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The Centro de Laseres Pulsados in Salamanca, Spain has recently started operation phase and the first user access period on the 6 J 30 fs 200 TW system (VEGA 2) already started at the beginning of 2018. In this paper we report on two commissioning experiments recently performed on the VEGA 2 system in preparation for the user campaign. VEGA 2 system has been tested in different configurations depending on the focusing optics and targets used. One configuration (long focal length
cm) is for underdense laser–matter interaction where VEGA 2 is focused onto a low density gas-jet generating electron beams (via laser wake field acceleration mechanism) with maximum energy up to 500 MeV and an X-ray betatron source with a 10 keV critical energy. A second configuration (short focal length
cm) is for overdense laser–matter interaction where VEGA 2 is focused onto a
thick Al target generating a proton beam with a maximum energy of 10 MeV and temperature of 2.5 MeV. In this paper we present preliminary experimental results.
OBJECTIVES/SPECIFIC AIMS: The Title V Cooperative Project of the UPR-MSC and UCC has demonstrated that educational interventions in CTR are very effective in fulfilling the objective of promoting awareness, stimulate interest and increase the knowledge, skills and opportunities, to US, GS and F (participants) in CTR. METHODS/STUDY POPULATION: The training sessions (TS) offered through the Title V initiative have become an engine for the involvement in CTR for participants from higher education institutions island-wide. TS consisted of cycles –level 1 and 2–: Research Education Towards Opportunities (RETO,I,II) and Mentorship Offering Training Opportunities for Research (MOTOR,I,II), ending in the formation of the Clinical and Translational Mentoring Teams (CTMT)s, in which participants, paired by their research interests, were mentored by a well-established CT researchers in their research project, to be developed in the Intensive Development and Experiences in Advancement of Research and Increased Opportunities (IDEARIO). RESULTS/ANTICIPATED RESULTS: Up to date, 4 TS-level 1 and 2 TS-level 2 were offered. Eighty (80) participants completed level 1, distributed: 42 (52.5%) US in RETO, 21 (26.25%) GS and 17 (21.25%) F in MOTOR and 17 participants completed level 2, distributed: 4 (23.52%) US in RETO, 6 (25.29%) GS and 7 (41.17%) F in MOTOR. From which, 15, with 8 CT researchers, formed 5 CTMTs in different research areas – cardio, neuro, liver, renal, Zika–. DISCUSSION/SIGNIFICANCE OF IMPACT: US, GS and F were integrated in the active process throughout educational levels for their development in CTR.
Gluten is only partially digested by intestinal enzymes and can generate peptides that can alter intestinal permeability, facilitating bacterial translocation, thus affecting the immune system. Few studies addressed the role of diet with gluten in the development of colitis. Therefore, we investigate the effects of wheat gluten-containing diet on the evolution of sodium dextran sulphate (DSS)-induced colitis. Mice were fed a standard diet without (colitis group) or with 4·5 % wheat gluten (colitis + gluten) for 15 d and received DSS solution (1·5 %, w/v) instead of water during the last 7 d. Compared with the colitis group, colitis + gluten mice presented a worse clinical score, a larger extension of colonic injury area, and increased mucosal inflammation. Both intestinal permeability and bacterial translocation were increased, propitiating bacteria migration for peripheral organs. The mechanism by which diet with gluten exacerbates colitis appears to be related to changes in protein production and organisation in adhesion junctions and desmosomes. The protein α-E-catenin was especially reduced in mice fed gluten, which compromised the localisation of E-cadherin and β-catenin proteins, weakening the structure of desmosomes. The epithelial damage caused by gluten included shortening of microvilli, a high number of digestive vacuoles, and changes in the endosome/lysosome system. In conclusion, our results show that wheat gluten-containing diet exacerbates the mucosal damage caused by colitis, reducing intestinal barrier function and increasing bacterial translocation. These effects are related to the induction of weakness and disorganisation of adhesion junctions and desmosomes as well as shortening of microvilli and modification of the endocytic vesicle route.
