gebhart/patrepeval huggingface dataset:
Signal Transduction: Multiple Pathways, Multiple Options for Therapy (2001)

Many aspects of cell behavior, such as growth, motility, differentiation, and apoptosis, are regulated by signals cells receive from their environment. Such signals are important, e.g., during embryonal development, wound healing, hematopoiesis, and in the regulation of the immune response, and may come from interactions with other cells or components of the extracellular matrix, or from binding of soluble signaling molecules to specific receptors at the cell membrane. Hereby different signaling pathways are initiated inside the cell. Perturbations of such signaling pathways are seen in several types of diseases, e.g., cancer, inflammatory conditions, and atherosclerosis. Thus, antagonists of several signaling pathways have potential clinical utility. Several such compounds are currently used or are in clinical trials; others are currently being analyzed in animal models.
Osteocyte-Derived Sclerostin Inhibits Bone Formation: Its Role in Bone Morphogenetic Protein and Wnt Signaling (2008)

Sclerosteosis and Van Buchem disease are rare, high-bone-mass disorders that have been linked to deficiency in the SOST gene, encoding sclerostin. Sclerostin belongs to the DAN family of glycoproteins, of which multiple family members have been shown to antagonize bone morphogenetic protein (BMP) and/or Wnt activity. Sclerostin is specifically expressed by osteocytes and inhibits BMP-induced osteoblast differentiation and ectopic bone formation. Sclerostin binds only weakly to BMPs and does not inhibit direct BMP-induced responses. Instead, sclerostin antagonizes canonical Wnt signaling by binding to Wnt coreceptors, low-density lipoprotein receptor-related protein 5 and 6. Several lipoprotein receptor-related protein-5 mutants that cause the high-bone-mass trait are defective in sclerostin binding. Thus, high bone mass in sclerosteosis and Van Buchem disease may result from increased Wnt signaling due to the absence of or insensitivity to sclerostin.
Eradication of B-CLL by autologous and allogeneic host nonreactive anti–third-party CTLs (2004)

Establishment of cell lines capable of killing leukemia cells, in the absence of alloreactivity against normal host cells, represents a most desirable goal in bone marrow transplantation (BMT) and cancer immunotherapy. By using a human --> mouse chimeric model, we demonstrate that allogeneic anti-third-party cytotoxic T lymphocytes (CTLs) depleted of alloreactivity are endowed with a potent anti-B-cell chronic lymphocytic leukemia (B-CLL) reactivity. Likewise, CTL preparations generated from autologous T cells of the same patients with B-CLL exhibited comparable leukemia eradication, suggesting that the reactivity of allogeneic anti-third-party CTLs is not mediated by residual antihost clones. This specificity was also exhibited in vitro, and annexin staining revealed that B-CLL killing is mediated by apoptosis. While the CTLs killing of third-party cells could be blocked by anti-CD3 antibody, the lysis of the B-CLL cells was not inhibited by this antibody, suggesting a T-cell receptor (TCR)-independent cytotoxicity. The role of cell contact leading to apoptosis of B-CLL cells is shown in transwell plates and by anti-lymphocyte function-associated antigen-1 (LFA-1)-blocking antibody. Up-regulation of CD54 and the subsequent apoptosis of B-CLL cells depend on the initial LFA-1/ICAM-1 (intercellular adhesion molecule 1) interaction. Taken together, these results suggest that allogeneic or autologous host nonreactive anti-third-party CTLs may represent a new therapeutic approach for patients with B-CLL.
Elevated levels of MIC‐1/GDF15 in the cerebrospinal fluid of patients are associated with glioblastoma and worse outcome (2009)

For patients with brain tumors identification of diagnostic and prognostic markers in easy accessible biological material, such as plasma or cerebrospinal fluid (CSF), would greatly facilitate patient management. MIC-1/GDF15 (growth differentiation factor 15) is a secreted protein of the TGF-beta superfamily and emerged as a candidate marker exhibiting increasing mRNA expression during malignant progression of glioma. Determination of MIC-1/GDF15 protein levels by ELISA in the CSF of a cohort of 94 patients with intracranial tumors including gliomas, meningioma and metastasis revealed significantly increased concentrations in glioblastoma patients (median, 229 pg/ml) when compared with control cohort of patients treated for non-neoplastic diseases (median below limit of detection of 156 pg/ml, p < 0.0001, Mann-Whitney test). However, plasma MIC-1/GDF15 levels were not elevated in the matching plasma samples from these patients. Most interestingly, patients with glioblastoma and increased CSF MIC-1/GDF15 had a shorter survival (p = 0.007, log-rank test). In conclusion, MIC-1/GDF15 protein measured in the CSF may have diagnostic and prognostic value in patients with intracranial tumors.
Geobacter sulfurreducens sp. nov., a hydrogen- and acetate-oxidizing dissimilatory metal-reducing microorganism (1994)

