Dynamics of Co-translational Membrane Protein Integration and Translocation via the Sec Translocon

An important aspect of cellular function is the correct targeting and delivery of newly synthesized proteins. Central to this task is the machinery of the Sec translocon, a transmembrane channel that is involved in both the translocation of nascent proteins across cell membranes and the integration of proteins into the membrane. Considerable experimental and computational effort has focused on the Sec translocon and its role in nascent protein biosynthesis, including the correct folding and expression of integral membrane proteins. However, the use of molecular simulation methods to explore Sec-facilitated protein biosynthesis is hindered by the large system sizes and long (i.e., minute) timescales involved. In this work, we describe the development and application of a coarse-grained simulation approach that addresses these challenges and allows for direct comparison with both in vivo and in vitro experiments. The method reproduces a wide range of experimental observations, providing new insights into the underlying molecular mechanisms, predictions for new experiments, and a strategy for the rational enhancement of membrane protein expression levels

Roe v. Wade and American Fertility

We consider the effect of abortion legalization on births in the United States. A simple theoretical model demonstrates that the impact of abortion legalization on the birth rate is ambiguous, because both pregnancy and abortion decisions could be affected. We use variation in the timing of legalization across states in the early 1970's to estimate the effect of abortion on birth rates. Our findings indicate that states legalizing abortion experienced a 5% decline in births relative to other states. The decline among teens, women over 35, and nonwhite women was even greater: 13%, 8%, and 12% respectively. Out-of-wedlock births declined by twice as much as births in wedlock. If legalization in some states affected birth rates in neighboring states (through travel to obtain an abortion), comparing births between states will underestimate the actual reduction. Using more distant comparison states increases the estimated impact of abortion legalization on birth rates to about 8%. Applying this estimate to the current level of births, a complete recriminalization of abortion would result in 320,000 additional births per year.

Algorithms for Reconstructing DDoS Attack Graphs using Probabilistic Packet Marking

DoS and DDoS attacks are widely used and pose a constant threat. Here we explore Probability Packet Marking (PPM), one of the important methods for reconstructing the attack-graph and detect the attackers. We present two algorithms. Differently from others, their stopping time is not fixed a priori. It rather depends on the actual distance of the attacker from the victim. Our first algorithm returns the graph at the earliest feasible time, and turns out to guarantee high success probability. The second algorithm enables attaining any predetermined success probability at the expense of a longer runtime. We study the performance of the two algorithms theoretically, and compare them to other algorithms by simulation. Finally, we consider the order in which the marks corresponding to the various edges of the attack graph are obtained by the victim. We show that, although edges closer to the victim tend to be discovered earlier in the process than farther edges, the differences are much smaller than previously thought.Comment: 30 pages, 4 figures, 4 table

Dislocation Emission around Nanoindentations on a (001) fcc Metal Surface Studied by STM and Atomistic Simulations

We present a combined study by Scanning Tunneling Microscopy and atomistic simulations of the emission of dissociated dislocation loops by nanoindentation on a (001) fcc surface. The latter consist of two stacking-fault ribbons bounded by Shockley partials and a stair-rod dislocation. These dissociated loops, which intersect the surface, are shown to originate from loops of interstitial character emitted along the directions and are usually located at hundreds of angstroms away from the indentation point. Simulations reproduce the nucleation and glide of these dislocation loops.Comment: 10 pages, 4 figure

Roe v. Wade and American Fertility

We consider the effect of abortion legalization on births in the United States. A simple theoretical model demonstrates that the impact of abortion legalization on the birth rate is ambiguous, because both pregnancy and abortion decisions could be affected. We use variation in the timing of legalization across states in the early 1970\u27s to estimate the effect of abortion on birth rates. Our findings indicate that states legalizing abortion experienced a 5% decline in births relative to other states. The decline among teens, women over 35, and nonwhite women was even greater: 13%, 8%, and 12% respectively. Out-of-wedlock births declined by twice as much as births in wedlock. If legalization in some states affected birth rates in neighboring states (through travel to obtain an abortion), comparing births between states will underestimate the actual reduction. Using more distant comparison states increases the estimated impact of abortion legalization on birth rates to about 8%. Applying this estimate to the current level of births, a complete recriminalization of abortion would result in 320,000 additional births per year

