Theory of Dispersed Fixed-Delay Interferometry for Radial Velocity Exoplanet Searches

The dispersed fixed-delay interferometer (DFDI) represents a new instrument concept for high-precision radial velocity (RV) surveys for extrasolar planets. A combination of Michelson interferometer and medium-resolution spectrograph, it has the potential for performing multi-object surveys, where most previous RV techniques have been limited to observing only one target at a time. Because of the large sample of extrasolar planets needed to better understand planetary formation, evolution, and prevalence, this new technique represents a logical next step in instrumentation for RV extrasolar planet searches, and has been proven with the single-object Exoplanet Tracker (ET) at Kitt Peak National Observatory, and the multi-object W. M. Keck/MARVELS Exoplanet Tracker at Apache Point Observatory. The development of the ET instruments has necessitated fleshing out a detailed understanding of the physical principles of the DFDI technique. Here we summarize the fundamental theoretical material needed to understand the technique and provide an overview of the physics underlying the instrument's working. We also derive some useful analytical formulae that can be used to estimate the level of various sources of error generic to the technique, such as photon shot noise when using a fiducial reference spectrum, contamination by secondary spectra (e.g., crowded sources, spectroscopic binaries, or moonlight contamination), residual interferometer comb, and reference cross-talk error. Following this, we show that the use of a traditional gas absorption fiducial reference with a DFDI can incur significant systematic errors that must be taken into account at the precision levels required to detect extrasolar planets.Comment: 58 pages, 11 figures, 1 table, 3 appendices. Accepted for publication in ApJS. Minor typographical corrections; update to acknowledgment

Rapid turnover of effector-memory CD4(+) T cells in healthy humans

Memory T cells can be divided into central-memory (T(CM)) and effector-memory (T(EM)) cells, which differ in their functional properties. Although both subpopulations can persist long term, it is not known whether they are maintained by similar mechanisms. We used in vivo labeling with deuterated glucose to measure the turnover of CD4(+) T cells in healthy humans. The CD45R0(+)CCR7(-) T(EM) subpopulation was shown to have a rapid proliferation rate of 4.7% per day compared with 1.5% per day for CD45R0(+)CCR7(+) T(CM) cells; these values are equivalent to average intermitotic (doubling) times of 15 and 48 d, respectively. In contrast, the CD45RA(+)CCR7(+) naive CD4(+) T cell population was found to be much longer lived, being labeled at a rate of only 0.2% per day (corresponding to an intermitotic time of approximately 1 yr). These data indicate that human CD4(+) T(EM) cells constitute a short-lived cell population that requires continuous replenishment in vivo

Characterization of Zika virus endocytic pathways in human glioblastoma cells

Zika virus (ZIKV) infections can cause microcephaly and neurological disorders. However, the early infection events of ZIKV in neural cells remain to be characterized. Here, by using a combination of pharmacological and molecular approaches and the human glioblastoma cell T98G as a model, we first observed that ZIKV infection was inhibited by chloroquine and NH4Cl, indicating a requirement of low intracellular pH. We further showed that dynamin is required as the ZIKV entry was affected by the specific inhibitor dynasore, small interfering RNA (siRNA) knockdown of dynamin, or by expressing the dominant-negative K44A mutant. Moreover, the ZIKV entry was significantly inhibited by chlorpromazine, pitstop2, or siRNA knockdown of clathrin heavy chain, indicating an involvement of clathrin-mediated endocytosis. In addition, genistein treatment, siRNA knockdown of caveolin-1, or overexpression of a dominant-negative caveolin mutant impacted the ZIKV entry, with ZIKV particles being observed to colocalize with caveolin-1, implying that caveola endocytosis can also be involved. Furthermore, we found that the endocytosis of ZIKV is dependent on membrane cholesterol, microtubules, and actin cytoskeleton. Importantly, ZIKV infection was inhibited by silencing of Rab5 and Rab7, while confocal microscopy showed that ZIKV particles localized in Rab5- and Rab7-postive endosomes. These results indicated that, after internalization, ZIKV likely moves to Rab5-positive early endosome and Rab7-positive late endosomes before delivering its RNA into the cytoplasm. Taken together, our study, for the first time, described the early infection events of ZIKV in human glioblastoma cell T98G

