gebhart/patrepeval huggingface dataset:
Effect of the entero-pancreatic hormones, gastric inhibitory polypeptide and glucagon-like polypeptide-1(7–36) amide, on fatty acid synthesis in explants of rat adipose tissue (1991)

The effect of gastric inhibitory polypeptide (GIP), glucagon-like peptide-1(7-36) amide, (GLP-1(7-36) amide), glucagon-like peptide-2 (GLP-2), glucagon and insulin on fatty acid synthesis in explants of rat adipose tissue from various sites was investigated. GIP, GLP-1(7-36) amide and insulin stimulated fatty acid synthesis, as determined by measuring the incorporation of [14C]acetate into saponifiable fat, in a dose-dependent manner, over the concentration range 5-15 ng/ml (0.87-2.61 nmol/l) for insulin and 0.5-7.5 ng/ml for GIP (0.10-1.50 nmol/l) and GLP-1(7-36) amide (0.15-2.27 nmol/l). Insulin and GIP caused a significantly greater stimulation of [14C]acetate incorporation into fatty acids in omental adipose tissue than in either epididymal or subcutaneous adipose tissue. Both GIP and GLP-1(7-36) amide had the ability to stimulate fatty acid synthesis within the physiological range of the circulating hormones. At lower concentrations of the hormones, GLP-1(7-36) amide was a more potent stimulator of fatty acid synthesis than GIP in omental adipose tissue culture; the basal rate of fatty acid synthesis was 0.41 +/- 0.03 pmol acetate incorporated/mg wet weight tissue per 2 h; at 0.10 nmol hormone/1 1.15 +/- 0.10 and 3.40 +/- 0.12 pmol acetate incorporated/mg wet weight tissue per 2 h for GIP and GLP-1(7-36) amide respectively (P less than 0.01). GLP-2 and glucagon were without effect on fatty acid synthesis in omental adipose tissue. The study indicates that GIP and GLP-1(7-36)amide, in addition to stimulating insulin secretion, may play a direct physiological role in vivo, in common with insulin, in promoting fatty acid synthesis in adipose tissue.
Machine Learning Methods for Classifying Human Physical Activity from On-Body Accelerometers (2010)

The use of on-body wearable sensors is widespread in several academic and industrial domains. Of great interest are their applications in ambulatory monitoring and pervasive computing systems; here, some quantitative analysis of human motion and its automatic classification are the main computational tasks to be pursued. In this paper, we discuss how human physical activity can be classified using on-body accelerometers, with a major emphasis devoted to the computational algorithms employed for this purpose. In particular, we motivate our current interest for classifiers based on Hidden Markov Models (HMMs). An example is illustrated and discussed by analysing a dataset of accelerometer time series.
Comparative topical absorption and antioxidant effectiveness of two forms of coenzyme q10 after a single dose and after long‐term supplementation in the skin of young and middle‐aged subjects (2006)

Coenzyme Q 10 is an endogenous antioxidant found in the skin along with vitamins A, C and E. Coenzyme Q 10 is used increasingly in cosmetic products and is advertised as a skin energizer, protector against skin aging, skin repairer and an anti‐wrinkling agent. As the outermost layer of skin, the stratum corneum is the interface between the body and the environment and requires antioxidants to protect it and the epidermis and dermis below it. Nutrient levels in the stratum corneum correlate with those in the skin. Two forms of coenzyme Q 10 (pure coenzyme Q 10 and a yeast‐based coenzyme Q 10 ) were investigated in a commercial vehicle. Two groups of subjects were tested aged 21–29 and 51–70, respectively. Coenzyme Q 10 absorption in the stratum corneum was determined after a 1‐h application and ethanol extraction. Significantly more yeast coenzyme Q 10 was absorbed than the pure coenzyme Q 10 and the middle‐aged subjects absorbed about twice as much coenzyme Q 10 as did the younger subjects. Skin antioxidants were significantly increased by yeast coenzyme Q 10 but not by pure coenzyme Q 10 . Peroxides declined in the stratum corneum after twice daily application of coenzyme Q 10 with both forms but the decrease was greater with the yeast form. The older subjects had significantly higher baseline levels of lipid peroxides than did the younger group, indicating an increase in skin oxidative damage with age. The yeast coenzyme Q 10 is the superior form of coenzyme Q 10 for human skin application.
Expression cloning of a human polysialyltransferase that forms the polysialylated neural cell adhesion molecule present in embryonic brain. (1995)

