Singular Short Range Potentials in the J-Matrix Approach

We use the tools of the J-matrix method to evaluate the S-matrix and then deduce the bound and resonance states energies for singular screened Coulomb potentials, both analytic and piecewise differentiable. The J-matrix approach allows us to absorb the 1/r singularity of the potential in the reference Hamiltonian, which is then handled analytically. The calculation is performed using an infinite square integrable basis that supports a tridiagonal matrix representation for the reference Hamiltonian. The remaining part of the potential, which is bound and regular everywhere, is treated by an efficient numerical scheme in a suitable basis using Gauss quadrature approximation. To exhibit the power of our approach we have considered the most delicate region close to the bound-unbound transition and compared our results favorably with available numerical data.Comment: 14 pages, 5 tables, 2 figure

Correlating preclinical animal studies and human clinical trials of a multifunctional, polymeric nanoparticle

Nanoparticles are currently being investigated in a number of human clinical trials. As information on how nanoparticles function in humans is difficult to obtain, animal studies that can be correlative to human behavior are needed to provide guidance for human clinical trials. Here, we report correlative studies on animals and humans for CRLX101, a 20- to 30-nm-diameter, multifunctional, polymeric nanoparticle containing camptothecin (CPT). CRLX101 is currently in phase 2 clinical trials, and human data from several of the clinical investigations are compared with results from multispecies animal studies. The pharmacokinetics of polymer-conjugated CPT (indicative of the CRLX101 nanoparticles) in mice, rats, dogs, and humans reveal that the area under the curve scales linearly with milligrams of CPT per square meter for all species. Plasma concentrations of unconjugated CPT released from CRLX101 in animals and humans are consistent with each other after accounting for differences in serum albumin binding of CPT. Urinary excretion of polymer-conjugated CPT occurs primarily within the initial 24 h after dosing in animals and humans. The urinary excretion dynamics of polymer-conjugated and unconjugated CPT appear similar between animals and humans. CRLX101 accumulates into solid tumors and releases CPT over a period of several days to give inhibition of its target in animal xenograft models of cancer and in the tumors of humans. Taken in total, the evidence provided from animal models on the CRLX101 mechanism of action suggests that the behavior of CRLX101 in animals is translatable to humans

Radio emission from Supernova Remnants

The explosion of a supernova releases almost instantaneously about 10^51 ergs of mechanic energy, changing irreversibly the physical and chemical properties of large regions in the galaxies. The stellar ejecta, the nebula resulting from the powerful shock waves, and sometimes a compact stellar remnant, constitute a supernova remnant (SNR). They can radiate their energy across the whole electromagnetic spectrum, but the great majority are radio sources. Almost 70 years after the first detection of radio emission coming from a SNR, great progress has been achieved in the comprehension of their physical characteristics and evolution. We review the present knowledge of different aspects of radio remnants, focusing on sources of the Milky Way and the Magellanic Clouds, where the SNRs can be spatially resolved. We present a brief overview of theoretical background, analyze morphology and polarization properties, and review and critical discuss different methods applied to determine the radio spectrum and distances. The consequences of the interaction between the SNR shocks and the surrounding medium are examined, including the question of whether SNRs can trigger the formation of new stars. Cases of multispectral comparison are presented. A section is devoted to reviewing recent results of radio SNRs in the Magellanic Clouds, with particular emphasis on the radio properties of SN 1987A, an ideal laboratory to investigate dynamical evolution of an SNR in near real time. The review concludes with a summary of issues on radio SNRs that deserve further study, and analyzing the prospects for future research with the latest generation radio telescopes.Comment: Revised version. 48 pages, 15 figure

Drug Discovery Using Chemical Systems Biology: Weak Inhibition of Multiple Kinases May Contribute to the Anti-Cancer Effect of Nelfinavir

Nelfinavir is a potent HIV-protease inhibitor with pleiotropic effects in cancer cells. Experimental studies connect its anti-cancer effects to the suppression of the Akt signaling pathway, but the actual molecular targets remain unknown. Using a structural proteome-wide off-target pipeline, which integrates molecular dynamics simulation and MM/GBSA free energy calculations with ligand binding site comparison and biological network analysis, we identified putative human off-targets of Nelfinavir and analyzed the impact on the associated biological processes. Our results suggest that Nelfinavir is able to inhibit multiple members of the protein kinase-like superfamily, which are involved in the regulation of cellular processes vital for carcinogenesis and metastasis. The computational predictions are supported by kinase activity assays and are consistent with existing experimental and clinical evidence. This finding provides a molecular basis to explain the broad-spectrum anti-cancer effect of Nelfinavir and presents opportunities to optimize the drug as a targeted polypharmacology agent

