Cancer progression is associated with genomic instability and an accumulation of gains and losses of DNA. The growing variety of tools for measuring genomic copy numbers, including various types of ...array-CGH, SNP arrays and high-throughput sequencing, calls for a coherent framework offering unified and consistent handling of single- and multi-track segmentation problems. In addition, there is a demand for highly computationally efficient segmentation algorithms, due to the emergence of very high density scans of copy number.
A comprehensive Bioconductor package for copy number analysis is presented. The package offers a unified framework for single sample, multi-sample and multi-track segmentation and is based on statistically sound penalized least squares principles. Conditional on the number of breakpoints, the estimates are optimal in the least squares sense. A novel and computationally highly efficient algorithm is proposed that utilizes vector-based operations in R. Three case studies are presented.
The R package copynumber is a software suite for segmentation of single- and multi-track copy number data using algorithms based on coherent least squares principles.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and purpose:
Evidence indicates that the endocannabinoid, 2‐arachidonoylglycerol (2‐AG), increases food intake when injected into the nucleus accumbens shell (NAcS), thereby potentially ...activating hypothalamic nuclei involved in food intake regulation. We aimed to evaluate potential orexigenic effects of the endocannabinoid anandamide and of AA5HT, a fatty acid amide hydrolase (FAAH) inhibitor, and OMDM‐1, an inhibitor of anandamide uptake, injected in the NAcS, as well as the effect of these treatments on activation of hypothalamic nuclei.
Experimental approach:
Drugs were given into the NAcS of rats and food intake quantified during the next 4 h. In other groups, after the same treatments the brains were processed for c‐Fos immunohistochemistry with focus on hypothalamic nuclei. Additional groups were used to quantify endocannabinoid levels in the nucleus accumbens and the hypothalamus after AA5HT and OMDM‐1 intra‐NAcS injections.
Key results
Our results indicate that the above treatments stimulate food intake during 4 h post‐injection. They also increase c‐Fos immunoreactivity in hypothalamic nuclei. The CB1 antagonist, AM251, blocked these effects. Finally, we found elevated levels of 2‐AG, but not anandamide, after intra‐NAcS injections of AA5HT.
Conclusions and implications:
These data support the involvement of the endocannabinoid system in feeding behavior at the level of the NAcS and hypothalamus. In addition, this is the first experimental demonstration that the pharmacological inhibition of endocannabinoid inactivation in the NAcS stimulates food intake, suggesting that the endocannabinoid degrading proteins can be a target for treating eating disorders.
British Journal of Pharmacology (2007) 151, 1109–1116; doi:10.1038/sj.bjp.0707313
There is a growing body of evidence that links nutrition to muscle mass, strength and function in older adults, suggesting that it has an important role to play both in the prevention and management ...of sarcopenia. This review summarises the discussions of a working group ESCEO working group meeting 8th September 2016 that met to review current evidence and to consider its implications for preventive and treatment strategies. The review points to the importance of ‘healthier’ dietary patterns that are adequate in quality in older age, to ensure sufficient intakes of protein, vitamin D, antioxidant nutrients and long-chain polyunsaturated fatty acids. In particular, there is substantial evidence to support the roles of dietary protein and physical activity as key anabolic stimuli for muscle protein synthesis. However, much of the evidence is observational and from high-income countries. Further high-quality trials, particularly from more diverse populations, are needed to enable an understanding of dose and duration effects of individual nutrients on function, to elucidate mechanistic links, and to define optimal profiles and patterns of nutrient intake for older adults.
A
bstract
This article describes BabyIAXO, an intermediate experimental stage of the International Axion Observatory (IAXO), proposed to be sited at DESY. IAXO is a large-scale axion helioscope that ...will look for axions and axion-like particles (ALPs), produced in the Sun, with unprecedented sensitivity. BabyIAXO is conceived to test all IAXO subsystems (magnet, optics and detectors) at a relevant scale for the final system and thus serve as prototype for IAXO, but at the same time as a fully-fledged helioscope with relevant physics reach itself, and with potential for discovery. The BabyIAXO magnet will feature two 10 m long, 70 cm diameter bores, and will host two detection lines (optics and detector) of dimensions similar to the final ones foreseen for IAXO. BabyIAXO will detect or reject solar axions or ALPs with axion-photon couplings down to
g
aγ
∼ 1
.
