Modeling of solvent flow effects in enzyme catalysis under physiological conditions

A stochastic model for the dynamics of enzymatic catalysis in explicit, effective solvents under physiological conditions is presented. Analytically-computed first passage time densities of a diffusing particle in a spherical shell with absorbing boundaries are combined with densities obtained from explicit simulation to obtain the overall probability density for the total reaction cycle time of the enzymatic system. The method is used to investigate the catalytic transfer of a phosphoryl group in a phosphoglycerate kinase-ADP-bis phosphoglycerate system, one of the steps of glycolysis. The direct simulation of the enzyme-substrate binding and reaction is carried out using an elastic network model for the protein, and the solvent motions are described by multiparticle collision dynamics, which incorporates hydrodynamic flow effects. Systems where solvent-enzyme coupling occurs through explicit intermolecular interactions, as well as systems where this coupling is taken into account by including the protein and substrate in the multiparticle collision step, are investigated and compared with simulations where hydrodynamic coupling is absent. It is demonstrated that the flow of solvent particles around the enzyme facilitates the large-scale hinge motion of the enzyme with bound substrates, and has a significant impact on the shape of the probability densities and average time scales of substrate binding for substrates near the enzyme, the closure of the enzyme after binding, and the overall time of completion of the cycle.Comment: 15 pages in double column forma

The Roles of Knowledge and Organizational Form on Opportunity Evaluation

What influences an individual to pursue one type of entrepreneurial opportunity versus another? Knowledge is central to the concept of opportunity identification and evaluation.  Using conjoint analysis to capture underlying decision policies, we explore the roles of both knowledge and organizational form in the evaluation of entrepreneurial opportunities.  Our findings suggest that, among respondents who considered entering a franchise agreement a viable alternative to founding an independent business, franchise versus independent form alone did not play a specific and significant role in the evaluation of the attractiveness of entrepreneurial opportunities.  Rather, organizational form appears to influence the impact of both human capital relatedness and the inimitability of resources attributes on opportunity attractiveness. 

Coulomb excitation of 102 Ru with 12 C and 16 O

The Coulomb excitation of 102Ru was performed with beams of 12C and 16O ions. The beam particles scattered at forward angles were momentum analyzed with a magnetic spectrograph. The resolution achieved enabled the populations of the 2+ 1 state, the unresolved 2+ 2 /4+ 1 , and 2+ 4 /3− 1 , doublets of states, and the 3− 2 state to be determined as a function of the scattering angle. These populations are compared with GOSIA calculations, yielding B(E2; 2+ 1 → 0+ 1 ) = 41.5 ± 2.3 W.u., B(E2; 2+ 2 → 0+ 1 ) = 1.75 ± 0.11 W.u., B(E3; 3− 1 → 0+ 1 ) = 31.5 ± 3.5 W.u., and B(E3; 3− 2 → 0+ 1 ) = 6.8 ± 0.5 W.u. The B(E3; 3− 1 → 0+ 1 ) value is significantly larger than previously measured. The weakly populated 2+ 3 state, presumed to be a member of the band built on the 0+ 2 state, was observed clearly for a single angle only, and a fit to its population results in B(E2; 2+ 3 → 0+ 1 ) = 0.053 ± 0.011 W.u. Using the known γ -ray branching ratios for the 2+ 3 level, the B(E2; 2+ 3 → 0+ 2 ) value is calculated to be 18 ± 4 W.u., substantially less than the B(E2; 2+ 1 → 0+ 1 ). This suggests that the deformation of the 0+ 2 state is lower than that of the 0+ 1 state. The results are compared with beyond-mean-field calculations with the Gogny-D1S interaction using the symmetry-conserving configuration-mixing method

Piscivorous Bird Use of Aquaculture and Natural Water Bodies in Mississippi

Double crested cormorants (Phalacrocorax auritus) and great egrets (Ardea alba) have an extensive history of human wildlife conflict with the aquaculture industry of western Mississippi, USA, due to their depredation of cultured catfish (Ictalurus spp.). Although aquaculture is abundant, western Mississippi also contains naturally occurring water bodies that offer alternative forage opportunities to these species. How cormorants or egrets distribute themselves among these 2 foraging options is unknown, but it has been generally assumed each species uses aquaculture disproportionately more because of the high density of available prey. To test this assumption, we surveyed these species on aquaculture and naturally occurring water bodies using aerial surveys from October through April of 2015–2016, 2016–2017, and 2017–2018. We modeled the proportion of each species on aquaculture as a function of year, date, and weather-related variables using quasi binomial generalized linear models. Egrets used aquaculture consistently more than what was proportionally available to them and use was not influenced by any of the variables we measured. Proportional use of aquaculture by cormorants was lowest during October through January but steadily increased through April, indicating a distribution shift toward aquaculture in the months immediately prior to their migration. The highest proportional use of aquaculture by cormorants occurred in 2016, a year when lethal control measures were not allowed against cormorants. Conversely, the least proportion of cormorants on aquaculture was in 2015 when cormorants could be lethally controlled under authority of an Aquaculture Depredation Order. This trend highlights the potential influence of changes in mortality risk, caused by changes in policy regarding lethal take of cormorants, on cormorant distribution between foraging option

