gebhart/patrepeval huggingface dataset:
Possible mechanisms of inhibition with atropine against noradrenaline‐induced contraction in the rabbit aorta (1992)

1. In the rabbit isolated aorta, atropine (3 x 10(-6) M-10(-4) M) inhibited contractile response to noradrenaline without affecting contraction to KCl. 2. In the presence of contraction to noradrenaline, atropine (3 x 10(-7) M-10(-4) M) caused concentration-dependent relaxation. Pretreatment with theophylline (10(-3) M) potentiated the relaxant action of atropine. Relaxation to atropine was not affected by the specific guanosine 3':5'-cyclic monophosphate phosphodiesterase inhibitor, M & B 22,948 (10(-4) M), tetraethylammonium (10 mM), indomethacin (10(-5) M), propranolol (10(-7) M), nifedipine (10(-6) M) or removal of the endothelium. 3. Relaxation to either atropine or prazosin was not affected by preincubation with prazosin and atropine, respectively. 4. In Ca(2+)-free medium containing EGTA and nifedipine, atropine (10(-7) M-10(-4) M) inhibited the residual noradrenaline response more than the subsequent Ca(2+)-induced contraction. Pretreatment with either theophylline (10(-3) M), forskolin (3 x 10(-7) M) or a low concentration of prazosin (3 x 10(-9) M) also inhibited the residual contraction to noradrenaline and Ca2+. The effect of combined treatment of atropine and any of these agents was much greater than with each individual agent. 5. Atropine (10(-6) M-10(-4) M) also inhibited increases in the level of inositol monophosphates (IP) in response to noradrenaline. Theophylline (10(-3) M) and a low concentration of prazosin (3 x 10(-9) M) also inhibited IP formation. Combined with atropine, the effect was much greater than with each of these agents individually. 6. Atropine did not affect adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels in the aorta and also failed to displace specific [3H]-prazosin binding.7. These results suggest the possibility that smooth muscle relaxation to atropine may be due to the inhibition of phosphoinositide metabolism. The relaxation is not apparently due to an action of atropine on ax-adrenoceptors, or a change in the level of cyclic AMP.
A FIELD STUDY OF INCLINE USE AND PREFERRED SPEEDS FOR THE LOCOMOTION OF LIZARDS (2000)

The maximal running speeds of lizards have commonly been measured using level racetracks in a laboratory, but the normal speeds of locomotion of lizards and most animals in their natural habitats are not well documented. Thus we quantified the locomotor activity of the lizard Uma scoparia in its natural sand-dune habitat to determine how commonly animals run near their maximal speed and how inclines in the environment might affect habitat use and the speed of locomotion. We used leaf blowers to erase footprints in the sand in three 40 m × 100 m plots differing in surface topography and vegetation and then measured attributes of the paths and tracks left by U. scoparia that were not disturbed (by observers) during their period of peak activity. Laboratory observations allowed us to estimate speed for each field measurement of stride length (n = 5993). The frequency distribution of stride speed had two distinct modes (mean values 0.25 and 2.00 m/s), for which only the lower one is likely to be aerobically sustainable. Bipedal locomotion was extremely rare (<0.5% of all strides), but much undisturbed locomotion was unexpectedly fast. The inclines of the surfaces upon which locomotion occurred conformed to random habitat use. In contrast, the inclines of paths made by lizards had lower than expected amounts of nearly horizontal locomotion and a propensity for traveling almost directly uphill, especially when surfaces were steep. Habitat structure varied significantly among plots and affected several aspects of locomotion. For example, path length, average speed per path, and average magnitudes of path and surface inclines per path varied significantly among the three plots. Multiple regression analysis also revealed that the average speed per 1-m interval was maximized for paths with relatively shallow downhill slopes (−6% grade) and decreased significantly both with increased amounts of vegetative cover and increased turning between successive intervals. Unexpectedly, during undisturbed and escape locomotion, lizards used inclines similarly.
Lipid requirements for the aggregation of CTP:phosphocholine cytidylyltransferase in rat liver cytosol (1979)

