Renormalization Group Running of Lepton Mixing Parameters in See-Saw Models with S4S_4 Flavor Symmetry

We study the renormalization group running of the tri-bimaximal mixing predicted by the two typical $S_4$ flavor models at leading order. Although the textures of the mass matrices are completely different, the evolution of neutrino mass and mixing parameters is found to display approximately the same pattern. For both normal hierarchy and inverted hierarchy spectrum, the quantum corrections to both atmospheric and reactor neutrino mixing angles are so small that they can be neglected. The evolution of the solar mixing angle $\theta_{12}$ depends on $\tan\beta$ and neutrino mass spectrum, the deviation from its tri-bimaximal value could be large. Taking into account the renormalization group running effect, the neutrino spectrum is constrained by experimental data on $\theta_{12}$ in addition to the self-consistency conditions of the models, and the inverted hierarchy spectrum is disfavored for large $\tan\beta$. The evolution of light-neutrino masses is approximately described by a common scaling factor.Comment: 23 pages, 6figure

Single-cell reconstruction of follicular remodeling in the human adult ovary

The ovary is perhaps the most dynamic organ in the human body, only rivaled by the uterus. The molecular mechanisms that regulate follicular growth and regression, ensuring ovarian tissue homeostasis, remain elusive. We have performed single-cell RNA-sequencing using human adult ovaries to provide a map of the molecular signature of growing and regressing follicular populations. We have identified different types of granulosa and theca cells and detected local production of components of the complement system by (atretic) theca cells and stromal cells. We also have detected a mixture of adaptive and innate immune cells, as well as several types of endothelial and smooth muscle cells to aid the remodeling process. Our results highlight the relevance of mapping whole adult organs at the single-cell level and reflect ongoing efforts to map the human body. The association between complement system and follicular remodeling may provide key insights in reproductive biology and (in) fertility

First Dark Matter Results from the XENON100 Experiment

The XENON100 experiment, in operation at the Laboratori Nazionali del Gran Sasso in Italy, is designed to search for dark matter WIMPs scattering off 62 kg of liquid xenon in an ultra-low background dual-phase time projection chamber. In this letter, we present first dark matter results from the analysis of 11.17 live days of non-blind data, acquired in October and November 2009. In the selected fiducial target of 40 kg, and within the pre-defined signal region, we observe no events and hence exclude spin-independent WIMP-nucleon elastic scattering cross-sections above 3.4 x 10^-44 cm^2 for 55 GeV/c^2 WIMPs at 90% confidence level. Below 20 GeV/c^2, this result constrains the interpretation of the CoGeNT and DAMA signals as being due to spin-independent, elastic, light mass WIMP interactions.Comment: 5 pages, 5 figures. Matches published versio

Material screening and selection for XENON100

Results of the extensive radioactivity screening campaign to identify materials for the construction of XENON100 are reported. This Dark Matter search experiment is operated underground at Laboratori Nazionali del Gran Sasso (LNGS), Italy. Several ultra sensitive High Purity Germanium detectors (HPGe) have been used for gamma ray spectrometry. Mass spectrometry has been applied for a few low mass plastic samples. Detailed tables with the radioactive contaminations of all screened samples are presented, together with the implications for XENON100.Comment: 8 pages, 1 figur

Dark Matter Results from 100 Live Days of XENON100 Data

We present results from the direct search for dark matter with the XENON100 detector, installed underground at the Laboratori Nazionali del Gran Sasso of INFN, Italy. XENON100 is a two-phase time projection chamber with a 62 kg liquid xenon target. Interaction vertex reconstruction in three dimensions with millimeter precision allows to select only the innermost 48 kg as ultra-low background fiducial target. In 100.9 live days of data, acquired between January and June 2010, no evidence for dark matter is found. Three candidate events were observed in a pre-defined signal region with an expected background of 1.8 +/- 0.6 events. This leads to the most stringent limit on dark matter interactions today, excluding spin-independent elastic WIMP-nucleon scattering cross-sections above 7.0x10^-45 cm^2 for a WIMP mass of 50 GeV/c^2 at 90% confidence level.Comment: 5 pages, 5 figures; matches accepted versio

