Aquifer Transport of Th, U, Ra and Rn in solution and on colloids

We have completed a theoretical study of the U-Th and radioactive decay series in an aquifer (Tricca et al, in press). Using this model as a guide, we have reassessed our results on the aquifer associated with Brookhaven National Laboratory. Based on our study and analyses of the U-Th series nuclei in this aquifer and the theoretical results, it was considered mandatory that a new set of samples be acquired. In addition to data from the groundwater samples, information concerning the addition of nuclides into the ground water system from the vadose zone was needed. A field study was then carried out and the samples returned to the laboratory. Sampling was done in consultation with hydrologists from the Brookhaven National Laboratory staff. The analyses are now almost completed and a draft of the final report is in preparation

Low Speed Aerodynamics of the X-38 CRV

This project was performed in support of the engineering development of the NASA X-38 Crew Return Vehicle (CRV)system. Wind tunnel experiments were used to visualize various aerodynamic phenomena encountered by the CRV during the final stages of descent and landing. Scale models of the CRV were used to visualize vortex structures above and below the vehicle, and in its wake, and to quantify their trajectories. The effect of flaperon deflection on these structures was studied. The structure and dynamics of the CRV's wake during the drag parachute deployment stage were measured. Regions of high vorticity were identified using surveys conducted in several planes using a vortex meter. Periodic shedding of the vortex sheets from the sides of the CRV was observed using laser sheet videography as the CRV reached high angles of attack during the quasi-steady pitch-up prior to parafoil deployment. Using spectral analysis of hot-film anemometer data, the Strouhal number of these wake fluctuations was found to be 0.14 based on the model span. Phenomena encountered in flight test during parafoil operation were captured in scale-model tests, and a video photogrammetry technique was implemented to obtain parafoil surface shapes during flight in the tunnel. Forces on the parafoil were resolved using tension gages on individual lines. The temporal evolution of the phenomenon of leading edge collapse was captured. Laser velocimetry was used to demonstrate measurement of the porosity of the parafoil surface. From these measurements, several physical explanations have been developed for phenomena observed at various stages of the X-38 development program. Quantitative measurement capabilities have also been demonstrated for continued refinement of the aerodynamic technologies employed in the X-38 project. Detailed results from these studies are given in an AIAA Paper, two slide presentations, and other material which are given on a Web-based archival resource. This is the Digital Library of the Georgia Tech Experimental Aerodynamics Group

Demonstration of Spatial Self Phase Modulation based photonic diode functionality in MoS2/h-BN medium

Spatial self-phase modulation (SSPM) is the optical nonlinear process and is a result of spatially varying refractive index profile along the line of propagation in a medium. SSPM is proved to be a method to demonstrate different photonic functionalities. Transition metal dichalcogenides play a key role in 2D nanophononics due to their unique and fascinating properties. MoS2 is the widely studied layered TMDs among all other 2D materials. This paper demonstrates such photonic functionality using thermally induced nonlinear optical response SSPM method, of MoS2 nano bottles. Thermally induced nonlinear optical parameters have been estimated by utilizing the saturable absorption response of h- BN, the nonreciprocal light propagation has been achieved. The diode actions have also been demonstrated in liquid-solid and solid-solid devices with the help of passive elements

Varicella-Zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line

Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells

Simian varicella virus infection of Chinese rhesus macaques produces ganglionic infection in the absence of rash

Varicella-zoster virus (VZV) causes varicella (chickenpox), becomes latent in ganglia along the entire neuraxis, and may reactivate to cause herpes zoster (shingles). VZV may infect ganglia via retrograde axonal transport from infected skin or through hematogenous spread. Simian varicella virus (SVV) infection of rhesus macaques provides a useful model system to study the pathogenesis of human VZV infection. To dissect the virus and host immune factors during acute SVV infection, we analyzed four SVV-seronegative Chinese rhesus macaques infected intratracheally with cell-associated 5 × 103 plaque-forming units (pfu) of SVV-expressing green fluorescent protein (n = 2) or 5 × 104 pfu of wild-type SVV (n = 2). All monkeys developed viremia and SVV-specific adaptive B- and T-cell immune responses, but none developed skin rash. At necropsy 21 days postinfection, SVV DNA was found in ganglia along the entire neuraxis and in viscera, and SVV RNA was found in ganglia, but not in viscera. The amount of SVV inoculum was associated with the extent of viremia and the immune response to virus. Our findings demonstrate that acute SVV infection of Chinese rhesus macaques leads to ganglionic infection by the hematogenous route and the induction of a virus-specific adaptive memory response in the absence of skin rash

A comprehensive analysis of the naturally occurring polymorphisms in HIV-1 Vpr: Potential impact on CTL epitopes

