gebhart/patrepeval huggingface dataset:
Asenapine monotherapy in the acute treatment of both schizophrenia and bipolar&nbsp;I disorder (2009)

Asenapine is a new atypical antipsychotic agent currently under development for the treatment of schizophrenia and bipolar disorder. It has high affinity for various receptors including antagonism at 5HT(2A), 5HT(2B), 5HT(2C), 5HT(6) and 5HT(7) serotonergic receptor subtypes, alpha(1A), alpha(2A), alpha(2B) and alpha(2C) adrenergic and D(3) and D(4) dopaminergic receptors. As with other atypicals, asenapine exhibits a high 5HT(2A):D(2) affinity ratio. Although similar to clozapine in its multi-target profile, it shows no appreciable affinity for muscarinic receptors. Asenapine has shown efficacy in alleviating both positive and negative symptoms of schizophrenia compared with placebo. Although promising, further studies are required in order to determine whether it has advantages over placebo and other antipsychotics in alleviating cognitive impairment associated with schizophrenia. It has also shown long-term efficacy comparable with olanzapine in bipolar I disorder. Asenapine is generally well tolerated and appears to be metabolically neutral. It has low propensity to cause weight gain and prolactin elevation. There were no concerns in the studies about its effects on the cardiovascular system and QTc prolongation. The incidence of extrapyramidal symptoms with asenapine however has been found to be higher than that with olanzapine. It may be a useful alternative to aripiprazole in schizophrenia and bipolar disorder in patients who are at high risk of metabolic abnormalities.
Towards quantitative analysis of retinal features in optical coherence tomography (2006)

The purpose of this paper was to propose a new computer method for quantitative evaluation of representative features of the retina using optical coherence tomography (OCT). A multi-step approach was devised and positively tested for segmentation of the three main retinal layers: the vitreo-retinal interface and the inner and outer retina. Following a preprocessing step, three regions of interest were delimited. Significant peaks corresponding to high and low intensity strips were located along the OCT A-scan lines and accurate boundaries between different layers were obtained by maximizing an edge likelihood function. For a quantitative description, thickness measurement, densitometry, texture and curvature analyses were performed. As a first application, the effect of intravitreal injection of triamcinolone acetonide (IVTA) for the treatment of vitreo-retinal interface syndrome was evaluated. Almost all the parameters, measured on a set of 16 pathologic OCT images, were statistically different before and after IVTA injection (p<0.05). Shape analysis of the internal limiting membrane confirmed the reduction of the pathological traction state. Other significant parameters, such as reflectivity and texture contrast, exhibited relevant changes both at the vitreo-retinal interface and in the inner retinal layers. Texture parameters in the inner and outer retinal layers significantly correlated with the visual acuity restoration. According to these findings an IVTA injection might be considered a possible alternative to surgery for selected patients. In conclusion, the proposed approach appeared to be a promising tool for the investigation of tissue changes produced by pathology and/or therapy.
Cocaine and its derivatives blunt neutrophil functions without influencing phosphorylation of a 47-kilodalton component of the reduced nicotinamide-adenine dinucleotide phosphate oxidase. (1990)

