Human Chromosome 18 and Acrocentrics: A Dangerous Liaison

The presence of thousands of repetitive sequences makes the centromere a fragile region subject to breakage. In this study we collected 31 cases of rearrangements of chromosome 18, of which 16 involved an acrocentric chromosome, during genetic screening done in three centers. We noticed a significant enrichment of reciprocal translocations between the centromere of chromosome 18 and the centromeric or pericentromeric regions of the acrocentrics. We describe five cases with translocation between chromosome 18 and an acrocentric chromosome, and one case involving the common telomere regions of chromosomes 18p and 22p. In addition, we bring evidence to support the hypothesis that chromosome 18 preferentially recombines with acrocentrics: (i) the presence on 18p11.21 of segmental duplications highly homologous to acrocentrics, that can justify a NAHR mechanism; (ii) the observation by 2D-FISH of the behavior of the centromeric regions of 18 respect to the centromeric regions of acrocentrics in the nuclei of normal subjects; (iii) the contact analysis among these regions on published Hi-C data from the human lymphoblastoid cell line (GM12878).     

Using Copy Number Alterations to Identify New Therapeutic Targets for Bladder Carcinoma

Bladder cancer represents the ninth most widespread malignancy throughout the world. It is characterized by the presence of two different clinical and prognostic subtypes: non-muscle-invasive bladder cancers (NMIBCs) and muscle-invasive bladder cancers (MIBCs). MIBCs have a poor outcome with a common progression to metastasis. Despite improvements in knowledge, treatment has not advanced significantly in recent years, with the absence of new therapeutic targets. Because of the limitations of current therapeutic options, the greater challenge will be to identify biomarkers for clinical application. For this reason, we compared our array comparative genomic hybridization (array-CGH) results with those reported in literature for invasive bladder tumors and, in particular, we focused on the evaluation of copy number alterations (CNAs) present in biopsies and retained in the corresponding cancer stem cell (CSC) subpopulations that should be the main target of therapy. According to our data, CCNE1, MYC, MDM2 and PPARG genes could be interesting therapeutic targets for bladder CSC subpopulations. Surprisingly, HER2 copy number gains are not retained in bladder CSCs, making the gene-targeted therapy less interesting than the others. These results provide precious advice for further study on bladder therapy; however, the clinical importance of these results should be explored.     

Work allocation strategies for serial assembly lines under high labour turnover

Labour turnover can be very detrimental to the performance of traditional serial assembly lines. It has been shown that high turnover rates can reduce annual production throughput in serial assembly lines by more than 16% when these lines operate under a balanced work allocation strategy. This paper investigates whether alternative production methods, such as Bucket Brigades, can out-perform traditional lines by utilizing dynamic work allocation and active operator replacement policies in order to absorb better the variability introduced by labour turnover. The study performed was divided into two phases. Phase I consisted of using a simple three-station linear assembly line to compare the performance of the Bucket Brigades method against a traditional line (fixed work allocation, static operator replacement), and a method using fixed work allocation along with a dynamic replacement policy. In Phase II, a six-station serial assembly line was used to compare the performance of Bucket Brigades against the traditional balanced line method. The analyses were based on simulation models that used monthly turnover rates of 0, 6 and 12%. Phase I showed that the Bucket Brigade method outperformed the other two methods consistently when operating under moderate (6%) and high (12%) turnover rates. Phase II demonstrated that the Bucket Brigade method was better than the traditional production method in every instance, including the case with 0% turnover.     

Modeling no-notice mass evacuation using a dynamic traffic flow optimization model

This paper presents a network transformation and demand specification approach for no-notice evacuation modeling. The research is aimed at formulating the Joint Evacuation Destination-Route-Flow-Departure (JEDRFD) problem of a no-notice mass evacuation into a system optimal dynamic traffic assignment model. The proposed network transformation technique permits the conversion of a typical transportation planning network to an evacuation network configuration in which a hot zone, evacuation destinations, virtual super-safe node and connectors are established. Combined with a demand specification method, the JEDRFD problem is formulated as a single-destination cell-transmission-model-based linear programming model. The advantage of the proposed model compared with prior studies in the literature is that the multi-dimensional evacuation operation decisions are jointly obtained at the optimum of the JEDRFD model. The linear single-destination structure of the proposed model implies another advantage in computational efficiency. A numerical example is given to illustrate the modeling procedure and solution properties. Real-time operational issues and data requirements are also discussed.     

Up-regulation of T lymphocyte and antibody production by inflammatory cytokines released by macrophage exposure to multi-walled carbon nanotubes

Our data demonstrate that multi-walled carbon nanotubes (MWCNTs) are internalized by macrophages, subsequently activating them to produce interleukin (IL)-12 (IL-12). This cytokine induced the proliferative response of T lymphocytes to a nonspecific mitogen and to ovalbumin (OVA). This increase in the proliferative response was accompanied by an increase in the expression of pro-inflammatory cytokines, such as interferon-gamma (IFNγ), tumor necrosis factor-alpha (TNFα) and IL-6, in mice inoculated with MWCNTs, whether or not they had been immunized with OVA. A decrease in the expression of transforming growth factor-beta (TGFβ) was observed in the mice treated with MWCNTs, whereas the suppression of the expression of both TGFβ and IL-10 was observed in mice that had been both treated and immunized. The activation of the T lymphocyte response by the pro-inflammatory cytokines leads to an increase in antibody production to OVA, suggesting the important immunostimulatory effect of carbon nanotubes.     

