[1] Two standard Tropical Rainfall Measuring Mission (TRMM) Multisatellite Precipitation Analysis (TMPA) products, 3B42RT and 3B42V6, were quantitatively evaluated in the Laohahe basin, China, located within the TMPA product latitude band (50°NS) but beyond the inclined TRMM satellite latitude band (36°NS). In general, direct comparison of TMPA rainfall estimates to collocated rain gauges from 2000 to 2005 show that the spatial and temporal rainfall characteristics over the region are well captured by the 3B42V6 estimates. Except for a few months with underestimation, the 3B42RT estimates show unrealistic overestimation nearly year round, which needs to be resolved in future upgrades to the real-time estimation algorithm. Both model-parameter error analysis and hydrologic application suggest that the three-layer Variable Infiltration Capacity (VIC-3L) model cannot tolerate the nonphysical overestimation behavior of 3B42RT through the hydrologic integration processes, and as such the 3B42RT data have almost no hydrologic utility, even at the monthly scale. In contrast, the 3B42V6 data can produce much better hydrologic predictions with reduced error propagation from input to streamflow at both the daily and monthly scales. This study also found the error structures of both RT and V6 have a significant geo-topography-dependent distribution pattern, closely associated with latitude and elevation bands, suggesting current limitations with TRMM-era algorithms at high latitudes and high elevations in general. Looking into the future Global Precipitation Measurement (GPM) era, the Geostationary Infrared (GEO-IR) estimates still have a long-term role in filling the inevitable gaps in microwave coverage, as well as in enabling sub-hourly estimates at typical 4-km grid scales. Thus, this study affirms the call for a real-time systematic bias removal in future upgrades to the IR-based RT algorithm using a simple scaling factor. This correction is based on MW-based monthly rainfall climatologies applied to the combined monthly satellite-gauge research products.

Oncolytic viruses capable of tumor-selective replication and cytolysis have shown early promise as cancer therapeutics. However, the host immune system remains a significant obstacle to effective systemic administration of virus in a clinical setting. Here, we demonstrate the severe negative impact of the adaptive immune response on the systemic delivery of oncolytic vesicular stomatitis virus (VSV) in an immune-competent murine tumor model, an effect mediated primarily by the neutralization of injected virions by circulating antibodies. We show that this obstacle can be overcome by administering virus within carrier cells that conceal viral antigen during delivery. Infected cells were delivered to tumor beds and released virus to infect malignant cells while sparing normal tissues. Repeated administration of VSV in carrier cells to animals bearing metastatic tumors greatly improved therapeutic efficacy when compared with naked virion injection. Whole-body molecular imaging revealed that carrier cells derived from solid tumors accumulate primarily in the lungs following intravenous injection, whereas leukemic carriers disseminate extensively throughout the body. Furthermore, xenogeneic cells were equally effective at delivering virus as syngeneic cells. These findings emphasize the importance of establishing cell-based delivery platforms in order to maximize the efficacy of oncolytic therapeutics.

Oncolytic viruses are generally designed to be cancer selective on the basis of a single genetic mutation. JX-594 is a thymidine kinase (TK) gene-inactivated oncolytic vaccinia virus expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) and lac-Z transgenes that is designed to destroy cancer cells through replication-dependent cell lysis and stimulation of antitumoral immunity. JX-594 has demonstrated a favorable safety profile and reproducible tumor necrosis in a variety of solid cancer types in clinical trials. However, the mechanism(s) responsible for its cancer-selectivity have not yet been well described. We analyzed the replication of JX-594 in three model systems: primary normal and cancer cells, surgical explants, and murine tumor models. JX-594 replication, transgene expression, and cytopathic effects were highly cancer-selective, and broad spectrum activity was demonstrated. JX-594 cancer-selectivity was multi-mechanistic; replication was activated by epidermal growth factor receptor (EGFR)/Ras pathway signaling, cellular TK levels, and cancer cell resistance to type-I interferons (IFNs). These findings confirm a large therapeutic index for JX-594 that is driven by common genetic abnormalities in human solid tumors. This appears to be the first description of multiple selectivity mechanisms, both inherent and engineered, for an oncolytic virus. These findings have implications for oncolytic viruses in general, and suggest that their cancer targeting is a complex and multifactorial process.

A simple formalism for the evaluation of 〈S2〉 in terms of the two-particle density matrix is presented. The implementation of the formalism in the restricted open-shell Hartree–Fock (ROHF), unrestricted HF (UHF) and density functional (DFT) based theories is discussed. Rules governing the nonzero S2 matrix elements in the UHF based methods are presented. Further examples are given of 〈S2〉 in several atomic and radical systems from very simple density functional models.

