gebhart/patrepeval huggingface dataset:
The Polycomb Group Protein EED Interacts with YY1, and Both Proteins Induce Neural Tissue in XenopusEmbryos (2001)

Polycomb group (PcG) proteins form multimeric protein complexes which are involved in the heritable stable repression of genes. Previously, we identified two distinct human PcG protein complexes. The EED-EZH protein complex contains the EED and EZH2 PcG proteins, and the HPC-HPH PcG complex contains the HPC, HPH, BMI1, and RING1 PcG proteins. Here we show that YY1, a homolog of the Drosophila PcG protein pleiohomeotic (Pho), interacts specificially with the human PcG protein EED but not with proteins of the HPC-HPH PcG complex. Since YY1 and Pho are DNA-binding proteins, the interaction between YY1 and EED provides a direct link between the chromatin-associated EED-EZH PcG complex and the DNA of target genes. To study the functional significance of the interaction, we expressed the Xenopus homologs of EED and YY1 in Xenopus embryos. Both Xeed and XYY1 induce an ectopic neural axis but do not induce mesodermal tissues. In contrast, members of the HPC-HPH PcG complex do not induce neural tissue. The exclusive, direct neuralizing activity of both the Xeed and XYY1 proteins underlines the significance of the interaction between the two proteins. Our data also indicate a role for chromatin-associated proteins, such as PcG proteins, in Xenopus neural induction.
RNAi off-targeting: Light at the end of the tunnel. (2006)

The broad post-transcriptional gene regulation induced by RNA interference (RNAi) is mediated by microRNAs (miRNAs). These small, highly structured, non-coding RNAs undergo extensive processing in both the nucleus and cytoplasm before partnering with the RNA Induced Silencing Complex (RISC) to target the 3′ UTR of messenger RNAs for degradation and/or translation attenuation.

Synthetic 19 base pair (bp) RNA duplexes (small interfering RNAs, siRNAs) can enter RISC directly and induce RNAi-mediated cleavage of targeted transcripts without additional processing. Though this ability has enormous potential, expansion of RNAi technology requires overcoming obstacles associated with siRNA functionality and specificity. Initial problems associated with inconsistent gene knockdown were found to be inherent in the sequence and thermodynamic properties of the siRNA and were addressed by development of algorithms that enabled the selection of highly functional sequences. In contrast, three separate attributes appear to contribute to overall siRNA specificity, thus making precise knockdown a surprisingly onerous problem.

Two of the features that contribute to a lack of siRNA specificity were found to be non-specific in nature. As demonstrated by Federov et al (Fedorov et al, 2005), cationic lipids typically used to deliver siRNA can induce broad changes in gene expression profiles. Separately, multiple labs have observed that particular sequence motifs as well as dsRNA lengths can induce broad, non-specific changes in gene expression that have origins in the induction of the interferon response pathway (Hornung et al, 2005; Judge et al, 2005). While these unanticipated effects can be eliminated by adopting stringent siRNA design filters and optimizing lipid concentrations and/or compositions, the most recent challenge, siRNA-mediated off-target effects, has required a more thorough understanding of the mechanism underlying RNAi.
Occurrence of dysplasia and adenocarcinoma after experimental chronic ulcerative colitis in hamsters induced by dextran sulphate sodium. (1992)

In this study, long term dextran sulphate sodium administration was studied to ascertain whether colorectal carcinoma could be produced in patients with long standing ulcerative colitis. Simultaneously, changes in the intestinal microflora were analysed. Low grade to high grade dysplasia was seen in three of the five hamsters treated with 1% dextran sulphate sodium solution for 100 days, while no dysplasia was detected in the eight animals concomitantly treated with metronidazole, an antianerobic microbial agent, which prevents colonic ulceration. In these two groups, none of the animals developed colorectal cancer over 100 day period. In a group treated for 180 days, seven of the eight animals had dysplasia, and one had two adenomas. Furthermore, four of the eight animals had adenocarcinoma in the transverse colon; they were protruding well differentiated adenocarcinoma in one and non-protruding lesions infiltrating into the musclaris propria in three. The three non-protruding infiltrating adenocarcinomas were classified to be well differentiated adenocarcinoma in one and mucinous adenocarcinoma in two, resembling the type of cancer which complicates ulcerative colitis in man.
Identification of canine pulmonary surfactant-associated glycoprotein A precursors (1985)

