gebhart/patrepeval huggingface dataset:
Chemokine-Mediated Robust Augmentation of Liver Engraftment: A Novel Approach (2014)

Effective repopulation of the liver is essential for successful clinical hepatocyte transplantation. The objective was to improve repopulation of the liver with human hepatocytes using chemokines. We used flow cytometry and immunohistochemistry assays to identify commonly expressed chemokine receptors on human fetal and adult hepatocytes. The migratory capacity of the cells to various chemokines was tested. For in vivo studies, we used a nude mouse model of partial hepatectomy followed by intraparenchymal injections of chemokine ligands at various concentrations. Human fetal liver cells transformed with human telomerase reverse transcriptase were used for intrasplenic cell transplantation. Repopulation and functionality were assessed 4 weeks after transplantation. The receptor CXCR3 was commonly expressed on both fetal and adult hepatocytes. Both cell types migrated efficiently toward corresponding CXC chemokine ligands 9, 10, and 11. In vivo, animals injected with recombinant chemokines showed the highest cell engraftment compared with controls (p<.05). The engrafted cells expressed several human hepatic markers such as cytokeratin 8 and 18 and albumin as well as transferrin, UGT1A1, hepatocyte nuclear factor (1α, 1β, and 4α), cytochrome CYP3A1, CCAAT/enhancer binding protein (α and β), and human albumin compared with controls. No inflammatory cells were detected in the livers at 4 weeks after transplantation. The improved repopulation of transplanted cells is likely a function of the chemokines to mediate cell homing and retention in the injured liver and might be an attractive strategy to augment repopulation of transplanted hepatocytes in vivo.
The role of marine omega‐3 (n‐3) fatty acids in inflammatory processes, atherosclerosis and plaque stability (2012)

Atherosclerosis has an important inflammatory component and acute cardiovascular events can be initiated by inflammatory processes occurring in advanced plaques. Fatty acids influence inflammation through a variety of mechanisms; many of these are mediated by, or associated with, the fatty acid composition of cell membranes. Human inflammatory cells are typically rich in the n-6 fatty acid arachidonic acid, but the contents of arachidonic acid and of the marine n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can be altered through oral administration of EPA and DHA. Eicosanoids produced from arachidonic acid have roles in inflammation. EPA also gives rise to eicosanoids and these are usually biologically weak. EPA and DHA give rise to resolvins which are anti-inflammatory and inflammation resolving. EPA and DHA also affect production of peptide mediators of inflammation (adhesion molecules, cytokines, etc.). Thus, the fatty acid composition of human inflammatory cells influences their function; the contents of arachidonic acid, EPA and DHA appear to be especially important. The anti-inflammatory effects of marine n-3 polyunsaturated fatty acids (PUFAs) may contribute to their protective actions towards atherosclerosis and plaque rupture.
Textbook of immunology: An introduction to immunochemistry and immunobiology (1983)

Textbook of immunology: an introduction to immunochemistry and immunology , Textbook of immunology: an introduction to immunochemistry and immunology , کتابخانه الکترونیک و دیجیتال - آذرسا
Nav1.7 Mutant A863P in Erythromelalgia: Effects of Altered Activation and Steady-State Inactivation on Excitability of Nociceptive Dorsal Root Ganglion Neurons (2006)

