A new class of de Sitter vacua in type IIB large volume compactifications

We construct a new class of metastable de Sitter vacua of flux compactifications of type IIB string theory. These solutions provide a natural extension of the `Large Volume Scenario' anti-de Sitter vacua, and can analogously be realised at parametrically large volume and weak string coupling, using standard ${\cal N}=1$ supergravity. For these new vacua, a positive vacuum energy is achieved from the inclusion of a small amount of flux-induced supersymmetry breaking in the complex structure and axio-dilaton sector, and no additional `uplift' contribution (e.g.~from anti-branes) is required. We show that the approximate no-scale structure of the effective theory strongly influences the spectrum of the stabilised moduli: one complex structure modulus remains significantly lighter than the supersymmetry breaking scale, and metastability requires only modest amounts of tuning. After discussing these general results, we provide a recipe for constructing de Sitter vacua on a given compactification manifold, and give an explicit example of a de Sitter vacuum for the compactification on the Calabi-Yau orientifold realised in $\mathbb{CP}^4_{11169}$. Finally, we note that these solutions have intriguing implications for phenomenology, predicting no superpartners in the spectrum below $\sim$50 TeV, and no WIMP dark matter.Comment: 34 page

Modelo estadístico de textura para detección de masas en mamografía

In this article we demonstrate the use of principal components analysis to visualizea high dimensional texture representation and understand its geometry. Our targetapplication is mass detection as texture abnormalities. We analyse a texture represen-tation based on the gray levels of a local neighborhood, we estimate a gaussian mixturemodel by means of the EM algorithm and graph the data along with the probabilisticmodel. Our results explain nature of the feature space and at the same time keepsaround 98% of the total variation.Kewords: Biomedical Engineering, Radiodiagnostic, Breast-Cancer, Statistical Meth-ods, Mathematical Models

Characterisation of large changes in wind power for the day-ahead market using a fuzzy logic approach

Wind power has become one of the renewable resources with a major growth in the electricity market. However, due to its inherent variability, forecasting techniques are necessary for the optimum scheduling of the electric grid, specially during ramp events. These large changes in wind power may not be captured by wind power point forecasts even with very high resolution Numerical Weather Prediction (NWP) models. In this paper, a fuzzy approach for wind power ramp characterisation is presented. The main benefit of this technique is that it avoids the binary definition of ramp event, allowing to identify changes in power out- put that can potentially turn into ramp events when the total percentage of change to be considered a ramp event is not met. To study the application of this technique, wind power forecasts were obtained and their corresponding error estimated using Genetic Programming (GP) and Quantile Regression Forests. The error distributions were incorporated into the characterisation process, which according to the results, improve significantly the ramp capture. Results are presented using colour maps, which provide a useful way to interpret the characteristics of the ramp events

Recovery of early meteorological records from Extremadura region (SW Iberia): The ''CliPastExtrem'' (v1.0) database

In this work, we provide instrumental meteorological data recovered for the Extremadura region (interior SW Iberia), from 1826 to mid-20th century. Meteorological variables such as air temperature, atmospheric pressure, precipitation, wind direction and humidity, among others, were retrieved. In total, more than 750 000 instrumental data in 157 meteorological series belonging to 131 different locations throughout Extremadura were rescued. It must be noted that daily resolution data constitutes 80% of the database. This great effort of digitization and data collection has been carried out with the aim of contributing to a significant expansion of the length of the databases with meteorological information in this region. Therefore, this database will provide a better understanding of climate variability, trends and extreme events of the Extremadura region

Global parameter search reveals design principles of the mammalian circadian clock

Background: Virtually all living organisms have evolved a circadian (~24 hour) clock that controls physiological and behavioural processes with exquisite precision throughout the day/night cycle. The suprachiasmatic nucleus (SCN), which generates these ~24 h rhythms in mammals, consists of several thousand neurons. Each neuron contains a gene-regulatory network generating molecular oscillations, and the individual neuron oscillations are synchronised by intercellular coupling, presumably via neurotransmitters. Although this basic mechanism is currently accepted and has been recapitulated in mathematical models, several fundamental questions about the design principles of the SCN remain little understood. For example, a remarkable property of the SCN is that the phase of the SCN rhythm resets rapidly after a 'jet lag' type experiment, i.e. when the light/ dark (LD) cycle is abruptly advanced or delayed by several hours. Results: Here, we describe an extensive parameter optimization of a previously constructed simplified model of the SCN in order to further understand its design principles. By examining the top 50 solutions from the parameter optimization, we show that the neurotransmitters' role in generating the molecular circadian rhythms is extremely important. In addition, we show that when a neurotransmitter drives the rhythm of a system of coupled damped oscillators, it exhibits very robust synchronization and is much more easily entrained to light/dark cycles. We were also able to recreate in our simulations the fast rhythm resetting seen after a 'jet lag' type experiment. Conclusion: Our work shows that a careful exploration of parameter space for even an extremely simplified model of the mammalian clock can reveal unexpected behaviours and non-trivial predictions. Our results suggest that the neurotransmitter feedback loop plays a crucial role in the robustness and phase resetting properties of the mammalian clock, even at the single neuron level

