Charge Transfer-oxy Radical Mechanism for Anti-cancer Agents

The proposal is advanced that anti-cancer drugs generally function by charge transfer resulting in formation of toxic oxy radicals which destroy the neoplasm. Electrochemical studies were performed with some of the main types of agents: iminium ions (adenine iminium from alkylating species, iminium metabolite of 6-mercaptopurine, nitidine, other polynuclear iminiums) and metal complexes (Pt(II)diaquodiammine-guanosine, copper salicylaldoximes). Reduction potentials ranged from -0.4 to -1.2 V. Literature data for quinones are presented and radiation is discussed. Based on the theoretical framework, a rationale is offered for the carcinogen-anti-cancer paradox and the role of antioxidants

DNA-Protein Binding Rates: Bending Fluctuation and Hydrodynamic Coupling Effects

We investigate diffusion-limited reactions between a diffusing particle and a target site on a semiflexible polymer, a key factor determining the kinetics of DNA-protein binding and polymerization of cytoskeletal filaments. Our theory focuses on two competing effects: polymer shape fluctuations, which speed up association, and the hydrodynamic coupling between the diffusing particle and the chain, which slows down association. Polymer bending fluctuations are described using a mean field dynamical theory, while the hydrodynamic coupling between polymer and particle is incorporated through a simple heuristic approximation. Both of these we validate through comparison with Brownian dynamics simulations. Neither of the effects has been fully considered before in the biophysical context, and we show they are necessary to form accurate estimates of reaction processes. The association rate depends on the stiffness of the polymer and the particle size, exhibiting a maximum for intermediate persistence length and a minimum for intermediate particle radius. In the parameter range relevant to DNA-protein binding, the rate increase is up to 100% compared to the Smoluchowski result for simple center-of-mass motion. The quantitative predictions made by the theory can be tested experimentally.Comment: 21 pages, 11 figures, 1 tabl

Meat Consumption and Risk of Developing Esophageal Cancer: A Meta-analysis

Background: Meat has been linked as a risk factor for several cancers. Red meat and processed meat specifically have been suggested as risk factors for esophageal cancer, but this has not been established. We performed a meta-analysis to summarize available evidence from case-control and cohort studies on this topic.Methods: A systematic search of MEDLINE, PubMed, EMBASE was completed up until November, 2013. Studies were included that reported confirmed histological diagnosis of cancer, odds ratios (OR) or relative risks (RR) and confidence intervals (CI). Pooled ORs and 95% CIs were calculated for the effect of different meats on the development of esophageal cancer using a random effects model. Studies were assessed for heterogeneity and publication bias.Results: 29 studies were included in this analysis, involving 1,208,768 individuals with a total of 8,620 cases and 44,574 controls. High consumption rates were associated with development of cancer for red meat (OR 1.59; 95% CI 1.31-1.93), processed meat (OR 1.75; 95% CI 1.28-2.38), barbecued meat (OR 1.54; 95% CI 1.25–1.91) and overall (OR 1.26; 95% CI 1.11-1.43). Low and medium consumption rates were also significant for red and barbecued meat. High and medium consumption of white meat was significantly protective. High consumption of fish was also found to be protective (OR 0.73; 95% CI 0.55-0.95).Conclusions: Findings of this meta-analysis demonstrated red meat, processed meat and barbecued meat are likely to increase the risk of esophageal cancer in a dose dependent relationship. Fish and white meat were shown to have a protective effect

Hawkes process as a model of social interactions: a view on video dynamics

We study by computer simulation the "Hawkes process" that was proposed in a recent paper by Crane and Sornette (Proc. Nat. Acad. Sci. USA 105, 15649 (2008)) as a plausible model for the dynamics of YouTube video viewing numbers. We test the claims made there that robust identification is possible for classes of dynamic response following activity bursts. Our simulated timeseries for the Hawkes process indeed fall into the different categories predicted by Crane and Sornette. However the Hawkes process gives a much narrower spread of decay exponents than the YouTube data, suggesting limits to the universality of the Hawkes-based analysis.Comment: Added errors to parameter estimates and further description. IOP style, 13 pages, 5 figure

Gaps between Jets in the High Energy Limit

We use perturbative QCD to calculate the parton level cross section for the production of two jets that are far apart in rapidity, subject to a limitation on the total transverse momentum Q0 in the interjet region. We specifically address the question of how to combine the approach which sums all leading logarithms in Q/Q0 (where Q is the jet transverse momentum) with the BFKL approach, in which leading logarithms of the scattering energy are summed. This paper constitutes progress towards the simultaneous summation of all important logarithms. Using an "all orders" matching, we are able to obtain results for the cross section which correctly reproduce the two approaches in the appropriate limits.Comment: 29 pages, 9 figures, minor corrections to text and improved figure

The Impact of Perspective in Identifying and Responding to Potential Sexual Misconduct: A Study of University Students

