A Computational Study of a Data Assimilation Algorithm for the Two-dimensional Navier--Stokes Equations

We study the numerical performance of a continuous data assimilation (downscaling) algorithm, based on ideas from feedback control theory, in the context of the two-dimensional incompressible Navier--Stokes equations. Our model problem is to recover an unknown reference solution, asymptotically in time, by using continuous-in-time coarse-mesh nodal-point observational measurements of the velocity field of this reference solution (subsampling), as might be measured by an array of weather vane anemometers. Our calculations show that the required nodal observation density is remarkably less that what is suggested by the analytical study; and is in fact comparable to the {\it number of numerically determining Fourier modes}, which was reported in an earlier computational study by the authors. Thus, this method is computationally efficient and performs far better than the analytical estimates suggest

Reassessing the Role of APOBEC3G in Human Immunodeficiency Virus Type 1 Infection of Quiescent CD4+ T-Cells

HIV-1 is restricted for infection of primary quiescent T-cells. After viral entry, reverse transcription is initiated but is not completed. Various hypotheses have been proposed for this cellular restriction including insufficient nucleotide pools and cellular factors, but none have been confirmed as the primary mechanism for restriction. A recent study by Chiu et al. implicates APOBEC3G, an anti-retroviral cytidine deaminase, as the cellular restriction factor. Here, we attempted to confirm these findings using the same strategy as reported by Chiu et al. of siRNA targeting knock-down of APOBEC3G expression. In contrast to the published study, our results do not support a role for APOBEC3G in restriction of HIV-1 in quiescent CD4+ T-cells. In our study, we tested the same siRNA as reported by Chiu et al. as well as two additional siRNAs targeting APOBEC3G, one of which showed 2-fold greater knock-down of APOBEC3G mRNA. However, none of the three siRNAs tested had a discernable effect on enhancing infection by HIV-1 in quiescent CD4+ T-cells. Therefore, we conclude that the primary mechanism of HIV-1 restriction in quiescent CD4+ T-cells remains to be elucidated

Novel Magnetic and Thermodynamic Properties of Thiospinel Compound CuCrZrS4_{4}

We have carried out dc magnetic susceptibility, magnetization and specific heat measurements on thiospinel CuCrZrS$_{4}$. Below $T_{\rm C}^{*} =$ 58 K, dc magnetic susceptibility and magnetization data show ferromagnetic behavior with a small spontaneous magnetization 0.27 $\mu_{\rm B}/$f. u.. In dc magnetic susceptibility, large and weak irreversibilities are observed below $T_{\rm f} =$ 6 K and in the range $T_{\rm f}< T < T_{\rm C}^{*}$ respectively. We found that there is no anomaly as a peak or step in the specific heat at $T_{\rm C}^{*}$.Comment: 11 pages, 4 figure

Hexokinase is necessary for glucose-mediated photosynthesis repression and lipid accumulation in a green alga.

Global primary production is driven largely by oxygenic photosynthesis, with algae as major contributors. The green alga Chromochloris zofingiensis reversibly switches off photosynthesis in the presence of glucose in the light and augments production of biofuel precursors (triacylglycerols) and the high-value antioxidant astaxanthin. Here we used forward genetics to reveal that this photosynthetic and metabolic switch is mediated by the glycolytic enzyme hexokinase (CzHXK1). In contrast to wild-type, glucose-treated hxk1 mutants do not shut off photosynthesis or accumulate astaxanthin, triacylglycerols, or cytoplasmic lipid droplets. We show that CzHXK1 is critical for the regulation of genes related to photosynthesis, ketocarotenoid synthesis and fatty acid biosynthesis. Sugars play fundamental regulatory roles in gene expression, physiology, metabolism, and growth in plants and animals, and we introduce a relatively simple, emerging model system to investigate conserved eukaryotic sugar sensing and signaling at the base of the green lineage

