Signatures of quantum phase transitions in parallel quantum dots: Crossover from local-moment to underscreened spin-1 Kondo physics

We study a strongly interacting "quantum dot 1" and a weakly interacting "dot 2" connected in parallel to metallic leads. Gate voltages can drive the system between Kondo-quenched and non-Kondo free-moment phases separated by Kosterlitz-Thouless quantum phase transitions. Away from the immediate vicinity of the quantum phase transitions, the physical properties retain signatures of first-order transitions found previously to arise when dot 2 is strictly noninteracting. As interactions in dot 2 become stronger relative to the dot-lead coupling, the free moment in the non-Kondo phase evolves smoothly from an isolated spin-one-half in dot 1 to a many-body doublet arising from the incomplete Kondo compensation by the leads of a combined dot spin-one. These limits, which feature very different spin correlations between dot and lead electrons, can be distinguished by weak-bias conductance measurements performed at finite temperatures.Comment: 7 pages, 7 figures. Accepted for publication in Phys. Rev.

The effects of resistant starch and whole grains on appetite, food intake and metabolic response.

With the rise in obesity, there has been an increased interest in foods which may beneficially affect appetite. Resistant starch (RS) and whole grains (of which RS is a main dietary fibre component) have been proposed to affect satiety and therefore may be beneficial in weight management. There is little direct evidence confirming this in humans. Whilst animal data suggest a positive effect of RS on appetite, the few existing human intervention studies provide inconsistent findings. For whole grains the majority of evidence is from epidemiological work as opposed to intervention studies. Therefore a series of studies was conducted to investigate effects of RS and whole grains on appetite and food intake. Two studies were conducted using RS. The first investigated the acute (24 hours) effects of 48 g RS in healthy adult males compared with an energy and available carbohydrate matched placebo. Following RS there was a significantly lower energy intake compared with placebo. There was also a significantly lower postprandial insulin response with RS, possibly explained by increased hepatic insulin clearance determined by a higher C-peptide to insulin ratio. In the second study 40 g RS consumed daily for 4 weeks was compared with the placebo, in overweight and obese participants. Effects on food intake were assessed and a frequently sampled intravenous glucose tolerance test (FSIVGTT) was conducted. This study found no effect on either appetite or energy intake, but did find significantly higher glucose, insulin and C-peptide concentrations, measured during the FSIVGTT, with the RS compared with the placebo, possibly explained by an improved first-phase insulin response. This finding did not translate into differences in parameters obtained from modelling the FSIVGTT data, but this and the lack of appetite and food intake differences could be explained by the small participant numbers. Two intervention studies were conducted with whole grains incorporated into bread rolls. The first, a crossover study, involved 3 weeks' daily consumption of 48 g milled whole grain or control, in young healthy adults. Whilst no significant difference was found between interventions in energy intake or subjective appetite ratings, a significantly lower systolic blood pressure was observed with the milled whole grains. The second was an 8 week parallel study (48 g intact or 48 g milled whole grains or control) in overweight and obese adults. No significant difference was found between groups on energy intake, subjective appetite ratings, cholesterol or postprandial metabolite concentrations. RS appears to be a possible satiating ingredient when consumed acutely and, whilst this was not confirmed in our chronic study, effects may have been masked by small participant numbers. A novel finding from our RS studies was an effect on the insulin response. These studies suggest that RS could have a beneficial role in weight management and favourable metabolic effects. Our whole grain interventions appear not to agree with epidemiological work that suggests a beneficial role on appetite, but there maybe effects on blood pressure regulation. In all instances further investigations are required in other population groups, with more participants and for longer time periods

Role of RPL39 in Metaplastic Breast Cancer

Background: Metaplastic breast cancer is one of the most therapeutically challenging forms of breast cancer because of its highly heterogeneous and chemoresistant nature. We have previously demonstrated that ribosomal protein L39 (RPL39) and its gain-of-function mutation A14V have oncogenic activity in triple-negative breast cancer and this activity may be mediated through inducible nitric oxide synthase (iNOS). The function of RPL39 and A14V in other breast cancer subtypes is currently unknown. The objective of this study was to determine the role and mechanism of action of RPL39 in metaplastic breast cancer. Methods: Both competitive allele-specific and droplet digital polymerase chain reaction were used to determine the RPL39 A14V mutation rate in metaplastic breast cancer patient samples. The impact of RPL39 and iNOS expression on patient overall survival was estimated using the Kaplan-Meier method. Co-immunoprecipitation and immunoblot analyses were used for mechanistic evaluation of RPL39. Results: The RPL39 A14V mutation rate was 97.5% (39/40 tumor samples). High RPL39 (hazard ratio = 0.71, 95% confidence interval = 0.55 to 0.91, P = .006) and iNOS expression (P = .003) were associated with reduced patient overall survival. iNOS inhibition with the pan-NOS inhibitor NG-methyl-L-arginine acetate decreased in vitro proliferation and migration, in vivo tumor growth in both BCM-4664 and BCM-3807 patient-derived xenograft models (P = .04 and P = .02, respectively), and in vitro and in vivo chemoresistance. Mechanistically, RPL39 mediated its cancer-promoting actions through iNOS signaling, which was driven by the RNA editing enzyme adenosine deaminase acting on RNA 1. Conclusion: NOS inhibitors and RNA editing modulators may offer novel treatment options for metaplastic breast cancer