High-Fidelity Spectroscopy at the Highest Resolutions

High-fidelity spectroscopy presents challenges for both observations and in designing instruments. High-resolution and high-accuracy spectra are required for verifying hydrodynamic stellar atmospheres and for resolving intergalactic absorption-line structures in quasars. Even with great photon fluxes from large telescopes with matching spectrometers, precise measurements of line profiles and wavelength positions encounter various physical, observational, and instrumental limits. The analysis may be limited by astrophysical and telluric blends, lack of suitable lines, imprecise laboratory wavelengths, or instrumental imperfections. To some extent, such limits can be pushed by forming averages over many similar spectral lines, thus averaging away small random blends and wavelength errors. In situations where theoretical predictions of lineshapes and shifts can be accurately made (e.g., hydrodynamic models of solar-type stars), the consistency between noisy observations and theoretical predictions may be verified; however this is not feasible for, e.g., the complex of intergalactic metal lines in spectra of distant quasars, where the primary data must come from observations. To more fully resolve lineshapes and interpret wavelength shifts in stars and quasars alike, spectral resolutions on order R=300,000 or more are required; a level that is becoming (but is not yet) available. A grand challenge remains to design efficient spectrometers with resolutions approaching R=1,000,000 for the forthcoming generation of extremely large telescopes.Comment: 6 pages, 4 figures, to appear in Reviews in Modern Astronomy vol. 22 (2010

HIV enteropathy and 'Slim disease': Historical and current perspectives.

OBJECTIVES: Chronic diarrhoea and severe wasting associated with HIV infection were first described in East African patients as slim disease (SD) in 1985. The main histological features are flattening of the villi (villous atrophy) and crypt hyperplasia (elongated crypts), i.e., HIV enteropathy (HIVE). Selective loss of mucosal clusters of differentiation 4 (CD4)+ T helper (Th)17+ lymphocytes is the immunological hallmark of HIVE. This review explores (i) the historical background of HIVE and SD, (ii) the relationship between gut mucosal CD4+ Th17+ and intestinal-resident intra-epithelial gamma delta (IRIE) T lymphocytes in pathogenesis of HIVE, (iii) the role of cytokines in regulation of intestinal epithelial proliferation, and (iv) the role of antiretroviral therapy in HIVE. METHODS: Recent studies have highlighted the role of IRIE T lymphocytes, mostly CD8+, in regulating gut epithelial regeneration. CD4+Th17+ and IRIE T cells are necessary to maintain intestinal barrier integrity and mucosal antimicrobial immune defence. However, the immunological cross-talk between such lymphocyte sub-sets culminating in HIVE is uncertain. We undertook a narrative literature review under the headings 'HIVE', 'SD', and 'Highly active antiretroviral therapy (HAART). Relevant studies were located using the electronic search engines Google Scholar and PubMed from 1984 to 2022. RESULTS: Depletion of Th17+ cells in the lamina propria, attributed to low-level viraemia, is accompanied by concomitant increase in the density of gut mucosal IRIE T lymphocytes in AIDS. The latter express a broad range of cytokines (interferon-gamma, tumor necrosis factor-alpha, interleukin-17) and chemokines e.g., keratinocyte growth factor, post exposure to HIV-infected cells. Keratinocyte growth factor induces epithelial proliferation mainly in the crypts, leading to functional immaturity of enterocytes, reduced gut absorptive surface area and malabsorption in animal experiments. Of note, the absence of IRIE T cells is associated with a reduction in epithelial cell turnover. Patients with HIVE receiving early HAART show enhanced expression of mucosal repair genes and improvement of gut symptoms. CONCLUSION: Multiple lines of enquiry suggest HIVE is directly related to HIV infection and is a consequence of perturbations in mucosal CD4+Th17+ and IRIE T lymphocytes. The pathological result is enterocyte immaturity and dysfunction. SD whose main features are malabsorption, diarrhoea and weight loss, is a severe clinical expression of HIVE. A better understanding of immuno-pathogenesis of HIVE opens a window of opportunity for the potential use of immunotherapy in HIV disease and other T cell-mediated enteropathies