Two forms of CTP:phosphocholine cytidylyltransferase were identified in rat liver cytosol by gel filtration chromatography. The low molecular weight form (L form) is the major form in fresh cytosol. The enzyme associates into a high molecular weight form (H form) upon storage of the cytosol at 4 degrees C. Aggregation of the purified L form of cytidylyltransferase is caused by total rat liver lipids, neutral lipids, diacylglycerol, or phosphatidylglycerol. Diacylglycerol was the only lipid isolated from the rat liver that caused aggregation of the purified enzyme. Although the addition of diacylglycerol to the cytosol did not change the amount of aggregation of the enzyme, a 2.5-fold increase in H form was observed in cytosol pretreated with phospholipase C, or in cytosol from rats fed a high cholesterol diet. In both of these cytosolic preparations, the concentration of diacylglycerol was elevated twofold. Phosphatidylglycerol did not seem to affect the association of the enzyme in cytosol since it is present in very low concentrations in the rat liver cytosol, and its degradation in cytosol by a specific phospholipase did not affect the rate of aggregation. The results suggest that diacylglycerol in an appropriate form is required for association of cytidylyltransferase in rat liver cytosol.
Action module planning and its application to an experimental climbing robot (2002)

This paper presents the application of an action module planning method to an experimental climbing robot named LIBRA. The method searches for a sequence of physically realizable actions, called action modules, to produce a plan for a given task. The search is performed with a hierarchical selection process that uses task and configuration filters to reduce the action module inventory to a reasonable search space. Then, a genetic algorithm search finds a sequence of actions that allows the robot to complete the task without violating any physical constraints. The results for the LIBRA climbing robot show the method is able to produce effective plans.
Imaging Biomarkers and their Role in Dementia Clinical Trials (2007)

There are five potential major roles for neuroimaging with respect to dementia; (1) as a cognitive neuroscience research tool, (2) for prediction of which normal or slightly impaired individuals will develop dementia and over what time frame, (3) for early diagnosis of Alzheimer's disease (AD) in demented individuals, (sensitivity) and separation of AD from other forms of dementia (specificity), (4) for monitoring of disease progression, and (5) for monitoring response to therapies. Focusing on the last role, no single imaging approach is yet ideal, as all trade-off speed, cost, and accuracy. Functional imaging (SPECT and PET) is best suited to tracking symptomatic therapy response, and anatomic (MRI volumetric) imaging or amyloid PET are more suited to reflect dementia modulation studies. The potential for imaging with respect to pharmacological studies of dementia--to provide surrogate markers for drug studies, to improve diagnosis, to speed evaluation of outcomes, and to decrease sample sizes--is huge. At the present time, however, no single measure has sufficient proven reliability, replicability, or robustness, to replace clinical primary outcome measures.
Mitral valve repair in the elderly: operative risk for patients over 70 years of age is acceptable. (2003)

Operative results for mitral valvuloplasty in the elderly are acceptable. Surgery should not be withheld on the basis of age alone.
Progress in Tritium NMR: 1990‐2005 (2007)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Microwave-driven plasmas in Hollow-Core Photonic Crystal Fibres (2013)

International audience
MHC-I genotype drives early immune selection of oncogenic mutations (2017)

MHC-I exposes the intracellular contents to immune cells for surveillance of cellular health. Due to high genomic variation, individuals' immune systems differ in their ability to expose and eliminate cancer-causing mutations. These personalized immune blind spots create specific oncogenic mutation predispositions within patients and influence their prevalence across populations.
Loss of <i>miR-203</i> regulates cell shape and matrix adhesion through ROBO1/Rac/FAK in response to stiffness (2016)

Breast tumor progression is accompanied by changes in the surrounding extracellular matrix (ECM) that increase stiffness of the microenvironment. Mammary epithelial cells engage regulatory pathways that permit dynamic responses to mechanical cues from the ECM. Here, we identify a SLIT2/ROBO1 signaling circuit as a key regulatory mechanism by which cells sense and respond to ECM stiffness to preserve tensional homeostasis. We observed that Robo1 ablation in the developing mammary gland compromised actin stress fiber assembly and inhibited cell contractility to perturb tissue morphogenesis, whereas SLIT2 treatment stimulated Rac and increased focal adhesion kinase activity to enhance cell tension by maintaining cell shape and matrix adhesion. Further investigation revealed that a stiff ECM increased Robo1 levels by down-regulating miR-203. Consistently, patients whose tumor expressed a low miR-203/high Robo1 expression pattern exhibited a better overall survival prognosis. These studies show that cells subjected to stiffened environments up-regulate Robo1 as a protective mechanism that maintains cell shape and facilitates ECM adherence.
Rheological and mechanical properties of thermotropic polyesters with long flexible spacers in the main chain (1994)