Cocaine and its derivatives blunted responses of neutrophils (cell/cell aggregation, up-regulation of the receptor for C3bi (CR3, CD11b/CD18), generation of superoxide anion (O2-) and degranulation to various stimuli. The order of potency of these agents was the same as that for local anesthesia: tetracaine greater than bupivacaine greater than cocaine greater than lidocaine. Neutrophil aggregation elicited by the chemoattractant FMLP (10(-7) M) was inhibited by cocaine (10 mM) to 13.6 +/- 6% of control (p less than 0.002); the IC50 was approximately 4 mM. Cocaine and the other local anesthetics not only inhibited the upregulation of CR3 and O2- generation, but also blocked degranulation of cytochalasin B-treated cells. Cocaine (10 mM) reduced beta-glucuronidase and lysozyme secretion to 4.3 +/- 0.7 and 13 +/- 2.2% controls, respectively; its IC50 was 4 mM. Local anesthetics added after ligand/receptor engagement (FMLP) interrupted aggregation and halted generation of O2-. Moreover, local anesthetics rapidly inhibited aggregation, O2- generation, and degranulation elicited by PMA (1 microgram/ml) or the Ca ionophore A23187 (10 microM): the effects of cocaine could therefore not be attributed to unique actions at the FMLP receptor. Peak levels of intracellular Ca2+ ([Ca]i) at 5 to 10 s, and levels of [Ca]i 120 s after FMLP in Fura 2-loaded cells were significantly lower in cells treated with lidocaine, findings that could be explained by enhanced 45Ca2+ efflux from neutrophils. In cells loaded with bis(carboxyethyl)carboxyfluorescine (pH indicator) local anesthetics failed to affect the initial FMLP-induced (0 to 15 s) drop of pHi but inhibited the later (120 s) realkalinization of the cytosol (lidocaine, bupivacaine). Most remarkably, autoradiographs of SDS gels prepared from stimulated, 32P-labeled neutrophils treated with local anesthetics showed no difference from resting cells, either with respect to patterns of phosphorylation and dephosphorylation or their kinetics. Labeling of a 47-kDa protein, a component of the reduced nicotinamide-adenine dinucleotide phosphate-oxidase system, was unchanged. The effects of local anesthetics, which blunt neutrophil responses without affecting protein phosphorylation, suggest that protein phosphorylation is an insufficient signal for neutrophil activation. Inasmuch as cocaine and its derivatives affect cell functions at sites distal to activation of protein kinase C, these agents should prove useful in uncoupling protein phosphorylation from functional responses.
The overexpression, purification and complete amino acid sequence of chorismate synthase from Escherichia coli K12 and its comparison with the enzyme from Neurospora crassa (1988)

The enzyme chorismate synthase was purified in milligram quantities from an overproducing strain of Escherichia coli. The amino acid sequence was deduced from the nucleotide sequence of the aroC gene and confirmed by determining the N-terminal amino acid sequence of the purified enzyme. The complete polypeptide chain consists of 357 amino acid residues and has a calculated subunit Mr of 38,183. Cross-linking and gel-filtration experiments show that the enzyme is tetrameric. An improved purification of chorismate synthase from Neurospora crassa is also described. Cross-linking and gel-filtration experiments on the N. crassa enzyme show that it is also tetrameric with a subunit Mr of 50,000. It is proposed that the subunits of the N. crassa enzyme are larger because they contain a diaphorase domain that is absent from the E. coli enzyme.
Hedgehog signalling in colorectal tumour cells: Induction of apoptosis with cyclopamine treatment (2004)

Hedgehog (Hh) signalling controls many aspects of development. It also regulates cell growth and differentiation in adult tissues and is activated in a number of human malignancies. Hh and Wnt signalling frequently act together in controlling cell growth and tissue morphogenesis. Despite the fact that the majority of colorectal tumours have a constitutively activated canonical Wnt pathway, few previous studies have investigated the expression of Hh signalling components in colorectal tumours. We describe here epithelial cell lines derived from both nonmalignant colorectal adenomas and colorectal adenocarcinomas that express both Sonic and Indian Hh. Interestingly, these cells also express the Hh receptor Patched and the downstream signalling components Smoothened and Gli1, suggesting autocrine Hh signalling in these cells. To test whether autocrine Hh signalling contributes to cell survival, we treated colorectal tumour cells with cyclopamine, a known inhibitor of Hh signalling. Cyclopamine treatment induced apoptosis in both adenoma- and carcinoma-derived cell lines, which could be partially rescued by further stimulation of Hh signalling. These data suggest that autocrine Hh signalling can increase aberrant cell survival in colorectal tumour cells and may be a novel target for colon cancer therapy using drugs such as cyclopamine.
The intra‐oral translocation of periodontopathogens jeopardises the outcome of periodontal therapy (2001)

Abstract Background: Although periodontitis has a multi‐factorial aetiology, the success of its therapy mainly focuses on the eradication/reduction of the exogenous/endogenous periodontopathogens. Most of the species colonise several niches within the oral cavity (e.g. the mucosae, the tongue, the saliva, the periodontal pockets and all intra‐oral hard surfaces) and even in the oro‐pharyngeal area (e.g., the sinus and the tonsils). Methods: This review article discusses the intra‐oral transmission of periodontopathogens between these niches and analyses clinical studies that support the idea and importance of such an intra‐oral translocation. Results and conclusions: Based on the literature, the oro‐pharyngeal area should indeed be considered as a microbiological entity. Because untreated pockets jeopardise the healing of recently instrumented sites, the treatment of periodontitis should involve “a one stage approach” of all pathologic pockets (1‐stage full‐mouth disinfection) or should at least consider the use of antiseptics during the intervals between consecutive instrumentations, in order to prevent a microbial translocation of periodontopathogens during the healing period. For the same reason, regeneration procedures or the local application of antibiotics should be postponed until a maximal improvement has been obtained in the remaining dentition. This more global approach offers significant additional clinical and microbiological benefits.
Charging Process and Coulomb-Force-Directed Printing of Nanoparticles with Sub-100-nm Lateral Resolution (2005)

