Human abasic endonuclease action on multilesion abasic clusters: implications for radiation-induced biological damage

Clustered damages—two or more closely opposed abasic sites, oxidized bases or strand breaks—are induced in DNA by ionizing radiation and by some radiomimetic drugs. They are potentially mutagenic or lethal. High complexity, multilesion clusters (three or more lesions) are hypothesized as repair-resistant and responsible for the greater biological damage induced by high linear energy transfer radiation (e.g. charged particles) than by low linear energy transfer X- or γ-rays. We tested this hypothesis by assessing human abasic endonuclease Ape1 activity on two- and multiple-lesion abasic clusters. We constructed cluster-containing oligonucleotides using a central variable cassette with abasic site(s) at specific locations, and 5′ and 3′ terminal segments tagged with visually distinctive fluorophores. The results indicate that in two- or multiple-lesion clusters, the spatial arrangement of uni-sided positive [in which the opposing strand lesion(s) is 3′ to the base opposite the reference lesion)] or negative polarity [opposing strand lesion(s) 5′ to the base opposite the reference lesion] abasic clusters is key in determining Ape1 cleavage efficiency. However, no bipolar clusters (minimally three-lesions) were good Ape1 substrates. The data suggest an underlying molecular mechanism for the higher levels of biological damage associated with agents producing complex clusters: the induction of highly repair-resistant bipolar clusters

Consideration sets, intentions and the inclusion of "Don't know" in a two-stage model for voter choice

We present a statistical model for voter choice that incorporates a consideration set stage and final vote intention stage. The first stageinvolves a multivariate probit model for the vector of probabilities that a candidate or a party gets considered. The second stage of the model is a multinomial probit model for the actual choice. In both stages we use asexplanatory variables data on voter choice at the previous election, as well as socio-demographic respondent characteristics. Importantly, our modelexplicitly accounts for the three types of "missing data" encountered in polling. First, we include a no-vote option in the final vote intention stage. Second, the "do not know" response is assumed to arise from too little difference in the utility between the two most preferred options in the consideration set. Third, the "do not want to say" response is modelled as a missing observation on the most preferred alternative in the consideration set. Thus, we consider the missing data generating mechanism to be non-ignorable and build a model based on utility maximization to describe the voting intentions of these respondents. We illustrate the merits of the model as we have information on a sample of about 5000 individuals from the Netherlands for who we know how they voted last time (if at all), which parties they would consider for the upcoming election,and what their voting intention is. A unique feature of the data set is that information is available on actual individual voting behavior, measured at the day of election. We find that the inclusion of the consideration set stage in the model enables the user to make more precise inferences on the competitive structure in the political domain and to get better out-of-sample forecasts.Bayesian method;Choice model;Election data;Polling;Probit model

Buckling Cascade of Thin Plates: Forms, Constraints and Similarity

We experimentally study compression of thin plates in rectangular boxes with variable height. A cascade of buckling is generated. It gives rise to a self-similar evolution of elastic reaction of plates with box height which surprisingly exhibits repetitive vanishing and negative stiffness. These features are understood from properties of Euler's equation for elastica

Size reduction and polymer encapsulation of carbon black in gas-expanded solvents