5 × 10
−
11
GeV
−
1
, and masses up to
m
a
∼ 0
.
25 eV. BabyIAXO will offer additional opportunities for axion research in view of IAXO, like the development of precision x-ray detectors to identify particular spectral features in the solar axion spectrum, and the implementation of radiofrequency-cavity-based axion dark matter setups.
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•MoTe2/MoSe2 flake composite films obtained by a hybrid process.•MoOy (2 < y < 3) nucleated first on Si (100) by sol–gel processing.•MoTe2/MoSe2 composite films achieved by H2 ...reduction and isothermal closed space vapor transport of the chalcogenides.•Multilayered nanocomposite MoTe2(1-x)Se2x/MoSe2 alloy films grown at 600 °C.•Out-of-plane flake-like structure confirmed by microscopy and spectroscopy.
This study describes the sol–gel processing of MoOy on Si (100) to subsequently achieve out-of-plane MoTe2/MoSe2 flake composite films by an isothermal closed space vapor transformation. The oxide precursor films have been prepared from a Mo isopropoxide solution in isopropanol and acid catalysis induced by HCl. Thermal annealing at 200, 400 and 600 °C enhanced the condensation after xerogel formation. An x-ray absorption analysis demonstrates that films condensed at 200 °C are at an intermediate chemical state between MoO3 and MoO2. To achieve MoTe2/MoSe2 composite films, the precursor oxide films were reduced in H2 and exposed to the chalcogenides by isothermal closed space vapor transport at 600 °C. The multilayered nanocomposite films grow with an out-of-plane flake-like structure and an evident integration of Se in the MoTe2 phase according to a MoTe2(1-x)Se2x alloy, with an estimation of x of 0.25. The alloy and the orientation of the flakes are consistent with the bands present in the Raman spectrum. These films are attractive for applications requiring high surface area interfaces favoring gas or ion exchange reactions with transition metal dichalcogenides.
Remains of molluscs were collected from the seafloor on the north-eastern margin of the Gulf of Cadiz, between 300 and 1000 m water depth, using different sampling methods (e.g. dredging, trawling ...and box-coring), during several deep-sea expeditions. Samples contained a suite of species which nowadays mostly occur northwards of the English Channel, together with other widespread species. Species now locally extinct in the Gulf of Cadiz and restricted to northern latitudes, which unequivocally indicate a faunal shift, include the gastropods Buccinum undatum, Colus gracilis, Liomesus ovum and Neptunea antiqua, the bivalves Arctica islandica, Chlamys islandica, Modiolus modiolus, Mya truncata and Nuculana pernula and the scaphopod Antalis entalis. These species represent “Boreal Guests” of marked palaeoclimatic significance, some of which are reported for the first time in the Gulf of Cadiz. The boreal species collected were mostly large (>5 cm) whereas smaller boreal species were extremely scarce, probably winnowed away by strong bottom currents. The pteropod Limacina retroversa, at present restricted to water masses northwards of the Iberian Peninsula but widespread in Mediterranean sediments of the last glaciation, was also recorded. Accelerator mass spectrometry (AMS) 14C dates obtained from nine specimens of molluscs ranged between 26.1 and 14.6 kyr B.P., thus confirming their attribution to a last glacial assemblage. The abundance of these molluscan remains in the present Mediterranean Outflow Water pathway could be explained if this outflow was reduced in intensity or more likely shifted to a deeper level, leaving the upper slope in contact with suitable Atlantic intermediate waters. The findings of Boreal Guests in the Gulf of Cadiz document the continuity of the faunal shift which is well-known in the Mediterranean basin. Species still living in the Gulf of Cadiz and the Alboran Sea nevertheless account for 84.6% of specimens among the larger species.
•Gulf of Cadiz, in 300–1000 m depth, yielded numerous shells of boreal molluscs.•Eight arctic species locally extinct in Gulf of Cádiz document a southwards faunal shift.•14C dates from 9 specimens ranged between 26.5 and 14.5 kyr B.P.•Our data support a deeper Mediterranean Outflow during the coldest episode.