The Coupled Routing and Excess STorage model (CREST, jointly developed by the University of Oklahoma and NASA SERVIR) is a distributed hydrological model developed to simulate the spatial and temporal variation of land surface, and subsurface water fluxes and storages by cell-to-cell simulation. CREST's distinguishing characteristics include: (1) distributed rainfall-runoff generation and cell-to-cell routing; (2) coupled runoff generation and routing via three feedback mechanisms; and (3) representation of sub-grid cell variability of soil moisture storage capacity and sub-grid cell routing (via linear reservoirs). The coupling between the runoff generation and routing mechanisms allows detailed and realistic treatment of hydrological variables such as soil moisture. Furthermore, the representation of soil moisture variability and routing processes at the sub-grid scale enables the CREST model to be readily scalable to multi-scale modelling research. This paper presents the model development and demonstrates its applicability for a case study in the Nzoia basin located in Lake Victoria, Africa.Key words distributed hydrological model; cell-to-cell routing; excess storage; water balance; CREST; Lake Victoria Le modèle hydrologique distribué couplé routage et stockage des excédents (CREST)Résumé Le modèle couplé routage et stockage des excédents (CREST, développé conjointement par l'Université de l'Oklahoma et NASA SERVIR) est un modèle hydrologique distribué développé pour simuler les variations spatiales et temporelles des flux d'eau de surface et souterraine ainsi que les stockages, par simulation de cellule à cellule. Les caractéristiques distinctives de CREST sont les suivantes: (1) production pluie-débit distribuée et routage de cellule à cellule; (2) couplage de la production et du routage du ruissellement via trois mécanismes de rétroaction; et (3) représentation de la variabilité sub-cellulaire de la capacité de stockage en eau du sol et du routage infra-cellulaire (via des réservoirs linéaires). Le couplage entre la genèse du ruissellement et les mécan-ismes de routage permet un traitement détaillé et réaliste des variables hydrologiques telles que l'humidité du sol. En outre, la représentation de la variabilité de l'humidité du sol et des processus de routage à l'échelle subcellulaire permet au modèle CREST d'être facilement étendu à la recherche sur la modélisation multi-échelles. Cet article présente le développement du modèle et démontre son applicabilité pour une étude de cas dans le bassin de la Nzoia, Lac Victoria, Afrique.Mots clefs modèle hydrologique distribué; routage de cellule à cellule; stockage des excédents; bilan hydrique; CREST; Lac Victoria

Renewal of nongermative epithelia is poorly understood. The novel mitogen “lacritin” is apically secreted by several nongermative epithelia. We tested 17 different cell types and discovered that lacritin is preferentially mitogenic or prosecretory for those types that normally contact lacritin during its glandular outward flow. Mitogenesis is dependent on lacritin's C-terminal domain, which can form an α-helix with a hydrophobic face, as per VEGF's and PTHLP's respective dimerization or receptor-binding domain. Lacritin targets downstream NFATC1 and mTOR. The use of inhibitors or siRNA suggests that lacritin mitogenic signaling involves Gαi or Gαo–PKCα-PLC–Ca2+–calcineurin–NFATC1 and Gαi or Gαo–PKCα-PLC–phospholipase D (PLD)–mTOR in a bell-shaped, dose-dependent manner requiring the Ca2+ sensor STIM1, but not TRPC1. This pathway suggests the placement of transiently dephosphorylated and perinuclear Golgi–translocated PKCα upstream of both Ca2+ mobilization and PLD activation in a complex with PLCγ2. Outward flow of lacritin from secretory cells through ducts may generate a proliferative/secretory field as a different unit of cellular renewal in nongermative epithelia where luminal structures predominate.

Many researchers seek to take advantage of the recently available and virtually uninterrupted supply of satellite-based rainfall information as an alternative and supplement to the ground-based observations in order to implement a cost-effective flood prediction in many under-gauged regions around the world. Recently, NASA Applied Science Program has partnered with USAID and African-RCMRD to implement an operational water-hazard warning system, SERVIR-Africa. The ultimate goal of the project is to build up disaster management capacity in East Africa by providing local governmental officials and international aid organizations a practical decision-support tool in order to better assess emerging flood impacts and to quantify spatial extent of flood risk, as well as to respond to such flood emergencies more expediently. The objective of this article is to evaluate the applicability of integrating NASA's standard satellite precipitation product with a flood prediction model for disaster management in Nzoia, sub-basin of Lake Victoria, Africa. This research first evaluated the TMPA real-time rainfall data against gauged rainfall data from the year 2002 through 2006. Then, the gridded Xinanjiang Model was calibrated to Nzoia basin for period of 1985-2006. Benchmark streamflow simulations were produced with the calibrated hydrological model using the rain gauge and observed streamflow data. Afterward, continuous discharge predictions forced by TMPA 3B42RT real-time data from 2002 through 2006 were simulated, and acceptable results were obtained in comparison with the benchmark performance according to the designated statistic indices such as bias ratio (20%) and NSCE (0.67). Moreover, it is identified that the flood prediction results were improved with systematically bias-corrected TMPA rainfall data with less bias (3.6%) and higher NSCE (0.71). Although the results justify to suggest to us that TMPA real-time data can be acceptably used to drive hydrological models for flood prediction purpose in Nzoia basin, continuous progress in space-borne rainfall estimation technology toward higher accuracy and higher spatial resolution is highly appreciated. Finally, it is also highly recommended that to increase flood forecasting lead time, more reliable and more accurate short-or medium-range quantitative precipitation forecasts is a must.

Reuse of AIP Publishing content is subject to the terms: https://publishing.aip.org/authors/rights-and-permissions. A model which treats spin diffusion and spin-lattice relaxation in multiphase polymers on the same footing is proposed. This new approach allows for more accurate determination of domain sizes and interfacial thickness in the probed polymers. In a poly͑styrene-b-isoprene͒ copolymer example a significant improvement in the agreement between the NMR measurements and the simulated results can be obtained with the incorporation of a spin-lattice relaxation term into the spin diffusion process. The obtained microphase structural parameters are similar to the small angle X-ray scattering results. In addition, the spin-lattice relaxation times ͑T 1 ) in different domains can be predicted reasonably well based on T 1 s of the component homopolymers and on the microphase structure in the present model.