Regioselective Magnesiations of Fluorinated Arenes and Heteroarenes Using Magnesium-bis-Diisopropylamide (MBDA) in Hydrocarbons

We report a convenient preparation of a new and storable magnesium amide (iPr(2)N)(2)Mg (magnesiumbis-diisopropylamide;MBDA) which proved to be especially suitable for the non-cryogenic magnesiation of fluoro-substituted arenes and heteroarenes providing arylmagnesium amides (ArMgDA) or bis-heteroaryl magnesiums (HetAr)(2)Mg in hydrocarbons. Further reactions with electrophiles (aldehydes, ketones, allylic bromides, aryl halides (Negishi cross-coupling)) furnished a range of polyfunctional fluoro-substituted unsaturated building blocks. Several postfunctionalizations were described as well as NMR-studies confirming the dimeric structure of the base

Spin Discrimination in Three-Body Decays

The identification of the correct model for physics beyond the Standard Model requires the determination of the spin of new particles. We investigate to which extent the spin of a new particle $X$ can be identified in scenarios where it decays dominantly in three-body decays $X\to f\bar{f} Y$. Here we assume that $Y$ is a candidate for dark matter and escapes direct detection at a high energy collider such as the LHC. We show that in the case that all intermediate particles are heavy, one can get information on the spins of $X$ and $Y$ at the LHC by exploiting the invariant mass distribution of the two standard model fermions. We develop a model-independent strategy to determine the spins without prior knowledge of the unknown couplings and test it in a series of Monte Carlo studies.Comment: 31+1 pages, 4 figures, 8 tables, JHEP.cls include

A Shift Symmetry in the Higgs Sector: Experimental Hints and Stringy Realizations

We interpret reported hints of a Standard Model Higgs boson at ~ 125 GeV in terms of high-scale supersymmetry breaking with a shift symmetry in the Higgs sector. More specifically, the Higgs mass range suggested by recent LHC data extrapolates, within the (non-supersymmetric) Standard Model, to a vanishing quartic Higgs coupling at a UV scale between 10^6 and 10^18 GeV. Such a small value of lambda can be understood in terms of models with high-scale SUSY breaking if the Kahler potential possesses a shift symmetry, i.e., if it depends on H_u and H_d only in the combination (H_u+\bar{H}_d). This symmetry is known to arise rather naturally in certain heterotic compactifications. We suggest that such a structure of the Higgs Kahler potential is common in a wider class of string constructions, including intersecting D7- and D6-brane models and their extensions to F-theory or M-theory. The latest LHC data may thus be interpreted as hinting to a particular class of compactifications which possess this shift symmetry.Comment: v2: References added. v3: References added, published versio

Invisible Higgs and Dark Matter

We investigate the possibility that a massive weakly interacting fermion simultaneously provides for a dominant component of the dark matter relic density and an invisible decay width of the Higgs boson at the LHC. As a concrete model realizing such dynamics we consider the minimal walking technicolor, although our results apply more generally. Taking into account the constraints from the electroweak precision measurements and current direct searches for dark matter particles, we find that such scenario is heavily constrained, and large portions of the parameter space are excluded.Comment: arXiv admin note: text overlap with arXiv:0912.229

Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker in bipolar disorder: a meta-analysis of 52 studies

Background: The neurotrophic hypothesis postulates that mood disorders such as bipolar disorder (BD) are associated with a lower expression of brain-derived neurotrophic factor (BDNF). However, its role in peripheral blood as a biomarker of disease activity and of stage for BD, transcending pathophysiology, is still disputed. In the last few years an increasing number of clinical studies assessing BDNF in serum and plasma have been published. Therefore, it is now possible to analyse the association between BDNF levels and the severity of affective symptoms in BD as well as the effects of acute drug treatment of mood episodes on BDNF levels. Methods: We conducted a systematic review and meta-analysis of all studies on serum and plasma BDNF levels in bipolar disorder. Results: Through a series of meta-analyses including a total of 52 studies with 6,481 participants, we show that, compared to healthy controls, peripheral BDNF levels are reduced to the same extent in manic (Hedges' g = -0.57, P = 0.010) and depressive (Hedges' g = -0.93, P = 0.001) episodes, while BDNF levels are not significantly altered in euthymia. In meta-regression analyses, BDNF levels additionally negatively correlate with the severity of both manic and depressive symptoms. We found no evidence for a significant impact of illness duration on BDNF levels. In addition, in plasma, but not serum, peripheral BDNF levels increase after the successful treatment of an acute mania episode, but not of a depressive one. Conclusions: In summary, our data suggest that peripheral BDNF levels, more clearly in plasma than in serum, is a potential biomarker of disease activity in BD, but not a biomarker of stage. We suggest that peripheral BDNF may, in future, be used as a part of a blood protein composite measure to assess disease activity in BD.BSF is supported by a postdoctoral scholarship and by a research grant MCTI/CNPQ/Universal 14/2014461833/2014-0, both from CNPq, Brazil. CAK is a recipient of a postdoctoral fellowship from CAPES, Brazil. JCS is supported by NIMH grant R01 085667, the Dunn Foundation and the JQ are supported by research fellowship awards from CNPq (Brazil, level IA). AFC is the recipient of a research fellowship from CNPq (Brazil, level II). MB is supported by a NHMRC Senior Principal Research Fellowship 1059660. None of these agencies had any role in the design and conduct of the study, or decision to submit the manuscript for publication. We thank all authors of the included papers, particularly Drs. Natalie L. Rasgon, Deniz Ceylan, Camilla Langan, Pedro Magalhaes, Antonio L. Teixeira, Yuan-Hwa Chou, Iria Grande, Chenyu Ye, Izabela Barbosa, Menan Rabie, Ru-Band Lu, Ana Gonzales-Pinto, Reiji Yoshimura, Flavio Kapczinski, and Christoph Laske, who kindly provided unpublished data for the paper

