gebhart/patrepeval huggingface dataset:
The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin (2000)

Prolonged fasting is associated with a downregulation of the hypothalamo-pituitary thyroid (H-P-T) axis, which is reversed by administration of leptin. The hypothalamic melanocortin system regulates energy balance and mediates a number of central effects of leptin. In this study, we show that hypothalamic melanocortins can stimulate the thyroid axis and that their antagonist, agouti-related peptide (Agrp), can inhibit it. Intracerebroventricular (ICV) administration of Agrp (83-132) decreased plasma thyroid stimulating hormone (TSH) in fed male rats. Intraparaventricular nuclear administration of Agrp (83-132) produced a long-lasting suppression of plasma TSH, and plasma T4. ICV administration of a stable alpha-MSH analogue increased plasma TSH in 24-hour-fasted rats. In vitro, alpha-MSH increased thyrotropin releasing hormone (TRH) release from hypothalamic explants. Agrp (83-132) alone caused no change in TRH release but antagonized the effect of alpha-MSH on TRH release. Leptin increased TRH release from hypothalami harvested from 48-hour-fasted rats. Agrp (83-132) blocked this effect. These data suggest a role for the hypothalamic melanocortin system in the fasting-induced suppression of the H-P-T axis.
Fed‐batch and perfusion culture processes: Economic, environmental, and operational feasibility under uncertainty (2012)

This article evaluates the current and future potential of batch and continuous cell culture technologies via a case study based on the commercial manufacture of monoclonal antibodies. The case study compares fed-batch culture to two perfusion technologies: spin-filter perfusion and an emerging perfusion technology utilizing alternating tangential flow (ATF) perfusion. The operational, economic, and environmental feasibility of whole bioprocesses based on these systems was evaluated using a prototype dynamic decision-support tool built at UCL encompassing process economics, discrete-event simulation and uncertainty analysis, and combined with a multi-attribute decision-making technique so as to enable a holistic assessment. The strategies were compared across a range of scales and titres so as to visualize how their ranking changes in different industry scenarios. The deterministic analysis indicated that the ATF perfusion strategy has the potential to offer cost of goods savings of 20% when compared to conventional fed-batch manufacturing processes when a fivefold increase in maximum viable cell densities was assumed. Savings were also seen when the ATF cell density dropped to a threefold increase over the fed-batch strategy for most combinations of titres and production scales. In contrast, the fed-batch strategy performed better in terms of environmental sustainability with a lower water and consumable usage profile. The impact of uncertainty and failure rates on the feasibility of the strategies was explored using Monte Carlo simulation. The risk analysis results demonstrated the enhanced robustness of the fed-batch process but also highlighted that the ATF process was still the most cost-effective option even under uncertainty. The multi-attribute decision-making analysis provided insight into the limited use of spin-filter perfusion strategies in industry. The resulting sensitivity spider plots enabled identification of the critical ratio of weightings of economic and operational benefits that affect the choice between ATF perfusion and fed-batch strategies.
Hydrogen Production in a Single Chamber Microbial Electrolysis Cell Lacking a Membrane (2008)