Effects of permafrost aggradation on peat properties as determined from a pan-arctic synthesis of plant macrofossils

©2015. American Geophysical Union. All Rights Reserved.This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/2015JG003061Permafrost dynamics play an important role in high-latitude peatland carbon balance and are key to understanding the future response of soil carbon stocks. Permafrost aggradation can control the magnitude of the carbon feedback in peatlands through effects on peat properties. We compiled peatland plant macrofossil records for the northern permafrost zone (515 cores from 280 sites) and classified samples by vegetation type and environmental class (fen, bog, tundra and boreal permafrost, thawed permafrost). We examined differences in peat properties (bulk density, carbon (C), nitrogen (N) and organic matter content, C/N ratio) and C accumulation rates among vegetation types and environmental classes. Consequences of permafrost aggradation differed between boreal and tundra biomes, including differences in vegetation composition, C/N ratios, and N content. The vegetation composition of tundra permafrost peatlands was similar to permafrost-free fens, while boreal permafrost peatlands more closely resembled permafrost-free bogs. Nitrogen content in boreal permafrost and thawed permafrost peatlands was significantly lower than in permafrost-free bogs despite similar vegetation types (0.9% versus 1.5% N). Median long-term C accumulation rates were higher in fens (23 g C m-2 y-1) than in permafrost-free bogs (18 g C m-2 y-1), and were lowest in boreal permafrost peatlands (14 g C m-2 y-1). The plant macrofossil record demonstrated transitions from fens to bogs to permafrost peatlands, bogs to fens, permafrost aggradation within fens, and permafrost thaw and re-aggradation. Using data synthesis, we've identified predominant peatland successional pathways, changes in vegetation type, peat properties, and C accumulation rates associated with permafrost aggradation.National Science FoundationUSGS Climate and Land-useChange Research and Development ProgramAcademy of FinlandRoyal Swedish Academy of ScienceYmer-80, Knut & Alice Wallenberg and Ahlmann Foundation

MCL-1 inhibition provides a new way to suppress breast cancer metastasis and increase sensitivity to dasatinib.

BACKGROUND: Metastatic disease is largely resistant to therapy and accounts for almost all cancer deaths. Myeloid cell leukemia-1 (MCL-1) is an important regulator of cell survival and chemo-resistance in a wide range of malignancies, and thus its inhibition may prove to be therapeutically useful. METHODS: To examine whether targeting MCL-1 may provide an effective treatment for breast cancer, we constructed inducible models of BIMs2A expression (a specific MCL-1 inhibitor) in MDA-MB-468 (MDA-MB-468-2A) and MDA-MB-231 (MDA-MB-231-2A) cells. RESULTS: MCL-1 inhibition caused apoptosis of basal-like MDA-MB-468-2A cells grown as monolayers, and sensitized them to the BCL-2/BCL-XL inhibitor ABT-263, demonstrating that MCL-1 regulated cell survival. In MDA-MB-231-2A cells, grown in an organotypic model, induction of BIMs2A produced an almost complete suppression of invasion. Apoptosis was induced in such a small proportion of these cells that it could not account for the large decrease in invasion, suggesting that MCL-1 was operating via a previously undetected mechanism. MCL-1 antagonism also suppressed local invasion and distant metastasis to the lung in mouse mammary intraductal xenografts. Kinomic profiling revealed that MCL-1 antagonism modulated Src family kinases and their targets, which suggested that MCL-1 might act as an upstream modulator of invasion via this pathway. Inhibition of MCL-1 in combination with dasatinib suppressed invasion in 3D models of invasion and inhibited the establishment of tumors in vivo. CONCLUSION: These data provide the first evidence that MCL-1 drives breast cancer cell invasion and suggests that MCL-1 antagonists could be used alone or in combination with drugs targeting Src kinases such as dasatinib to suppress metastasis

