gebhart/patrepeval huggingface dataset:
Analysis ofPTCH/SMO/SHH pathway genes in medulloblastoma (2000)

Inactivation of the PTCH tumor suppressor gene occurs in a subset of sporadic medulloblastomas, suggesting that alterations in the PTCH pathway may be important in the development of this tumor. In order to address the frequency of genetic alterations affecting genes in this pathway, we used a combination of loss of heterozygosity (LOH) analysis, single-stranded conformational polymorphism (SSCP) analysis, and direct sequencing of DNA samples from sporadic primitive neuroectodermal tumors (PNETs). To identify alterations in the PTCH gene, we performed LOH analysis on 37 tumor DNA samples. Of those with matched constitutional DNA samples, one demonstrated LOH. Of those without matched constitutional DNA, six were homozygous with all markers. All exons of the PTCH gene were sequenced in these seven tumors, and three mutations were found. To identify alterations in the SHH and SMO genes, we analyzed all exons of both genes in 24 tumors with SSCP and sequenced any exons that showed aberrant band patterns. No mutations were found in either SHH or SMO in any tumor. We also identified the following genes as candidate tumor suppressors based on their roles in controlling hh/ptc signaling in Drosophila: EN-1 and EN-2, deletion of which results in a lack of cerebellar development in mice; SMAD family members 1-7, and protein kinase A subunits RIalpha, RIbeta, RIIbeta, Calpha, and Cbeta. Each of these genes was investigated in a panel of 24 matched constitutional and tumor DNA samples. Our search revealed no mutations in any of these genes. Thus, PTCH is the only gene in this complex pathway that is mutated with notable frequency in PNET. Genes Chromosomes Cancer 27:44-51, 2000.
Endothelial β1 Integrin-Mediated Adaptation to Myocardial Ischemia (2021)

We showed that endothelial β1 integrin is required for adaptation of the heart to cardiac ischemia and protection from myocardial infarction.
Generation and intracellular trafficking of a polysialic acid-carrying fragment of the neural cell adhesion molecule NCAM to the cell nucleus (2017)

Polysialic acid (PSA) and its major protein carrier, the neural cell adhesion molecule NCAM, play important roles in many nervous system functions during development and in adulthood. Here, we show that a PSA-carrying NCAM fragment is generated at the plasma membrane by matrix metalloproteases and transferred to the cell nucleus via endosomes and the cytoplasm. Generation and nuclear import of this fragment in cultured cerebellar neurons is induced by a function-triggering NCAM antibody and a peptide comprising the effector domain (ED) of myristoylated alanine-rich C kinase substrate (MARCKS) which interacts with PSA within the plane of the plasma membrane. These treatments lead to activation of the fibroblast growth factor (FGF) receptor, phospholipase C (PLC), protein kinase C (PKC) and phosphoinositide-3-kinase (PI3K), and subsequently to phosphorylation of MARCKS. Moreover, the NCAM antibody triggers calmodulin-dependent activation of nitric oxide synthase, nitric oxide (NO) production, NO-dependent S-nitrosylation of matrix metalloprotease 9 (MMP9) as well as activation of matrix metalloprotease 2 (MMP2) and MMP9, whereas the ED peptide activates phospholipase D (PLD) and MMP2, but not MMP9. These results indicate that the nuclear PSA-carrying NCAM fragment is generated by distinct and functionally defined signal transducing mechanisms.
MacA, a Diheme c -Type Cytochrome Involved in Fe(III) Reduction by Geobacter sulfurreducens (2004)

A 36-kDa diheme c-type cytochrome abundant in Fe(III)-respiring Geobacter sulfurreducens, designated MacA, was more highly expressed during growth with Fe(III) as the electron acceptor than with fumarate. Although MacA has homology to proteins with in vitro peroxidase activity, deletion of macA had no impact on response to oxidative stress. However, the capacity for Fe(III) reduction was greatly diminished, indicating that MacA, which is predicted to be localized in the periplasm, is a key intermediate in electron transfer to Fe(III).
Application of New Sodium Vinyl Sulfonate–co-2-Acrylamido-2-me[thylpropane Sulfonic Acid Sodium Salt-Magnetite Cryogel Nanocomposites for Fast Methylene Blue Removal from Industrial Waste Water (2018)

