Analysis of Oxidized DNA Fragments by Gel Electrophoresis

Polyacrylamide gel electrophoresis is used to define and quantify products of deoxyribose oxidation in DNA, based on the unique electrophoretic mobility of DNA fragments possessing deoxyribose oxidation products on their termini. This approach allows initial estimation of the chemistry. Once the chemical identity of damage products has been confirmed, this technique allows sensitive quantitation of the various damage products.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143665/1/cpnc1008.pd

Cytotoxic chemotherapy: Still the mainstay of clinical practice for all subtypes metastatic breast cancer

Cytotoxic chemotherapy remains central to the treatment of all subtypes of metastatic breast cancer (MBC). We review evidence-based chemotherapy options for women with MBC after an anthracycline and a taxane including re-challenge with anthracycline or taxane, capecitabine, eribulin and ixabepilone as a single agent or combination with capecitabine (not approved in the EU); and the vinca alkaloid vinflunine as single agent or combined with either capecitabine/gemcitabine (also not approved EU or USA). Etirinotecan pegol, comprising irinotecan bound to polyethylene glycol by a biodegradable linker, is a new cytotoxic agent for patients with MBC that has achieved encouraging response rates in phase II studies; it has been further evaluated in the phase III BEACON trial. New cytotoxics should address novel targets or modes of delivery, achieve meaningful improvements in outcomes and seek to identify predictive biomarker(s)

High Spin Gauge Fields and Two-Time Physics

All possible interactions of a point particle with background electromagnetic, gravitational and higher-spin fields is considered in the two-time physics worldline formalism in (d,2) dimensions. This system has a counterpart in a recent formulation of two-time physics in non-commutative field theory with local Sp(2) symmetry. In either the worldline or field theory formulation, a general Sp(2) algebraic constraint governs the interactions, and determines equations that the background fields of any spin must obey. The constraints are solved in the classical worldline formalism (h-bar=0 limit) as well as in the field theory formalism (all powers of h-bar). The solution in both cases coincide for a certain 2T to 1T holographic image which describes a relativistic particle interacting with background fields of any spin in (d-1,1) dimensions. Two disconnected branches of solutions exist, which seem to have a correspondence as massless states in string theory, one containing low spins in the zero Regge slope limit, and the other containing high spins in the infinite Regge slope limit.Comment: LaTeX 22 pages. Typos corrected in version

A remote sensing and modeling integrated approach for constructing continuous time series of daily actual evapotranspiration

Satellite remote sensing-based surface energy balance (SEB) techniques have emerged as useful tools for quantifying spatialized actual evapotranspiration at various temporal and spatial scales. However, discontinuous data acquisitions and/or gaps in image acquisition due to cloud cover can limit the applicability of satellite remote sensing (RS) in agriculture water management where continuous time series of daily crop actual evapotranspiration (ETc act) are more valued. The aim of the research is to construct continuous time series of daily ETc act starting from temporal estimates of actual evapotranspiration obtained by SEB modelling (ETa eb) on Landsat-TM images. SEBAL model was integrated with the FAO 56 evaporation model, RS-retrieved vegetative biomass dynamics (by NDVI) and on-field measurements of soil moisture and potential evapotranspiration. The procedure was validated by an eddy covariance tower on a vineyard with partial soil coverage in the south of Sardinia Island, Italy. The integrated modeling approach showed a good reproduction of the time series dynamics of observed ETc act (R2 =0.71, MAE=0.54 mm d-1, RMSE=0.73 mm d-1). A daily and a cumulative monthly temporal analysis showed the importance of integrating parameters that capture changes in the soil-plant-atmosphere (SPA) continuum between Landsat acquisitions. The comparison with daily ETc act obtained by the referenced ET fraction (ETrF) method that considers only weather variability (by ETo) confirmed the lead of the proposed procedure in the spring/early summer periods when vegetation biomass changes and soil water evaporation have a significant weight in the ET process. The applied modelling approach was also robust in constructing the missing ETc act data under scenarios of limited cloud-free Landsat acquisitions. The presented integrated approach has a great potential for the near real time monitoring and scheduling of irrigation practices. Further testing of this approach with diverse dataset and the integration with the soil water modeling is to be analyzed in future work

Subgroup analyses from a phase 3, open-label, randomized study of eribulin mesylate versus capecitabine in pretreated patients with advanced or metastatic breast cancer

