Instrumental neutron activation analysis of an enriched 28Si single-crystal

The determination of the Avogadro constant plays a key role in the redefinition of the kilogram in terms of a fundamental constant. The present experiment makes use of a silicon single-crystal highly enriched in 28Si that must have a total impurity mass fraction smaller than a few parts in 109. To verify this requirement, we previously developed a relative analytical method based on neutron activation for the elemental characterization of a sample of the precursor natural silicon crystal WASO 04. The method is now extended to fifty-nine elements and applied to a monoisotopic 28Si single-crystal that was grown to test the achievable enrichment. Since this crystal was likely contaminated, this measurement tested also the detection capabilities of the analysis. The results quantified contaminations by Ge, Ga, As, Tm, Lu, Ta, W and Ir and, for a number of the detectable elements, demonstrated that we can already reach the targeted 1 ng/g detection limit.Comment: 9 pages, 1 figure, 1 tabl

Modal analysis of the lysozyme protein considering all-atom and coarse-grained finite element models

Proteins are the fundamental entities of several organic activities. They are essential for a broad range of tasks in a way that their shapes and folding processes are crucial to achieving proper biological functions. Low-frequency modes, generally associated with collective movements at terahertz (THz) and sub-terahertz frequencies, have been appointed as critical for the conformational processes of many proteins. Dynamic simulations, such as molecular dynamics, are vastly applied by biochemical researchers in this field. However, in the last years, proposals that define the protein as a simplified elastic macrostructure have shown appealing results when dealing with this type of problem. In this context, modal analysis based on different modelization techniques, i.e., considering both an all-atom (AA) and coarse-grained (CG) representation, is proposed to analyze the hen egg-white lysozyme. This work presents new considerations and conclusions compared to previous analyses. Experimental values for the B-factor, considering all the heavy atoms or only one representative point per amino acid, are used to evaluate the validity of the numerical solutions. In general terms, this comparison allows the assessment of the regional flexibility of the protein. Besides, the low computational requirements make this approach a quick method to extract the protein’s dynamic properties under scrutiny

Intercomparison of oceanic and atmospheric forced and coupled mesoscale simulations <br>Part I: Surface fluxes

International audienceA mesoscale non-hydrostatic atmospheric model has been coupled with a mesoscale oceanic model. The case study is a four-day simulation of a strong storm event observed during the SEMAPHORE experiment over a 500 × 500 km2 domain. This domain encompasses a thermohaline front associated with the Azores current. In order to analyze the effect of mesoscale coupling, three simulations are compared: the first one with the atmospheric model forced by realistic sea surface temperature analyses; the second one with the ocean model forced by atmospheric fields, derived from weather forecast re-analyses; the third one with the models being coupled. For these three simulations the surface fluxes were computed with the same bulk parametrization. All three simulations succeed well in representing the main oceanic or atmospheric features observed during the storm. Comparison of surface fields with in situ observations reveals that the winds of the fine mesh atmospheric model are more realistic than those of the weather forecast re-analyses. The low-level winds simulated with the atmospheric model in the forced and coupled simulations are appreciably stronger than the re-analyzed winds. They also generate stronger fluxes. The coupled simulation has the strongest surface heat fluxes: the difference in the net heat budget with the oceanic forced simulation reaches on average 50 Wm-2 over the simulation period. Sea surface-temperature cooling is too weak in both simulations, but is improved in the coupled run and matches better the cooling observed with drifters. The spatial distributions of sea surface-temperature cooling and surface fluxes are strongly inhomogeneous over the simulation domain. The amplitude of the flux variation is maximum in the coupled run. Moreover the weak correlation between the cooling and heat flux patterns indicates that the surface fluxes are not responsible for the whole cooling and suggests that the response of the ocean mixed layer to the atmosphere is highly non-local and enhanced in the coupled simulation

Evaluation of the pharmacodynamic and pharmacokinetic interaction between pagoclone and ethanol

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109936/1/cptclpt2003353.pd

Hyperparameter optimization for recommender systems through Bayesian optimization

