pinecone/core-2020-05-10-deduplication huggingface dataset:
Ethanol-induced sensitization depends preferentially on D-1 rather than D-2 dopamine receptors

Behavioral sensitization, defined as a progressive increase in the locomotor stimulant effects elicited by repeated exposure to drugs of abuse, has been used as an animal model for drug craving in humans. the mesoaccumbens dopaminergic system has been proposed to be critically involved in this phenomenon; however, few studies have been designed to systematically investigate the effects of dopaminergic antagonists on development and expression of behavioral sensitization to ethanol in Swiss mice. We first tested the effects of D-1 antagonist SCH-23390 (0-0.03 mg/kg) or D-2 antagonist Sulpiride (0-30 mg/kg) on the locomotor responses to an acute injection of ethanol (2.0 g/kg). Results showed that all tested doses of the antagonists were effective in blocking ethanol's stimulant effects. in another set of experiments, mice were pretreated intraperitoneally with SCH-23390 (0.01 mg/kg) or Sulpiride (10 mg/kg) 30 min before saline or ethanol injection, for 21 days. Locomotor activity was measured weekly for 20 min. Four days following this pretreatment, all mice were challenged with ethanol. Both antagonists attenuated the development of ethanol sensitization, but only SCH-23390 blocked the expression of ethanol sensitization according to this protocol. When we tested a single dose (30 min before tests) of either antagonist in mice treated chronically with ethanol, both antagonists attenuated ethanol-induced effects. the present findings demonstrate that the concomitant administration of ethanol with D-1 but not D-2 antagonist prevented the expression of ethanol sensitization, suggesting that the neuroadaptations underlying ethanol behavioral sensitization depend preferentially on D-1 receptor actions. (C) 2010 Elsevier Inc. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ São Paulo, Inst Ciencias Biomed, Dept Farmacol, BR-05508900 São Paulo, BrazilUniv São Paulo, Fac Ciencias Farmaceut, BR-05508900 São Paulo, BrazilUniv Fed ABC, Ctr Matemat Comp & Cognicao, Santo Andre, SP, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, São Paulo, BrazilWeb of Scienc
International preoperative rectal cancer management: staging, neoadjuvant treatment, and impact of multidisciplinary teams

Law, WL is one of the members of the International Rectal Cancer Study GroupBACKGROUND: Little is known regarding variations in preoperative treatment and practice for rectal cancer (RC) on an international level, yet practice variation may result in differences in recurrence and survival rates. METHODS: One hundred seventy-three international colorectal centers were invited to participate in a survey of preoperative management of rectal cancer. RESULTS: One hundred twenty-three (71%) responded, with a majority of respondents from North America, Europe, and Asia. Ninety-three percent have more than 5 years' experience with rectal cancer surgery. Fifty-five percent use CT scan, 35% MRI, 29% ERUS, 12% digital rectal examination and 1% PET scan in all RC cases. Seventy-four percent consider threatened circumferential margin (CRM) an indication for neoadjuvant treatment. Ninety-two percent prefer 5-FU-based long-course neoadjuvant chemoradiation therapy (CRT). A significant difference in practice exists between the US and non-US surgeons: poor histological differentiation as an indication for CRT (25% vs. 7.0%, p = 0.008), CRT for stage II and III rectal cancer (92% vs. 43%, p = 0.0001), MRI for all RC patients (20% vs. 42%, p = 0.03), and ERUS for all RC patients (43% vs. 21%, p = 0.01). Multidisciplinary team meetings significantly influence decisions for MRI (RR = 3.62), neoadjuvant treatment (threatened CRM, RR = 5.67, stage II + III RR = 2.98), quality of pathology report (RR = 4.85), and sphincter-saving surgery (RR = 3.81). CONCLUSIONS: There was little consensus on staging, neoadjuvant treatment, and preoperative management of rectal cancer. Regular multidisciplinary team meetings influence decisions about neoadjuvant treatment and staging methods.published_or_final_versio
Evaluation of the XRCC1 gene as a phenotypic modifier in BRCA1/2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.BACKGROUND: Single-nucleotide polymorphisms (SNPs) in genes involved in DNA repair are good candidates to be tested as phenotypic modifiers for carriers of mutations in the high-risk susceptibility genes BRCA1 and BRCA2. The base excision repair (BER) pathway could be particularly interesting given the relation of synthetic lethality that exists between one of the components of the pathway, PARP1, and both BRCA1 and BRCA2. In this study, we have evaluated the XRCC1 gene that participates in the BER pathway, as phenotypic modifier of BRCA1 and BRCA2.\ud
METHODS:\ud
Three common SNPs in the gene, c.-77C>T (rs3213245) p.Arg280His (rs25489) and p.Gln399Arg (rs25487) were analysed in a series of 701 BRCA1 and 576 BRCA2 mutation carriers.\ud
RESULTS:\ud
An association was observed between p.Arg280His-rs25489 and breast cancer risk for BRCA2 mutation carriers, with rare homozygotes at increased risk relative to common homozygotes (hazard ratio: 22.3, 95% confidence interval: 14.3-34, P<0.001). This association was further tested in a second series of 4480 BRCA1 and 3016 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2. CONCLUSIONS AND INTERPRETATION: No evidence of association was found when the larger series was analysed which lead us to conclude that none of the three SNPs are significant modifiers of breast cancer risk for mutation carriers
A Y-shaped RNA structure in the 3' untranslated region together with the trans-activator and core promoter of Red clover necrotic mosaic virus RNA2 is required for its negative-strand RNA synthesis.

