Study of isotopic variations in black powder: reflections on the use of stable isotopes in forensic science for source inference.

Isotope ratio mass spectrometry (IRMS) has recently made its appearance in the forensic community. This high-precision technology has already been applied to a broad range of forensic fields such as illicit drugs, explosives and flammable liquids, where current, routinely used techniques have limited powers of discrimination. The conclusions drawn from the majority of these IRMS studies appear to be very promising. Used in a comparative process, as in food or drug authentication, the measurement of stable isotope ratios is a new and remarkable analytical tool for the discrimination or the identification of a substance with a definite source or origin. However, the research consists mostly of preliminary studies. The significance of this 'new' piece of information needs to be evaluated in light of a forensic framework to assess the actual potential and validity of IRMS, considering the characteristics of each field. Through the isotopic study of black powder, this paper aims at illustrating the potential of the method and the limitations of current knowledge in stable isotopes when facing forensic problems.

The Besançon Galaxy Model renewed. I. Constraints on the Galactic thin disc evolution from Tycho data

Context. The understanding of Galaxy evolution can be facilitated by the use of population synthesis models, which allow to test hypotheses on the star formation history, star evolution, as well as chemical and dynamical evolution of the Galaxy. Aims. The new version of the Besanc¸on Galaxy Model (hereafter BGM) aims to provide a more flexible and powerful tool to investigate the Initial Mass Function (IMF) and Star Formation Rate (SFR) of the Galactic disc. Methods. We present a new strategy for the generation of thin disc stars which assumes the IMF, SFR and evolutionary tracks as free parameters. We have updated most of the ingredients for the star count production and, for the first time, binary stars are generated in a consistent way. We keep in this new scheme the local dynamical self-consistency as in Bienayme et al (1987). We then compare simulations from the new model with Tycho-2 data and the local luminosity function, as a first test to verify and constrain the new ingredients. The effects of changing thirteen different ingredients of the model are systematically studied. Results. For the first time, a full sky comparison is performed between BGM and data. This strategy allows to constrain the IMF slope at high masses which is found to be close to 3.0, excluding a shallower slope such as Salpeter"s one. The SFR is found decreasing whatever IMF is assumed. The model is compatible with a local dark matter density of 0.011 M pc−3 implying that there is no compelling evidence for significant amount of dark matter in the disc. While the model is fitted to Tycho2 data, a magnitude limited sample with V<11, we check that it is still consistent with fainter stars. Conclusions. The new model constitutes a new basis for further comparisons with large scale surveys and is being prepared to become a powerful tool for the analysis of the Gaia mission data.

When cholesterol is not cholesterol: a note on the enzymatic determination of its concentration in model systems containing vegetable extracts

Background: Experimental evidences demonstrate that vegetable derived extracts inhibit cholesterol absorption in the gastrointestinal tract. To further explore the mechanisms behind, we modeled duodenal contents with several vegetable extracts. Results: By employing a widely used cholesterol quantification method based on a cholesterol oxidase-peroxidase coupled reaction we analyzed the effects on cholesterol partition. Evidenced interferences were analyzed by studying specific and unspecific inhibitors of cholesterol oxidase-peroxidase coupled reaction. Cholesterol was also quantified by LC/MS. We found a significant interference of diverse (cocoa and tea-derived) extracts over this method. The interference was strongly dependent on model matrix: while as in phosphate buffered saline, the development of unspecific fluorescence was inhibitable by catalase (but not by heat denaturation), suggesting vegetable extract derived H2O2 production, in bile-containing model systems, this interference also comprised cholesterol-oxidase inhibition. Several strategies, such as cholesterol standard addition and use of suitable blanks containing vegetable extracts were tested. When those failed, the use of a mass-spectrometry based chromatographic assay allowed quantification of cholesterol in models of duodenal contents in the presence of vegetable extracts. Conclusions: We propose that the use of cholesterol-oxidase and/or peroxidase based systems for cholesterol analyses in foodstuffs should be accurately monitored, as important interferences in all the components of the enzymatic chain were evident. The use of adequate controls, standard addition and finally, chromatographic analyses solve these issues.

