Simultaneous cross-linking of CD6 and CD28 induces cell proliferation in resting T cells

In the present study, we showed that simultaneous ligation of the monoclonal antibodies (mAb) against CD6 and CD28 induces T-cell proliferation in purified resting T lymphocytes in the absence of T-cell receptor (TCR) occupancy. No cell proliferation was observed when the mAb were cross-linked alone or used simultaneously in the soluble form. T-cell proliferation mediated through CD6/CD28 is accompanied by the up-regulation of interleukin-2 (IL-2) mRNA and expression of IL-2 receptors on the cell surface. In the presence of IL-2-neutralizing mAb the proliferative response of the T cell induced through CD6/CD28 was inhibited dose dependently. Cross-linking mAb to CD6 and CD28 alone or together did not down-regulate the CD3/TCR complex. T-cell proliferation mediated through CD6/CD28 was only partially blocked by the immunosuppressive drug, cyclosporin A (CsA), whereas anti-CD28-induced T-cell proliferation in the presence of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), was unaffected. In sharp contrast T-cell proliferation mediated by anti-CD6 in the presence of TPA was efficiently blocked by CsA. In addition, two protein kinase C (PKC) inhibitors, GF 109203X and H-7 dose-dependently inhibited T-cell proliferation mediated through CD6/CD28, suggesting that PKC activation may be involved. Furthermore, there was a marked differential dose-dependent inhibitory effect of the PKC inhibitors on T-cell proliferation mediated by the co-ligation of anti-CD6 or anti-CD28 in the presence of anti-CD3, with the former being more sensitive to PKC inhibition. Taken collectively, our results suggest that T-cell activation can occur through an antigen-independent pathway by cross-linking the accessory molecules, CD6 and CD28, and that these two cell surface antigens may have distinct signalling pathways.     

Neuropathology of bovine herpesvirus type 5 (BHV-5) meningo-encephalitis in a rabbit seizure model

CI-994 (acetyldinaline) is an orally active anticancer drug currently in Phase 1 clinical trials. To assess its preclinical toxicity, CI-994 was administered orally as suspensions to Wistar rats (10/sex/dose) and in capsules to beagle dogs (3/sex/dose) once daily for two weeks. Doses were 1.5, 5, and 15 mg/kg for rats (9, 30, and 90 mg/m2, respectively), and 0.5, 2, and 5 mg/kg for dogs (10, 40, and 100 mg/m2, respectively). Systemic exposure was dose-proportional based on toxicokinetic analysis in dogs. Severe clinical signs and mortality occurred at the highest dose in both species beginning on Day 10. Neutropenia, lymphocytopenia, thrombocytopenia, lymphoid depletion, bone marrow hypocellularity, and testicular degeneration were observed in both species, primarily at the mid- and high-doses. Despite continued treatment, neutrophil counts in dogs returned to control levels in Week 2. Other microscopic findings in rats included splenic hematopoietic depletion at all doses and epithelial cell necrosis in various tissues at 15 mg/kg. Additional bone marrow changes in dogs involved myeloid and megakaryocyte hyperplasia at 2 mg/kg and abnormal myeloid and megakaryocyte maturation at 2 and 5 mg/kg. Except for the testicular effects in both species, all changes were reversible within a 4-week (rat) or 9-week (dog) recovery period. The results of these studies show that target organ effects of CI-994 principally involve tissues with rapidly dividing cell populations and that bone marrow suppression is the dose-limiting toxicity. CI-994 also seems to interfere with the release and/or maturation of cells in the bone marrow.     

停止强制驱逐——来自巴西库里蒂巴的报告

2003年10月1日清晨，城市警卫队的队员在巴西的库里蒂巴对一处叫Sambaqui的贫民窟住区进行了封锁，把居住在那里的72个人从他们的家中驱赶了出去。警卫队摧毁了这些人的房屋，点燃大火，把屋子里的床垫、器具和其它的日用品，甚至还包括一名老妇人喂养的小猫都丢进了大火中。武装的警卫队员还在一次未经官方批准的行动中对六个人实施了殴打。那些从自己的家园被驱赶出来的人不得不暂时住在为他们提供的一处市中心的工会大楼中。     

Iron, folic acid and vitamin B12 deficiencies related to anemia in adolescents from a region with a high incidence of congenital malformations in Venezuela

Since in recent years for certain age groups, the main cause of anemia is not iron deficiency, we intended to study the effect of iron, folic acid and vitamin B12 deficiencies on anemia prevalence in adolescents from Venezuela. One hundred adolescents aged between 12 and 19 years participated in the study. Each subject was interviewed about antecedents and habits and a physical examination and a 24-hour food recall questionnaire were performed. From a blood sample, hemoglobin and hematocrit concentrations were determined and serum was separated for quantification of ferritin, folic acid and vitamin B12 concentrations. Prevalence of anemia was 78% and for iron, folic acid and vitamin B12 deficiencies were 34.66, 90.9 and 18.18%, respectively. From anemic cases, 35.89% presented iron deficiency, while 91.02% presented folic acid deficiency. Only 19.23% of adolescents with anemia presented also vitamin B12 deficiency, but all the cases with vitamin B12 deficiency, were anemic. Simultaneous iron and folic acid deficiencies affected 30.76% of anemic cases. The high prevalence of deficiencies found in this work could be explained by insufficient intake and inadequate food habits. The prevalence of anemia was associated to folic acid deficiency rather than to iron deficiency, due to the high prevalence of folic acid deficiency. The high prevalence of nutritional deficiencies found in this work, especially regarding folic acid deficiency, require immediate interventions.     