A dissimilatory metal- and sulfur-reducing microorganism was isolated from surface sediments of a hydrocarbon-contaminated ditch in Norman, Okla. The isolate, which was designated strain PCA, was an obligately anaerobic, nonfermentative nonmotile, gram-negative rod. PCA grew in a defined medium with acetate as an electron donor and ferric PPi, ferric oxyhydroxide, ferric citrate, elemental sulfur, Co(III)-EDTA, fumarate, or malate as the sole electron acceptor. PCA also coupled the oxidation of hydrogen to the reduction of Fe(III) but did not reduce Fe(III) with sulfur, glucose, lactate, fumarate, propionate, butyrate, isobutyrate, isovalerate, succinate, yeast extract, phenol, benzoate, ethanol, propanol, or butanol as an electron donor. PCA did not reduce oxygen, Mn(IV), U(VI), nitrate, sulfate, sulfite, or thiosulfate with acetate as the electron donor. Cell suspensions of PCA exhibited dithionite-reduced minus air-oxidized difference spectra which were characteristic of c-type cytochromes. Phylogenetic analysis of the 16S rRNA sequence placed PCA in the delta subgroup of the proteobacteria. Its closest known relative is Geobacter metallireducens. The ability to utilize either hydrogen or acetate as the sole electron donor for Fe(III) reduction makes strain PCA a unique addition to the relatively small group of respiratory metal-reducing microorganisms available in pure culture. A new species name, Geobacter sulfurreducens, is proposed.
Triplet repeats form secondary structures that escape DNA repair in yeast (1999)

Several human neurodegenerative diseases result from expansion of CTG/CAG or CGG/CCG triplet repeats. The finding that single-stranded CNG repeats form hairpin-like structures in vitro has led to the hypothesis that DNA secondary structure formation is an important component of the expansion mechanism. We show that single-stranded DNA loops containing 10 CTG/CAG or CGG/CCG repeats are inefficiently repaired during meiotic recombination in Saccharomyces cerevisiae . Comparisons of the repair of DNA loops with palindromic and nonpalindromic sequences suggest that this inefficient repair reflects the ability of these sequences to form hairpin structures in vivo .
Identification of differentially expressed mRNA transcripts in drug-resistant versus parental human melanoma cell lines. (2006)

Genes with altered expression were identified in drug-resistant variants. The identified molecules may provide new insights into the molecular basis for melanoma resistance to chemotherapy.
Activation events during thymic selection. (1992)

During their differentiation in the mouse thymus, CD4+8- cells undergo several of the sequential changes observed upon normal activation of mature, peripheral CD4+ lymphocytes. Expression of CD69, an early activation marker, is first observed on a minority of cells at the T cell receptor (TCR)lo/med double-positive stage, is maximal (50-90%) on heat-stable antigen (HSA)hi TCRhi double-positive, HSAhi TCRmed CD4+8lo, and HSAhi TCRhi CD4+8- cells, and is downmodulated at the mature HSAlo CD4+8- stage. In contrast, CD44, a late activation marker, is selectively expressed at the HSAlo stage. The set of lymphokines that CD4+8- thymocytes can produce upon stimulation also characteristically expands from mainly interleukin 2 (IL-2) at the HSAhi stage, to IL-2 and very large amounts of IL-4, IL-5, IL-10, and interferon gamma (IFN-gamma) at the HSAlo stage. 1 in 30 HSAlo CD4+8- adult thymocytes secrete IL-4 upon stimulation through their TCR. This frequency is 25% of the frequency of IL-2 producers, about 100-fold above that of peripheral (mainly resting) CD4+ T cells. With time after their generation in organ culture, CD4+8- thymocytes lose their capacity to secrete IL-4, IL-5, and IFN-gamma, but not IL-2. Similarly, the frequency of IL-4, but not of IL-2, producers progressively decreases after emigration to the periphery as judged by direct comparison between thymic and splenic CD4+ cells in newborns, or by following the fate of intrathymically labeled CD4+8- cells in adults after their migration to the spleen. This sequence suggests that thymic selection results from an activation process rather than a simple rescue from death at the double-positive stage, and shows that the functional changes induced after intrathymic activation, although transient, are still evident after export to the periphery.
Increased preferential absorption in human atherosclerotic plaque with oral beta carotene. Implications for laser endarterectomy. (1988)