Hydrogen gas can be produced by electrohydrogenesis in microbial electrolysis cells (MECs) at greater yields than fermentation and at greater energy efficiencies than water electrolysis. It has been assumed that a membrane is needed in an MEC to avoid hydrogen losses due to bacterial consumption of the product gas. However, high cathodic hydrogen recoveries (78 +/- 1% to 96 +/- 1%) were achieved in an MEC despite the absence of a membrane between the electrodes (applied voltages of 0.3 < E(ap) < 0.8 V; 7.5 mS/cm solution conductivity). Through the use of a membrane-less system, a graphite fiber brush anode, and close electrode spacing, hydrogen production rates reached a maximum of 3.12 +/- 0.02 m3 H2/m3 reactor per day (292 +/- 1 A/m3) at an applied voltage of E(ap) = 0.8 V. This production rate is more than double that obtained in previous MEC studies. The energy efficiency relative to the electrical input decreased with applied voltage from 406 +/- 6% (E(ap) = 0.3 V) to 194 +/- 2% (E(ap) = 0.8 V). Overall energy efficiency relative to both E(ap) and energy of the substrate averaged 78 +/- 4%, with a maximum of 86 +/- 2% (1.02 +/- 0.05 m3 H2/m3 day, E(ap) = 0.4 V). At E(ap) = 0.2 V, the hydrogen recovery substantially decreased, and methane concentrations increased from an average of 1.9 +/- 1.3% (E(ap) = 0.3-0.8 V) to 28 +/- 0% of the gas, due to the long cycle time of the reactor. Increasing the solution conductivity to 20 mS/ cm increased hydrogen production rates for E(ap) = 0.3-0.6 V, but consistent reactor performance could not be obtained in the high conductivity solution at E(ap) > 0.6 V. These results demonstrate that high hydrogen recovery and production rates are possible in a single chamber MEC without a membrane, potentially reducing the costs of these systems and allowing for new and simpler designs.
Responsiveness of the Numeric Pain Rating Scale in Patients with Low Back Pain (2005)

Clinicians can be confident that a 2-point change on the NPRS represents clinically meaningful change that exceeds the bounds of measurement error.
Review article: faecal transplantation therapy for gastrointestinal disease (2011)

Faecal transplantation has been reported with good outcomes for fulminant and refractory C. difficile. No adverse effects of faecal transplantation have been reported. However, there are no level 1 data of faecal transplantation and reports to date may suffer from reporting bias of positive outcomes and under-reporting of adverse effects. This therapy holds great promise, where a dysbiosis of the gut microbiota is responsible for disease and further studies are necessary to explore this potential.
A novel, fast and cost effective graphene-modified graphite pencil electrode for trace quantification ofl-tyrosine (2015)

A simple and novel method for detecting<sc>l</sc>-tyrosine in urine was introduced using a graphene-modified graphite pencil electrode (GR-modified GPE).
An apple-to-apple comparison of Learning-to-rank algorithms in terms of Normalized Discounted Cumulative Gain (2012)

International audience
Multiscale image segmentation using wavelet-domain hidden Markov models (2001)

We introduce a new image texture segmentation algorithm, HMTseg, based on wavelets and the hidden Markov tree (HMT) model. The HMT is a tree-structured probabilistic graph that captures the statistical properties of the coefficients of the wavelet transform. Since the HMT is particularly well suited to images containing singularities (edges and ridges), it provides a good classifier for distinguishing between textures. Utilizing the inherent tree structure of the wavelet HMT and its fast training and likelihood computation algorithms, we perform texture classification at a range of different scales. We then fuse these multiscale classifications using a Bayesian probabilistic graph to obtain reliable final segmentations. Since HMTseg works on the wavelet transform of the image, it can directly segment wavelet-compressed images without the need for decompression into the space domain. We demonstrate the performance of HMTseg with synthetic, aerial photo, and document image segmentations.
Mesenchymal stem cells from human bone marrow or adipose tissue differently modulate mitogen‐stimulated B‐cell immunoglobulin production in vitro (2008)

Mesenchymal stem cells (MSC) have been characterized as multipotent cells which are able to differentiate into several mesodermal and nonmesodermal lineage cells and this feature along with their extensive growth and comprehensive immunomodulatory properties establish them as a promising tool for therapeutic applications, including cell-based tissue engineering and treatment of immune-mediated disorders. Although bone marrow (BM) is the most common MSC source, cells with similar characteristics have been shown to be present in several other adult tissues. Adipose tissue (AT), large quantities of which can be easily obtained, represents an attractive alternative to BM in isolating adipose tissue-derived MSC (AT-MSC). BM-MSCs and AT-MSCs share some immunomodulatory properties as they are both not inherently immunogenic and suppress the proliferation of alloantigen- or mitogen-stimulated T-cells. Our purpose was to comparatively examine under appropriate in vitro conditions, phenotypes, morphology and some functional properties of BM-MSCs and AT-MSCs, such as differentiation potential and especially the ability to suppress the immunoglobulin production by mitogen-stimulated B-cells. While the morphological, immunophenotypical, colony-forming and adipogenic characteristics of both types of cells were almost identical, AT-MSCs showed less potential for osteogenic differentiation than BM-MSCs. We found that AT-MSCs not only inhibited the Ig-production but also suppressed this B-cell function to a much greater extent compared to BM-MSC. This finding supports the potential role of AT-MSCs as an alternative to BM-MSCs for clinical purposes.
Correlation image sensor: two-dimensional matched detection of amplitude-modulated light (2003)

