First passage time statistics of Brownian motion with purely time dependent drift and diffusion

Systems where resource availability approaches a critical threshold are common to many engineering and scientific applications and often necessitate the estimation of first passage time statistics of a Brownian motion (Bm) driven by time-dependent drift and diffusion coefficients. Modeling such systems requires solving the associated Fokker-Planck equation subject to an absorbing barrier. Transitional probabilities are derived via the method of images, whose applicability to time dependent problems is shown to be limited to state-independent drift and diffusion coefficients that only depend on time and are proportional to each other. First passage time statistics, such as the survival probabilities and first passage time densities are obtained analytically. The analysis includes the study of different functional forms of the time dependent drift and diffusion, including power-law time dependence and different periodic drivers. As a case study of these theoretical results, a stochastic model for water availability from surface runoff in snowmelt dominated regions is presented, where both temperature effects and snow-precipitation input are incorporated

Elastic scattering of O-17+Pb-208 at energies near the Coulomb barrier

Within the frame of the commissioning of a new experimental apparatus EXPADES we undertook the measurement of the elastic scattering angular distribution for the system O-17+Pb-208 at energy around the Coulomb barrier. The reaction dynamics induced by loosely bound Radioactive Ion Beams is currently being extensively studied [4]. In particular the study of the elastic scattering process allows to obtain direct information on the total reaction cross section of the exotic nuclei. In order to understand the effect of the low binding energy on the reaction mechanism it is important to compare radioactive weakly bound nuclei with stable strongly-bound nuclei. In this framework the study of the O-17+Pb-208 elastic scattering can be considered to be complementary to a previous measurement of the total reaction cross section for the system F-17+Pb-208 at energies of 86, 90.4 MeV [5, 6]. The data will be compared with those obtained for the neighboring systems O-16,O-18+Pb-208 and others available in literature

Ambient Metals, Elemental Carbon, and Wheeze and Cough in New York City Children through 24 Months of Age

Rationale: The effects of exposure to specific components of ambient fine particulate matter (PM2.5), including metals and elemental carbon (EC), have not been fully characterized in young children. Objectives: To compare temporal associations among PM2.5; individual metal constituents of ambient PM2.5, including nickel (Ni), vanadium (V), and zinc (Zn); and EC and longitudinal reports of respiratory symptoms through 24 months of age. Methods: Study participants were selected from the Columbia Center for Children's Environmental Health birth cohort recruited in New York City between 1998 and 2006. Respiratory symptom data were collected by questionnaire every 3 months through 24 months of age. Ambient pollutant data were obtained from state-operated stationary monitoring sites located within the study area. For each subject, 3-month average inverse-distance weighted concentrations of Ni, V, Zn, EC, and PM2.5 were calculated for each symptom-reporting period based on the questionnaire date and the preceding 3 months. Associations between pollutants and symptoms were characterized using generalized additive mixed effects models, adjusting for sex, ethnicity, environmental tobacco smoke exposure, and calendar time. Measurements and Main Results: Increases in ambient Ni and V concentrations were associated significantly with increased probability of wheeze. Increases in EC were associated significantly with cough during the cold/flu season. Total PM2.5 was not associated with wheeze or cough. Conclusions: These results suggest that exposure to ambient metals and EC from heating oil and/or traffic at levels characteristic of urban environments may be associated with respiratory symptoms among very young children