Red clover necrotic mosaic virus (RCNMV) is a positive-strand RNA virus with a bipartite genome. RNA1 encodes N-terminally overlapping replication proteins, p27 and p88. RNA2 is replicated efficiently by the replication proteins supplied in trans, whereas RNA1 needs p88 preferentially in cis for its replication. cis-Acting elements required for RNA2 replication have been mapped to the 3' terminal stem-loop structure conserved between RNA1 and RNA2, and to the protein-coding region including the trans-activator. Here, we have identified a Y-shaped RNA structure with three-way RNA junctions predicted in the 3' untranslated region of RNA2 as a novel element required for negative-strand synthesis using an in vitro translation/replication system. We also show that, in addition to the 3' terminal core promoter, several RNA elements including the trans-activator are also required for negative-strand synthesis. Functional roles and structural requirements of these cis-acting elements in RCNMV RNA replication are discussed
A new comprehensive 2D model of the point spread functions of the XMM-Newton EPIC telescopes: spurious source suppression and improved positional accuracy

Aims. We describe here a new full 2D parameterization of the PSFs of the three XMM-Newton EPIC telescopes as a function of instrument, energy, off-axis angle and azimuthal angle, covering the whole field-of-view (FoV) of the three EPIC detectors. It models the general PSF envelopes, the primary and secondary spokes, their radial dependencies, and the large-scale azimuthal variations.\ud
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Methods. This PSF model has been constructed via the stacking and centering of a large number of bright, but not significantly piled-up point sources from the full FoV of each EPIC detector, and azimuthally filtering the resultant PSF envelopes to form the spoke structures and the gross azimuthal shapes observed.\ud
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Results. This PSF model is available for use within the XMM-Newton science analysis system via the usage of current calibration files XRTi_XPSF_0011.CCF and later versions. Initial source-searching tests showed substantial reductions in the numbers of spurious sources being detected in the wings of bright point sources. Furthermore, we have uncovered a systematic error in the previous PSF system, affecting the entire mission to date, whereby returned source RA and Dec values are seen to vary sinusoidally about the true position (amplitude  ≈0.8″) with source azimuthal position.\ud
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Conclusions. The new PSF system is now available and is seen as a major improvement with regard to the detection of spurious sources. The new PSF also largely removes the discovered astrometry error and is seen to improve the positional accuracy of EPIC. The modular nature of the PSF system allows for further refinements in the future.Peer-reviewedPublisher Version10148
Probability boxes on totally preordered spaces for multivariate modelling.

