Release of NO(x) from sunlight-irradiated midlatitude snow

Photochemical production and release of gas-phase NO(x) (NO + NO2) from the natural snowpack at a remote site in northern Michigan were investigated during the Snow Nitrogen and Oxidants in Winter study in January 1999. Snow was collected in an open 34 L chamber, which was then sealed with a transparent Teflon cover and used as an outdoor flow and reaction chamber. Significant increases in NO(x) mixing ratio were observed in synthetic and ambient air pulled through the sunlit chamber. [NO(x)] enhancements were correlated to ultraviolet sunlight intensity, reaching ~300 pptv under partially overcast midday, mid-winter conditions. These findings are consistent with NO(x) production from photolysis of snowpack NO3 -; the observed NO(x) release implies production of significant amounts of OH within the snow. Snowpack NO3 - photolysis may therefore significantly alter boundary layer levels of both NO(x) and oxidized compounds over wide regions of the atmosphere

Spacetime Emergence and General Covariance Transmutation

Spacetime emergence refers to the notion that classical spacetime "emerges" as an approximate macroscopic entity from a non-spatio-temporal structure present in a more complete theory of interacting fundamental constituents. In this article, we propose a novel mechanism involving the "soldering" of internal and external spaces for the emergence of spacetime and the twin transmutation of general covariance. In the context of string theory, this mechanism points to a critical four dimensional spacetime background.Comment: 11 pages, v2: version to appear in MPL

Adverse effects of cannabidiol:a systematic review and meta-analysis of randomized clinical trials

Cannabidiol (CBD) is being investigated as a treatment for several medical disorders but there is uncertainty about its safety. We conducted the first systematic review and meta-analysis of the adverse effects of CBD across all medical indications. Double-blind randomized placebo-controlled clinical trials lasting ≥7 days were included. Twelve trials contributed data from 803 participants to the meta-analysis. Compared with placebo, CBD was associated with an increased likelihood of withdrawal for any reason (OR 2.61, 95% CI: 1.38-4.96) or due to adverse events (OR 2.65, 95% CI: 1.04-6.80), any serious adverse event (OR 2.30, 95% CI: 1.18-4.48), serious adverse events related to abnormal liver function tests (OR 11.19, 95% CI: 2.09-60.02) or pneumonia (OR 5.37, 95% CI: 1.17-24.65), any adverse event (OR 1.55, 95% CI: 1.03-2.33), adverse events due to decreased appetite (OR 3.56, 95% CI: 1.94-6.53), diarrhoea (OR 2.61, 95% CI: 1.46-4.67), somnolence (OR 2.23, 95% CI: 1.07-4.64) and sedation (OR 4.21, 95% CI: 1.18-15.01). Associations with abnormal liver function tests, somnolence, sedation and pneumonia were limited to childhood epilepsy studies, where CBD may have interacted with other medications such as clobazam and/or sodium valproate. After excluding studies in childhood epilepsy, the only adverse outcome associated with CBD treatment was diarrhoea (OR 5.03, 95% CI: 1.44-17.61). In summary, the available data from clinical trials suggest that CBD is well tolerated and has relatively few serious adverse effects, however interactions with other medications should be monitored carefully. Additional safety data from clinical trials outside of childhood epilepsy syndromes and from studies of over-the-counter CBD products are needed to assess whether the conclusions drawn from clinical trials can be applied more broadly.</p

A longer vernal window: The role of winter coldness and snowpack in driving spring thresholds and lags

Climate change is altering the timing and duration of the vernal window, a period that marks the end of winter and the start of the growing season when rapid transitions in ecosystem energy, water, nutrient, and carbon dynamics take place. Research on this period typically captures only a portion of the ecosystem in transition and focuses largely on the dates by which the system wakes up. Previous work has not addressed lags between transitions that represent delays in energy, water, nutrient, and carbon flows. The objectives of this study were to establish the sequence of physical and biogeochemical transitions and lags during the vernal window period and to understand how climate change may alter them. We synthesized observations from a statewide sensor network in New Hampshire, USA, that concurrently monitored climate, snow, soils, and streams over a three-year period and supplemented these observations with climate reanalysis data, snow data assimilation model output, and satellite spectral data. We found that some of the transitions that occurred within the vernal window were sequential, with air temperatures warming prior to snow melt, which preceded forest canopy closure. Other transitions were simultaneous with one another and had zero-length lags, such as snowpack disappearance, rapid soil warming, and peak stream discharge. We modeled lags as a function of both winter coldness and snow depth, both of which are expected to decline with climate change. Warmer winters with less snow resulted in longer lags and a more protracted vernal window. This lengthening of individual lags and of the entire vernal window carries important consequences for the thermodynamics and biogeochemistry of ecosystems, both during the winter-to-spring transition and throughout the rest of the year

\u3ci\u3eParelaphostrongylus odocoilei\u3c/i\u3e in Columbia Black-Tailed Deer from Oregon

