Measurement of Neutrino Oscillation Parameters from Muon Neutrino Disappearance with an Off-Axis Beam

The T2K collaboration reports a precision measurement of muon neutrino disappearance with an off-axis neutrino beam with a peak energy of 0.6 GeV. Near detector measurements are used to constrain the neutrino flux and cross section parameters. The Super-Kamiokande far detector, which is 295 km downstream of the neutrino production target, collected data corresponding to 3.01×1020 protons on target. In the absence of neutrino oscillations, 205±17 (syst.) events are expected to be detected and only 58 muon neutrino event candidates are observed. A fit to the neutrino rate and energy spectrum assuming three neutrino flavors, normal mass hierarchy and θ23≤π/4 yields a best-fit mixing angle sin2(2θ23)=1.000 and mass splitting |Δm232|=2.44×10−3 eV2/c4. If θ23≥π/4 is assumed, the best-fit mixing angle changes to sin2(2θ23)=0.999 and the mass splitting remains unchanged.

Exposure to food allergens through inflamed skin promotes intestinal food allergy through the thymic stromal lymphopoietin-basophil axis.

BACKGROUND Exposure to food allergens through a disrupted skin barrier has been recognized as a potential factor in the increasing prevalence of food allergy. OBJECTIVE We sought to test the immunologic mechanisms by which epicutaneous sensitization to food allergens predisposes to intestinal food allergy. METHODS Mice were epicutaneously sensitized with ovalbumin or peanut on an atopic dermatitis-like skin lesion, followed by intragastric antigen challenge. Antigen-specific serum IgE levels and T(H)2 cytokine responses were measured by ELISA. Expression of type 2 cytokines and mast cell proteases in the intestine were measured by using real-time PCR. Accumulation of basophils in the skin and mast cells in the intestine was examined by using flow cytometry. In vivo basophil depletion was achieved by using diphtheria toxin treatment of Baso-DTR mice. For cell-transfer studies, the basophil population was expanded in vivo by means of hydrodynamic tail vein injection of thymic stromal lymphopoietin (TSLP) cDNA plasmid. RESULTS Sensitization to food allergens through an atopic dermatitis-like skin lesion is associated with an expansion of TSLP-elicited basophils in the skin that promote antigen-specific T(H)2 cytokine responses, increased antigen-specific serum IgE levels, and accumulation of mast cells in the intestine, promoting the development of intestinal food allergy. Critically, disruption of TSLP responses or depletion of basophils reduced the susceptibility to intestinal food allergy, whereas transfer of TSLP-elicited basophils into intact skin promoted disease. CONCLUSION Epicutaneous sensitization on a disrupted skin barrier is associated with accumulation of TSLP-elicited basophils, which are necessary and sufficient to promote antigen-induced intestinal food allergy.

Precise Measurement of the Neutrino Mixing Parameter θ₂₃ from Muon Neutrino Disappearance in an Off-Axis Beam

New data from the T2K neutrino oscillation experiment produce the most precise measurement of the neutrino mixing parameter θ 23 . Using an off-axis neutrino beam with a peak energy of 0.6 GeV and a data set corresponding to 6.57×10 20 protons on target, T2K has fit the energy-dependent ν μ oscillation probability to determine oscillation parameters. The 68% confidence limit on sin 2 (θ 23 ) is 0.514 +0.055 −0.056 (0.511±0.055 ), assuming normal (inverted) mass hierarchy. The best-fit mass-squared splitting for normal hierarchy is Δm 2 32 =(2.51±0.10)×10 −3   eV 2 /c 4 (inverted hierarchy: Δm 2 13 =(2.48±0.10)×10 −3   eV 2 /c 4 ). Adding a model of multinucleon interactions that affect neutrino energy reconstruction is found to produce only small biases in neutrino oscillation parameter extraction at current levels of statistical uncertainty.

Appraisal-driven somatovisceral response patterning: effects of intrinsic pleasantness and goal conduciveness.

Several componential emotion theories suggest that appraisal outcomes trigger characteristic somatovisceral changes that facilitate information processing and prepare the organism for adaptive behavior. The current study tested predictions derived from Scherer's Component Process Model. Participants viewed unpleasant and pleasant pictures (intrinsic pleasantness appraisal) and were asked to concurrently perform either an arm extension or an arm flexion, leading to an increase or a decrease in picture size. Increasing pleasant stimuli and decreasing unpleasant stimuli were considered goal conducive; decreasing pleasant stimuli and increasing unpleasant stimuli were considered goal obstructive (goal conduciveness appraisal). Both appraisals were marked by several somatovisceral changes (facial electromyogram, heart rate (HR)). As predicted, the changes induced by the two appraisals showed similar patterns. Furthermore, HR results, compared with data of earlier studies, suggest that the adaptive consequences of both appraisals may be mediated by stimulus proximity.

Cardiovascular-renal axis disorders in the domestic dog and cat: a veterinary consensus statement.