A pair of lower and upper cumulative distribution functions, also called probability box or p-box, is among the most popular models used in imprecise probability theory. They arise naturally in expert elicitation, for instance in cases where bounds are specified on the quantiles of a random variable, or when quantiles are specified only at a finite number of points. Many practical and formal results concerning p-boxes already exist in the literature. In this paper, we provide new efficient tools to construct multivariate p-boxes and develop algorithms to draw inferences from them. For this purpose, we formalise and extend the theory of p-boxes using Walley's behavioural theory of imprecise probabilities, and heavily rely on its notion of natural extension and existing results about independence modeling. In particular, we allow p-boxes to be defined on arbitrary totally preordered spaces, hence thereby also admitting multivariate p-boxes via probability bounds over any collection of nested sets. We focus on the cases of independence (using the factorization property), and of unknown dependence (using the Fréchet bounds), and we show that our approach extends the probabilistic arithmetic of Williamson and Downs. Two design problems - a damped oscillator, and a river dike - demonstrate the practical feasibility of our results.\u
Genetic algorithms and the search for viable string vacua.

Genetic Algorithms are introduced as a search method for finding string vacua with viable phenomenological properties. It is shown, by testing them against a class of Free Fermionic models, that they are orders of magnitude more efficient than a randomised search. As an example, three generation, exophobic, Pati-Salam models with a top Yukawa occur once in every 1010 models, and yet a Genetic Algorithm can find them after constructing only 105 examples. Such non-deterministic search methods may be the only means to search for Standard Model string vacua with detailed phenomenological requirements
The functional foetal brain : a systematic preview of methodological factors in reporting foetal visual and auditory capacity.

Due to technological advancements in functional brain imaging, foetal brain responses to visual and auditory stimuli is a growing area of research despite being relatively small with much variation between research laboratories. A number of inconsistencies between studies are, nonetheless, present in the literature. This article aims to explore the potential contribution of methodological factors to variation in reports of foetal neural responses to external stimuli. Some of the variation in reports can be explained by methodological differences in aspects of study design, such as brightness and wavelength of light source. In contrast to visual foetal processing, auditory foetal processing has been more frequently investigated and findings are more consistent between different studies. This is an early preview of an emerging field with many articles reporting small sample sizes with techniques that are yet to be replicated. We suggest areas for improvement for the field as a whole, such as the standardisation of stimulus delivery and a more detailed reporting of methods and results. This will improve our understanding of foetal functional response to light and sound. We suggest that enhanced technology will allow for a more reliable description of the developmental trajectory of foetal processing of light stimuli
‘The judgement of God on an indolent and unself-reliant people’? : the impact of the Great Irish Famine on Ireland's religious demography.

It has suited both sides of Ireland's religious and political divide to portray the Great Famine that affected Ireland in the late 1840s as primarily affecting the Catholic population. However, while the geographies of the Famine have been explored in detail in recent years its religious dimensions have been largely ignored, albeit with a few exceptions. As a consequence, the assumption that the Great Famine was a Catholic famine has not been sufficiently challenged. Drawing on a relatively untapped source, the 1834 Commission on ‘the state of religion and other instruction in Ireland,’ as well as census data, this paper explores the relationship between religion, poverty and population loss over the Famine period. It shows that Catholics were disproportionately affected by the Famine because the Famine was most severe in areas whose population was overwhelmingly Catholic. In more mixed areas, however, the Protestant population seems to have been at least as affected as Catholics if not more so. This conundrum explains why the Famine actually had a surprisingly small impact on Ireland's religious demography
Mental health law and the UN Convention on the rights of persons with disabilities.

