gebhart/patrepeval huggingface dataset:
Gαo mediates WNT-JNK signaling through Dishevelled 1 and 3, RhoA family members, and MEKK 1 and 4 in mammalian cells (2008)

In Drosophila, activation of Jun N-terminal Kinase (JNK) mediated by Frizzled and Dishevelled leads to signaling linked to planar cell polarity. A biochemical delineation of WNT-JNK planar cell polarity was sought in mammalian cells, making use of totipotent mouse F9 teratocarcinoma cells that respond to WNT3a via Frizzled-1. The canonical WNT-beta-catenin signaling pathway requires both G alpha o and G alpha q heterotrimeric G-proteins, whereas we show that WNT-JNK signaling requires only G alpha o protein. G alpha o propagates the signal downstream through all three Dishevelled isoforms, as determined by epistasis experiments using the Dishevelled antagonist Dapper1 (DACT1). Suppression of either Dishevelled-1 or Dishevelled-3, but not Dishevelled-2, abolishes WNT3a activation of JNK. Activation of the small GTPases RhoA, Rac1 and Cdc42 operates downstream of Dishevelled, linking to the MEKK 1/MEKK 4-dependent cascade, and on to JNK activation. Chemical inhibitors of JNK (SP600125), but not p38 (SB203580), block WNT3a activation of JNK, whereas both the inhibitors attenuate the WNT3a-beta-catenin pathway. These data reveal both common and unique signaling elements in WNT3a-sensitive pathways, highlighting crosstalk from WNT3a-JNK to WNT3a-beta-catenin signaling.
Integrating automated test generation into the WYSIWYT spreadsheet testing methodology (2006)

Spreadsheet languages, which include commercial spreadsheets and various research systems, have had a substantial impact on end-user computing. Research shows, however, that spreadsheets often contain faults. Thus, in previous work we presented a methodology that helps spreadsheet users test their spreadsheet formulas. Our empirical studies have shown that end users can use this methodology to test spreadsheets more adequately and efficiently; however, the process of generating test cases can still present a significant impediment. To address this problem, we have been investigating how to incorporate automated test case generation into our testing methodology in ways that support incremental testing and provide immediate visual feedback. We have used two techniques for generating test cases, one involving random selection and one involving a goal-oriented approach. We describe these techniques and their integration into our testing environment, and report results of an experiment examining their effectiveness and efficiency.
Regulation of endothelin-1 gene expression by cell shape and the microfilament network in vascular endothelium (1997)

Endothelial synthesis and release of endothelin-1 (ET-1) are exquisitely regulated by external shear and strain. We tested the hypothesis that manipulation of endothelial cell shape can regulate ET-1 gene expression. Treatment of bovine aortic endothelial cell (BAEC) monolayers with cytochalasin D disrupted F-actin and induced cell retraction and rounding, in parallel with time- and dose-dependent specific decreases in ET-1 mRNA levels. Treatments with forskolin, phorbol 12-myristate 13-acetate, staurosporine, and genistein also induced cell shape change and decreased F-actin staining and ET-1 mRNA levels. BAEC plated onto nonadhesive petri dishes coated with decreasing concentrations of synthetic RGD polymer showed RGD dose-dependent decreases in cell spreading and in F-actin microfilament elaboration. These changes were specifically accompanied by decreases in ET-1 peptide secretion (60%) and, via posttranscriptional mechanisms, ET-1 mRNA (94%) and were not due to decreased cell-cell contact. We conclude that the shape and microfilament network of endothelial cells are potent posttranscriptional regulators of ET-1 gene expression.
The human U5 snRNP-specific 100-kD protein is an RS domain-containing, putative RNA helicase with significant homology to the yeast splicing factor Prp28p. (1997)

