Flow system modeling with applications to fuel cell systems

Fuel cell systems have garnered much attention recently as a possible source of clean, efficient energy. These systems are presently being designed in various arrangements to combine the use of fuel cells with other efficient power producing devices such as gas turbines, producing a system which is more efficient than either the fuel cell or gas turbine alone. The accurate modeling of these types of systems is an important contribution to the increasing development of such technologies. Of particular interest is the transient behavior of these systems, including the flow and thermal behavior of the air and fuel used. The contribution of this work is the development of a numerical, one-dimensional, variable-area duct model to predict the transient flow and thermal behavior of gasses moving through the system. Additional transient models for plenum, tee, and elbow components are created, and these parts are connected with the duct model to perform simulations of simple flow systems. Some thermal and flow characteristics of these systems are analyzed and discussed. As a verification of the models created, a portion of an actual fuel cell system is modeled and the results are compared with experimental data

Modeling the public health impact of malaria vaccines for developers and policymakers

Efforts to develop malaria vaccines show promise. Mathematical model-based estimates of the potential demand, public health impact, and cost and financing requirements can be used to inform investment and adoption decisions by vaccine developers and policymakers on the use of malaria vaccines as complements to existing interventions. However, the complexity of such models may make their outputs inaccessible to non-modeling specialists. This paper describes a Malaria Vaccine Model (MVM) developed to address the specific needs of developers and policymakers, who need to access sophisticated modeling results and to test various scenarios in a user-friendly interface. The model's functionality is demonstrated through a hypothetical vaccine.; The MVM has three modules: supply and demand forecast; public health impact; and implementation cost and financing requirements. These modules include pre-entered reference data and also allow for user-defined inputs. The model includes an integrated sensitivity analysis function. Model functionality was demonstrated by estimating the public health impact of a hypothetical pre-erythrocytic malaria vaccine with 85% efficacy against uncomplicated disease and a vaccine efficacy decay rate of four years, based on internationally-established targets. Demand for this hypothetical vaccine was estimated based on historical vaccine implementation rates for routine infant immunization in 40 African countries over a 10-year period. Assumed purchase price was $5 per dose and injection equipment and delivery costs were$0.40 per dose.; The model projects the number of doses needed, uncomplicated and severe cases averted, deaths and disability-adjusted life years (DALYs) averted, and cost to avert each. In the demonstration scenario, based on a projected demand of 532 million doses, the MVM estimated that 150 million uncomplicated cases of malaria and 1.1 million deaths would be averted over 10 years. This is equivalent to 943 uncomplicate cases and 7 deaths averted per 1,000 vaccinees. In discounted 2011 US dollars, this represents $11 per uncomplicated case averted and$1,482 per death averted. If vaccine efficacy were reduced to 75%, the estimated uncomplicated cases and deaths averted over 10 years would decrease by 14% and 19%, respectively.; The MVM can provide valuable information to assist decision-making by vaccine developers and policymakers, information which will be refined and strengthened as field studies progress allowing further validation of modeling assumptions

A Gene Expression Fingerprint of C. Elegans Embryonic Motor Neurons

Differential gene expression specifies the highly diverse cell types that constitute the nervous system. With its sequenced genome and simple, well-defined neuroanatomy, the nematode C. elegans is a useful model system in which to correlate gene expression with neuron identity. The UNC-4 transcription factor is expressed in thirteen embryonic motor neurons where it specifies axonal morphology and synaptic function. These cells can be marked with an unc-4::GFP reporter transgene. Here we describe a powerful strategy, Micro-Array Profiling of C. elegans cells (MAPCeL), and confirm that this approach provides a comprehensive gene expression profile of unc-4::GFP motor neurons in vivo.

Improved particle size control for the dispersion polymerization of methyl methacrylate in supercritical carbon dioxide

Dispersion polymerization is a well-established method of producing polymer particles that are easily handled and processed. With careful choice of reaction conditions this technique can yield well defined, spherical particles for a wide range of applications. The use of supercritical carbon dioxide (scCO2) as a reaction medium offers a route to performing these syntheses without excessive use of volatile organic solvents and minimizes work-up and disposal steps. However a significant drawback has been the fact that up till now the control of particle size and morphology from CO2 have been limited. This study presents control of particle size and morphology over an unprecedented range for a single stabilizer in scCO2 by coordinating a few simple parameters to tailor the conditions toward different sizes. Further, this study introduces the novel approach in scCO2 of using delayed monomer addition which allows considerable reduction of the batch-to-batch variability as well as reduced agglomeration between particles

