High-intensity exercise to promote accelerated improvements in cardiorespiratory fitness (HI-PACE): study protocol for a randomized controlled trial

Background: African Americans have a disproportionate prevalence and incidence of type 2 diabetes compared with Caucasians. Recent evidence indicates that low cardiorespiratory fitness (CRF) level, an independent risk factor for type 2 diabetes, is also more prevalent in African Americans than Caucasians. Numerous studies in Caucasian populations suggest that vigorous exercise intensity may promote greater improvements in CRF and other type 2 diabetes risk factors (e.g., reduction of glucose/insulin levels, pulse wave velocity, and body fat) than moderate intensity. However, current evidence comparing health benefits of different aerobic exercise intensities on type 2 diabetes risk factors in African Americans is negligible. This is clinically important as African Americans have a greater risk for type 2 diabetes and are less likely to meet public health recommendations for physical activity than Caucasians. The purpose of the HI-PACE (High-Intensity exercise to Promote Accelerated improvements in CardiorEspiratory fitness) study is to evaluate whether high-intensity aerobic exercise elicits greater improvements in CRF, insulin action, and arterial stiffness than moderate-intensity exercise in African Americans. Methods/Design: A randomized controlled trial will be performed on overweight and obese (body mass index of 25–45 kg/m2) African Americans (35–65 years) (n = 60). Participants will be randomly assigned to moderate-intensity (MOD-INT) or high-intensity (HIGH-INT) aerobic exercise training or a non-exercise control group (CON) for 24 weeks. Supervised exercise will be performed at a heart rate associated with 45–55% and 70–80% of VO2 max in the MOD-INT and HIGH-INT groups, respectively, for an exercise dose of 600 metabolic equivalents of task (MET)-minutes per week (consistent with public health recommendations). The primary outcome is change in CRF. Secondary outcomes include change in insulin sensitivity (measured via an intravenous glucose tolerance test), skeletal muscle mitochondrial oxidative capacity (via near-infrared spectroscopy), skeletal muscle measurements (i.e., citrate synthase, COX IV, GLUT-4, CPT-1, and PGC1-α), arterial stiffness (via carotid-femoral pulse wave velocity), body fat, C-reactive protein, and psychological outcomes (quality of life/exercise enjoyment). Discussion: The anticipated results of the HI-PACE study will provide vital information on the health effects of high-intensity exercise in African Americans. This study will advance health disparity research and has the potential to influence future public health guidelines for physical activity

Extremely short duration interval exercise improves 24-h glycaemia in men with type 2 diabetes

PurposeReduced-exertion high-intensity interval training (REHIT) is a genuinely time-efficient exercise intervention that improves aerobic capacity and blood pressure in men with type 2 diabetes. However, the acute effects of REHIT on 24-h glycaemia have not been examined.Methods11 men with type 2 diabetes (mean ± SD: age, 52 ± 6 years; BMI, 29.7 ± 3.1 kg/m2; HbA1c, 7.0 ± 0.8%) participated in a randomised, four-trial crossover study, with continual interstitial glucose measurements captured during a 24-h dietary-standardised period following either (1) no exercise (CON); (2) 30 min of continuous exercise (MICT); (3) 10 × 1 min at ~ 90 HRmax (HIIT; time commitment, ~ 25 min); and (4) 2 × 20 s ‘all-out’ sprints (REHIT; time commitment, 10 min).ResultsCompared to CON, mean 24-h glucose was lower following REHIT (mean ± 95%CI: − 0.58 ± 0.41 mmol/L, p = 0.008, d = 0.55) and tended to be lower with MICT (− 0.37 ± 0.41 mmol/L, p = 0.08, d = 0.35), but was not significantly altered following HIIT (− 0.37 ± 0.59 mmol/L, p = 0.31, d = 0.35). This seemed to be largely driven by a lower glycaemic response (area under the curve) to dinner following both REHIT and MICT (− 11%, p  0.9 for both) but not HIIT (− 4%, p = 0.22, d = 0.38). Time in hyperglycaemia appeared to be reduced with all three exercise conditions compared with CON (REHIT: − 112 ± 63 min, p = 0.002, d = 0.50; MICT: -115 ± 127 min, p = 0.08, d = 0.50; HIIT − 125 ± 122 min, p = 0.04, d = 0.54), whilst indices of glycaemic variability were not significantly altered.ConclusionREHIT may offer a genuinely time-efficient exercise option for improving 24-h glycaemia in men with type 2 diabetes and warrants further study