Purpose and methods: Our secondary analyses compared survival with eribulin versus capecitabine in various patient subgroups from a phase 3, open-label, randomized study. Eligible women aged ≥18 years with advanced/metastatic breast cancer and ≤3 prior chemotherapies (≤2 for advanced/metastatic disease), including an anthracycline and taxane, were randomized 1:1 to intravenous eribulin mesylate 1.4 mg/m² on days 1 and 8 or twice-daily oral capecitabine 1250 mg/m² on days 1–14 (21-day cycles). Results: In the intent-to-treat population (eribulin 554 and capecitabine 548), overall survival appeared longer with eribulin than capecitabine in various subgroups, including patients with human epidermal growth factor receptor 2-negative (15.9 versus 13.5 months, respectively), estrogen receptor-negative (14.4 versus 10.5 months, respectively), and triple-negative (14.4 versus 9.4 months, respectively) disease. Progression-free survival was similar between the treatment arms. Conclusions: Patients with advanced/metastatic breast cancer and human epidermal growth factor receptor 2-, estrogen receptor-, or triple-negative disease may gain particular benefit from eribulin as first-, second-, and third-line chemotherapies

Phase III Open-Label Randomized Study of Eribulin Mesylate Versus Capecitabine in Patients With Locally Advanced or Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane

Purpose: This phase III randomized trial (ClinicalTrials.gov identifier: NCT00337103) compared eribulin with capecitabine in patients with locally advanced or metastatic breast cancer (MBC). Patients and Methods: Women with MBC who had received prior anthracycline- and taxane-based therapy were randomly assigned to receive eribulin or capecitabine as their first-, second-, or third-line chemotherapy for advanced/metastatic disease. Stratification factors were human epidermal growth factor receptor-2 (HER2) status and geographic region. Coprimary end points were overall survival (OS) and progression-free survival (PFS). Results: Median OS times for eribulin (n = 554) and capecitabine (n = 548) were 15.9 and 14.5 months, respectively (hazard ratio [HR], 0.88; 95% CI, 0.77 to 1.00; P = .056). Median PFS times for eribulin and capecitabine were 4.1 and 4.2 months, respectively (HR, 1.08; 95% CI, 0.93 to 1.25; P = .30). Objective response rates were 11.0% for eribulin and 11.5% for capecitabine. Global health status and overall quality-of-life scores over time were similar in the treatment arms. Both treatments had manageable safety profiles consistent with their known adverse effects; most adverse events were grade 1 or 2. Conclusion: In this phase III study, eribulin was not shown to be superior to capecitabine with regard to OS or PFS

Assessing Responses of \u3ci\u3eBetula papyrifera\u3c/i\u3e to Climate Variability in a Remnant Population along the Niobrara River Valley in Nebraska U.S. through Dendroecological and Remote Sensing Techniques

Remnant populations of Betula papyrifera have persisted in the Great Plains after the Wisconsin Glaciation along the Niobrara River Valley, Nebraska. Population health has declined in recent years, and has been hypothesized to be due to climate change. We used dendrochronological techniques to assess the response of B. papyrifera to microclimate (1950-2014), and satellite imagery [Landsat 5 TM (1985-2011) and MODIS (2000-2014)] derived NDVI as a proxy for population health. Growing-season streamflow and precipitation were positively correlated with raw and standardized tree-ring widths and basal area increment increase. Increasing winter and spring temperatures were unfavorable for tree growth while increasing summer temperatures were favorable in the absence of drought. The strongest predictor for standardized tree-rings was the Palmer Drought Severity Index, suggesting that B. papyrifera is highly responsive to a combination of temperature and water availability. The NDVI from vegetation community was positively correlated with standardized tree-ring growth, indicating the potential of these techniques to be used as a proxy for ex-situ monitoring of B. papyrifera. These results aid in forecasting the dynamics of the species in the face of climate variability and change in both remnant populations and across its current distribution in northern latitudes of North America

M-Theory on (K3 X S^1)/Z_2

We analyze $M$-theory compactified on $(K3\times S^1)/Z_2$ where the $Z_2$ changes the sign of the three form gauge field, acts on $S^1$ as a parity transformation and on K3 as an involution with eight fixed points preserving SU(2) holonomy. At a generic point in the moduli space the resulting theory has as its low energy limit N=1 supergravity theory in six dimensions with eight vector, nine tensor and twenty hypermultiplets. The gauge symmetry can be enhanced (e.g. to $E_8$) at special points in the moduli space. At other special points in the moduli space tensionless strings appear in the theory.Comment: LaTeX file, 11 page