The geometry of the light-cone cell decomposition of moduli space

S.R. is supported by STFC consolidated Grant No. ST/L000415/1 “String Theory, Gauge Theory and Dualit

BRAFV600E mutations in malignant melanoma are associated with increased expressions of BAALC

<p>Abstract</p> <p>Bachground</p> <p>Activating <it>BRAF </it>mutations are present in approximately 50% of melanomas. Although different downstream target genes of the most common mutant V600E have been identified, the contribution of activating <it>BRAF </it>mutations to malignant transformation needs further clarification.</p> <p>Methods</p> <p>Microarray gene analysis was performed for human melanoma cell lines harboring BRAF^V600Emutations in comparison to cell lines without this mutation.</p> <p>Results</p> <p>This analysis revealed a more than two fold down-regulation of 43 and an increase of 39 gene products. <it>BAALC </it>(<it>Brain and acute Leukaemia, cytoplasmatic</it>) was most prominently regulated, since it was up-regulated in mutated cell lines by a mean of 11.45. Real time PCR analyses with RNA from melanoma cell lines (n = 30) confirmed the <it>BRAF</it>-activation dependent up-regulation of <it>BAALC</it>.</p> <p>Conclusion</p> <p><it>BAALC</it>, which has been associated with cell dedifferentiation and migration, may function as a downstream effector of activating <it>BRAF </it>mutations during melanomagenesis.</p

Uptake of sympagic organic carbon by the Barents Sea benthos linked to sea ice seasonality

On Arctic shelves, where primary production occurs in both the pelagic and sympagic (ice-associated) habitats, sympagic organic material (OM) can constitute a disproportionate fraction of benthic diets due to higher sinking rates and lower grazing pressure than pelagic OM. Less documented is how sympagic OM assimilation across feeding guilds varies seasonally and in relation to sea ice duation. We therefore investigated the relative abundance of sympagic vs pelagic OM in Barents Sea shelf megabenthos in the summer and winter of 2018 and 2019, from 10 stations where sea ice duration ranged from 0 to 245 days per year. We use highly branched isoprenoids, which are lipid biomarkers produced with distinct molecular structures by diatoms in sea ice and the water column, to determine the ratio of sympagic-to-pelagic OM assimilated by benthic organisms. From 114 samples of 25 taxa analysed, we found that the proportion of sympagic OM assimilated ranged from 0.4% to 95.8% and correlated strongly (r2 = 0.754) with the duration of sea ice cover. The effect of sea ice duration was more evident in fauna collected during summer than winter, indicating that sympagic signals are more evident in the summer than in the winter at higher latitudes. Our data show that sympagic production can supply a high fraction of carbon for Barents Sea benthos, although this is highly variable and likely dependent on availability and patchiness of sympagic OM deposition. These results are comparable to similar studies conducted on benthos in the Pacific Arctic and highlight the variable importance of sympagic OM in the seasonal ice zone of Arctic inflow shelves, which are the Arctic regions with highest rates of sea ice loss.publishedVersio

A new common functional coding variant at the DDC gene change renal enzyme activity and modify renal dopamine function.

The intra-renal dopamine (DA) system is highly expressed in the proximal tubule and contributes to Na+ and blood pressure homeostasis, as well as to the development of nephropathy. In the kidney, the enzyme DOPA Decarboxylase (DDC) originating from the circulation. We used a twin/family study design, followed by polymorphism association analysis at DDC locus to elucidate heritable influences on renal DA production. Dense single nucleotide polymorphism (SNP) genotyping across the DDC locus on chromosome 7p12 was analyzed by re-sequencing guided by trait-associated genetic markers to discover the responsible genetic variation. We also characterized kinetics of the expressed DDC mutant enzyme. Systematic polymorphism screening across the 15-Exon DDC locus revealed a single coding variant in Exon-14 that was associated with DA excretion and multiple other renal traits indicating pleiotropy. When expressed and characterized in eukaryotic cells, the 462Gln variant displayed lower Vmax (maximal rate of product formation by an enzyme) (21.3 versus 44.9 nmol/min/mg) and lower Km (substrate concentration at which half-maximal product formation is achieved by an enzyme.)(36.2 versus 46.8 μM) than the wild-type (Arg462) allele. The highly heritable DA excretion trait is substantially influenced by a previously uncharacterized common coding variant (Arg462Gln) at the DDC gene that affects multiple renal tubular and glomerular traits, and predicts accelerated functional decline in chronic kidney disease