THE HIDDEN SYSTEM COSTS OF WIND GENERATION IN A DEREGULATED ELECTRICITY MARKET

WP 2011-01Earlier research has shown that adding wind capacity to a network can lower the total annual operating cost of meeting a given pattern of loads by displacing conventional generation. At the same time, the variability of wind generation and the need for higher levels of reserve generating capacity to maintain reliability standards impose additional costs on the system that should not be ignored. The important implication for regulators is that the capacity payments [“missing money”] for eachMW of peak system load is now much higher. Hence, the economic benefits to a network of using storage, controllable load and other mechanisms to reduce the peak system load will be higher with high penetrations of wind generation. These potential benefits are illustrated in a case study using a test network and a security constrained OPF with endogenous reserves (SuperOPF). The capabilities of the SuperOPF provide a consistent economic framework for evaluating Operating Reliability in real-time markets and System Adequacy for planning purposes. The scenarios considered make it possible to determine 1) the amount of conventional generating capacity needed to meet the peak system load and maintain System Adequacy, and the amount of wind dispatched, 2) total payments by customers in the Wholesale Market, and the amount of missing money paid to generators to maintain their Financial Adequacy, 3) changes in the congestion rents for transmission that are collected by the system operator, and finally, 4) the total annual system costs paid by customers directly in the Wholesale Market and, indirectly, as missing money. The results show that the benefits (i.e. the reduction in the total annual system costs) from making an investment in wind capacity and/of upgrading a tie line are very sensitive to 1) how much of the inherent variability of wind generation is mitigated, and 2) how the missing money paid to conventional generators is determined (e.g. comparing a regulated market with a deregulated market).This research was supported by the US Department of Energy through the Consortium for Electric Reliability Technology Solutions (CERTS) and by the Power Systems Engineering Research Center (PSERC)

Differentiating Plasmodium falciparum alleles by transforming Cartesian X,Y data to polar coordinates

<p>Abstract</p> <p>Background</p> <p>Diagnosis of infectious diseases now benefits from advancing technology to perform multiplex analysis of a growing number of variables. These advances enable simultaneous surveillance of markers characterizing species and strain complexity, mutations associated with drug susceptibility, and antigen-based polymorphisms in relation to evaluation of vaccine effectiveness. We have recently developed assays detecting single nucleotide polymorphisms (SNPs) in the <it>P. falciparum </it>genome that take advantage of post-PCR ligation detection reaction and fluorescent microsphere labeling strategies. Data from these assays produce a spectrum of outcomes showing that infections result from single to multiple strains. Traditional methods for distinguishing true positive signal from background can cause false positive diagnoses leading to incorrect interpretation of outcomes associated with disease treatment.</p> <p>Results</p> <p>Following analysis of <it>Plasmodium falciparum </it>dihydrofolate reductase SNPs associated with resistance to a commonly used antimalarial drug, Fansidar (Sulfadoxine/pyrimethamine), and presumably neutral SNPs for parasite strain differentiation, we first evaluated our data after setting a background signal based on the mean plus three standard deviations for known negative control samples. Our analysis of single allelic controls suggested that background for the absent allele increased as the concentration of the target allele increased. To address this problem, we introduced a simple change of variables from customary (<it>X,Y</it>) (Cartesian) coordinates to planar polar coordinates (<it>X </it>= <it>r</it>cos(<it>θ</it>), <it>Y </it>= <it>r</it>sin(<it>θ</it>)). Classification of multidimensional fluorescence signals based on histograms of angular and radial data distributions proved more effective than classification based on Cartesian thresholds. Comparison with known diallelic dilution controls suggests that histogram-based classification is effective for major:minor allele concentration ratios as high as 10:1.</p> <p>Conclusion</p> <p>We have observed that the diallelic SNP data resulting from analysis of <it>P. falciparum </it>mutations is more accurately diagnosed when a simple polar transform of the (<it>X,Y</it>) data into (<it>r,θ</it>) is used. The development of high through-put methods for genotyping <it>P. falciparum </it>SNPs and the refinement of analytical approaches for evaluating these molecular diagnostic results significantly advance the evaluation of parasite population diversity and antimalarial drug resistance.</p