Evaluation of Just-In-Time alternatives in the electric wire-harness industry

This paper investigates some of the theoretical and practical issues for the introduction of Just-in-Time (JIT) techniques into an automotive wire-harness assembly line. Some of the issues explored include the number of production kanbans and the unit load size to be used for every air of subassemblyassembly stations in a production line. An associated probability of stockout for different combinations is also determined. Simulation is used to validate the results obtained through an analytical method and to compare two commonly used strategies: the 'on-line' strategy which uses the subassembly operations adjacent to the assembly stations and the 'off-line' strategy which has the subassembly operation at some distance from the assembly line. Four performance criteria are used to evaluate the strategies: throughput, work-inprocess inventory, lead time, and subassembly equipment utilization.     

ISOLATION AND CHARACTERIZATION OF PARAFFINIC COMPONENTS FROM VENEZUELAN ASPHALTS EFFECTS OF PARAFFIN DOPANTS ON RHEOLOGICAL PROPERTIES OF SOME ASPHALTS

ABSTRACT

Paraffinic concentrates were isolated from a couple of Venezuelan asphalts, one paraffinic in nature and the other naphteno-aromatic Multigram scale isolation required two steps. The first one was the separation of neutral hydrocarbons by means of soxhlet extractors filled with clay and extracted with hot cyclohexane. The second step comprised the cryogenic wax crystallization and filtration from neutral hydrocarbons diluted in methyl ethyl ketone, brought to -10°C. Typical operations comprised 800g of asphalt and recovery of 20g of waxes.     

U.S. manufacturing aggregate energy intensity decomposition: The application of multivariate regression analysis

This paper introduces the use of a multivariate regression analysis to explain factors that impact aggregate energy intensity. This kind of study is useful to evaluate the past and predicts the future trends for energy‐policy evaluation. Historical aggregate fuel and electricity intensities of the entire U.S. manufacturing sector (Standard Industrial Classification, SIC, codes of 20–39) over the 1977–1998 period are used to develop the proposed multivariate regression model. The proposed model allows identifying the structural effect of aggregate energy intensity changes without relying on detailed disaggregated energy data. Its results are validated by comparison with those from conventional decomposition techniques based on economic index numbers. For illustration, the historical aggregate fuel intensity of the U.S. primary metal industry (SIC 33) is used as an example of a situation for which economic index numbers fail to decompose the historical aggregate energy intensity since the disaggregated energy data are unavailable, while the multivariate regression analysis can still be applied. Empirical results show that a structural shift contributes to decreases of about 28, 41 and 19% of total declines of U.S. manufacturing aggregate fuel, U.S. manufacturing aggregate electricity, and U.S. primary metal industry aggregate fuel intensities, respectively, for the 1977–1998 period. The method based on multivariate regression models estimates the time series structural effects within deviation averages of 8.5 and 7.0% of the time series structural effect estimates based on the economic index numbers for the U.S. manufacturing aggregate fuel and electricity intensities, respectively, even though the multivariate regression model does not require disaggregated energy data. Copyright © 2007 John Wiley & Sons, Ltd.     

Production and stability of water‐dispersible astaxanthin oleoresin from Phaffia rhodozyma

The process of extracting the astaxanthin oleoresin from pretreated Phaffia rhodozyma cells was optimised using a Box‐Behnken response surface design. Microwaving the cells at 105 W for 1 min followed by ethyl acetate extraction was the best pretreatment, and the optimal extraction conditions were 65 °C for 24 min using a solvent–solid ratio of 19:1. The order of the ability to disperse the astaxanthin oleoresin was propylene glycol> Tween 80 > Tween 20 > α‐cyclodextrin, β‐cyclodextrin. It was determined that the degradation of the colour of the water‐dispersible oleoresin followed a first‐order kinetics model. The greatest stability was observed at pH 4 and at the lowest temperature evaluated (40 °C). The thermal degradation of the pigment occurs in two steps, the first one from 0 to 1.5 h, with an E_aI = 10.31 kJ mol^?1, and the second one from 1.5 to 5 h, with an E_aII = 30.06 kJ mol^?1     

GSH and Zinc Supplementation Attenuate Cadmium-Induced Cellular Stress and Stimulation of Choline Uptake in Cultured Neonatal Rat Choroid Plexus Epithelia

Choroid plexus (CP) sequesters cadmium and other metals, protecting the brain from these neurotoxins. These metals can induce cellular stress and modulate homeostatic functions of CP, such as solute transport. We previously showed in primary cultured neonatal rat CP epithelial cells (CPECs) that cadmium induced cellular stress and stimulated choline uptake at the apical membrane, which interfaces with cerebrospinal fluid in situ. Here, in CPECs, we characterized the roles of glutathione (GSH) and Zinc supplementation in the adaptive stress response to cadmium. Cadmium increased GSH and decreased the reduced GSH-to-oxidized GSH (GSSG) ratio. Heat shock protein-70 (Hsp70), heme oxygenase (HO-1), and metallothionein (Mt-1) were induced along with the catalytic and modifier subunits of glutamate cysteine ligase (GCL), the rate-limiting enzyme in GSH synthesis. Inhibition of GCL by l-buthionine sulfoximine (BSO) enhanced stress protein induction and stimulation of choline uptake by cadmium. Zinc alone did not induce Hsp70, HO-1, or GCL subunits, or modulate choline uptake. Zinc supplementation during cadmium exposure attenuated stress protein induction and stimulation of choline uptake; this effect persisted despite inhibition of GSH synthesis. These data indicated up-regulation of GSH synthesis promotes adaptation to cadmium-induced cellular stress in CP, but Zinc may confer cytoprotection independent of GSH.