Bifunctional CD4-DC-SIGN fusion proteins demonstrate enhanced avidity to gp120 and inhibit HIV-1 infection and dissemination.

Early stages of mucosal infection are potential targets for HIV-1 prevention. CD4 is the primary receptor in HIV-1 infection whereas DC-SIGN likely plays an important role in HIV-1 dissemination, particularly during sexual transmission. To test the hypothesis that an inhibitor simultaneously targeting both CD4 and DC-SIGN binding sites on gp120 may provide a potent anti-HIV strategy, we designed constructs by fusing the extracellular CD4 and DC-SIGN domains together with varied arrangements of the lengths of CD4, DC-SIGN and the linker. We expressed, purified and characterized a series of soluble CD4-linker–DC-SIGN (CLD) fusion proteins. Several CLDs, composed of a longer linker and an extra neck domain of DC-SIGN, had enhanced affinity for gp120 as evidenced by molecular-interaction analysis. Furthermore, such CLDs exhibited significantly enhanced neutralization activity against both laboratory-adapted and primary HIV-1 isolates. Moreover, CLDs efficiently inhibited HIV-1 infection in trans via a DC-SIGN-expressing cell line and primary human dendritic cells. This was further strengthened by the results from the human cervical explant model, showing that CLDs potently prevented both localized and disseminated infections. This is the first time that soluble DC-SIGN-based bifunctional proteins have demonstrated anti-HIV potency. Our study provides proof of the concept that targeting both CD4 and DC-SIGN binding sites on gp120 represents a novel antiviral strategy. Given that DC-SIGN binding to gp120 increases exposure of the CD4 binding site and that the soluble forms of CD4 and DC-SIGN occur in vivo, further improvement of CLDs may render them potentially useful in prophylaxis or therapeutics

Ability of SP12 mutant of S. typhi to effectively induce antibody responses to the mucosal antigen enterotoxigenic E. coli heat labile toxin B subunit after oral delivery to humans

We have evaluated an oral vaccine based on an Salmonella enteric serovar typhi (S. typhi) Ty2 derivative TSB7 harboring deletion mutations in ssaV (SPI-2) and aroC together with a chromosomally integrated copy of eltB encoding the B subunit of enterotoxigenic Escherichia coli heat labile toxin (LT-B) in volunteers. Two oral doses of 108 or 109 CFU were administered to two groups of volunteers and both doses were well tolerated, with no vaccinemia, and only transient stool shedding. Immune responses to LT-B and S. typhi lipopolysaccharide were demonstrated in 67 and 97% of subjects, respectively, without evidence of anti-carrier immunity preventing boosting of LT-B responses in many cases. Further development of this salmonella-based (spi-VEC) system for oral delivery of heterologous antigens appears warranted

Money in Islamic banking system

The idea of revisiting currency and the gold dinar from an Islamic standpoint is an interesting topic of discussion in the context of the current monetary system. This chapter examines the historical aspects and supremacy of a gold currency and the weakness of fiat money using a maslahah-mafsadah approach. It considers some possible alternative forms of gold as money and then discusses some obstacles and barriers in the hope of finding a model of gold as money to implement in the current economic system. A deductive method is used to explore the implementation of a gold currency based on historical study and library research. The findings reveal that money is not limited to gold and silver. However, by deriving new law from original law process, the law (hukm) of gold or silver as money is permissible