Spherical collapse of dark energy with an arbitrary sound speed

We consider a generic type of dark energy fluid, characterised by a constant equation of state parameter w and sound speed c_s, and investigate the impact of dark energy clustering on cosmic structure formation using the spherical collapse model. Along the way, we also discuss in detail the evolution of dark energy perturbations in the linear regime. We find that the introduction of a finite sound speed into the picture necessarily induces a scale-dependence in the dark energy clustering, which in turn affects the dynamics of the spherical collapse in a scale-dependent way. As with other, more conventional fluids, we can define a Jeans scale for the dark energy clustering, and hence a Jeans mass M_J for the dark matter which feels the effect of dark energy clustering via gravitational interactions. For bound objects (halos) with masses M >> M_J, the effect of dark energy clustering is maximal. For those with M << M_J, the dark energy component is effectively homogeneous, and its role in the formation of these structures is reduced to its effects on the Hubble expansion rate. To compute quantitatively the virial density and the linearly extrapolated threshold density, we use a quasi-linear approach which is expected to be valid up to around the Jeans mass. We find an interesting dependence of these quantities on the halo mass M, given some w and c_s. The dependence is the strongest for masses lying in the vicinity of M ~ M_J. Observing this M-dependence will be a tell-tale sign that dark energy is dynamic, and a great leap towards pinning down its clustering properties.Comment: 25 pages, 6 figures, matches version published in JCA

Linkage disequilibrium blocks, haplotype structure, and htSNPs of human CYP7A1 gene

BACKGROUND: Cholesterol 7-alpha-hydroxylase (CYP7A1) is the rate limiting enzyme for converting cholesterol into bile acids. Genetic variations in the CYP7A1 gene have been associated with metabolic disorders of cholesterol and bile acids, including hypercholesterolemia, hypertriglyceridemia, arteriosclerosis, and gallstone disease. Current genetic studies are focused mainly on analysis of a single nucleotide polymorphism (SNP) at A-278C in the promoter region of the CYP7A1 gene. Here we report a genetic approach for an extensive analysis on linkage disequilibrium (LD) blocks and haplotype structures of the entire CYP7A1 gene and its surrounding sequences in Africans, Caucasians, Asians, Mexican-Americans, and African-Americans. RESULT: The LD patterns and haplotype blocks of CYP7A1 gene were defined in Africans, Caucasians, and Asians using genotyping data downloaded from the HapMap database to select a set of haplotype-tagging SNPs (htSNP). A low cost, microarray-based platform on thin-film biosensor chips was then developed for high-throughput genotyping to study transferability of the HapMap htSNPs to Mexican-American and African-American populations. Comparative LD patterns and haplotype block structure was defined across all test populations. CONCLUSION: A constant genetic structure in CYP7A1 gene and its surrounding sequences was found that may lead to a better design for association studies of genetic variations in CYP7A1 gene with cholesterol and bile acid metabolism

Design of small molecule-responsive microRNAs based on structural requirements for Drosha processing

MicroRNAs (miRNAs) are prevalent regulatory RNAs that mediate gene silencing and play key roles in diverse cellular processes. While synthetic RNA-based regulatory systems that integrate regulatory and sensing functions have been demonstrated, the lack of detail on miRNA structure–function relationships has limited the development of integrated control systems based on miRNA silencing. Using an elucidated relationship between Drosha processing and the single-stranded nature of the miRNA basal segments, we developed a strategy for designing ligand-responsive miRNAs. We demonstrate that ligand binding to an aptamer integrated into the miRNA basal segments inhibits Drosha processing, resulting in titratable control over gene silencing. The generality of this control strategy was shown for three aptamer–small molecule ligand pairs. The platform can be extended to the design of synthetic miRNAs clusters, cis-acting miRNAs and self-targeting miRNAs that act both in cis and trans, enabling fine-tuning of the regulatory strength and dynamics. The ability of our ligand-responsive miRNA platform to respond to user-defined inputs, undergo regulatory performance tuning and display scalable combinatorial control schemes will help advance applications in biological research and applied medicine

Are short-term variations in solar oscillation frequencies the signature of a second solar dynamo?

In addition to the well-known 11-year solar cycle, the Sun's magnetic activity also shows significant variation on shorter time scales, e.g. between one and two years. We observe a quasi-biennial (2-year) signal in the solar p-mode oscillation frequencies, which are sensitive probes of the solar interior. The signal is visible in Sun-as-a-star data observed by different instruments and here we describe the results obtained using BiSON, GOLF, and VIRGO data. Our results imply that the 2-year signal is susceptible to the influence of the main 11-year solar cycle. However, the source of the signal appears to be separate from that of the 11-year cycle. We speculate as to whether it might be the signature of a second dynamo, located in the region of near-surface rotational shear.Comment: 6 pages, 2 figures, proceedings for SOHO-24/GONG 2010 conference, to be published in JPC

