A comparative study of FMS tool allocation and part type selection approaches for a varying part type mix

Hankins and Rovito (1984) examined the impact of different tool policies on cutting tool inventory levels and spindle utilization for a flexible manufacturing system (FMS). This study provides a broader perspective of the impact of tool allocation approaches on flow times, tardiness, percent of orders tardy, machine utilization, and robot utilization. Part type selection procedures have been suggested for the FMS prerelease planning problem. However, very little research has specifically evaluated the part type selection procedures across different tool allocation approaches. Also, with the exception of Stecke and Kim (1988, 1991) no other known study has provided any insights on what tool allocation approaches are appropriate when processing different mixes of part types. This research is devoted to addressing those issues. Three tool allocation approaches, three production scheduling rules, and three levels of part mix are evaluated in this study through a similation model of a flexible manufacturing system. The specific impacts of the tool approaches, their interaction effects with the part type selection rules, and their effectiveness at different part type mix levels are provided through the use of a regression metamodel.     

Empirical studies of escape behavior find mixed support for the race for life model

Escape theory has been exceptionally successful in conceptualizing and accurately predicting effects of numerous factors that affect predation risk and explaining variation in flight initiation distance (FID; predator–prey distance when escape begins). Less explored is the relative orientation of an approaching predator, prey, and its eventual refuge. The relationship between an approaching threat and its refuge can be expressed as an angle we call the “interpath angle” or “Φ,” which describes the angle between the paths of predator and prey to the prey’s refuge and thus expresses the degree to which prey must run toward an approaching predator. In general, we might expect that prey would escape at greater distances if they must flee toward a predator to reach its burrow. The “race for life” model makes formal predictions about how Φ should affect FID. We evaluated the model by studying escape decisions in yellow-bellied marmots Marmota flaviventer, a species which flees to burrows. We found support for some of the model’s predictions, yet the relationship between Φ and FID was less clear. Marmots may not assess Φ in a continuous fashion; but we found that binning angle into 4 45° bins explained a similar amount of variation as models that analyzed angle continuously. Future studies of Φ, especially those that focus on how different species perceive relative orientation, will likely enhance our understanding of its importance in flight decisions.     

Reasons for Missing Antiretroviral Therapy: Results from a Multi-Country Study in Tanzania,Uganda, and Zambia

Objectives

To identify the reasons patients miss taking their antiretroviral therapy (ART) and the proportion who miss their ART because of symptoms; and to explore the association between symptoms and incomplete adherence.

Methods

Secondary analysis of data collected during a cross-sectional study that examined ART adherence among adults from 18 purposefully selected sites in Tanzania, Uganda, and Zambia. We interviewed 250 systematically selected patients per facility (≥18 years) on reasons for missing ART and symptoms they had experienced (using the HIV Symptom Index). We abstracted clinical data from the patients’ medical, pharmacy, and laboratory records. Incomplete adherence was defined as having missed ART for at least 48 consecutive hours during the past 3 months.

Results

Twenty-nine percent of participants reported at least one reason for having ever missed ART (1278/4425). The most frequent reason was simply forgetting (681/1278 or 53%), followed by ART-related hunger or not having enough food (30%), and symptoms (12%). The median number of symptoms reported by participants was 4 (IQR: 2–7). Every additional symptom increased the odds of incomplete adherence by 12% (OR: 1.1, 95% CI: 1.1–1.2). Female participants and participants initiated on a regimen containing stavudine were more likely to report greater numbers of symptoms.

Conclusions

Symptoms were a common reason for missing ART, together with simply forgetting and food insecurity. A combination of ART regimens with fewer side effects, use of mobile phone text message reminders, and integration of food supplementation and livelihood programmes into HIV programmes, have the potential to decrease missed ART and hence to improve adherence and the outcomes of ART programmes.     

Caenorhabditis elegans,a pluricellular model organism to screen new genes involved in mitochondrial genome maintenance

The inheritance of functional mitochondria depends on faithful replication and transmission of mitochondrial DNA (mtDNA). A large and heterogeneous group of human disorders is associated with mitochondrial genome quantitative and qualitative anomalies. Several nuclear genes have been shown to account for these severe OXPHOS disorders. However, in several cases, the disease-causing mutations still remain unknown.Caenorhabditis elegans has been largely used for studying various biological functions because this multicellular organism has short life cycle and is easy to grow in the laboratory. Mitochondrial functions are relatively well conserved between human and C. elegans, and heteroplasmy exists in this organism as in human. C. elegans therefore represents a useful tool for studying mtDNA maintenance. Suppression by RNA interference of genes involved in mtDNA replication such as polg-1, encoding the mitochondrial DNA polymerase, results in reduced mtDNA copy number but in a normal phenotype of the F1 worms. By combining RNAi of genes involved in mtDNA maintenance and EtBr exposure, we were able to reveal a strong and specific phenotype (developmental larval arrest) associated to a severe decrease of mtDNA copy number. Moreover, we tested and validated the screen efficiency for human orthologous genes encoding mitochondrial nucleoid proteins. This allowed us to identify several genes that seem to be closely related to mtDNA maintenance in C. elegans.This work reports a first step in the further development of a large-scale screening in C. elegans that should allow to identify new genes of mtDNA maintenance whose human orthologs will obviously constitute new candidate genes for patients with quantitative or qualitative mtDNA anomalies.     

