Examination of the aerosol indirect effect under contrasting environments during the ACE-2 experiment

International audienceThe Active Tracer High-resolution Atmospheric Model (ATHAM) has been adopted to examine the aerosol indirect effect in contrasting clean and polluted cloudy boundary layers during the Second Aerosol Characterization Experiment (ACE-2). Model results are in good agreement with available in-situ observations, which provides confidence in the results of ATHAM. Sensitivity tests have been conducted to examine the response of the cloud fraction (CF), cloud liquid water path (LWP), and cloud optical depth (COD) to changes in aerosols in the clean and polluted cases. It is shown for two cases that CF and LWP would decrease or remain nearly constant with an increase in aerosols, a result which shows that the second aerosol indirect effect is positive or negligibly small in these cases. Further investigation indicates that the background meteorological conditions play a critical role in the response of CF and LWP to aerosols. When large-scale subsidence is weak as in the clean case, the dry overlying air above the cloud is more efficiently entrained into the cloud, and in so doing, removes cloud water more efficiently, and results in lower CF and LWP when aerosol burden increases. However, when the large-scale subsidence is strong as in the polluted case, the growth of the cloud top is suppressed and the entrainment drying makes no significant difference when aerosol burden increases. Therefore, the CF and LWP remain nearly constant. In both the clean and polluted cases, the COD tends to increase with aerosols, and the total aerosol indirect effect (AIE) is negative even when the CF and LWP decrease with an increase in aerosols. Therefore, the first AIE dominates the response of the cloud to aerosols

Polymorphism of DNA mismatch repair genes in endometrial cancer

Endometrial cancer (EC) is the second most common malignancy associated with hereditary non-polyposis colorectal cancer (HNPCC) family. The development of HNPCC is associated with defects in DNA mismatch repair (MMR) pathway resulting in microsatellite instability (MSI). MSI is present in a greater number of EC than can be accounted for by inherited MMR mutations, therefore alternative mechanisms may underline defective MMR in EC, including polymorphic variation. Aim: We checked the association between EC occurrence and two polymorphisms of MMR genes: a 1032G>A (rs4987188) transition in the hMSH2 gene resulting in a Gly22Asp substitution and a –93G>A (rs1800734) transition in the promoter of the hMLH1 gene. Material and methods: These polymorphisms were genotyped in DNA from peripheral blood lymphocytes of 100 EC patients and 100 age-matched women by restriction fragment length polymorphism PCR. Results: A positive association (OR 4.18; 95% CI 2.23–7.84) was found for the G/A genotype of the –93G>A polymorphism of the hMLH1 gene and EC occurrence. On the ot­her hand, the A allele of this polymorphism was associated with decreased EC occurrence. The Gly/Gly genotype slightly increased the effect of the –93G>A-G/A genotype (OR 4.52; CI 2.41–8.49). Our results suggest that the –93G>A polymorphism of the hMLH1 gene singly and in combination with the Gly322Asp polymorphism of the hMSH2 gene may increase the risk of EC. Key Words: hMSH2, hMLH1, endometrial cancer, genetic polymorphism, MMR

Customer Focused Price Optimisation

Tesco want to better understand how to set online prices for their general merchandise (i.e. not groceries or clothes) in the UK. Because customers can easily compare prices from different retailers we expect they will be very sensitive to price, so it is important to get it right. There are four aspects of the problem. • Forecasting: Estimating the customer demand as a function of the price chosen (especially hard for products with no sales history or infrequent sales). • Objective function: What exactly should Tesco aim to optimise? Sales volume? Profit? Profit margin? Conversion rates? • Optimisation: How to choose prices for many related products to optimise the chosen objective function. • Evalution: How to demonstrate that the chosen prices are optimal, especially to people without a mathematical background. Aggregate sales data was provided for about 400 products over about 2 years so that quantitive approaches could be tested. For some products competitors’ prices were also provided