Effect of gibberellic acid and the biostimulant stimulate® on the initial growth of tamarind

Plant growth regulators and biostimulants have been used as an agronomic technique to optimize the production of seedlings in various crops. This study aimed to evaluate the influence of gibberellic acid and the biostimulant Stimulate® on the initial growth of tamarind (Tamarindus indica L.). The experiments were conducted in a nursery with 50% shading, in a randomized block design with five replications and five plants per plot. Thirty eight days after sowing, the leaves were sprayed seven times a day with 0.0 (control), 0.8, 1.6, 2.4 and 3.2 mL of gibberellic acid L-1 aqueous solution and with 0.0 (control), 6.0,12.0, 18.0, and 24.0 mL Stimulate® L-1 aqueous solution. Stem diameter (SD), plant height (PH), longest root length (LRL), shoot dry mass (SDM), root dry mass (RDM) and RDM:SDM ratio were evaluated ninety days after sowing. Variance and regression analysis showed that GA3 at 4% promoted plant growth (height), but had no significant effect on stem diameter, longest root length, shoot and root dry mass and the RDM:SDM ratio. On the other hand, all concentrations of Stimulate® significantly increased plant height and shoot and root dry mass of tamarind seedlings.

On the relationship between C and N fixation in nodulated alfalfa (Medicago sativa)

Legumes such as alfalfa (Medicago sativa L.) are vital N2-fixing crops accounting for a global N2 fixation of ~35 MtNyear-1. Although enzymatic and molecular mechanisms of nodule N2 fixation are now well documented, some uncertainty remains as to whether N2 fixation is strictly coupled with photosynthetic carbon fixation. That is, the metabolic origin and redistribution of carbon skeletons used to incorporate nitrogen are still relatively undefined. Here, we conducted isotopic labelling with both 15N2 and 13C-depleted CO2 on alfalfa plants grown under controlled conditions and took advantage of isotope ratio mass spectrometry to investigate the relationship between carbon and nitrogen turn-over in respired CO2, total organic matter and amino acids. Our results indicate that CO2 evolved by respiration had an isotopic composition similar to that in organic matter regardless of the organ considered, suggesting that the turn-over of respiratory pools strictly followed photosynthetic input. However, carbon turn-over was nearly three times greater than N turn-over in total organic matter, suggesting that new organic material synthesised was less N-rich than pre-existing organic material (due to progressive nitrogen elemental dilution) or that N remobilisation occurred to sustain growth. This pattern was not consistent with the total commitment into free amino acids where the input of new C and N appeared to be stoichiometric. The labelling pattern in Asn was complex, with contrasted C and N commitments in different organs, suggesting that neosynthesis and redistribution of new Asn molecules required metabolic remobilisation. We conclude that the production of new organic material during alfalfa growth depends on both C and N remobilisation in different organs. At the plant level, this remobilisation is complicated by allocation and metabolism in the different organs. Additional keywords: carbon exchange, carbon isotopes, nitrogen fixation, nitrogen 15 isotope

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 analysed using a population pharmacokinetic approach. The percentage of individuals with 25(OH)D concentrations within the recommended range of 20-40 ng/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/ritonavir and the genetic variant in GC (rs2282679) on 25(OH)D concentrations. 11% of the inter-individual 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 300,000 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.

Effect of sex and prior exposure to a cafeteria diet on the distribution of sex hormones between plasma and blood cells