Twenty-First Century Climate Change and Submerged Aquatic Vegetation in a Temperate Estuary: The Case of Chesapeake Bay

Introduction: The Chesapeake Bay was once renowned for expansive meadows of submerged aquatic vegetation (SAV). However, only 10% of the original meadows survive. Future restoration effortswill be complicated by accelerating climate change, including physiological stressors such as a predicted mean temperature increase of 2-6°C and a 50-160% increase in CO2 concentrations. Outcomes: As the Chesapeake Bay begins to exhibit characteristics of a subtropical estuary, summer heat waves will become more frequent and severe. Warming alone would eventually eliminate eelgrass (Zostera marina) from the region. It will favor native heat-tolerant species such as widgeon grass (Ruppia maritima) while facilitating colonization by non-native seagrasses (e.g., Halodule spp.). Intensifying human activity will also fuel coastal zone acidification and the resulting high CO2/low pH conditions may benefit SAV via a CO2 fertilization effect. . Discussion: Acidification is known to offset the effects of thermal stress and may have similar effects in estuaries, assuming water clarity is sufficient to support CO2-stimulated photosynthesis and plants are not overgrown by epiphytes. However, coastal zone acidification is variable, driven mostly by local biological processes that may or may not always counterbalance the effects of regional warming. This precarious equipoise between two forces - thermal stress and acidification - will be critically important because it may ultimately determine the fate of cool-water plants such as Zostera marina in the Chesapeake Bay. Conclusion: The combined impacts of warming, coastal zone acidification, water clarity, and overgrowth of competing algae will determine the fate of SAV communities in rapidly changing temperate estuaries

Relationships Among Disease, Social Support, and Perceived Health: A Lifespan Approach

We examined the relationship between the cumulative presence of major disease (cancer, stroke, diabetes, heart disease, and hypertension), social support, and self‐reported general and emotional well‐being in a community representative sample of predominantly White and African American respondents (N = 1349). Across all ages, greater presence of disease predicted poorer reported general health, and predicted lower emotional well‐being for respondents 40 and above. In contrast, social support predicted better‐reported general and emotional well‐being. We predicted that different types of social support (blood relatives, children, friends, community members) would be relatively more important for health in different age groups based on a lifespan or life stage model. This hypothesis was supported; across all ages, social support was related to better reported general and emotional health, but sources of support differed by age. Broadly, those in younger age groups tended to list familial members as their strongest sources of support, whereas older group members listed their friends and community members. As a whole, social support mediated the effect of disease on reported well‐being, however, moderated mediation by type of support was not significant. The results are consistent with a lifespan approach to changing social ties throughout the life course.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116357/1/ajcp9758.pd

Evaluation of Sandwich Structure Bonding In Out-of-Autoclave Processing

The out-of-autoclave-vacuum-bag-only (OOA-VBO) process is low in capital expenditures compared to the traditional autoclave, however, the material challenges for OOA-VBO workable material systems are high. Presently there are few such aerospace grade prepreg materials available commercially. In this study, we evaluated processing and properties of honeycomb sandwich structure (HC/SS) panels fabricated by co-curing composite face sheet with adhesives by the OOA-VBO process in an oven. The prepreg materials were IM7/MTM 45-1 and T40-800B/5320. Adhesives studied were AF-555M, XMTA-241/PM15, FM-309-1M and FM-300K. Aluminum H/C cores with and without perforations were included. It was found that adhesives in IM7/MTM 45-1/AF-555M, T40-800B/5320/FM 309-1M and T40-800B/5320/FM-300K panels all foamed but yielded high flatwise tensile (FWT) strength values above 8,275 kPA (1,200 psi). IM7/MTM 45-1/XMTA-241/PM15 did not foam, yet yielded a low FWT strength. SEM photomicrographs revealed that the origin of this low strength was poor adhesion in the interfaces between the adhesive and face sheet composite due to poor wetting associated with the high initial viscosity of the XMTA-241/PM15 adhesive