Measuring Active-Sterile Neutrino Oscillations with a Stopped Pion Neutrino Source

The question of the existence of light sterile neutrinos is of great interest in many areas of particle physics, astrophysics, and cosmology. Furthermore, should the MiniBooNE experiment at Fermilab confirm the LSND oscillation signal, then new measurements are required to identify the mechanism responsible for these oscillations. Possibilities include sterile neutrinos, CP or CPT violation, variable mass neutrinos, Lorentz violation, and extra dimensions. In this paper, we consider an experiment at a stopped pion neutrino source to determine if active-sterile neutrino oscillations with delta-m greater than 0.1 eV2 can account for the signal. By exploiting stopped pi+ decay to produce a monoenergetic nu_mu source, and measuring the rate of the neutral current reaction nu_x + 12C -> nu_x +12C* as a function of distance from the source, we show that a convincing test for active-sterile neutrino oscillations can be performed.Comment: 10 pages, 9 figure

The external benefits of higher education

The private market benefits of education are widely studied at the micro level, although the magnitude of their macroeconomic impact is disputed. However, there are additional benefits of education, which are less well understood. In this paper the macroeconomic effects of external benefits of higher education are estimated using the “micro-to-macro” simulation approach. Two types of externalities are explored: technology spillovers and productivity spillovers in the labour market. These links are illustrated and the results suggest they could be very large. However, this is qualified by the dearth of microeconomic evidence, for which we hope to encourage further work

3N Scattering in a Three-Dimensional Operator Formulation

A recently developed formulation for a direct treatment of the equations for two- and three-nucleon bound states as set of coupled equations of scalar functions depending only on vector momenta is extended to three-nucleon scattering. Starting from the spin-momentum dependence occurring as scalar products in two- and three-nucleon forces together with other scalar functions, we present the Faddeev multiple scattering series in which order by order the spin-degrees can be treated analytically leading to 3D integrations over scalar functions depending on momentum vectors only. Such formulation is especially important in view of awaiting extension of 3N Faddeev calculations to projectile energies above the pion production threshold and applications of chiral perturbation theory 3N forces, which are to be most efficiently treated directly in such three-dimensional formulation without having to expand these forces into a partial wave basis.Comment: 25 pages, 0 figure

Inhibition of DNA replication fork progression and mutagenic potential of 1, N6-ethenoadenine and 8-oxoguanine in human cell extracts

Comparative mutagenesis of 1,N6-ethenoadenine (εA) and 8-oxoguanine (8-oxoG), two endogenous DNA lesions that are also formed by exogenous DNA damaging agents, have been evaluated in HeLa and xeroderma pigmentosum variant (XPV) cell extracts. Two-dimensional gel electrophoresis of the duplex M13mp2SV vector containing these lesions established that there was significant inhibition of replication fork movement past εA, whereas 8-oxoG caused only minor stalling of fork progression. In extracts of HeLa cells, εA was weakly mutagenic inducing all three base substitutions in approximately equal frequency, whereas 8-oxoG was 10-fold more mutagenic inducing primarily G→T transversions. These data suggest that 8-oxoG is a miscoding lesion that presents a minimal, if any, block to DNA replication in human cells. We hypothesized that bypass of εA proceeded principally by an error-free mechanism in which the undamaged strand was used as a template, since this lesion strongly blocked fork progression. To examine this, we determined the sequence of replication products derived from templates in which a G was placed across from the εA. Consistent with our hypothesis, 93% of the progeny were derived from replication of the undamaged strand. When translesion synthesis occurred, εA→T mutations increased 3-fold in products derived from the mismatched εA: G construct compared with those derived from the εA: T construct. More efficient repair of εA in the εA: T construct may have been responsible for lower mutation frequency. Primer extension studies with purified pol η have shown that this polymerase is highly error-prone when bypassing εA. To examine if pol η is the primary mutagenic translesion polymerase in human cells, we determined the lesion bypass characteristics of extracts derived from XPV cells, which lack this polymerase. The εA: T construct induced εA→G and εA→C mutant frequencies that were approximately the same as those observed using the HeLa extracts. However, εA→T events were increased 5-fold relative to HeLa extracts. These data support a model in which pol η-mediated translesion synthesis past this adduct is error-free in the context of semiconservative replication in the presence of fidelity factors such as PCNA

Acute inhibition of MEK suppresses congenital melanocytic nevus syndrome in a murine model driven by activated NRAS and Wnt signaling

Congenital melanocytic nevus (CMN) syndrome is the association of pigmented melanocytic nevi with extra-cutaneous features, classically melanotic cells within the central nervous system, most frequently caused by a mutation of NRAS codon 61. This condition is currently untreatable and carries a significant risk of melanoma within the skin, brain, or leptomeninges. We have previously proposed a key role for Wnt signaling in the formation of melanocytic nevi, suggesting that activated Wnt signaling may be synergistic with activated NRAS in the pathogenesis of CMN syndrome. Some familial pre-disposition suggests a germ-line contribution to CMN syndrome, as does variability of neurological phenotypes in individuals with similar cutaneous phenotypes. Accordingly, we performed exome sequencing of germ-line DNA from patients with CMN to reveal rare or undescribed Wnt-signaling alterations. A murine model harboring activated NRASQ61K and Wnt signaling in melanocytes exhibited striking features of CMN syndrome, in particular neurological involvement. In the first model of treatment for this condition, these congenital, and previously assumed permanent, features were profoundly suppressed by acute post-natal treatment with a MEK inhibitor. These data suggest that activated NRAS and aberrant Wnt signaling conspire to drive CMN syndrome. Post-natal MEK inhibition is a potential candidate therapy for patients with this debilitating condition