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, February 2010.Cataloged from PDF version of thesis.Includes bibliographical references.Ink jet printing is a demanding application that requires carefully formulated inks in order to quickly and reliably produce high-quality printed images. Although ink jet inks are currently produced via an aqueous process, supercritical fluids (SCF) and gas-expanded liquids (GXL) present alternative processing media for particle coating operations that may offer significant benefits with respect to the production of polymer-encapsulated pigment particles for these inks. The main thesis objective is the demonstration and analysis of a particle size reduction and encapsulation process which takes place in CO₂-expanded acetone and produces colloidal carbon black particles. These particles should be uniformly coated with functionalized hydrophobic resins such that they are easily redispersed in water or solvent to form stable nanoparticle dispersions suitable for use in ink jet inks. A prototype size reduction and encapsulation system has been constructed based on a high-pressure stirred reaction vessel designed to operate at pressures up to 200 bar (3000 psi). The prototype vessel has a fluid volume of 1 liter with a multidisc agitator capable of rotating at more than 3400 RPM. Pigment particles are initially milled in a solution of non-aqueous solvent and dissolved dispersing resin. Size reduction is achieved within the apparatus via the grinding action of 1.2 mm spherical ceramic media contacting the micron-size pigment particles. As milling progresses, high-pressure CO₂ is slowly introduced to the vessel; the CO₂ acts as an anti-solvent, lowering polymer solubility and driving adsorption of the dispersing resin onto the pigment particles as new surface area is exposed.(cont.) After encapsulation is complete, the system is flushed with CO₂ and the product particles are retained as a dry powder in a high-pressure filter. The solvent-free particles are then recovered by venting the system to atmospheric pressure, and subsequently re-dispersed in water for analysis in inks. The apparatus under investigation provides a new process approach to particle size reduction and coating that affords greater freedom in ink formulation, while offering a path to improved ink quality and possible cost savings in a highly competitive market. Specifically, the use of CO₂-expanded liquids enables the deposition of hydrophobic polymers on the surface of particles for use in aqueous inks, thus significantly increasing the variety of polymers that are available for use in these systems. A representative model system of carbon black pigment and benzyl methacrylate/methacrylic acid (BzMA/MAA) copolymer dispersing resins of varying monomer compositions (BzMA/MAA mass ratio = 85/15, 80/20, and 75/25) has been studied in order to assess the feasibility of the high-pressure milling and encapsulation process for ink jet applications. These components have been successfully employed in high-pressure coating operations to produce encapsulated carbon black particles which were recovered as a dry, flowable powder. Dry product particles were redispersed in water to obtain stable aqueous dispersions with a number average particle size of 135-190 nm.(cont.) In order to guide the selection of appropriate process conditions for the encapsulation system, the high-pressure solid-liquid-vapor phase equilibrium of ternary CO₂-solvent-polymer systems has been probed experimentally and modeled with the PC-SAFT equation of state. Precipitation of BzMA/MAA copolymers generally required a larger overall CO 2 mole fraction - and thus a higher system pressure - for more dilute polymer solutions; however, a minimum in the precipitation pressure was observed for all polymer compositions and temperatures near a CO₂-free polymer mass fraction of 0.03. The ternary systems were characterized by a rapid reduction in polymer solubility over a relatively narrow range of pressure (between 200 psig and 400 psig, depending on the polymer and system temperature); the precipitation pressure increased with increasing temperature and BzMA mass fraction (per polymer mass unit). The PC-SAFT EOS was successfully employed to correlate the phase behavior data by adjusting only two binary interaction parameters; the average relative error associated with the predictions of precipitation pressure for each polymer was 3.7%. Characterization of the encapsulation process also requires knowledge of the thermodynamics and kinetics of polymer adsorption onto particle surfaces from CO₂- expanded solvents. To this end, interactions with the particle surface have been investigated through the collection and correlation of experimental adsorption isotherm data.(cont.) Adsorption of 85/15 and 75/25 BzMA/MAA polymers onto carbon black from CO₂-expanded acetone was measured at 35°C and pressures between 0 psig and 300 psig over a range of mixture compositions relevant to particle coating operations. Pressurization with CO₂ to pressures up to 200 psig caused a decrease in the amount of polymer adsorbed on particle surfaces, but further increases in pressure resulted in higher polymer loadings. In the case of 75/25 BzMA/MAA polymer, the polymer loading increased significantly between 200 psig and 300 psig as the solubility limit was approached or exceeded. Our results are valuable not only in providing quantitative data to facilitate process optimization, but also in offering a more fundamental understanding of interactions among the pigment particles, the dispersant resin, and the gas-expanded liquid media. Such information is important to both process and product design.by Scott M. Paap.Ph.D

Modeling Unobserved Consideration Sets for Household Panel Data

We propose a new method to model consumers' consideration and choice processes. We develop a parsimonious probit type model for consideration and a multinomial probit model for choice, given consideration. Unlike earlier models of consideration ours is not prone to the curse of dimensionality, while we allow for very general structures of unobserved dependence in consideration among brands. In addition, our model allows for state dependence and marketing mix effects on consideration. Unique to this study is that we attempt to establish the validity of existing practice to infer consideration sets from observed choices in panel data. To this end, we use data collected in an on-line choice experiment involving interactive supermarket shelves and post-choice questionnaires to measure the choice protocol and stated consideration levels. We show with these experimental data that underlying consideration sets can be successfully retrieved from choice data alone and that there is substantial convergent validity of the stated and inferred consideration sets. We further find that consideration is a function of point-of-purchase marketing actions such as display and shelf space, and of consumer memory for recent choices. Next, we estimate the model on IRI panel data. We have three main results. First, compared with the single-stage probit model, promotion effects are larger and are inferred with smaller variances when they are included in the consideration stage of the two-stage model. Promotion effects are significant only in the two-stage model that includes consideration, whereas they are not in a single-stage choice model. Second, the price response curves of