KOMBINIRANO DJELOVANJE BITURATA I EKSTRAKTA YUCCA SCHIDIGERI NA GASTROINTESTINALNI SUSTAV SVINJA OKO ODBIJANJA

After the banning of antibiotics as growth promoters, animal production in the EU faced the problem of increased post-weaning disorders, and several solutions were proposed (acidifiers, probiotics, herb extracts, enzyme cocktails, etc.). Short chain fatty acids (SCFA) are the main end product of bacterial fermentation in the hind gut in monogastric animals and can be used as energy supply for the epithelial cells of gut mucosa. Thus the aim of the study was to test the usefulness of novel microencapsulated sodium butyrate and Yucca Schidigera extract (encourages friendly bacteria growth, reduces ammonia) preparation on pig performance and small intestine development in the critical weaning period. Microencapsulation helps to avoid stomach degradation and provides better distribution of the compounds along the small intestine. Suckling piglets, 14-day old, were divided into 2 groups, control and with butyrate addition. Control pigs received a standard feed supplemented with a microencapsulated acidifier (0.3%). Butyrate pigs received the same feed and acidifier, as controls, supplemented with butyrate/yucca preparation (0.3%). At days 28 (weaning), 35 and 56 of life, 6 pigs from each group were killed and the gastrointestinal tract was harvested and measured. The initial body weight (14 d) of pigs from the control group was higher than that of the experimental, but at day 56 it did not differ significantly (P=0.48). The relative stomach and pancreas weights in the experimental group showed a tendency toward higher values in all time points, and the small intestine relative weight in day 35 was higher as compared to the controls. The growth rate of the pigs at day 35 decreased significantly in the control (P=0.007), but did not in the experimental (P=0.058) group compared to day 31. Measurements of the small intestine sections revealed increased mucosa thickness in butyrate treated pigs. This was due to both villi and crypt enlargement. In conclusion, our results demonstrated the effectiveness sodium butyrate and Yucca Shidigera extract in the prevention of weaning problems in pigs, however further research on the novel preparation is needed.Nakon zabrane antibiotika kao promotora rasta, proizvodnja životinja u EU suočila se sa sve više poremećaja nakon odbijanja pa je predloženo nekoliko rješenja (acidifikatori, probiotici, biljni ekstrakti, kokteli enzima, itd.). Kratkolančane masne kiseline glavni su krajnji proizvod bakterijske fermentacije u stražnjem crijevu u monogastričnih životinja pa se mogu upotrijebiti za snabdijevanje energijom epitelnih stanica crijevne sluznice /mukoze. Stoga je cilj ovog rada bio testirati korisnost novog natrijevog biturata u mikrokapsuli i pripravka ekstrakta Yucca Schidigera (potiče rast dobročudnih bakterija, smanjuje amonijak) na performansu svinja i razvoj tankog crijeva u kritičnom razdoblju odbijanja. Mikrokapsule pomažu da se izbjegne oštećenje želuca i pruža bolju razdiobu spojeva duž tankog crijeva. Praščići na sisi, u dobi od 14 dana, bili su podijeljeni u dvije skupine, kontrolnu i skupinu s dodavanjem biturata. Kontrolni praščići dobivali su standardnu hranu s dodatkom acidifikatora/zakiseljivača u mikrokapsuli (0.03%). Praščići na bituratima dobivali su istu hranu i acidifikator/zakiseljivač s dodatkom biturata/yucca pripravka (0.03%). U dobi od 28 (odbijanje), 35 i 56 dana žrtvovano je 6 svinja iz svake skupine te je pregledan i izmjeren gastrointestinalni sustav. Početna tjelesna masa (14. dan) svinja iz kontrolne skupine bila je veća od mase svinja pokusne skupine ali 56. dan nije se značajno razlikovala (P=0.48). Relativne mase želuca i gušterače u pokusnoj skupini pokazale su tendenciju viših vrijednosti u svim razdobljima, a relativna masa tankog crijeva 35. dana bila je viša u usporedbi s kontrolnom skupinom. Stopa rasta svinja 35. dana znatno se smanjila u kontrolnoj skupini (P=0.007) ali ne u kontrolnoj skupini (P=0.058) u usporedbi s 31. danom. Mjere tankog crijeva pokazale su povećanu debljinu sluznice u svinja tretiranih bituratom. To se pripisuje povećanju dlačica i udubina (villi i crypt). U zaključku, naši su rezultati pokazali djelotvornost natrijevog biturata i ekstrakta Yucca Schidigeri u prevenciji problema odbijanja u svinja, međutim, potrebna su dalja istraživanja novih pripravaka