Inorganic nanoparticles based on magnetite were used to improve the mechanical, thermal, and magnetic properties of microporous cryogel polymer composites. Here we report the synthesis of microporous cryogel based on the crosslinked sodium vinyl sulfonate (Na-VS) and 2-acrylamido-2-methylpropane sulfonic acid sodium salt (Na-AMPS). The magnetite nanoparticles were incorporated into Na-VS/Na-AMPS cryogel networks either during its crosslinking polymerization or by the <i>in-situ</i> technique after its crosslinking. The morphology, particle sizes, thermal stability, and magnetite contents of Na-VS/Na-AMPS cryogel and its magnetite composite were investigated. The prepared Na-VS/Na-AMPS cryogel and its magnetite composite were used as adsorbents for methylene blue (MB) cationic dye using optimum conditions. The magnetite Na-VS/Na-AMPS cryogel composite prepared by in-situ technique achieved the best adsorption MB removal capacity for 7 cycles among the other adsorbents via chemical adsorption mechanism at room temperature.
Identification of isoniazid mono-resistance is delayed despite whole genome sequencing (2021)

<b>Background:</b> The UK has implemented routine use of whole genome sequencing (WGS) in TB diagnostics. WHO recommends addition of a fluoroquinolone for isoniazid (INH) mono-resistance, so early detection may be of use. <b>Aims:</b> To describe the utility of WGS on treatment decisions on INH mono-resistance in a low incidence high resource setting. <b>Methods:</b> A retrospective analysis of TB cases from January 2018 to March 2019 in London. Susceptibility and turnaround times (TAT) by WGS, drug sensitivity testing (DST), TB PCR were correlated to drug changes. <b>Results:</b> 189 TB cases were identified; median age 44 years (IQR 28-60), m:f ratio 112:77, 7 with HIV and 6 with previous TB. 80/189 cases had a positive culture and WGS result. 50/80 were fully sensitive to 1st line treatment on WGS, and the rest required additional DST. 22/80 cases required drug changes; 12 were defined by WGS: 9 cases had INH mono-resistance, 2 had MDR-TB and 1 had ethambutol resistance. The median TAT for positive culture was 16 days (IQR 13.5-19.5); for WGS was 35 days (IQR 32.5-36.25) and for DST was 86 days (IQR 70.5-94.25), resulting in non-WHO regimens for a median of 50.5 days (IQR 28-59). 9/12 has TB PCRs, with a median TAT of 1 day. <b>Conclusion:</b> 15% of treatment changes were defined by WGS enabling correct drug regimens but the TAT was over a month. Point of care testing to also identify INH mono-resistance is required to minimise the time on non-WHO treatment regimens.
Reversibility of defective adipocyte insulin receptor kinase activity in non-insulin-dependent diabetes mellitus. Effect of weight loss. (1988)

Insulin-stimulated kinase activity of adipocyte-derived insulin receptors is reduced in subjects with non-insulin-dependent diabetes mellitus (NIDDM) but normal in obese nondiabetics. To assess the reversibility of the kinase defect in NIDDM, insulin receptor kinase activity was measured before and after weight loss in 10 NIDDM and 5 obese nondiabetic subjects. Peripheral insulin action was also assessed in vivo by glucose disposal rates (GDR) measured during a hyperinsulinemic (300 mU/M2 per min) euglycemic clamp. In the NIDDMs, insulin receptor kinase activity was reduced by 50-80% and rose to approximately 65-90% (P less than 0.01) of normal after 13.2 +/- 2.0 kg (P less than 0.01) weight loss; comparable weight loss (18.2 +/- 1.5 kg, P less than 0.01) in the nondiabetics resulted in no significant change in insulin receptor kinase activity. Relative to GDR measured in lean nondiabetics, GDR in the NIDDMs was 35% of normal initially and 67% (P less than 0.01) of normal after diet therapy; weight loss in the nondiabetics resulted in an increase in GDR from 53 to 76% of normal (P less than 0.05). These results indicate that the insulin receptor kinase defect that is present in NIDDM is largely reversible after weight reduction. In contrast, the improvement in GDR, in the absence of any change in insulin receptor kinase activity in the nondiabetics, suggests that the main cause of insulin resistance in obesity lies distal to the kinase.
Diffuse Alveolar Damage in a Young Cat (2011)

