An Exact Algorithm for Side-Chain Placement in Protein Design

Computational protein design aims at constructing novel or improved functions on the structure of a given protein backbone and has important applications in the pharmaceutical and biotechnical industry. The underlying combinatorial side-chain placement problem consists of choosing a side-chain placement for each residue position such that the resulting overall energy is minimum. The choice of the side-chain then also determines the amino acid for this position. Many algorithms for this NP-hard problem have been proposed in the context of homology modeling, which, however, reach their limits when faced with large protein design instances. In this paper, we propose a new exact method for the side-chain placement problem that works well even for large instance sizes as they appear in protein design. Our main contribution is a dedicated branch-and-bound algorithm that combines tight upper and lower bounds resulting from a novel Lagrangian relaxation approach for side-chain placement. Our experimental results show that our method outperforms alternative state-of-the art exact approaches and makes it possible to optimally solve large protein design instances routinely

Implementing a small media intervention to increase colorectal cancer screening in primary care clinics

Colorectal cancer (CRC) is one of the most common cancers in the USA. In 2017, an estimated 135,420 people were diagnosed with CRC and 50,260 people died from CRC. Several screening modalities are recommended by the United States Preventive Services Task Force (USPSTF), including annual stool tests that are usually completed at home and under-used compared with colonoscopy despite stated patient preferences for an alternative to colonoscopy. The Community Preventive Services Task Force recommends use of small media interventions (SMIs) to increase CRC screening and calls for a greater understanding of its independent impact on screening participation. This study tested whether a SMI increased the likelihood of participant return of a USPSTF recommended Fecal Immunochemical Test (FIT). In total, 804 individuals participated in a two-group, prospective randomized controlled trial. Descriptive statistics with chi-square tests compared differences in participant characteristics and return rates. Multivariable log-binomial modeling estimated combined effects of patient characteristics with FIT return rates. No differences in return rates were observed overall or by participant characteristics other than the year of enrollment. A multivariable model controlling for all covariates, found gender, insurance type, and regular place for healthcare to be significantly associated with return rates. Receipt of the SMI did not independently increase overall return rates but it may have improved the ease of completing the FIT by some participants, particularly women, those with insurance, and those with a regular place for healthcare

Influence of young cement water on the corrosion of the International Simple Glass

Understanding the corrosion of nuclear waste glass is critical to predicting its safe disposal within a geological facility. The corrosion mechanisms and kinetics of the International Simple Glass, a simplified version of high-level nuclear waste glass, was shown to be significantly influenced by a high pH cement solution representative of disposal conditions. We provide the first microscopic characterisation of the porous, Zr-rich aluminoalkali-silica gel corrosion layer that was observed. Ca, Na and K from the cement solution were incorporated into the corrosion layer to charge compensate Si, Al and Zr species; the incorporation of Al was postulated to result in precipitation of an aluminosilicate-rich gel with large voids, facilitating rapid transport of species through the gel layer and significantly enhancing the corrosion rate. Precipitation of Al-containing zeolite and phyllosilicate phases was also observed, indicating that cementitious solutions may promote the detrimental ‘rate resumption’ stage of glass corrosion

Future Fire Impacts on Smoke Concentrations, Visibility, and Health in the Contiguous United States

Fine particulate matter (PM2.5) from U.S. anthropogenic sources is decreasing. However, previous studies have predicted that PM2.5 emissions from wildfires will increase in the midcentury to next century, potentially offsetting improvements gained by continued reductions in anthropogenic emissions. Therefore, some regions could experience worse air quality, degraded visibility, and increases in population-level exposure. We use global climate model simulations to estimate the impacts of changing fire emissions on air quality, visibility, and premature deaths in the middle and late 21st century. We find that PM2.5 concentrations will decrease overall in the contiguous United States (CONUS) due to decreasing anthropogenic emissions (total PM2.5 decreases by 3% in Representative Concentration Pathway [RCP] 8.5 and 34% in RCP4.5 by 2100), but increasing fire-related PM2.5 (fire-related PM2.5 increases by 55% in RCP4.5 and 190% in RCP8.5 by 2100) offsets these benefits and causes increases in total PM2.5 in some regions. We predict that the average visibility will improve across the CONUS, but fire-related PM2.5 will reduce visibility on the worst days in western and southeastern U.S. regions. We estimate that the number of deaths attributable to total PM2.5 will decrease in both the RCP4.5 and RCP8.5 scenarios (from 6% to 4–5%), but the absolute number of premature deaths attributable to fire-related PM2.5 will double compared to early 21st century. We provide the first estimates of future smoke health and visibility impacts using a prognostic land-fire model. Our results suggest the importance of using realistic fire emissions in future air quality projections

Herbivorous turtle ants obtain essential nutrients from a conserved nitrogen-recycling gut microbiome.

