The living aortic valve: From molecules to function.

The aortic valve lies in a unique hemodynamic environment, one characterized by a range of stresses (shear stress, bending forces, loading forces and strain) that vary in intensity and direction throughout the cardiac cycle. Yet, despite its changing environment, the aortic valve opens and closes over 100,000 times a day and, in the majority of human beings, will function normally over a lifespan of 70-90 years. Until relatively recently heart valves were considered passive structures that play no active role in the functioning of a valve, or in the maintenance of its integrity and durability. However, through clinical experience and basic research the aortic valve can now be characterized as a living, dynamic organ with the capacity to adapt to its complex mechanical and biomechanical environment through active and passive communication between its constituent parts. The clinical relevance of a living valve substitute in patients requiring aortic valve replacement has been confirmed. This highlights the importance of using tissue engineering to develop heart valve substitutes containing living cells which have the ability to assume the complex functioning of the native valve

Genomic Diversity among Beijing and non-Beijing Mycobacterium tuberculosis Isolates from Myanmar

Background: The Beijing family of Mycobacterium tuberculosis is dominant in countries in East Asia. Genomic polymorphisms are a source of diversity within the M. tuberculosis genome and may account for the variation of virulence among M. tuberculosis isolates. Till date there are no studies that have examined the genomic composition of M. tuberculosis isolates from the high TB-burden country, Myanmar. Methodology/Principle Findings: Twenty-two M. tuberculosis isolates from Myanmar were screened on whole-genome arrays containing genes from M. tuberculosis H37Rv, M. tuberculosis CDC1551 and M. bovis AF22197. Screening identified 198 deletions or extra regions in the clinical isolates compared to H37Rv. Twenty-two regions differentiated between Beijing and non-Beijing isolates and were verified by PCR on an additional 40 isolates. Six regions (Rv0071-0074 [RD105], Rv1572-1576c [RD149], Rv1585c-1587c [RD149], MT1798-Rv1755c [RD152], Rv1761c [RD152] and Rv0279c) were deleted in Beijing isolates, of which 4 (Rv1572-1576c, Rv1585c-1587c, MT1798-Rv1755c and Rv1761c) were variably deleted among ST42 isolates, indicating a closer relationship between the Beijing and ST42 lineages. The TbD1 region, Mb1582-Mb1583 was deleted in Beijing and ST42 isolates. One M. bovis gene of unknown function, Mb3184c was present in all isolates, except 11 of 13 ST42 isolates. The CDC1551 gene, MT1360 coding for a putative adenylate cyclase, was present in all Beijing and ST42 isolates (except 1). The pks15/1 gene, coding for a putative virulence factor, was intact in all Beijing and non-Beijing isolates, except in ST42 and ST53 isolates. Conclusion: This study describes previously unreported deletions/extra regions in Beijing and non-Beijing M. tuberculosis isolates. The modern and highly frequent ST42 lineage showed a closer relationship to the hypervirulent Beijing lineage than to the ancient non-Beijing lineages. The pks15/1 gene was disrupted only in modern non-Beijing isolates. This is the first report of an in-depth analysis on the genomic diversity of M. tuberculosis isolates from Myanmar

Breaking of the overall permutation symmetry in nonlinear optical susceptibilities of one-dimensional periodic dimerized Huckel model

Based on infinite one-dimensional single-electron periodic models of trans-polyacetylene, we show analytically that the overall permutation symmetry of nonlinear optical susceptibilities is, albeit preserved in the molecular systems with only bound states, no longer generally held for the periodic systems. The overall permutation symmetry breakdown provides a fairly natural explanation to the widely observed large deviations of Kleinman symmetry for periodic systems in off-resonant regions. Physical conditions to experimentally test the overall permutation symmetry break are discussed.Comment: 7 pages, 1 figur

Dissipative Tunneling in 2 DEG: Effect of Magnetic Field, Impurity and Temperature

We have studied the transport process in the two dimensional electron gas (2DEG) in presence of a magnetic field and a dissipative environment at temperature T. By means of imaginary time series functional integral method we calculate the decay rates at finite temperature and in the presence of dissipation. We have studied decay rates for wide range of temperatures -- from the thermally activated region to very low temperature region where the system decays by quantum tunneling. We have shown that dissipation and impurity helps the tunneling. We have also shown that tunneling is strongly affected by the magnetic field. We have demonstrated analytical results for all the cases mentioned above.Comment: 8 pages, 2 figure

Potassium availability triggers Mycobacterium tuberculosis transition to, and resuscitation from, non-culturable (dormant) states.