Boundary Limitation of Wavenumbers in Taylor-Vortex Flow

We report experimental results for a boundary-mediated wavenumber-adjustment mechanism and for a boundary-limited wavenumber-band of Taylor-vortex flow (TVF). The system consists of fluid contained between two concentric cylinders with the inner one rotating at an angular frequency $\Omega$. As observed previously, the Eckhaus instability (a bulk instability) is observed and limits the stable wavenumber band when the system is terminated axially by two rigid, non-rotating plates. The band width is then of order $\epsilon^{1/2}$ at small $\epsilon$ ($\epsilon \equiv \Omega/\Omega_c - 1$) and agrees well with calculations based on the equations of motion over a wide $\epsilon$-range. When the cylinder axis is vertical and the upper liquid surface is free (i.e. an air-liquid interface), vortices can be generated or expelled at the free surface because there the phase of the structure is only weakly pinned. The band of wavenumbers over which Taylor-vortex flow exists is then more narrow than the stable band limited by the Eckhaus instability. At small $\epsilon$ the boundary-mediated band-width is linear in $\epsilon$. These results are qualitatively consistent with theoretical predictions, but to our knowledge a quantitative calculation for TVF with a free surface does not exist.Comment: 8 pages incl. 9 eps figures bitmap version of Fig

Botanical gardens as key resources and hazards for biosecurity

Biodiversity and economic losses resulting from invasive plant pests and pathogens are increasing globally. For these impacts and threats to be managed effectively, appropriate methods of surveillance, detection and identification are required. Botanical gardens provide a unique opportunity for biosecurity as they accommodate diverse collections of exotic and native plant species. These gardens are also often located close to high-risk sites of accidental invasions such as ports and urban areas. This, coupled with routine activities such as the movement of plants and plant material, and visits by millions of people each year, place botanical gardens at risk to the arrival and establishment of pests and pathogens. Consequently, botanical gardens can pose substantial biosecurity risks to the environment, by acting as bridgeheads for pest and pathogen invasions. Here we review the role of botanical gardens in biosecurity on a global scale. The role of botanical gardens has changed over time. Initially, they were established as physic gardens (gardens with medicinal plants), and their links with academic institutions led to their crucial role in the accumulation and dissemination of botanical knowledge. During the second half of the 20th century, botanical gardens developed a strong focus on plant conservation, and in recent years there has been a growing acknowledgement of their value in biosecurity research as sentinel sites to identify pest and pathogen risks (novel pest-host associations); for early detection and eradication of pests and pathogens; and for host range studies. We identify eight specific biosecurity hazards associated with botanical gardens and note potential management interventions and the opportunities these provide for improving biosecurity. We highlight the value of botanical gardens for biosecurity and plant health research in general, and the need for strategic thinking, resources, and capacity development to make them models for best practices in plant health

The importance of harmonising diagnostic criteria sets for pathological grief

Five diagnostic criteria sets for pathological grief are currently used in research. Studies evaluating their performance indicate that it is not justified to generalise findings regarding prevalence rates and predictive validity across studies using different diagnostic criteria of pathological grief. We provide recommendations to move the bereavement field forward

Retrieving unobserved consideration sets from household panel data

We propose a new model to describe consideration, consisting of a multivariate probit model component for consideration and a multinomial probit model component for choice, given consideration. The approach allows one to analyze stated consideration set data, revealed consideration set (choice) data or both, while at the same time it allows for unobserved dependence in consideration among brands. In addition, the model accommodates different effects of the marketing mix on consideration and choice, an error process that is correlated over time, and unobserved consumer heterogeneity in both processes. We attempt to establish the validity of existing practice to infer consideration sets from observed choices in panel data. To this end, we collect data in an on-line choice experiment involving interactive supermarket shelves and post-choice questionnaires to measure the choice protocol and stated consideration levels. We show with these experimental data that underlying consideration sets can be reliably retrieved from choice data alone. Next, we estimate the model on IRI panel data. We have two main results. First, compared with the single-stage multinomial probit model, promotion effects are larger when they are included in the consideration stage of the two-stage model. Second, we find that consideration of brands does not covary greatly across brands once we account for observed effects