The effects of aging on cardiac mechanics

It is well established that the aging heart exhibits left ventricular (LV) diastolic dysfunction and changes in mechanical properties, which have been attributed to alterations in the extracellular matrix (ECM). The investigators tested the hypothesis that the mechanical properties of cardiac myocytes significantly change with aging thereby contributing to the LV diastolic dysfunction. Cellular mechanical properties were determined by indenting cells with an atomic force microscope (AFM). The indentation results were interpreted by modeling the AFM probe as a blunted cone and determining an apparent elastic modulus (B) with classical infinitesimal strain theory (CIST). A commercially available finite element software package (ABAQUS) was used to further explore nano-indentation and the use of CIST to determine material properties. The cellular mechanical property changes, measured in young and old cardiac cells isolated from rats, showed a significant increase (p\u3c0.05) in B with aging. Cellular protein changes were assessed by immunoblot (western) analyses in order to establish if material property changes also occurred with aging. The western results indicate significant (p\u3c0.05) changes in cytoskeletal and mechanotransduction proteins with aging. These data support the concept that the mechanism mediating LV diastolic dysfunction in the aging hearts resides, in part, at the level of the myocyte. The effect of these aging induced cellular changes on global cardiac function will be further explored with instrumentation developed for implantation in an in vivo animal model

Atomic force microscopy used to determine the Young\u27s modulus of vascular smooth muscle cells

The Young\u27s modulus of cultured mouse and rat vascular smooth muscle cells (VSMC) was measured with an atomic force microscope (AFM). The AFM can image the three-dimensional structure of biological cells in a physiological environment enabling real-time biochemical and physiological processes to be monitored at a resolution similar to that obtained for the electron microscope (EM). Cellular mechanical properties were determined by indenting the cell\u27s body, and analyzing the indentation data with classical infinitesimal strain theory. This calculation was accomplished by modeling the AFM probe as a cone. as well as a blunted cone. The blunted cone geometry fits the AFM force indentation data well and was used to calculate the Young\u27s Modulus (E) of the respective VSMC cell body under various conditions. HEPES, a buffer solution commonly used to maintain pH in culture was found to alter the Young\u27s Modulus (E) and the morphology of rat cells. Old mouse VSMCs had a higher Young\u27s Modulus (E) than younger ones, with a clear change in cytoskeleton morphology. A change in cell body morphology was seen after application of drug, treatment

First-principles study of the Young's modulus of Si <001> nanowires

We report the results of first-principles density functional theory calculations of the Young's modulus and other mechanical properties of hydrogen-passivated Si nanowires. The nanowires are taken to have predominantly {100} surfaces, with small {110} facets. The Young's modulus, the equilibrium length and the residual stress of a series of prismatic wires are found to have a size dependence that scales like the surface area to volume ratio for all but the smallest wires. We analyze the physical origin of the size dependence, and compare the results to two existing models.Comment: 5 pages, 3 figure

Statistical inference of the generation probability of T-cell receptors from sequence repertoires

Stochastic rearrangement of germline DNA by VDJ recombination is at the origin of immune system diversity. This process is implemented via a series of stochastic molecular events involving gene choices and random nucleotide insertions between, and deletions from, genes. We use large sequence repertoires of the variable CDR3 region of human CD4+ T-cell receptor beta chains to infer the statistical properties of these basic biochemical events. Since any given CDR3 sequence can be produced in multiple ways, the probability distribution of hidden recombination events cannot be inferred directly from the observed sequences; we therefore develop a maximum likelihood inference method to achieve this end. To separate the properties of the molecular rearrangement mechanism from the effects of selection, we focus on non-productive CDR3 sequences in T-cell DNA. We infer the joint distribution of the various generative events that occur when a new T-cell receptor gene is created. We find a rich picture of correlation (and absence thereof), providing insight into the molecular mechanisms involved. The generative event statistics are consistent between individuals, suggesting a universal biochemical process. Our distribution predicts the generation probability of any specific CDR3 sequence by the primitive recombination process, allowing us to quantify the potential diversity of the T-cell repertoire and to understand why some sequences are shared between individuals. We argue that the use of formal statistical inference methods, of the kind presented in this paper, will be essential for quantitative understanding of the generation and evolution of diversity in the adaptive immune system.Comment: 20 pages, including Appendi

Hole Spin Coherence in a Ge/Si Heterostructure Nanowire

Relaxation and dephasing of hole spins are measured in a gate-defined Ge/Si nanowire double quantum dot using a fast pulsed-gate method and dispersive readout. An inhomogeneous dephasing time $T_2^* \sim 0.18~\mathrm{\mu s}$ exceeds corresponding measurements in III-V semiconductors by more than an order of magnitude, as expected for predominately nuclear-spin-free materials. Dephasing is observed to be exponential in time, indicating the presence of a broadband noise source, rather than Gaussian, previously seen in systems with nuclear-spin-dominated dephasing.Comment: 15 pages, 4 figure

