Metformin Decreases the Incidence of Pancreatic Ductal Adenocarcinoma Promoted by Diet-induced Obesity in the Conditional KrasG12D Mouse Model.

Pancreatic ductal adenocarcinoma (PDAC) is a particularly deadly disease. Chronic conditions, including obesity and type-2 diabetes are risk factors, thus making PDAC amenable to preventive strategies. We aimed to characterize the chemo-preventive effects of metformin, a widely used anti-diabetic drug, on PDAC development using the KrasG12D mouse model subjected to a diet high in fats and calories (HFCD). LSL-KrasG12D/+;p48-Cre (KC) mice were given control diet (CD), HFCD, or HFCD with 5 mg/ml metformin in drinking water for 3 or 9 months. After 3 months, metformin prevented HFCD-induced weight gain, hepatic steatosis, depletion of intact acini, formation of advanced PanIN lesions, and stimulation of ERK and mTORC1 in pancreas. In addition to reversing hepatic and pancreatic histopathology, metformin normalized HFCD-induced hyperinsulinemia and hyperleptinemia among the 9-month cohort. Importantly, the HFCD-increased PDAC incidence was completely abrogated by metformin (p < 0.01). The obesogenic diet also induced a marked increase in the expression of TAZ in pancreas, an effect abrogated by metformin. In conclusion, administration of metformin improved the metabolic profile and eliminated the promoting effects of diet-induced obesity on PDAC formation in KC mice. Given the established safety profile of metformin, our findings have a strong translational potential for novel chemo-preventive strategies for PDAC

Multiregional Satellite Precipitation Products Evaluation over Complex Terrain

An extensive evaluation of nine global-scale high-resolution satellite-based rainfall (SBR) products is performed using a minimum of 6 years (within the period of 2000-13) of reference rainfall data derived from rain gauge networks in nine mountainous regions across the globe. The SBR products are compared to a recently released global reanalysis dataset from the European Centre for Medium-Range Weather Forecasts (ECMWF). The study areas include the eastern Italian Alps, the Swiss Alps, the western Black Sea of Turkey, the French Cévennes, the Peruvian Andes, the Colombian Andes, the Himalayas over Nepal, the Blue Nile in East Africa, Taiwan, and the U.S. Rocky Mountains. Evaluation is performed at annual, monthly, and daily time scales and 0.25° spatial resolution. The SBR datasets are based on the following retrieval algorithms: Tropical Rainfall Measuring Mission Multisatellite Precipitation Analysis (TMPA), the NOAA/Climate Prediction Center morphing technique (CMORPH), Precipitation Estimation from Remotely Sensed Information Using Artificial Neural Networks (PERSIANN), and Global Satellite Mapping of Precipitation (GSMaP). SBR products are categorized into those that include gauge adjustment versus unadjusted. Results show that performance of SBR is highly dependent on the rainfall variability. Many SBR products usually underestimate wet season and overestimate dry season precipitation. The performance of gauge adjustment to the SBR products varies by region and depends greatly on the representativeness of the rain gauge network

Nonlinear modulational stability of periodic traveling-wave solutions of the generalized Kuramoto-Sivashinsky equation

In this paper we consider the spectral and nonlinear stability of periodic traveling wave solutions of a generalized Kuramoto-Sivashinsky equation. In particular, we resolve the long-standing question of nonlinear modulational stability by demonstrating that spectrally stable waves are nonlinearly stable when subject to small localized (integrable) perturbations. Our analysis is based upon detailed estimates of the linearized solution operator, which are complicated by the fact that the (necessarily essential) spectrum of the associated linearization intersects the imaginary axis at the origin. We carry out a numerical Evans function study of the spectral problem and find bands of spectrally stable periodic traveling waves, in close agreement with previous numerical studies of Frisch-She-Thual, Bar-Nepomnyashchy, Chang-Demekhin-Kopelevich, and others carried out by other techniques. We also compare predictions of the associated Whitham modulation equations, which formally describe the dynamics of weak large scale perturbations of a periodic wave train, with numerical time evolution studies, demonstrating their effectiveness at a practical level. For the reader's convenience, we include in an appendix the corresponding treatment of the Swift-Hohenberg equation, a nonconservative counterpart of the generalized Kuramoto-Sivashinsky equation for which the nonlinear stability analysis is considerably simpler, together with numerical Evans function analyses extending spectral stability analyses of Mielke and Schneider.Comment: 78 pages, 11 figure