Differential nanofiller cluster formations in dental adhesive systems

Nanofillers are added to dental adhesives to improve mechanical properties of the hybrid layer. Ethanol or water added to the demineralized dentin to improve adhesive infiltration may produce filler aggregation. OBJECTIVE: To assess the effect of 5 vol% water or ethanol addition on nanoparticles distribution in dental adhesives. METHODS: Six available commercial adhesives systems were selected: Clearfil SE Bond (CSE), Clearfil Protect Bond (CPB), FL‐Bond (FLB), Clearfil S3 (CS3), Bond Force (BF), One Up Bond F plus (OUB), and an experimental adhesive system without filler (EXP). Polymer films were obtained by adding 0 (control) or 5 vol% water or ethanol into the bonding resins. Preparations were light‐cured (40 s). Three specimens were analyzed for each mixture. Three phases and 3D images were taken from each specimen by means of an atomic force microscope in taping mode (TM/AFM). Cluster sizes and surface nanoroughness were assessed. RESULTS: Control specimens from CSE, FLB, OUB, and BF presented clusters. The addition of solvents lead to particles aggregation in tested bonding resins. Ethanol addition produced more aggregates, particularly in adhesives containing fluoraluminosilicate as fillers. CONCLUSIONS: Nanofillers aggregation occurred in all adhesive systems in presence of additional solvents. In general, aggregate sizes were higher after the addition of ethanol. Formed clusters size values are always above the dimensions of the spaces existing between the demineralized collagen fibers. Microsc. Res. Tech. 75:749–757, 2012. © 2011 Wiley Periodicals, Inc.     

An MIP model to optimize a Colombian cash supply chain

Financial institutions operate a supply chain where only one product is moved across the network. Although the cash is kept in several nodes to service the demand of final customers, availability causes opportunity cost related with its investment options. When planning the inventory of cash that should be maintained across the network, transportation decisions are also expected to be made. Cash transportation has a high cost, associated with the high risk of theft. Increasing the inventory can reduce the need for transportation, but the opportunity cost can be very high. Moreover, the inventory is also related with the service level perceived for final customers; therefore because of low inventory some people are not able to make some transactions. The aim of this work is to find optimal decisions related with cash inventory and transportation across the network, trying to balance the cost of the service and the quality perceived for final users.     

Experimental study of drop impacts and spreading on epicarps: Effect of fluid properties

The fluid mechanic of liquid drop impacts on solid food plays an important role in food engineering, e.g. when a spray technology is used to apply a coating. In the present work, drop impact behavior on banana and purple cabbage epicarps using high speed camera was studied. Drop velocity was controlled by modifying the height from which drop was ejected. Weber number varied from 100 to 800, whereas Reynolds number ranged from 1000 to 12,500. Liquid drop viscosity and surface tension effects on drop impact behavior were evaluated and temporal evolution of both spreading and flattening factors are presented. Results show that viscosity and epicarp surface properties had great influence on impact dynamics. For low viscosity liquid drops (water and Tween 20-water), the maximum spread factor, ξ_max, scaled with We^0.25±0.02, whereas for viscous fluid (water-glycerol mixture) it scaled with We^0.16±0.02. Finally, a new model was proposed to better fit the experimental data than the Roisman’s and Scheller’s models.     

Astringency sub-qualities of red wines and the influence of wine–saliva aggregates

Astringency is a sensory attribute, related to the quality and mouthfeel of red wines. However, the origin of astringency sub-qualities, such as the typical drying astringency found in immature grapes, is still unknown. Astringency of red wines with similar tannin content but different astringency sub-qualities, from different harvest dates, is studied. Astringency was characterised in terms of friction coefficient, polyphenol content, sensory analysis and tannin/salivary–proteins aggregates characterisation. A different evolution during ripening was found for both Cabernet Sauvignon and Carménère, and tannin–protein aggregates showed differences in size, shape and surface. The velvety sub-quality appears to be related to aggregates with low precipitation, and with specific surface characteristics as roundness and Feret diameter. Results from this work propose an effect of aggregates on sensory perception and opens the possibility to explore their effect on oral lubrication.     

Taste perception and purchase intent of oil‐in‐water spreads: effects of oil types and salt (NaCl or KCl) concentrations

Associations of sodium intake with heart‐related problems are creating awareness towards reducing sodium. Potassium chloride (KCl), a substitute for sodium chloride (NaCl), has the disadvantage of imparting bitterness at high concentrations. We evaluated physical characteristics, taste perception and purchase intent of KCl and NaCl in oil‐in‐water spreads/emulsions composed by olive, rice bran and soya bean oils. Consumers (N = 300) evaluated saltiness/bitterness of emulsions prepared with 65% oil, and NaCl (0.5% and 1.0%) or KCl (0.75% and 1.5%). Olive oil spreads (104.07–107.43 Pa s) had higher viscosity compared to other spreads (59.16–74.96 Pa s). Type of oil had significant effects on bitterness, overall taste liking and viscosity. Taste liking decreased due to bitterness of olive oil spreads (mean drop=1.72–2.43). Purchase intent was positively associated with saltiness and pH and increased with oil claims (increase = 1.3%–22.1%) compared to sodium claims (increase = 0.0%–12.9%). These findings are useful for understanding taste perception of emulsions.