Clusters of Adaptive Evolution in the Human Genome

Considerable work has been devoted to identifying regions of the human genome that have been subjected to recent positive selection. Although detailed follow-up studies of putatively selected regions are critical for a deeper understanding of human evolutionary history, such studies have received comparably less attention. Recently, we have shown that ALMS1 has been the target of recent positive selection acting on standing variation in Eurasian populations. Here, we describe a careful follow-up analysis of genetic variation across the ALMS1 region, which unexpectedly revealed a cluster of substrates of positive selection. Specifically, through the analysis of SNP data from the HapMap and Human Genome Diversity Project–Centre d’Etude du Polymorphisme Humain samples as well sequence data from the region, we find compelling evidence for three independent and distinct signals of recent positive selection across this 3 Mb region surrounding ALMS1. Moreover, we analyzed the HapMap data to identify other putative clusters of independent selective events and conservatively discovered 19 additional clusters of adaptive evolution. This work has important implications for the interpretation of genome-scans for positive selection in humans and more broadly contributes to a better understanding of how recent positive selection has shaped genetic variation across the human genome

The Dehn invariants of the Bricard octahedra

We prove that the Dehn invariants of any Bricard octahedron remain constant during the flex and that the Strong Bellows Conjecture holds true for the Steffen flexible polyhedron.Comment: 13 pages, 10 figure

Determination of Peptide and Protein Ion Charge States by Fourier Transformation of Isotope-Resolved Mass Spectra

We report an automated method for determining charge states from high-resolution mass spectra. Fourier transforms of isotope packets from high-resolution mass spectra are compared to Fourier transforms of modeled isotopic peak packets for a range of charge states. The charge state for the experimental ion packet is determined by the model isotope packet that yields the best match in the comparison of the Fourier transforms. This strategy is demonstrated for determining peptide ion charge states from “zoom scan” data from a linear quadrupole ion trap mass spectrometer, enabling the subsequent automated identification of singly- through quadruply-charged peptide ions, while reducing the numbers of conflicting identifications from ambiguous charge state assignments. We also apply this technique to determine the charges of intact protein ions from LC-FTICR data, demonstrating that it is more sensitive under these experimental conditions than two existing algorithms. The strategy outlined in this paper should be generally applicable to mass spectra obtained from any instrument capable of isotopic resolution

X-Ray Groups of Galaxies in the Aegis Deep and Wide Fields

We present the results of a search for extended X-ray sources and their corresponding galaxy groups from 800-ks Chandra coverage of the All-wavelength Extended Groth Strip International Survey (AEGIS). This yields one of the largest X-ray selected galaxy group catalogs from a blind survey to date. The red-sequence technique and spectroscopic redshifts allow us to identify 100$$ of reliable sources, leading to a catalog of 52 galaxy groups. The groups span the redshift range $z\sim0.066-1.544$ and virial mass range $M_{200}\sim1.34\times 10^{13}-1.33\times 10^{14}M_\odot$. For the 49 extended sources which lie within DEEP2 and DEEP3 Galaxy Redshift Survey coverage, we identify spectroscopic counterparts and determine velocity dispersions. We select member galaxies by applying different cuts along the line of sight or in projected spatial coordinates. A constant cut along the line of sight can cause a large scatter in scaling relations in low-mass or high-mass systems depending on the size of cut. A velocity dispersion based virial radius can more overestimate velocity dispersion in comparison to X-ray based virial radius for low mass systems. There is no significant difference between these two radial cuts for more massive systems. Independent of radial cut, overestimation of velocity dispersion can be created in case of existence of significant substructure and also compactness in X-ray emission which mostly occur in low mass systems. We also present a comparison between X-ray galaxy groups and optical galaxy groups detected using the Voronoi-Delaunay method (VDM) for DEEP2 data in this field.Comment: Accepted for publication in AP

Design and Development of Stable, Water-soluble, Human Toll-like Receptor 2-Specific, Monoacyl Lipopeptides as Candidate Vaccine Adjuvants

Antigens in modern subunit vaccines are largely soluble and poorly immunogenic proteins inducing relatively short-lived immune responses. Appropriate adjuvants initiate early innate immune responses, amplifying subsequent adaptive immune responses. Agonists of TLR2 are devoid of significant pro-inflammatory activity in ex vivo human blood models, and yet potently adjuvantic, suggesting that this chemotype may be a safe and effective adjuvant. Our earlier work on the monoacyl lipopeptide class of TLR2 agonists led to the design of a highly potent lead, but with negligible aqueous solubility, necessitating the reintroduction of aqueous solubility. We explored several strategies of introducing ionizable groups on the lipopeptide, as well as the systematic evaluation of chemically stable bioisosteres of the ester-linked palmitoyl group. These studies have led to a fully optimized, chemically stable, and highly water-soluble, human TLR2-specific agonist, which was found to have an excellent safety profile and displayed prominent adjuvantic activities in rabbit models