MCL-1 antagonism enhances the anti-invasive effects of dasatinib in pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies. It is phenotypically heterogeneous with a highly unstable genome and provides few common therapeutic targets. We found that MCL1, Cofilin1 (CFL1) and SRC mRNA were highly expressed by a wide range of these cancers, suggesting that a strategy of dual MCL-1 and SRC inhibition might be efficacious for many patients. Immunohistochemistry revealed that MCL-1 protein was present at high levels in 94.7% of patients in a cohort of PDACs from Australian Pancreatic Genome Initiative (APGI). High MCL1 and Cofilin1 mRNA expression was also strongly predictive of poor outcome in the TCGA dataset and in the APGI cohort. In culture, MCL-1 antagonism reduced the level of the cytoskeletal remodeling protein Cofilin1 and phosphorylated SRC on the active Y416 residue, suggestive of reduced invasive capacity. The MCL-1 antagonist S63845 synergized with the SRC kinase inhibitor dasatinib to reduce cell viability and invasiveness through 3D-organotypic matrices. In preclinical murine models, this combination reduced primary tumor growth and liver metastasis of pancreatic cancer xenografts. These data suggest that MCL-1 antagonism, while reducing cell viability, may have an additional benefit in increasing the antimetastatic efficacy of dasatinib for the treatment of PDAC

Enhancement of Water Transport and Microstructural Changes Induced by High-Intesity Ultrasound Application on Orange Peel Drying

The main aim of this work was to evaluate the effect of high-intensity ultrasound (US) on the drying kinetics of orange peel as well as its influence on the microstructural changes induced during drying. Convective drying kinetics of orange peel slabs were carried out at a relative humidity of 26.5±0.9%, 40 °C and 1 m/s with (AIR+US) and without (AIR) ultrasound application. In order to identify the US effect on water transport, drying kinetics were analyzed by taking the diffusion theory into account. Fresh, AIR and AIR+US dried samples were analyzed using Cryo-Scanning Electron Microscopy. Results showed that the drying kinetics of orange peel were significantly improved by US application, which involved a significant (p<0.05) improvement of mass transfer coefficient and effective moisture diffusivity. The effects on mass transfer properties were confirmed with microstructural observations. In the cuticle surface of flavedo, the pores were obstructed by the spread of the waxy components, this fact evidencing US effects on the air solid interfaces. Furthermore, the cells of the albedo were disrupted by US, as it created large intercellular air spaces facilitating water transfer through the tissue.The authors would like to acknowledge the financial support of MICINN and CEE (European Regional Development Fund) from projects Ref. DPI2009-14549-C04-04, PSE-060000-2009-003, and FP6-2004-FOOD-23140 HIGHQ RTE.García Pérez, JV.; Ortuño Cases, C.; Puig Gómez, CA.; Cárcel Carrión, JA.; Pérez Munuera, IM. (2012). Enhancement of Water Transport and Microstructural Changes Induced by High-Intesity Ultrasound Application on Orange Peel Drying. Food and Bioprocess Technology. 5(6):2256-2265. https://doi.org/10.1007/s11947-011-0645-0S2256226556Alandes, L., Perez-Munuera, I., Llorca, E., Quiles, A., & Hernando, I. (2009). 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DNA aneuploidy as a topographic malignant transformation pattern in a pleomorphic adenoma of long-term evolution: a case report

<p>Abstract</p> <p>Introduction</p> <p>We present a case of long-term evolution of a submandibular pleomorphic adenoma. There is little information about topographic malignant transformation patterns of pleomorphic adenomas.</p> <p>Case presentation</p> <p>We extensively analyze a giant submandibular mixed tumor of 25-year evolution in a 57-year-old Caucasian woman. Deoxyribonucleic acid ploidy was evaluated in different superficial and deep areas using flow cytometry analysis and correlated with pathological and immunohistochemical characteristics. Superficial areas exhibited a typical histological pleomorphic adenoma pattern and were deoxyribonucleic acid diploid. Deep samples showed deoxyribonucleic acid aneuploidy, atypical histological benign features and expression of markers involved at an early-stage of malignant transformation, such as tumor protein 53 and antigen Ki67.</p> <p>Conclusion</p> <p>These findings revealed that deep tumor compartments may be involved in the initial stages of malignant transformation. Deoxyribonucleic acid ploidy analysis may provide an additional diagnosis tool and indicate 'uncertain' areas that require careful study to avoid diagnostic errors. Larger studies are needed to confirm our results and to evaluate the usefulness of the technique.</p