It is generally assumed that steroid hormones are carried in the blood free and/or bound to plasma proteins. We investigated whether blood cells were also able to bind/carry sex-related hormones: estrone, estradiol, DHEA and testosterone. Wistar male and female rats were fed a cafeteria diet for 30 days, which induced overweight. The rats were fed the standard rat diet for 15 additional days to minimize the immediate effects of excess ingested energy. Controls were always kept on standard diet. After the rats were killed, their blood was used for 1) measuring plasma hormone levels, 2) determining the binding of labeled hormones to washed red blood cells (RBC), 3) incubating whole blood with labeled hormones and determining the distribution of label between plasma and packed cells, discounting the trapped plasma volume, 4) determining free plasma hormone using labeled hormones, both through membrane ultrafiltration and dextrancharcoal removal. The results were computed individually for each rat. Cells retained up to 32% estrone, and down to 10% of testosterone, with marked differences due to sex and diet (the latter only for estrogens, not for DHEA and testosterone). Sex and diet also affected the concentrations of all hormones, with no significant diet effects for estradiol and DHEA, but with considerable interaction between both factors. Binding to RBC was non-specific for all hormones. Estrogen distribution in plasma compartments was affected by sex and diet. In conclusion: a) there is a large non-specific RBC-carried compartment for estrone, estradiol, DHEA and testosterone deeply affected by sex; b) Prior exposure to a cafeteria (hyperlipidic) diet induced hormone distribution changes, affected by sex, which hint at sex-related structural differences in RBC membranes; c) We postulate that the RBC compartment may contribute to maintain free (i.e., fully active) sex hormone levels in a way similar to plasma proteins non-specific binding.

Effect of radar rainfall time resolution on the predictive capability of a distributed hydrologic model

The performance of a hydrologic model depends on the rainfall input data, both spatially and temporally. As the spatial distribution of rainfall exerts a great influence on both runoff volumes and peak flows, the use of a distributed hydrologic model can improve the results in the case of convective rainfall in a basin where the storm area is smaller than the basin area. The aim of this study was to perform a sensitivity analysis of the rainfall time resolution on the results of a distributed hydrologic model in a flash-flood prone basin. Within such a catchment, floods are produced by heavy rainfall events with a large convective component. A second objective of the current paper is the proposal of a methodology that improves the radar rainfall estimation at a higher spatial and temporal resolution. Composite radar data from a network of three C-band radars with 6-min temporal and 2 × 2 km2 spatial resolution were used to feed the RIBS distributed hydrological model. A modification of the Window Probability Matching Method (gauge-adjustment method) was applied to four cases of heavy rainfall to improve the observed rainfall sub-estimation by computing new Z/R relationships for both convective and stratiform reflectivities. An advection correction technique based on the cross-correlation between two consecutive images was introduced to obtain several time resolutions from 1 min to 30 min. The RIBS hydrologic model was calibrated using a probabilistic approach based on a multiobjective methodology for each time resolution. A sensitivity analysis of rainfall time resolution was conducted to find the resolution that best represents the hydrological basin behaviour.

Influence of Gilbert's syndrome on the formation of ethyl glucuronide.

A drinking experiment with participants suffering from Gilbert's syndrome was performed to study the possible influence of this glucuronidation disorder on the formation of ethyl glucuronide (EtG). Gilbert's syndrome is a rather common and, in most cases, asymptomatic congenital metabolic aberration with a prevalence of about 5 %. It is characterized by a reduction of the enzyme activity of the uridine diphosphate glucuronosyltransferase (UGT) isoform 1A1 up to 80 %. One of the glucuronidation products is EtG, which is formed in the organism following exposure to ethanol. EtG is used as a short-term marker for ethyl alcohol consumption to prove abstinence in various settings. After 2 days of abstinence from ethanol and giving a void urine sample, 30 study participants drank 0.1 L of sparkling wine (9 g ethanol). 3, 6, 12, and 24 h after drinking, urine samples were collected. 3 hours after drinking, an additional blood sample was taken, in which liver enzyme activities, ethanol, hematological parameters, and bilirubin were measured. EtG and ethyl sulfate (EtS), another short-term marker of ethanol consumption, were determined in the urine samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS); creatinine was measured photometrically. In all participants, EtG and EtS were detected in concentrations showing a wide range (EtG: 3 h sample 0.5-18.43 mg/L and 6 h sample 0.67-13.8 mg/L; EtS: 3 h sample 0.87-6.87 mg/L and 6 h sample 0.29-4.48 mg/L). No evidence of impaired EtG formation was found. Thus, EtG seems to be a suitable marker for ethanol consumption even in individuals with Gilbert's syndrome.

Botulinum neurotoxin type A blocks the morphological changes induced by chemical stimulation on the presynaptic membrane of Torpedo synaptosomes.