Polysialic acid is a developmentally regulated posttranslational modification of the neural cell adhesion molecule (N-CAM). It has been suggested that this large anionic carbohydrate modulates the adhesive property of N-CAM, but the precise function of polysialic acid is not known. Here we describe the isolation and functional expression of a cDNA encoding a human polysialyltransferase. For this expression cloning, COS-1 cells were cotransfected with a human fetal brain cDNA library and a cDNA encoding human N-CAM. Transfected COS-1 cells were stained with a monoclonal antibody specific for polysialic acid and enriched by fluorescence-activated cell sorting. Sibling selection of recovered plasmids resulted in a cDNA clone that directs the expression of polysialic acid on the cell surface. The deduced amino acid sequence indicates that the polysialyltransferase shares a common sequence motif with other sialyltransferases cloned so far. The polysialyltransferase is, however, distinct by having two clusters of basic amino acids. The amount of the polysialyltransferase transcripts correlates well with the formation of polysialic acid in various human tissues, and is abundant in the fetal brain but not in the adult brain. Moreover, HeLa cells stably expressing polysialic acid and N-CAM promoted neurite outgrowth and sprouting. These results indicate that the cloned polysialyltransferase forms polysialylated, embryonic N-CAM, which is critical for plasticity of neural cells.
The rhd6 Mutation of Arabidopsis thaliana Alters Root-Hair Initiation through an Auxin- and Ethylene-Associated Process (1994)

Root-hair initiation in Arabidopsis thaliana provides a model for studying cell polarity and its role in plant morphogenesis. Root hairs normally emerge at the apical end of root epidermal cells, implying that these cells are polarized. We have identified a mutant, rhd6, that displays three defects: (a) a reduction in the number of root hairs, (b) an overall basal shift in the site of root-hair emergence, and (c) a relatively high frequency of epidermal cells with multiple root hairs. These defects implicate the RHD6 gene in root-hair initiation and indicate that RHD6 is normally associated with the establishment of, or response to, root epidermal cell polarity. Similar alterations in the site of root-hair emergence, although less extreme, were also discovered in roots of the auxin-, ethylene-, abscisic acid-resistant mutant axr2 and the ethylene-resistant mutant etr1. All three rhd6 mutant phenotypes were rescued when either auxin (indoleacetic acid) or an ethylene precursor (1-aminocyclopropane-1-carboxylic acid) was included in the growth medium. The rhd6 root phenotypes could be phenocopied by treating wild-type seedlings with an inhibitor of the ethylene pathway (aminoethoxyvinylglycine). These results indicate that RHD6 is normally involved in directing the selection or assembly of the root-hair initiation site through a process involving auxin and ethylene.
Set-membership localization and tracking of autonomous underwater vehicles (2002)

Algorithms are presented for localization and tracking of Autonomous Underwater Vehicles&#13;\n(AUVs) from acoustic time-of-flight measurements received by a field of surface floating buoys.&#13;\nThe algorithms assume that measurements and AUV dynamics uncertainties are unknown but&#13;\nbounded, with known bounds, and produce as output the set in a 3-D space of admissible AUV&#13;\npositions. The algorithms are taylored for a shallow water situation, and account for realistic&#13;\nvariations of the sound speed profile in sea water. The algorithms have been validated by&#13;\nsimulations in which uncertainty models have been obtained from field data at sea. Localization&#13;\nperformance of the algorithm are shown comparable with those previously reported in the&#13;\nliterature by other approaches who assume knowledge of the statistics of measurement&#13;\nuncertainties. Tracking performance is shown worse than that of Extended Kalman Filter (EKF)&#13;\nwhen uncertainties are unbiased. In presence of non-zero mean disturbances (as currents, tides,&#13;\netc.), the set-membership tracking algorithm outperforms EKF.
Mobility enhancements to the Scout robot platform (2003)

