Vitamin D time profile based on the contribution of non-genetic and genetic factors in HIV-infected individuals of European ancestry

BACKGROUND Vitamin D deficiency is prevalent in HIV-infected individuals and vitamin D supplementation is proposed according to standard care. This study aimed at characterizing the kinetics of 25(OH)D in a cohort of HIV-infected individuals of European ancestry to better define the influence of genetic and non-genetic factors on 25(OH)D levels. These data were used for the optimization of vitamin D supplementation in order to reach therapeutic targets. METHODS 1,397 25(OH)D plasma levels and relevant clinical information were collected in 664 participants during medical routine follow up visits. They were genotyped for 7 SNPs in 4 genes known to be associated with 25(OH)D levels. 25(OH)D concentrations were analyzed using a population pharmacokinetic approach. The percentage of individuals with 25(OH)D concentrations within the recommended range of 20-40ng/ml during 12 months of follow up and several dosage regimens were evaluated by simulation. RESULTS A one-compartment model with linear absorption and elimination was used to describe 25(OH)D pharmacokinetics, while integrating endogenous baseline plasma concentrations. Covariate analyses confirmed the effect of seasonality, body mass index, smoking habits, the analytical method, darunavir/r and the genetic variant in GC (rs2282679) on 25(OH)D concentrations. 11% of the interindividual variability in 25(OH)D levels was explained by seasonality and other non-genetic covariates and 1% by genetics. The optimal supplementation for severe vitamin D deficient patients was 300000 IU two times per year. CONCLUSIONS This analysis allowed identifying factors associated with 25(OH)D plasma levels in HIV-infected individuals. Improvement of dosage regimen and timing of vitamin D supplementation is proposed based on those results.

In vitro activity of clinically implemented β-lactams against Aerococcus urinae: presence of non-susceptible isolates in Switzerland.

We analyzed the in vitro susceptibility to several ?-lactams and vancomycin of 80 Aerococcus urinae isolates col- lected during 2011-2012 in Switzerland. MICs were determined by Etest (bioMérieux) on Müller-Hinton agar with 5% sheep blood and interpreted according to the CLSI and EUCAST criteria set for viridans streptococci. MIC50/90 for penicillin, amoxicillin, ceftriaxone and vancomycin were 0.016/0.064 mg/l, 0.032/0.064 mg/l, 0.125/0.5 mg/l and 0.38/0.5 mg/l, respectively. Three (3.8%) isolates were resistant to ceftriaxone regardless of the criteria used (MICs ?2 mg/l); one of them was also non-susceptible to penicillin (MIC of 0.25 mg/l) according to CLSI. ?-lactam resis- tance in A. urinae is a concern and suggests that more studies are needed to determine the molecular mechanisms of such resistance.

Quantum Simulation of Non-Abelian Lattice Gauge Theories

We use quantum link models to construct a quantum simulator for U(N) and SU(N) lattice gauge theories. These models replace Wilson’s classical link variables by quantum link operators, reducing the link Hilbert space to a finite number of dimensions. We show how to embody these quantum link models with fermionic matter with ultracold alkaline-earth atoms using optical lattices. Unlike classical simulations, a quantum simulator does not suffer from sign problems and can thus address the corresponding dynamics in real time. Using exact diagonalization results we show that these systems share qualitative features with QCD, including chiral symmetry breaking and we study the expansion of a chirally restored region in space in real time.

Facebook style: The use of non-standard features in virtual speech conditioned by the medium Facebook

Over the last few years Facebook has become a widespread and continuously expanding medium of communication. Being a new medium of social interaction, Facebook produces its own communication style. My focus of analysis is how Facebook users from the city of Malaga create this style by means of phonic features typical of the Andalusian variety and how the users reflect on the use of these phonic features. This project is based on a theoretical framework which combines variationist sociolinguistics with CMC to study the emergence of a style peculiar of the online social networks. In a corpus of Facebook users from three zones of Malaga, I have analysed the use of non-standard phonic features and then compared them with the same features in a reference corpus collected on three beaches of Malaga. From this comparison it can be deduced that the analysed social and linguistic factors work differently in real and virtual speech. Due to these different uses we can consider the peculiar electronic communication of Facebook as a style constrained by the electronic medium. It is a style which serves the users to create social meaning and to express their linguistic identities.

Increased number of non-degranulated mast cells in pancreatic ductal adenocarcinoma but not in acute pancreatitis.