In this paper, we describe a novel imaging device, the correlation image sensor, whose pixel circuit consists of a photodetector and source-coupled MOS transistors with individual capacitive loads and readout switches. It accepts differential or three-phase reference signals to produce one or two correlation integrals between the incident light intensity and the reference signals. The correlation results stored as charges in the capacitors are read out via MOS scanning circuits. We describe a functional model of the circuit and a quadrature detection method of amplitude-modulated light. We fabricated 64/spl times/64 and 100/spl times/100 pixel devices and obtained a correlation signal-to-noise ratio of 34 dB and a phase accuracy of 0.85/spl deg/ using only two-frame integration. We also describe application methods of this sensor to cross-correlation imagers, amplitude modulation-phase modulation demodulation imagers, and correlation matching imagers.
Role of the central melanocortin system in cachexia. (2001)

Individuals affected with either acute or chronic diseases often show disorders of nutrient balance. In some cases, a devastating state of malnutrition known as cachexia arises, brought about by a synergistic combination of a dramatic decrease in appetite and an increase in metabolism of fat and lean body mass. Stimulation of the hypothalamic melanocortin 4 receptor (MC4-R) produces relative anorexia and increased metabolic rate, even in a relatively starved state. Here we demonstrate that cachexia induced by lipopolysaccharide administration and by tumor growth is ameliorated by central MC4-R blockade. MC4-R knock-out mice or mice administered the MC3-R/MC4-R antagonist, agouti-related peptide, resist tumor-induced loss of lean body mass, and maintain normal circadian activity patterns during tumor growth. The final tumor mass is not affected in these animals, providing further support for the potential role of MC4-R antagonism in the treatment of cachexia in disease states.
Heat Generation and Transport in Nanometer-Scale Transistors (2006)

As transistor gate lengths are scaled towards the 10-nm range, thermal device design is becoming an important part of microprocessor engineering. Decreasing dimensions lead to nanometer-scale hot spots in the transistor drain region, which may increase the drain series and source injection electrical resistances. Such trends are accelerated by the introduction of novel materials and nontraditional transistor geometries, including ultrathin body, FinFET, or nanowire devices, which impede heat conduction. Thermal analysis is complicated by subcontinuum phenomena including ballistic electron transport, which reshapes the heat generation region compared with classical diffusion theory predictions. Ballistic phonon transport from the hot spot and between material boundaries impedes conduction cooling. The increased surface to volume ratio of novel transistor designs also leads to a larger contribution from material boundary thermal resistance. This paper surveys trends in transistor geometries and materials, from bulk silicon to carbon nanotubes, along with their implications for the thermal design of electronic systems
Exploitation of Bile Acid Transport Systems in Prodrug Design (2007)

The enterohepatic circulation of bile acids is one of the most efficient recycling routes in the human body. It is a complex process involving numerous transport proteins, which serve to transport bile acids from the small intestine into portal circulation, from the portal circulation into the hepatocyte, from the hepatocyte into the bile, and from the gall bladder to the small intestine. The tremendous transport capacity and organ specificity of enterohepatic circulation combined with versatile derivatization possibilities, rigid steroidal backbone, enantiomeric purity, availability, and low cost have made bile acids attractive tools in designing pharmacological hybrid molecules and prodrugs with the view of improving intestinal absorption, increasing the metabolic stability of pharmaceuticals, specifically targeting drugs to organs involved in enterohepatic circulation, as well as sustaining therapeutically reasonable systemic concentrations of active agents. This article briefly describes bile acid transport proteins involved in enterohepatic circulation, summarizes the key factors affecting on the transport by these proteins, and reviews the use of bile acids and their derivatives in designing prodrugs capable of exploiting the bile acid transport system.
Pharmacologic Analysis of Drug Receptor Interaction (1988)

