Is gene therapy a good therapeutic approach for HIV-positive patients?

Despite advances and options available in gene therapy for HIV-1 infection, its application in the clinical setting has been challenging. Although published data from HIV-1 clinical trials show safety and proof of principle for gene therapy, positive clinical outcomes for infected patients have yet to be demonstrated. The cause for this slow progress may arise from the fact that HIV is a complex multi-organ system infection. There is uncertainty regarding the types of cells to target by gene therapy and there are issues regarding insufficient transduction of cells and long-term expression. This paper discusses state-of-the-art molecular approaches against HIV-1 and the application of these treatments in current and ongoing clinical trials

Two-Dimensional Controlled Syntheses of Polypeptide Molecular Brushes via N-Carboxyanhydride Ring-Opening Polymerization and Ring-Opening Metathesis Polymerization.

Well-defined molecular brushes bearing polypeptides as side chains were prepared by a "grafting through" synthetic strategy with two-dimensional control over the brush molecular architectures. By integrating N-carboxyanhydride ring-opening polymerizations (NCA ROPs) and ring-opening metathesis polymerizations (ROMPs), desirable segment lengths of polypeptide side chains and polynorbornene brush backbones were independently constructed in controlled manners. The N2 flow accelerated NCA ROP was utilized to prepare polypeptide macromonomers with different lengths initiated from a norbornene-based primary amine, and those macromonomers were then polymerized via ROMP. It was found that a mixture of dichloromethane and an ionic liquid were required as the solvent system to allow for construction of molecular brush polymers having densely-grafted peptide chains emanating from a polynorbornene backbone, poly(norbornene-graft-poly(β-benzyl-l-aspartate)) (P(NB-g-PBLA)). Highly efficient postpolymerization modification was achieved by aminolysis of PBLA side chains for facile installment of functional moieties onto the molecular brushes

Number fields and function fields:Coalescences, contrasts and emerging applications

The similarity between the density of the primes and the density of irreducible polynomials defined over a finite field of q elements was first observed by Gauss. Since then, many other analogies have been uncovered between arithmetic in number fields and in function fields defined over a finite field. Although an active area of interaction for the past half century at least, the language and techniques used in analytic number theory and in the function field setting are quite different, and this has frustrated interchanges between the two areas. This situation is currently changing, and there has been substantial progress on a number of problems stimulated by bringing together ideas from each field. We here introduce the papers published in this Theo Murphy meeting issue, where some of the recent developments are explained

Unbiased taxonomic annotation of metagenomic samples

The classification of reads from a metagenomic sample using a reference taxonomy is usually based on first mapping the reads to the reference sequences and then classifying each read at a node under the lowest common ancestor of the candidate sequences in the reference taxonomy with the least classification error. However, this taxonomic annotation can be biased by an imbalanced taxonomy and also by the presence of multiple nodes in the taxonomy with the least classification error for a given read. In this article, we show that the Rand index is a better indicator of classification error than the often used area under thereceiver operating characteristic (ROC) curve andF-measure for both balanced and imbalanced reference taxonomies, and we also address the second source of bias by reducing the taxonomic annotation problem for a whole metagenomic sample to a set cover problem, for which a logarithmic approximation can be obtained in linear time and an exact solution can be obtained by integer linear programming. Experimental results with a proof-of-concept implementation of the set cover approach to taxonomic annotation in a next release of the TANGO software show that the set cover approach further reduces ambiguity in the taxonomic annotation obtained with TANGO without distorting the relative abundance profile of the metagenomic sample.Peer ReviewedPostprint (published version

High VEGF with Rapid Growth and Early Metastasis in a Mouse Osteosarcoma Model

A murine model of osteosarcoma was developed to investigate the association between the expression of VEGF and the progression of osteosarcoma. Two human osteosarcoma cell lines with distinct VEGF expressions were introduced into proximal tibiae of immuno-deficient SCID mice, either by direct injection through the cortical bone or surgical exposing and drilling on the tibial metaphysis to seed tumor cells. Bone tumors were obvious on microCT within 4 weeks following osteosarcoma cell inoculation through surgical delivery. In contrast, direct injection without drilling often resulted in periosteal tumors. Although neoplasms were developed regardless of VEGF levels, orthotopic tumors derived from high VEGF-expressing cells were detected 2 weeks earlier on CT images than the ones from VEGF negative cells. At sacrifice, high VEGF tumors were distinctively larger in size and more frequently invaded the adjacent bone tissue. Multiple metastatic lesions were found in all the lung tissues at 8 weeks from high VEGF group, whereas only 1 of 7 VEGF negative tumors exhibited pulmonary metastasis. Overall, this model developed with the surgical tumor cell delivery results in histological and radiographic features more consistent with primary osteosarcoma. Interestingly, VEGF expression correlates with the early establishment, rapid tumor growth, and the development of pulmonary metastasis

The Missouri soil saving dam : low-cost structure for use in farm plans for water management

Cover title."A revision of Bulletin 434" -- P. [3]

The White Dwarfs within 20 Parsecs of the Sun: Kinematics and Statistics

We present the kinematical properties, distribution of spectroscopic subtypes, stellar population subcomponents of the white dwarfs within 20 pc of the sun. We find no convincing evidence of halo white dwarfs in the total 20 pc sample of 129 white dwarfs nor is there convincing evidence of genuine thick disk subcomponent members within 20 parsecs. Virtually the entire 20 pc sample likely belongs to the thin disk. The total DA to non-DA ratio of the 20 pc sample is 1.6, a manifestation of deepening envelope convection which transforms DA stars with sufficiently thin H surface layers into non-DAs. The addition of 5 new stars to the 20 pc sample yields a revised local space density of white dwarfs of $4.9\pm0.5 \times 10^{-3}$ M_{\sun}/yr and a corresponding mass density of $3.3\pm0.3 \times 10^{-3}$ M_{\sun}/pc$^{3}$. We find that at least 15% of the white dwarfs within 20 parsecs of the sun (the DAZ and DZ stars) have photospheric metals that possibly originate from accretion of circumstellar material (debris disks) around them. If this interpretation is correct, this suggests the possibility that the same percentage have planets or asteroid-like bodies orbiting them.Comment: Accepted for publication in The Astronomical Journa

Restrictions Limiting the Generation of DNA Double Strand Breaks during Chromosomal V(D)J Recombination

Antigen receptor loci are composed of numerous variable (V), diversity (D), and joining (J) gene segments, each flanked by recombination signal sequences (RSSs). The V(D)J recombination reaction proceeds through RSS recognition and DNA cleavage steps making it possible for multiple DNA double strand breaks (DSBs) to be introduced at a single locus. Here we use ligation-mediated PCR to analyze DNA cleavage intermediates in thymocytes from mice with targeted RSS mutations at the endogenous TCRβ locus. We show that DNA cleavage does not occur at individual RSSs but rather must be coordinated between RSS pairs flanking gene segments that ultimately form coding joins. Coordination of the DNA cleavage step occurs over great distances in the chromosome and favors intra- over interchromosomal recombination. Furthermore, through several restrictions imposed on the generation of both nonpaired and paired DNA DSBs, this requirement promotes antigen receptor gene integrity and genomic stability in developing lymphocytes undergoing V(D)J recombination