Collective Excitations of Holographic Quantum Liquids in a Magnetic Field

We use holography to study N=4 supersymmetric SU(Nc) Yang-Mills theory in the large-Nc and large-coupling limits coupled to a number Nf << Nc of (n+1)-dimensional massless supersymmetric hypermultiplets in the Nc representation of SU(Nc), with n=2,3. We introduce a temperature T, a baryon number chemical potential mu, and a baryon number magnetic field B, and work in a regime with mu >> T,\sqrt{B}. We study the collective excitations of these holographic quantum liquids by computing the poles in the retarded Green's function of the baryon number charge density operator and the associated peaks in the spectral function. We focus on the evolution of the collective excitations as we increase the frequency relative to T, i.e. the hydrodynamic/collisionless crossover. We find that for all B, at low frequencies the tallest peak in the spectral function is associated with hydrodynamic charge diffusion. At high frequencies the tallest peak is associated with a sound mode similar to the zero sound mode in the collisionless regime of a Landau Fermi liquid. The sound mode has a gap proportional to B, and as a result for intermediate frequencies and for B sufficiently large compared to T the spectral function is strongly suppressed. We find that the hydrodynamic/collisionless crossover occurs at a frequency that is approximately B-independent.Comment: 45 pages, 8 png and 47 pdf images in 22 figure

Quantum field theoretic approach to neutrino oscillations in matter

We consider neutrino oscillations in non-uniform matter in a quantum field theoretic (QFT) approach, in which neutrino production, propagation and detection are considered as a single process. We find the conditions under which the oscillation probability can be sensibly defined and demonstrate how the properly normalized oscillation probability can be obtained in the QFT framework. We derive the evolution equation for the oscillation amplitude and discuss the conditions under which it reduces to the standard Schr\"odinger-like evolution equation. It is shown that, contrary to the common usage, the Schr\"odinger-like evolution equation is not applicable in certain cases, such as oscillations of neutrinos produced in decays of free pions provided that sterile neutrinos with $\Delta m^2\gtrsim 1$ eV$^2$ exist.Comment: LaTeX, 24 pages + 16 pages of appendices, 1 figure. V2: typos correcte

Prediction-Coherent LSTM-based Recurrent Neural Network for Safer Glucose Predictions in Diabetic People

In the context of time-series forecasting, we propose a LSTM-based recurrent neural network architecture and loss function that enhance the stability of the predictions. In particular, the loss function penalizes the model, not only on the prediction error (mean-squared error), but also on the predicted variation error. We apply this idea to the prediction of future glucose values in diabetes, which is a delicate task as unstable predictions can leave the patient in doubt and make him/her take the wrong action, threatening his/her life. The study is conducted on type 1 and type 2 diabetic people, with a focus on predictions made 30-minutes ahead of time. First, we confirm the superiority, in the context of glucose prediction, of the LSTM model by comparing it to other state-of-the-art models (Extreme Learning Machine, Gaussian Process regressor, Support Vector Regressor). Then, we show the importance of making stable predictions by smoothing the predictions made by the models, resulting in an overall improvement of the clinical acceptability of the models at the cost in a slight loss in prediction accuracy. Finally, we show that the proposed approach, outperforms all baseline results. More precisely, it trades a loss of 4.3\% in the prediction accuracy for an improvement of the clinical acceptability of 27.1\%. When compared to the moving average post-processing method, we show that the trade-off is more efficient with our approach

Requirements for Membrane Attack Complex Formation and Anaphylatoxins Binding to Collagen-Activated Platelets