AbstractRecommender systems represent one of the most successful applications of machine learning in B2C online services, to help the users in their choices in many web services. Recommender system aims to predict the user preferences from a huge amount of data, basically the past behaviour of the user, using an efficient prediction algorithm. One of the most used is the matrix-factorization algorithm. Like many machine learning algorithms, its effectiveness goes through the tuning of its hyper-parameters, and the associated optimization problem also called hyper-parameter optimization. This represents a noisy time-consuming black-box optimization problem. The related objective function maps any possible hyper-parameter configuration to a numeric score quantifying the algorithm performance. In this work, we show how Bayesian optimization can help the tuning of three hyper-parameters: the number of latent factors, the regularization parameter, and the learning rate. Numerical results are obtained on a benchmark problem and show that Bayesian optimization obtains a better result than the default setting of the hyper-parameters and the random search

Blood Pressure and Cognitive Decline Over 8 Years in Middle-Aged and Older Black and White Americans

Although the association between high blood pressure (BP), particularly in midlife, and late-life dementia is known, less is known about variations by race and sex. In a prospective national study of 22 164 blacks and whites ≥45 years without baseline cognitive impairment or stroke from the REGARDS cohort study (Reasons for Geographic and Racial Differences in Stroke), enrolled 2003 to 2007 and followed through September 2015, we measured changes in cognition associated with baseline systolic and diastolic BP (SBP and DBP), as well as pulse pressure (PP) and mean arterial pressure, and we tested whether age, race, and sex modified the effects. Outcomes were global cognition (Six-Item Screener; primary outcome), new learning (Word List Learning), verbal memory (Word List Delayed Recall), and executive function (Animal Fluency Test). Median follow-up was 8.1 years. Significantly faster declines in global cognition were associated with higher SBP, lower DBP, and higher PP with increasing age ( P<0.001 for age×SBP×follow-up-time, age×DBP×follow-up-time, and age×PP×follow-up-time interaction). Declines in global cognition were not associated with mean arterial pressure after adjusting for PP. Blacks, compared with whites, had faster declines in global cognition associated with SBP ( P=0.02) and mean arterial pressure ( P=0.04). Men, compared with women, had faster declines in new learning associated with SBP ( P=0.04). BP was not associated with decline of verbal memory and executive function, after controlling for the effect of age on cognitive trajectories. Significantly faster declines in global cognition over 8 years were associated with higher SBP, lower DBP, and higher PP with increasing age. SBP-related cognitive declines were greater in blacks and men

From traditional orchards to advanced fruitculture: establishing the bases of commercial horticulture in Afghanistan

The Afghan economy is based essentially on the primary sector and, namely, on fruit production. A cross road of trade along the "Silk route", local traditional fruitculture based on the bagh (home garden) is widely variegated in terms of species and varieties. Afghan fresh and dried fruits (namely raisins) and nuts, sweet and rich in flavors, are demanded by domestic and foreign consumers. The lack of traceability and quality of the propagation material has been considered one of the basic bottle necks hindering development of an advanced horticulture. During the period 2006-2015 the Perennial Horticulture Development Project (PHDP), funded by the EC-EuropeAid Program, has been supporting the Ministry of Agriculture, Irrigation and Livestock of Afghanistan through a process of collection and selection of local fruit varieties in order to improve the private nursery system, as well as perennial horticulture. About 850 accessions of different fruit tree species have been collected and entered into the National Collections at six PHD Centres, where they undergo a standardised characterisation and identification procedure in order to be formally registered in a national list, hence contributing to their safeguard and protection. The best accessions were used as source for a traced propagation system after phytosanitary indexing and also in numerous adaptive experimentations. The PHDP contributed in capacity building at technical and institutional level, fostering the establishment of nursery sector associations, providing expertise and developing the Afghanistan National Nursery Growers Organization (ANNGO) and the apex Afghanistan National Horticulture Development Organization (ANHDO), mainly concerned with value chains