Alternate Fuels and Chemicals From Synthesis Gas: Vinyl Acetate Monomer. Final Report

There has been a long-standing desire on the part of industry and the U.S. Department of Energy to replace the existing ethylene-based vinyl acetate monomer (VAM) process with an entirely synthesis gas-based process. Although there are a large number of process options for the conversion of synthesis gas to VAM, Eastman Chemical Company undertook an analytical approach, based on known chemical and economic principles, to reduce the potential candidate processes to a select group of eight processes. The critical technologies that would be required for these routes were: (1) the esterification of acetaldehyde (AcH) with ketene to generate VAM, (2) the hydrogenation of ketene to acetaldehyde, (3) the hydrogenation of acetic acid to acetaldehyde, and (4) the reductive carbonylation of methanol to acetaldehyde. This report describes the selection process for the candidate processes, the successful development of the key technologies, and the economic assessments for the preferred routes. In addition, improvements in the conversion of acetic anhydride and acetaldehyde to VAM are discussed. The conclusion from this study is that, with the technology developed in this study, VAM may be produced from synthesis gas, but the cost of production is about 15% higher than the conventional oxidative acetoxylation of ethylene, primarily due to higher capital associated with the synthesis gas-based processes

SYNTHESIS OF METHYL METHACRYLATE FROM COAL-DERIVED SYNGAS

Research Triangle Institute (RTI), Eastman Chemical Company, and Bechtel collectively are developing a novel three-step process for the synthesis of methyl methacrylate (MMA) from coal-derived syngas that consists of the steps of synthesis of a propionate, its condensation with formaldehyde to form methacrylic acid (MAA), and esterification of MAA with methanol to produce MMA. The research team has completed the research on the three-step methanol-based route to MMA. Under an extension to the original contract, we are currently evaluating a new DME-based process for MMA. The key research need for DME route is to develop catalysts for DME partial oxidation reactions and DME condensation reactions. During the April-June quarter(04-06/99) the first in-situ formaldehyde generation from DME and condensation with methyl propionate is demonstrated and the results are summarized. The supported niobium catalyst shows better condensation activity, but supported tungsten catalyst has higher formaldehyde selectivity. The project team has also completed a 200-hour long term test of PA-HCHO condensation over 30% Nb{sub 2}O{sub 5}/SiO{sub 2}. Three activity cycles and two regeneration cycles were carried out. 30% Nb{sub 2}O{sub 5}/SiO{sub 2} showed similar MAA yields as 10% Nb{sub 2}O{sub 5}/SiO{sub 2} at 300 C. However, the deactivation appears to be slower with 30% Nb{sub 2}O{sub 5}/SiO{sub 2} than 10% Nb{sub 2}O{sub 5}/SiO{sub 2}. An detailed economic analysis of PA-HCHO condensation process for a 250 million lb/yr MMA plant is currently studied by Bechtel. Using the Amoco data-based azeotropic distillation model as the basis, an ASPEN flow sheet model was constructed to simulate the formaldehyde and propionic acid condensation processing section based on RTI's design data. The RTI MAA effluent azeotropic distillation column was found to be much more difficult to converge. The presence of non-condensible gases along with the byproduct DEK (both of which were not presented in Amoco's data) appear to the culprits

