Involvement of Serine Threonine Protein Kinase, PknL, from Mycobacterium Tuberculosis H37Rv in Starvation Response of Mycobacteria

The adaptation to nutrient depletion in bacteria involves a highly organized series of intracellular events that enable them to adapt to starvation conditions. The regulatory effect of serine threonine protein kinase, PknL, from Mycobacterium tuberculosis strain H37Rv was investigated under nutrient deprived conditions that simulate circumstances leading to latency. Recombinant PknL was expressed in Mycobacterium smegmatis strain mc2155 in its wild type and mutant forms. In vitro growth kinetics experiments revealed that clone expressing active PknL had a significant growth advantage under nutrient limiting conditions. Experiments were conducted to ascertain the in silico predictions of the involvement of PknL in regulating glutamine metabolism in mycobacteria. Furthermore, a role for PknL in cell wall biogenesis/cell division was shown by scanning electron microscopy

Predicting dissolution patterns in variable aperture fractures: 1. Development and evaluation of an enhanced depth-averaged computational model

Water-rock interactions within variable-aperture fractures can lead to dissolution of fracture surfaces and local alteration of fracture apertures, potentially transforming the transport properties of the fracture over time. Because fractures often provide dominant pathways for subsurface flow and transport, developing models that effectively quantify the role of dissolution on changing transport properties over a range of scales is critical to understanding potential impacts of natural and anthropogenic processes. Dissolution of fracture surfaces is controlled by surface-reaction kinetics and transport of reactants and products to and from the fracture surfaces. We present development and evaluation of a depth-averaged model of fracture flow and reactive transport that explicitly calculates local dissolution-induced alterations in fracture apertures. The model incorporates an effective mass transfer relationship that implicitly represents the transition from reaction-limited dissolution to transport-limited dissolution. We evaluate the model through direct comparison to previously reported physical experiments in transparent analog fractures fabricated by mating an inert, transparent rough surface with a smooth single crystal of potassium dihydrogen phosphate (KDP), which allowed direct measurement of fracture aperture during dissolution experiments using well-established light transmission techniques [Detwiler, et al., 2003]. Comparison of experiments and simulations at different flow rates demonstrate the relative impact of the dimensionless Peclet and Damkohler numbers on fracture dissolution and the ability of the computational model to simulate dissolution. Despite some discrepancies in the small-scale details of dissolution patterns, the simulations predict the evolution of large-scale features quite well for the different experimental conditions. This suggests that our depth-averaged approach to simulating fracture dissolution provides a useful approach for extending laboratory results that are often limited in scale to scales that are more representative of geologic processes of interest

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SHAKTI: Subglacial Hydrology and Kinetic, Transient Interactions v1.0

Subglacial hydrology has a strong influence on glacier and ice sheet dynamics, particularly through the dependence of sliding velocity on subglacial water pressure. Significant challenges are involved in modeling subglacial hydrology, as the drainage geometry and flow mechanics are constantly changing, with complex feedbacks that play out between water and ice. A clear tradition has been established in the subglacial hydrology modeling literature of distinguishing between channelized (efficient) and sheetlike (inefficient or distributed) drainage systems or components and using slightly different forms of the governing equations in each subsystem to represent the dominant physics. Specifically, many previous subglacial hydrology models disregard opening by melt in the sheetlike system or redistribute it to adjacent channel elements in order to avoid runaway growth that occurs when it is included in the sheetlike system. We present a new subglacial hydrology model, SHAKTI (Subglacial Hydrology and Kinetic, Transient Interactions), in which a single set of governing equations is used everywhere, including opening by melt in the entire domain. SHAKTI employs a generalized relationship between the subglacial water flux and the hydraulic gradient that allows for the representation of laminar, turbulent, and transitional regimes depending on the local Reynolds number. This formulation allows for the coexistence of these flow regimes in different regions, and the configuration and geometry of the subglacial system evolves naturally to represent sheetlike drainage as well as systematic channelized drainage under appropriate conditions. We present steady and transient example simulations to illustrate the features and capabilities of the model and to examine sensitivity to mesh size and time step size. The model is implemented as part of the Ice Sheet System Model (ISSM).</p

The Annual Glaciohydrology Cycle in the Ablation Zone of the Greenland Ice Sheet: Part 1. Hydrology Model

