Metabolomic analysis of prostate cancer risk in a prospective cohort: The alpha‐tocolpherol, beta‐carotene cancer prevention (ATBC) study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113106/1/ijc29576.pd

Prospective serum metabolomic profiling of lethal prostate cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152026/1/ijc32218.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152026/2/ijc32218_am.pd

Process Optimization of Bismaleimide (BMI) Resin Infused Carbon Fiber Composite

Engineers today are presented with the opportunity to design and build the next generation of space vehicles out of the lightest, strongest, and most durable materials available. Composites offer excellent structural characteristics and outstanding reliability in many forms that will be utilized in future aerospace applications including the Commercial Crew and Cargo Program and the Orion space capsule. NASA's Composites for Exploration (CoEx) project researches the various methods of manufacturing composite materials of different fiber characteristics while using proven infusion methods of different resin compositions. Development and testing on these different material combinations will provide engineers the opportunity to produce optimal material compounds for multidisciplinary applications. Through the CoEx project, engineers pursue the opportunity to research and develop repair patch procedures for damaged spacecraft. Working in conjunction with Raptor Resins Inc., NASA engineers are utilizing high flow liquid infusion molding practices to manufacture high-temperature composite parts comprised of intermediate modulus 7 (IM7) carbon fiber material. IM7 is a continuous, high-tensile strength composite with outstanding structural qualities such as high shear strength, tensile strength and modulus as well as excellent corrosion, creep, and fatigue resistance. IM7 carbon fiber, combined with existing thermoset and thermoplastic resin systems, can provide improvements in material strength reinforcement and deformation-resistant properties for high-temperature applications. Void analysis of the different layups of the IM7 material discovered the largest total void composition within the [ +45 , 90 , 90 , -45 ] composite panel. Tensile and compressional testing proved the highest mechanical strength was found in the [0 4] layup. This paper further investigates the infusion procedure of a low-cost/high-performance BMI resin into an IM7 carbon fiber material and the optical, chemical, and mechanical analyses performed

Ring-Closing Metathesis of Olefinic Peptides: Design, Synthesis, and Structural Characterization of Macrocyclic Helical Peptides

Heptapeptides containing residues with terminal olefin-derivatized side chains (3 and 4) have been treated with ruthenium alkylidene 1 and undergone facile ring-closing olefin metathesis (RCM) to give 21- and 23-membered macrocyclic peptides (5 and 6). The primary structures of peptides 3 and 4 were based upon a previously studied heptapeptide (2), which was shown to adopt a predominantly 3_(10)-helical conformation in CDCl_3 solution and an α-helical conformation in the solid state. Circular dichroism, IR, and solution-phase ^1H NMR studies strongly suggested that acyclic precursors 3 and 4 and the fully saturated macrocyclic products 7 and 8 also adopted helical conformations in apolar organic solvents. Single-crystal X-ray diffraction of cyclic peptide 8 showed it to exist as a right-handed 3_(10)-helix up to the fifth residue. Solution-phase NMR structures of both acyclic peptide 4 and cyclic peptide 8 in CD_2Cl_2 indicated that the acyclic diene assumes a loosely 3_(10)-helical conformation, which is considerably rigidified upon macrocyclization. The relative ease of introducing carbon−carbon bonds into peptide secondary structures by RCM and the predicted metabolic stability of these bonds renders olefin metathesis an exceptional methodology for the synthesis of rigidified peptide architectures

Serum Metabolomic Response to Long-Term Supplementation with all-rac

Background. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a randomized controlled cancer prevention trial, showed a 32% reduction in prostate cancer incidence in response to vitamin E supplementation. Two other trials were not confirmatory, however. Objective. We compared the change in serum metabolome of the ATBC Study participants randomized to receive vitamin E to those who were not by randomly selecting 50 men from each of the intervention groups (50 mg/day all-rac-α-tocopheryl acetate (ATA), 20 mg/day β-carotene, both, placebo). Methods. Metabolomic profiling was conducted on baseline and follow-up fasting serum (Metabolon, Inc.). Results. After correction for multiple comparisons, five metabolites were statistically significantly altered (β is the change in metabolite level expressed as number of standard deviations on the log scale): α-CEHC sulfate (β=1.51, p=1.45×10-38), α-CEHC glucuronide (β=1.41, p=1.02×10-31), α-tocopherol (β=0.97, p=2.22×10-13), γ-tocopherol (β=-0.90, p=1.76×10-11), and β-tocopherol (β=-0.73, p=9.40×10-8). Glutarylcarnitine, beta-alanine, ornithine, and N6-acetyllysine were also decreased by ATA supplementation (β range 0.40 to −0.36), but not statistically significantly. Conclusions. Comparison of the observed metabolite alterations resulting from ATA supplementation to those in other vitamin E trials of different populations, dosages, or formulations may shed light on the apparently discordant vitamin E-prostate cancer risk findings