Drug receptor/theory seven transmembrane receptor behaviour human recombinant receptor systems stimulus-response mechanisms drug response mechanisms diffusion and drug concentration in receptor compartments statistical assessment of biological significance from data affinity efficacy competitive antagonism allotopic, noncompetitive, and irreversible antagonism methods of drug and receptor classification kinetics of drug and reaction.
Computational optimisation of targeted DNA sequencing for cancer detection (2013)

Despite recent progress thanks to next-generation sequencing technologies, personalised cancer medicine is still hampered by intra-tumour heterogeneity and drug resistance. As most patients with advanced metastatic disease face poor survival, there is need to improve early diagnosis. Analysing circulating tumour DNA (ctDNA) might represent a non-invasive method to detect mutations in patients, facilitating early detection. In this article, we define reduced gene panels from publicly available datasets as a first step to assess and optimise the potential of targeted ctDNA scans for early tumour detection. Dividing 4,467 samples into one discovery and two independent validation cohorts, we show that up to 76% of 10 cancer types harbour at least one mutation in a panel of only 25 genes, with high sensitivity across most tumour types. Our analyses demonstrate that targeting "hotspot" regions would introduce biases towards in-frame mutations and would compromise the reproducibility of tumour detection.
Protection from lethal coronavirus infection by immunoglobulin fragments. (1995)

Molecular mechanisms of in vitro and in vivo virus neutralization by specific Ab remain largely undefined. Murine coronaviruses provide an excellent animal model for such studies. To determine the role of Ab bivalency and the contribution of its Fc portion in the neutralization of viral infectivity and passive protection of mice by an in vitro neutralizing and in vivo protective mAb (7-10A), F(ab')2 and Fab fragments were generated and their biologic properties were examined. The two fragments reacted in ELISA like the whole Ab against viral Ag or specific anti-idiotypic Abs. The affinity constants of the different Ab preparations were determined by surface plasmon resonance using immobilized anti-idiotypic Abs. The apparent affinity constant of the whole Ab molecule was 7.0 x 10(9) M-1 and was reduced 2-fold for F(ab')2 fragments and 14-fold for Fab molecules. Like whole Ab, both F(ab')2 and Fab fragments could neutralize virus in vitro and passively protect mice in vivo. However, the efficiency of in vivo neutralization by Fab fragments was reduced compared with the bivalent molecules, despite almost identical half-lives of both types of Ab fragments. These results demonstrate that in vitro and in vivo virus neutralization mechanisms by this Ab are independent of Fc-mediated functions and bivalency, but are probably influenced by Ab avidity. Also, this is the first report of in vivo protection against a viral infection by Fab fragments of antiviral Ab.
Inhibition of Neointimal Proliferation with188Re-labeled Self-Expanding Nitinol Stent in a Sheep Model (2003)

As compared with a nonradioactive stent, a beta particle-emitting stent, through endovascular irradiation, significantly inhibits neointimal formation inside the stent but not at the stent edges.
Electrophoretic characterization of purified bovine, porcine, murine, rat, and human uterine estrogen receptors. (1985)

The calf uterine estrogen receptor (E2R) in the presence of sodium molybdate has been purified, 7,000-fold by a single passage over an estradiol affinity column. A dominant 70,000-dalton band and two minor bands at 50,000 and 30,000 daltons were observed by electrophoretic analysis. These bands had been eluted using estradiol, sodium sulfocyanate, CHAPS, and HEPES (pH 7.4) with insulin as a carrier protein. The identities of the protein bands were initially confirmed by their failure to bind the affinity column when saturated with estradiol. This single step purification procedure was reproducible and rapid, with yields of 10-20%, providing 25% purity. Diffusion blot analysis, with specific 35S- and 125I-labeled monoclonal antibodies to E2R, confirmed that the 70,000-dalton band represented the estrogen receptor. Specificity was demonstrated by inhibition of binding of purified E2R by both estradiol and diethylstilbestrol but not testosterone, progesterone, corticosterone, aldosterone, or hydrocortisone. The relative binding affinity of the purified receptor was: ethynyl estradiol greater than 17 beta estradiol greater than estriol greater than or equal to estrone greater than or equal to 17 alpha-estradiol greater than mestranol. Pig, human, mouse, and rat uterine estrogen receptors were similarly purified with the affinity column. As with the calf uterine preparations, a dominant 70,000-dalton band with minor bands at 50,000 and 30,000 daltons was identified by diffusion blot analysis in all the species examined.
The Neutralization of Interferons by Antibody. II. Neutralizing Antibody Unitage and Its Relationship to Bioassay Sensitivity: The Tenfold Reduction Unit (2001)