A probabilistic sediment cascade model of sediment transfer in the Illgraben

We present a probabilistic sediment cascade model to simulate sediment transfer in a mountain basin (Illgraben, Switzerland) where sediment is produced by hillslope landslides and rockfalls and exported out of the basin by debris flows and floods. The model conceptualizes the fluvial system as a spatially lumped cascade of connected reservoirs representing hillslope and channel storages where sediment goes through cycles of storage and remobilization by surface runoff. The model includes all relevant hydrological processes that lead to runoff formation in an Alpine basin, such as precipitation, snow accumulation, snowmelt, evapotranspiration, and soil water storage. Although the processes of sediment transfer and debris flow generation are described in a simplified manner, the model produces complex sediment discharge behavior which is driven by the availability of sediment and antecedent wetness conditions (system memory) as well as the triggering potential (climatic forcing). The observed probability distribution of debris flow volumes and their seasonality in 2000–2009 are reproduced. The stochasticity of hillslope sediment input is important for reproducing realistic sediment storage variability, although many details of the hillslope landslide triggering procedures are filtered out by the sediment transfer system. The model allows us to explicitly quantify the division into transport and supply-limited sediment discharge events. We show that debris flows may be generated for a wide range of rainfall intensities because of variable antecedent basin wetness and snowmelt contribution to runoff, which helps to understand the limitations of methods based on a single rainfall threshold for debris flow initiation in Alpine basins

Heterozygous missense mutations in steroidogenic factor 1 (SF1/Ad4BP, NR5A1) are associated with 46,XY disorders of sex development with normal adrenal function

Context: Steroidogenic factor 1 ( SF1/AdBP4/FTZF1, NR5A1) is a nuclear receptor transcription factor that plays a key role in regulating adrenal and gonadal development, steroidogenesis, and reproduction. Targeted deletion of Nr5a1 ( Sf1) in the mouse results in adrenal and gonadal agenesis, XY sex-reversal, and persistent Mullerian structures in males. Consistent with the murine phenotype, human mutations in SF1 were described initially in two 46, XY individuals with female external genitalia, Mullerian structures ( uterus), and primary adrenal failure.Objective: Given recent case reports of haploinsufficiency of SF1 affecting testicular function in humans, we aimed to identify SF1 mutations in a cohort of individuals with a phenotypic spectrum of 46, XY gonadal dysgenesis/impaired androgenization ( now termed 46, XY disorders of sex development) with normal adrenal function.Methods and Patients: The study included mutational analysis of NR5A1 in 30 individuals with 46, XY disorders of sex development, followed by functional studies of SF1 activity.Results: Heterozygous missense mutations in NR5A1 were found in four individuals ( four of 30, 13%) with this phenotype. These mutations ( V15M, M78I, G91S, L437Q) were shown to impair transcriptional activation through abnormal DNA binding ( V15M, M78I, G91S), altered subnuclear localization ( V15M, M78I), or disruption of the putative ligand-binding pocket ( L437Q). Two mutations appeared to be de novo or germline changes. The other two mutations appeared to be inherited in a sex-limited dominant manner because the mother is heterozygous for the change.Conclusions: These studies demonstrate that SF1 mutations are more frequent than previously suspected causes of impaired fetal and postnatal testicular function in 46, XY individuals

Clinical pregenetic screening for stroke monogenic diseases: Results from lombardia GENS registry

BACKGROUND AND PURPOSE: Lombardia GENS is a multicentre prospective study aimed at diagnosing 5 single-gene disorders associated with stroke (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry disease, MELAS [mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes], hereditary cerebral amyloid angiopathy, and Marfan syndrome) by applying diagnostic algorithms specific for each clinically suspected disease METHODS: We enrolled a consecutive series of patients with ischemic or hemorrhagic stroke or transient ischemic attack admitted in stroke units in the Lombardia region participating in the project. Patients were defined as probable when presenting with stroke or transient ischemic attack of unknown etiopathogenic causes, or in the presence of <3 conventional vascular risk factors or young age at onset, or positive familial history or of specific clinical features. Patients fulfilling diagnostic algorithms specific for each monogenic disease (suspected) were referred for genetic analysis. RESULTS: In 209 patients (57.4\ub114.7 years), the application of the disease-specific algorithm identified 227 patients with possible monogenic disease. Genetic testing identified pathogenic mutations in 7% of these cases. Familial history of stroke was the only significant specific feature that distinguished mutated patients from nonmutated ones. The presence of cerebrovascular risk factors did not exclude a genetic disease. CONCLUSIONS: In patients prescreened using a clinical algorithm for monogenic disorders, we identified monogenic causes of events in 7% of patients in comparison to the 1% to 5% prevalence reported in previous series