Surfactant-associated glycoproteins A were identified by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis of crude surfactant from canine alveolar lavage: an unglycosylated form (protein A1), 27,000-28,000 daltons; glycoprotein A2, 32,000-34,000 daltons; and glycoprotein A3, 37,000-38,000 daltons; pH at isoelectric point (pI) 4.5-5.0. Glycoproteins A2 and A3 were electroeluted and used to prepare a monospecific antiserum that identified proteins A1, A2, and A3 in immunoblots of crude surfactant obtained from dog lung lavage. This antiserum precipitated several proteins from in vitro translated canine lung poly(A)+ mRNA; proteins of 27,000 daltons, pI 5.0, and 28,000 daltons, pI 4.8-5.0, which precisely comigrated with proteins A1 from canine surfactant. Cotranslational processing of the primary translation products by canine pancreatic microsomal membranes resulted in larger proteins of 31,000-34,000 daltons, pI 4.8-5.0. Treatment of these processed forms of glycoprotein A with endoglycosidase F, to remove N-linked carbohydrate, resulted in proteins of 27,000-28,000 daltons which precisely comigrated with surfactant protein A1. These observations demonstrate that the polypeptide precursors to the glycoproteins A complex are extensively modified by addition of asparagine N-linked complex carbohydrate and are subsequently secreted as glycoproteins A2 and A3.
Adaptation of Swinepox Virus to an Established Cell Line (1972)

Swinepox virus was successfully adapted to the PK-15 cell line, but not the MDBK cell line. Virus titers obtained in the PK-15 host cell system were comparable to diploid swine kidney cell cultures.
Dehydroepiandrosterone sulphate interferes with the Abbott Architect direct immunoassay for testosterone (2006)

DHEA-S cross-reacts in the Abbott Architect direct immunoassay for testosterone to a clinically significant effect. This cross-reactivity is likely to be responsible for much of the interference observed when measuring testosterone in women by this method.
A novel technique for measuring variations in DNA copy-number: competitive genomic polymerase chain reaction (2007)

CGP is a moderate throughput technique for analyzing changes in genomic copy numbers. Because CGP can measure any genomic locus using PCR primers, it is especially useful for detailed analysis of a genomic region of interest.
Expression of miR-17-92 enhances anti-tumor activity of T-cells transduced with the anti-EGFRvIII chimeric antigen receptor in mice bearing human GBM xenografts (2013)

These results warrant the development of novel CAR-T-cell strategies that incorporate miR-17-92 to improve therapeutic potency, especially in patients with GBM.
Niemann-Pick Type C1 I1061T Mutant Encodes a Functional Protein That Is Selected for Endoplasmic Reticulum-associated Degradation Due to Protein Misfolding (2008)

Over 200 disease-causing mutations have been identified in the NPC1 gene. The most prevalent mutation, NPC1(I1061T), is predicted to lie within the cysteine-rich luminal domain and is associated with the classic juvenile-onset phenotype of Niemann-Pick type C disease. To gain insight into the molecular mechanism by which the NPC1(I1061T) mutation causes disease, we examined expression of the mutant protein in human fibroblasts homozygous for the NPC1(I1061T) mutation. Despite similar NPC1 mRNA levels between wild type and NPC1(I1061T) fibroblasts, NPC1 protein levels are decreased by 85% in NPC1(I1061T) cells. Metabolic labeling studies demonstrate that unlike wild type protein, which undergoes a glycosylation pattern shift from Endo H-sensitive to Endo H-resistant species, NPC1(I1061T) protein remains almost exclusively Endo H-sensitive and exhibits a reduced half-life (t((1/2)) 6.5 h) versus wild type Endo H-resistant species (t((1/2)) 42 h). Treatment with chemical chaperones, growth at permissive temperature, or inhibition of proteasomal degradation increases NPC1(I1061T) protein levels, indicating that the mutant protein is likely targeted for endoplasmic reticulum-associated degradation (ERAD) due to protein misfolding. Overexpression of NPC1(I1061T) in NPC1-deficient cells results in late endosomal localization of the mutant protein and complementation of the NPC mutant phenotype, likely due to a small proportion of the nascent NPC1(I1061T) protein that is able to fold correctly and escape the endoplasmic reticulum quality control checkpoints. Our findings provide the first description of an endoplasmic reticulum trafficking defect as a mechanism for human NPC disease, shedding light on the mechanism by which the NPC1(I1061T) mutation causes disease and suggesting novel approaches to treat NPC disease caused by the NPC1(I1061T) mutation.
ADP Receptors and Clinical Bleeding Disorders (1999)