Through UV-crosslinking experiments, we previously provided evidence suggesting that a U5 snRNP protein with a molecular weight in the 100-kDa range is an ATP-binding protein (Laggerbauer B, Lauber J, Lührmann R, 1996, Nucleic Acid Res 24:868-875). Separation of HeLa U5 snRNP proteins on 2D gels revealed multiple variants with apparent molecular masses of 100 kDa. Subsequent microsequencing of these variants led to the isolation of a cDNA encoding a protein with an N-terminal RS domain and a C-terminal domain that contains all of the conserved motifs characteristic of members of the DEAD-box family of RNA-stimulated ATPases and RNA helicases. Antibodies raised against cDNA-encoded 100-kDa protein specifically recognized native U5-100kD both on immunoblots and in purified HeLa U5 snRNPs or [U4/U6.U5] tri-snRNP complexes, confirming that the bona fide 100-kDa cDNA had been isolated. In vitro phosphorylation studies demonstrated that U5-100kD can serve as a substrate for both Clk/Sty and the U1 snRNP-associated kinase, and further suggested that the multiple U5-100kD variants observed on 2D gels represent differentially phosphorylated forms of the protein. A database homology search revealed a significant degree of homology (60% similarity, 37% identity) between the Saccharomyces cerevisiae splicing factor, Prp28p, which lacks an N-terminal RS domain, and the C-terminal domain of U5-100kD. Consistent with their designation as structural homologues, anti-Prp28 antibodies recognized specifically the human U5-100kD protein on immunoblots. Together with the DEXH-box U5-200kD protein (Lauber J et al., 1996, EMBO J 15:4001-4015), U5-100kD is the second example of a putative RNA helicase that is tightly associated with the U5 snRNP. Given the recent identification of the U5-116kD protein as a homologue of the ribosomal translocase EF-2 (Fabrizio P, Laggerbauer B, Lauber J, Lane WS, Lührmann R, 1997, EMBO J 16:4092-4106), at least three integral U5 snRNP proteins thus potentially facilitate conformational changes in the spliceosome during nuclear pre-mRNA splicing.
Glioma Formation in Neurofibromatosis 1 Reflects Preferential Activation of K-RAS in Astrocytes (2005)

Abstract Children with the tumor predisposition syndrome, neurofibromatosis 1 (NF1), develop optic pathway gliomas. The NF1 gene product, neurofibromin, functions as a negative regulator of RAS, such that NF1 inactivation results in RAS hyperactivation. Recent studies have highlighted the divergent biological and biochemical properties of the various RAS isoforms, which prompted us to examine the consequence of Nf1 inactivation in astrocytes on RAS isoform activation in vitro and in vivo. In this report, we show that only K-RAS is activated in Nf1−/− astrocytes and that activation of K-RAS, but not H-RAS, accounts for the proliferative advantage and abnormal actin cytoskeleton–mediated processes observed in Nf1−/− astrocytes in vitro. Moreover, dominant inhibitory K-RAS corrects these abnormalities in Nf1−/− astrocytes invitro. Lastly, we show that Nf1+/− mice with astrocyte-specific activated K-RAS expression in vivo develop optic pathway gliomas, similar to our previously reported Nf1+/− mice with astrocyte Nf1 inactivation. Collectively, our results show that K-RAS is the primary target for neurofibromin GTPase-activating protein activity in vitro and in vivo and that K-RAS activation in astrocytes recapitulates the biochemical, biological, and tumorigenic properties of neurofibromin loss.
Laboratory detection of antiphospholipid antibodies (1996)

'Antiphospholipid' (aPL) antibodies are a heterogenous group of autoantibodies that are now considered to be directed mainly to plasma proteins or protein-phospholipid complexes. Standardisation of assays for anticardiolipin (aCL) antibodies and lupus anticoagulants (LA) have been fraught with difficulty despite numerous attempts to perform this by International Standardisation Workshops and Committees.
Concept Drift Adaptive Physical Event Detection for Social Media Streams (2019)

Event detection has long been the domain of physical sensors operating in a static dataset assumption. The prevalence of social media and web access has led to the emergence of social, or human sensors who report on events globally. This warrants development of event detectors that can take advantage of the truly dense and high spatial and temporal resolution data provided by more than 3 billion social users. The phenomenon of concept drift, which causes terms and signals associated with a topic to change over time, renders static machine learning ineffective. Towards this end, we present an application for physical event detection on social sensors that improves traditional physical event detection with concept drift adaptation. Our approach continuously updates its machine learning classifiers automatically, without the need for human intervention. It integrates data from heterogeneous sources and is designed to handle weak-signal events (landslides, wildfires) with around ten posts per event in addition to large-signal events (hurricanes, earthquakes) with hundreds of thousands of posts per event. We demonstrate a landslide detector on our application that detects almost 350% more land-slides compared to static approaches. Our application has high performance: using classifiers trained in 2014, achieving event detection accuracy of 0.988, compared to 0.762 for static approaches.
Study on Anti-cataract Drugs from Natural Sources. II. Effects of Buddlejae Flos on in Vitro Aldose Reductase Activity. (1995)