Patients undergoing carotid endarterectomy were pretreated with low-dose, oral beta carotene to determine whether the carotenoid content of plaque could be increased in vivo. Beta carotene-treated patients had a 50-fold increase in their plaque beta carotene level from 0.066 to 3.3 micrograms beta carotene/g plaque. Microscopy and microspectrophotometry demonstrated that plaque from beta carotene-treated patients had higher carotenoid levels and higher absorption (450-500 nm) compared with control specimens, but normal media was unaffected. This demonstration of increased preferential absorption by plaque suggests that selective ablation of atherosclerotic plaque may be enhanced by pretreating patients with oral beta carotene.
Gastric endocrine cells: gene expression, processing, and targeting of active products (1996)

Endocrine cells of the gastric epithelium secrete biologically active peptides and small messenger molecules such as histamine, serotonin, and gamma-aminobutyric acid. The secretory products may act locally (paracrine or autocrine effects) or at distant targets after delivery in the circulation (hormonal effects). the contents of the gastric lumen control both secretion of gastric endocrine cells and the expression of genes involved in the synthesis of their active secretory products; in some cases, gene regulation may occur over periods as short as that required for digestion of a single meal. The conversion of inactive peptide precursors to their active forms takes place during transit along the secretory pathway and is only completed after sequestration in secretory granules. the processing of the gastrin precursor provides a useful model for studying prohormone processing. Generation of the well-known amidated gastrins requires prohormone cleavage and COOH-terminal amidation; the products stimulate acid secretion and mucosal growth. However, recent work indicates that biosynthetic intermediates that do not stimulate acid secretion may nevertheless act at a novel receptor to stimulate growth, so that control of prohormone processing determines which of two alternative types of biologically active peptide is released by gastrin cells. Gastric endocrine cells also have the capacity to accumulate small messenger molecules in secretory vesicles, via proton exchangers. Recent work indicates physiological regulation of the expression of genes encoding cytosolic enzymes such as histidine decarboxylase, which converts histidine to histamine, and of secretory granule transporters such as vesicular monoamine transporter type 2, which concentrates amines in secretory vesicles. Together these findings suggest that modulation of regulatory peptide and amine biosynthesis in gastric endocrine cells constitutes a primary response of the stomach to the arrival of a meal.
Bite Force and Influential Factors on Bite Force Measurements: A Literature Review (2010)

Maximum voluntary bite force is an indicator of the functional state of the masticatory system and the level of maximum bite force results from the combined action of the jaw elevator muscles modified by jaw biomechanics and reflex mechanisms. The measurement of bite force can provide useful data for the evaluation of jaw muscle function and activity. It is also an adjunctive value in assessing the performance of dentures. Technological advances in signal detection and processing have improved the quality of the information extracted from bite force measurements. However, these measurements are difficult and the reliability of the result depends on a number of factors, such as presence of pain and temporomandibular disorders, gender, age, cranio-facial morphology, and occlusal factors. In addition to these physiological factors, recording devices and techniques are important factors in bite force measurement. Therefore, one should be careful when comparing the bite force values reported in the research.
New paradigms for access control in open environments (2006)

Many access control models and policies have been proposed in recent years for different purposes. Access control is now evolving with the complex environments that it support. In open environments such as the Internet, the decision to grant access to a resource is often based on the characteristics of the requestor rather than its identity. Also, people have often little control over their personal information once it has been disclosed to third parties. Privacy and secondary usage regulations are increasingly demanding attention. In this paper, we present the emerging trends in the access control field to address the new needs and desiderata of today's systems.
Streptococcus zooepidemicus Meningitis and Bacteraemia (2003)