The enormous genetic variability reported in HIV-1 has posed problems in the treatment of infected individuals. This is evident in the form of HIV-1 resistant to antiviral agents, neutralizing antibodies and cytotoxic T lymphocytes (CTLs) involving multiple viral gene products. Based on this, it has been suggested that a comprehensive analysis of the polymorphisms in HIV proteins is of value for understanding the virus transmission and pathogenesis as well as for the efforts towards developing anti-viral therapeutics and vaccines. This study, for the first time, describes an in-depth analysis of genetic variation in Vpr using information from global HIV-1 isolates involving a total of 976 Vpr sequences. The polymorphisms at the individual amino acid level were analyzed. The residues 9, 33, 39, and 47 showed a single variant amino acid compared to other residues. There are several amino acids which are highly polymorphic. The residues that show ten or more variant amino acids are 15, 16, 28, 36, 37, 48, 55, 58, 59, 77, 84, 86, 89, and 93. Further, the variant amino acids noted at residues 60, 61, 34, 71 and 72 are identical. Interestingly, the frequency of the variant amino acids was found to be low for most residues. Vpr is known to contain multiple CTL epitopes like protease, reverse transcriptase, Env, and Gag proteins of HIV-1. Based on this, we have also extended our analysis of the amino acid polymorphisms to the experimentally defined and predicted CTL epitopes. The results suggest that amino acid polymorphisms may contribute to the immune escape of the virus. The available data on naturally occurring polymorphisms will be useful to assess their potential effect on the structural and functional constraints of Vpr and also on the fitness of HIV-1 for replication

Targeting quiescent leukemic stem cells using second generation autophagy inhibitors

In chronic myeloid leukemia (CML), tyrosine kinase inhibitor (TKI) treatment induces autophagy that promotes survival and TKI-resistance in leukemic stem cells (LSCs). In clinical studies hydroxychloroquine (HCQ), the only clinically approved autophagy inhibitor, does not consistently inhibit autophagy in cancer patients, so more potent autophagy inhibitors are needed. We generated a murine model of CML in which autophagic flux can be measured in bone marrow-located LSCs. In parallel, we use cell division tracing, phenotyping of primary CML cells, and a robust xenotransplantation model of human CML, to investigate the effect of Lys05, a highly potent lysosomotropic agent, and PIK-III, a selective inhibitor of VPS34, on the survival and function of LSCs. We demonstrate that long-term haematopoietic stem cells (LT-HSCs: Lin−Sca-1+c-kit+CD48−CD150+) isolated from leukemic mice have higher basal autophagy levels compared with non-leukemic LT-HSCs and more mature leukemic cells. Additionally, we present that while HCQ is ineffective, Lys05-mediated autophagy inhibition reduces LSCs quiescence and drives myeloid cell expansion. Furthermore, Lys05 and PIK-III reduced the number of primary CML LSCs and target xenografted LSCs when used in combination with TKI treatment, providing a strong rationale for clinical use of second generation autophagy inhibitors as a novel treatment for CML patients with LSC persistence

Intrinsic Defect in T Cell Production of Interleukin (IL)-13 in the Absence of Both IL-5 and Eotaxin Precludes the Development of Eosinophilia and Airways Hyperreactivity in Experimental Asthma

Interleukin (IL)-5 and IL-13 are thought to play key roles in the pathogenesis of asthma. Although both cytokines use eotaxin to regulate eosinophilia, IL-13 is thought to operate a separate pathway to IL-5 to induce airways hyperreactivity (AHR) in the allergic lung. However, identification of the key pathway(s) used by IL-5 and IL-13 in the disease process is confounded by the failure of anti–IL-5 or anti–IL-13 treatments to completely inhibit the accumulation of eosinophils in lung tissue. By using mice deficient in both IL-5 and eotaxin (IL-5/eotaxin−/−) we have abolished tissue eosinophilia and the induction of AHR in the allergic lung. Notably, in mice deficient in IL-5/eotaxin the ability of CD4+ T helper cell (Th)2 lymphocytes to produce IL-13, a critical regulator of airways smooth muscle constriction and obstruction, was significantly impaired. Moreover, the transfer of eosinophils to IL-5/eotaxin−/− mice overcame the intrinsic defect in T cell IL-13 production. Thus, factors produced by eosinophils may either directly or indirectly modulate the production of IL-13 during Th2 cell development. Our data show that IL-5 and eotaxin intrinsically modulate IL-13 production from Th2 cells and that these signaling systems are not necessarily independent effector pathways and may also be integrated to regulate aspects of allergic disease

VNToR: Network Virtualization at the Top-of-Rack Switch

Cloud providers typically implement abstractions for net- work virtualization on the server, within the operating sys- tem that hosts the tenant virtual machines or containers. Despite being flexible and convenient, this approach has funda- mental problems: incompatibility with bare-metal support, unnecessary performance overhead, and susceptibility to hypervisor breakouts. To solve these, we propose to offload the implementation of network-virtualization abstractions to the top-of-rack switch (ToR). To show that this is feasible and beneficial, we present VNToR, a ToR that takes over the implementation of the security-group abstraction. Our prototype combines commodity switching hardware with a custom software stack and is integrated in OpenStack Neutron. We show that VNToR can store tens of thousands of access rules, adapts to traffic-pattern changes in less than a millisecond, and significantly outperforms the state of the art