Lyman Alpha Emitters in the Hierarchically Clustering Galaxy Formation

We present a new theoretical model for the luminosity functions (LFs) of Lyman alpha (Lya) emitting galaxies in the framework of hierarchical galaxy formation. We extend a semi-analytic model of galaxy formation that reproduces a number of observations for local and high-z galaxies, without changing the original model parameters but introducing a physically-motivated modelling to describe the escape fraction of Lya photons from host galaxies (f_esc). Though a previous study using a hierarchical clustering model simply assumed a constant and universal value of f_esc, we incorporate two new effects on f_esc: extinction by interstellar dust and galaxy-scale outflow induced as a star formation feedback. It is found that the new model nicely reproduces all the observed Lya LFs of the Lya emitters (LAEs) at different redshifts in z ~ 3-6. Especially, the rather surprisingly small evolution of the observed LAE Lya LFs compared with the dark halo mass function is naturally reproduced. Our model predicts that galaxies with strong outflows and f_esc ~ 1 are dominant in the observed LFs. This is also consistent with available observations, while the simple universal f_esc model requires f_esc << 1 not to overproduce the brightest LAEs. On the other hand, we found that our model significantly overpredicts LAEs at z > 6, and absorption of Lya photons by neutral hydrogen in intergalactic medium (IGM) is a reasonable interpretation for the discrepancy. This indicates that the IGM neutral fraction x_HI rapidly evolves from x_HI << 1 at z < 6 to a value of order unity at z ~ 6-7, which is broadly consistent with other observational constraints on the reionization history.Comment: 14 pages, 7 figures, 1 table; accepted to ApJ; the html abstract is replaced to match the accepted version, the .ps and .pdf files are strictly identical between the 2nd and the 3rd version

A New Experimental Approach to Evaluate Plasma-induced Damage in Microcantilever

Plasma&nbsp; etching,&nbsp; during&nbsp; micro-fabrication&nbsp; processing&nbsp; is&nbsp; indispensable&nbsp; for&nbsp; fabricating&nbsp; MEMS&nbsp; structures.&nbsp; During&nbsp; the plasma&nbsp; processes,&nbsp; two&nbsp; major matters,&nbsp; charged&nbsp; ions&nbsp; and&nbsp; vacuum&ndash;ultraviolet&nbsp; (VUV)&nbsp; irradiation&nbsp; damage,&nbsp; take&nbsp; charge&nbsp; of reliability&nbsp; degradation.&nbsp; The&nbsp; charged&nbsp; ions&nbsp; induce&nbsp; unwanted&nbsp; sidewall&nbsp; etching,&nbsp; generally&nbsp; called&nbsp; as&nbsp; &ldquo;notching&rdquo;,&nbsp; which causes&nbsp; degradation&nbsp; in&nbsp; brittle&nbsp; strength.&nbsp; Furthermore,&nbsp; the&nbsp; VUV&nbsp; irradiation&nbsp; gives&nbsp; rise&nbsp; to&nbsp; crystal&nbsp; defects&nbsp; on&nbsp; the&nbsp; etching surface.&nbsp; To&nbsp; overcome&nbsp; the&nbsp; problem,&nbsp; neutral&nbsp; beam&nbsp; etching&nbsp; (NBE),&nbsp; which&nbsp; use&nbsp; neutral&nbsp; particles&nbsp; without&nbsp; the&nbsp; VUV irradiation,&nbsp; has&nbsp; been&nbsp; developed.&nbsp; In&nbsp; order&nbsp; to&nbsp; evaluate&nbsp; the&nbsp; effect&nbsp; of&nbsp; the&nbsp; NBE&nbsp; quantitatively,&nbsp; we&nbsp; measured&nbsp; the&nbsp; resonance property of a micro-cantilever before and after NBE treatment. The thickness of damage layer (&delta;) times the imaginary part&nbsp; of&nbsp; the&nbsp; complex&nbsp; Young's&nbsp; modulus&nbsp; (Eds)&nbsp; were&nbsp; then&nbsp; compared,&nbsp; which&nbsp; is&nbsp; a&nbsp; parameter&nbsp; of&nbsp; surface&nbsp; damage.&nbsp; Although plasma processes&nbsp; make the initial surface of cantilevers damaged during their fabrication, the removal of that damage by NBE was confirmed as the reduction in &delta;Eds. NBE will realize a damage-free surface for microstructures

Systemically Administered RNAi Molecule Sensitizes Malignant Pleural Mesotheliomal Cells to Pemetrexed Therapy

Pemetrexed (PMX) is a key drug for the management of malignant pleural mesothelioma (MPM). However, its therapeutic efficacy is cruelly restricted in many clinical settings by the overexpression of thymidylate synthase (TS) gene. Recently, we emphasized the efficacy of locally administered shRNA designed against TS gene in enhancing the cytotoxic effect of PMX against orthotopically implanted MPM cells in tumor xenograft tumor model. Herein, we explored the efficiency of systemic, rather than local, delivery of TS RNAi molecule in sensitizing MPM cells to the cytotoxic effect of PMX. We here designed a PEG-coated TS shRNA-lipoplex (PEG-coated TS shRNA-lipoplex) for systemic injection. PEG modification efficiently delivered TS shRNA in the lipoplex to tumor tissue following intravenous administration as indicated by a significant suppression of TS expression level in tumor tissue. In addition, the combined treatment of PMX with systemic injection of PEG-coated TS shRNA-lipoplex exerted a potent antitumor activity in a s.c. xenograft tumor model, compared to a single treatment with either PMX or PEG-coated TS shRNA-lipoplex. Metastasis, or the spread, of mesothelioma substantially dedicates the effectiveness of treatment options. The systemic, in addition to local, delivery of tumor targeted anti-TS RNAi system we propose in this study might be an effective option to extend the clinical utility of PMX in treating malignant mesothelioma

