Targeting chromatin aging - the epigenetic impact of longevity-associated interventions

A rapidly growing body of evidence has shown that chromatin undergoes radical alterations as an organism ages, but how these changes relate to aging itself is an open question. It is likely that these processes contribute to genomic instability and loss of transcriptional fidelity, which in turn drives deleterious age-related phenotypes. Interventions associated with increased healthspan and longevity such as reduced insulin/IGF signalling (IIS), inhibition of mTOR and energy depletion resulting in SIRT1/AMPK activation, all have beneficial effects which ameliorate multiple facets of age-associated decline. The impact of these interventions on the epigenome is less certain. In this review we highlight the potential of these interventions to act directly upon the epigenome and promote a youthful chromatin landscape, maintaining genetic and transcriptional memory throughout the lifecourse. We propose that this is a fundamental mechanism through which these interventions are able to curtail the incidence of age-related disease. By revisiting these well characterised interventions, we may be able to identify targetable effectors of chromatin function and use this knowledge to enhance healthspan and longevity in human populations through the measured application of dietary and small molecule interventions

Analysis of the stress state in an Iosipescu sheartest specimen

The state of stress in an Iosipescu shear test specimen is analyzed, utilizing a finite element computer program. The influence of test fixture configuration on this stress state is included. Variations of the standard specimen configuration, including notch depth, notch angle, and notch root radius are modeled. The purpose is to establish guidelines for a specimen geometry which will accommodate highly orthotropic materials while minimizing stress distribution nonuniformities. Materials ranging from isotropic to highly orthotropic are considered. An optimum specimen configuration is suggested, along with changes in the test fixture

Iosipescu shear properties of graphite fabric/epoxy composite laminates

The Iosipescu shear test method is used to measure the in-plane and interlaminar shear properties of four T300 graphite fabric/934 epoxy composite materials. Different weave geometries tested include an Oxford weave, a 5-harness satin weave, an 8-harness satin weave, and a plain weave with auxiliary warp yarns. Both orthogonal and quasi-isotropic layup laminates were tested. In-plane and interlaminar shear properties are obtained for laminates of all four fabric types. Overall, little difference in shear properties attributable to the fabric weave pattern is observed. The auxiliary warp material is significantly weaker and less stiff in interlaminar shear parallel to its fill direction. A conventional strain gage extensometer is modified to measure shear strains for use with the Iosipescu shear test. While preliminary results are encouraging, several design iterations failed to produce a reliable shear transducer prototype. Strain gages are still the most reliable shear strain transducers for use with this test method

Verification and application of the Iosipescu shear test method

Finite element models were used to study the effects of notch angle variations on the stress state within an Iosipescu shear test speciment. These analytical results were also studied to determine the feasibility of using strain gage rosettes and a modified extensometer to measure shear strains in this test specimen. Analytical results indicate that notch angle variations produced only small differences in simulated shear properties. Both strain gage rosettes and the modified extensometer were shown to be feasible shear strain transducers for the test method. The Iosipoescu shear test fixture was redesigned to incorporate several improvements. These improvements include accommodation of a 50 percent larger specimen for easier measurement of shear train, a clamping mechanism to relax strict tolerances on specimen width, and a self contained alignment tool for use during specimen installation. A set of in-plane and interlaminar shear properties were measured for three graphite fabric/epoxy composites of T300/934 composite material. The three weave patterns were Oxford, 5-harness satin, and 8-harness satin

The energy dependence of p_t angular correlations inferred from mean-p_t fluctuation scale dependence in heavy ion collisions at the SPS and RHIC

We present the first study of the energy dependence of pt angular correlations inferred from event-wisemean transverse momentum (pt) fluctuations in heavy ion collisions. We compare our large-acceptancemeasurements at CM energies √^sNN = 19.6, 62.4, 130 and 200 GeV to SPS measurements at 12.3 and 17.3 GeV. p_t angular correlation structure suggests that the principal source of p_t correlations and fluctuations is minijets (minimum-bias parton fragments). We observe a dramatic increase in correlations and fluctuations from SPS to RHIC energies, increasing linearly with ln √^sNN from the onset of observable jet-related (p_t) fluctuations near 10 GeV

Two-particle correlations on transverse momentum and momentum dissipation in Au–Au collisions at √sNN = 130 GeV

Measurements of two-particle correlations on transverse momentum p_t for Au–Au collisions at √^sNN = 130 GeV are presented. Significant largemomentum-scale correlations are observed for charged primary hadrons with 0.15 ≤ p_t ≤ 2 GeV/c and pseudorapidity |η| ≤ 1.3. Such correlations were not observed in a similar study at lower energy and are not predicted by theoretical collision models. Their direct relation to mean-p_t fluctuations measured in the same angular acceptance is demonstrated. Positive correlations are observed for pairs of particles which have large pt values while negative correlations occur for pairs in which one particle has large p_t and the other has much lower p_t . The correlation amplitudes per final state particle increase with collision centrality. The observed correlations are consistent with a scenario in which the transverse momentum of hadrons associated with initial-stage semi-hard parton scattering is dissipated by the medium to lower p_t

Stiffness reductions during tensile fatigue testing of graphite/epoxy angle-ply laminates

Tensile fatigue data was generated under carefully controlled test conditions. A computerized data acquisition system was used to permit the measurement of dynamic modulus without interrupting the fatigue cycling. Two different 8-ply laminate configurations, viz, + or - 45 (2s) and + or - 67.5 (2s), of a T300/5208 graphite/epoxy composite were tested. The + or - 45 (2s) laminate did exhibit some modulus decay, although there was no well-defined correlation with applied stress level or number of cycles. The + or - 67.5 (2s) laminate did not exhibit any measurable modulus decay. Secondary effects observed included a small but distinct difference between modulus as measured statically and dynamically, a slight recovery of the modulus decay after a test interruption, and a significant viscoelastic (creep) response of the + or - 45 (2s) laminate during fatigue testing

Remote Stratigraphic Analysis: Combined TM and AIS Results in the Wind River/bighorn Basin Area, Wyoming

An in-progress study demonstrates the utility of airborne imaging spectrometer (AIS) data for unraveling the stratigraphic evolution of a North American, western interior foreland basin. AIS data are used to determine the stratigraphic distribution of mineralogical facies that are diagnostic of specific depositional environments. After wavelength and amplitude calibration using natural ground targets with known spectral characteristics, AIS data identify calcite, dolomite, gypsum and montmorillonite-bearing strata in the Permian-Cretaceous sequence. Combined AIS and TM results illustrate the feasibility of spectral stratigraphy, remote analysis of stratigraphic sequences

Integrated maneuvering and life support system simulation Final report

Integrated maneuvering and life support system simulatio