This article reports on a new charging process and Coulomb-force-directed assembly of nanoparticles onto charged surface areas with sub-100-nm resolution. The charging is accomplished using a flexible nanostructured thin silicon electrode. Electrical nanocontacts have been created as small as 50 nm by placing the nanostructured electrode onto an electret surface. The nanocontacts have been used to inject charge into 50 nm sized areas. Nanoparticles were assembled onto the charge patterns, and a lateral resolution of 60 nm has been observed for the first time. A comparison of the nanoparticle patterns with the surface potential distribution recorded by Kelvin probe force microscopy (KFM) revealed a mismatch in the lateral resolution. One possible explanation is that nanoparticles may visualize charge patterns at a sub-60-nm length scale that is not well resolved using KFM.
A Status Report on the 0Z Project (2011)

We present an update on the status of the 0Z Survey, an effort to datamine the Hamburg/ESO Survey to find and study in detail a large sample of extremely metal-poor Galactic halo field stars with [Fe/H] &lt; -3 dex. After searching 1,565 moderate resolution spectra of candidates selected from the HES, we have acquired high resolution spectra of 103 of the most metal-poor of them. Detailed abundance analyses have been performed for all these stars. This has resulted in the discovery of 18 new stars below [Fe/H] -3.5 dex and 57 below -3.0 dex. Some results are presented regarding our search for outliers in chemical abundances of particular species among the sample of 103 stars. Ignoring C and N, about 15% of the sample are "abnormal" in some way. Our plans to complete this project and write the final set of papers are described.
A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for Myelofibrosis (2012)

Ruxolitinib, as compared with placebo, provided significant clinical benefits in patients with myelofibrosis by reducing spleen size, ameliorating debilitating myelofibrosis-related symptoms, and improving overall survival. These benefits came at the cost of more frequent anemia and thrombocytopenia in the early part of the treatment period. (Funded by Incyte; COMFORT-I ClinicalTrials.gov number, NCT00952289.).
[Mouse brain gangliosides during development: demonstration of a new ganglioside]. (1976)

The study of gangliosides as a function of age indicates that four of the main components GD1a (G3), GD1b (G2), GT1 (G1) and GQ (G0) are present at birth. They increase with age. On thin-layer chromatography, GD1a seems to be maximum at 18 days and GD1b continues to increase. GM1 increases also from birth to adult age. A new ganglioside has been detected in Mouse brain during its development. Not detected 5 days after birth, it is present at 18 days and in maximal quantity at adult age. This compound does not seem to be correlated to myelination process.
Limnological succession in reservoirs: a paleolimnological comparison of two methods of reservoir formation (1999)

Analysis of diatoms, algal pigments, and chironomids in sediment cores from two otherwise similar prairie reservoirs demonstrated that differences in reservoir formation (river valley impoundment versus lake inundation) and hydrological regime (variable versus stable water level) resulted in distinct patterns of aquatic community change. Lake Diefenbaker, a 500-km 2 reservoir created by damming the South Saskatchewan River in 1968, experiences water level fluctuations of 6 m·year -1 . In contrast, impoundment of Buffalo Pound Lake in 1952 flooded a natural lake, raised mean water levels ~2.0 m, and reduced water level fluctuations from ~3 to &lt;1 m·year -1 . Comparison of fossil records showed that reservoir formation did not inevitably lead to eutrophication. Lake Diefenbaker exhibited typical reservoir ontogeny with three trophic periods, including an initial ~4-year period of eutrophy, a decade of mesotrophy, and a gradual shift to modern productive conditions. Planktonic taxa dominated diatom communities at all times, whereas benthic chironomid and algal remains were rare. In contrast, pigment analyses suggested that phytoplankton standing crops declined after impoundment in Buffalo Pound Lake but that chironomid and macrophyte populations expanded. Such site specificity in trophic development appears to result from differences in the extent of inundation (500 versus ~5 km 2 ) and the magnitude of subsequent water level fluctuations (6.3 versus &lt;1 m).
Protection Against Streptococcal Pharyngeal Colonization with a Vaccinia: M Protein Recombinant (1989)