Recent events have demonstrated a divergent understanding of sexual harassment and other forms of sexual misconduct. Although sociocultural standards regarding sexual misconduct have changed over time, including improved social and workplace standards and protections, it is clear that not everyone views these events through the same lens. The lens is even less clear when potential misconduct is viewed from the distinct perspectives of a “victim” and a “perpetrator.” We surveyed 424 undergraduate and graduate students at Indiana University Kokomo to identify the impact of perspective and various sociodemographic characteristics that may influence perceptions of what is, and is not, sexual misconduct. In addition, we examined if these factors also influence opinions on the severity of response toward this misconduct. Students completed a gender-neutral survey that presented eight potential sexualmisconduct scenarios in a first-person narrative. In each scenario, the fact pattern was identical, but some surveys were in the perspective of the “victim” and some were in the perspective of the “perpetrator.” We find that perspective matters, as do reported preconceived attitudes toward sexual misconduct. We also find preliminary evidence that the impact of perspective and the severity of the response may depend on whether the misconduct occurs in an organizational setting, in a date setting, or without a distinct victim

Project Zeus: Design of a Broadband Network and its Application on a University Campus

This is a report of the results of the initial step in a plan for the design, deployment and operation of a high speed campus network at Washington University. The network is based on ATM switching technology that has been developed here during the last several years. This network will support ubiquitous multimedia workstations with high-resolution graphics and video capabilities, open up a wide range of new applications in research and education. It will support aggregate throughputs of hundreds of gigabits per second and will be designed to support port of 100 MB/s is now in operation. The next phase of network implementation will operate at 155 Mb/s port rates, with higher rates introduced as the demand arises and as economics permits. We propose to move this technology quickly into a production setting where the objectives of network use and network research can be pursued concurrently

A diagnostic procedure for applying the social-ecological systems framework in diverse cases

The framework for analyzing sustainability of social-ecological systems (SES) framework of Elinor Ostrom is a multitier collection of concepts and variables that have proven to be relevant for understanding outcomes in diverse SES. The first tier of this framework includes the concepts resource system (RS) and resource units (RU), which are then further characterized through lower tier variables such as clarity of system boundaries and mobility. The long-term goal of framework development is to derive conclusions about which combinations of variables explain outcomes across diverse types of SES. This will only be possible if the concepts and variables of the framework can be made operational unambiguously for the different types of SES, which, however, remains a challenge. Reasons for this are that case studies examine other types of RS than those for which the framework has been developed or consider RS for which different actors obtain different kinds of RU. We explore these difficulties and relate them to antecedent work on common-pool resources and public goods. We propose a diagnostic procedure which resolves some of these difficulties by establishing a sequence of questions that facilitate the step-wise and unambiguous application of the SES framework to a given case. The questions relate to the actors benefiting from the SES, the collective goods involved in the generation of those benefits, and the action situations in which the collective goods are provided and appropriated. We illustrate the diagnostic procedure for four case studies in the context of irrigated agriculture in New Mexico, common property meadows in the Swiss Alps, recreational fishery in Germany, and energy regions in Austria. We conclude that the current SES framework has limitations when applied to complex, multiuse SES, because it does not sufficiently capture the actor interdependencies introduced through RS and RU characteristics and dynamics

Detection of 1.6 × 10^(10) M_⊙ of Molecular Gas in the Host Galaxy of the z = 5.77 SDSS Quasar J0927+2001

We have detected emission by the CO(5-4) and (6-5) rotational transitions at z = 5.7722 ± 0.0006 from the host galaxy of the SDSS quasar J0927+2001 using the Plateau de Bure Interferometer. The peak line flux density for the CO(5-4) line is 0.72 ± 0.09 mJy, with a line FWHM = 610 ± 110 km s^(-1). The implied molecular gas mass is (1.6 ± 0.3) × 10^(10) M_⊙. We also detect the 90 GHz continuum at 0.12 ± 0.03 mJy, consistent with a 47 K dust spectrum extrapolated from higher frequencies. J0927+2001 is the second example of a huge molecular gas reservoir within the host galaxy of a quasar within 1 Gyr of the big bang. Observations of J0927+2001 are consistent with a massive starburst coeval with a bright quasar phase in the galaxy, suggesting the rapid formation of both a supermassive black hole through accretion, and the stellar host spheroid, at a time close to the end of cosmic reionization

Effector memory differentiation increases detection of replication-competent HIV-l in resting CD4+ T cells from virally suppressed individuals.

Studies have demonstrated that intensive ART alone is not capable of eradicating HIV-1, as the virus rebounds within a few weeks upon treatment interruption. Viral rebound may be induced from several cellular subsets; however, the majority of proviral DNA has been found in antigen experienced resting CD4+ T cells. To achieve a cure for HIV-1, eradication strategies depend upon both understanding mechanisms that drive HIV-1 persistence as well as sensitive assays to measure the frequency of infected cells after therapeutic interventions. Assays such as the quantitative viral outgrowth assay (QVOA) measure HIV-1 persistence during ART by ex vivo activation of resting CD4+ T cells to induce latency reversal; however, recent studies have shown that only a fraction of replication-competent viruses are inducible by primary mitogen stimulation. Previous studies have shown a correlation between the acquisition of effector memory phenotype and HIV-1 latency reversal in quiescent CD4+ T cell subsets that harbor the reservoir. Here, we apply our mechanistic understanding that differentiation into effector memory CD4+ T cells more effectively promotes HIV-1 latency reversal to significantly improve proviral measurements in the QVOA, termed differentiation QVOA (dQVOA), which reveals a significantly higher frequency of the inducible HIV-1 replication-competent reservoir in resting CD4+ T cells