Genome-wide DNA-(de)methylation is associated with Noninfectious Bud-failure exhibition in Almond (Prunus dulcis [Mill.] D.A.Webb).

Noninfectious bud-failure (BF) remains a major threat to almond production in California, particularly with the recent rapid expansion of acreage and as more intensive cultural practices and modern cultivars are adopted. BF has been shown to be inherited in both vegetative and sexual progeny, with exhibition related to the age and propagation history of scion clonal sources. These characteristics suggest an epigenetic influence, such as the loss of juvenility mediated by DNA-(de)methylation. Various degrees of BF have been reported among cultivars as well as within sources of clonal propagation of the same cultivar. Genome-wide methylation profiles for different clones within almond genotypes were developed to examine their association with BF levels and association with the chronological time from initial propagation. The degree of BF exhibition was found to be associated with DNA-(de)methylation and clonal age, which suggests that epigenetic changes associated with ageing may be involved in the differential exhibition of BF within and among almond clones. Research is needed to investigate the potential of DNA-(de)methylation status as a predictor for BF as well as for effective strategies to improve clonal selection against age related deterioration. This is the first report of an epigenetic-related disorder threatening a major tree crop

Computations of Torque-Balanced Coaxial Rotor Flows

Interactional aerodynamics has been studied for counter-rotating coaxial rotors in hover. The effects of torque balancing on the performance of coaxial-rotor systems have been investigated. The three-dimensional unsteady Navier-Stokes equations are solved on overset grids using high-order accurate schemes, dual-time stepping, and a hybrid turbulence model. Computational results for an experimental model are compared to available data. The results for a coaxial quadcopter vehicle with and without torque balancing are discussed. Understanding interactions in coaxial-rotor flows would help improve the design of next-generation autonomous drones

Cord blood in regenerative medicine: do we need immune suppression?

Cord blood is currently used as an alternative to bone marrow as a source of stem cells for hematopoietic reconstitution after ablation. It is also under intense preclinical investigation for a variety of indications ranging from stroke, to limb ischemia, to myocardial regeneration. A major drawback in the current use of cord blood is that substantial morbidity and mortality are associated with pre-transplant ablation of the recipient hematopoietic system. Here we raise the possibility that due to unique immunological properties of both the stem cell and non-stem cell components of cord blood, it may be possible to utilize allogeneic cells for regenerative applications without needing to fully compromise the recipient immune system. Issues raised will include: graft versus host potential, the immunogeneicity of the cord blood graft, and the parallels between cord blood transplantation and fetal to maternal trafficking. The previous use of unmatched cord blood in absence of any immune ablation, as well as potential steps for widespread clinical implementation of allogeneic cord blood grafts will also be discussed

On finitely ambiguous B\"uchi automata

Unambiguous B\"uchi automata, i.e. B\"uchi automata allowing only one accepting run per word, are a useful restriction of B\"uchi automata that is well-suited for probabilistic model-checking. In this paper we propose a more permissive variant, namely finitely ambiguous B\"uchi automata, a generalisation where each word has at most $k$ accepting runs, for some fixed $k$. We adapt existing notions and results concerning finite and bounded ambiguity of finite automata to the setting of $\omega$-languages and present a translation from arbitrary nondeterministic B\"uchi automata with $n$ states to finitely ambiguous automata with at most $3^n$ states and at most $n$ accepting runs per word

Steric constraints in model proteins

A simple lattice model for proteins that allows for distinct sizes of the amino acids is presented. The model is found to lead to a significant number of conformations that are the unique ground state of one or more sequences or encodable. Furthermore, several of the encodable structures are highly designable and are the non-degenerate ground state of several sequences. Even though the native state conformations are typically compact, not all compact conformations are encodable. The incorporation of the hydrophobic and polar nature of amino acids further enhances the attractive features of the model.Comment: RevTex, 5 pages, 3 postscript figure

