of free doxorubicin from the endocytic vesicles and subsequent cytotoxicity. Combination studies with standard anti-cancer agents, undertaken to further increase the potency of this targeted therapy, identified significant synergistic anti-tumor activity of cBR96-Dox and either of the taxanes paclitaxel or docetaxel. Treatment with cBR96-Dox 24 hr prior to paclitaxel resulted in a steady increase in the percentage of G(2) tumor cells and corresponding increase in sensitivity to taxanes. Cell cycle analysis indicated the cBR96-delivered doxorubicin was most effective against S-phase cells, yet cells exposed to even subtoxic levels progressed to and arrested in G(2), at a point of high sensitivity to the anti-tubulin agent paclitaxel. The synergy obtained by staged combination of cBR96-Dox and paclitaxel in vitro was reflected in significant anti-tumor efficacy in vivo against xenograft models of human lung and breast tumors that could not be achieved by either agent alone. The staged combination elicited significant or complete regressions of established human Le(y)-positive tumor xenografts using significantly reduced drug levels. Taken together, these data demonstrate a mechanistic approach to the selective elimination of Le(y)-positive tumors by using targeted doxorubicin followed by taxane treatment.
Ras Activation of the Raf Kinase: Tyrosine Kinase Recruitment of the MAP Kinase Cascade (2001)

A continuing focus of our work has been an effort to understand the signal transduction pathways through which insulin achieves its cellular actions. In the mid-1970s, we and others observed that insulin promoted an increase in Ser/Thr phosphorylation of a subset of cellular proteins. This finding was unanticipated, inasmuch as nearly all of the actions of insulin then known appeared to result from protein dephosphorylation. In fact, nearly 15 years elapsed before any physiologic response to insulin attributable to stimulated (Ser/Thr) phosphorylation was established. Nevertheless, based on the hypothesis that insulin-stimulated Ser/Thr phosphorylation reflected the activation of protein (Ser/Thr) kinases downstream of the insulin receptor, we sought to detect and purify these putative, insulin-responsive protein (Ser/Thr) kinases. Our effort was based on the presumption that an understanding of the mechanism for their activation would provide an entry into the biochemical reactions through which the insulin receptor activated its downstream effectors. To a degree that, in retrospect, is surprising, this goal was accomplished, much in the way originally envisioned. It is now well known that receptor tyrosine kinases (RTKs) recruit a large network of protein (Ser/Thr) kinases to execute their cellular programs. The first of these insulin-activated protein kinase networks to be fully elucidated was the Ras-Raf-mitogen-activated protein kinase (MAPK) cascade. This pathway is a central effector of cellular differentiation in development; moreover, its inappropriate and continuous activation provides a potent promitogenic force and is a very common occurrence in human cancers. Conversely, this pathway contributes minimally, if at all, to insulin's program of metabolic regulation. Nevertheless, the importance of the Ras-MAPK pathway in metazoan biology and human malignancies has impelled us to an ongoing analysis of the functions and regulation of Ras and Raf. This chapter will summarize briefly the way in which work from this and other laboratories on insulin signaling led to the discovery of the mammalian MAP kinase cascade and, in turn, to the identification of unique role of the Raf kinases in RTK activation of this protein (Ser/Thr) kinase cascade. We will then review in more detail current understanding of the biochemical mechanism through which the Ras proto-oncogene, in collaboration with the 14-3-3 protein and other protein kinases, initiates activation of the Raf kinase.
Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin (1999)

Because of the role of thrombin and platelets in myocardial infarction and other pathological processes, identifying and blocking the receptors by which thrombin activates platelets has been an important goal. Three protease-activated receptors (PARs) for thrombin -- PAR1, PAR3, and PAR4 -- are now known. PAR1 functions in human platelets, and the recent observation that a PAR4-activating peptide activates human platelets suggests that PAR4 also acts in these cells. Whether PAR1 and PAR4 account for activation of human platelets by thrombin, or whether PAR3 or still other receptors contribute, is unknown. We have examined the roles of PAR1, PAR3, and PAR4 in platelets. PAR1 and PAR4 mRNA and protein were detected in human platelets. Activation of either receptor was sufficient to trigger platelet secretion and aggregation. Inhibition of PAR1 alone by antagonist, blocking antibody, or desensitization blocked platelet activation by 1 nM thrombin but only modestly attenuated platelet activation by 30 nM thrombin. Inhibition of PAR4 alone using a blocking antibody had little effect at either thrombin concentration. Strikingly, simultaneous inhibition of both PAR1 and PAR4 virtually ablated platelet secretion and aggregation, even at 30 nM thrombin. These observations suggest that PAR1 and PAR4 account for most, if not all, thrombin signaling in platelets and that antagonists that block these receptors might be useful antithrombotic agents.
Physical Activity, Tumor PTGS2 Expression, and Survival in Patients with Colorectal Cancer (2013)

Immunohistochemical PTGS2 expression in colorectal carcinoma may serve as a predictive biomarker in pathology practice, which may predict stronger benefit from exercise.