Abstract Linear thermotropic liquid crystalline polymers based on two bisphenol monomers and terephthaloyldichloride were prepared via melt polymerization. Fibers from liquid crystalline polymers were spun above the mesophase transition temperature. In this work, the mechanical and morphological properties of fibers based on such polymers were studied. High values of tensile strength and tensile modulus were obtained, and we tried to prove these high mechanical properties quantitavely by using rheological properties of these polymers and morphology of their fibers. These values were varied by the take‐up speed.
In vitro Activity of BAY 12-8039, a New 8-Methoxyquinolone (1996)

BAY 12-8039 is a new 8-methoxyquinolone with antibacterial activity against gram-positive bacteria which is significantly better than those of sparfloxacin or ciprofloxacin. The minimal inhibitory concentrations (MICs) for 90% of methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis were 0.062 and 2 mg/l, respectively. The MIC90s for ciprofloxacin-resistant, methicillin-susceptible and methicillin-resistant S. aureus were 8 mg/l. Against the staphylococcal strains tested sparfloxacin was 2-fold and ciprofloxacin > or = 10-fold less active. MIC90s for Streptococcus pneumoniae, Streptococcus pyogenes and Streptococcus agalactiae were 0.125-0.5 mg/l, irrespective of whether strains with diminished ciprofloxacin susceptibility or ciprofloxacin-susceptible strains were tested. Against the streptococci sparfloxacin was 2- to 4-fold less active. Against gram-negative bacteria BAY 12-8039 is almost as active as ciprofloxacin, except for Pseudomonas aeruginosa. Against Bacteroides fragilis, Bacteroides spp. and Clostridium spp. BAY 12-8039 was as active as metronidazole. The bactericidal activity against S. aureus and S. pneumoniae was in contrast to that of the other quinolones tested, penicillin G, amoxicillin+/-clavulanate, cefuroxime and clarithromycin, concentration-dependent. As compared to ciprofloxacin, development of resistance was less pronounced. The spontaneous mutation frequency towards BAY 12-8039 resistance was 2.8 x 10(-8) in Escherichia coli, 7.06 x 10(-8) in S. aureus and < 1.4 x 10(-9) in S. pneumoniae.
Quantitative Auflichtmikroskopie mit Hilfe aufgedampfter Interferenzschichten (1965)

Aufgabe quantitativer mikroskopischer Untersuchungen. Quantitative Darstellung der Gefügeentwicklung durch Interferenz-Aufdampfschichten. Herleitung eines Verfahrens zur Ermittlung der optischen Konstanten von Gefügebestandteilen durch Mikroreflexionsmessungen. Optische Konstanten der α- und γ-Phase von Eisenlegierungen. Messung von Phasenwinkelunterschieden zur Kennzeichnung von Gefügebestandteilen. The task of quantitative microscopical investigations. Quantitative representation of the development of structure by evaporated interference layers. Deduction of a method to determine the optical components by microreflection measurements. Optical constants of the α and γ phases of ferrous alloys. Use of measurement of phase angle differences to identify structural components. Rôle des recherches quantitatives au microscope. Représentation quantitative du développement de la structure par les couches d'interférences. Procédé dérivé pour déterminer les constantes optiques des constituants structuraux par mesure des microréflexions. Constantes optiques des phases α et γ des alliages ferreux. Mesure des différences angulaires des phases pour caractériser les constituants structuraux.
Activating Shp2 Mutations Cause Progressive Myeloproliferative Disorder in Mice. (2006)