A 10-month-old cat was diagnosed with congenital subvalvular aortic stenosis. To resolve its hypoxia, oxygen therapy was administered a couple of times a week during two months. The oxygen partial pressure in the chamber was maintained between 30 and 35%, and the time for one procedure was 12-24 hr. The animal died due to severe respiratory failure. At necropsy, the lungs were voluminous and had a rubbery texture. Histologically, large type II pneumocytes with occasional atypia had diffusely proliferated within the lungs. Interstitial fibrosis was not observed, although some alveolar septa were thickened along with fibrinous exudates and neutrophilic infiltration. The histology of these lesions was consistent with diffuse alveolar damage (DAD), which might have been partially due to oxygen toxicity.
Accelerated white matter lesion analysis based on simultaneous T1 and T2∗ quantification using magnetic resonance fingerprinting and deep learning (2021)

MRF is a fast and robust tool for quantitative <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>T</mml:mi><mml:mn>1</mml:mn></mml:msub></mml:math> and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msubsup><mml:mi>T</mml:mi><mml:mn>2</mml:mn><mml:mo>∗</mml:mo></mml:msubsup></mml:math> mapping. Its long reconstruction and several postprocessing steps can be facilitated and accelerated using deep learning.
Spherical Assemblies of Semiconductor Nanoparticles in Water-Soluble Block Copolymer Aggregates (1998)

Novel spherical assemblies of CdS-containing block copolymer reverse micelles in aqueous solution have been formed by the slow addition of water to mixtures of the reverse micelles and a polystyrene-b-poly(acrylic acid) stabilizer. The structures are large compound micelles (LCMs) with quantum-confined CdS nanoparticles dispersed throughout a spherical PS matrix, which is stabilized in water by a layer of solubilized hydrophilic chains. The size of the CdS particles (2RCdS ∼ 3 nm) is controlled by the ionic block length, NB, of the block copolymer making up the reverse micelle. LCM formation is found to be dependent on the amount of added stabilizing copolymer. When the weight of stabilizer relative to the total polymer weight is 12% for the specific system under study, a single population of LCMs is formed (Dave = 64 nm); each of these LCMs consists of an average of 58 reverse micelles and 87 stabilizing chains, with an average surface area per stabilizing chain of 148 nm.2 At 10% stabilizer, two LCM populations, Dave = 52 nm and Dave = 152 nm, are formed. When the concentration of stabilizing copolymer is increased to 21 and 35%, regular micelles with no internal structure coexist with LCMs. Without added stabilizing copolymer, most reverse micelles undergo macroscopic precipitation upon water addition, although some LCMs are observed in the remaining solution.
ASSESSING SHOCK RESUSCITATION STRATEGIES BY OXYGEN DEBT REPAYMENT (2010)

Identification of occult shock is a major clinical problem compounded by inadequate criteria for assessing the efficacy of fluid resuscitation. We suggest that these problems may be resolved in part by understanding both the physiological mechanisms underlying oxygen debt accumulation and, more importantly, the debt repayment schedule during resuscitation. We present a simplified tutorial that incorporates the concept of the oxygen supply-delivery relationship with that of oxygen debt and show how this is relevant to the understanding of shock and resuscitation. Use of oxygen debt metrics as end points for shock have been controversial; however, much of the controversy may have been due to incomplete understanding of basic physiology of shock and semantic confusion between the various metrics proposed as end points. Here, we provide working definitions for the frequently misunderstood concepts of oxygen deficit and oxygen debt and discuss the relatively novel concept of oxygen debt repayment schedule. We introduce predictions made on the basis of data derived from animal models of hemorrhagic shock. Our calculations suggest that the amount of debt repaid in the first 2 h of resuscitation, rather than the restoration of volume per se, influences the likelihood of organ damage. Because of difficulties inherent in measuring oxygen debt in the prehospital and emergency settings, various metabolic end points such as lactate and base deficit have been proposed as surrogates. We demonstrate the heuristic value of this model in providing a predictive framework for both the optimum therapeutic time window and optimum fluid loadings before critical transitions to an irreversible shock state can occur. The model also provides an unambiguous and objective standard for quantifying the behavior of various postulated shock "markers".
Correlation-feedback technique in optical flow determination (1998)

In this correspondence, we present a new algorithm to determine optical flow that utilizes a correlation-feedback technique. Several experiments are presented to demonstrate that our method performs generally better than some standard correlation and gradient-based methods in terms of accuracy.
A Prescription for Information Prospecting, Data Mining, and Design Refinement (1997)