When a distributed robotic system is assigned to perform reconnaissance or surveillance, restrictions inherent to the design of an individual robot limit the system's performance in certain environments. Finding an ideal portable robotic platform capable of deploying and returning information in spatially restrictive areas is not a simple task. The Scout robot, developed at the University of Minnesota, is a viable robotic platform for these types of missions. The small form factor of the Scout allows for deployment, placement, and concealment of a team of robots equipped with a variety of sensory packages. However, the design of the Scout requires a compromise in power, sensor types, locomotion, and size; together these factors prevent an individual Scout from operating ideally in some environments. Several attempts to address these deficiencies have been implemented and are discussed. Among the prototype solutions are actuating wheels, allowing the Scout to increase ground clearance in varying terrains, a grappling hook enabling the Scout to obtain a position of elevated observation, and infrared emitters to facilitate low light operation.
Inhibition of p38 mitogen-activated protein kinase provides neuroprotection in cerebral focal ischemia (2001)

Mitogen-activated protein kinases (MAPKs) are involved in many cellular processes. The stress-activated MAPK, p38, has been linked to inflammatory cytokine production and cell death following cellular stress. Here, we demonstrate focal ischemic stroke-induced p38 enzyme activation (i.e., phosphorylation) in the brain. The second generation p38 MAPK inhibitor SB 239063 was identified to exhibit increased kinase selectivity and improved cellular and in vivo activity profiles, and thus was selected for evaluation in two rat models of permanent focal ischemic stroke. SB 239063 was administered orally pre- and post-stroke and intravenously post-stroke. Plasma concentration levels were achieved in excess of those that effectively inhibit p38 activity. In both moderate and severe stroke, SB 239063 reduced infarct size by 28-41%, and neurological deficits by 25-35%. In addition, neuroprotective plasma concentrations of SB 239063 that reduced p38 activity following stroke also reduced the stroke-induced expression of IL-1beta and TNFalpha (i.e., cytokines known to contribute to stroke-induced brain injury). SB 239063 also provided direct protection of cultured brain tissue to in vitro ischemia. This robust SB 239063-induced neuroprotection emphasizes a significant opportunity for targeting MAPK pathways in ischemic stroke injury, and also suggests that p38 inhibition be evaluated for protective effects in other experimental models of nervous system injury and neurodegeneration.
Electrospinning collagen and elastin: preliminary vascular tissue engineering (2004)

Significant challenges must be overcome before the true benefit and economic impact of vascular tissue engineering can be fully realized. Toward that end, we have pioneered the electrospinning of micro- and nano-fibrous scaffoldings from the natural polymers collagen and elastin and applied these to development of biomimicking vascular tissue engineered constructs. The vascular wall composition and structure is highly intricate and imparts unique biomechanical properties that challenge the development of a living tissue engineered vascular replacement that can withstand the high pressure and pulsatile environment of the bloodstream. The potential of the novel scaffold presented here for the development of a viable vascular prosthetic meets these stringent requirements in that it can replicate the complex architecture of the blood vessel wall. This replication potential creates an "ideal" environment for subsequent in vitro development of a vascular replacement. The research presented herein provides preliminary data toward the development of electrospun collagen and elastin tissue engineering scaffolds for the development of a three layer vascular construct.
Vimentin expression in different types of breast carcinoma immunohistochemical study. (1996)

Vimentin was preferentially expressed in medullary and high grade ductal not otherwise specified (NOS) carcinomas. It was not expressed in lobular carcinoma whether of the classical or the variant types. In the present study, 58 cases of invasive breast carcinomas were tested for vimentin on formaldehyde fixed paraffin embedded sections. Vimentin was expressed in 14/ 44 (32%) of infiltrating duct carcinoma NOS. It was expressed in less than 10% of tumour cells in 5/44 (11.4%) and in > or = 10% of tumour cells in 4/7 (57%). However, none of the lobular carcinoma expressed vimentin. Vimentin was expressed in 9 of 18 (50%) of grade III infiltrating duct NOS carcinoma versus 5 of 21 (24%) of grade II and 0 of 5 (0%) of grade I carcinoma. It was preferentially expressed in tumour growing in broad anastomosing bands or sheets with numerous mitoses, high nuclear grade, scanty supportive stroma and extensive necrosis.
Role of vascular endothelial growth factor in the pathogenesis of chronic obstructive pulmonary disease. (2007)