Current cosmological bounds on neutrino masses and relativistic relics

We combine the most recent observations of large-scale structure (2dF and SDSS galaxy surveys) and cosmic microwave anisotropies (WMAP and ACBAR) to put constraints on flat cosmological models where the number of massive neutrinos and of massless relativistic relics are both left arbitrary. We discuss the impact of each dataset and of various priors on our bounds. For the standard case of three thermalized neutrinos, we find an upper bound on the total neutrino mass sum m_nu < 1.0 (resp. 0.6) eV (at 2sigma), using only CMB and LSS data (resp. including priors from supernovae data and the HST Key Project), a bound that is quite insensitive to the splitting of the total mass between the three species. When the total number of neutrinos or relativistic relics N_eff is left free, the upper bound on sum m_nu (at 2sigma, including all priors) ranges from 1.0 to 1.5 eV depending on the mass splitting. We provide an explanation of the parameter degeneracy that allows larger values of the masses when N_eff increases. Finally, we show that the limit on the total neutrino mass is not significantly modified in the presence of primordial gravitational waves, because current data provide a clear distinction between the corresponding effects.Comment: 13 pages, 6 figure

Mutant p53 drives clonal hematopoiesis through modulating epigenetic pathway

Clonal hematopoiesis of indeterminate potential (CHIP) increases with age and is associated with increased risks of hematological malignancies. While TP53 mutations have been identified in CHIP, the molecular mechanisms by which mutant p53 promotes hematopoietic stem and progenitor cell (HSPC) expansion are largely unknown. Here we discover that mutant p53 confers a competitive advantage to HSPCs following transplantation and promotes HSPC expansion after radiation-induced stress. Mechanistically, mutant p53 interacts with EZH2 and enhances its association with the chromatin, thereby increasing the levels of H3K27me3 in genes regulating HSPC self-renewal and differentiation. Furthermore, genetic and pharmacological inhibition of EZH2 decreases the repopulating potential of p53 mutant HSPCs. Thus, we uncover an epigenetic mechanism by which mutant p53 drives clonal hematopoiesis. Our work will likely establish epigenetic regulator EZH2 as a novel therapeutic target for preventing CHIP progression and treating hematological malignancies with TP53 mutations

Phytochemicals as antibiotic alternatives to promote growth and enhance host health

There are heightened concerns globally on emerging drug-resistant superbugs and the lack of new antibiotics for treating human and animal diseases. For the agricultural industry, there is an urgent need to develop strategies to replace antibiotics for food-producing animals, especially poultry and livestock. The 2nd International Symposium on Alternatives to Antibiotics was held at the World Organization for Animal Health in Paris, France, December 12-15, 2016 to discuss recent scientific developments on strategic antibiotic-free management plans, to evaluate regional differences in policies regarding the reduction of antibiotics in animal agriculture and to develop antibiotic alternatives to combat the global increase in antibiotic resistance. More than 270 participants from academia, government research institutions, regulatory agencies, and private animal industries from >25 different countries came together to discuss recent research and promising novel technologies that could provide alternatives to antibiotics for use in animal health and production; assess challenges associated with their commercialization; and devise actionable strategies to facilitate the development of alternatives to antibiotic growth promoters (AGPs) without hampering animal production. The 3-day meeting consisted of four scientific sessions including vaccines, microbial products, phytochemicals, immune-related products, and innovative drugs, chemicals and enzymes, followed by the last session on regulation and funding. Each session was followed by an expert panel discussion that included industry representatives and session speakers. The session on phytochemicals included talks describing recent research achievements, with examples of successful agricultural use of various phytochemicals as antibiotic alternatives and their mode of action in major agricultural animals (poultry, swine and ruminants). Scientists from industry and academia and government research institutes shared their experience in developing and applying potential antibiotic-alternative phytochemicals commercially to reduce AGPs and to develop a sustainable animal production system in the absence of antibiotics.Fil: Lillehoj, Hyun. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Liu, Yanhong. University of California; Estados UnidosFil: Calsamiglia, Sergio. Universitat Autònoma de Barcelona; EspañaFil: Fernandez Miyakawa, Mariano Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Chi, Fang. Amlan International; Estados UnidosFil: Cravens, Ron L.. Amlan International; Estados UnidosFil: Oh, Sungtaek. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Gay, Cyril G.. United States Department of Agriculture. Agricultural Research Service; Argentin

Kinetic Phenomena in Thin Film Electronic Materials

Contains reports on twelve research projects.National Science Foundation (Grant ECS 85-06505)U.S. Air Force - Office of Scientific Research (Contract AFOSR-85-0154)Semiconductor Research Corporation (Contract 87-SP-080)National Science Foundation (Grant ECS 85-06565)International Business Machines, Inc.Sony International Business Machines, Inc.National Science Foundation (Grant DMR 84-18718)International Business Machines, Thomas J. Watson Research CenterJoint Services Electronics Program (Contract DAALO3-86-K-0002)National Science Foundation (Grant DMR 85-06030)Charles Stark Draper Laboratory (Contract DL-H-261827)Nippon Telegraph and Telephone, Inc