We apply a novel one-dimensional glacier hydrology model that calculates hydraulic head to the tidewater-terminating Sermeq Avannarleq flowline of the Greenland ice sheet. Within a plausible parameter space, the model achieves a quasi-steady-state annual cycle in which hydraulic head oscillates close to flotation throughout the ablation zone. Flotation is briefly achieved during the summer melt season along a approx.17 km stretch of the approx.50 km of flowline within the ablation zone. Beneath the majority of the flowline, subglacial conduit storage closes (i.e. obtains minimum radius) during the winter and opens (i.e. obtains maximum radius) during the summer. Along certain stretches of the flowline, the model predicts that subglacial conduit storage remains open throughout the year. A calculated mean glacier water residence time of approx.2.2 years implies that significant amounts of water are stored in the glacier throughout the year. We interpret this residence time as being indicative of the timescale over which the glacier hydrologic system is capable of adjusting to external surface meltwater forcings. Based on in situ ice velocity observations, we suggest that the summer speed-up event generally corresponds to conditions of increasing hydraulic head during inefficient subglacial drainage. Conversely, the slowdown during fall generally corresponds to conditions of decreasing hydraulic head during efficient subglacial drainage

The Annual Glaciohydrology Cycle in the Ablation Zone of the Greenland Ice Sheet: Part 2. Observed and Modeled Ice Flow

Ice velocities observed in 2005/06 at three GPS stations along the Sermeq Avannarleq flowline, West Greenland, are used to characterize an observed annual velocity cycle. We attempt to reproduce this annual ice velocity cycle using a 1-D ice-flow model with longitudinal stresses coupled to a 1-D hydrology model that governs an empirical basal sliding rule. Seasonal basal sliding velocity is parameterized as a perturbation of prescribed winter sliding velocity that is proportional to the rate of change of glacier water storage. The coupled model reproduces the broad features of the annual basal sliding cycle observed along this flowline, namely a summer speed-up event followed by a fall slowdown event. We also evaluate the hypothesis that the observed annual velocity cycle is due to the annual calving cycle at the terminus. We demonstrate that the ice acceleration due to a catastrophic calving event takes an order of magnitude longer to reach CU/ETH ('Swiss') Camp (46km upstream of the terminus) than is observed. The seasonal acceleration observed at Swiss Camp is therefore unlikely to be the result of velocity perturbations propagated upstream via longitudinal coupling. Instead we interpret this velocity cycle to reflect the local history of glacier water balance

Dynamic contrast-enhanced magnetic resonance imaging in patients with pulmonary arterial hypertension.

Dynamic contrast-enhanced (DCE) time-resolved magnetic resonance (MR) imaging is a technique whereby the passage of an intravenous contrast bolus can be tracked through the pulmonary vascular system. The aim of this study was to investigate the prognostic significance of DCE-MR pulmonary blood transit times in patients with pulmonary arterial hypertension (PAH). Seventy-nine patients diagnosed with PAH underwent pulmonary DCE imaging at 1.5 T using a time-resolved three-dimensional spoiled gradient echo sequence. The prognostic significance of two DCE parameters, full width at half maximum (FWHM) of the first-pass clearance curve and pulmonary transit time (PTT), along with demographic and invasive catheter measurements, was evaluated by univariate and bivariate Cox proportional hazards regression and Kaplan-Meier analysis. DCE-MR transit times were most closely correlated with cardiac index (CI) and pulmonary vascular resistance index (PVRI) and were both found to be accurate for detecting reduced CI (FWHM area under the curve [AUC] at receiver operating characteristic analysis = 0.91 and PTT AUC = 0.92, respectively) and for detecting elevated PVRI (FWHM AUC = 0.88 and PTT AUC = 0.84, respectively). During the follow-up period, 25 patients died. Patients with longer measurements of FWHM (P = 0.0014) and PTT (P = 0.004) were associated with poor outcome at Kaplan-Meier analysis, and both parameters were strong predictors of adverse outcome from Cox proportional hazards analysis (P = 0.013 and 0.010, respectively). At bivariate analysis, DCE measurements predicted mortality independent of age, gender, and World Health Organization functional class; however, invasive hemodynamic indexes CI, PVRI, and DCE measurements were not independent of one another. In conclusion, DCE-MR transit times predict mortality in patients with PAH and are closely associated with clinical gold standards CI and PVRI

Search for the Lepton-Number-Violating Decay Ξ−→pμ−μ−\Xi^- \to p \mu^- \mu^-

A sensitive search for the lepton-number-violating decay $\Xi^-\to p \mu^-\mu^-$ has been performed using a sample of $\sim10^9$ $\Xi^-$ hyperons produced in 800 GeV/$c$ $p$-Cu collisions. We obtain $\mathcal{B}(\Xi^-\to p \mu^-\mu^-)< 4.0\times 10^{-8}$ at 90% confidence, improving on the best previous limit by four orders of magnitude.Comment: 9 pages, 5 figures, to be published in Phys. Rev. Let