The inhibitory effects of nine crude drugs were tested on unpurified rat lens aldose reductase, an enzyme involved in the complications of diabetes. Among the crude drugs, a 70% methanolic extract of Buddlejae Flos (flower of Buddleja officinalis) exhibited the highest inhibition. Luteolin, luteolin-7-O-beta-D-glucopyranoside, apigenin and acacetin-7-O-alpha-L-rhamnopyranosyl-(6-1)-beta-D-glucopyranoside isolated from Buddlejae Flos showed the inhibitory activity, the IC50 (concentration of 50% inhibitory percentage) values of which were 0.21, 0.28, 0.58 and 0.75 microM, respectively. It is suggested that the inhibitory effect of Buddlejae Flos on aldose reductase is partially attributable to these flavonols or their glycosides.
Superior Capacitance of Functionalized Graphene (2011)

We report the superior capacitance of functionalized graphene prepared by controlled reduction of graphene oxide (GO). In a solvothermal method, GO dispersed in dimethylformamide (DMF) was thermally treated at a moderate temperature (150 °C), which allows a fine control of the density of functionalities. Surface functionalities on graphene would enable a high pseudocapacitance, good wetting property, and acceptable electric conductivity. A specific capacitance up to 276 F/g was achieved based on functionalized graphene at a discharge current of 0.1 A/g in a 1 M H2SO4 electrolyte, which is much higher than the benchmark material. The excellent performance of the functionalized graphene signifies the importance of controlling the surface chemistry of graphene-based materials.
Cross-Sectional Study of Soluble Intercellular Adhesion Molecule-1 and Cardiovascular Risk Factors in Apparently Healthy Men (1999)

An elevated plasma concentration of the soluble intercellular adhesion molecule-1 (sICAM-1) is associated with increased risk for future coronary events. However, data exploring the interrelations of sICAM-1 with known cardiovascular risk factors are sparse. We determined sICAM-1 levels in 948 middle-aged men with no prior history of cardiovascular disease. sICAM-1 levels increased with age (P<0.001) and were significantly associated with smoking (P<0.001), hypertension (P<0.05), and frequent alcohol consumption (P=0.006). Positive correlations were observed between sICAM-1 and triglycerides (r=0.15; P<0.001), fibrinogen (r=0.21; P<0.001), tissue-type plasminogen activator antigen (r=0.17; P<0.001), and total homocysteine (r=0.09; P=0.02); whereas a negative correlation was observed for high density lipoprotein cholesterol (r=-0.15; P<0. 001). Overall, plasma concentrations of sICAM-1 increased with increasing prevalence of usual cardiovascular risk factors; mean plasma concentrations were 231, 236, 245, 257, and 312 ng/mL for those subjects with 0, 1, 2, 3, and >4 risk factors, respectively (P<0.01 for trend). In multivariate analysis, age, smoking status, diabetes, systolic blood pressure, positive family history of coronary disease, and serum levels of total homocysteine and fibrinogen were all independently associated with sICAM-1 levels (all P</=0.05). sICAM-1 levels are associated with several established cardiovascular risk factors. Further studies will be needed to evaluate whether these associations reflect the role of sICAM-1 as a marker of preclinical atherosclerosis, and whether such interrelations might have a causal basis.
Emotion inference from human body motion (2021)