People with a mental illness may be subject to the UN Convention on the Rights of Persons with Disabilities (CRPD), depending on definitions of terms such as ‘impairment’, ‘long-term’ and the capaciousness of the word ‘includes’ in the Convention's characterisation of persons with disabilities. Particularly challenging under the CRPD is the scope, if any, for involuntary treatment.\ud
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Conventional mental health legislation, such as the Mental Health Act (England and Wales) appears to violate, for example, Article 4 (‘no discrimination of any kind on the basis of disability’), Article 12 (persons shall ‘enjoy legal capacity on an equal basis with others in all aspects of life’) and Article 14 (‘the existence of a disability shall in no case justify a deprivation of liberty’).\ud
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We argue that a form of mental health law, such as the Fusion Law proposal, is consistent with the principles of the CRPD. Such law is aimed at eliminating discrimination against persons with a mental illness. It covers all persons regardless of whether they have a ‘mental’ or a ‘physical’ illness, and only allows involuntary treatment when a person's decision-making capability (DMC) for a specific treatment decision is impaired — whatever the health setting or cause of the impairment — and where supported decision making has failed. In addition to impaired DMC, involuntary treatment would require an assessment that such treatment gives the person's values and perspective paramount importance
Resurgence of the cusp anomalous dimension.

We revisit the strong coupling limit of the cusp anomalous dimension in planar N=4N=4 super Yang-Mills theory. It is known that the strong coupling expansion is asymptotic and non-Borel summable. As a consequence, the cusp anomalous dimension receives non-perturbative corrections, and the complete strong coupling expansion should be a resurgent transseries. We reveal that the perturbative and non-perturbative parts in the transseries are closely interrelated. Solving the Beisert-Eden-Staudacher equation systematically, we analyze in detail the large order behavior in the strong coupling pertur- bative expansion and show that the non-perturbative information is indeed encoded there. An ambiguity of (lateral) Borel resummations of the perturbative expansion is precisely canceled by the contributions from the non-perturbative sectors, and the final result is real and unambiguous
From mantle to critical zone: A review of large and giant sized deposits of the rare earth elements

The rare earth elements are unusual when de quoted as total rare earth oxide, but the importance of a deposit may be related to the grade for individual, or a limited group of the elements. Taking the total REE resource, only one currently known deposit (Bayan Obo) would class as giant ( classify as large ( Olympic Dam IOCG deposit, all of these deposits are related to alkaline igneous activity or agpaitic nepheline syenites. The total resource in these deposits must relate to the scale of the primary igneous source, but the grade is a complex function of igneous source, magmatic crystallisation, hydrothermal modi that the sources conducive to the formation of large REE deposits are developed in subcontinental lithospheric mantle, enriched in trace elements either by plume activity, or by previous subduction. The reactivation of such enriched mantle domains in relatively restricted geographical areas may have played a role in the formation of some of the largest deposits (e.g. Bayan Obo). Hydrothermal activity involvingfining giant-sized ore deposits, as resources are often>1.7 107 tonnes contained metal), but a range of others>1.7 106 tonnes). With the exception of unclassified resource estimates from thee either carbonatitesfication and supergene enrichment during weathering. Isotopic data suggest fl grade, depending on primary mineralogy and the availability of ligands. Weathering and supergene enrichment of carbonatite has played a role in the formation of the highest grade deposits at MountWeld (Australia) and Tomtor (Russia). For the individual REE with the current highest economic value (Nd and the HREE), the boundaries for the large and giant size classes are two orders of magnitude lower, and deposits enriched in these metals (agpaitic systems, ion absorption deposits) may have signi economic impact in the near future.uids from magmatic to meteoric sources may result in the redistribution of the REE and increases infican
Magneto-static modelling of the mixed plasma Beta solar atmosphere based
  on SUNRISE/IMaX data