Abstract Mutations in the SH2-containing tyrosine phosphatase, Shp2 (PTPN11) have been found in human diseases. Germ-line Shp2 mutations cause ~50% of Noonan Syndrome (NS), which is associated with an increased risk of juvenile myelomonocytic leukemia (JMML). Somatic Shp2 mutations are found in ~35% of sporadic JMML, most other cases have either activating Ras mutations or homozygous Nf1 deficiency. Shp2 mutations are also found at lower incidence in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and B-cell acute lymphoblastic leukemia (B-ALL). NS and leukemia-associated Shp2 mutations often affect the same residue, but result in different substitution. We previously showed that leukemia-associated mutants E76K or D61Y, but not wild type (WT) Shp2 could transform bone marrow (BM) or fetal liver cells and give rise to cytokine-independent myeloid colony formation. Transplantation of E76K- or D61Y- (but not parental virus or WT Shp2) transduced BM evoked invasive MPD in most recipients and majority of them died at 6–7 months. We have generated knock-in mice for the Shp2 mutants D61G and D61Y to better understand the effects of these mutations under endogenous promoter control. Whereas D61G is associated with both NS and leukemia, D61Y is only found in leukemia and catalytically more active than D61G in basal state. D61G/+ mice exhibited all major features of NS and a mild, well-tolerated MPD for ~1 year and then progressed to fatal MPD. Constitutive expression of the D61Y heterozygous allele was embryonic lethal. However, when an inducible allele of D61Y (inD61Y) was crossed to Mx-Cre mice and expressed upon pI-pC induction, these mice rapidly developed MPD and ~50% mice died within a period of 4–7 months. Immunophenotypic analysis of bone marrow and spleen of these mice showed marked expansion of Gr-1/Mac-1 positive population indicating that these mice died of infiltrating MPD. Bone marrow macrophages from D61G/+ and inD61Y mice showed increased GM-CSF-evoked proliferation and increased overall tyrosine phosphorylation. Likewise GM-CSF-evoked activation of Erk, Akt, Jak2 and Stat5 were enhanced, as was Ras loading suggesting that leukemogenic Shp2 causes MPD by enhancing both Ras/Erk and Jak2/Stat5 pathways. The results of our retroviral and knock-in models suggest that leukemia-associated Shp2 mutant is sufficient to initiate myeloid leukemogenesis in mice.
Emerging Lung Cancer Therapeutic Targets Based on the Pathogenesis of Bone Metastases (2014)

Lung cancer is the second most common cancer and the leading cause of cancer related mortality in both men and women. Each year, more people die of lung cancer than of colon, breast, and prostate cancers combined. It is widely accepted that tumor metastasis is a formidable barrier to effective treatment of lung cancer. The bone is one of the frequent metastatic sites for lung cancer occurring in a large number of patients. Bone metastases can cause a wide range of symptoms that could impair quality of life of lung cancer patients and shorten their survival. We strongly believe that molecular targets (tumor-related and bone microenvironment based) that have been implicated in lung cancer bone metastases hold great promise in lung cancer therapeutics. Thus, this paper discusses some of the emerging molecular targets that have provided insights into the cascade of metastases in lung cancer with the focus on bone invasion. It is anticipated that the information gathered might be useful in future efforts of optimizing lung cancer treatment strategies.
Synthesis and antimicrobial activity of novel naphtho[2,1-b]furo-5H-[3,2-d][1,3,4]thiadiazolo[3,2-a]pyrimidin-5-ones (2008)

Ethyl 3-aminonaphtho[2,1-b]furan-2-carboxylate 1 was converted into 3-amino-2mercaptonaphthofuro[3,2-d]pyrimidin-4(3H)-one 4 by reacting it with carbon disulphide followed by methylation and condensation with hydrazine hydrate. The compound 4 on treatment with aryl isothiocyanates produced 2 [3,2-a]pyrimidin-5-ones 5(a-h). The title compounds 6(a-h) were obtained also by reacting 4 with aromatic acids in presence of phosphorus oxychloride. The structures of the newly synthesized compounds were confirmed by IR, 1 H NMR, 13 C NMR and mass spectral studies and elemental analysis. All the synthesized compounds have been screened for antimicrobial activity.
Assay of some antifungal antibiotics using Piricularia oryzae as the test organism. (1957)