Increasing evidence indicates that tumor microenvironment (TME) is crucial in tumor survival and metastases. Inflammatory cells accumulate around tumors and strangely appear to be permissive to their growth. One key stroma cell is the mast cell (MC), which can secrete numerous pro- and antitumor molecules. We investigated the presence and degranulation state of MC in pancreatic ductal adenocarcinoma (PDAC) as compared to acute ancreatitis (AP). Three different detection methods: (a) toluidine blue staining, as well as immunohistochemistry for (b) tryptase and (c) c-kit, were utilized to assess the number and extent of degranulation of MC in PDAC tissue (n=7), uninvolved pancreatic tissue derived from tumor-free margins (n=7) and tissue form AP (n=4). The number of MC detected with all three methods was significantly increased in PDAC, as compared to normal pancreatic tissue derived from tumor-free margins (p<0.05). The highest number of MC was identified by c-kit, 22.2∓7.5 per high power field (HPF) in PDAC vs 9.7∓5.1 per HPF in normal tissue. Contrary to MC in AP, where most of the detected MC were found degranulated, MC in PDAC appeared intact. In conclusion, MC are increased in number, but not degranulated in PDAC, suggesting that they may contribute to cancer growth by permitting selective release of pro-tumorogenic molecules.

De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy.

Epileptic encephalopathies are a phenotypically and genetically heterogeneous group of severe epilepsies accompanied by intellectual disability and other neurodevelopmental features. Using next-generation sequencing, we identified four different de novo mutations in KCNA2, encoding the potassium channel KV1.2, in six isolated patients with epileptic encephalopathy (one mutation recurred three times independently). Four individuals presented with febrile and multiple afebrile, often focal seizure types, multifocal epileptiform discharges strongly activated by sleep, mild to moderate intellectual disability, delayed speech development and sometimes ataxia. Functional studies of the two mutations associated with this phenotype showed almost complete loss of function with a dominant-negative effect. Two further individuals presented with a different and more severe epileptic encephalopathy phenotype. They carried mutations inducing a drastic gain-of-function effect leading to permanently open channels. These results establish KCNA2 as a new gene involved in human neurodevelopmental disorders through two different mechanisms, predicting either hyperexcitability or electrical silencing of KV1.2-expressing neurons.

The applicability of using different energy levels in CT imaging for differentiation or identification of dental restorative materials.

PURPOSE The goal of this study was to investigate whether different computed tomography (CT) energy levels could supply additional information for the differentiation of dental materials for forensic investigations. METHODS Nine different commonly used restorative dental materials were investigated in this study. A total of 75 human third molars were filled with the restorative dental materials and then scanned using the forensic reference phantom in singlesource mode. The mean Hounsfield unit values and standard deviations (SDs) of each material were calculated at 120, 80 and 140 kVp. RESULTS Most of the dental materials could be differentiated at 120 kVp. We found that greater X-ray density of a material resulted in higher SDs and that the material volume could influence the measurements. CONCLUSION Differentiation of dental materials in CT was possible in many cases using single-energy CT scans at 120 kVp. Because of the number of dental restorative materials available and scanner and scan parameter dependence, as well as the CT imaging artifacts, the identification (in contrast to differentiation) was problematic.

Competitive fitness in coronaviruses is not correlated with size or number of double-membrane vesicles under reduced-temperature growth conditions.

Positive-stranded viruses synthesize their RNA in membrane-bound organelles, but it is not clear how this benefits the virus or the host. For coronaviruses, these organelles take the form of double-membrane vesicles (DMVs) interconnected by a convoluted membrane network. We used electron microscopy to identify murine coronaviruses with mutations in nsp3 and nsp14 that replicated normally while producing only half the normal amount of DMVs under low-temperature growth conditions. Viruses with mutations in nsp5 and nsp16 produced small DMVs but also replicated normally. Quantitative reverse transcriptase PCR (RT-PCR) confirmed that the most strongly affected of these, the nsp3 mutant, produced more viral RNA than wild-type virus. Competitive growth assays were carried out in both continuous and primary cells to better understand the contribution of DMVs to viral fitness. Surprisingly, several viruses that produced fewer or smaller DMVs showed a higher fitness than wild-type virus at the reduced temperature, suggesting that larger and more numerous DMVs do not necessarily confer a competitive advantage in primary or continuous cell culture. For the first time, this directly demonstrates that replication and organelle formation may be, at least in part, studied separately during infection with positive-stranded RNA virus. IMPORTANCE The viruses that cause severe acute respiratory syndrome (SARS), poliomyelitis, and hepatitis C all replicate in double-membrane vesicles (DMVs). The big question about DMVs is why they exist in the first place. In this study, we looked at thousands of infected cells and identified two coronavirus mutants that made half as many organelles as normal and two others that made typical numbers but smaller organelles. Despite differences in DMV size and number, all four mutants replicated as efficiently as wild-type virus. To better understand the relative importance of replicative organelles, we carried out competitive fitness experiments. None of these viruses was found to be significantly less fit than wild-type, and two were actually fitter in tests in two kinds of cells. This suggests that viruses have evolved to have tremendous plasticity in the ability to form membrane-associated replication complexes and that large and numerous DMVs are not exclusively associated with efficient coronavirus replication.