Our aim is to model the 3D magnetic field structure of the upper solar
atmosphere, including regions of non-negligible plasma beta. We use
high-resolution photospheric magnetic field measurements from SUNRISE/IMaX as
boundary condition for a magneto-static magnetic field model. The high
resolution of IMaX allows us to resolve the interface region between
photosphere and corona, but modelling this region is challenging for the
following reasons. While the coronal magnetic field is thought to be force-free
(the Lorentz-force vanishes), this is not the case in the mixed plasma $\beta$
environment in the photosphere and lower chromosphere. In our model, pressure
gradients and gravity forces are taken self-consistently into account and
compensate the non-vanishing Lorentz-force. Above a certain height (about 2 Mm)
the non-magnetic forces become very weak and consequently the magnetic field
becomes almost force-free. Here we apply a linear approach, where the electric
current density consists of a superposition of a field-line parallel current
and a current perpendicular to the Sun's gravity field. We illustrate the
prospects and limitations of this approach and give an outlook for an extension
towards a non-linear model.Comment: ApJ, accepted, 6 Pages, 4 Figure
Local integrands for two-loop all-plus Yang-Mills amplitudes

We express the planar five- and six-gluon two-loop Yang-Mills amplitudes with
all positive helicities in compact analytic form using D-dimensional local
integrands that are free of spurious singularities. The integrand is fixed from
on-shell tree amplitudes in six dimensions using D-dimensional generalised
unitarity cuts. The resulting expressions are shown to have manifest infrared
behaviour at the integrand level. We also find simple representations of the
rational terms obtained after integration in 4-2epsilon dimensions.Comment: 24 pages + refs + ancillary file; v3 published versio
Multiplication of the depth of detectability using γ11n arrays

The depth from which one can get information has always been a crucial parameter in the geophysical exploration.\ud
This paper deals with the depth of detectability (DD) of 2D electric resistivity tomography configurations.\ud
DD is the maximal depth from which a given model body is detectable in the presence of a given noise level.\ud
Based on previous DDcalculations for conventional electrode arrays it is shownin this paper that there is a nearly\ud
linear relation between the maximumvalue of their parameter-sensitivity (PS) maps and their DD values. Studying\ud
the PS maps of other arrays, as well, we found that many of them have higher PSmax values than those of the\ud
conventional arrays. These so-called γ11n arrays are therefore expected to have larger DD values, too. The performed\ud
DD-calculations have confirmed this expectation. γ11n arrays are linear geoelectric arrays where γ refers\ud
to the CPCP order of the current (C) and potential (P) electrodes whilst the subscript numbers refer to the distance\ud
of the neighbouring electrodes. In case of the studied prismand dyke models the γ11n arrays – if n is larger\ud
or equal to 2 – consistently produced higher DD-values than the best conventional arrays. The DD value of these\ud
arrays can be even 2–3 times larger than that of the best conventional array value. Such an increase in the DD\ud
value is especially useful if the available place for measurements is limited, e.g. due to infrastructural conditions.\ud
Anomalies in large depth, for example, which are not seen by traditionally used arrays, may become detectable\ud
using γ11n arrays as it was verified also by numerical studies. These arrays require moreover less measurement\ud
than most conventional arrays resulting in shorter measuring time
TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma

Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner. We analyzed the TERT promoter by direct sequencing and genotyping in 466 medulloblastomas. The mutational distributions were determined according to subgroup affiliation, demographics, and clinical, prognostic, and molecular features. Integrated genomics approaches were used to identify specific somatic copy number alterations in TERT promoter-mutated and wild-type tumors. Overall, TERT promoter mutations were identified in 21 % of medulloblastomas. Strikingly, the highest frequencies of TERT mutations were observed in SHH (83 %; 55/66) and WNT (31 %; 4/13) medulloblastomas derived from adult patients. Group 3 and Group 4 harbored this alteration in <5 % of cases and showed no association with increased patient age. The prognostic implications of these mutations were highly subgroup-specific. TERT mutations identified a subset with good and poor prognosis in SHH and Group 4 tumors, respectively. Monosomy 6 was mostly restricted to WNT tumors without TERT mutations. Hallmark SHH focal copy number aberrations and chromosome 10q deletion were mutually exclusive with TERT mutations within SHH tumors. TERT promoter mutations are the most common recurrent somatic point mutation in medulloblastoma, and are very highly enriched in adult SHH and WNT tumors. TERT mutations define a subset of SHH medulloblastoma with distinct demographics, cytogenetics, and outcomes