ENSO-driven interhemispheric Pacific mass transports

Previous studies have shown that ENSO's anomalous equatorial winds, including the observed southward shift of zonal winds that occurs around the event peak, can be reconstructed with the first two Empirical Orthogonal Functions (EOFs) of equatorial region wind stresses. Using a high-resolution ocean general circulation model, we investigate the effect of these two EOFs on changes in warm water volume (WWV), interhemispheric mass transports, and Indonesian Throughflow (ITF). Wind stress anomalies associated with the first EOF produce changes in WWV that are dynamically consistent with the conceptual recharge oscillator paradigm. The ITF is found to heavily damp these WWV changes, reducing their variance by half. Wind stress anomalies associated with the second EOF, which depicts the southward wind shift, are responsible for WWV changes that are of comparable magnitude to those driven by the first mode. The southward wind shift is also responsible for the majority of the observed interhemispheric upper ocean mass exchanges. These winds transfer mass between the Northern and the Southern Hemisphere during El Niño events. Whilst water is transferred in the opposite direction during La Niña events, the magnitude of this exchange is roughly half of that seen during El Niño events. Thus, the discharging of WWV during El Niño events is meridionally asymmetric, while the WWV recharging during a La Niña event is largely symmetric. The inclusion of the southward wind shift is also shown to allow ENSO to exchange mass with much higher latitudes than that allowed by the first EOF alone

Lunar In Situ Materials-Based Surface Structure Technology Development Efforts at NASA/MSFC

For long-duration missions on other planetary bodies, the use of in situ materials will become increasingly critical. As man's presence on these bodies expands, so must the structures to accommodate them, including habitats, laboratories, berms, radiation shielding for surface reactors, garages, solar storm shelters, greenhouses, etc. The use of in situ materials will significantly offset required launch upmass and volume issues. Under the auspices of the In Situ Fabrication & Repair (ISFR) Program at NASA/Marshall Space Flight Center (MSFC), the Surface Structures project has been developing materials and construction technologies to support development of these in situ structures. This paper will report on the development of several of these technologies at MSFC's Prototype Development Laboratory (PDL). These technologies include, but are not limited to, development of extruded concrete and inflatable concrete dome technologies based on waterless and water-based concretes, development of regolith-based blocks with potential radiation shielding binders including polyurethane and polyethylene, pressure regulation systems for inflatable structures, production of glass fibers and rebar derived from molten lunar regolith simulant, development of regolithbag structures, and others, including automation design issues. Results to date and lessons learned will be presented, along with recommendations for future activities

Integrin-mediated traction force enhances paxillin molecular associations and adhesion dynamics that increase the invasiveness of tumor cells into a three-dimensional extracellular matrix.

Metastasis requires tumor cells to navigate through a stiff stroma and squeeze through confined microenvironments. Whether tumors exploit unique biophysical properties to metastasize remains unclear. Data show that invading mammary tumor cells, when cultured in a stiffened three-dimensional extracellular matrix that recapitulates the primary tumor stroma, adopt a basal-like phenotype. Metastatic tumor cells and basal-like tumor cells exert higher integrin-mediated traction forces at the bulk and molecular levels, consistent with a motor-clutch model in which motors and clutches are both increased. Basal-like nonmalignant mammary epithelial cells also display an altered integrin adhesion molecular organization at the nanoscale and recruit a suite of paxillin-associated proteins implicated in invasion and metastasis. Phosphorylation of paxillin by Src family kinases, which regulates adhesion turnover, is similarly enhanced in the metastatic and basal-like tumor cells, fostered by a stiff matrix, and critical for tumor cell invasion in our assays. Bioinformatics reveals an unappreciated relationship between Src kinases, paxillin, and survival of breast cancer patients. Thus adoption of the basal-like adhesion phenotype may favor the recruitment of molecules that facilitate tumor metastasis to integrin-based adhesions. Analysis of the physical properties of tumor cells and integrin adhesion composition in biopsies may be predictive of patient outcome

Economic, social and demographic impacts of drought on treatment adherence among people living with HIV in rural South Africa: A qualitative analysis

The 2015 El Niño-triggered drought in Southern Africa caused widespread economic and livelihood disruption in South Africa, imposing multiple physical and health challenges for rural populations including people living with HIV (PLHIV). We examined the economic, social and demographic impacts of drought drawing on 27 in-depth interviews in two cohorts of PLHIV in Hlabisa, uMkhanyakude district, KwaZulu-Natal. Thematic analysis revealed how drought-enforced soil water depletion, dried-up rivers, and dams culminated in a continuum of events such as loss of livestock, reduced agricultural production, and insufficient access to water and food which was understood to indirectly have a negative impact on HIV treatment adherence. This was mediated through disruptions in incomes, livelihoods and food systems, increased risk to general health, forced mobility and exacerbation of contextual vulnerabilities linked to poverty and unemployment. The systems approach, drawn from interview themes, hypothesises the complex pathways of plausible networks of impacts from drought through varying socioeconomic factors, exacerbating longstanding contextual precarity, and ultimately challenging HIV care utilisation. Understanding the multidimensional relationships between climate change, especially drought, and poor HIV care outcomes through the prism of contextual vulnerabilities is vital for shaping policy interventions