Superspace description of wagnerite-group minerals (Mg,Fe,Mn) 2 (PO 4 )(F,OH)

Reinvestigation of more than 40 samples of minerals belonging to the wagnerite group (Mg, Fe, Mn)2(PO4)(F,OH) from diverse geological environments worldwide, using single-crystal X-ray diffraction analysis, showed that most crystals have incommensurate structures and, as such, are not adequately described with known polytype models (2b), (3b), (5b), (7b) and (9b). Therefore, we present here a unified superspace model for the structural description of periodically and aperiodically modulated wagnerite with the (3+1)-dimensional superspace group C2/c(0[beta]0)s0 based on the average triplite structure with cell parameters a [asymptotically equal to] 12.8, b [asymptotically equal to] 6.4, c [asymptotically equal to] 9.6 Å, [beta] [asymptotically equal to] 117° and the modulation vectors q = [beta]b*. The superspace approach provides a way of simple modelling of the positional and occupational modulation of Mg/Fe and F/OH in wagnerite. This allows direct comparison of crystal properties.

The Nile perch invasion in Lake Victoria: cause or consequence of the haplochromine decline?

We review alternative hypotheses and associated mechanisms to explain Lake Victoria’s Nile perch takeover and concurrent reduction in haplochromines through a (re)analysis of long term climate, limnological and stock observations in comparison with size-spectrum model predictions of co-existence, extinction and demographic change. The empirical observations are in agreement with the outcomes of the model containing two interacting species with life-histories matching Nile perch and a generalized haplochromine. The dynamic interactions may have depended on size related differences in early juvenile mortality: mouth-brooding haplochromines escape predation mortality in early life stages, unlike Nile perch that have miniscule planktonic eggs and larvae. In our model predation on the latter by planktivorous haplochromine fry act as a stabilizing factor for co-existence, but external mortality on the haplochromines would disrupt this balance in favor of Nile perch. To explain the observed switch, mortality on haplochromines would need to be much higher than the fishing mortality that can be realistically re-constructed from observations. Abrupt concomitant changes in algal and zooplankton composition, decreased water column transparency, and widespread hypoxia from increased eutrophication most likely caused haplochromine biomass decline. We hypothesize that the shift to Nile perch was a consequence of an externally caused, climate triggered, decrease in haplochromine biomass and associated recruitment failure rather than a direct cause of the introduction.

Photometric monitoring of non-resolved space debris and databases of optical light curves.

The population of space debris increased drastically during the last years. Collisions involving massive objects may produce large number of fragments leading to significantly growth of the space debris population. An effective remediation measure in order to stabilize the population in LEO, is therefore the removal of large, massive space debris. To remove these objects, not only precise orbits, but also more detailed information about their attitude states will be required. One important property of an object targeted for removal is its spin period and spin axis orientation. If we observe a rotating object, the observer sees different surface areas of the object which leads to changes in the measured intensity. Rotating objects will produce periodic brightness vari ations with frequencies which are related to the spin periods. Photometric monitoring is the real tool for remote diagnostics of the satellite rotation around its center of mass. This information is also useful, for example, in case of contingency. Moreover, it is also important to take into account the orientation of non-spherical body (e.g. space debris) in the numerical integration of its motion when a close approach with the another spacecr aft is predicted. We introduce the two databases of light curves: the AIUB data base, which contains about a thousand light curves of LEO, MEO and high-altitude debris objects (including a few functional objects) obtained over more than seven years, and the data base of the Astronomical Observatory of Odessa University (Ukraine), which contains the results of more than 10 years of photometric monitoring of functioning satellites and large space debris objects in low Earth orbit. AIUB used its 1m ZIMLAT telescope for all light curves. For tracking low-orbit satellites, the Astronomical Observatory of Odessa used the KT-50 telescope, which has an alt-azimuth mount and allows tracking objects moving at a high angular velocity. The diameter of the KT-50 main mirror is 0.5 m, and the focal length is 3 m. The Odessa's Atlas of light curves includes almost 5,5 thousand light curves for ~500 correlated objects from a time period of 2005-2014. The processing of light curves and the determination of the rotation period in the inertial frame is challenging. Extracted frequencies and reconstructed phases for some interesting targets, e.g. GLONASS satellites, for which also SLR data were available for confirmation, will be presented. The rotation of the Envisat satellite after its sudden failure will be analyzed. The deceleration of its rotation rate within 3 years is studied together with the attempt to determine the orientation of the rotation axis.