Sequential expression of putative stem cell markers in gastric carcinogenesis

Gastric carcinogenesis has been well documented in the step-wise histopathological model, known as Correa pathway. Several biomarkers including CD44, Musashi-1 and CD133 have been reported as putative stem cell (PSC) markers.

Threats and knowledge gaps for ecosystem services provided by kelp forests: a northeast Atlantic perspective.

Kelp forests along temperate and polar coastlines represent some of most diverse and productive habitats on the Earth. Here, we synthesize information from >60 years of research on the structure and functioning of kelp forest habitats in European waters, with particular emphasis on the coasts of UK and Ireland, which represents an important biogeographic transition zone that is subjected to multiple threats and stressors. We collated existing data on kelp distribution and abundance and reanalyzed these data to describe the structure of kelp forests along a spatial gradient spanning more than 10° of latitude. We then examined ecological goods and services provided by kelp forests, including elevated secondary production, nutrient cycling, energy capture and flow, coastal defense, direct applications, and biodiversity repositories, before discussing current and future threats posed to kelp forests and identifying key knowledge gaps. Recent evidence unequivocally demonstrates that the structure of kelp forests in the NE Atlantic is changing in response to climate- and non-climate-related stressors, which will have major implications for the structure and functioning of coastal ecosystems. However, kelp-dominated habitats along much of the NE Atlantic coastline have been chronically understudied over recent decades in comparison with other regions such as Australasia and North America. The paucity of field-based research currently impedes our ability to conserve and manage these important ecosystems. Targeted observational and experimental research conducted over large spatial and temporal scales is urgently needed to address these knowledge gaps.

Discriminating Taxonomic Categories and Domains in Mental Simulations of Concepts of Varying Concreteness

Most studies of conceptual knowledge in the brain focus on a narrow range of concrete conceptual categories, rely on the researchers' intuitions about which object belongs to these categories, and assume a broadly taxonomic organization of knowledge. In this fMRI study, we focus on concepts with a variety of concreteness levels; we use a state of the art lexical resource (WordNet 3.1) as the source for a relatively large number of category distinctions and compare a taxonomic style of organization with a domain-based model (associating concepts with scenarios). Participants mentally simulated situations associated with concepts when cued by text stimuli. Using multivariate pattern analysis, we find evidence that all Taxonomic categories and Domains can be distinguished from fMRI data and also observe a clear concreteness effect: Tools and Locations can be reliably predicted for unseen participants, but less concrete categories (e.g., Attributes, Communications, Events, Social Roles) can only be reliably discriminated within participants. A second concreteness effect relates to the interaction of Domain and Taxonomic category membership: Domain (e.g., relation to Law vs. Music) can be better predicted for less concrete categories. We repeated the analysis within anatomical regions, observing discrimination between all/most categories in the left middle occipital and temporal gyri, and more specialized discrimination for concrete categories Tool and Location in the left precentral and fusiform gyri, respectively. Highly concrete/abstract Taxonomic categories and Domain were segregated in frontal regions. We conclude that both Taxonomic and Domain class distinctions are relevant for interpreting neural structuring of concrete and abstract concepts.

A SPECIFICATION OF A COMPLEX PROGRAMMING LANGUAGE STATEMENT

A formal specification of a complex programming language statement is presented. The subject matter was selected as being typical of the kind confronting a small software house. It is shown that formal specification notations may be applied, with benefit, to 'messy' problems. Emphasis is placed upon producing a specification which is readable by, and useful to a reader not familiar with formal notations.

A Four-element Antenna System for Mobile Phones

In this letter, a multiantenna system with four printed monopoles is presented. The monopoles that occupy relatively small area are positioned at the four corners of a printed circuit board, so that the four-element antenna system can be equipped on the lid of a folder-type mobile phone, leaving enough space for the circuits and reducing the effect of human hands. Based on simulation, a prototype for the Universal Mobile Telecommunications System (UMTS) operation has been constructed and tested. The measured -10-dB impedance bandwidths of the four elements are larger than 320 MHz with higher than 11.5-dB isolation. Moreover, the proposed antenna can provide spatial and pattern diversity in a diversity/multiple-input-multiple-output (MIMO) system.

Genetic assessment of parentage in the caridean rock shrimp Rhynchocinetes typus based on microsatellite markers

Over the past decade, the common rock shrimp, Rhynchocinetes typus H. Milne Edwards, 1837, has been the focus of extensive investigations on mating behaviour. The species is now perceived as a model system for the study of reproductive strategies and sexual conflict in crustaceans displaying external fertilization. Using molecular markers, the current study assesses whether social mating behaviour in common rock shrimp translates into true genetic parentage. In a large mesocosm tank with >200 individuals of both sexes, the analysis of 15 families (22 eggs per female) for three informative microsatellites unambiguously confirmed multiple paternity in 11 instances (73%) involving, in each case, two to four males. Where more than one male was identified siring a particular brood, reproductive skew was apparent towards a single individual. Results suggest that multiple paternity in this species results from subordinate male coercive behaviour, female solicitation of multiple male matings or a combination of both.