SYNTHESIS OF METHYL METHACRYLATE FROM COAL-DERIVED SYNGAS

Research Triangle Institute (RTI), Eastman Chemical Company, and Bechtel collectively are developing a novel three-step process for the synthesis of methyl methacrylate (MMA) from coal-derived syngas that consists of the steps of synthesis of a propionate, its condensation with formaldehyde to form methacrylic acid (MAA), and esterification of MAA with methanol to produce MMA. RTI has completed the research on the three-step methanol-based route to MMA. Under an extension to the original contract, RTI is currently evaluating a new DME-based process for MMA. The key research need for DME route is to develop catalysts for DME partial oxidation reactions and DME condensation reactions. Over the last quarter (July-September, 1998), the project team has completed the continuous condensation of formaldehyde with propionic acid over 10% Nb{sub 2}O{sub 5}/SiO{sub 2} at 300 C. Six activity and five regeneration cycles have been completed. The results show that 10% Nb{sub 2}O{sub 5}/SiO{sub 2} deactivates slowly with time but can be regenerated to its original activity with 2% O{sub 2} in nitrogen over night at 400 C. We have investigated the effects of regeneration, propionic acid/formaldehyde ratio (PA/HCHO = 4.5/1 to 1.5/1) and reaction temperature(280-300 C) on reaction activity and product selectivity over 20% Nb{sub 2}O{sub 5}/SiO{sub 2} catalysts. The regeneration effect on 20% Nb{sub 2}O{sub 5}/SiO{sub 2} is similar to the effect on 10% Nb{sub 2}O{sub 5}/SiO{sub 2}. The regeneration can bring the deactivated catalyst to its original activity. However, the selectivity to MAA decreases with regeneration while the selectivity to DEK and CO{sub 2} increases. When PA/HCHO ratio is decreased from 4.5/1 to 2.25/1 then to 1.5/1 at 300 C the MAA yield decreases but the MAA selectivity first increases then decreases. Decreasing the reaction temperature from 300 C to 280 C decreases the MAA yield from 39.5% to 30.7% but increases the MAA selectivity from 73.7% to 82.2%. The results indicate that both temperature and PA/HCHO ratio are important parameters to optimize the economic of the condensation between propionic acid and formaldehyde

SYNTHESIS OF METHYL METHACRYLATE FROM COAL-DERIVED SYNGAS

Research Triangle Institute (RTI), Eastman Chemical Company, and Bechtel collectively are developing a novel three-step process for the synthesis of methyl methacrylate (MMA) from coal-derived syngas that consists of the steps of synthesis of a propionate, its condensation with formaldehyde to form methacrylic acid (MAA), and esterification of MAA with methanol to produce MMA. The research team has completed the research on the three-step methanol-based route to MMA. Under an extension to the original contract, we are currently evaluating a new DME-based process for MMA. The key research need for DME route is to develop catalysts for DME partial oxidation reactions and DME condensation reactions. Over the last quarter(Oct.-Dec./98), we have investigated the condensation between methyl propionate and formaldehyde (MP/HCHO=4.5/1) at various reaction temperatures(280-360EC) over 5%, 10%, and 20% Nb O /SiO catalysts. The conversion of HCHO increases with reaction 2 5 2 temperature and niobium loading. MMA+MAA selectivity goes through a maximum with the temperature over both 10% and 20% Nb O /SiO . The selectivities to MMA+MAA are 67.2%, 2 5 2 72.3%and 58.1% at 320EC over 5%, 10%, 20% Nb O /SiO , respectively. However, the 2 5 2 conversion of formaldehyde decreases rapidly with time on stream. The results suggest that silica supported niobium catalysts are active and selective for condensation of MP with HCHO, but deactivation needs to be minimized for the consideration of commercial application. We have preliminarily investigated the partial oxidation of dimethyl ether(DME) over 5% Nb O /SiO catalyst. Reactant gas mixture of 0.1% DME, 0.1% O and balance nitrogen is 2 5 2 2 studied with temperature ranging from 200°C to 500°C. The conversion of DME first increases with temperature reaching an maximum at 400°C then decreases. The selectivity to HCHO also increases with reaction temperature first. But the selectivity to HCHO decreases at temperature above 350°C accompanied by the increasing selectivity to CO . The results suggest that silica 2 supported niobium catalysts are active for partial oxidation of DME to HCHO. Best temperatures for partial oxidation are between 300 and 400°C. A short paper submitted to the ACS National Meeting at Anaheim(March 1999) was accepted for oral presentation. The title is �Catalytic Synthesis of Methacrylates over Silica Supported Niobium Catalysts� and will appear in the ACS preprints