Group C streptococci are common causative agents of epidemic infections in animals and a rare cause of meningitis in humans. The case is reported of a 75-y-old man with meningitis caused by a group C streptococcus (Streptococcus zooepidemicus). He had frequent contact with horses, which were a possible source of infection. In spite of treatment with a third generation cephalosporin, the outcome was fatal.
New yeast expression platforms based on methylotrophic and and on dimorphic and – A comparison (2005)

Yeasts combine the ease of genetic manipulation and fermentation of a microbial organism with the capability to secrete and to modify proteins according to a general eukaryotic scheme. Yeasts thus provide attractive platforms for the production of recombinant proteins. Here, four important species are presented and compared: the methylotrophic Hansenula polymorpha and Pichia pastoris, distinguished by an increasingly large track record as industrial platforms, and the dimorphic species Arxula adeninivorans and Yarrrowia lipolytica, not yet established as industrial platforms, but demonstrating promising technological potential, as discussed in this article.
Continuing Medical Education Activity in Echocardiography (2012)

Article Title: Preimplant Transthoracic Echocardiographic Assessment of Continuous Flow Left Ventricular Assist Device (Echocardiography 2012;29:51)
Monitoring treatment of alcoholic liver disease: evaluation of various severity indices. (1991)

Monitoring the effectiveness of treatment sfor alcoholic liver disease involves the use of variables that have prognostic significance and are unaffected by the treatment in unspecific ways. Here we review the value of histological and functional variables for this purpose. We conclude that histological variables, although important in defining the characteristics of the sample, have several practical problems. The functional variables are most effective when used in combinations, e.g., in global indices such as the Combined Clinical and Laboratory Index, the Child-Turcotte-Pugh Index, or the Cox model. In situations involving mortality and dropouts, functional indices cannot be used to measure changes in severity; in such cases, mortality might be the only measure for assessing the effectiveness of a treatment. In clinical trials, it is essential to determine the risk of a Type II error, to monitor compliance and drinking, and to trace appropriately all the patients who were not compliant or who dropped out of the trial.
Mammalian DNA Ligase III: Molecular Cloning, Chromosomal Localization, and Expression in Spermatocytes Undergoing Meiotic Recombination (1995)

Three biochemically distinct DNA ligase activities have been identified in mammalian cell extracts. We have recently purified DNA ligase II and DNA ligase III to near homogeneity from bovine liver and testis tissue, respectively. Amino acid sequencing studies indicated that these enzymes are encoded by the same gene. In the present study, human and murine cDNA clones encoding DNA ligase III were isolated with probes based on the peptide sequences. The human DNA ligase III cDNA encodes a polypeptide of 862 amino acids, whose sequence is more closely related to those of the DNA ligases encoded by poxviruses than to replicative DNA ligases, such as human DNA ligase I. In vitro transcription and translation of the cDNA produced a catalytically active DNA ligase similar in size and substrate specificity to the purified bovine enzyme. The DNA ligase III gene was localized to human chromosome 17, which eliminated this gene as a candidate for the cancer-prone disease Bloom syndrome that is associated with DNA joining abnormalities. DNA ligase III is ubiquitously expressed at low levels, except in the testes, in which the steady-state levels of DNA ligase III mRNA are at least 10-fold higher than those detected in other tissues and cells. Since DNA ligase I mRNA is also present at high levels in the testes, we examined the expression of the DNA ligase genes during spermatogenesis. DNA ligase I mRNA expression correlated with the contribution of proliferating spermatogonia cells to the testes, in agreement with the previously defined role of this enzyme in DNA replication. In contrast, elevated levels of DNA ligase III mRNA were observed in primary spermatocytes undergoing recombination prior to the first meiotic division. Therefore, we suggest that DNA ligase III seals DNA strand breaks that arise during the process of meiotic recombination in germ cells and as a consequence of DNA damage in somatic cells.
Septic Shock and Acute Lung Injury in Rabbits with Peritonitis (2001)