Gray matter (GM) atrophy is common in multiple sclerosis (MS), as is cognitive dysfunction. Understanding the exact relationship between atrophy and cognition requires further investigation. The aim ...of this study was to investigate the relationship between subcortical GM atrophy and cognition in early relapsing onset MS.
Structural MRI and neuropsychological evaluations were performed in 120 patients (80 women) and 50 controls (30 women), part of an early inception cohort, 6 years postdiagnosis. Deep GM volumes were segmented automatically. Cognition was assessed in 7 domains. Stepwise linear regression was used to predict average cognition in the patient group.
Most deep GM volumes were reduced in patients, with larger effects on average in men (-11%) than in women (-6.3%). Only the bilateral hippocampus, amygdala, and right nucleus accumbens in men, and right hippocampus and nucleus accumbens, bilateral amygdala, and putamen in women, showed no atrophy compared to controls. All cognitive domains except visuospatial memory were affected in men; none were significantly affected in women. In the MS group, average cognition was best predicted by thalamic volume, sex, and education (adjusted R(2) = 0.31), while lesion volume was not a significant predictor in the model.
Six years postdiagnosis, almost all subcortical structures were affected by MS, especially in men. Cognition was most severely affected in male patients. Thalamic volume, sex, and education best predicted average cognition. These results underline the relevance of specific subcortical structures to cognition, as well as the relevance of (sex-specific) atrophy in MS.
MoO2 thin films were subjected to a laser localized oxidation process that allowed us to obtain different well defined MoOx phases. In particular, the spatially resolved MoO2, α-MoO3, β-MoO3, ...amorphous a-MoO3, and Mo4O11 regions were obtained as a function of the laser power and the distance to the laser focus. The origin of this spatial phase separation was investigated through a careful and exhaustive Raman mapping study covering several micrometres away from the laser focus and taking into account the thermochemical properties of the species involved. It was found that a sublimation/deposition process, driven by the different vapour pressures of the species, was responsible for the phase separation. At higher laser powers, a solid state reaction was observed to contribute as well. In the laser annealed tracks, distant lateral sidebands of oxide deposition were observed with composition that depended on the laser power and the distance to the centre of the track. The electrical measurements between the irradiated and non-irradiated regions showed a strong rectifying behaviour, revealing a transformation from metal-like to semiconducting Mo oxide phases, which may open the way to the development of laser written all-oxide electronic circuits.
Patients with multiple sclerosis (MS) are increasingly demanding access to reliable information regarding their disease. The objective of the INFOSEEK-MS study was to assess what are the strategies ...people with MS use when searching for information on their disease, including sources, frequency, reliability, and preferred content.
A non-interventional, cross-sectional study was conducted. Patients with a diagnosis of MS according to the 2010 McDonald criteria were included. The InfoSeek questionnaire was used to assess patients' strategies when seeking information about the disease. Clinical characteristics and other variables, including disability, quality of life, fatigue, cognition, anxiety and depression, were analysed using the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Impact Scale (MSIS-29), 5-item Modified Fatigue Scale (MFIS-5), Symbol Digit Modalities Test (SDMT), and Hospital Anxiety and Depression Scale (HADS), respectively.
Three hundred and two patients were studied (mean age: 42.3 ± 10 years, 64% female, mean disease duration: 9.6 ± 7.0 years, 90% with relapsing-remitting MS, and mean EDSS score: 2.6 ± 1.9). The internet (either via mobile or computer) is a frequently reported source of information. Lifestyle-related information (67.2%), research and emerging treatments (63.6%), symptom control (49.7%), sharing experiences with other patients (46.4%), and disease prognosis (46.4%) were the most searched topics. Neurologists and nurses were the most trusted source of information. Younger patients and higher SDMT scores were associated with all search resources (M = 37.7 and M = 49.97, respectively). The frequency of searches was related to the number of relapses (R
= 0.07), EDSS (R
= 0.14), MSIS-29 physical and psychological components (R
= 0.132) and inversely with depression (R
= 0.132).
Although healthcare professionals are considered the most reliable source of information for people with MS, searching for information on the Internet is very frequent. An individualized information strategy considering the different factors involved is needed.
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