Inherited erythromelalgia/erythermalgia (IEM) is a neuropathy characterized by pain and redness of the extremities that is triggered by warmth. IEM has been associated with missense mutations of the voltage-gated sodium channel Na(V)1.7, which is preferentially expressed in most nociceptive dorsal root ganglia (DRGs) and sympathetic ganglion neurons. Several mutations occur in cytoplasmic linkers of Na(V)1.7, with only two mutations in segment 4 (S4) and S6 of domain I. We report here a simplex case with an alanine 863 substitution by proline (A863P) in S5 of domain II of Na(V)1.7. The functional effect of A863P was investigated by voltage-clamp analysis in human embryonic kidney 293 cells and by current-clamp analysis to determine the effects of A863P on firing properties of small DRG neurons. Activation of mutant channels was shifted by -8 mV, whereas steady-state fast inactivation was shifted by +10 mV, compared with wild-type (WT) channels. There was a marked decrease in the rate of deactivation of mutant channels, and currents elicited by slow ramp depolarizations were 12 times larger than for WT. These results suggested that A863P could render DRG neurons hyperexcitable. We tested this hypothesis by studying properties of rat DRG neurons transfected with either A863P or WT channels. A863P depolarized resting potential of DRG neurons by +6 mV compared with WT channels, reduced the threshold for triggering single action potentials to 63% of that for WT channels, and increased firing frequency of neurons when stimulated with suprathreshold stimuli. Thus, A863P mutant channels produce hyperexcitability in DRG neurons, which contributes to the pathophysiology of IEM.
A double dissociation revealing bidirectional competition between striatum and hippocampus during learning (2008)

The multiple memory systems framework proposes that distinct circuits process and store different sorts of information; for example, spatial information is processed by a circuit that includes the hippocampus, whereas certain forms of instrumental conditioning depend on the striatum. Disruption of hippocampal function can enhance striatum-dependent learning in some paradigms, which has been interpreted as evidence that these systems can compete with one another in an intact animal. However, it remains unclear whether such competition can occur in the opposite direction, as suggested by the multiple memory systems framework, or is unidirectional. We addressed this question using lesions and genetic manipulations in mice. Impairment of dorsal striatal function with either excitotoxic lesions or transgenic inhibition of the transcription factor cAMP response element-binding protein, which disrupts striatal synaptic plasticity, impaired striatum-dependent cued learning but enhanced hippocampus-dependent spatial learning. Conversely, excitotoxic lesions of the dorsal hippocampus disrupted spatial learning and enhanced cued learning. This double dissociation demonstrates bidirectional competition that constitutes strong evidence for the parallel operation of distinct memory systems.
Controlling cell position in complex heterotypic 3D microtissues by tissue fusion (2008)

Tissue fusion and cell sorting are processes fundamental to developmental biology with applications in tissue engineering. We have designed a fusion assay to investigate the factors governing the fusion of microtissues and the cell sorting that occurs after fusion. Normal human fibroblast (NHF) spheroids were self-assembled and cultured for 1, 4, or 7 days, then combined in trough shaped recesses. Over a 24-h period the spheroids fused to become a rod shaped microtissue and the kinetics and extent of fusion could be quantified by assessing rod contraction. By varying the amount of spheroid culture time prior to fusion (1-7 days), the rate of fusion, the coherence of the building units (as measured by fusion angle) and the steady state length of the structure could be easily controlled. Longer pre-culture times for the spheroids resulted in slower fusion, less coherence and increased length of rod microtissues. The fusion kinetics and steady length of rods formed by smaller versus larger spheroids ( approximately 100 vs. 300 microm diameter) were indistinguishable, even though smaller spheroids had twice the surface area and greater numbers of contacts between units. Both small and large spheroids were strongly influenced by spheroid pre-culture time. Pre-culture time could also be used to control cell sorting and cell position when combinations of NHFs and H35s, a rat hepatocyte cell line, were fused to form heterotypic microtissues. Control of fusion and cell position are important parameters for creating functional heterotypic microtissues as well as the use of microtissues as building units to create larger tissue structures.
Theano: new features and speed improvements (2012)

Theano is a linear algebra compiler that optimizes a user's symbolically-specified mathematical computations to produce efficient low-level implementations. In this paper, we present new features and efficiency improvements to Theano, and benchmarks demonstrating Theano's performance relative to Torch7, a recently introduced machine learning library, and to RNNLM, a C++ library targeted at recurrent neural networks.
ChemInform Abstract: Synthetic Libraries of Fungal Natural Products (2007)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Orexin Receptor Antagonists: A New Concept In CNS Disorders? (2010)

