Search

Predicting how a point mutation alters a protein's stability can guide pharmaceutical drug design initiatives which aim to counter the effects of serious diseases. Conducting mutagenesis studies in physical proteins can give insights about the effects of amino acid substitutions, but such wet-lab work is prohibitive due to the time as well as financial resources needed to assess the effect of even a single amino acid substitution. Computational methods for predicting the effects of a mutation on a protein structure can complement wet-lab work, and varying approaches are available with promising accuracy rates. In this work we compare and assess the utility of several machine learning methods and their ability to predict the effects of single and double mutations. We in silico generate mutant protein structures, and compute several rigidity metrics for each of them. We use these as features for our Support Vector Regression (SVR), Random Forest (RF), and Deep Neural Network (DNN) methods. We validate the predictions of our in silico mutations against experimental Δ Δ G stability data, and attain Pearson Correlation values upwards of 0.71 for single mutations, and 0.81 for double mutations. We perform ablation studies to assess which features contribute most to a model's success, and also introduce a voting scheme to synthesize a single prediction from the individual predictions of the three models., Competing Interests: The authors declare no conflict of interest.

Background: Researchers have reported rampant caries among methamphetamine users. The authors investigated the prevalence of dental disease and associated risk behaviors in methamphetamine users compared with those in heroin users., Methods: This pilot project was a cross-sectional study of an ongoing cohort of young adult injection-drug users (IDUs) in San Francisco. Participants completed an oral health questionnaire administered by a research assistant, and dentists performed clinical examinations to record the participants' data in terms of scores on the decayed-missing-filled surfaces (DMFS) index, presence of residual roots, scores on an oral hygiene index and whether any salivary hypofunction was observed., Results: The prevalence of dental disease among 58 young adult IDUs was strikingly high compared with that in the U.S. general population; however, the authors found no difference in the level of dental disease between users of methamphetamine and users of heroin. The mean DMFS score and number of decayed surfaces exceeded 28 in both groups., Conclusions: Although the authors detected no difference in dental disease between methamphetamine and heroin users, they found a high prevalence of caries and caries-associated behaviors in the sample of young adult IDUs., Clinical Implications: Given the high level of dental disease observed in this population of young adult IDUs, one next step may be to explore the feasibility and effectiveness of providing low-intensity preventive measures (such as distribution of chlorhexidine rinses or xylitol gum or application of fluoride varnishes) through outreach workers.

A vegetation mapping system for change detection was tested at the Havasu National Wildlife Refuge (HNWR) on the Lower Colorado River. A low-cost, aerial photomosaic of the 4200 ha, study area was constructed utilizing an automated digital camera system, supplemented with oblique photographs to aid in determining species composition and plant heights. Ground-truth plots showed high accuracy in distinguishing native cottonwood (Populus fremontii) and willow (Salix gooddingii) trees from other vegetation on aerial photos. Marsh vegetation (mainly cattails, Typha domengensis) was also easily identified. However, shrubby terrestrial vegetation, consisting of saltcedar (Tamarix ramosissima), arrowweed (Pluchea sericea), and mesquite trees (Prosopis spp.), could not be accurately distinguished from each other and were combined into a single shrub layer on the final vegetation map. The final map took the form of a base, shrub and marsh layer, which was displayed as a Normalized Difference Vegetation Index map from a Landsat Enhanced Thematic Mapper (ETM+) image to show vegetation intensity. Native willow and cottonwood trees were digitized manually on the photomosaic and overlain on the shrub layer in a GIS. By contrast to present, qualitative mapping systems used on the Lower Colorado River, this mapping system provides quantitative information that can be used for accurate change detection. However, better methods to distinguish between saltcedar, mesquite, and arrowweed are needed to map the shrub layer.

Background: Dentists experience more neck, shoulder and lower back pain than do practitioners in other occupational groups. The authors examined the prevalence of musculoskeletal pain in dental students, by sex., Methods: The authors investigated the body distribution and severity of reported musculoskeletal pain in a population of dental students, considering increased exposure to clinical experience with years in dental school. A total of 271 dental students in all four school years completed a questionnaire focusing on pain reported in five general body regions., Results: Forty-six to 71 percent of students reported body pain, with the percentage generally increasing with years in dental school. Women reported having the worst pain in their neck/shoulder region (chi2, P = .004); men reported having the worst pain in their mid- to lower back regions (chi2, P = .015). Frequency and daily duration of the worst pain were higher in the third year of dental school than in the first year (Bonferroni test, P = .014 and P = .001, respectively), as was the persistence (in months) of the most symptomatic body pain (P = .001). Pain intensity was higher for women than for men (two-way analysis of variance, P < .05). The perception of how performance of dental procedures affects pain increased significantly with number of years in dental school (P = .001)., Conclusions: Chronic musculoskeletal pain appears early in dental careers, with more than 70 percent of dental students of both sexes reporting pain by their third year., Clinical Implications: Musculoskeletal pain is a common complaint of dental professionals that may lead to serious physical disability. Since this type of pain occurs early in dental training, dentistry is obligated to further examine the mental, physical and ergonomic factors that may be contributory.

The study was designed to describe the functional significance of gaze and mutual gaze in the context of the free-play conversation of preschool children. It was hypothesized that mutual gaze is not a fortuitous event in young children but a result of a gaze-action-gaze-reaction sequential process. Eleven high- and 11 low-friendship dyads were formed on the basis of the frequency of interaction in freeplay. Each dyad was videotaped for 15-minute play sessions. The videotapes were analyzed for the occurrence of gaze-related utterances and the occurrence of mutual gaze. When the speaker gazed at the listener the contingent probability of gaze response in the listener was 45% (as compared to a base rate of 3% gaze-related utterances). When the listener gazed at the speaker, the probability of gaze response was 38%. Gaze-related utterances were longer, more likely to result in a relevant response from the listener and less likely to result in nonresponse than utterances unaccompanied by gaze. Friendship between dyad members had no effect on any of the measures. It was concluded that gaze and mutual gaze are systematic components of the conversational behavior of preschool children.