OBJECTIVES There is a growing understanding of the complexity of interplay between renal and cardiovascular systems in both health and disease. The medical profession has adopted the term "cardiorenal syndrome" (CRS) to describe the pathophysiological relationship between the kidney and heart in disease. CRS has yet to be formally defined and described by the veterinary profession and its existence and importance in dogs and cats warrant investigation. The CRS Consensus Group, comprising nine veterinary cardiologists and seven nephrologists from Europe and North America, sought to achieve consensus around the definition, pathophysiology, diagnosis and management of dogs and cats with "cardiovascular-renal disorders" (CvRD). To this end, the Delphi formal methodology for defining/building consensus and defining guidelines was utilised. METHODS Following a literature review, 13 candidate statements regarding CvRD in dogs and cats were tested for consensus, using a modified Delphi method. As a new area of interest, well-designed studies, specific to CRS/CvRD, are lacking, particularly in dogs and cats. Hence, while scientific justification of all the recommendations was sought and used when available, recommendations were largely reliant on theory, expert opinion, small clinical studies and extrapolation from data derived from other species. RESULTS Of the 13 statements, 11 achieved consensus and 2 did not. The modified Delphi approach worked well to achieve consensus in an objective manner and to develop initial guidelines for CvRD. DISCUSSION The resultant manuscript describes consensus statements for the definition, classification, diagnosis and management strategies for veterinary patients with CvRD, with an emphasis on the pathological interplay between the two organ systems. By formulating consensus statements regarding CvRD in veterinary medicine, the authors hope to stimulate interest in and advancement of the understanding and management of CvRD in dogs and cats. The use of a formalised method for consensus and guideline development should be considered for other topics in veterinary medicine.

Vascular Patterning: More Than Just Auxin?

The plant hormone auxin has long been known to play a pivotal role in vascular patterning and differentiation. But auxin is not the whole story: recent genetic analyses have identified additional factors required for vascular patterning, one of them involving sterols.

Inactivation of the p53-KLF4-CEBPA Axis in Acute Myeloid Leukemia.

PURPOSE In acute myeloid leukemia (AML), the transcription factors CEBPA and KLF4 as well as the universal tumor suppressor p53 are frequently deregulated. Here, we investigated the extent of dysregulation, the molecular interactions, and the mechanisms involved. EXPERIMENTAL DESIGN One hundred ten AML patient samples were analyzed for protein levels of CEBPA, KLF4, p53, and p53 modulators. Regulation of CEBPA gene expression by KLF4 and p53 or by chemical p53 activators was characterized in AML cell lines. RESULTS We found that CEBPA gene transcription can be directly activated by p53 and KLF4, suggesting a p53-KLF4-CEBPA axis. In AML patient cells, we observed a prominent loss of p53 function and concomitant reduction of KLF4 and CEBPA protein levels. Assessment of cellular p53 modulator proteins indicated that p53 inactivation in leukemic cells correlated with elevated levels of the nuclear export protein XPO1/CRM1 and increase of the p53 inhibitors MDM2 and CUL9/PARC in the cytoplasm. Finally, restoring p53 function following treatment with cytotoxic chemotherapy compounds and p53 restoring non-genotoxic agents induced CEBPA gene expression, myeloid differentiation, and cell-cycle arrest in AML cells. CONCLUSIONS The p53-KLF4-CEBPA axis is deregulated in AML but can be functionally restored by conventional chemotherapy and novel p53 activating treatments. Clin Cancer Res; 22(3); 746-56. ©2015 AACR.

Conserved regulation of proximodistal limb axis development by Meis1/Hth.

Vertebrate limbs grow out from the flanks of embryos, with their main axis extending proximodistally from the trunk. Distinct limb domains, each with specific traits, are generated in a proximal-to-distal sequence during development. Diffusible factors expressed from signalling centres promote the outgrowth of limbs and specify their dorsoventral and anteroposterior axes. However, the molecular mechanism by which limb cells acquire their proximodistal (P-D) identity is unknown. Here we describe the role of the homeobox genes Meis1/2 and Pbx1 in the development of mouse, chicken and Drosophila limbs. We find that Meis1/2 expression is restricted to a proximal domain, coincident with the previously reported domain in which Pbx1 is localized to the nucleus, and resembling the distribution of the Drosophila homologues homothorax (hth) and extradenticle (exd); that Meis1 regulates Pbx1 activity by promoting nuclear import of the Pbx1 protein; and that ectopic expression of Meis1 in chicken and hth in Drosophila disrupts distal limb development and induces distal-to-proximal transformations. We suggest that restriction of Meis1/Hth to proximal regions of the vertebrate and insect limb is essential to specify cell fates and differentiation patterns along the P-D axis of the limb.

Measurement of the νμ charged current quasielastic cross section on carbon with the T2K on-axis neutrino beam

We report a measurement of the νµ charged current quasi-elastic cross-sections on carbon in the T2K on-axis neutrino beam. The measured charged current quasi-elastic cross-sections on carbon at mean neutrino energies of 1.94 GeV and 0.93 GeV are (11.95 ± 0.19(stat.) +1.82−1.47(syst.)) ×10^−39 cm^2/neutron, and (10.64 ± 0.37(stat.)+2.03−1.65(syst.)) × 10^−39 cm^2/neutron, respectively. These results agree well with the predictions of neutrino interaction models. In addition, we investigated the effects of the nuclear model and the multi-nucleon interaction.

Measurement of Muon Antineutrino Oscillations with an Accelerator-Produced Off-Axis Beam

T2K reports its first measurements of the parameters governing the disappearance of νµ in an off-axis beam due to flavor change induced by neutrino oscillations. The quasimonochromatic νµ beam, produced with a peak energy of 0.6 GeV at J-PARC, is observed at the far detector SuperKamiokande, 295 km away, where the νµ survival probability is expected to be minimal. Using a dataset corresponding to 4.01×10²⁰ protons on target, 34 fully contained µ-like events were observed. The best-fit oscillation parameters are sin²(θ₂₃) = 0.45 and |∆m^2_32| = 2.51 × 10⁻³ eV² with 68% confidence intervals of 0.38 - 0.64 and 2.26 - 2.80 ×10⁻³ eV² respectively. These results are in agreement with existing antineutrino parameter measurements and also with the νµ disappearance parameters measured by T2K.