Orexin receptor antagonists are of high interest to the pharmaceutical industry. Two compounds, almorexant from Actelion Pharmaceuticals Ltd and MK-4305 from Merck & Co., are currently undergoing clinical evaluation. This Minireview summarizes recent molecular biology, pharmacology and medicinal chemistry research efforts in this field.
Novel facts about an old marker: the LE cell (2001)

For more than fifty years, lupus erythematosus (LE) cells were believed to result from in vitro opsonization of bare nuclei by serum antinuclear antibodies and their ultimate phagocytosis by neutrophils. Twenty years ago, we described that certain antinuclear antibodies could enter into viable cells, and later on, it was proved that penetration of anti-DNA antibodies into cells results in protracted active cell death. Recent findings indicate that the material engulfed by LE cells are apoptotic blebs as residuals of cells dying after penetration of anti-DNA antibodies. These observations not only change the interpretation of the presence of the LE cell phenomenon, but also stress the potential pathophysiological role of antibodies to intracellular antigens in autoimmune diseases.
The Long QT Syndrome A Review of Recent Molecular Genetic and Physiologic Discoveries (1996)

There is great reason for optimism in the field of research into the long QT syndrome (LQT). We have made considerable progress, but there is much more to be done. We used molecular genetics to identify genes responsible for 2 forms of LQT (cardiac potassium and sodium channel genes HERG and SCN5A, respectively). These discoveries have led to improved mechanistic undertaking of the disorder and created the possibility for genetic testing. We are working to develop genetic tests for autosomal dominant LQT, but this will require identification of additional LQT genes. Specialized research laboratories like ours can provide genetic testing for many families, but these tests are not yet generally available. These tests may be particularly useful for families with LQT, since asymptomatic LQT gene carriers are still at risk for sudden death. Finally, molecular genetic and physiologic studies offer the possibility of new strategies for treatment and prevention of this cardiovascular disease.
Two distinct mechanisms alter p53 in breast cancer: mutation and nuclear exclusion. (1992)

Twenty-seven cases of inflammatory breast cancer were screened for the presence of the p53 protein by immunocytochemical methods using a monoclonal antibody directed against the p53 protein. Three groups were detected: 8 cases (30%) had high levels of p53 in the nucleus of the cancer cells; 9 cases (33%) had a complete lack of detectable staining; 10 cases (37%) showed a pattern of cytoplasmic staining with nuclear sparing. Nucleotide sequence analysis of p53 cDNAs derived from the samples with cytoplasmic staining revealed only wild-type p53 alleles in 6 out of 7 cases. An eighth case was determined to be wild type by a single-strand conformation polymorphism. In contrast, the samples containing nuclear p53 contained a variety of missense mutations and a nonsense mutation. The p53 cDNAs from 3 of the tumors that lacked detectable p53 staining were analyzed, and all 3 had wild-type nucleotide sequences. Interestingly, a case of normal lactating breast tissue also showed intense cytoplasmic staining for p53 with nuclear sparing. These data suggest that some breast cancers that contain the wild-type form of p53 protein may inactivate its tumor-suppressing activity by sequestering this protein in the cytoplasm, away from its site of action in the cell nucleus. The detection of cytoplasmic p53 in normal lactating breast tissue could suggest that this is the mechanism employed in specific physiological situations to permit transient cell proliferation. This observation could explain how some breast cancer tissues inactivate p53 function without mutation.
Feature subset selection using the wrapper method: overfltting and dynamic search space topology (1995)

Before diagnosis, BCSs had similar adherence to health behaviours compared to cancer-free women. Initial positive changes to health behaviours were observed post BC diagnosis, except healthy body weight, but maintenance of such changes over the long-term was poor. BCSs may benefit from additional advice and support to make healthy lifestyle choices throughout survivorship.
Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking. (1988)