The importance of establishing a common method of reporting neutralizing antibody levels is emphasized by the fact that patients injected repeatedly with a human interferon (HuIFN) may develop such antibodies that can abrogate the beneficial effects of the treatment. The earlier experimental and theoretical constructs of Kawade led to certain recommendations by the World Health Organization (WHO) concerning the methodology of neutralization tests and how to report the resultant data. A WHO international collaborative study on two human sera with antibodies against HuIFN-alpha and HuIFN-beta provided the opportunity not only to test the theoretical concepts concerning the neutralization reaction with data obtained in different bioassay systems in different laboratories but also to obtain enough data points for statistical evaluation with bioassays having a great range of sensitivity to IFN. The analyses substantiate and extend the original conclusions of Kawade that the neutralization follows the reaction mode of low-affinity antibody, in accord with the constant proportion hypothesis by which antibody reduces IFN activity in a set ratio of added/residual biologically active IFN, a consequence of the low molar concentration of free IFN at the neutralization end point. The present results support the recommendation that the preferred way to state the index of neutralization of antibodies is a titer (t), calculated by the formula t = f(n - 1)/9, where f is the reciprocal of the antibody dilution achieving the end point, and n is the IFN concentration measured in that day's titration. The tenfold reduction unit (TRU) of neutralization is proposed for use in expressing the quantity, or unitage, of IFN neutralizing antibody. The utility of its application is explained. The use of the index of neutralization described and the proposed derivative term of antibody unitage, TRU, should help make the results from different laboratories employing different bioassay systems more readily comparable and interpretable, provided the bioassays are sufficiently sensitive to IFN.
Pronouncing names by a combination of rule-based and case-based reasoning (1992)

A novel architecture is presented for improving the accuracy of a rule-based system through case-based reasoning. The central idea is to use the rules to generate an approximate answer to the target problem, and to use cases to handle exceptions to the rules. This provides a way of enhancing an imperfect rule set with relatively little knowledge-engineering effort--obtaining cases is often much easier than the alternative of extending and tuning the rules. The architecture has been applied to the task of pronouncing surnames, and has been found to achieve an accuracy in the ballpark of the best commercial name-pronunciation systems.
The architecture is structured as a core method and a set of support modules. The core method is the part that actually solves problems. It incorporates two key ideas: prediction-based indexing, a way of indexing cases to make them accessible for improving the rules; and the compellingness predicate, which combines the results of rule-based and case-based reasoning. As for the support modules, their role is to convert the knowledge inputs of the architecture into a form that can be used directly by the core method. There are three support modules: rational reconstruction, theory extension, and threshold setting.
Instantiating the architecture for name pronunciation resulted in Anapron, a hybrid RBR/CBR system for pronouncing names. Anapron required two principal extensions to the architecture: similarity-based indexing, an auxiliary indexing scheme to help the system cope with the large case library involved (5000 cases); and positive analogies, a method for resolving nondeterminism in the pronunciation rules.
A variety of experimental results were collected for Anapron. One was to demonstrate the analogical decline; this says that good analogies are somewhat harder to find for rare names than for common ones. A second result, mentioned above, was that Anapron was found to perform in the ballpark of the best commercial name-pronunciation systems. However, of more interest than the absolute performance of the system is a third result, which was that this performance was better than what the system could have achieved with its rules alone. This illustrates the capacity of the architecture to improve on the rule-based system that it starts with.