The action of botulinum neurotoxin on acetylcholine release, and on the structural changes at the presynaptic membrane associated with the transmitter release,was studied by using a subcellular fraction of cholinergic nerve terminals (synaptosomes) isolated from the Torpedo electric organ. Acetylcholine and ATP release were continuously monitored by chemiluminescent methods.To catch the membrane morphological changes, the quick-freezing method was applied. Our results show that botulinum neurotoxin inhibits the release of acetylcholine from these isolated nerve terminals in a dose-dependent manner, whereas ATP release is not affected. The maximal inhibition (70%) is achieved at neurotoxin concentrations as low as 125 pM with an incubation time of 6 min. This effect is not linked to an alteration of the integrity of the synaptosomes since, after poisoning by botulinum neurotoxin type A, they show a nonmodified occluded lactate dehydrogenase activity. Moreover, membrane potential is not altered by the toxin with respect to the control, either in resting condition or after potassium depolarization. In addition to acetylcholine release inhibition, botulinum neurotoxin blocks the rearrangement of the presynaptic intramembrane particles induced by potassium stimulation. The action of botulinum neurotoxin suggests that the intramembrane particle rearrangement is related to the acetylcholine secretion induced by potassium stimulation in synaptosomes isolated from the electric organ of Torpedo marmorata.

On the Analysis and Control of a Linear Synchronous Servomotor with a Flexible Load

Industry's growing need for higher productivity is placing new demands on mechanisms connected with electrical motors, because these can easily lead to vibration problems due to fast dynamics. Furthermore, the nonlinear effects caused by a motor frequently reduce servo stability, which diminishes the controller's ability to predict and maintain speed. Hence, the flexibility of a mechanism and its control has become an important area of research. The basic approach in control system engineering is to assume that the mechanism connected to a motor is rigid, so that vibrations in the tool mechanism, reel, gripper or any apparatus connected to the motor are not taken into account. This might reduce the ability of the machine system to carry out its assignment and shorten the lifetime of the equipment. Nonetheless, it is usually more important to know how the mechanism, or in other words the load on the motor, behaves. A nonlinear load control method for a permanent magnet linear synchronous motor is developed and implemented in the thesis. The purpose of the controller is to track a flexible load to the desired velocity reference as fast as possible and without awkward oscillations. The control method is based on an adaptive backstepping algorithm with its stability ensured by the Lyapunov stability theorem. As a reference controller for the backstepping method, a hybrid neural controller is introduced in which the linear motor itself is controlled by a conventional PI velocity controller and the vibration of the associated flexible mechanism is suppressed from an outer control loop using a compensation signal from a multilayer perceptron network. To avoid the local minimum problem entailed in neural networks, the initial weights are searched for offline by means of a differential evolution algorithm. The states of a mechanical system for controllers are estimated using the Kalman filter. The theoretical results obtained from the control design are validated with the lumped mass model for a mechanism. Generalization of the mechanism allows the methods derived here to be widely implemented in machine automation. The control algorithms are first designed in a specially introduced nonlinear simulation model and then implemented in the physical linear motor using a DSP (Digital Signal Processor) application. The measurements prove that both controllers are capable of suppressing vibration, but that the backstepping method is superior to others due to its accuracy of response and stability properties.

The Besançon Galaxy Model renewed. I. Constraints on the Galactic thin disc evolution from Tycho data