Phagocytosis of group A streptococci requires type-specific antibodies directed against the variable determinants of the bacterial surface M protein molecule. As a step toward developing a broadly protective anti-streptococcal vaccine, a vaccinia virus (VV) recombinant was constructed that expresses the conserved region of the structural gene encoding the M6 molecule (VV:M6'). Mice immunized intranasally with the VV:M6' virus showed markedly reduced pharyngeal colonization by streptococci after intranasal and oral challenge with these bacteria. M protein-specific serum immunoglobulin G was significantly elevated in vaccinated animals and absent in controls. A similar approach may prove useful for the identification of protective determinants present on other bacterial and viral pathogens.
Recombinant immunotoxins containing anti-Tac(Fv) and derivatives of Pseudomonas exotoxin produce complete regression in mice of an interleukin-2 receptor-expressing human carcinoma (1994)

Anti-Tac(Fv)-PE40 is a recombinant single-chain immunotoxin composed of the variable domains of the monoclonal antibody anti-Tac, which binds to the p55 subunit of the interleukin-2 receptor (IL-2R), and a truncated form of Pseudomonas exotoxin (PE), which does not bind to the PE receptor (Chaudhary et al, Nature 339:394, 1989). Whereas its cytotoxic activity toward autoimmune and malignant target cells has been established, its efficacy in vivo remains unknown. To establish an animal model, we produced ATAC-4 cells by transfecting the gene encoding the low-affinity IL-2R (p55) into A431 epidermoid carcinoma cells. ATAC-4 cells contained low-affinity IL-2Rs (2 x 10(5)/cell) and formed tumors in nude mice. In tissue culture, protein synthesis in ATAC-4 cells was inhibited 50% (IC50) at 0.06 ng/mL (0.9 pmol/L) of anti-Tac(Fv)-PE40. IC50s for the derivatives anti-Tac(Fv)-PE38, which is missing PE amino acids 365–380, and anti-Tac(Fv)-PE38KDEL, which contains the same deletion plus the KDEL carboxyl terminus, were 0.04 and 0.025 ng/mL, respectively. All the agents produced complete tumor regressions in ATAC-4 tumor-bearing mice and anti-Tac(Fv)-PE38KDEL had significant antitumor activity at 1% of the LD50. The dose limiting toxicity of anti-Tac(Fv)-PE38KDEL was from hemorrhagic liver necrosis, which was observed at approximately 55% of the LD50.
Topographically specific hippocampal projections target functionally distinct prefrontal areas in the rhesus monkey (1995)

The sources of ipsilateral projections from the hippocampal formation, the presubiculum, area 29a-c, and parasubiculum to medial, orbital, and lateral prefrontal cortices were studied with retrograde tracers in 27 rhesus monkeys. Labeled neurons within the hippocampal formation (CA1, CA1', prosubiculum, and subiculum) were found rostrally, although some were noted throughout the entire rostrocaudal extent of the hippocampal formation. Most labeled neurons in the hippocampal formation projected to medial prefrontal cortices, followed by orbital areas. In addition, there were differences in the topography of afferent neurons projecting to medial when compared with orbital cortices. Labeled neurons innervating medial cortices were found mainly in the CA1' and CA1 fields rostrally, but originated in the subicular fields caudally. In contrast, labeled neurons which innervated orbital cortices were considerably more focal, emanating from the same relative position within a field throughout the rostrocaudal extent of the hippocampal formation. In marked contrast to the pattern of projection to medial and orbital prefrontal cortices, lateral prefrontal areas received projections from only a few labeled neurons found mostly in the subicular fields. Lateral prefrontal cortices received the most robust projections from the presubiculum and the supracallosal area 29a-c. Orbital, and to a lesser extent medial, prefrontal areas received projections from a smaller but significant number of neurons from the presubiculum and area 29a-c. Only a few labeled neurons were found in the parasubiculum, and most projected to medial prefrontal areas. The results suggest that functionally distinct prefrontal cortices receive projections from different components of the hippocampal region. Medial and orbital prefrontal cortices may have a role in long-term mnemonic processes similar to those associated with the hippocampal formation with which they are linked. Moreover, the preponderance of projection neurons from the hippocampal formation innervating medial when compared with orbital prefrontal areas followed the opposite trend from what we had observed previously for the amygdala (Barbas and De Olmos [1990] (J Comp Neurol 301:1-23). Thus, the hippocampal formation, associated with mnemonic processes, targets predominantly medial prefrontal cortices, whereas the amygdala, associated with emotional aspects of memory, issues robust projections to orbital limbic cortices. Lateral prefrontal cortices receive robust projections from the presubiculum and area 29a-c and sparse projections from the hippocampal formation. These findings are consistent with the idea that the role of lateral prefrontal cortices in memory is distinct from that of either medial or orbital cortices. The results suggest that signals from functionally distinct limbic structures to some extent follow parallel pathways to functionally distinct prefrontal cortices.
Independent Risk Factors for Atrial Fibrillation in a Population-Based Cohort (1994)