Measuring neutrino masses with a future galaxy survey

We perform a detailed forecast on how well a Euclid-like photometric galaxy and cosmic shear survey will be able to constrain the absolute neutrino mass scale. Adopting conservative assumptions about the survey specifications and assuming complete ignorance of the galaxy bias, we estimate that the minimum mass sum of sum m_nu ~ 0.06 eV in the normal hierarchy can be detected at 1.5 sigma to 2.5 sigma significance, depending on the model complexity, using a combination of galaxy and cosmic shear power spectrum measurements in conjunction with CMB temperature and polarisation observations from Planck. With better knowledge of the galaxy bias, the significance of the detection could potentially reach 5.4 sigma. Interestingly, neither Planck+shear nor Planck+galaxy alone can achieve this level of sensitivity; it is the combined effect of galaxy and cosmic shear power spectrum measurements that breaks the persistent degeneracies between the neutrino mass, the physical matter density, and the Hubble parameter. Notwithstanding this remarkable sensitivity to sum m_nu, Euclid-like shear and galaxy data will not be sensitive to the exact mass spectrum of the neutrino sector; no significant bias (< 1 sigma) in the parameter estimation is induced by fitting inaccurate models of the neutrino mass splittings to the mock data, nor does the goodness-of-fit of these models suffer any significant degradation relative to the true one (Delta chi_eff ^2< 1).Comment: v1: 29 pages, 10 figures. v2: 33 pages, 12 figures; added sections on shape evolution and constraints in more complex models, accepted for publication in JCA

Rapidly evolving marmoset MSMB genes are differently expressed in the male genital tract

BACKGROUND: Beta-microseminoprotein, an abundant component in prostatic fluid, is encoded by the potential tumor suppressor gene MSMB. Some New World monkeys carry several copies of this gene, in contrast to most mammals, including humans, which have one only. Here we have investigated the background for the species difference by analyzing the chromosomal organization and expression of MSMB in the common marmoset (Callithrix jacchus). METHODS: Genes were identified in the Callithrix jacchus genome database using bioinformatics and transcripts were analyzed by RT-PCR and quantified by real time PCR in the presence of SYBR green. RESULTS: The common marmoset has five MSMB: one processed pseudogene and four functional genes. The latter encompass homologous genomic regions of 32-35 kb, containing the genes of 12-14 kb and conserved upstream and downstream regions of 14-19 kb and 3-4 kb. One gene, MSMB1, occupies the same position on the chromosome as the single human gene. On the same chromosome, but several Mb away, is another MSMB locus situated with MSMB2, MSMB3 and MSMB4 arranged in tandem. Measurements of transcripts demonstrated that all functional genes are expressed in the male genital tract, generating very high transcript levels in the prostate. The transcript levels in seminal vesicles and testis are two and four orders of magnitude lower. A single gene, MSMB3, accounts for more than 90% of MSMB transcripts in both the prostate and the seminal vesicles, whereas in the testis around half of the transcripts originate from MSMB2. These genes display rapid evolution with a skewed distribution of mutated nucleotides; in MSMB2 they affect nucleotides encoding the N-terminal Greek key domain, whereas in MSMB3 it is the C-terminal MSMB-unique domain that is affected. CONCLUSION: Callitrichide monkeys have four functional MSMB that are all expressed in the male genital tract, but the product from one gene, MSMB3, will predominate in seminal plasma. This gene and MSMB2, the predominating testicular gene, have accumulated mutations that affect different parts of the translation products, suggesting an ongoing molecular specialization that presumably yields functional differences in accessory sex glands and testis

Discovery of an orally active benzoxaborole prodrug effective in the treatment of Chagas disease in non-human primates

Trypanosoma cruzi, the agent of Chagas disease, probably infects tens of millions of people, primarily in Latin America, causing morbidity and mortality. The options for treatment and prevention of Chagas disease are limited and underutilized. Here we describe the discovery of a series of benzoxaborole compounds with nanomolar activity against extra- and intracellular stages of T. cruzi. Leveraging both ongoing drug discovery efforts in related kinetoplastids, and the exceptional models for rapid drug screening and optimization in T. cruzi, we have identified the prodrug AN15368 that is activated by parasite carboxypeptidases to yield a compound that targets the messenger RNA processing pathway in T. cruzi. AN15368 was found to be active in vitro and in vivo against a range of genetically distinct T. cruzi lineages and was uniformly curative in non-human primates (NHPs) with long-term naturally acquired infections. Treatment in NHPs also revealed no detectable acute toxicity or long-term health or reproductive impact. Thus, AN15368 is an extensively validated and apparently safe, clinically ready candidate with promising potential for prevention and treatment of Chagas disease

Efficient multiphoton sampling of molecular vibronic spectra on a superconducting bosonic processor

The efficient simulation of quantum systems is a primary motivating factor for developing controllable quantum machines. For addressing systems with underlying bosonic structure, it is advantageous to utilize a naturally bosonic platform. Optical photons passing through linear networks may be configured to perform quantum simulation tasks, but the efficient preparation and detection of multiphoton quantum states of light in linear optical systems are challenging. Here, we experimentally implement a boson sampling protocol for simulating molecular vibronic spectra [Nature Photonics $\textbf{9}$, 615 (2015)] in a two-mode superconducting device. In addition to enacting the requisite set of Gaussian operations across both modes, we fulfill the scalability requirement by demonstrating, for the first time in any platform, a high-fidelity single-shot photon number resolving detection scheme capable of resolving up to 15 photons per mode. Furthermore, we exercise the capability of synthesizing non-Gaussian input states to simulate spectra of molecular ensembles in vibrational excited states. We show the re-programmability of our implementation by extracting the spectra of photoelectron processes in H$_2$O, O$_3$, NO$_2$, and SO$_2$. The capabilities highlighted in this work establish the superconducting architecture as a promising platform for bosonic simulations, and by combining them with tools such as Kerr interactions and engineered dissipation, enable the simulation of a wider class of bosonic systems