Dissipation in Quasi One-Dimensional Superconducting Single-Crystal Sn Nanowires

Electrical transport measurements were made on single-crystal Sn nanowires to understand the intrinsic dissipation mechanisms of a one-dimensional superconductor. While the resistance of wires of diameter larger than 70 nm drops precipitately to zero at Tc near 3.7 K, a residual resistive tail extending down to low temperature is found for wires with diameters of 20 and 40 nm. As a function of temperature, the logarithm of the residual resistance appears as two linear sections, one within a few tenths of a degree below Tc and the other extending down to at least 0.47 K, the minimum temperature of the measurements. The residual resistance is found to be ohmic at all temperatures below Tc of Sn. These findings are suggestive of a thermally activated phase slip process near Tc and quantum fluctuation-induced phase slip process in the low temperature regime. When the excitation current exceeds a critical value, the voltage-current (V-I) curves show a series of discrete steps in approaching the normal state. These steps cannot be fully understood with the classical Skocpol-Beasley-Tinkham phase slip center model (PSC), but can be qualitatively accounted for partly by the PSC model modified by Michotte et al.Comment: 7 pages, 5 figures. To be appeared on Physical Review B 71, 200

Metabolic gatekeeper function of B-lymphoid transcription factors.

B-lymphoid transcription factors, such as PAX5 and IKZF1, are critical for early B-cell development, yet lesions of the genes encoding these transcription factors occur in over 80% of cases of pre-B-cell acute lymphoblastic leukaemia (ALL). The importance of these lesions in ALL has, until now, remained unclear. Here, by combining studies using chromatin immunoprecipitation with sequencing and RNA sequencing, we identify a novel B-lymphoid program for transcriptional repression of glucose and energy supply. Our metabolic analyses revealed that PAX5 and IKZF1 enforce a state of chronic energy deprivation, resulting in constitutive activation of the energy-stress sensor AMPK. Dominant-negative mutants of PAX5 and IKZF1, however, relieved this glucose and energy restriction. In a transgenic pre-B ALL mouse model, the heterozygous deletion of Pax5 increased glucose uptake and ATP levels by more than 25-fold. Reconstitution of PAX5 and IKZF1 in samples from patients with pre-B ALL restored a non-permissive state and induced energy crisis and cell death. A CRISPR/Cas9-based screen of PAX5 and IKZF1 transcriptional targets identified the products of NR3C1 (encoding the glucocorticoid receptor), TXNIP (encoding a glucose-feedback sensor) and CNR2 (encoding a cannabinoid receptor) as central effectors of B-lymphoid restriction of glucose and energy supply. Notably, transport-independent lipophilic methyl-conjugates of pyruvate and tricarboxylic acid cycle metabolites bypassed the gatekeeper function of PAX5 and IKZF1 and readily enabled leukaemic transformation. Conversely, pharmacological TXNIP and CNR2 agonists and a small-molecule AMPK inhibitor strongly synergized with glucocorticoids, identifying TXNIP, CNR2 and AMPK as potential therapeutic targets. Furthermore, our results provide a mechanistic explanation for the empirical finding that glucocorticoids are effective in the treatment of B-lymphoid but not myeloid malignancies. Thus, B-lymphoid transcription factors function as metabolic gatekeepers by limiting the amount of cellular ATP to levels that are insufficient for malignant transformation

The anisotropic hyperelastic biomechanical response of the vocal ligament and implications for frequency regulation: A case study

One of the primary mechanisms to vary one's vocal frequency is through vocal fold length changes. As stress and deformation are linked to each other, it is hypothesized that the anisotropy in the biomechanical properties of the vocal fold tissue would affect the phonation characteristics. A biomechanical model of vibrational frequency rise during vocal fold elongation is developed which combines an advanced biomechanical characterization protocol of the vocal fold tissue with continuum beam models. Biomechanical response of the tissue is related to a microstructurally informed, anisotropic, nonlinear hyperelastic constitutive model. A microstructural characteristic (the dispersion of collagen) was represented through a statistical orientation function acquired from a second harmonic generation image of the vocal ligament. Continuum models of vibration were constructed based upon Euler–Bernoulli and Timoshenko beam theories, and applied to the study of the vibration of a vocal ligament specimen. From the natural frequency predictions in dependence of elongation, two competing processes in frequency control emerged, i.e., the applied tension raises the frequency while simultaneously shear deformation lowers the frequency. Shear becomes much more substantial at higher modes of vibration and for highly anisotropic tissues. The analysis was developed as a case study based on a human vocal ligament specimen