This is the first report on the development and characterization of eight monoclonal antibodies (MABs) generated against whole- and membrane-enriched tachyzoite extracts of the apicomplexan parasite Besnoitia besnoiti. Confocal laser scanning immunofluorescence microscopy was used to localize respective epitopes in B. besnoiti tachyzoites along the lytic cycle. A pattern compatible with dense granule staining was observed with MABs 2.A.12, 2.F.3 and 2.G.4, which could be confirmed by immunogold electron microscopy for MABs 2.A.12 and 2.F.3. In particular, MABs 2.F.3 and 2.G.4 were secreted during early invasion, proliferation and egress phases. MABs 3.10.8 and 5.5.11 labelled the tachyzoite surface, whilst MABs 1.17.8, 8.9.2 and 2.G.A recognized the apical tip, which is reminiscent for microneme localization. Besides, the epitopes recognized by the latter two (MABs 8.9.2 and 2.G.A) exhibited a redistribution from the anterior part across the parasite surface towards the posterior end during invasion. Most MABs developed were genus-specific. Indeed, the MABs cross-reacted neither with T. gondii nor with N. caninum tachyzoites. In summary, we have generated MABs that will be useful to study the key processes in the lytic cycle of the parasite and with additional promising diagnostic value. However, the molecular identity of the antigens recognized remains to be elucidated.
A Q fever outbreak was declared in February 2016 in a company that manufactures hoists and chains and therefore with no apparent occupational-associated risk. Coxiella burnetii infection was diagnosed by serology in eight of the 29 workers of the company; seven of them had fever or flu-like signs and five had pneumonia, one requiring hospitalisation. A further case of C. burnetii pneumonia was diagnosed in a local resident. Real-time PCR (RTi–PCR) showed a widespread distribution of C. burnetii DNA in dust samples collected from the plant facilities, thus confirming the exposure of workers to the infection inside the factory. Epidemiological investigations identified a goat flock with high C. burnetii seroprevalence and active shedding which was owned and managed by one of the workers of the company as possible source of infection. Genotyping by multispacer sequence typing (MST) and a 10-loci single-nucleotide polymorphism (SNP) discrimination using RTi–PCR identified the same genotype (MST18 and SNP type 8, respectively) in the farm and the factory. These results confirmed the link between the goat farm and the outbreak and allowed the identification of the source of infection. The circumstances and possible vehicles for the bacteria entering the factory are discussed.
Omicron Andromedae is a multiple system of at least four stars: a B ↔Be star (component A), a spectroscopic binary (components B1–B2) and a close companion (component a). According to several studies (see Hill et al. 1988, 1989):
-the distance between A and the B1–B2 system decreased from 0.39″ in 1975 to 0.25″ in 1987 (McAlister and Hartkopf 1988)
-the few previous speckle measurements of component a have shown the possibility of a 3.7 years orbit around A, according to the 1975 to 1984 observations (mean distance 0.05″). The calculations with this 3.7 yr orbit lead to the prediction of a maximum distance of 0.77″ at 1992.738, i.e. at the end of september 1992, with a North-South orientation.
A simulation model is presented, where temperature, phases and internal stresses can be predicted as a function of time during the heating of large steel ingots for forging. Heating cycle measurements and computer simulations are compared for an A105 steel grade 34-Ton tapered ingot. A study of the heat transfer inside a natural gas-fired furnace was carried out to make an estimation of internal stresses due to thermal expansion and phase transformation from α ferrite and pearlite to γ austenite during heating. The model was validated with a second test of an AISI 4330 steel grade 35.4-Ton ingot. The simulation model described can calculate internal stresses in any ingot in order to optimize its heating cycle without compromising ingot internal quality, reducing energy consumption and increasing productivity of the furnace.