Documenting the occurrence of Parelaphostrongylus odocoilei has historically relied on the morphological examination of adult worms collected from the skeletal muscle of definitive hosts, including deer. Recent advances in the knowledge of protostrongylid genetic sequences now permit larvae to be identified. Dorsal-spined larvae (DSLs) collected in 2003–2004 from the lung and feces of six Columbian black-tailed deer (Odocoileus hemionus columbianus) from Oregon were characterized genetically. The sequences from unknown DSLs were compared to those from morphologically validated adults and larvae of P. odocoilei at both the second internal transcribed spacer (ITS-2) of ribosomal DNA and the mitochondrial cytochrome oxidase II gene. We provide the first unequivocal identification of P. odocoilei in Columbian black-tailed deer from Oregon. The broader geographic distribution, prevalence, and pathology of P. odocoilei are not known in populations of Oregon deer

Discovery of an inhibitor of DNA-driven inflammation that preferentially targets the AIM2 inflammasome

Inflammation driven by DNA sensors is now understood to be important to dis-ease pathogenesis. Here, we describe new inhibitors of DNA sensing, primarily of the inflammasome forming sensor AIM2. Biochemistry and molecular modeling has revealed 4-sulfonic calixarenes as potent inhibitors of AIM2 that likely work by binding competitively to the DNA-binding HIN domain. Although less potent, these AIM2 inhibitors also inhibit DNA sensors cGAS and TLR9 demonstrating a broad utility against DNA-driven inflammatory responses. The 4-sulfonic calixar-enes inhibited AIM2-dependent post-stroke T cell death, highlighting a proof of concept that the 4-sulfonic calixarenes could be effective at combating post -stroke immunosuppression. By extension, we propose a broad utility against DNA-driven inflammation in disease. Finally, we reveal that the drug suramin, by virtue of its structural similarities, is an inhibitor of DNA-dependent inflamma-tion and propose that suramin could be rapidly repurposed to meet an increasing clinical need

Finite SU(N)^k Unification

We consider N=1 supersymmetric gauge theories based on the group SU(N)_1 x SU(N)_2 x ... x SU(N)_k with matter content (N,N*,1,...,1) + (1,N,N*,...,1) + >... + (N*,1,1,...,N) as candidates for the unification symmetry of all particles. In particular we examine to which extent such theories can become finite and we find that a necessary condition is that there should be exactly three families. We discuss further some phenomenological issues related to the cases (N,k) = (3,3), (3,4), and (4,3), in an attempt to choose those theories that can become also realistic. Thus we are naturally led to consider the SU(3)^3 model which we first promote to an all-loop finite theory and then we study its additional predictions concerning the top quark mass, Higgs mass and supersymmetric spectrum.Comment: 15 page

Genetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to myeloproliferative neoplasms

Clonal proliferation in myeloproliferative neoplasms (MPN) is driven by somatic mutations in JAK2, CALR or MPL, but the contribution of inherited factors is poorly characterized. Using a three-stage genome-wide association study of 3,437 MPN cases and 10,083 controls, we identify two SNPs with genome-wide significance in JAK2V617F-negative MPN: rs12339666 (JAK2; meta-analysis P=1.27 × 10−10) and rs2201862 (MECOM; meta-analysis P=1.96 × 10−9). Two additional SNPs, rs2736100 (TERT) and rs9376092 (HBS1L/MYB), achieve genome-wide significance when including JAK2V617F-positive cases. rs9376092 has a stronger effect in JAK2V617F-negative cases with CALR and/or MPL mutations (Breslow–Day P=4.5 × 10−7), whereas in JAK2V617F-positive cases rs9376092 associates with essential thrombocythemia (ET) rather than polycythemia vera (allelic χ2 P=7.3 × 10−7). Reduced MYB expression, previously linked to development of an ET-like disease in model systems, associates with rs9376092 in normal myeloid cells. These findings demonstrate that multiple germline variants predispose to MPN and link constitutional differences in MYB expression to disease phenotype

Estimation of Dietary Iron Bioavailability from Food Iron Intake and Iron Status

Currently there are no satisfactory methods for estimating dietary iron absorption (bioavailability) at a population level, but this is essential for deriving dietary reference values using the factorial approach. The aim of this work was to develop a novel approach for estimating dietary iron absorption using a population sample from a sub-section of the UK National Diet and Nutrition Survey (NDNS). Data were analyzed in 873 subjects from the 2000–2001 adult cohort of the NDNS, for whom both dietary intake data and hematological measures (hemoglobin and serum ferritin (SF) concentrations) were available. There were 495 men aged 19–64 y (mean age 42.7±12.1 y) and 378 pre-menopausal women (mean age 35.7±8.2 y). Individual dietary iron requirements were estimated using the Institute of Medicine calculations. A full probability approach was then applied to estimate the prevalence of dietary intakes that were insufficient to meet the needs of the men and women separately, based on their estimated daily iron intake and a series of absorption values ranging from 1–40%. The prevalence of SF concentrations below selected cut-off values (indicating that absorption was not high enough to maintain iron stores) was derived from individual SF concentrations. An estimate of dietary iron absorption required to maintain specified SF values was then calculated by matching the observed prevalence of insufficiency with the prevalence predicted for the series of absorption estimates. Mean daily dietary iron intakes were 13.5 mg for men and 9.8 mg for women. Mean calculated dietary absorption was 8% in men (50th percentile for SF 85 µg/L) and 17% in women (50th percentile for SF 38 µg/L). At a ferritin level of 45 µg/L estimated absorption was similar in men (14%) and women (13%). This new method can be used to calculate dietary iron absorption at a population level using data describing total iron intake and SF concentration