Implications on Inelastic Dark Matter from 100 Live Days of XENON100 Data

The XENON100 experiment has recently completed a dark matter run with 100.9 live-days of data, taken from January to June 2010. Events in a 48kg fiducial volume in the energy range between 8.4 and 44.6 keVnr have been analyzed. A total of three events have been found in the predefined signal region, compatible with the background prediction of (1.8 \pm 0.6) events. Based on this analysis we present limits on the WIMP-nucleon cross section for inelastic dark matter. With the present data we are able to rule out the explanation for the observed DAMA/LIBRA modulation as being due to inelastic dark matter scattering off iodine at a 90% confidence level.Comment: 3 pages, 3 figure

Genome-Wide Identification of Binding Sites Defines Distinct Functions for Caenorhabditis elegans PHA-4/FOXA in Development and Environmental Response

Transcription factors are key components of regulatory networks that control development, as well as the response to environmental stimuli. We have established an experimental pipeline in Caenorhabditis elegans that permits global identification of the binding sites for transcription factors using chromatin immunoprecipitation and deep sequencing. We describe and validate this strategy, and apply it to the transcription factor PHA-4, which plays critical roles in organ development and other cellular processes. We identified thousands of binding sites for PHA-4 during formation of the embryonic pharynx, and also found a role for this factor during the starvation response. Many binding sites were found to shift dramatically between embryos and starved larvae, from developmentally regulated genes to genes involved in metabolism. These results indicate distinct roles for this regulator in two different biological processes and demonstrate the versatility of transcription factors in mediating diverse biological roles.Molecular and Cellular Biolog

Circadian variation in tamoxifen pharmacokinetics in mice and breast cancer patients

The anti-estrogen tamoxifen is characterized by a large variability in response, partly due to pharmacokinetic differences. We examined circadian variation in tamoxifen pharmacokinetics in mice and breast cancer patients. Pharmacokinetic analysis was performed in mice, dosed at six different times (24-h period). Tissue samples were used for mRNA expression analysis of drug-metabolizing enzymes. In patients, a cross-over study was performed. During three 24-h periods, after tamoxifen dosing at 8 a.m., 1 p.m., and 8 p.m., for at least 4 weeks, blood samples were collected for pharmacokinetic measurements. Differences in tamoxifen pharmacokinetics between administration times were assessed. The mRNA expression of drug-metabolizing enzymes showed circadian variation in mouse tissues. Tamoxifen exposure seemed to be highest after administration at midnight. In humans, marginal differences were observed in pharmacokinetic parameters between morning and evening administration. Tamoxifen Cmax and area under the curve (AUC)0–8 h were 20 % higher (P max was shorter (2.1 vs. 8.1 h; P = 0.001), indicating variation in absorption. Systemic exposure (AUC0–24 h) to endoxifen was 15 % higher (P < 0.001) following morning administration. The results suggest that dosing time is of marginal influence on tamoxifen pharmacokinetics. Our study was not designed to detect potential changes in clinical outcome or toxicity, based on a difference in the time of administration. Circadian rhythm may be one of the many determinants of the interpatient and intrapatient pharmacokinetic variability of tamoxifen

Copper-Mediated Amidation of Heterocyclic and Aromatic C−H Bonds

A copper-mediated aerobic coupling reaction enables direct amidation of heterocycles or aromatics having weakly acidic C−H bonds with a variety of nitrogen nucleophiles. These reactions provide efficient access to many biologically important skeletons, including ones with the potential to serve as inhibitors of HMTs.Chemistry and Chemical Biolog

High Content Image Analysis Identifies Novel Regulators of Synaptogenesis in a High-Throughput RNAi Screen of Primary Neurons

The formation of synapses, the specialized points of chemical communication between neurons, is a highly regulated developmental process fundamental to establishing normal brain circuitry. Perturbations of synapse formation and function causally contribute to human developmental and degenerative neuropsychiatric disorders, such as Alzheimer's disease, intellectual disability, and autism spectrum disorders. Many genes controlling synaptogenesis have been identified, but lack of facile experimental systems has made systematic discovery of regulators of synaptogenesis challenging. Thus, we created a high-throughput platform to study excitatory and inhibitory synapse development in primary neuronal cultures and used a lentiviral RNA interference library to identify novel regulators of synapse formation. This methodology is broadly applicable for high-throughput screening of genes and drugs that may rescue or improve synaptic dysfunction associated with cognitive function and neurological disorders.National Institutes of Health (U.S.) (MH095096)National Institutes of Health (U.S.) (R01 GM089652