The ATP-binding cassette transporter G2/breast cancer resistance protein (ABCG2/BCRP) is an efflux protein involved in the bioavailability and milk secretion of endogenous and exogenous compounds, actively affecting milk composition. A limited number of physiological substrates have been identified. However, no studies have reported the specific effect of this polymorphism on the secretion into milk of compounds implicated in milk quality such as vitamins or endogenous compounds. The bovine ABCG2 Y581S polymorphism is described as a gain-of-function polymorphism that increases milk secretion and decreases plasma levels of its substrates. This work aims to study the impact of Y581S polymorphism on plasma disposition and milk secretion of compounds such as riboflavin (vitamin B2), enterolactone, a microbiota-derived metabolite from the dietary lignan secoisolariciresinol and uric acid. In vitro transport of these compounds was assessed in MDCK-II cells overexpressing the bovine ABCG2 (WT-bABCG2) and its Y581S variant (Y581S-bABCG2). Plasma and milk levels were obtained from Y/Y homozygous and Y/S heterozygous cows. The results show that riboflavin was more efficiently transported in vitro by the Y581S variant, although no differences were noted in vivo. Both uric acid and enterolactone were substrates in vitro of the bovine ABCG2 variants and were actively secreted into milk with a two-fold increase in the milk/plasma ratio for Y/S with respect to Y/Y cows. The in vitro ABCG2-mediated transport of the drug mitoxantrone, as a model substrate, was inhibited by enterolactone in both variants, suggesting the possible in vivo use of this enterolignan to reduce ABCG2-mediated milk drug transfer in cows. The Y581S variant was inhibited to a lesser extent probably due to its higher transport capacity. All these findings point to a significant role of the ABCG2 Y581S polymorphism in the milk disposition of enterolactone and the endogenous molecules riboflavin and uric acid, which could affect both milk quality and functionality.
The Euclid space mission proposes to survey 15000 square degrees of the extragalactic sky during 6 years, with a step-and-stare technique. The scheduling of observation sequences is driven by the primary scientific objectives, spacecraft constraints, calibration requirements and physical properties of the sky. We present the current reference implementation of the Euclid survey and on-going work on survey optimization.
LOFT (Large Observatory For X-ray Timing) is one of the four candidate missions currently
under assessment study for the M3 mission in ESAs Cosmic Vision program to be launched in
2024. LOFT will carry two instruments with prime sensitivity in the 2–30 keV range: a 10
m2 class large area detector (LAD) with a <1° collimated field of view
and a wide field monitor (WFM) instrument. The WFM is based on the coded mask principle,
and 5 camera units will provide coverage of more than 1/3 of the sky. The prime goal of
the WFM is to detect transient sources to be observed by the LAD. With its wide field of
view and good energy resolution of <500 eV, the WFM will be an excellent instrument
for detecting and studying GRBs and X-ray flashes. The WFM will be able to detect
~150 gamma ray bursts per year, and a burst alert system will enable the
distribution of ~100 GRB positions per year with a ~1 arcmin location
accuracy within 30 s of the burst.
The main goal of the current work was to develop and validate an in vitro fluke egg hatch test, as a method for the detection of albendazole (ABZ) resistance in the liver fluke, Fasciola hepatica. Fluke eggs (200/ml, n= 5) from six different isolates were used in the current experimental work. They were obtained from different geographical locations and named Cullompton (UK), CEDIVE (Chascomus, Argentina), INTA-Bariloche (Bariloche, Argentina), Rubino (Uruguay), Cajamarca (Perú) and Río Chico (Catamarca, Argentina). The fluke eggs were incubated (25°C) for a 12-h period in the presence of either ABZ or its sulphoxide metabolite (ABZ.SO) (5, 0.5 or 0.05 nmol/ml). Untreated eggs were incubated as a control. Incubated eggs (with or without drug present) were kept in darkness at 25°C for 15 days. Afterwards, the trematode eggs were exposed to daylight over a 2-h period. Hatched and unhatched eggs were evaluated using an optical microscope, and the ovicidal activity was assessed for each fluke isolate. A very low ovicidal activity ( ≤ 13.4%) was observed in the ABZ-resistant CEDIVE isolate for both ABZ and ABZ.SO. Conversely, in the INTA-Bariloche and Río Chico isolates, which are suspected to be susceptible to ABZ, ovicidal activities ≥ 70.3% were observed after incubation with ABZ at the lowest concentration tested (0.05 nmol/ml). This finding correlates with that previously described for the ABZ-susceptible Cullompton. Finally, the Cajamarca and Rubino isolates behaved as ABZ resistant, since no ovicidal activity was observed after eggs were incubated with ABZ at 0.5 nmol/ml. Considering the specific results obtained for each isolate under assessment, the egg hatch test described here may be a suitable method for detection of ABZ resistance in F. hepatica.