Historic and contemporary use of catfish aquaculture by piscivorous birds in the Mississippi Delta

Piscivorous birds are the primary source of catfish (Ictalurus spp.) depredation at aquaculture facilities in northwestern Mississippi. Of particular concern is the Double-crested Cormorant (Phalacrocorax auritus), which can cost aquaculture producers millions of dollars annually through the depredation of cultured fish. Historical research conducted in the early 2000s estimated cormorant use of aquaculture ponds in the region, but aquaculture area has decreased by more than 70% since those estimates were made. With less aquaculture available, we predicted cormorant densities on aquaculture would be greater today than historically. Applying a similar methodology as in historical studies, we used aerial surveys to collect data on cormorants at night roosts and using catfish aquaculture ponds during 3 consecutive winter seasons, beginning in 2015. Although the mean annual number of cormorants at roosts in the Delta during our study was 64% less than historically, we found no significant change in densities on aquaculture, suggesting that aquaculture area is likely the factor influencing cormorant occurrence in northwestern Mississippi. During contemporary surveys we also measured the abundance of Great Blue Herons (Ardea herodias) and Great Egrets (A. alba) on the aquaculture clusters, and built predictive models of abundance relative to variables associated with forage at and surrounding the clusters. We found abundance of all 3 species was strongly related to the amount of aquaculture area both within and surrounding a cluster, although patterns varied by species. Cormorant abundance was also greater on clusters with proportionately more food fish (≥20 cm in length) than fingerlings (\u3c20 cm) and was positively related to the proximity and size of night roosts. The relationships described here can be used by producers and wildlife managers to predict the abundance of these piscivorous birds at aquaculture facilities and to design efficient management plans to mitigate potential impacts of depredation and disease

Fine Scale Characteristics of Catfish Aquaculture Ponds Influencing Use by Double-Crested Cormorants (Phalacrocorax auritus) in Northwest Mississippi

Double-crested Cormorants (Phalacrocorax auritus) are the main source of depredation at catfish aquaculture facilities in Northwest Mississippi, resulting in significant economic loss. Understanding factors related to pond selection by cormorants could aid in mitigation practices to minimize further loss. We constructed occupancy models to estimate the probability of cormorant presence on catfish ponds against multiple variables associated with each ponds physical surroundings and internal conditions. We also explored cormorant use of aquaculture and natural habitat by using logistic regression to model the proportion of cormorants on aquaculture compared to natural habitat and influences of seasonal variation. Cormorant presence data was collected by aerial survey (n=35) from October to April, of 2015-2017, accounting for an average of 973 catfish ponds and 26 natural water bodies each year. Our results indicate ponds located farther away from trees and activity centers, such as farm workshops, have a higher probability of cormorant use. Larger ponds, and ponds nearer the edge of pond clusters also have an increased probability of use. Specific pond contents influenced cormorant use, including fish species cultured, pond systems, and fish types. From October through January cormorants were distributed more on natural habitat. However, cormorants’ proportional use of aquaculture steadily increased beginning in February. This temporal shift from natural habitat toward aquaculture coincides with cormorant spring migration, indicating an increase in foraging of catfish in preparation for the migration north

Long term changes in aquaculture influence migration, regional abundance, and distribution of an avian species

Agricultural development has been causing changes to the environment and the abundance and distribution of avian species. Agriculture is dynamic with changes in products occurring at large scales over relatively short time periods. The catfish aquaculture industry is one such agriculture industry that has undergone dramatic changes over the last 25 years. The double-crested cormorant (Nannopterum auritum) is a piscivorous bird that has an extensive history with the aquaculture industry of Mississippi due to its depredation of cultured catfish. A large-scale monitoring program began in 1989 to estimate the abundance and location of cormorants at every known roost in the primary catfish producing region of the state, regionally known as the Delta. We used this data set to address hypotheses pertaining to cormorant ecology within the Delta over time, particularly in relation to aquaculture. We found that, although the Midwest breeding population of cormorants has been increasing, the abundance of cormorants wintering in the Delta has been decreasing, closely following the decline of aquaculture, suggesting aquaculture area is the primary reason for cormorant inhabitation of the region. We also modeled cormorant presence and abundance at all roost sites to determine what factors most influenced cormorant distribution. Aquaculture area around roosts was a significant predictor of both cormorant presence and abundance. However, the influence of aquaculture area was seasonally dependent, with greater positive influences occurring prior to migration. Lastly, we found peak cormorant abundance in the Delta is occurring 2.14 days earlier each year, which may be indicative of changes to migration phenology. Information gained using this large dataset aids in cormorant damage mitigation and to further our understanding of cormorant ecology. Data indicate changes in agriculture, and potentially climate change, can influence phenology, distribution, and abundance of avian species at large geographic scales