Speech delays and behavioral problems are the predominant features in individuals with developmental delays and 16p11.2 microdeletions and microduplications

Microdeletions and microduplications encompassing a ~593-kb region of 16p11.2 have been implicated as one of the most common genetic causes of susceptibility to autism/autism spectrum disorder (ASD). We report 45 microdeletions and 32 microduplications of 16p11.2, representing 0.78% of 9,773 individuals referred to our laboratory for microarray-based comparative genomic hybridization (aCGH) testing for neurodevelopmental and congenital anomalies. The microdeletion was de novo in 17 individuals and maternally inherited in five individuals for whom parental testing was available. Detailed histories of 18 individuals with 16p11.2 microdeletions were reviewed; all had developmental delays with below-average intelligence, and a majority had speech or language problems or delays and various behavioral problems. Of the 16 individuals old enough to be evaluated for autism, the speech/behavior profiles of seven did not suggest the need for ASD evaluation. Of the remaining nine individuals who had speech/behavior profiles that aroused clinical suspicion of ASD, five had formal evaluations, and three had PDD-NOS. Of the 19 microduplications with parental testing, five were de novo, nine were maternally inherited, and five were paternally inherited. A majority with the microduplication had delayed development and/or specific deficits in speech or language, though these features were not as consistent as seen with the microdeletions. This study, which is the largest cohort of individuals with 16p11.2 alterations reported to date, suggests that 16p11.2 microdeletions and microduplications are associated with a high frequency of cognitive, developmental, and speech delay and behavior abnormalities. Furthermore, although features associated with these alterations can be found in individuals with ASD, additional factors are likely required to lead to the development of ASD

Genome-wide association study of dental caries in the Hispanic Communities Health Study/Study of Latinos (HCHS/SOL)

Dental caries is the most common chronic disease worldwide, and exhibits profound disparities in the USA with racial and ethnic minorities experiencing disproportionate disease burden. Though heritable, the specific genes influencing risk of dental caries remain largely unknown. Therefore, we performed genome-wide association scans (GWASs) for dental caries in a population-based cohort of 12 000 Hispanic/Latino participants aged 18–74 years from the HCHS/SOL. Intra-oral examinations were used to generate two common indices of dental caries experience which were tested for association with 27.7 M genotyped or imputed single-nucleotide polymorphisms separately in the six ancestry groups. A mixed-models approach was used, which adjusted for age, sex, recruitment site, five principal components of ancestry and additional features of the sampling design. Meta-analyses were used to combine GWAS results across ancestry groups. Heritability estimates ranged from 20–53% in the six ancestry groups. The most significant association observed via meta-analysis for both phenotypes was in the region of the NAMPT gene (rs190395159; P-value = 6 × 10−10), which is involved in many biological processes including periodontal healing. Another significant association was observed for rs72626594 (P-value = 3 × 10−8) downstream of BMP7, a tooth development gene. Other associations were observed in genes lacking known or plausible roles in dental caries. In conclusion, this was the largest GWAS of dental caries, to date and was the first to target Hispanic/Latino populations. Understanding the factors influencing dental caries susceptibility may lead to improvements in prediction, prevention and disease management, which may ultimately reduce the disparities in oral health across racial, ethnic and socioeconomic strata

Homeostatic expansion of autoreactive immunoglobulin-secreting cells in the Rag2 mouse model of Omenn syndrome

Hypomorphic RAG mutations, leading to limited V(D)J rearrangements, cause Omenn syndrome (OS), a peculiar severe combined immunodeficiency associated with autoimmune-like manifestations. Whether B cells play a role in OS pathogenesis is so far unexplored. Here we report the detection of plasma cells in lymphoid organs of OS patients, in which circulating B cells are undetectable. Hypomorphic Rag2R229Q knock-in mice, which recapitulate OS, revealed, beyond severe B cell developmental arrest, a normal or even enlarged compartment of immunoglobulin-secreting cells (ISC). The size of this ISC compartment correlated with increased expression of Blimp1 and Xbp1, and these ISC were sustained by elevated levels of T cell derived homeostatic and effector cytokines. The detection of high affinity pathogenic autoantibodies toward target organs indicated defaults in B cell selection and tolerance induction. We hypothesize that impaired B cell receptor (BCR) editing and a serum B cell activating factor (BAFF) abundance might contribute toward the development of a pathogenic B cell repertoire in hypomorphic Rag2R229Q knock-in mice. BAFF-R blockade reduced serum levels of nucleic acid-specific autoantibodies and significantly ameliorated inflammatory tissue damage. These findings highlight a role for B cells in OS pathogenesis