The major goal of this study was to investigate the mechanisms that link the host response to a local infection in the peritoneal cavity with the development of sepsis and lung injury. Rabbits were infected by intraperitoneal inoculation of fibrin clots containing Escherichia coli at 10(8), 10(9), or 10(10) cfu/clot. Physiologic, bacteriologic, and inflammatory responses were monitored, and the lungs were examined postmortem. At a dose of 10(8) cfu/clot the animals had resolving infection, and a dose of 10(9) cfu/clot resulted in persistent infection at 24 h, with minimal systemic manifestations. In contrast, inoculation of 10(10) cfu/clot resulted in rapidly lethal local infection, with septic shock and lung injury. The onset of septic shock was associated with a paradoxical lack of identifiable polymorphonuclear leukocytes (PMN; neutrophils) in the peritoneal cavity. The absence of PMN in the peritoneum was due in part to lysis of intraperitoneal PMN, because the peritoneal fluids contained free myeloperoxidase and induced rapid death of normal rabbit PMN in vitro. Although most animals became bacteremic, only those with a severe systemic inflammation response developed lung injury. These data show that control of an infection in the first compartment in which bacteria enter the host is a critical determinant of the systemic response. Above a threshold dose of bacteria, failure of the local neutrophil response is a key mechanism associated with deleterious systemic responses. Bacteremia alone is not sufficient to cause lung injury. Lung injury occurs only in the setting of a severe systemic inflammatory response and an inadequate leukocyte response at the primary site of infection.
Analysis of the serotype-specific epitopes of avian infectious bronchitis virus strains Ark99 and Mass41 (1996)

The Ark and Mass serotype-specific epitopes of infectious bronchitis virus were studied by immunofluorescence and immunoprecipitation of mutant and recombinant spike glycoproteins (S protein) expressed in mouse L cells. Serotype-specific monoclonal antibodies could bind to the recombinant proteins of Ark99 and Mass41 expressed from the chimeras in which the N-terminal thirds of the S1 sequences were reciprocally exchanged. Therefore, it appears that the respective serotype-specific epitopes of both strains were localized within the C-terminal two-thirds of the S1 proteins. Deletion and insertion of a five-amino-acid fragment on the S1 proteins of Ark99 and Mass41, altered the serotype-specific epitopes. This result implies that the five-amino-acid insertion on the S1 protein of the Ark serotype was involved in determining the conformation of the protein, probably acting as a spacer. In addition, it appears that an interaction between sequences of the N-terminal third and the remaining portion of the S1 protein determines the tertiary structure of the protein as well as the conformation of the serotype-specific epitope.
Efficient mobilization of haematopoietic progenitors after a single injection of pegylated recombinant human granulocyte colony‐stimulating factor in mouse strains with distinct marrow‐cell pool sizes (2000)

We have compared the efficacy of a single injection of SD/01, a newly engineered, pegylated form of recombinant human granulocyte colony stimulating factor (rhG‐CSF), with a single injection of glycosylated rhG‐CSF (Filgrastim). SD/01 was administered to regular and recombinant inbred strains of mice (AKR, C57L/J, DBA/2, C57BL/6, AKXL) known to have widely distinct marrow‐cell pool sizes and proliferation kinetics. A single injection of G‐CSF was unable to mobilize granulocyte–macrophage colony‐forming units (CFU‐GM). In sharp contrast, a single dose of SD/01 resulted in massive mobilization of progenitors and stem cells. Although all mice strains showed qualitatively similar mobilization responses, large interstrain differences remained. C57L and C57BL/6 mice mobilized relatively poorly, whereas AKR and DBA/2 mice showed threefold to tenfold superior responses. In order to explain these different phenotypes, we studied the effects of SD/01 in nine AKXL recombinant inbred strains, derived from well‐responding AKR and poorly responding C57L parental strains. The best predictor for SD/01 responsiveness in these strains was marrow cellularity prior to mobilization. Comparison of the AKXL strain distribution pattern for marrow cellularity with loci previously mapped in these strains showed complete concordance with Aat , a serine protease inhibitor mapping to chromosome 12.
Effects of dipole position, orientation and noise on the accuracy of EEG source localization (2003)

It was found that if the signal-to-noise ratio is above a certain threshold, localization errors in realistic head models are, on average the same for deep and superficial sources. As the noise increases, localization errors increase, particularly for deep sources.
The angiogenic ?vascular endothelial growth factor/flk-1(KDR) receptor? pathway in patients with endometrial carcinoma (2001)

sMVD and the angiogenic factor VEGF are important indicators of a poor prognosis in patients with endometrial carcinoma. VEGF/KDR complexes define a subgroup of patients with endometrial carcinoma with an even worse prognosis.