ADP plays a key role in hemostasis and thrombosis. Despite its early identification in 1961 as the first known aggregating agent, the molecular basis of ADP-induced platelet activation is only beginning to be understood. The present review proposes a model of 3 purinergic receptors contributing separately to the complex process of ADP-induced platelet aggregation: the P2X(1) ionotropic receptor, responsible for rapid influx of ionized calcium into the cytosol; the P2Y(1) metabotropic receptor, responsible for mobilization of ionized calcium from internal stores, which initiates aggregation; and an as-yet-unidentified P2Y receptor coupled to G(alphai2), which is essential for the full aggregation response to ADP. It is probable that this as-yet-unidentified receptor is the molecular target of the ADP-selective antiaggregating drugs ticlopidine and clopidogrel. In addition, it is probably defective in patients with a bleeding diathesis that is characterized by selective impairment of platelet responses to ADP.
Quantitative determination of apolipoproteins C-I and C-II in human plasma by separate electroimmunoassays. (1981)

Abstract Separate electroimmunoassays are described for measuring human plasma apolipoproteins C-I and C-II. Purified apolipoproteins C-I and CII were used in preparing monospecific antisera and as the primary standards. These assays are sensitive (maximal sensitivity, 20 ng), specific, rapid, precise (the within- and between-assay coefficients of variation for both assays were 5 and 8%, respectively), and accurate (accuracy was based on comparison of calculated and measured C-I, C-II, and C-III contents of an ApoC-containing column-eluent fraction) and are applicable to measurement of C-I and C-II polypeptides in whole plasma and density classes. However, plasma samples with triglyceride (triacylglycerol) concentrations greater than 6000 mg/L must be delipidized before analysis for C-II, as must those with greater than 12 000 mg/L before analysis for C-I polypeptide. Mean concentrations (and SD) of C-I in plasma of normolipidemic subjects and hyperlipoproteinemic phenotypes IIa, IIb, IV, and V were 60 (15), 70 (20), 100 (20), 100 (20), and 260 (94) mg/L, respectively. The corresponding C-II values were 40 (20), 43 (20), 68 (20), 65 (20), and 210 (70), respectively. C-I and C-II concentrations in patients with phenotypes IIb v, IV, or V significantly (p less than 0.001) exceeded those in normal persons or phenotype IIa. The observed correlations (r = 0.92 and r = 0.94) between triglyceride and C-I and C-II values suggest that these two polypeptides, like C-III, are excellent plasma markers for assessing the state of triglyceride metabolism.
Progesterone administration by nasal spray in menopausal women: Comparison between two different spray formulations (1992)

The aim of the study was to compare the bioavailability of progesterone dissolved in almond oil or dimethicone, and administered by nasal spray. Twenty healthy menopausal women were randomly allocated to treatment by four doses of intranasal spray either of a progesterone solution in almond oil, 2 mg/0.1 ml, corresponding to a total dose of approximately 11 mg of progesterone, or a progesterone solution in dimethicone 5 mg/0.1 ml corresponding to a total dose of approximately 28 mg of progesterone. Circulating progesterone levels were calculated at various time intervals following administration. The formulation with almond oil yielded a maximum progesterone concentration (Cmax of 3.75 ng/ml at Tmax = 60 min, and the area under the curve (AUC0-720) value was 1481.6 +/- 343. The formulation with dimethicone yielded a mean Cmax of 1.049 ng/ml at Tmax = 30 min; the AUC0-720 value was 302.06 +/- 37.5. Therefore, bioavailability of progesterone dissolved in almond oil proved to be largely superior compared to the solution in dimethicone. The crucial role of the carrier in the spray formulations is discussed; in addition to ensuring clinical safety, it must have good solubility for progesterone, be fluid enough to enable efficient 'spraying' and also must allow progesterone to be absorbed through the nasal mucosa.
A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome (2009)