Synthesis of Methyl Methacrylate from Coal-Derived Syngas

Research Triangle Institute (RTI), Eastman Chemical Company, and Bechtel collectively are developing a novel three-step process for the synthesis of methyl methacrylate (MMA) from coal-derived syngas that consists of the steps of synthesis of a propionate, its condensation with formaldehyde to form methacrylic acid (MAA), and esterification of MAA with methanol to produce MMA. RTI has completed the research on the three-step methanol-based route to MMA. Under an extension to the original contract, RTI is currently evaluating a new DME-based process for MMA. The key research need for DME route is to develop catalysts for DME partial oxidation reactions and DME condensation reactions. Over the last month, RTI has finalized the design of a fixed-bed microreactor system for DME partial oxidation reactions. RTI incorporated some design changes to the feed blending system, so as to be able to blend varying proportions of DME and oxygen. RTI has also examined the flammability limits of DME-air mixtures. Since the lower flammability limit of DME in air is 3.6 volume percent, RTI will use a nominal feed composition of 1.6 percent in air, which is less than half the lower explosion limit for DME-air mixtures. This nominal feed composition is thus considered operationally safe, for DME partial oxidation reactions. RTI is also currently developing an analytical system for DME partial oxidation reaction system

Viral mitochondria-localized inhibitor of apoptosis (UL37 exon 1 protein) does not protect human neural precursor cells from human cytomegalovirus-induced cell death.

Congenital human cytomegalovirus (HCMV) infection can cause severe brain abnormalities. Apoptotic HCMV-infected brain cells have been detected in a congenitally infected infant. In biologically relevant human neural precursor cells (hNPCs), cultured in physiological oxygen tensions, HCMV infection (m.o.i. of 1 or 3) induced cell death within 3 days post-infection (p.i.) and increased thereafter. Surprisingly, its known anti-apoptotic genes, including the potent UL37 exon 1 protein (pUL37x1) or viral mitochondria-localized inhibitor of apoptosis (vMIA), which protects infected human fibroblasts (HFFs) from apoptosis and from caspase-independent, mitochondrial serine protease-mediated cell death, were expressed by 2 days p.i. Consistent with this finding, an HCMV UL37x1 mutant, BADsubstitutionUL37x1 (BADsubUL37x1) induced cell death in hNPCs (m.o.i. = 1) to level which were indistinguishable from parental virus (BADwild-type)-infected hNPCs. Surprisingly, although BADsubUL37x1 is growth defective in permissive HFFs, it produced infectious progeny in hNPCs with similar kinetics and to levels comparable to BADwild-type-infected hNPCs (m.o.i. = 1). While delayed at a lower multiplicity (m.o.i. = 0.3), the BADsubUL37x1 mutant reached similar levels to revertant within 12 days, in contrast to its phenotype in HFFs. The inability of pUL37x1/vMIA to protect hNPCs from HCMV-induced cell death did not result from impaired trafficking as pUL37x1/vMIA trafficked efficiently to mitochondria in transfected hNPCs and in HCMV-infected hNPCs. These results establish that pUL37x1/vMIA, although protective in permissive HFFs, does not protect HCMV-infected hNPCs from cell death under physiologically relevant oxygen tensions. They further suggest that pUL37x1/vMIA is not essential for HCMV growth in hNPCs and has different cell type-specific roles