Abstract We present a prescriptive methodology for conceptual design based on a process of information gathering and refinement. While these activities are generic to conceptual design, a mathematical framework is developed toward structuring the design space, approximating the design space by generalizing design data, and formalizing the iterative process of narrowing the design space while refining the level detail in the design specification. As a prescription for conceptual design, this method formalizes the conceptual design process around a key tradeoff — the value to be gained by making design commitments balanced against the reduction in size of design space these commitments bring. Because conceptual design decisions carry tremendous leverage through to all downstream processes, formalizing conceptual design toward reducing arbitrary design decisions and focusing attention on the most critical design concerns holds the potential to improve greatly the ultimate product of the overall design process.
Design and analysis of computer experiments for efficient model-based active thermography in the agro-food sector (2016)

Finite element models simulating the heat transfer in active thermography are studied intensively. Together with improved model accuracy, the related complexity and required computational power are increasing. In the agro-food sector, the material properties of the inspected objects, and thus the input parameters of heat transfer models, are prone to biological variability. In this work, a strategy called 'Design and Analysis of Computer Experiments' was applied to efficiently obtain the heat transfer output for an arbitrary combination of input parameters without running every single simulation. A metamodel was set up, interpolating between the output of a few carefully selected simulations.
New CMOS universal constant-Gm input stage (2002)

Conceptually new constant-Gm input-stage architecture is presented. It provides near constant net transconductance independent of transistor operating region-strong, moderate or weak inversion. One possible implementation of the proposed architecture is discussed in details. Its operation has been experimentally verified. Results from performed measurements are included.
De la nécessité de justifier sa compétence juridictionnelle en cas d'ouverture d'une procédure européenne d'insolvabilité (2020)

International audience
4-O-methylascochlorin stabilizes hypoxia-inducible factor-1 in a manner different from hydroxylase inhibition by iron chelating or substrate competition (2019)

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays essential roles in human diseases including cancer. The synthetic ascochlorin derivative 4-<i>O</i>-methylascochlorin stabilizes HIF-1α protein, and activates its transcriptional activity, resulting to induce gene expression of its downstream targets such as <i>VEGF</i> and <i>GLUT-1</i>. Here, we quantified protein level of HIF-1α in human osteosarcoma U2OS cells treated with ascochlorin-related compounds and typical HIF-1α stabilizers to characterize properties of HIF-1α stabilization by 4-<i>O</i>-methylascochlorin. Structure-activity relationship studies suggested that the aromatic moiety and hydrophobic substitution of the 4'-hydroxyl group are important for HIF-1α stabilization by ascochlorin-related compounds. 4-<i>O</i>-Methylascochlorin-induced HIF-1α stabilization was suppressed by ascorbic acid and compound C, but not by Fe(II), whereas ascorbic acid only suppressed HIF-1α stabilization by dimethyloxaloylglycine, an analog of the HIF-1 hydroxylase substrate. Fe(II) completely suppressed iron chelator-induced stabilization. These results suggest that ascochlorin-related compounds stabilize HIF-1α in a manner distinct from iron chelating or substrate competition.
Symptomatic and Functional Response and Remission From the Open-Label Treatment-Optimization Phase of a Study With DR/ER-MPH in Children With ADHD (2021)

<b><i>Trial Registration:</i></b> Data used in this post hoc analysis came from the study with ClinicalTrials.gov identifier: NCT02493777.
Perilla Pomace, a By-product of Oil Extraction, Is Rich in Nutrients and Can Favorably Modulate Lipid Metabolism in Sprague-Dawley Rats (2023)