By running the Swedish twin registry containing about 25,000 pairs of twins of the same sex together with the central national diagnosis register of hospital inpatients, 80 twin pairs suffering from inflammatory bowel disease were found. In the ulcerative colitis group one of 16 monozygotic pairs was concordant for the disease, but all the other 20 pairs (dizygotic or unknown zygosity) were discordant. In the Crohn's disease group eight of 18 monozygotic pairs and one of 26 dizygotic pairs were concordant. The proband concordance rate among monozygotic twins was 6.3% for ulcerative colitis and 58.3% for Crohn's disease. The calculated heritability of liability based on monozygotic pairs was 0.53 and 1.0 respectively. Thus heredity as an aetiological factor is stronger in Crohn's disease than in ulcerative colitis. Monozygotic twins with Crohn's disease were more likely to be smokers than monozygotic twins with ulcerative colitis. Smoking did not explain the discordance of twin pairs with either ulcerative colitis, or Crohn's disease. The combination of identical heredity and similar smoking habit is not sufficient to cause disease.
Role for Stearoyl-CoA Desaturase-1 in Leptin-Mediated Weight Loss (2002)

Leptin elicits a metabolic response that cannot be explained by its anorectic effects alone. To examine the mechanism underlying leptin's metabolic actions, we used transcription profiling to identify leptin-regulated genes in ob/ob liver. Leptin was found to specifically repress RNA levels and enzymatic activity of hepatic stearoyl-CoA desaturase-1 (SCD-1), which catalyzes the biosynthesis of monounsaturated fatty acids. Mice lacking SCD-1 were lean and hypermetabolic. ob/ob mice with mutations in SCD-1 were significantly less obese than ob/ob controls and had markedly increased energy expenditure. ob/ob mice with mutations in SCD-1 had histologically normal livers with significantly reduced triglyceride storage and VLDL (very low density lipoprotein) production. These findings suggest that down-regulation of SCD-1 is an important component of leptin's metabolic actions.
Synthesis and Characterization of Biocompatible and Size-Tunable Multifunctional Porous Silica Nanoparticles (2009)

In this work, size-controlled multifunctional mesoporous silica nanoparticles having large surface areas, embedded luminescence, high magnetization, and excellent aqueous dispersity have been successfully prepared by using a simple one-pot synthesis. The size and pore ordering of these particles can be easily controlled based on the number density of Fe3O4 nanoparticle nucleation sites introduced during the silica condensation reaction. Dissolution of the embedded Fe3O4 nanoparticles yields hollow mesoporous silica nanoparticles as well. These multifunctional porous nanoparticles were characterized by transmission electron microscopy, X-ray diffraction, nitrogen adsorption−desorption behavior, dynamic light scattering, zeta potential, magnetic susceptibility, and photoluminescence. Furthermore, in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and hemolysis assays were performed to evaluate any unintended cytotoxicity. The biocompatibility of the multifunctional nanoparticles, even at very high doses, ensures their potential in biomedical applications.
Mithramycin blocks transcriptional initiation of the c-myc P1 and P2 promoters (1991)

The c-myc protooncogene plays an important role in the regulation of cellular proliferation. Mithramycin, a DNA binding antibiotic which binds G-C-rich DNA, inhibits c-myc expression in both differentiating and nondifferentiating cells. The G-C-rich nature of the c-myc promoter suggests that mithramycin may act by directly inhibiting promoter function. The mithramycin binding sites in the c-myc promoter regions were determined by DNAse I footprinting. Particularly prominent mithramycin binding is noted in the regions just 5' of the P1 and P2 promoter TATA boxes. Gel retardation experiments performed in the presence of mithramycin demonstrate that drug binding can prevent the formation of discrete complexes between HeLa cell nuclear proteins and c-myc promoter DNA fragments. Mithramycin also directly blocks the binding of the transcription factor Sp1 to the P1 promoter region. In vitro run-off transcription demonstrates that mithramycin can completely inhibit the in vitro function of both the P1 and P2 promoters. These data suggest that mithramycin inhibits transcription of the c-myc protooncogene by blocking the binding of important regulatory factors, thus preventing formation of the c-myc transcription initiation complex.
New potential treatments for protection of pancreatic B‐cell function in Type 1 diabetes (2008)