(1) Piricularia oryze was used as the most senstive test organism of microassaying some antifungal antibiotics by the cup or the paper disc method. Spores of P. oryzae were obtained by cultivating the organism on the yeast starch agar slants at 28°C for 2 weeks. The concentration of spores in the assay medium necessary for optimum results was about 17 -34×104 spores per ml (Fig. 3).(2) A Study was made on the factors affecting the Blasticidin assay. The most important factors to be controlled in the assay of Blasticidin were hydrogen ion concentrations of the assay medium . and of the sample solutions. As shown in Fig. 1 and 2, Blasticidin gave the highest activity against P. oryzae at pH 5.0 in both of them.(3) The cup method for assaying Blasticidin was established. The assay medium was as follows: Soluble starch 10g, yeast extract 1g, agar 15g and 0.1M PO4 buffer of pH 5.0 1, 000 ml. The sample solutions were made with 0.1 M PO4 buffer of pH 5.0. As shown in Fig 4, the excellence of log dose-response curve and its linearity within the range of 0.2-2.0mcg/ml warrants the use of the cup method.(4) The paper disc method was adapted to the assay of Antimycin A and Blastmycin. The assay media were made with distilled water. Samples were dissolved in methanol The linear relations were found between the diameters of inhibition zones and the log concentrations within the ranges of 0.05-5.0mcg/ml of Antimycin A and 0.05-0.5mcg/ml of Blastmycin. The potency are calculated on the basis of this relation.
Reversible Resistance Induced by FLT3 Inhibition: A Novel Resistance Mechanism in Mutant FLT3-Expressing Cells (2011)

We found that MOLM13 cells readily developed cross-resistance when exposed to either midostaurin or HG-7-85-01. Resistance in both lines was associated with dramatically elevated levels of cell surface FLT3 and elevated levels of phosphor-MAPK, but not phospho-STAT5. The increase in FLT3-ITD expression was at least in part due to reduced turnover of the receptor, with prolonged half-life. Importantly, the drug-resistant phenotype could be rapidly reversed upon withdrawal of either inhibitor. Consistent with this phenotype, no significant evidence of FLT3 gene amplification, kinase domain mutations, or elevated levels of mRNA was observed, suggesting that protein turnover may be part of an auto-regulatory pathway initiated by FLT3 kinase activity. Interestingly, FLT3 inhibitor resistance also correlated with resistance to cytosine arabinoside. Over-expression of FLT3 protein in response to kinase inhibitors may be part of a novel mechanism that could contribute to clinical resistance.
A phase II trial of paclitaxel (Taxol) in advanced esophageal cancer: preliminary report. (1994)

A cooperative, phase II single-arm trial was conducted at two large tertiary referral cancer centers to evaluate the antineoplastic activity and toxicities of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of patients with advanced esophageal cancer. The drug was given at a dose of 250 mg/m2 as a 24-hour continuous infusion. Repeat courses were given at 21-day intervals. De-escalation was based primarily on myelosuppression. All patients received recombinant human granulocyte colony-stimulating factor to minimize the risk of neutropenic fever. The primary goal of the study was tumor response. In the trial, which is ongoing, 42 patients have been assessed to date. Adenocarcinoma was the predominant histology in 30 patients, while epidermoid cancer was seen in 13 patients. Paclitaxel was identified as an active agent. Thirty percent of patients with adenocarcinoma and 25% of the smaller group with epidermoid carcinoma have had partial remissions. Complete remissions have not been seen to date. The median duration of response was 9 weeks. The major toxicity was myelosuppression; 11 patients required admission for neutropenic fever on 13 different occasions. Paclitaxel is an active drug in the treatment of esophageal cancer. Currently, there does not appear to be a difference in response on the basis of histologic subtype. Further studies with paclitaxel in combination with other drugs (eg, cisplatin and 5-fluorouracil), on different treatment schedules, and as part of multimodality therapy are indicated.
A partially open porous media flow with chaotic advection: towards a model of coupled fields (2009)

In nature, dissipative fluxes of fluid, heat and/or reacting species couple to each other and may also couple to deformation of a surrounding porous matrix. We use the well-known analogy of Hele-Shaw flow to Darcy flow to make a model porous medium with porosity proportional to local cell height. Time- and space-varying fluid injection from multiple source/sink wells lets us create many different kinds of chaotic flows and chemical concentration patterns. Results of an initial time-dependent potential flow model illustrate that this is a partially open flow, in which parts of the material transported by the flow remain in the cell forever and parts pass through with residence time and exit time distributions that have self-similar features in the control parameter space of the stirring. We derive analytically the existence boundary in stirring control parameter space between where isolated fluid regions can and cannot remain forever in the open flow. Experiments confirm the predictions.