On the Relationship between Convex Bodies Related to Correlation Experiments with Dichotomic Observables

In this paper we explore further the connections between convex bodies related to quantum correlation experiments with dichotomic variables and related bodies studied in combinatorial optimization, especially cut polyhedra. Such a relationship was established in Avis, Imai, Ito and Sasaki (2005 J. Phys. A: Math. Gen. 38 10971-87) with respect to Bell inequalities. We show that several well known bodies related to cut polyhedra are equivalent to bodies such as those defined by Tsirelson (1993 Hadronic J. S. 8 329-45) to represent hidden deterministic behaviors, quantum behaviors, and no-signalling behaviors. Among other things, our results allow a unique representation of these bodies, give a necessary condition for vertices of the no-signalling polytope, and give a method for bounding the quantum violation of Bell inequalities by means of a body that contains the set of quantum behaviors. Optimization over this latter body may be performed efficiently by semidefinite programming. In the second part of the paper we apply these results to the study of classical correlation functions. We provide a complete list of tight inequalities for the two party case with (m,n) dichotomic observables when m=4,n=4 and when min{m,n}<=3, and give a new general family of correlation inequalities.Comment: 17 pages, 2 figure

A Neuro-hormonal Circuit for Paternal Behavior Controlled by a Hypothalamic Network Oscillation

Parental behavior is pervasive throughout the animal kingdom and essential for species survival. However, the relative contribution of the father to offspring care differs markedly across animals, even between related species. The mechanisms that organize and control paternal behavior remain poorly understood. Using Sprague-Dawley rats and C57BL/6 mice, two species at opposite ends of the paternal spectrum, we identified that distinct electrical oscillation patterns in neuroendocrine dopamine neurons link to a chain of low dopamine release, high circulating prolactin, prolactin receptor-dependent activation of medial preoptic area galanin neurons, and paternal care behavior in male mice. In rats, the same parameters exhibit inverse profiles. Optogenetic manipulation of these rhythms in mice dramatically shifted serum prolactin and paternal behavior, whereas injecting prolactin into non-paternal rat sires triggered expression of parental care. These findings identify a frequency-tuned brain-endocrine-brain circuit that can act as a gain control system determining a species’ parental strategy

A Neuro-hormonal Circuit for Paternal Behavior Controlled by a Hypothalamic Network Oscillation

Parental behavior is pervasive throughout the animal kingdom and essential for species survival. However, the relative contribution of the father to offspring care differs markedly across animals, even between related species. The mechanisms that organize and control paternal behavior remain poorly understood. Using Sprague-Dawley rats and C57BL/6 mice, two species at opposite ends of the paternal spectrum, we identified that distinct electrical oscillation patterns in neuroendocrine dopamine neurons link to a chain of low dopamine release, high circulating prolactin, prolactin receptor-dependent activation of medial preoptic area galanin neurons, and paternal care behavior in male mice. In rats, the same parameters exhibit inverse profiles. Optogenetic manipulation of these rhythms in mice dramatically shifted serum prolactin and paternal behavior, whereas injecting prolactin into non-paternal rat sires triggered expression of parental care. These findings identify a frequency-tuned brain-endocrine-brain circuit that can act as a gain control system determining a species’ parental strategy

Automated bolus advisor control and usability study (ABACUS): does use of an insulin bolus advisor improve glycaemic control in patients failing multiple daily insulin injection (MDI) therapy? [NCT01460446]