Revisiting the mechanism of coagulation factor XIII activation and regulation from a structure/functional perspective

The activation and regulation of coagulation Factor XIII (FXIII) protein has been the subject of active research for the past three decades. Although discrete evidence exists on various aspects of FXIII activation and regulation a combinatorial structure/functional view in this regard is lacking. In this study, we present results of a structure/function study of the functional chain of events for FXIII. Our study shows how subtle chronological submolecular changes within calcium binding sites can bring about the detailed transformation of the zymogenic FXIII to its activated form especially in the context of FXIIIA and FXIIIB subunit interactions. We demonstrate what aspects of FXIII are important for the stabilization (first calcium binding site) of its zymogenic form and the possible modes of deactivation (thrombin mediated secondary cleavage) of the activated form. Our study for the first time provides a structural outlook of the FXIIIA 2 B 2 heterotetramer assembly, its association and dissociation. The FXIIIB subunits regulatory role in the overall process has also been elaborated upon. In summary, this study provides detailed structural insight into the mechanisms of FXIII activation and regulation that can be used as a template for the development of future highly specific therapeutic inhibitors targeting FXIII in pathological conditions like thrombosis

A grid of chemical evolution models as a tool to interpret spiral and irregular galaxies data

We present a generalization of the multiphase chemical evolution model applied to a wide set of theoretical galaxies with different masses and evolutionary rates. This generalized set of models has been computed using the so-called Universal Rotation Curve from Persic et al (1996) to calculate the radial mass distribution of 44 theoretical protogalaxies. This distribution is a fundamental input which, besides its own effect on the galaxy evolution, defines the characteristic collapse time-scale or gas infall rate onto the disc.We have adopted 10 sets of values, between 0 and 1, for the molecular cloud and star formation efficiencies, as corresponding to their probability nature, for each one of the radial distributions of total mass. Thus, we have constructed a bi-parametric grid of models, depending on those efficiency sets and on the rotation velocity, whose results are valid in principle for any spiral or irregular galaxy. The model results provide the time evolution of different regions of the disc and the halo along galactocentric distance, measured by the gas (atomic and molecular) and stellar masses, the star formation rate and chemical abundances of 14 elements, for a total of 440 models. This grid may be used to estimate the evolution of a given galaxy for which only present time information -- such as radial distributions of elemental abundances, gas densities and/or star formation, which are the usual observational constraints of chemical evolution models -- is available.Comment: 27 pag., 20 fig, to be published in MNRA

Critical literacy as a pedagogical goal in English language teaching

In this chapter, the authors provide an overview of the area of critical literacy as it pertains to second language pedagogy (curriculum and instruction). After considering the historical origins of critical literacy (from antiquity, and including in first language education), they consider how it began to penetrate the field of applied linguistics. They note the geographical and institutional spread of critical literacy practice as documented by published accounts. They then sketch the main features of L2 critical literacy practice. To do this, they acknowledge how practitioners have reported on their practices regarding classroom content and process. The authors also draw attention to the outcomes of these practices as well as challenges that practitioners have encountered in incorporating critical literacy into their second language classrooms

The Indian cobra reference genome and transcriptome enables comprehensive identification of venom toxins

Snakebite envenoming is a serious and neglected tropical disease that kills ~100,000 people annually. High-quality, genome-enabled comprehensive characterization of toxin genes will facilitate development of effective humanized recombinant antivenom. We report a de novo near-chromosomal genome assembly of Naja naja, the Indian cobra, a highly venomous, medically important snake. Our assembly has a scaffold N50 of 223.35 Mb, with 19 scaffolds containing 95% of the genome. Of the 23,248 predicted protein-coding genes, 12,346 venom-gland-expressed genes constitute the \u27venom-ome\u27 and this included 139 genes from 33 toxin families. Among the 139 toxin genes were 19 \u27venom-ome-specific toxins\u27 (VSTs) that showed venom-gland-specific expression, and these probably encode the minimal core venom effector proteins. Synthetic venom reconstituted through recombinant VST expression will aid in the rapid development of safe and effective synthetic antivenom. Additionally, our genome could serve as a reference for snake genomes, support evolutionary studies and enable venom-driven drug discovery

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Social Relationships and Mortality Risk: A Meta-analytic Review

In a meta-analysis, Julianne Holt-Lunstad and colleagues find that individuals' social relationships have as much influence on mortality risk as other well-established risk factors for mortality, such as smoking