Antilocalization of Coulomb Blockade in a Ge-Si Nanowire

The distribution of Coulomb blockade peak heights as a function of magnetic field is investigated experimentally in a Ge-Si nanowire quantum dot. Strong spin-orbit coupling in this hole-gas system leads to antilocalization of Coulomb blockade peaks, consistent with theory. In particular, the peak height distribution has its maximum away from zero at zero magnetic field, with an average that decreases with increasing field. Magnetoconductance in the open-wire regime places a bound on the spin-orbit length ($l_{so}$ < 20 nm), consistent with values extracted in the Coulomb blockade regime ($l_{so}$ < 25 nm).Comment: Supplementary Information available at http://bit.ly/19pMpd

Architecture of the Short External Rotator Muscles of the Hip.

BackgroundMuscle architecture, or the arrangement of sarcomeres and fibers within muscles, defines functional capacity. There are limited data that provide an understanding of hip short external rotator muscle architecture. The purpose of this study was thus to characterize the architecture of these small hip muscles.MethodsEight muscles from 10 independent human cadaver hips were used in this study (n = 80 muscles). Architectural measurements were made on pectineus, piriformis, gemelli, obturators, quadratus femoris, and gluteus minimus. Muscle mass, fiber length, sarcomere length, and pennation angle were used to calculate the normalized muscle fiber length, which defines excursion, and physiological cross-sectional area (PCSA), which defines force-producing capacity.ResultsGluteus minimus had the largest PCSA (8.29 cm2) followed by obturator externus (4.54 cm2), whereas superior gemellus had the smallest PCSA (0.68 cm2). Fiber lengths clustered into long (pectineus - 10.38 cm and gluteus minimus - 10.30 cm), moderate (obturator internus - 8.77 cm and externus - 8.04 cm), or short (inferior gemellus - 5.64 and superior gemellus - 4.85). There were no significant differences among muscles in pennation angle which were all nearly zero. When the gemelli and obturators were considered as a single functional unit, their collective PCSA (10.00 cm2) exceeded that of gluteus minimus as a substantial force-producing group.ConclusionsThe key findings are that these muscles have relatively small individual PCSAs, short fiber lengths, and low pennation angles. The large collective PCSA and short fiber lengths of the gemelli and obturators suggest that they primarily play a stabilizing role rather than a joint rotating role

Fact Sheet: Cohort Differences in Parental Care Needs

There has been considerable concern about the availability of informal and especially family care when the baby boom cohorts reach old age (Ryan and Smith et al., 2012). However, as care needs typically arise in late old age (age 70 or later), a more immediate issue is the care burden faced by the baby boomer cohorts themselves as their parents now reach late old age. To assess the potential care burden faced by baby boom adult children one first needs to assess their parents’ care needs. Such assessment is also essential as research shows that parental care needs do not only affect the caregivers themselves but also the whole family network (Amirkhanyan and Wolf, 2003). Non-caregiving family members, such as siblings of caregiving adult children, can be adversely affected by the caregiving situation. In order to see if parental care needs have changed over time, we explored cohort differences in care needs among baby boomers’ parents using nationally representative data from 1992 through 2010

Magnetoconductance oscillations in quasiballistic multimode nanowires

We calculate the conductance of quasi-one-dimensional nanowires with electronic states confined to a surface charge layer, in the presence of a uniform magnetic field. Two-terminal magnetoconductance (MC) between two leads deposited on the nanowire via tunnel barriers is dominated by density-of-states (DOS) singularities, when the leads are well apart. There is also a mesoscopic correction due to a higher-order coherent tunneling between the leads for small lead separation. The corresponding MC structure depends on the interference between electron propagation via different channels connecting the leads, which in the simplest case, for the magnetic field along the wire axis, can be crudely characterized by relative winding numbers of paths enclosing the magnetic flux. In general, the MC oscillations are aperiodic, due to the Zeeman splitting, field misalignment with the wire axis, and a finite extent of electron distribution across the wire cross section, and are affected by spin-orbit coupling. The quantum-interference MC traces contain a wealth of information about the electronic structure of multichannel wires, which would be complimentary to the DOS measurements. We propose a four-terminal configuration to enhance the relative contribution of the higher-order tunneling processes and apply our results to realistic InAs nanowires carrying several quantum channels in the surface charge-accumulation layer.Comment: 11 pages, 8 figure