Chronic fatigue syndrome (CFS) is complex illness of unknown etiology. Among the broad range of symptoms, many patients report disturbances in the emotional realm, the most frequent of which is anxiety. Research shows that patients with CFS and other so-called functional somatic disorders have alterations in the intestinal microbial flora. Emerging studies have suggested that pathogenic and non-pathogenic gut bacteria might influence mood-related symptoms and even behavior in animals and humans. In this pilot study, 39 CFS patients were randomized to receive either 24 billion colony forming units of Lactobacillus casei strain Shirota (LcS) or a placebo daily for two months. Patients provided stool samples and completed the Beck Depression and Beck Anxiety Inventories before and after the intervention. We found a significant rise in both Lactobacillus and Bifidobacteria in those taking the LcS, and there was also a significant decrease in anxiety symptoms among those taking the probiotic vs controls (p = 0.01). These results lend further support to the presence of a gut-brain interface, one that may be mediated by microbes that reside or pass through the intestinal tract.
Functional Role of Inflammatory Cytokines and Antiinflammatory Molecules in Seizures and Epileptogenesis (2002)

This study shows that limbic seizures in rodents rapidly and reversibly induce proinflammatory cytokines in glia and suggests that changes in the IL-1Ra/IL-1beta ratio in brain may represent an effective physiopathologic mechanism to control seizures.
Differential responsiveness of human breast cancer cell lines MCF-7 and T47D to growth factors and 17 beta-estradiol. (1988)

A completely serum-free assay method has been used to compare the mitogenic activities of polypeptide growth factors and estrogens with MCF-7 and T47D human breast cancer cells in culture. The lines were maintained in a viable, slowly dividing condition in Ham's F12 and Dulbecco's modified Eagle's medium (1:1) supplemented with sodium bicarbonate (2.2 g/liter), 15 mM 4-(2-hydroxyethyl)-1-piperazineethane-sulfonic acid, human transferrin (10 micrograms/ml), and bovine serum albumin (200 micrograms/ml) (designated Tf/BSA). This medium allowed the assay of mitogenic activities as measured by multiple rounds of cell division and permitted comparisons of the biological potencies of growth factors within functional families as well as of dissimilar mitogens. Insulin-like growth factor I (IGF-I) was the most potent mitogen studied, showing ED50 values of 160 pg/ml and 1.7 ng/ml with the MCF-7 and T47D cells, respectively. Insulin-like growth factor II and insulin were less active, with ED50 values of 0.55 and 1.2 ng/ml with MCF-7 cells and 4.3 and 10 ng/ml with the T47D cell line, respectively. Mitogens sharing epidermal growth factor-like functional properties had ED50 values from 35 pg/ml to 2.5 ng/ml, while transforming growth factor type beta and platelet-derived growth factor had no detectable stimulatory effects. Basic fibroblast growth factor had ED50 values of 0.42 ng/ml and 3.7 ng/ml for the MCF-7 and T47D cells, respectively, while acidic fibroblast growth factor was nearly inactive. In phenol red-free Tf/BSA, 17 beta-estradiol caused a 60% increase in MCF-7 cell numbers over controls in 8 days while having no effect on growth of the T47D cell line. From MCF-7 conditioned Tf/BSA medium, IGF-I was identified by biological activity, by radioimmunoassay (approximately equal to 2 pg/ml) and by estimation of molecular weight (8,000) under dissociating conditions. The concentration of IGF-I was not affected by 17 beta-estradiol treatment. The data indicate that induction of acid stable, low molecular weight autocrine growth factors involved more regulation than defined by estrogens alone. The minimal effects of 17 beta-estradiol in Tf/BSA opened several possibilities including the putative roles of other serum-borne hormones, growth factors and regulators in autocrine growth factor induction.
Dengue 2 Vaccine: Dose Response in Volunteers in Relation to Yellow Fever Immune Status (1983)

A live dengue 2 vaccine was tested in 38 volunteers in an evaluation of the safety, infectivity, and immunogenicity of doses of 10(1.8)-10(5.5) plaque-forming units. Twenty yellow fever-immune and 18 yellow fever-nonimmune individuals received 0.5 ml of vaccine sc. Immunization was dose related in yellow fever-immune volunteers, with a 50% immunizing dose of 10(3.3) plaque-forming units. In the group not immune to yellow fever, some but not all recipients of each vaccine dilution were immunized, and no 50% immunizing dose could be estimated. Volunteers immune to yellow fever developed adequate titers of neutralizing antibody to dengue 2 virus and maintained them for at least three years; those not immune to yellow fever developed lower antibody titers that disappeared within six months in half of the cases. More than 40 isolates of dengue 2 virus from 12 volunteers retained the in vitro growth characteristics of the vaccine virus; this result affirmed the genetic stability of the virus. Common clinical signs in immunized individuals were leukopenia (55%), macular rash (15%), and fever (10%).
[New esters of substituted anilinonicotinic and phenylanthranilic acids]. (1981)