Type 1 diabetes mellitus results from the progressive and specific autoimmune destruction of insulin-secreting pancreatic B-cells, which develops over a period of years and continues after the initial clinical presentation. The ultimate goal of therapeutic intervention is prevention or reversal of the disease by the arrest of autoimmunity and by preservation/restoration of B-cell mass and function. Recent clinical trials of antigen-specific or non-specific immune therapies have proved that modulation of islet specific autoimmunity in humans and prevention of insulin secretion loss in the short term after the onset of disease is achievable. The identification of suitable candidates for therapy, appropriate dosage and timing, specificity of intervention and the side-effect profile are crucial for the success of any approach. Considering the complexity of the disease, it is likely that a rationally designed approach of combined immune-based therapies that target suppression of B-cell specific autoreactivity and maintenance of immune tolerance, coupled with islet regeneration or replacement of the destroyed B-cell mass, will prove to be most effective in causing remission/reversal of disease in a durable fashion.
Comparison of clinical and videofluoroscopic evaluation of children with feeding and swallowing difficulties (2005)

The objectives of this study were threefold: (1) to evaluate the accuracy of clinical evaluation compared with videofluoroscopic swallowing studies (VFSSs) in the detection of penetration and aspiration in children of age 0 to 15 years presenting with feeding and swallowing problems; (2) to assess the relationship between therapists' confidence ratings in making judgements about the presence or absence of penetration and aspiration, and the accuracy of their evaluation as confirmed by VFSSs; (3) to identify clinical predictors of penetration and aspiration during clinical evaluation of children with feeding and swallowing difficulties. We used a prospective study to evaluate the sensitivity, specificity, and positive and negative predictive values of a diagnostic clinical evaluation compared with VFSSs (criterion standard). Clinical evaluation and videofluoroscopy forms for oral motor and swallowing evaluation, which included potential indicators of aspiration, were designed for this project. Seventy-five children with feeding problems participated (33 females, 42 males; age range 0 to 14 years, mean 2 years; 62% of participants younger than 12 months). For fluids, clinical evaluation showed a sensitivity of 92% for aspiration. For solids, sensitivity for detecting aspiration was 33%. Analysis of the therapists' mean confidence ratings compared with the accuracy of their judgement demonstrated that when therapists were very sure that the child was aspirating or penetrating or not, they were correct. When the therapists were unsure, then the accuracy of prediction was not as good. Cough was the most significant predictor (p < 0.05) of fluid aspiration and penetration. We conclude that clinical evaluation with experienced clinicians can detect aspiration and penetration of fluids in children of varied ages and diagnoses, but that it is not accurate with solids.
Pressure balanced, low hysteresis, finger seal test results (1999)

The purpose of this presentation is to demonstrate: low cost photoetching fabrication technique; pressure balanced finger seal design; and finger seal operation. The tests and analyses includes: finger seal air leakage analysis; rotor-run out and endurance tests; and extensive analytical work and rig testing.
Intracellular effectors regulating the activity of the Lactococcus lactis CodY pleiotropic transcription regulator (2004)

CodY is a pleiotropic transcriptional regulator conserved in low-G+C Gram-positive bacteria. Two distinct signals have been shown independently to influence the activity of this regulator: the level of intracellular GTP in Bacillus subtilis and the level of intracellular branched-chain amino acids (BCAA) isoleucine, leucine and valine in Lactococcus lactis. Measurement of BCAA and GTP levels in several environmental conditions showed that L. lactis CodY responded to the intracellular BCAA concentrations but not to physiological fluctuations in intracellular GTP. In addition, we demonstrated that CodY from L. lactis did not respond to intracellular GTP even when complementing CodY activity in B. subtilis. However, L. lactis CodY activity could still be modulated in B. subtilis by adding a rich nitrogen source to the growth media. This finding suggests that only BCAA are sensed by L. lactis CodY, whereas both GTP and BCAA signals may be integrated by B. subtilis CodY. The difference in the function of CodY from B. subtilis and L. lactis seems to reflect the difference in the physiology of these two bacteria.