Herpes zoster vaccination in the elderly subjects: improving awareness and uptake

Armando Stefanati, Nicoletta Valente, Silvia Lupi, Sara Previato, Matilde Giordani, Giovanni Gabutti Department of Medical Sciences, University of Ferrara, Ferrara, Italy Abstract: Herpes zoster (HZ) is a common disease in adults and older subjects solely related to the reactivation of latent varicella zoster virus in ganglia. The incidence of the disease increases with aging and the decline of varicella zoster virus-specific cell-mediated immunity. HZ has a significant impact on the quality of life of subjects during the acute phase. Besides, pain can persist even for a long time becoming chronic. The chronic pain following HZ is called postherpetic neuralgia, and it is a debilitating long-lasting condition, characterized by metameric pain, allodynia, and hyperalgesia. Therapeutic options against HZ and postherpetic neuralgia are often suboptimal and the impact of the disease and its complications on daily living activities is significant, especially in older subjects. Nowadays, a preventive approach to the disease is possible; as a matter of fact, a high-antigen content live vaccine is available. This vaccine has a good profile in terms of immunogenicity, efficacy, effectiveness, and safety and its use may prevent both HZ and postherpetic neuralgia. Nevertheless, the evaluation of the issues raised in countries that introduced this immunization show that both provider and patient barriers could have prevented a more robust uptake of HZ vaccination. In the USA, HZ immunization storage was expensive, reimbursement was cumbersome, and supply shortages may have limited promotion by the interests of the manufacturer and provider. The doctors did not actively recommend HZ vaccination; on the other hand, subjects were mostly unaware of the HZ vaccine. Several demographic factors, including sex and educational level, could have negatively affected the coverage rates; besides, the clinicians who treat adults focus less on vaccination than those taking care of children. On the other hand, when health care professionals undertook every effort to maximize the uptake of the shingles vaccine (eg, in the UK), the vaccine coverage rate increased very quickly. Keywords: herpes zoster, postherpetic neuralgia, vaccin

The trypanocidal benzoxaborole AN7973 inhibits trypanosome mRNA processing

Kinetoplastid parasites—trypanosomes and leishmanias—infect millions of humans and cause economically devastating diseases of livestock, and the few existing drugs have serious deficiencies. Benzoxaborole-based compounds are very promising potential novel anti-trypanosomal therapies, with candidates already in human and animal clinical trials. We investigated the mechanism of action of several benzoxaboroles, including AN7973, an early candidate for veterinary trypanosomosis. In all kinetoplastids, transcription is polycistronic. Individual mRNA 5'-ends are created by trans splicing of a short leader sequence, with coupled polyadenylation of the preceding mRNA. Treatment of Trypanosoma brucei with AN7973 inhibited trans splicing within 1h, as judged by loss of the Y-structure splicing intermediate, reduced levels of mRNA, and accumulation of peri-nuclear granules. Methylation of the spliced leader precursor RNA was not affected, but more prolonged AN7973 treatment caused an increase in S-adenosyl methionine and methylated lysine. Together, the results indicate that mRNA processing is a primary target of AN7973. Polyadenylation is required for kinetoplastid trans splicing, and the EC50 for AN7973 in T. brucei was increased three-fold by over-expression of the T. brucei cleavage and polyadenylation factor CPSF3, identifying CPSF3 as a potential molecular target. Molecular modeling results suggested that inhibition of CPSF3 by AN7973 is feasible. Our results thus chemically validate mRNA processing as a viable drug target in trypanosomes. Several other benzoxaboroles showed metabolomic and splicing effects that were similar to those of AN7973, identifying splicing inhibition as a common mode of action and suggesting that it might be linked to subsequent changes in methylated metabolites. Granule formation, splicing inhibition and resistance after CPSF3 expression did not, however, always correlate and prolonged selection of trypanosomes in AN7973 resulted in only 1.5-fold resistance. It is therefore possible that the modes of action of oxaboroles that target trypanosome mRNA processing might extend beyond CPSF3 inhibition