A DIRECT INVERSION METHOD FOR SURFACE-STRUCTURE DETERMINATION FROM LEED INTENSITIES

LOW-ENERGY electron diffraction (LEED) has become the most successful technique in surface crystallography1, but because of the complexity of the surface-electron scattering interactions, analyses of LEED data are still conducted on a trial-and-error basis: a direct-inversion method for treating LEED intensity data remains an attractive goal2. Building on recent theoretical and experimental developments in electron holography from surface structures3-16, we show here that three-dimensional images with atomic resolution can be obtained by a direct transform of conventional LEED intensity spectra.

Selective deuterium ion acceleration using the Vulcan petawatt laser

We report on the successful demonstration of selective acceleration of deuterium ions by target-normal sheath acceleration (TNSA) with a high-energy petawatt laser. TNSA typically produces a multi-species ion beam that originates from the intrinsic hydrocarbon and water vapor contaminants on the target surface. Using the method first developed by Morrison et al. [Phys. Plasmas 19, 030707 (2012)], an ion beam with >99% deuterium ions and peak energy 14 MeV/nucleon is produced with a 200 J, 700 fs, > 10 20 W/cm 2 laser pulse by cryogenically freezing heavy water (D<inf>2</inf>O) vapor onto the rear surface of the target prior to the shot. Within the range of our detectors (0°-8.5°), we find laser-to-deuterium-ion energy conversion efficiency of 4.3% above 0.7 MeV/nucleon while a conservative estimate of the total beam gives a conversion efficiency of 9.4%.

Convergent genetic and expression data implicate immunity in Alzheimer's disease

Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis.

Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain.

Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05).

Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics. (C) 2015 Published by Elsevier Inc. on behalf of The Alzheimer's Association.

On the progenitor of the Type Ic SN 2013dk in the Antennae galaxies

We report the results of our search for the progenitor candidate of SN 2013dk, a Type Ic supernova (SN) that exploded in the Antennae galaxy system. We compare pre-explosion Hubble Space Telescope (HST) archival images with SN images obtained using adaptive optics at the ESO Very Large Telescope. We isolate the SN position to within 3σ uncertainty radius of 0.02 arcsec and show that there is no detectable point source in any of the HST filter images within the error circle. We set an upper limit to the absolute magnitude of the progenitor to be MF555W ≳ -5.7, which does not allow Wolf-Rayet (WR) star progenitors to be ruled out. A bright source appears 0.17 arcsec away, which is either a single bright supergiant or compact cluster, given its absolute magnitude of MF555W = -9.02 ± 0.28 extended wings and complex environment. However, even if this is a cluster, the spatial displacement of SN 2013dk means that its membership is not assured. The strongest statement that we can make is that in the immediate environment of SN 2013dk (within 10 pc or so), we find no clear evidence of either a point source coincident with the SN or a young stellar cluster that could host a massive WR progenitor.

MErCuRIC1: A Phase I study of MEK1/2 inhibitor PD-0325901 with cMET inhibitor crizotinib in RASMT and RASWT (with aberrant c-MET) metastatic colorectal cancer (mCRC) patients.

Background: RAS is mutated (RASMT) in ~55% of mCRC, and phase III studies have shown that patients harbouring RAS mutations do not benefit from anti-EGFR MoAbs. In addition, ~50% of RAS Wild Type (RASWT) will not benefit from the addition of an EGFR MoAb to standard chemotherapy. Hence, novel treatment strategies are urgently needed for RASMT and > 50% of RASWT mCRC patients. c-MET is overexpressed in ~50-60%, amplified in ~2-3% and mutated in ~3-5% of mCRC. Recent preclinical studies have shown that c-MET is an important mediator of resistance to MEK inhibitors (i) in RASMT mCRC, and that combined MEKi/METi resulted in synergistic reduction in tumour growth in RASMT xenograft models (1). A number of recent studies have highlighted the role of c-MET in mediating primary/secondary resistance to anti-EGFR MoAbs in mCRC, suggesting that patient with RASWT tumours with aberrant c-MET (RASWT/c-MET+) may benefit from anti-c-MET targeted therapies (2). These preclinical data supported the further clinical evaluation of combined MEKi/METi treatment in RASMT and RASWT CRC patients with aberrant c-MET signalling (overexpression, amplification or mutation; RASWT/c-MET+). Methods: MErCuRIC1 is a phase I combination study of METi crizotinib with MEKi PD-0325901. The dose escalation phase, utilizing a rolling six design, recruits 12-24 patients with advanced solid tumours and aims to assess safety/toxicity of combination, recommended phase II (RPII) dose, pharmacokinetics (PK) and pharmacodynamics (PD) (pERK1/2 in PBMC and tumour; soluble c-MET). In the dose expansion phase an additional 30-42 RASMT and RASWT/c-MET mCRC patients with biopsiable disease will be treated at the RPII dose to further evaluate safety, PK, PD and treatment response. In the dose expansion phase additional biopsy and blood samples will be obtained to define mechanisms of response/resistance to crizotinib/PD-0325901 therapy. Enrolment into the dose escalation phase began in December 2014 with cohort 1 still ongoing. EudraCT registry number: 2014-000463-40. (1) Van Schaeybroeck S et al. Cell Reports 2014;7(6):1940-55; (2) Bardelli A et al. Cancer Discov 2013;3(6):658-73. Clinical trial information: 2014-000463-40.