The effects of bread consumption change over time on anthropometric measures have been scarcely studied. We analysed 2213 participants at high risk for CVD from the PREvención con DIeta MEDiterránea (PREDIMED) trial to assess the association between changes in the consumption of bread and weight and waist circumference gain over time. Dietary habits were assessed with validated FFQ at baseline and repeatedly every year during 4 years of follow-up. Using multivariate models to adjust for covariates, long-term weight and waist circumference changes according to quartiles of change in energy-adjusted white and whole-grain bread consumption were calculated. The present results showed that over 4 years, participants in the highest quartile of change in white bread intake gained 0·76 kg more than those in the lowest quartile (P for trend = 0·003) and 1·28 cm more than those in the lowest quartile (P for trend < 0·001). No significant dose–response relationships were observed for change in whole-bread consumption and anthropometric measures. Gaining weight (>2 kg) and gaining waist circumference (>2 cm) during follow-up was not associated with increase in bread consumption, but participants in the highest quartile of changes in white bread intake had a reduction of 33 % in the odds of losing weight (>2 kg) and a reduction of 36 % in the odds of losing waist circumference (>2 cm). The present results suggest that reducing white bread, but not whole-grain bread consumption, within a Mediterranean-style food pattern setting is associated with lower gains in weight and abdominal fat.
Orientational ordering of faceted nanocrystals in nanocrystal arrays has been directly observed for the first time, by use of transmission electron microscopy imaging and diffraction to resolve the structure of thin molecular-crystalline films of silver nanocrystals passivated by alkylthiolate self-assembled monolayers. The type of ordering found is determined by the nanocrystals faceted morphology, as mediated by the interactions of surfactant groups tethered to the facets on neighboring nanocrystals. Orientational ordering is crucial for the understanding of the fundamental properties of quantum-dot arrays, as well as for their optimal utilization in optical and electronic applications.
A study has been carried out to determine whether the action of triclabendazole (TCBZ) against the liver fluke, Fasciola hepatica is altered by inhibition of the cytochrome P450 (CYP 450)-mediated drug metabolism pathway. The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible fluke isolates were used for these experiments, the basic design of which is given in the paper by Devine et al. (2010a). Piperonyl butoxide (PB) was the CYP P450 inhibitor used. Morphological changes resulting from drug treatment and following metabolic inhibition were assessed by means of transmission electron microscopy. After treatment with either TCBZ or TCBZ.SO on their own, there was greater disruption to the TCBZ-susceptible than TCBZ–resistant isolate. However, co-incubation with PB+TCBZ, but more particularly PB+TCBZ.SO, led to greater changes to the TCBZ-resistant isolate than with each drug on its own, with blebbing of the apical plasma membrane, severe swelling of the basal infolds and their associated mucopolysaccharide masses in the syncytium and flooding in the internal tissues. Golgi complexes were greatly reduced or absent in the tegumental cells and the synthesis and production of secretory bodies were badly disrupted. The mitochondria were swollen throughout the tegumental system and the somatic muscle blocks were disrupted. With the TCBZ-susceptible Cullompton isolate, there was a limited increase in drug action following co-incubation with PB. The results provide evidence that the condition of a TCBZ-resistant fluke can be altered by inhibition of drug metabolism. Moreover, they support the concept that altered drug metabolism contributes to the mechanism of resistance to TCBZ.