In the search for new non-steroidal antiinflammatory drugs with low ulcerogenic activity, phthalidyl and pivaloyloxymethyl esters of anilinonicotinic and N-phenylanthranilic acids were synthesized. One of them, the 3-phthalidyl ester of 2-([3-(trifluoromethyl)phenyl]amino)-3-pyridinecarboxylic acid, also named talniflumate, showed lower ulcerogenic activity and toxicity and greater antiinflammatory activity than the niflumic acid.
Studies on the Mechanism of Activation of Adipose Tissue Pyruvate Dehydrogenase by Insulin (1973)

Abstract Incubation of rat epididymal adipose tissue fragments with insulin led to increases of up to 2.4-fold in the activity of pyruvate dehydrogenase subsequently assayed in tissue homogenates. The activation of pyruvate dehydrogenase by insulin was greatest when tissue was incubated in the presence of bicarbonate ions and when 2 mg of glucose or fructose per ml was added to the incubation medium. Several other agents known to inhibit lipolysis and to decrease cyclic AMP levels in fat cells, including niacin, 5-methylpyrazole-3-carboxylic acid, and prostaglandin E1 were also effective in activating pyruvate dehydrogenase. Severe depletion of tissue ATP levels caused by the addition of oligomycin or dinitrophenol, by anaerobic incubation, or by prolonged incubation with epinephrine in the absence of albumin also activated pyruvate dehydrogenase. Incubation of adipose tissue with 1 mm oleate, 1.5 mm octanoate, 1.5 mm heptanoate, 1 mm butyrate, or 3 mm dl-β-hydroxybutyrate decreased pyruvate dehydrogenase activity 20 to 70%. The addition of 5 mm acetate, 5 mm propionate, or 3 mm 4-pentenoate led to 70 to 160% activation of pyruvate dehydrogenase, whereas 1.5 mm pentanoate had no effect. High concentrations of glucose (20 mg per ml) or of pyruvate-lactate (5 and 30 mm, respectively) also increased tissue pyruvate dehydrogenase activity.
T&I engine (2011)

Ray tracing naturally supports high-quality global illumination effects, but it is computationally costly. Traversal and intersection operations dominate the computation of ray tracing. To accelerate these two operations, we propose a hardware architecture integrating three novel approaches. First, we present an ordered depth-first layout and a traversal architecture using this layout to reduce the required memory bandwidth. Second, we propose a three-phase ray-triangle intersection architecture that takes advantage of early exit. Third, we propose a latency hiding architecture defined as the ray accumulation unit. Cycle-accurate simulation results indicate our architecture can achieve interactive distributed ray tracing.
Human Placental Cytotrophoblasts Attract Monocytes and Cd56bright Natural Killer Cells via the Actions of Monocyte Inflammatory Protein 1α (2001)

During human pregnancy, the specialized epithelial cells of the placenta (cytotrophoblasts) come into direct contact with immune cells in several locations. In the fetal compartment of the placenta, cytotrophoblast stem cells lie adjacent to macrophages (Hofbauer cells) that reside within the chorionic villus stroma. At sites of placental attachment to the mother, invasive cytotrophoblasts encounter specialized maternal natural killer (NK) cells (CD56(bright)), macrophages, and T cells that accumulate within the uterine wall during pregnancy. Here we tested the hypothesis that fetal cytotrophoblasts can direct the migration of these maternal immune cells. First, we assayed the chemotactic activity of cytotrophoblast conditioned medium samples, using human peripheral blood mononuclear cells as targets. The placental samples preferentially attracted NK cells (both CD56(dim) and CD56(bright)), monocytes, and T cells, suggesting that our hypothesis was correct. A screen to identify chemokine activity through the induction of a Ca(2)+ flux in cells transfected with individual chemokine receptors suggested that cytotrophoblasts secreted monocyte inflammatory protein (MIP)-1alpha. This was confirmed by localizing the corresponding mRNA and protein, both in vitro and in vivo. MIP-1alpha protein in conditioned medium was further characterized by immunoblotting and enzyme-linked immunosorbent assay. Immunodepletion of MIP-1alpha from cytotrophoblast conditioned medium showed that this chemokine was responsible for a significant portion of the induced monocyte and CD56(bright) NK cell chemotaxis. These data suggest the specific conclusion that cytotrophoblasts can attract monocytes and CD56(bright) NK cells by producing MIP-1alpha and the more general hypothesis that these cells may organize and act on leukocytes at the maternal-fetal interface.