Improving inventory and distribution in an aerospace parts and service organization

Thesis (M.B.A.)--Massachusetts Institute of Technology, Sloan School of Management; and, (S.M.)--Massachusetts Institute of Technology, Engineering Systems Division; in conjunction with the Leaders for Global Operations Program at MIT, 2011.Cataloged from PDF version of thesis.Includes bibliographical references (p. 80).Hamilton Sundstrand has made several changes to their supply chain in recent years, including increased offshore and outsourced production, new service offerings and relocation of facilities, to meet shifting business needs to remain a top competitor in the aerospace systems industry. This thesis reviews the distribution network of their aftermarket parts and service business to ensure that Hamilton Sundstrand meets customer needs through efficient supply chain design and aligning business strategy with inventory planning. A review of the current state is employed to locate gaps in strategic design, operating efficiencies and customer service levels. Improvement opportunities identified in the current state analysis are addressed with proposed alternatives to adjust the distribution network to meet current and future needs while minimizing cost and maintaining or raising service levels. The combined proposals of relocating distribution center volumes, reducing on hand inventory at co-located sites and closing a forward stocking location are estimated to result in over one million dollars in annual cost savings.by Steven Allan Wessels, Jr.S.M.M.B.A

Band-edge properties of a semiconductor alloy: An NMR study of Hg1−xCdxTe

We report Hg199 NMR measurements of narrow-gap Hg1−xCdxTe alloys in the range x=0.20–0.28. By studying temperature dependences, we have identified intrinsic Knight shifts in these alloys. This provides a measure of Hg orbital contributions to conduction-electron states, and we find a consistently strong average contribution from Hg s orbitals. Furthermore, we identify local variations in the Knight shift with spatial variations in conduction-electron densities and symmetries. These characteristics have been related to randomly populated sites within the alloys. We also discuss Hg199 chemical shifts and their relation to local orbital charges

Contribution of citizen science to improve knowledge on marine biodiversity in the Gulf Region

Monitoring marine biodiversity is costly and practical solutions have to be implemented to identify species and their preferred habitats, particularly in this era of rapid global change. Citizen science has proven to be effective and with high potential for monitoring efforts, and has been extensively applied to biodiversity. We have used the citizen science approach to engage the general public and stakeholders to contribute improving the current knowledge of sea snake biodiversity in Qatar and the Gulf Region. Logistic regression analysis using demographic data from interview surveys conducted in Qatar has indicated that the people having seen more sea snakes are older than 30 years and are Qatari citizens and/or fishermen from India. Of the ten species of sea snakes listed in the literature to be present in the Gulf Region, most of them have been reported for Qatar, Bahrain, United Arab Emirates and Saudi Arabia. However, the number of species present is often assumed based on their occurrence within the Arabian Gulf rather than on actual captures and appropriate identification. The creation of marine reference biological scientific collections to properly identify the species and make accurate biodiversity inventories is an urgent priority for the countries in the Gulf region. To this end, contributions by stakeholders and the general public for this study have proven to be very useful. However a larger networking with local and international scientists and stakeholders is still needed to adequately survey the country''s current biodiversity, identify research priorities and eventually provide the scientific input needed to assist biodiversity management related to renewable resource management and marine conservation in the Arabian Gulf Region

Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)

BACKGROUND:Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. METHODOLOGY/PRINCIPAL FINDINGS:Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB's DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. CONCLUSIONS:Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators

Gene expression changes associated with Barrett's esophagus and Barrett's-associated adenocarcinoma cell lines after acid or bile salt exposure

<p>Abstract</p> <p>Background</p> <p>Esophageal reflux and Barrett's esophagus represent two major risk factors for the development of esophageal adenocarcinoma. Previous studies have shown that brief exposure of the Barrett's-associated adenocarcinoma cell line, SEG-1, or primary cultures of Barrett's esophageal tissues to acid or bile results in changes consistent with cell proliferation. In this study, we determined whether similar exposure to acid or bile salts results in gene expression changes that provide insights into malignant transformation.</p> <p>Methods</p> <p>Using previously published methods, Barrett's-associated esophageal adenocarcinoma cell lines and primary cultures of Barrett's esophageal tissue were exposed to short pulses of acid or bile salts followed by incubation in culture media at pH 7.4. A genome-wide assessment of gene expression was then determined for the samples using cDNA microarrays. Subsequent analysis evaluated for statistical differences in gene expression with and without treatment.</p> <p>Results</p> <p>The SEG-1 cell line showed changes in gene expression that was dependent on the length of exposure to pH 3.5. Further analysis using the Gene Ontology, however, showed that representation by genes associated with cell proliferation is not enhanced by acid exposure. The changes in gene expression also did not involve genes known to be differentially expressed in esophageal adenocarcinoma. Similar experiments using short-term primary cultures of Barrett's esophagus also did not result in detectable changes in gene expression with either acid or bile salt exposure.</p> <p>Conclusion</p> <p>Short-term exposure of esophageal adenocarcinoma SEG-1 cells or primary cultures of Barrett's esophagus does not result in gene expression changes that are consistent with enhanced cell proliferation. Thus other model systems are needed that may reflect the impact of acid and bile salt exposure on the esophagus <it>in vivo</it>.</p