Multifunctional platform based on electrospun nanofibers and plasmonic hydrogel. A smart nanostructured pillow for near-infrared light-driven biomedical applications

Multifunctional nanomaterials with the ability to respond to near-infrared (NIR) light stimulation are vital for the development of highly efficient biomedical nanoplatforms with a polytherapeutic approach. Inspired by the mesoglea structure of jellyfish bells, a biomimetic multifunctional nanostructured pillow with fast photothermal responsiveness for NIR light-controlled on-demand drug delivery is developed. We fabricate a nanoplatform with several hierarchical levels designed to generate a series of controlled, rapid, and reversible cascade-like structural changes upon NIR light irradiation. The mechanical contraction of the nanostructured platform, resulting from the increase of temperature to 42 °C due to plasmonic hydrogel-light interaction, causes a rapid expulsion of water from the inner structure, passing through an electrospun membrane anchored onto the hydrogel core. The mutual effects of the rise in temperature and water flow stimulate the release of molecules from the nanofibers. To expand the potential applications of the biomimetic platform, the photothermal responsiveness to reach the typical temperature level for performing photothermal therapy (PTT) is designed. The on-demand drug model penetration into pig tissue demonstrates the efficiency of the nanostructured platform in the rapid and controlled release of molecules, while the high biocompatibility confirms the pillow potential for biomedical applications based on the NIR light-driven multitherapy strategy

Phase I/II Trial of Liver-derived Mesenchymal Stem Cells in Pediatric Liver-based Metabolic Disorders: A Prospective, Open Label, Multicenter, Partially Randomized, Safety Study of One Cycle of Heterologous Human Adult Liver-derived Progenitor Cells (HepaStem) in Urea Cycle Disorders and Crigler-Najjar Syndrome Patients

Background. Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases. Objective. This phase I/II prospective, open label, multicenter, randomized trial aimed primarily at evaluating the safety of Heterologous Human Adult Liver–derived Progenitor Cells (HepaStem) in pediatric patients with urea cycle disorders (UCDs) or Crigler-Najjar (CN) syndrome 6 months posttransplantation. The secondary objective included the assessment of safety up to 12 months postinfusion and of preliminary efficacy. Methods. Fourteen patients with UCDs and 6 with CN syndrome were divided into 3 cohorts by body weight and intraportally infused with 3 doses of HepaStem. Clinical status, portal vein hemodynamics, morphology of the liver, de novo detection of circulating anti–human leukocyte antigen antibodies, and clinically significant adverse events (AEs) and serious adverse events to infusion were evaluated by using an intent-to-treat analysis. Results. The overall safety of HepaStem was confirmed. For the entire study period, patient-month incidence rate was 1.76 for the AEs and 0.21 for the serious adverse events, of which 38% occurred within 1 month postinfusion. There was a trend of higher events in UCD as compared with CN patients. Segmental left portal vein thrombosis occurred in 1 patient and intraluminal local transient thrombus in a second patient. The other AEs were in line with expectations for catheter placement, cell infusion, concomitant medications, age, and underlying diseases. Conclusions. This study led to European clinical trial authorization for a phase II study in a homogeneous patient cohort, with repeated infusions and intermediate doses