Long-term Correction of Very Long-chain Acyl-CoA Dehydrogenase Deficiency in Mice Using AAV9 Gene Therapy

Very long-chain acyl-coA dehydrogenase (VLCAD) is the rate-limiting step in mitochondrial fatty acid oxidation. VLCAD-deficient mice and patients clinical symptoms stem from not only an energy deficiency but also long-chain metabolite accumulations. VLCAD-deficient mice were treated systemically with 1 × 1012 vector genomes of recombinant adeno-associated virus 9 (rAAV9)-VLCAD. Biochemical correction was observed in vector-treated mice beginning 2 weeks postinjection, as characterized by a significant drop in long-chain fatty acyl accumulates in whole blood after an overnight fast. Changes persisted through the termination point around 20 weeks postinjection. Magnetic resonance spectroscopy (MRS) and tandem mass spectrometry (MS/MS) revealed normalization of intramuscular lipids in treated animals. Correction was not observed in liver tissue extracts, but cardiac muscle extracts showed significant reduction of long-chain metabolites. Disease-specific phenotypes were characterized, including thermoregulation and maintenance of euglycemia after a fasting cold challenge. Internal body temperatures of untreated VLCAD−/− mice dropped below 20 °C and the mice became lethargic, requiring euthanasia. In contrast, all rAAV9-treated VLCAD−/− mice and the wild-type controls maintained body temperatures. rAAV9-treated VLCAD−/− mice maintained euglycemia, whereas untreated VLCAD−/− mice suffered hypoglycemia following a fasting cold challenge. These promising results suggest rAAV9 gene therapy as a potential treatment for VLCAD deficiency in humans

Genetic Effects on Bone Loss in Peri- and Postmenopausal Women: A Longitudinal Twin Study

This longitudinal twin study was designed to assess the heritability of bone loss in peri- and postmenopausal women. A sample of 724 female twins was studied. Baseline and repeat BMD measurements were performed. Results of genetic model-fitting analysis indicated genetic effects on bone loss account for similar to 40% of the between-individual variation in bone loss at the lumbar spine, forearm, and whole body. Introduction: BMD and bone loss are important predictors of fracture risk. Although the heritability of peak BMD is well documented, it is not clear whether bone loss is also under genetic regulation. This study was designed to assess the heritability of bone loss in peri- and postmenopausal women. Materials and Methods: A sample of 724 female twins (177 monozygotic [MZ] and 185 dizygotic [DZ] pairs), 45-82 yr of age, was studied. Each individual had baseline BMD measurements at the lumbar spine, hip, forearm, and total body by DXA and at least one repeat measure, on average 4.9 yr later. Change in BMD (Delta BMD) was expressed as percent of gain or loss per year. Intraclass correlation coefficients for ABMD were calculated for MZ and DZ pairs. Genetic model-fitting analysis was conducted to partition the total variance of ABMD into three components: genetic (G), common environment (C), and specific environment, including measurement error (E). The index of heritability was estimated as the ratio of genetic variance over total variance. Results: The mean annual Delta BMD was -0.37 +/- 1.43% (SD) per year at the lumbar spine, -0.27 +/- 1.32% at the total hip, -0.77 +/- 1.66% at the total forearm, -0.36 +/- 56% at the femoral neck, and -0.16 +/- 0.81% at the whole body. Intraclass correlation coefficients were significantly higher in MZ than in DZ twins for all studied parameters, except at the hip sites. Results of genetic model-fitting analysis indicated that the indices of heritability for ABMD were 0.38, 0.49, and 0.44 for the lumbar spine, total forearm, and whole body, respectively. However, the genetic effect on ABMD at all hip sites was not significant. Conclusions: These data suggest that, although genetic effects on bone loss with aging are less pronounced than on peak bone mass, they still account for similar to 40% of the between-individual variation in bone loss for the lumbar spine, total forearm, and whole body in peri- and postmenopausal women. These findings are relevant for studies aimed at identification of genes that are involved in the regulation of bone loss