BACKGROUND: People with T1DM and insulin-treated T2DM often do not follow and/or adjust their insulin regimens as needed. Key contributors to treatment non-adherence are fear of hypoglycaemia, difficulty and lack of self-efficacy associated with insulin dose determination. Because manual calculation of insulin boluses is both complex and time consuming, people may rely on empirical estimates, which can result in persistent hypoglycaemia and/or hyperglycaemia. Use of automated bolus advisors (BA) has been shown to help insulin pump users to more accurately meet prandial insulin dosage requirements, improve postprandial glycaemic excursions, and achieve optimal glycaemic control with an increased time within optimal range. Use of a BA containing an early algorithm based on sliding scales for insulin dosing has also been shown to improve HbA1c levels in people treated with multiple daily insulin injections (MDI). We designed a study to determine if use of an automated BA can improve clinical and psychosocial outcomes in people treated with MDI. METHODS/DESIGN: The Automated Bolus Advisor Control and Usability Study (ABACUS) is a 6-month, prospective, randomised, multi-centre, multi-national trial to determine if automated BA use improves glycaemic control as measured by a change in HbA1c in people using MDI with elevated HbA1c levels (#62;7.5%). A total of 226 T1DM and T2DM participants will be recruited. Anticipated attrition of 20% will yield a sample size of 90 participants, which will provide #62;80% power to detect a mean difference of 0.5%, with SD of 0.9%, using a one-sided 5% t-test, with 5% significance level. Other measures of glycaemic control, self-care behaviours and psychosocial issues will also be assessed. DISCUSSION: It is critical that healthcare providers utilise available technologies that both facilitate effective glucose management and address concerns about safety and lifestyle. Automated BAs may help people using MDI to manage their diabetes more effectively and minimise the risk of long-term diabetes related complications. Findings from a recent study suggest that BA use positively addresses both safety and lifestyle concerns; however, randomised trials are needed to confirm these perceptions and determine whether bolus advisor use improves clinical outcomes. Our study is designed to make these assessments. TRIAL REGISTRATION: NCT0146044

Usage of NASA's Near Real-Time Solar and Meteorological Data for Monitoring Building Energy Systems Using RETScreen International's Performance Analysis Module

This paper describes building energy system production and usage monitoring using examples from the new RETScreen Performance Analysis Module, called RETScreen Plus. The module uses daily meteorological (i.e., temperature, humidity, wind and solar, etc.) over a period of time to derive a building system function that is used to monitor building performance. The new module can also be used to target building systems with enhanced technologies. If daily ambient meteorological and solar information are not available, these are obtained over the internet from NASA's near-term data products that provide global meteorological and solar information within 3-6 days of real-time. The accuracy of the NASA data are shown to be excellent for this purpose enabling RETScreen Plus to easily detect changes in the system function and efficiency. This is shown by several examples, one of which is a new building at the NASA Langley Research Center that uses solar panels to provide electrical energy for building energy and excess energy for other uses. The system shows steady performance within the uncertainties of the input data. The other example involves assessing the reduction in energy usage by an apartment building in Sweden before and after an energy efficiency upgrade. In this case, savings up to 16% are shown

Assessing Coral Reef Fish Population and Community Changes in Response to Marine Reserves in the Dry Tortugas, Florida, USA

The efficacy of no-take marine reserves (NTMRs) to enhance and sustain regional coral reef fisheries was assessed in Dry Tortugas, Florida, through 9 annual fishery-independent research surveys spanning 2 years before and 10 years after NTMR implementation. A probabilistic sampling design produced precise estimates of population metrics of more than 250 exploited and non-target reef fishes. During the survey period more than 8100 research dives utilizing SCUBA Nitrox were optimally allocated using stratified random sampling. The survey domain covered 326 km2, comprised of eight reef habitats in four management areas that offered different levels of resource protection: the Tortugas North Ecological Reserve (a NTMR), Dry Tortugas National Park (recreational angling only), Dry Tortugas National Park Research Natural Area (a NTMR), and southern Tortugas Bank (open to all types of fishing). Surveys detected significant changes in population occupancy, density, and abundance within management zones for a suite of exploited and non-target species. Increases in size, adult abundance, and occupancy rates were detected for many principal exploited species in protected areas, which harbored a disproportionately greater number of adult spawning fishes. In contrast, density and occupancy rates for aquaria and non-target reef fishes fluctuated above and below baseline levels in each management zone. Observed decreases in density of exploited species below baseline levels only occurred at the Tortugas Bank area open to all fishing. Our findings indicate that these NTMRs, in conjunction with traditional fishery management control strategies, are helping to build sustainable fisheries while protecting the fundamental ecological dynamics of the Florida Keys coral-reef ecosystem