The human body has evolved to perform sophisticated tasks from locomotion to the use of tools. At the same time our body movements can carry information indicative of our intentions, inter-personal attitudes and emotional states. Because our body is specialised to perform a variety of everyday tasks, in most situations emotional effects are only visible through subtle changes in the qualities of movements and actions. This dissertation focuses on the automatic analysis of emotional effects in everyday actions. In the past most efforts to recognise emotions from the human body have focused on expressive gestures which are archetypal and exaggerated expressions of emotions. While these are easier to recognise by humans and computational pattern recognisers they very rarely occur in natural scenarios. The principal contribution of this dissertation is hence the inference of emotional states from everyday actions such as walking, knocking and throwing. The implementation of the system draws inspiration from a variety of disciplines including psychology, character animation and speech recognition. Complex actions are modelled using Hidden Markov Models and motion primitives. The manifestation of emotions in everyday actions is very subtle and even humans are far from perfect at picking up and interpreting the relevant cues because emotional influences are usually minor compared to constraints arising from the action context or differences between individuals. This dissertation describes a holistic approach which models emotional, action and personal influences in order to maximise the discriminability of different emotion classes. A pipeline is developed which incrementally removes the biases introduced by different action contexts and individual differences. The resulting signal is described in terms of posture and dynamic features and classified into one of several emotion classes using statistically trained Support Vector Machines. The system also goes beyond isolated expressions and is able to classify natural action sequences. I use Level Building to segment action sequences and combine component classifications using an incremental voting scheme which is suitable for online applications. The system is comprehensively evaluated along a number of dimensions using a corpus of motion-captured actions. For isolated actions I evaluate the generalisation performance to new subjects. For action sequences I study the effects of reusing models trained on the isolated cases vs adapting models to connected samples. The dissertation also evaluates the role of modelling the influence of individual user differences. I develop and evaluate a regression-based adaptation scheme. The results bring us an important step closer to recognising emotions from body movements, embracing the complexity of body movements in natural scenarios.
Aging Decreases Oxidative Metabolism and the Release and Synthesis of Acetylcholine (1981)

Acetylcholine (ACh) synthesis in vivo is known to decrease during the aging process (senescence). To elucidate the molecular mechanism(s) of this age-related decline, we studied brain slices from 3-, 10-, and 30-month-old mice of two strains (C57B1 and Balb/c). In low K+ media, oxidative metabolism as measured by 14CO2 production decreased with aging from 100% (3 months) to 85% (10 months) or 71% (30 months) whether [U-14C]glucose, [3,4-14C]glucose, or [1-14C]pyruvate was the substrate. In the aged brain (30 months) the increase in 14CO2 production with K+ stimulation was about twofold higher than in the young brain (3 months). Thus, in high K+ media, only slight decreases (less than 10%) in oxidative metabolism occurred with aging. Changes in ACh synthesis paralleled the decreases in 14CO2 production. Synthesis of [14C]ACh from [U-14C]glucose in low K+ media declined from 100% (3 months) to 85% (10 months) or 66% (30 months), while in high K+ media only slight decreases (less than 10.5%) occurred with aging. The Ca2+-dependent, K+-stimulated release of [14C]ACh declined from 100% (3 months) to 58% (10 months) or 25% (30 months). Only the decrease in he release of ACh declined to the same extent as the reduced in vivo synthesis of ACh with aging. The results suggest that decreases in oxidative metabolism, ACh synthesis, and in the release of ACh contribute to a reduction in cholinergic function in senescent brain.
Polariton emission from polysilane-based organic microcavities (2003)

We report the observation of strong coupling between exciton and photon modes in a conjugated polymer-based semiconductor microcavity. Thin films of the σ-conjugated poly[bis(p-butylphenyl)silane] (PBPS) were inserted between metal and dielectric mirrors to form the microcavity structures. Variation of the PBPS film thickness between 80 and 140 nm allowed the cavity photon resonance to be tuned in the vicinity of the free exciton energy. The expected anticrossing behavior, with intensity and linewidth averaging, was observed at room temperature in the cavity reflection spectra and the vacuum Rabi splitting was found to be ⩽430 meV. This large value is consistent with the expectations of transfer matrix reflectivity calculations performed with optical constants data derived from a Kramers–Kronig analysis of the PBPS absorption spectrum. Angle-dependent photoluminescence measurements were performed for the microcavity with a 120 nm thickness PBPS layer. Unlike the emission from a standard, weakly coupled, cavity, the polariton emission shows almost no blueshift with angle, a desirable feature for potential display applications.
Immuno-Chemotherapy Using Repeated Vaccine Treatment Can Produce Successful Clinical Responses in Advanced Metastatic Melanoma (2010)

