Characterization of three vasopressin receptor 2 variants: an apparent polymorphism (V266A) and two loss-of-function mutations (R181C and M311V).

Arginine vasopressin (AVP) is released from the posterior pituitary and controls water homeostasis. AVP binding to vasopressin V2 receptors (V2Rs) located on kidney collecting duct epithelial cells triggers activation of Gs proteins, leading to increased cAMP levels, trafficking of aquaporin-2 water channels, and consequent increased water permeability and antidiuresis. Typically, loss-of-function V2R mutations cause nephrogenic diabetes insipidus (NDI), whereas gain-of-function mutations cause nephrogenic syndrome of inappropriate antidiuresis (NSIAD). Here we provide further characterization of two mutant V2Rs, R181C and M311V, reported to cause complete and partial NDI respectively, together with a V266A variant, in a patient diagnosed with NSIAD. Our data in HEK293FT cells revealed that for cAMP accumulation, AVP was about 500- or 30-fold less potent at the R181C and M311V mutants than at the wild-type receptor respectively (and about 4000- and 60-fold in COS7 cells respectively). However, in contrast to wild type V2R, the R181C mutant failed to increase inositol phosphate production, while with the M311V mutant, AVP exhibited only partial agonism in addition to a 37-fold potency decrease. Similar responses were detected in a BRET assay for β-arrestin recruitment, with the R181C receptor unresponsive to AVP, and partial agonism with a 23-fold decrease in potency observed with M311V in both HEK293FT and COS7 cells. Notably, the V266A V2R appeared functionally identical to the wild-type receptor in all assays tested, including cAMP and inositol phosphate accumulation, β-arrestin interaction, and in a BRET assay of receptor ubiquitination. Each receptor was expressed at comparable levels. Hence, the M311V V2R retains greater activity than the R181C mutant, consistent with the milder phenotype of NDI associated with this mutant. Notably, the R181C mutant appears to be a Gs protein-biased receptor incapable of signaling to inositol phosphate or recruiting β-arrestin. The etiology of NSIAD in the patient with V266A V2R remains unknown

Verification of calculation code THERM in accordance with BS EN ISO 10077-2

Calculation codes are useful in predicting the heat transfer features in the fenestration industry. THERM is a finite element analysis based code, which can be used to compute thermal transmittance of windows, doors and shutters. It is important to verify results of THERM as per BS EN ISO 10077-2 to meet the compliance requirements. In this report, two-dimensional thermal conductance parameters were computed. Three versions of THERM, 5.2, 6.3 and 7.1, were used at two successive finite element mesh densities to assess their comparability. The results were all compliant with the aforementioned British Standard

Availability Evaluation of Service Function Chains Under Different Protection Schemes

Network Function Virtualization (NFV) calls for a new resource management approach where virtualized network functions (VNFs) replace traditional network hardware appliances. Thanks to NFV, operators are given a much greater flexibility, as these VNFs can be deployed as virtual nodes and chained together to form Service Function Chains (SFCs). An SFC represents a set of dedicated virtualized resources deployed to provide a certain service to the consumer. One of its most important performance requirements is availability. In this paper, the availability achieved by SFCs is evaluated analytically, by modelling several protection schemes and given different availability values for the network components. The cost of each protection scheme, based on its network resource consumption, is also taken into account. Extensive numerical results are reported, considering various SFC characteristics, such as availability requirements, number of NFV nodes and availability values of network components. The lowest-cost protection strategy, in terms of number of occupied network components, which meets availability requirement, is identified. Our analysis demonstrates that, in most cases, resource-greedy protection schemes, such as end-to-end protection, can be replaced by less aggressive schemes, even when availability requirements are in the order of five or six nines, depending on the number of elements in the service function chain

Tubulin response to intense nanosecond-scale electric field in molecular dynamics simulation

Intense pulsed electric fields are known to act at the cell membrane level and are already being exploited in biomedical and biotechnological applications. However, it is not clear if electric pulses within biomedically-attainable parameters could directly influence intra-cellular components such as cytoskeletal proteins. If so, a molecular mechanism of action could be uncovered for therapeutic applications of such electric fields. To help clarify this question, we first identified that a tubulin heterodimer is a natural biological target for intense electric fields due to its exceptional electric properties and crucial roles played in cell division. Using molecular dynamics simulations, we then demonstrated that an intense - yet experimentally attainable - electric field of nanosecond duration can affect the bβ-tubulin’s C-terminus conformations and also influence local electrostatic properties at the GTPase as well as the binding sites of major tubulin drugs site. Our results suggest that intense nanosecond electric pulses could be used for physical modulation of microtubule dynamics. Since a nanosecond pulsed electric field can penetrate the tissues and cellular membranes due to its broadband spectrum, our results are also potentially significant for the development of new therapeutic protocols