Tau Kinetics in Neurons and the Human Central Nervous System

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Cu(II) organizes beta-2-microglobulin oligomers but is released upon amyloid formation

beta-2-Microglobulin (beta2m) is deposited as amyloid fibrils in the bones and joints of patients undergoing long-term dialysis treatment as a result of kidney failure. Previous work has shown that biologically relevant amounts of Cu(II) can cause beta2m to be converted to amyloid fibrils under physiological conditions in vitro. In this work, dynamic light scattering, mass spectrometry, and size-exclusion chromatography are used to characterize the role that Cu plays in the formation of oligomeric intermediates that precede fibril formation. Cu(II) is found to be necessary for the stability of the dimer and an initial form of the tetramer. The initially formed tetramer then undergoes a structural change to a state that no longer binds Cu(II) before progressing to a hexameric state. Based on these results, we propose that the lag phase associated with beta2m fibril formation is partially accounted for by the structural transition of the tetramer that results in Cu(II) loss. Consistent with this observation is the determination that the mature beta2m amyloid fibrils do not contain Cu. Thus, Cu(II) appears to play a catalytic role by enabling the organization of the necessary oligomeric intermediates that precede beta2m amyloid formation.     

The role of the anion in the reaction of reducing sugars with ammonium salts

Reactions of reducing sugars with ammonia and its compounds are important commercially, particularly in the preparation of flavors and caramel colors. However, such reactions generally produce a complex series of products ranging from simple molecules to complex polymeric materials, particularly since commercial systems generally involve mixtures of sugars as opposed to single sugars. This complexity has made understanding the mechanisms of such reactions difficult. Therefore, investigatory work has generally been focused on model systems. Herein we report one such study with model systems: the effects of the nature of the anion of the reactions of reducing sugars with ammonium salts. D-Glucose was reacted in aqueous solution with each of the following ammonium salts: acetate, bicarbonate, carbonate, chloride, citrate, formate, monohydrogenphosphate (DAP), sulfate, and sulfite. These reactions were carried out in a Parr bomb at 93 degrees C for 2.5 h. The initial pH of the reaction mixtures was adjusted to pH 8.0 at 25 degrees C. The resulting mixtures were analyzed by LC-MS, and the results were analyzed by comparing the product yields and distributions with those obtained with DAP. The major reaction product of interest was 2,6-deoxyfructosazine, as it had been shown to be a marker for the polymeric material formed from such reactions. It was found that ammonium salts of weak acids were much more effective in effecting the desired reactions than were those of strong acids; however, none was as effective as DAP.     

Stable isotope labeling tandem mass spectrometry (SILT): integration with peptide identification and extension to data-dependent scans

Quantitation of relative or absolute amounts of proteins by mass spectrometry can be prone to large errors. The use of MS/MS ion intensities and stable isotope labeling, which we term stable isotope labeling tandem mass spectrometry (SILT), decreases the effects of contamination from unrelated compounds. We present a software package (SILTmass) that automates protein identification and quantification by the SILT method. SILTmass has the ability to analyze the kinetics of protein turnover, in addition to relative and absolute protein quantitation. Instead of extracting chromatograms to find elution peaks, SILTmass uses only scans in which a peptide is identified and that meet an ion intensity threshold. Using only scans with identified peptides, the accuracy and precision of SILT is shown to be superior to precursor ion intensities, particularly at high or low dilutions of the isotope labeled compounds or with low amounts of protein. Using example scans, we demonstrate likely reasons for the improvements in quantitation by SILT. The appropriate use of variable modifications in peptide identification is described for measurement of protein turnover kinetics. The combination of identification with SILT facilitates quantitation without peak detection and helps to ensure the appropriate use of variable modifications for kinetics experiments.     

Factors affecting the choice of cooking fuel, cooking place and respiratory health in the Accra metropolitan area, Ghana

Indoor air pollution resulting from the combustion of solid fuels has been identified as a major health threat in the developing world. This study examines how the choice of cooking fuel, place of cooking and behavioural risk factors affect respiratory health infections in Accra, Ghana. About 65.3% of respondents use charcoal and 4.2% use unprocessed wood. A total of 241 (25.4%) respondents who cook had had respiratory health symptoms in the two weeks preceding the study. Household socioeconomic status and educational attainment of respondents were found to have a significant impact on respiratory health through their particular influence on the choice of cooking fuel. Households that use wood and charcoal have a high incidence of respiratory health symptoms. The poor are more affected by respiratory health problems due to their heavy dependence on solid fuels as compared with their wealthy counterparts. Households that cook in multiple purpose rooms are more affected by respiratory health problems than those that cook outdoors. There is a positive correlation between the presence of children in the kitchen during cooking and the incidence of respiratory health symptoms among children (r=0.31, p<0.0001). Poverty and lack of education and awareness are the major factors affecting the choice of cooking fuel, place of cooking and respiratory health in Accra.     

Mycobacterium tuberculosis functional network analysis by global subcellular protein profiling

Trends in increased tuberculosis infection and a fatality rate of approximately 23% have necessitated the search for alternative biomarkers using newly developed postgenomic approaches. Here we provide a systematic analysis of Mycobacterium tuberculosis (Mtb) by directly profiling its gene products. This analysis combines high-throughput proteomics and computational approaches to elucidate the globally expressed complements of the three subcellular compartments (the cell wall, membrane, and cytosol) of Mtb. We report the identifications of 1044 proteins and their corresponding localizations in these compartments. Genome-based computational and metabolic pathways analyses were performed and integrated with proteomics data to reconstruct response networks. From the reconstructed response networks for fatty acid degradation and lipid biosynthesis pathways in Mtb, we identified proteins whose involvements in these pathways were not previously suspected. Furthermore, the subcellular localizations of these expressed proteins provide interesting insights into the compartmentalization of these pathways, which appear to traverse from cell wall to cytoplasm. Results of this large-scale subcellular proteome profile of Mtb have confirmed and validated the computational network hypothesis that functionally related proteins work together in larger organizational structures.