Nitrogen acquisition is a major challenge for herbivorous animals, and the repeated origins of herbivory across the ants have raised expectations that nutritional symbionts have shaped their diversification. Direct evidence for N provisioning by internally housed symbionts is rare in animals; among the ants, it has been documented for just one lineage. In this study we dissect functional contributions by bacteria from a conserved, multi-partite gut symbiosis in herbivorous Cephalotes ants through in vivo experiments, metagenomics, and in vitro assays. Gut bacteria recycle urea, and likely uric acid, using recycled N to synthesize essential amino acids that are acquired by hosts in substantial quantities. Specialized core symbionts of 17 studied Cephalotes species encode the pathways directing these activities, and several recycle N in vitro. These findings point to a highly efficient N economy, and a nutritional mutualism preserved for millions of years through the derived behaviors and gut anatomy of Cephalotes ants

Alteration layer formation of Ca- and Zn-oxide bearing alkali borosilicate glasses for immobilisation of UK high level waste: A vapour hydration study

The UK high level nuclear waste glass modified with CaO/ZnO was investigated using the vapour phase hydration test, performed at 200 °C, with the aim of understanding the impact of the modification on the chemical composition and microstructure of the alteration layer. Experiments were undertaken on non-modified and CaO/ZnO-modified base glass, with or without 25 wt% of simulant Magnox waste calcine. The modification resulted in a dramatic reduction in gel layer thickness and also a reduction in the reaction rate, from 3.4 ± 0.3 g m−2 d−1 without CaO/ZnO modification to 0.9 ± 0.1 g m−2 d−1 with CaO/ZnO. The precipitated phase assemblage for the CaO/ZnO-modified compositions was identified as hydrated Ca- and Zn-bearing silicate phases, which were absent from the non-modified counterpart. These results are in agreement with other recent studies showing the beneficial effects of ZnO additions on glass durability

The induction of behavioural sensitization is associated with cocaine-induced structural plasticity in the core (but not shell) of the nucleus accumbens

Repeated exposure to cocaine increases the density of dendritic spines on medium spiny neurons in the nucleus accumbens (Acb) and pyramidal cells in the medial prefrontal cortex (mPFC). To determine if this is associated with the development of psychomotor sensitization, rats were given daily i.p. injections of 15 mg/kg of cocaine (or saline) for 8 days, either in their home cage (which failed to induce significant psychomotor sensitization) or in a distinct and relatively novel test cage (which induced robust psychomotor sensitization). Their brains were obtained 2 weeks after the last injection and processed for Golgi–Cox staining. In the Acb core (AcbC) cocaine treatment increased spine density only in the group that developed psychomotor sensitization (i.e. in the Novel but not Home group), and there was a significant positive correlation between the degree of psychomotor sensitization and spine density. In the Acb shell (AcbS) cocaine increased spine density to the same extent in both groups; i.e. independent of psychomotor sensitization. In the mPFC cocaine increased spine density in both groups, but to a significantly greater extent in the Novel group. Furthermore, when rats were treated at Home with a higher dose of cocaine (30 mg/kg), cocaine now induced psychomotor sensitization in this context, and also increased spine density in the AcbC. Thus, the context in which cocaine is experienced influences its ability to reorganize patterns of synaptic connectivity in the Acb and mPFC, and the induction of psychomotor sensitization is associated with structural plasticity in the AcbC and mPFC, but not the AcbS.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73532/1/j.1460-9568.2004.03612.x.pd

Yukawa coupling unification and non-universal gaugino mediation of supersymmetry breaking

The requirement of Yukawa coupling unification highly constrains the SUSY parameter space. In several SUSY breaking scenarios it is hard to reconcile Yukawa coupling unification with experimental constraints from B(b->s gamma) and the muon anomalous magnetic moment a_mu. We show that b-tau or even t-b-tau Yukawa unification can be satisfied simultaneously with b->s gamma and a_mu in the non-universal gaugino mediation scenario. Non-universal gaugino masses naturally appear in higher dimensional grand unified models in which gauge symmetry is broken by orbifold compactification. Relations between SUSY contributions to fermion masses, b->s gamma and a_mu which are typical for models with universal gaugino masses are relaxed. Consequently, these phenomenological constraints can be satisfied simultaneously with a relatively light SUSY spectrum, compared to models with universal gaugino masses.Comment: 20 pages, 8 figures. References added. A copy of the paper with better resolution figures can be found at http://www.hep.fsu.edu/~balazs/Physics/Papers/2003

Neutralino-Nucleon Cross Section and Charge and Colour Breaking Constraints

We compute the neutralino-nucleon cross section in several supersymmetric scenarios, taking into account all kind of constraints. In particular, the constraints that the absence of dangerous charge and colour breaking minima imposes on the parameter space are studied in detail. In addition, the most recent experimental constraints, such as the lower bound on the Higgs mass, the $b\to s\gamma$ branching ratio, and the muon $g-2$ are considered. The astrophysical bounds on the dark matter density are also imposed on the theoretical computation of the relic neutralino density, assuming thermal production. This computation is relevant for the theoretical analysis of the direct detection of dark matter in current experiments. We consider first the supergravity scenario with universal soft terms and GUT scale. In this scenario the charge and colour breaking constraints turn out to be quite important, and \tan\beta\lsim 20 is forbidden. Larger values of $\tan\beta$ can also be forbidden, depending on the value of the trilinear parameter $A$. Finally, we study supergravity scenarios with an intermediate scale, and also with non-universal scalar and gaugino masses where the cross section can be very large.Comment: Final version to appear in JHE

Neutralino Dark Matter from MSSM Flat Directions in light of WMAP Result

The minimal supersymmetric standard model (MSSM) has a truly supersymmetric way to explain both the baryon asymmetry and cold dark matter in the present Universe, that is, ``Affleck-Dine baryo/DM-genesis.'' The associated late-time decay of Q-balls directly connects the origins of the baryon asymmetry and dark matter, and also predicts a specific nature of the LSP. In this paper, we investigate the prospects for indirect detection of these dark matter candidates observing high energy neutrino flux from the Sun, and hard positron flux from the halo. We also update the previous analysis of the direct detection in hep-ph/0205044 by implementing the recent result from WMAP satellite.Comment: 32 pages, including 40 figure