Genetic and Multilocation Evaluation of High Yielding Provenances of Bhimal (\u3cem\u3eGrewia optiva\u3c/em\u3e) on Farmers’ Fields in North Western Himalayas

Agroforestry is the inclusion of woody perennial within farming systems, has been practiced as a traditional land use and livelihood option since time immemorial (FSI 2013). It is being practiced on agricultural lands for fuel wood and fodder (Khybri et al., 1992), as well as medicinal and fruit trees (Bijalwan, 2011; Rathore et al., 2014) enabling food security (Narain 1998), non timber forest products, timber and shelter etc. A number of different (185) agroforestry systems are popular among farmers in different agro-climatic regions (Solanki, 2006). Grewia optiva Drummond (Bhimal) is an important agroforestry tree species primarily grown for green fodder in the north west Himalayas (Khybri et al., 1992; Dhyani, 2009). It is distributed throughout the sub-Himalayan tract upto an altitude of 1800m. Therefore, the present study was envisaged to monitor the performance of three best provenances of Bhimal (Mehta et al., 2011) on farmers’ fields at four locations comprising middle hill elevations and valley zones and their effect on field crops

Exploring the performances of the vibrating barriers for the seismic protection of the Zoser Pyramid

In this paper we aim to investigate the use of the Vibrating Barrier (ViBa) as a potential strategy to mitigate the effects of the seismic action on the Zoser Pyramid. The Vibrating Barrier is a structure buried in the soil that is able to absorb a significant portion of the dynamic energy arising from the ground motion. The working principle exploits the dynamic interaction among vibrating structures resting on a compliant semi-infinite space, namely the structure–soil–structure interaction. A reliable numerical simulation of the Zoser Pyramid and the surrounding soil undergoing a stochastic ground motion excitation representing the seismicity in Saqqara is presented. Due to the unique structural form, the ViBa is herein optimized through an ad-hoc procedure to minimize a response strain energy spectral density used as a synthetic performance parameter. Various layouts of the ViBa have been considered and presented in the paper. The efficiency of the ViBa is assessed by numerical simulation of the finite element model of the ViBa-Soil-Pyramid system. Results from a pertinent Monte Carlo study show an evident reduction of the stresses in the Pyramid manifesting the feasibility of this novel strategy to protect historic structures from earthquake-induced ground motion

Finite one dimensional impenetrable Bose systems: Occupation numbers

Bosons in the form of ultra cold alkali atoms can be confined to a one dimensional (1d) domain by the use of harmonic traps. This motivates the study of the ground state occupations $\lambda_i$ of effective single particle states $\phi_i$, in the theoretical 1d impenetrable Bose gas. Both the system on a circle and the harmonically trapped system are considered. The $\lambda_i$ and $\phi_i$ are the eigenvalues and eigenfunctions respectively of the one body density matrix. We present a detailed numerical and analytic study of this problem. Our main results are the explicit scaled forms of the density matrices, from which it is deduced that for fixed $i$ the occupations $\lambda_i$ are asymptotically proportional to $\sqrt{N}$ in both the circular and harmonically trapped cases.Comment: 22 pages, 8 figures (.eps), uses REVTeX

Coastal Ocean Forecasting: science foundation and user benefits

The advancement of Coastal Ocean Forecasting Systems (COFS) requires the support of continuous scientific progress addressing: (a) the primary mechanisms driving coastal circulation; (b) methods to achieve fully integrated coastal systems (observations and models), that are dynamically embedded in larger scale systems; and (c) methods to adequately represent air-sea and biophysical interactions. Issues of downscaling, data assimilation, atmosphere-wave-ocean couplings and ecosystem dynamics in the coastal ocean are discussed. These science topics are fundamental for successful COFS, which are connected to evolving downstream applications, dictated by the socioeconomic needs of rapidly increasing coastal populations