Advanced Stage IV and IIIc melanoma has a dismal survival, with or without, standard chemotherapy. New therapies are required to improve survival and reduce morbidity. Repeated vaccine dosing does not appear to have been explored, so Vaccinia Melanoma Cell Lysate (VMCL) vaccine repetitive therapy was tested, either alone, or combined with chemotherapy. 37 patients (31 Stage IV [M1a(6), b(7), c(18)] and 6 Stage IIIc) were studied using intra-dermal VMCL vaccine therapy. If disease progressed, vaccine was continued with standard chemotherapy (DTIC and/or Fotemustine). Overall survival was assessed and clinical responses were also recorded. From vaccine commencement, median overall follow-up was 10 months. Survivals ranged from 4 to 73 months. Median (mean) overall survival was 10 (23.5) months; overall survival at 1, 2 and 3 years was 40.5%, 21.6% and 10.8% respectively. CR and PR occurred in 18.9% (7) and 18.9% (7) of patients; these were durable for up to 6.1 years in 4 patients. Stable disease was noted in a further 17 patients (45.9%). In 6 patients (16.2%) no response to therapy was apparent. Repeated vaccinations with or without chemotherapy produced strong, durable clinical responses with overall survival > 23 months occurring in nearly 25% of advanced melanoma patients. The overall disease control rate (CR, PR and SD) was 83.7%, including CR in very advanced cases. These results, in a largely unselected population of advanced metastatic melanoma patients, compare very favourably with other regimens, and notably were associated with minimal, if any, toxicity. Further analysis of this approach appears warranted.
Design and Performance of a Low Btu Fuel Rich-Quench-Lean Gas Turbine Combustor (1996)

General Electric Company is developing gas turbines and a high temperature desulfurization system for use in integrated gasification combined cycle (IGCC) power plants. High temperature desulfurization, or hot gas cleanup (HGCU), offers many advantages over conventional low temperature desulfurization processes, but does not reduce the relatively high concentrations of fuel bound nitrogen (FBN) that are typically found in low Btu fuel. When fuels containing bound nitrogen are burned in conventional gas turbine combustors, a significant portion of the FBN is converted to NO{sub x}. Methods of reducing the NO{sub x} emissions from IGCC power plants equipped with HGCU are needed. Rich-quench-lean (RQL) combustion can decrease the conversion of FBN to NO{sub x} because a large fraction of the FBN is converted into non-reactive N{sub 2} in a fuel rich stage. Additional air, required for complete combustion, is added in a quench stage. A lean stage provides sufficient residence time for complete combustion. Objectives General Electric has developed and tested a rich-quench-lean gas turbine combustor for use with low Btu fuels containing FBN. The objective of this work has been to design an RQL combustor that has a lower conversion of FBN to N{sub x} than a conventional low Btu combustor and is suitable for use in a GE heavy duty gas turbine. Such a combustor must be of appropriate size and scale, configuration (can-annular), and capable of reaching ``F`` class firing conditions (combustor exit temperature = 2550{degrees}F).
The Effects of Acidic Fluoride Solutions on Early Enamel Erosion in vivo (2009)

Acidic fluoride solutions may reduce dental erosion. The aim of this study was to compare the effect of different acidic fluoride solutions on enamel dissolution using an established in vivo model. When possible 4 anterior teeth (255 teeth in a total of 67 subjects) were isolated and exposed to 0.01 M citric acid. The acid was collected in test tubes before (etch I) and 5 min after (etch II) application of test fluoride preparations. Acidic fluoride solutions (pH range 1.5-2.9), i.e. SnF(2), TiF(4) and hydrogen fluoride (HF) (all approx. 0.1 M F), HF (0.027, 0.055, 0.082 M F) and neutral NaF solution (0.1 M F) as control were applied to the labial surfaces of the teeth for 1 min (6 ml/min). Enamel dissolution was examined by chemical analysis of calcium content in the citric acid etch solutions using atom absorption spectrometry. The change in calcium concentration (DeltaCa) and the percentage of mean calcium reduction were calculated from the difference in calcium loss between etch I and etch II. Statistical analysis was carried out using the Wilcoxon signed rank test and Kruskal-Wallis tests with Dunn's multiple comparison. Results showed a mean DeltaCa of 0.671 mg/l (SD 0.625) for SnF(2), and ranged from 0.233 mg/l (SD 0.248) for the weakest HF solution to 0.373 mg/l (SD 0.310) for the strongest HF solution. This represented a 67% reduction in enamel dissolution for SnF(2) and a 40-76% reduction for the HF solutions. No reduction was observed for TiF(4) or NaF. The types of metal, pH and fluoride concentration are all important for the in vivo effect.