Dormancy in non-sporulating bacteria is an interesting and underexplored phenomenon with significant medical implications. In particular, latent tuberculosis may result from the maintenance of Mycobacterium tuberculosis bacilli in non-replicating states in infected individuals. Uniquely, growth of M. tuberculosis in aerobic conditions in potassium-deficient media resulted in the generation of bacilli that were non-culturable (NC) on solid media but detectable in liquid media. These bacilli were morphologically distinct and tolerant to cell-wall-targeting antimicrobials. Bacterial counts on solid media quickly recovered after washing and incubating bacilli in fresh resuscitation media containing potassium. This resuscitation of growth occurred too quickly to be attributed to M. tuberculosis replication. Transcriptomic and proteomic profiling through adaptation to, and resuscitation from, this NC state revealed a switch to anaerobic respiration and a shift to lipid and amino acid metabolism. High concordance with mRNA signatures derived from M. tuberculosis infection models suggests that analogous NC mycobacterial phenotypes may exist during disease and may represent unrecognized populations in vivo. Resuscitation of NC bacilli in potassium-sufficient media was characterized by time-dependent activation of metabolic pathways in a programmed series of processes that probably transit bacilli through challenging microenvironments during infection

Gravity from self-interaction redux

I correct some recent misunderstandings about, and amplify some details of, an old explicit non-geometrical derivation of GR.Comment: Final, amplified, published version; GRG (2009

Climate change response: a report to establish the knowledge required for a TIANZ response and policy formulation with the Government post Kyoto Protocol ratification

The Tourism Industry Association of New Zealand commissioned this report ‘as a definitive reference point for the Tourism sector with regard to its greenhouse gas emissions (CO₂) and the potential impacts on the sector, in order to establish the underpinning knowledge required for a subsequent TIANZ response and policy formulation with the Government post the Kyoto Protocol ratification’. The value of the tourism sector, in terms of GDP and employment is self-evident but there is also growing awareness of the New Zealand environment by the international market which is critical to New Zealand’s future prosperity. Both the tourism sector and the Government recognise the importance of the ‘state of New Zealand’s environment’ and the need to genuinely sustain the image of ‘100% Pure New Zealand’, as it is implicitly linked to maintaining credibility and growth in a highly competitive market.Prepared for the Tourism Industry Association New Zealand (TIANZ), Landcare Research Contract Report, LC0102/107

Propagation and interaction of ultrashort electromagnetic pulses in nonlinear media with a quadratic-cubic nonlinearity

Propagation of extremely short unipolar pulses of electromagnetic field ("videopulses") is considered in the framework of a model in which the material medium is represented by anharmonic oscillators (approximating bound electrons) with quadratic and cubic nonlinearities. Two families of exact analytical solutions (with positive or negative polarity) are found for the moving solitary pulses. Direct simulations demonstrate that the pulses are very robust against perturbations. Two unipolar pulses collide nearly elastically, while collisions between pulses with opposite polarities and a small relative velocity are inelastic, leading to emission of radiation and generation of a small-amplitude additional pulse.Comment: 12 pages, 10 figure

Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions

Antimicrobials targeting cell wall biosynthesis are generally considered inactive against nonreplicating bacteria. Paradoxically, we found that under nonpermissive growth conditions, exposure of Mycobacterium bovis BCG bacilli to such antimicrobials enhanced their survival. We identified a transcriptional regulator, RaaS (for regulator of antimicrobial-assisted survival), encoded by bcg1279 (rv1219c) as being responsible for the observed phenomenon. Induction of this transcriptional regulator resulted in reduced expression of specific ATP-dependent efflux pumps and promoted long-term survival of mycobacteria, while its deletion accelerated bacterial death under nonpermissive growth conditions in vitro and during macrophage or mouse infection. These findings have implications for the design of antimicrobial drug combination therapies for persistent infectious diseases, such as tuberculosis