Study of the γ decay of high-lying states in 208Pb via inelastic scattering of 17O ions

High-lying states in 208Pb nucleus were populated via inelastic scattering of a 17O beam at bombarding energy of 20 MeV/u. Their subsequent gamma decay was measured with the detector system AGATA Demonstrator based on HPGe detectors, coupled to an array of large volume LaBr3:Ce scintillators. Preliminary results in comparison with (γ,γ′) data, for states in the 5–8 MeV energy interval, seem to indicate that in that region the states belong to two different groups one with a isoscalar character and the other with a isovector nature. This is similar to what was observed in other stable nuclei with (α,α′γ) experiments. The multipolarity of the observed gamma transitions is determined with remarkable sensitivity thanks to angular distribution measurements. Data aiming at studying the neutron decay of the Giant Quadrupole Resonance in the 208Pb by the high resolution measurement of the following gamma decay are also presented in their preliminary form

Shape evolution in the neutron-rich osmium isotopes:Prompt γ-ray spectroscopy of Os 196

The shape transition in the neutron-rich Os isotopes is studied by investigating the neutron-rich 196Os nucleus through in-beam γ-ray spectroscopy using a two-proton transfer reaction from a 198Pt target to a 82Se beam. The beam-like recoils were detected and identified with the large-acceptance magnetic spectrometer PRISMA, and the coincident γ rays were measured with the advanced gamma tracking array (AGATA) demonstrator. The de-excitation of the low-lying levels of the yrast-band of 196Os were identified for the first time. The results are compared with state-of-the-art beyond-mean-field calculations, performed for the even-even 188-198Os isotopes. The new results suggest a smooth transition in the Os isotopes from a more axial rotational behavior towards predominately vibrational nuclei through triaxial configurations. An almost perfect γ-unstable/triaxial rotor yrast band is predicted for 196Os which is in agreement with the experimentally measured excited state

Footprint of Positive Selection in Treponema pallidum subsp. pallidum Genome Sequences Suggests Adaptive Microevolution of the Syphilis Pathogen

In the rabbit model of syphilis, infection phenotypes associated with the Nichols and Chicago strains of Treponema pallidum (T. pallidum), though similar, are not identical. Between these strains, significant differences are found in expression of, and antibody responses to some candidate virulence factors, suggesting the existence of functional genetic differences between isolates. The Chicago strain genome was therefore sequenced and compared to the Nichols genome, available since 1998. Initial comparative analysis suggested the presence of 44 single nucleotide polymorphisms (SNPs), 103 small (≤3 nucleotides) indels, and 1 large (1204 bp) insertion in the Chicago genome with respect to the Nichols genome. To confirm the above findings, Sanger sequencing was performed on most loci carrying differences using DNA from Chicago and the Nichols strain used in the original T. pallidum genome project. A majority of the previously identified differences were found to be due to errors in the published Nichols genome, while the accuracy of the Chicago genome was confirmed. However, 20 SNPs were confirmed between the two genomes, and 16 (80.0%) were found in coding regions, with all being of non-synonymous nature, strongly indicating action of positive selection. Sequencing of 16 genomic loci harboring SNPs in 12 additional T. pallidum strains, (SS14, Bal 3, Bal 7, Bal 9, Sea 81-3, Sea 81-8, Sea 86-1, Sea 87-1, Mexico A, UW231B, UW236B, and UW249C), was used to identify “Chicago-“ or “Nichols -specific” differences. All but one of the 16 SNPs were “Nichols-specific”, with Chicago having identical sequences at these positions to almost all of the additional strains examined. These mutations could reflect differential adaptation of the Nichols strain to the rabbit host or pathoadaptive mutations acquired during human infection. Our findings indicate that SNPs among T. pallidum strains emerge under positive selection and, therefore, are likely to be functional in nature