The activation of complement during platelet activation is incompletely understood.We sought to explore the formation of C5b-9 and anaphylatoxins binding to collagen-activated platelets.C5b-9, anaphylatoxins C3a, C4a and C5a, and anaphylatoxin receptors C3aR1 and C5aR were measured by flow cytometry and/or confocal microscopy. Platelet microparticles were quantified by flow cytometry, and their C5b-9 content was determined by western blot analyses. In all experiments, sodium citrate was used for blood anticoagulation.C5b-9 rapidly formed on the platelet surface following activation with collagen, TRAP, ADP or A23187, but was surprisingly restricted to a subset of platelets (1 to 15%) independently of P-selectin or phosphatidylserine exposure. Following collagen activation, C5b-9-positive platelets in thrombi were found associated with collagen fibres. C5b-9 formation was obliterated by Mg(2+)-EGTA and significantly reduced by the thrombin inhibitor hirudin (-37%, p<0.05), but was unaffected by chondroitinase, compstatin, SCH79797 (PAR-1 inhibitor), or in the PRP of a MBL-deficient donor. Compstatin and Mg(2+)-EGTA, but not hirudin, SCH79797 or chondroitinase, inhibited the formation of collagen-induced microparticles (-71% and -44%, respectively, p<0.04). These microparticles contained greater amounts of C5b-9 compared with the other agonists. Platelet activation by collagen or convulxin resulted in the strong binding of anaphylatoxins and the exposure of receptors C3aR1 and C5aR (CD88) on their surface.C5b-9 formation on collagen-activated platelets is i) partially controlled by thrombin, ii) restricted to a subset of platelets, and iii) can occur without P-selectin expression or phosphatidylserine exposure. Activated platelets bind anaphylatoxins on their surface and express C3a and C5a receptors, which may contribute to the localization of inflammatory processes during thrombosis

Morphology control and optical properties of SiGe nanostructures grown on glass substrate

With the rapid progress of nanotechnology, nanostructures with different morphologies have been realized, which may be very promising to enhance the performance of semiconductor devices. In this study, SiGe nanostructures with several kinds of configurations have been synthesized through a chemical vapor deposition process. By controlling growth conditions, different SiGe nanostructures can be easily tuned. Structures and compositions of the nanostructures were determined by scanning electron microscopy, transmission electron microscopy, and X-ray diffraction. The optical properties of various SiGe nanostructures revealed some dependence with their morphologies, which may be suitable for solar cell applications. The control of the SiGe morphology on nanoscale provides a convenient route to produce diverse SiGe nanostructures and creates new opportunities to realize the integration of future devices

Traditional electrosurgery and a low thermal injury dissection device yield different outcomes following bilateral skin-sparing mastectomy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Although a skin- and nipple-sparing mastectomy technique offers distinct cosmetic and reconstructive advantages over traditional methods, partial skin flap and nipple necrosis remain a significant source of post-operative morbidity. Prior work has suggested that collateral thermal damage resulting from electrocautery use during skin flap development is a potential source of this complication. This report describes the case of a smoker with recurrent ductal carcinoma <it>in situ </it>(DCIS) who experienced significant unilateral skin necrosis following bilateral skin-sparing mastectomy while participating in a clinical trial examining mastectomy outcomes with two different surgical devices. This unexpected complication has implications for the choice of dissection devices in procedures requiring skin flap preservation.</p> <p>Case presentation</p> <p>The patient was a 61-year-old Caucasian woman who was a smoker with recurrent DCIS of her right breast. As part of the clinical trial, each breast was randomized to either the standard of care treatment group (a scalpel and a traditional electrosurgical device) or treatment with a novel, low thermal injury dissection device, allowing for a direct, internally controlled comparison of surgical outcomes. Post-operative follow-up at six days was unremarkable for both operative sites. At 16 days post-surgery, the patient presented with a significant wound necrosis in the mastectomy site randomized to the control study group. Following debridement and closure, this site progressively healed over 10 weeks. The contralateral mastectomy, randomized to the alternative device, healed normally.</p> <p>Conclusion</p> <p>We hypothesize that thermal damage to the subcutaneous microvasculature during flap dissection may have contributed to this complication and that the use of a low thermal injury dissection device may be advantageous in select patients undergoing skin- and nipple-sparing mastectomy.</p