Chronic obstructive pulmonary disease (COPD) is a major worldwide health problem that has an increasing prevalence and mortality. However, the exact mechanism of initiation and progression of this disease has not been fully elucidated. Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis, which has multiple effects in lung development and physiology. VEGF is expressed in several amounts or parts in the lung, while it has been shown that differences in its expression play a significant role in the pathophysiology of two major phenotypes of COPD (emphysema and chronic bronchitis). VEGF is known to maintain the homeostasis of alveolar compartment, and therefore the decrease in VEGF expression affects the pathogenesis of emphysema. In emphysema, pulmonary endothelial cell apoptosis via reduction in VEGF activity causes alveolar epithelial cell apoptosis, thereby increasing the sensitivity of alveolar walls to oxidative stress and proteases. Therefore, the lack of VEGF in emphysema may provide implications for its substitution, whereas its over-expression in chronic bronchitis has led to interventions for the attenuation of its action. The scope of the present review is to summarize from a clinical point of view the role of VEGF in the pathogenesis of COPD and focus on its diagnostic and therapeutic implications.
Downbeat prediction by listening and learning (2006)

The perception of downbeat is not yet very well understood, although it generally "feels" natural and intuitive to music listeners. We propose an unbiased and predictive modeling strategy of downbeat by combining psychoacoustic models of music listening with time-lag embedded segment learning. The model is causal, tempo independent, and could inform in a top-down manner a bottom-up beat tracker. Results with particularly complex music examples are presented.
Kinetic isotope effects and ligand binding in PQQ-dependent methanol dehydrogenase (2005)

The reaction of PQQ (2,7,9-tricarboxypyrroloquinoline quinone)-dependent MDH (methanol dehydrogenase) from Methylophilus methylotrophus has been studied under steady-state conditions in the presence of an alternative activator [GEE (glycine ethyl ester)] and compared with similar reactions performed with ammonium (used more generally as an activator in steady-state analysis of MDH). Studies of initial velocity with methanol (protiated methanol, C1H3O1H) and [2H]methanol (deuteriated methanol, C2H3O2H) as substrate, performed with different concentrations of GEE and PES (phenazine ethosulphate), indicate competitive binding effects for substrate and PES on the stimulation and inhibition of enzyme activity by GEE. GEE is more effective at stimulating activity than ammonium at low concentrations, suggesting tighter binding of GEE to the active site. Inhibition of activity at high GEE concentration is less pronounced than at high ammonium concentration. This suggests a close spatial relationship between the stimulatory (KS) and inhibitory (KI) binding sites in that binding of GEE to the KS site sterically impairs the binding of GEE to the KI site. The binding of GEE is also competitive with the binding of PES, and GEE is more effective than ammonium in competing with PES. This competitive binding of GEE and PES lowers the effective concentration of PES at the site competent for electron transfer. Accordingly, the oxidative half-reaction, which is second-order with respect to PES concentration, is more rate-limiting in steady-state turnover with GEE than with ammonium. The smaller methanol C-1H/C-2H kinetic isotope effects observed with GEE are consistent with a larger contribution made by the oxidative half-reaction to rate limitation. Cyanide is much less effective at suppressing 'endogenous' activity in the presence of GEE than with ammonium, which is attributed to impaired binding of cyanide to the catalytic site through steric interaction with GEE bound at the KS site. The kinetic model developed previously for reactions of MDH with ammonium [Hothi, Basran, Sutcliffe and Scrutton (2003) Biochemistry 42, 3966-3978] is consistent with data obtained with GEE, although a more detailed structural interpretation is given here. Molecular-modelling studies rationalize the kinetic observations in terms of a complex binding scenario at the molecular level involving two spatially distinct inhibitory sites (KI and KI'). The KI' site caps the entrance to the active site and is interpreted as the PES binding site. The KI site is adjacent to, and, for GEE, overlaps with, the KS site, and is located in the active-site cavity close to the PQQ cofactor and the catalytic site for methanol oxidation.
COSMID: A Web-based Tool for Identifying and Validating CRISPR/Cas Off-target Sites (2014)