Deterministic Classifiers Accuracy Optimization for Cancer Microarray Data

The objective of this study was to improve classification accuracy in cancer microarray gene expression data using a collection of machine learning algorithms available in WEKA. State of the art deterministic classification methods, such as: Kernel Logistic Regression, Support Vector Machine, Stochastic Gradient Descent and Logistic Model Trees were applied on publicly available cancer microarray datasets aiming to discover regularities that provide insights to help characterization and diagnosis correctness on each cancer typology. The implemented models, relying on 10-fold cross-validation, parameterized to enhance accuracy, reached accuracy above 90%. Moreover, although the variety of methodologies, no significant statistic differences were registered between them, at significance level 0.05, confirming that all the selected methods are effective for this type of analysis.info:eu-repo/semantics/publishedVersio

A Critical Role of a Cellular Membrane Traffic Protein in Poliovirus RNA Replication

Replication of many RNA viruses is accompanied by extensive remodeling of intracellular membranes. In poliovirus-infected cells, ER and Golgi stacks disappear, while new clusters of vesicle-like structures form sites for viral RNA synthesis. Virus replication is inhibited by brefeldin A (BFA), implicating some components(s) of the cellular secretory pathway in virus growth. Formation of characteristic vesicles induced by expression of viral proteins was not inhibited by BFA, but they were functionally deficient. GBF1, a guanine nucleotide exchange factor for the small cellular GTPases, Arf, is responsible for the sensitivity of virus infection to BFA, and is required for virus replication. Knockdown of GBF1 expression inhibited virus replication, which was rescued by catalytically active protein with an intact N-terminal sequence. We identified a mutation in GBF1 that allows growth of poliovirus in the presence of BFA. Interaction between GBF1 and viral protein 3A determined the outcome of infection in the presence of BFA

Comparison of normalisation methods for surface-enhanced laser desorption and ionisation (SELDI) time-of-flight (TOF) mass spectrometry data

<p>Abstract</p> <p>Background</p> <p>Mass spectrometry for biological data analysis is an active field of research, providing an efficient way of high-throughput proteome screening. A popular variant of mass spectrometry is SELDI, which is often used to measure sample populations with the goal of developing (clinical) classifiers. Unfortunately, not only is the data resulting from such measurements quite noisy, variance between replicate measurements of the same sample can be high as well. Normalisation of spectra can greatly reduce the effect of this technical variance and further improve the quality and interpretability of the data. However, it is unclear which normalisation method yields the most informative result.</p> <p>Results</p> <p>In this paper, we describe the first systematic comparison of a wide range of normalisation methods, using two objectives that should be met by a good method. These objectives are minimisation of inter-spectra variance and maximisation of signal with respect to class separation. The former is assessed using an estimation of the coefficient of variation, the latter using the classification performance of three types of classifiers on real-world datasets representing two-class diagnostic problems. To obtain a maximally robust evaluation of a normalisation method, both objectives are evaluated over multiple datasets and multiple configurations of baseline correction and peak detection methods. Results are assessed for statistical significance and visualised to reveal the performance of each normalisation method, in particular with respect to using no normalisation. The normalisation methods described have been implemented in the freely available MASDA R-package.</p> <p>Conclusion</p> <p>In the general case, normalisation of mass spectra is beneficial to the quality of data. The majority of methods we compared performed significantly better than the case in which no normalisation was used. We have shown that normalisation methods that scale spectra by a factor based on the dispersion (e.g., standard deviation) of the data clearly outperform those where a factor based on the central location (e.g., mean) is used. Additional improvements in performance are obtained when these factors are estimated locally, using a sliding window within spectra, instead of globally, over full spectra. The underperforming category of methods using a globally estimated factor based on the central location of the data includes the method used by the majority of SELDI users.</p

Thermoregulation of Capsule Production by Streptococcus pyogenes

The capsule of Streptococcus pyogenes serves as an adhesin as well as an anti-phagocytic factor by binding to CD44 on keratinocytes of the pharyngeal mucosa and the skin, the main entry sites of the pathogen. We discovered that S. pyogenes HSC5 and MGAS315 strains are further thermoregulated for capsule production at a post-transcriptional level in addition to the transcriptional regulation by the CovRS two-component regulatory system. When the transcription of the hasABC capsular biosynthetic locus was de-repressed through mutation of the covRS system, the two strains, which have been used for pathogenesis studies in the laboratory, exhibited markedly increased capsule production at sub-body temperature. Employing transposon mutagenesis, we found that CvfA, a previously identified membrane-associated endoribonuclease, is required for the thermoregulation of capsule synthesis. The mutation of the cvfA gene conferred increased capsule production regardless of temperature. However, the amount of the capsule transcript was not changed by the mutation, indicating that a post-transcriptional regulator mediates between CvfA and thermoregulated capsule production. When we tested naturally occurring invasive mucoid strains, a high percentage (11/53, 21%) of the strains exhibited thermoregulated capsule production. As expected, the mucoid phenotype of these strains at sub-body temperature was due to mutations within the chromosomal covRS genes. Capsule thermoregulation that exhibits high capsule production at lower temperatures that occur on the skin or mucosal surface potentially confers better capability of adhesion and invasion when S. pyogenes penetrates the epithelial surface