The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC)

Study, a randomized controlled cancer prevention trial, showed a 32% reduction in prostate cancer incidence in response to vitamin E supplementation. Two other trials were not confirmatory, however. Objective. We compared the change in serum metabolome of the ATBC Study participants randomized to receive vitamin E to those who were not by randomly selecting 50 men from each of the intervention groups (50 mg/day all-rac--tocopheryl acetate (ATA), 20 mg/day -carotene, both, placebo). Methods. Metabolomic profiling was conducted on baseline and follow-up fasting serum (Metabolon, Inc.). Results. After correction for multiple comparisons, five metabolites were statistically significantly altered ( is the change in metabolite level expressed as number of standard deviations on the log scale): -CEHC sulfate ( = 1.51, = 1.45 × 10 −38 ), -CEHC glucuronide ( = 1.41, = 1.02 × 10 −31 ), -tocopherol ( = 0.97, = 2.22 × 10 −13 ), -tocopherol ( = −0.90, = 1.76 × 10 −11 ), and -tocopherol ( = −0.73, = 9.40 × 10 −8 ). Glutarylcarnitine, betaalanine, ornithine, and N6-acetyllysine were also decreased by ATA supplementation ( range 0.40 to −0.36), but not statistically significantly. Conclusions. Comparison of the observed metabolite alterations resulting from ATA supplementation to those in other vitamin E trials of different populations, dosages, or formulations may shed light on the apparently discordant vitamin E-prostate cancer risk findings

Characterisation of PduS, the pdu Metabolosome Corrin Reductase, and Evidence of Substructural Organisation within the Bacterial Microcompartment

PduS is a corrin reductase and is required for the reactivation of the cobalamin-dependent diol dehydratase. It is one component encoded within the large propanediol utilisation (pdu) operon, which is responsible for the catabolism of 1,2-propanediol within a self-assembled proteinaceous bacterial microcompartment. The enzyme is responsible for the reactivation of the cobalamin coenzyme required by the diol dehydratase. The gene for the cobalamin reductase from Citrobacter freundii (pduS) has been cloned to allow the protein to be overproduced recombinantly in E. coli with an N-terminal His-tag. Purified recombinant PduS is shown to be a flavoprotein with a non-covalently bound FMN that also contains two coupled [4Fe-4S] centres. It is an NADH-dependent flavin reductase that is able to mediate the one-electron reductions of cob(III)alamin to cob(II)alamin and cob(II)alamin to cob(I)alamin. The [4Fe-4S] centres are labile to oxygen and their presence affects the midpoint redox potential of flavin. Evidence is presented that PduS is able to bind cobalamin, which is inconsistent with the view that PduS is merely a flavin reductase. PduS is also shown to interact with one of the shell proteins of the metabolosome, PduT, which is also thought to contain an [Fe-S] cluster. PduS is shown to act as a corrin reductase and its interaction with a shell protein could allow for electron passage out of the bacterial microcompartment

Does Proximity to Retailers Influence Alcohol and Tobacco Use Among Latino Adolescents?

Despite decades of research surrounding determinants of alcohol and tobacco (A&T) use among adolescents, built environment influences have only recently been explored. This study used ordinal regression on 205 Latino adolescents to explore the influence of the built environment (proximity to A&T retailers) on A&T use, while controlling for recognized social predictors. The sample was 45% foreign-born. A&T use was associated with distance from respondents’ home to the nearest A&T retailer (−), acculturation (+), parents’ consistent use of contingency management (−), peer use of A&T (+), skipping school (+), attending school in immediate proximity to the US/Mexico border (+), and the interaction between the distance to the nearest retailer and parents’ consistent use of contingency management (+). The association between decreasing distance to the nearest A&T retailer and increased A&T use in Latino adolescents reveals an additional risk behavior determinant in the US–Mexico border region

Addendum Guidelines for the Prevention of Peanut Allergy in the United States: Report of the National Institute of Allergy and Infectious Diseasesâ Sponsored Expert Panel

BackgroundFood allergy is an important public health problem because it affects children and adults, can be severe and even lifeâ threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanutâ containing foods beginning in infancy.ObjectivesPrompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy.ResultsThe addendum provides three separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanutâ containing foods in the health care provider’s office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation.ConclusionsGuidelines have been developed for early introduction of peanutâ containing foods into the diets of infants at various risk levels for peanut allergy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135514/1/pde13093_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135514/2/pde13093.pd