Psychological Factors Shaping Public Responses to COVID-19 Digital Contact Tracing Technologies in Germany

The COVID-19 pandemic has seen one of the first large-scale uses of digital contact tracing to track a chain of infection and contain the spread of a virus. The new technology has posed challenges both for governments aiming at high and effective uptake and for citizens weighing its benefits (e.g., protecting others’ health) against the potential risks (e.g., loss of data privacy). Our cross-sectional survey with repeated measures across four samples in Germany ([Formula: see text] ) focused on psychological factors contributing to the public adoption of digital contact tracing. We found that public acceptance of privacy-encroaching measures (e.g., granting the government emergency access to people’s medical records or location tracking data) decreased over the course of the pandemic. Intentions to use contact tracing apps—hypothetical ones or the Corona-Warn-App launched in Germany in June 2020—were high. Users and non-users of the Corona-Warn-App differed in their assessment of its risks and benefits, in their knowledge of the underlying technology, and in their reasons to download or not to download the app. Trust in the app’s perceived security and belief in its effectiveness emerged as psychological factors playing a key role in its adoption. We incorporate our findings into a behavioral framework for digital contact tracing and provide policy recommendations

Ligity: A Non-Superpositional, Knowledge-Based Approach to Virtual Screening

We present Ligity, a hybrid ligand-structurebased, non-superpositional method for virtual screening of large databases of small molecules. Ligity uses the relative spatial distribution of pharmacophoric interaction points (PIPs) derived from the conformations of small molecules. These are compared with the PIPs derived from key interaction features found in protein−ligand complexes and are used to prioritize likely binders. We investigated the effect of generating PIPs using the single lowest energy conformer versus an ensemble of conformers for each screened ligand, using different bin sizes for the distance between two features, utilizing triangular sets of pharmacophoric features (3-PIPs) versus chiral tetrahedral sets (4-PIPs), fusing data for targets with multiple protein−ligand complex structures, and applying different similarity measures. Ligity was benchmarked using the Directory of Useful Decoys-Enhanced (DUD-E). Optimal results were obtained using the tetrahedral PIPs derived from an ensemble of bound ligand conformers and a bin size of 1.5 Å, which are used as the default settings for Ligity. The high-throughput screening mode of Ligity, using only the lowest-energy conformer of each ligand, was used for benchmarking against the whole of the DUD-E, and a more resource-intensive, “information-rich” mode of Ligity, using a conformational ensemble of each ligand, were used for a representative subset of 10 targets. Against the full DUD-E database, mean area under the receiver operating characteristic curve (AUC) values ranged from 0.44 to 0.99, while for the representative subset they ranged from 0.61 to 0.86. Data fusion further improved Ligity’s performance, with mean AUC values ranging from 0.64 to 0.95. Ligity is very efficient compared to a protein−ligand docking method such as AutoDock Vina: if the time taken for the precalculation of Ligity descriptors is included in the comparison, then Ligity is about 20 times faster than docking. A direct comparison of the virtual screening steps shows Ligity to be over 5000 times faster. Ligity highly ranks the lowest-energy conformers of DUD-E actives, in a statistically significant manner, behavior that is not observed for DUD-E decoys. Thus, our results suggest that active compounds tend to bind in relatively low-energy conformations compared to decoys. This may be because actives - and thus their lowest-energy conformations - have been optimized for conformational complementarity with their cognate binding sites

Young Adults View Smartphone Tracking Technologies for COVID-19 as Acceptable:The Case of Taiwan

Taiwan has been successful in controlling the spread of SARS-CoV-2 during the COVID-19 pandemic; however, without a vaccine the threat of a second outbreak remains. Young adults who show few to no symptoms when infected have been identified in many countries as driving the virus' spread through unidentifiable community transmission. Mobile tracking technologies register nearby contacts of a user and notifies them if one later tests positive to the virus, potentially solving this issue; however, the effectiveness of these technologies depends on their acceptance by the public. The current study assessed attitudes towards three tracking technologies (telecommunication network tracking, a government app, and Apple and Google's Bluetooth exposure notification system) among four samples of young Taiwanese adults (aged 25 years or younger). Using Bayesian methods, we find high acceptance for all three tracking technologies (>75%), with acceptance for each technology surpassing 90% if additional privacy measures were included. We consider the policy implications of these results for Taiwan and similar cultures