A study has been carried out to investigate whether the action of triclabendazole (TCBZ) against Fasciola hepatica is altered by inhibition of drug metabolism. The cytochrome P450 (CYP P450) system was inhibited using piperonyl butoxide (PB). The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible isolates were used for these experiments. The CYP P450 system was inhibited by a 2 h pre-incubation in PB (100 μm). Flukes were then incubated for a further 22 h in NCTC medium containing either PB; PB+nicotinamide adenine dinucleotide phosphate (NADPH) (1 nm); PB+NADPH+TCBZ (15 μg/ml); or PB+NADPH+TCBZ.SO (15 μg/ml). Morphological changes resulting from drug treatment and following metabolic inhibition were assessed using scanning electron microscopy. After treatment with either TCBZ or TCBZ.SO alone, there was greater disruption to the TCBZ-susceptible than the resistant isolate. However, co-incubation with PB and TCBZ/TCBZ.SO lead to more severe surface changes to the TCBZ-resistant Oberon isolate than with each drug on its own. With the TCBZ-susceptible Cullompton isolate, there was limited potentiation of drug action, and only with TCBZ.SO. The results support the concept of altered drug metabolism in TCBZ-resistant flukes and this process may play a role in the development of drug resistance.
This paper describes a vehicle detection system based on support vector machine (SVM) and monocular vision. The final goal is to provide vehicle-to-vehicle time gap for automatic cruise control (ACC) applications in the framework of intelligent transportation systems (ITS). The challenge is to use a single camera as input, in order to achieve a low cost final system that meets the requirements needed to undertake serial production in automotive industry. The basic feature of the detected objects are first located in the image using vision and then combined with a SVM-based classifier. An intelligent learning approach is proposed in order to better deal with objects variability, illumination conditions, partial occlusions and rotations. A large database containing thousands of object examples extracted from real road scenes has been created for learning purposes. The classifier is trained using SVM in order to be able to classify vehicles, including trucks. In addition, the vehicle detection system described in this paper provides early detection of passing cars and assigns lane to target vehicles. In the paper, we present and discuss the results achieved up to date in real traffic conditions.
The earthworm species belonging to the Lumbricidae family (Annelida, Oligochaeta) posses a complex oesophageal organ known as “calciferous gland” which secretes a concentrated suspension of calcium carbonate. Previous studies have demonstrated the non-crystalline structure of this calcareous fluid representing an interesting example of biomineralisation.
Shared vulnerabilities have been described across disorders of impulse control, including pathological gambling (PG) and bulimia nervosa (BN). Our aim was to compare the executive functioning of PG and BN females in order to confirm their similarity at a neurocognitive level. A total of 15 BN females, 15 PG females, and 15 healthy control (HC) females were administered the Wisconsin Card Sorting Test (WCST) and the Stroop Color and Word Test. Analysis of covariance adjusted for age and education was conducted to compare groups. PG showed the greatest impairment, that is, the highest percentage of WCST perseverative errors (p = .023), the lowest percentage of conceptual-level responses (p = .034), and the highest number of total trials administered (p = .021), while BN showed the highest percentage of WCST nonperseverative errors (p = .003). Both BN and PG females demonstrated executive dysfunction relative to HCs but different specific correlates (i.e., greater vulnerability to distraction in BN, but more cognitive inflexibility in PG). (JINS, 2009, 15, 302–306.)
A study has been carried out to investigate whether the action of triclabendazole (TCBZ) is altered in the presence of a metabolic inhibitor. The flavin monooxygenase system (FMO) was inhibited using methimazole (MTZ) to see whether a TCBZ-resistant isolate could be made more sensitive to TCBZ action. The Oberon TCBZ-resistant and Cullompton TCBZ-sensitive isolates were used for these experiments. The FMO system was inhibited by a 2-h pre-incubation in methimazole (100 μm). Flukes were then incubated for a further 22 h in NCTC medium containing either MTZ; MTZ+nicotinamide adenine dinucleotide phosphate (NADPH) (1 nm); MTZ+NADPH+TCBZ (15 μg/ml); or MTZ+NADPH+triclabendazole sulphoxide (TCBZ.SO) (15 μg/ml). Morphological changes resulting from drug treatment and following metabolic inhibition were assessed using scanning electron microscopy. After treatment with either TCBZ or TCBZ.SO alone, there was greater surface disruption to the triclabendazole-susceptible than -resistant isolate. However, co-incubation with MTZ and TCBZ/TCBZ.SO lead to more severe surface changes to the TCBZ-resistant isolate than with each drug on its own; this was not seen for the TCBZ-susceptible Cullompton isolate. Results of this study support the concept of altered drug metabolism in TCBZ-resistant flukes and this process may play a role in the development of drug resistance.