Growth and Competitive Effects of Centaurea stoebe Populations in Response to Simulated Nitrogen Deposition

Increased resource availability can promote invasion by exotic plants, raising concerns over the potential effects of global increases in the deposition of nitrogen (N). It is poorly understood why increased N favors exotics over natives. Fast growth may be a general trait of good invaders and these species may have exceptional abilities to increase growth rates in response to N deposition. Additionally, invaders commonly displace locals, and thus may have inherently greater competitive abilities. The mean growth response of Centaurea stoebe to two N levels was significantly greater than that of North American (NA) species. Growth responses to N did not vary among C. stoebe populations or NA species. Without supplemental N, NA species were better competitors than C. stoebe, and C. stoebe populations varied in competitive effects. The competitive effects of C. stoebe populations increased with N whereas the competitive effects of NA species decreased, eliminating the overall competitive advantage demonstrated by NA species in soil without N added. These results suggest that simulated N deposition may enhance C. stoebe invasion through increasing its growth and relative competitive advantage, and also indicate the possibility of local adaptation in competitive effects across the introduced range of an invader

Nutrition and inflammation serum biomarkers are associated with 12-week mortality among malnourished adults initiating antiretroviral therapy in Zambia

<p>Abstract</p> <p>Background</p> <p>A low body mass index (BMI) at antiretroviral therapy (ART) initiation is a strong predictor of mortality among HIV-infected adults in resource-constrained settings. The relationship between nutrition and inflammation-related serum biomarkers and early treatment outcomes (e.g., less than 90 days) in this population is not well described.</p> <p>Methods</p> <p>An observational cohort of 142 HIV-infected adults in Lusaka, Zambia, with BMI under 16 kg/m²or CD4⁺lymphocyte counts of less than 50 cells/mm³, or both, was followed prospectively during the first 12 weeks of ART. Baseline and serial post-treatment phosphate, albumin, ferritin and highly sensitive C-reactive protein (hsCRP) serum levels were measured. The primary outcome was mortality.</p> <p>Results</p> <p>Lower baseline phosphate and albumin serum levels, and higher ferritin and hsCRP, were significantly associated with mortality prior to 12 weeks (p < 0.05 for all comparisons), independent of known risk factors for early ART-associated mortality in sub-Saharan Africa. The time-dependent interval change in albumin was associated with mortality after adjusting for the baseline value (AHR 0.62 [0.43, 0.89] per 5 g/L increase), but changes in the other biomarkers were not.</p> <p>Conclusions</p> <p>The predictive value of serum biomarkers for early mortality in a cohort of adults with malnutrition and advanced HIV in a resource-constrained setting was primarily driven by pre-treatment values, rather than post-ART changes. Interventions to promote earlier HIV diagnosis and treatment, address nutritional deficiencies, and identify the etiologies of increased systemic inflammation may improve ART outcomes in this vulnerable population.</p

SNW1 Is a Critical Regulator of Spatial BMP Activity, Neural Plate Border Formation, and Neural Crest Specification in Vertebrate Embryos

In frog and fish embryos, SNW1 is a protein required for the spatio-temporal activity of BMP signaling necessary for neural plate border formation and specification of neural crest tissue

Fever as a Cause of Hypophosphatemia in Patients with Malaria

Hypophosphatemia occurs in 40 to 60% of patients with acute malaria, and in many other conditions associated with elevations of body temperature. To determine the prevalence and causes of hypophosphatemia in patients with malaria, we retrospectively studied all adults diagnosed with acute malaria during a 12-year period. To validate our findings, we analyzed a second sample of malaria patients during a subsequent 10-year period. Serum phosphorus correlated inversely with temperature (n = 59, r = −0.62; P<0.0001), such that each 1°C increase in body temperature was associated with a reduction of 0.18 mmol/L (0.56 mg/dL) in the serum phosphorus level (95% confidence interval: −0.12 to −0.24 mmol/L [−0.37 to −0.74 mg/dL] per 1°C). A similar effect was observed among 19 patients who had repeat measurements of serum phosphorus and temperature. In a multiple linear regression analysis, the relation between temperature and serum phosphorus level was independent of blood pH, PCO2, and serum levels of potassium, bicarbonate, calcium, albumin, and glucose. Our study demonstrates a strong inverse linear relation between body temperature and serum phosphorus level that was not explained by other factors known to cause hypophosphatemia. If causal, this association can account for the high prevalence of hypophosphatemia, observed in our patients and in previous studies of patients with malaria. Because hypophosphatemia has been observed in other clinical conditions characterized by fever or hyperthermia, this relation may not be unique to malaria. Elevation of body temperature should be added to the list of causes of hypophosphatemia