Precise genome editing using engineered nucleases can significantly facilitate biological studies and disease treatment. In particular, clustered regularly interspaced short palindromic repeats (CRISPR) with CRISPR-associated (Cas) proteins are a potentially powerful tool for modifying a genome by targeted cleavage of DNA sequences complementary to designed guide strand RNAs. Although CRISPR/Cas systems can have on-target cleavage rates close to the transfection rates, they may also have relatively high off-target cleavage at similar genomic sites that contain one or more base pair mismatches, and insertions or deletions relative to the guide strand. We have developed a bioinformatics-based tool, COSMID (CRISPR Off-target Sites with Mismatches, Insertions, and Deletions) that searches genomes for potential off-target sites (http://crispr.bme.gatech.edu). Based on the user-supplied guide strand and input parameters, COSMID identifies potential off-target sites with the specified number of mismatched bases and insertions or deletions when compared with the guide strand. For each site, amplification primers optimal for the chosen application are also given as output. This ranked-list of potential off-target sites assists the choice and evaluation of intended target sites, thus helping the design of CRISPR/Cas systems with minimal off-target effects, as well as the identification and quantification of CRISPR/Cas induced off-target cleavage in cells.
Identification of a novel psoriasis susceptibility locus at 1p and evidence of epistasis between PSORS1 and candidate loci (2001)

The pathogenesis of all forms of psoriasis remains obscure. Segregation analysis and twin studies together with ethnic differences in disease frequency all point to an underlying genetic susceptibility to psoriasis, which is both complex and likely to reflect the action of a number of genes. We performed a genome wide analysis using a total of 271 polymorphic autosomal markers on 284 sib relative pairs identified within 158 independent families. We detected evidence for linkage at 6p21 (PSORS1) with a non-parametric linkage score (NPL)=4.7, p=2 x 10(-6) and at chromosome 1p (NPL=3.6, p=1.9 x 10(-4)) in all families studied. Significant excess (p=0. 004) paternal allele sharing was detected for markers spanning the PSORS1 locus. A further three regions reached NPL scores of 2 or greater, including a region at chromosome 7 (NPL 2.1), for which linkage for a number of autoimmune disorders has been reported. Partitioning of the data set according to allele sharing at 6p21 (PSORS1) favoured linkage to chromosomes 2p (NPL 2.09) and 14q (NPL 2.0), both regions implicated in previous independent genome scans, and suggests evidence for epistasis between PSORS1 and genes at other genomic locations. This study has provided linkage evidence in favour of a novel susceptibility locus for psoriasis and provides evidence of the complex mechanisms underlying the genetic predisposition to this common skin disease.
Localization of mRNA and Receptor Binding Sites for the alpha sub 1a-Adrenoceptor Subtype in the Rat, Monkey and Human Urinary Bladder and Prostate (1997)

The alpha 1A-AR represents the major subtype in the smooth muscle of rat, monkey and human urinary systems. Selective alpha 1A-AR agents are therefore potentially useful in the treatment of multiple urinary smooth muscle related disorders.
Folding/unfolding/refolding of proteins: Present methodologies in comparison with capillary zone electrophoresis (2001)

A series of techniques for monitoring protein folding/unfolding/misfolding equilibria are here assessed and compared with capillary zone electrophoresis (CZE). They include spectroscopic techniques, such as circular dichroism, intrinsic fluorescence, nuclear magnetic resonance, Fourier transform infrared and Raman spectroscopy, small-angle X-ray scattering, as well as techniques based on biological assays, such as limited proteolysis and immunochemical analysis of different conformational states. Some unusual probes, such as mass spectrometry for probing unfolding transitions, are also discussed. Size-exclusion chromatography is also evaluated in view of the fact that this technique, like all electrophoretic techniques, and unlike spectroscopic probes, which can only see an average signal in mixed populations, can indeed physically separate folded vs. unfolded macromolecules, especially in the case of slow equilibria. Particular emphasis is devoted to electrophoretic techniques, such as gel-slab electrophoresis in transverse urea or thermal gradients, and CZE. In the latter case, a number of applications are shown, demonstrating the excellent correlation of CZE with more traditional probes, such as intrinsic fluorescence monitoring. It is additionally shown that CZE can be used for measuring the deltaG degrees of unfolding over the pH scale, in good agreement with theoretical calculations on the electrostatic free energy of folding vs. pH, as calculated with a linearized Poisson-Boltzmann equation. Finally, it is demonstrated that CZE can probe also aggregate formation in the presence of helix-inducing agents, such as trifluorethanol.