First-principles study on the intermediate compounds of LiBH4_4

We report the results of the first-principles calculation on the intermediate compounds of LiBH$_4$. The stability of LiB$_3$H$_8$ and Li$_2$B$_n$H$_n (n=5-12)$ has been examined with the ultrasoft pseudopotential method based on the density functional theory. Theoretical prediction has suggested that monoclinic Li$_2$B$_{12}$H$_{12}$ is the most stable among the candidate materials. We propose the following hydriding/dehydriding process of LiBH$_4$ via this intermediate compound : LiBH$_4 \leftrightarrow {1/12}$Li$_{2}$B$_{12}$H$_{12} + {5/6}$ LiH $+ {13/12}$H$_2 \leftrightarrow$LiH $+$ B $+ {3/2}$H$_2$. The hydrogen content and enthalpy of the first reaction are estimated to be 10 mass% and 56 kJ/mol H$_2$, respectively, and those of the second reaction are 4 mass% and 125 kJ/mol H$_2$. They are in good agreement with experimental results of the thermal desorption spectra of LiBH$_4$. Our calculation has predicted that the bending modes for the $\Gamma$-phonon frequencies of monoclinic Li$_2$B$_{12}$H$_{12}$ are lower than that of LiBH$_4$, while stretching modes are higher. These results are very useful for the experimental search and identification of possible intermediate compounds.Comment: 7 pages, 5 figures, submitted to PR

Stable reduction of CCR5 by RNAi through hematopoietic stem cell transplant in non-human primates

RNAi is a powerful method for suppressing gene expression that has tremendous potential for therapeutic applications. However, because endogenous RNAi plays a role in normal cellular functions, delivery and expression of siRNAs must be balanced with safety. Here we report successful stable expression in primates of siRNAs directed to chemokine (c-c motif) receptor 5 (CCR5) introduced through CD34+ hematopoietic stem/progenitor cell transplant. After hematopoietic reconstitution, to date 14 months after transplant, we observe stably marked lymphocytes expressing siRNAs and consistent down-regulation of chemokine (c-c motif) receptor 5 expression. The marked cells are less susceptible to simian immunodeficiency virus infection ex vivo. These studies provide a successful demonstration that siRNAs can be used together with hematopoietic stem cell transplant to stably modulate gene expression in primates and potentially treat blood diseases such as HIV-1

Metronomic S-1 dosing and thymidylate synthase silencing have synergistic antitumor efficacy in a colorectal cancer xenograft model

Metronomic chemotherapy is currently considered an emerging therapeutic option in clinical oncology. S-1, an oral formulation of Tegafur (TF), a prodrug of 5-fluorouracil (5-FU), is designed to improve the antitumor activity of 5-FU in tandem with reducing its toxicity. Clinically, metronomic S-1 dosing has been approved for the standard first- and second-line treatment of metastatic or advanced stage of colorectal (CRC). However, expression of intratumor thymidylate synthase (TS), a significant gene in cellular proliferation, is associated with poor outcome to 5-FU-based chemotherapeutic regimens. In this study, therefore, we examined the effect of a combination of TS silencing by an RNA interfering molecule, chemically synthesized short hairpin RNA against TS (shTS), and 5-FU on the growth of human colorectal cancer cell (DLD-1) both in vitro and in vivo. The combined treatment of both shTS with 5-FU substantially inhibited cell proliferation in vitro. For in vivo treatments, the combined treatment of metronomic S-1 dosing with intravenously injected polyethylene glycol (PEG)-coated shTS-lipoplex significantly suppressed tumor growth, compared to a single treatment of either S-1 or PEG-coated shTS-lipoplex. In addition, the combined treatment increased the proportion of apoptotic cells in the DLD-1 tumor tissue. Our results suggest that metronomic S-1 dosing combined with TS silencing might represent an emerging therapeutic strategy for the treatment of patients with advanced CRC