Perilla pomace, a by-product of oil extraction, is rich in nutrients, such as proteins, but it has not been used for purposes other than livestock feeding. The aim of this study was to determine how perilla pomace modulates glucose and lipid metabolism in Sprague-Dawley rats. Dried perilla pomace was added to diet at a concentration of 16%. One experimental group was administered perilla oil equivalent to that in the perilla pomace. After four weeks, the animals were euthanized, and biochemical parameters were measured. Two experiments were conducted using a low-fat (7% by weight) and a high-fat (21% by weight) diet. Regardless of the level of fat in the diets, no differences in food intake were found among the groups. In the low-fat diet-fed rats (Experiment 1), epididymal adipose tissue weight was slightly, but not significantly, lower in perilla pomace-fed rats than in those fed the control diet. Hepatic triglyceride and cholesterol levels were significantly reduced by perilla pomace compared to those in the control group. Serum lipid profiles (triglycerides and cholesterol) were similar to those in the liver, without statistically significant differences. Perilla pomace significantly diminished hepatic fatty acid synthase (FAS) activity. In high-fat diet-fed rats (Experiment 2), pomace did not significantly lower epididymal adipose tissue weight. Hepatic cholesterol levels were lower in rats on the perilla oil than in control rats. The activity of hepatic enzymes involved in fat oxidation was significantly higher in rats fed the perilla pomace than in those fed the control diet. Collectively, these results show that perilla pomace favorably modulates fat metabolism, and the specific effects depend on the fat content in the diet.
Adhesion of the genome-sequenced Lactococcus lactis subsp. cremoris IBB477 strain is mediated by specific molecular determinants (2016)

Understanding the nature of mucus-microbe interactions will provide important information that can help to elucidate the mechanisms underlying probiotic adhesion. This study focused on the adhesive properties of the Lactococcus lactis subsp. cremoris IBB477 strain, previously shown to persist in the gastrointestinal tract of germ-free rats. The shear flow-induced detachment of L. lactis cells was investigated under laminar flow conditions. Such a dynamic approach demonstrated increased adhesion to bare and mucin-coated polystyrene for IBB477, compared to that observed for the MG1820 control strain. To identify potential genetic determinants giving adhesive properties to IBB477, the improved high-quality draft genome sequence comprising chromosome and five plasmids was obtained and analysed. The number of putative adhesion proteins was determined on the basis of surface/extracellular localisation and/or the presence of adhesion domains. To identify proteins essential for the IBB477 specific adhesion property, nine deletion mutants in chromosomal genes have been constructed and analysed using adhesion tests on bare polystyrene as well as mucin-, fibronectin- or collagen IV-coated polystyrene plates in comparison to the wild-type strain. These experiments demonstrated that gene AJ89_07570 encoding a protein containing DUF285, MucBP and four Big_3 domains is involved in adhesion to bare and mucin-coated polystyrene. To summarise, in the present work, we characterised the adhesion of IBB477 under laminar flow conditions; identified the putative adherence factors present in IBB477, which is the first L. lactis strain exhibiting adhesive and mucoadhesive properties to be sequenced and demonstrated that one of the proteins containing adhesion domains contributes to adhesion.
Radiation resistance of single and multilayer coatings against synchrotron radiation (2004)

Optical coatings for the use in free electron laser systems have to withstand high power laser radiation and the intense energetic background radiation of the synchrotron radiation source. In general, the bombardment with high energetic photons leads to irreversible changes and a discoloration of the specimen. For the development of appropriate optical coatings, the degradation mechanisms of available optical materials have to be characterized. In this contribution the degradation mechanisms of single layer coatings (fluoride and oxide materials) and multilayer systems will be presented. Fluoride and oxide single layers were produced by thermal evaporation and high energetic ion beam sputter deposition. The same methods were employed for the deposition of multilayer systems. High reflecting coatings for the wavelength region around 180 nm were chosen for the irradiation tests. All samples were characterized after production by spectrophotometry covering the VUV , VIS, and MIR spectral range. Mechanical coating stress was evaluated with interferometric methods. Synchrotron irradiation tests were performed at ELETTRA, using a standardized irradiation cycle for all tests. Ambient pressure and possible contamination in the vacuum environment were monitored by mass spectrometry. For comparison, the optical coatings were investigated again in the VUV, VIS, and MIR spectral range after irradiation. On selected samples XRD measurements were performed. The observed degradation mechanisms comprise severe damages like coating and substrate surface ablation. Color centre formation in the VIS spectral range and an increase of VUV absorption were found as a major origin for a severe degradation of VUV transmittance On the basis of the performed investigations, a selection of coating materials and coating systems is possible in respect to the damage effects caused by synchrotron radiation.
A language design for concurrent processes (1968)

In conventional programming languages, the sequence of execution is specified by rules such as:(1) The statement GO TO is followed by the statement labelled L (Branching rule).(2) The last statement in the range of an iteration is followed, under certain conditions, by the first statement in the range (Looping rule).(3) The last statement of a subroutine is followed by the statement immediately after its CALL (Out-of-line code rule).... (Other rules)(n) In other cases, each statement is followed by the statement immediately after it (Order rule).