Context. The understanding of Galaxy evolution can be facilitated by the use of population synthesis models, which allow to test hypotheses on the star formation history, star evolution, as well as chemical and dynamical evolution of the Galaxy. Aims. The new version of the Besanc¸on Galaxy Model (hereafter BGM) aims to provide a more flexible and powerful tool to investigate the Initial Mass Function (IMF) and Star Formation Rate (SFR) of the Galactic disc. Methods. We present a new strategy for the generation of thin disc stars which assumes the IMF, SFR and evolutionary tracks as free parameters. We have updated most of the ingredients for the star count production and, for the first time, binary stars are generated in a consistent way. We keep in this new scheme the local dynamical self-consistency as in Bienayme et al (1987). We then compare simulations from the new model with Tycho-2 data and the local luminosity function, as a first test to verify and constrain the new ingredients. The effects of changing thirteen different ingredients of the model are systematically studied. Results. For the first time, a full sky comparison is performed between BGM and data. This strategy allows to constrain the IMF slope at high masses which is found to be close to 3.0, excluding a shallower slope such as Salpeter"s one. The SFR is found decreasing whatever IMF is assumed. The model is compatible with a local dark matter density of 0.011 M pc−3 implying that there is no compelling evidence for significant amount of dark matter in the disc. While the model is fitted to Tycho2 data, a magnitude limited sample with V<11, we check that it is still consistent with fainter stars. Conclusions. The new model constitutes a new basis for further comparisons with large scale surveys and is being prepared to become a powerful tool for the analysis of the Gaia mission data.

MicroRNAs and the functional β cell mass: For better or worse.

Insulin secretion from pancreatic β cells plays a central role in the control of blood glucose levels. The amount of insulin released by β cells is precisely adjusted to match organism requirements. A number of conditions that arise during life, including pregnancy and obesity, can result in a decreased sensitivity of insulin target tissues and a consequent rise in insulin needs. To preserve glucose homoeostasis, the augmented insulin demand requires a compensatory expansion of the pancreatic β cell mass and an increase in its secretory activity. This compensatory process is accompanied by modifications in β cell gene expression, although the molecular mechanisms underlying the phenomenon are still poorly understood. Emerging evidence indicates that at least part of these compensatory events may be orchestrated by changes in the level of a novel class of gene regulators, the microRNAs. Indeed, several of these small, non-coding RNAs have either positive or negative impacts on β cell proliferation and survival. The studies reviewed here suggest that the balance between the actions of these two groups of microRNAs, which have opposing functional effects, can determine whether β cells expand sufficiently to maintain blood glucose levels in the normal range or fail to meet insulin demand and thus lead, as a consequence, towards diabetes manifestation. A better understanding of the mechanisms governing changes in the microRNA profile will open the way for the development of new strategies to prevent and/or treat both type 2 and gestational diabetes.

Pedaling rate is an important determinant of human oxygen uptake during exercise on the cycle ergometer.

Estimation of human oxygen uptake (V˙o2) during exercise is often used as an alternative when its direct measurement is not feasible. The American College of Sports Medicine (ACSM) suggests estimating human V˙o2 during exercise on a cycle ergometer through an equation that considers individual's body mass and external work rate, but not pedaling rate (PR). We hypothesized that including PR in the ACSM equation would improve its V˙o2 prediction accuracy. Ten healthy male participants' (age 19-48 years) were recruited and their steady-state V˙o2 was recorded on a cycle ergometer for 16 combinations of external work rates (0, 50, 100, and 150 W) and PR (50, 70, 90, and 110 revolutions per minute). V˙o2 was calculated by means of a new equation, and by the ACSM equation for comparison. Kinematic data were collected by means of an infrared 3-D motion analysis system in order to explore the mechanical determinants of V˙o2. Including PR in the ACSM equation improved the accuracy for prediction of sub-maximal V˙o2 during exercise (mean bias 1.9 vs. 3.3 mL O2 kg(-1) min(-1)) but it did not affect the accuracy for prediction of maximal V˙o2 (P > 0.05). Confirming the validity of this new equation, the results were replicated for data reported in the literature in 51 participants. We conclude that PR is an important determinant of human V˙o2 during cycling exercise, and it should be considered when predicting oxygen consumption.

Some Notes and Comments on the Efficient use of Information in Repeated Games with Poisson Signals

In the present paper we characterize the optimal use of Poisson signals to establish incentives in the "bad" and "good" news models of Abreu et al. [1]. In the former, for small time intervals the signals' quality is high and we observe a "selective" use of information; otherwise there is a "mass" use. In the latter, for small time intervals the signals' quality is low and we observe a "fine" use of information; otherwise there is a "non-selective" use. JEL: C73, D82, D86. KEYWORDS: Repeated Games, Frequent Monitoring, Public Monitoring, Infor- mation Characteristics.