<h3>Objective.</h3> —To determine the independent risk factors for atrial fibrillation. <h3>Design.</h3> —Cohort study. <h3>Setting.</h3> —The Framingham Heart Study. <h3>Subjects.</h3> —A total of 2090 men and 2641 women members of the original cohort, free of a history of atrial fibrillation, between the ages of 55 and 94 years. <h3>Main Outcome Measures.</h3> —Sex-specific multiple logistic regression models to identify independent risk factors for atrial fibrillation, including age, smoking, diabetes, electrocardiographic left ventricular hypertrophy, hypertension, myocardial infarction, congestive heart failure, and valve disease. <h3>Results.</h3> —During up to 38 years of follow-up, 264 men and 298 women developed atrial fibrillation. After adjusting for age and other risk factors for atrial fibrillation, men had a 1.5 times greater risk of developing atrial fibrillation than women. In the full multivariable model, the odds ratio (OR) of atrial fibrillation for each decade of advancing age was 2.1 for men and 2.2 for women (<i>P</i>&lt;.0001). In addition, after multivariable adjustment, diabetes (OR, 1.4 for men and 1.6 for women), hypertension (OR, 1.5 for men and 1.4 for women), congestive heart failure (OR, 4.5 for men and 5.9 for women), and valve disease (OR, 1.8 for men and 3.4 for women) were significantly associated with risk for atrial fibrillation in both sexes. Myocardial infarction (OR, 1.4) was significantly associated with the development of atrial fibrillation in men. Women were significantly more likely than men to have valvular heart disease as a risk factor for atrial fibrillation. The multivariable models were largely unchanged after eliminating subjects with valvular heart disease. <h3>Conclusion.</h3> —In addition to intrinsic cardiac causes such as valve disease and congestive heart failure, risk factors for cardiovascular disease also predispose to atrial fibrillation. Modification of risk factors for cardiovascular disease may have the added benefit of diminishing the incidence of atrial fibrillation. (<i>JAMA</i>. 1994;271:840-844)
The iterative time reversal process: Analysis of the convergence (1995)

The efficiency of a time reversal acoustic mirror to focus on a reflective target through an inhomogeneous media has been demonstrated. In a multitarget media, the ability of such a mirror to work in an iterative mode in order to focus selectively on the strongest target was shown [C. Prada, F. Wu, and M. Fink, J. Acoust. Soc. Am. 90, 1119 (1991)]. The theory of how the iterative time reversal process is built is based on a matrix formalism and treats the array of L transducers in a given medium as a linear system of L inputs/L outputs. The system is characterized at each frequency by its transfer matrix K and the time reversal iterative process is then described by a time reversal operator K*K. Because of the reciprocity principle, this operator is Hermitian. The following result is shown: If the scattering medium is a set of well resolved targets of different reflectivities then each eigenvector of the operator K*K with nonzero eigenvalue corresponds to one of the targets in the set and provides the optimum phase law to focus on it. Furthermore, the eigenvalue is proportional to the reflectivity of the target. In particular, the ‘‘brightest’’ target is associated to the eigenvector of greatest eigenvalue so that the iterative time reversal process leads to a wave focusing on this target. This analysis is illustrated by numerical and experimental results.