William T. Hawkens\u27 Pamphlet to Homeward Bound Americans, ca. 1919

William T. Hawkens\u27 Pamphlet to Homeward Bound Americans, ca. 1919https://digitalmaine.com/hawkens_241498/1000/thumbnail.jp

A small step toward generalizability: training a machine learning scoring function for structure-based virtual screening

Over the past few years, many machine learning-based scoring functions for predicting the binding of small molecules to proteins have been developed. Their objective is to approximate the distribution which takes two molecules as input and outputs the energy of their interaction. Only a scoring function that accounts for the interatomic interactions involved in binding can accurately predict binding affinity on unseen molecules. However, many scoring functions make predictions based on data set biases rather than an understanding of the physics of binding. These scoring functions perform well when tested on similar targets to those in the training set but fail to generalize to dissimilar targets. To test what a machine learning-based scoring function has learned, input attribution, a technique for learning which features are important to a model when making a prediction on a particular data point, can be applied. If a model successfully learns something beyond data set biases, attribution should give insight into the important binding interactions that are taking place. We built a machine learning-based scoring function that aimed to avoid the influence of bias via thorough train and test data set filtering and show that it achieves comparable performance on the Comparative Assessment of Scoring Functions, 2016 (CASF-2016) benchmark to other leading methods. We then use the CASF-2016 test set to perform attribution and find that the bonds identified as important by PointVS, unlike those extracted from other scoring functions, have a high correlation with those found by a distance-based interaction profiler. We then show that attribution can be used to extract important binding pharmacophores from a given protein target when supplied with a number of bound structures. We use this information to perform fragment elaboration and see improvements in docking scores compared to using structural information from a traditional, data-based approach. This not only provides definitive proof that the scoring function has learned to identify some important binding interactions but also constitutes the first deep learning-based method for extracting structural information from a target for molecule design

Pressure-Induced Excitations in the Out-of-Plane Optical Response of the Nodal-Line Semimetal ZrSiS

The anisotropic optical response of the layered, nodal-line semimetal ZrSiS at ambient and high pressure is investigated by frequency-dependent reflectivity measurements for the polarization along and perpendicular to the layers. The highly anisotropic optical conductivity is in very good agreement with results from density-functional theory calculations and confirms the anisotropic character of ZrSiS. Whereas the in-plane optical conductivity shows only modest pressure-induced changes, we found strong effects on the out-of-plane optical conductivity spectrum of ZrSiS, with the appearance of two prominent excitations. These pronounced pressure-induced effects can neither be attributed to a structural phase transition according to our single-crystal x-ray diffraction measurements, nor can they be explained by electronic correlation and electron-hole pairing effects, as revealed by theoretical calculations. Our findings are discussed in the context of the recently proposed excitonic insulator phase in ZrSiS

Non-perturbatively renormalised light quark masses from a lattice simulation with N_f=2

We present results for the light quark masses obtained from a lattice QCD simulation with N_f=2 degenerate Wilson dynamical quark flavours. The sea quark masses of our lattice, of spacing a ~ 0.06 fm, are relatively heavy, i.e., they cover the range corresponding to 0.60 <~ M_P/M_V <~ 0.75. After implementing the non-perturbative RI-MOM method to renormalise quark masses, we obtain m_{ud}^{MS}(2 GeV)=4.3 +- 0.4^{+1.1}_{-0} MeV, and m_s^{MS}(2 GeV)=101 +- 8^{+25}_{-0} MeV, which are about 15% larger than they would be if renormalised perturbatively. In addition, we show that the above results are compatible with those obtained in a quenched simulation with a similar lattice.Comment: 18 pages, 5 figure

One health in our backyard: Design and evaluation of an experiential learning experience for veterinary medical students

Background: New educational approaches are needed to improve student understanding of the wider sociological and ecological determinants of health as well as professional responsibilities in related areas. Field trips allow students to observe interaction between plant, animal and human communities, making them an ideal tool for teaching One Health concepts. Methods: Veterinary medical students participated in a field trip to a local parklands area, frequented by humans, dogs, horses, and wildlife. Students rotated through 5 learning activities (‘stations’) that focused on: (1) response to exotic animal disease incursion (equine influenza); (2) impact of cultures and belief systems on professional practice; (3) management of dangerous dogs; (4) land use change, biodiversity and emerging infectious disease; and (5) management of environmentally-acquired zoonoses (botulism). Intended learning outcomes were for students to: evaluate the various roles and responsibilities of veterinarians in society; compare the benefits and risks associated with human-animal and animal-animal interactions; and evaluate the contributions made by various professionals in safeguarding the health and welfare of animals, humans and the environment. Following the field trip, students participated in a debrief exercise and completed an online survey on their experiences. Results: Feedback from students collected in 2016/2017 (n = 211) was overwhelmingly positive. The learning experience at each station was rated as 4 (‘Good’) or 5 (‘Very Good’) out of 5 by 82–96% of students. Responses to closed- and open-ended questions − as well as outputs generated in the debrief session − indicated that students achieved the learning outcomes. Overall, 94% of students agreed or strongly agreed that they had a better understanding of One Health because of the field trip. Conclusions: Field trips to local parklands are effective in promoting learning about One Health and can be incorporated into the core curriculum to maximize student exposure at relatively low cost. Keywords: One health, Field trip, Experiential learning, Veterinary education, Cultural competence, Zoonoses, Animal behavio

Bone Marrow Changes in Adolescent Girls With Anorexia Nervosa

Early osteoporosis is common among adolescent girls with anorexia nervosa (AN) and may result from premature conversion of red (RM) to yellow bone marrow. We performed right knee magnetic resonance imaging (MRI) on a 1.0 T extremity scanner in 20 patients and 20 healthy controls, aged 16.2 ± 1.6 years (mean ± SD). Coronal T1-weighted (T1W) images and T1 maps were generated from T1 relaxometry images. Blinded radiologists visually assessed RM in the distal femoral and proximal tibial metaphyses in T1W images using a scale of signal intensity from 0 (homogeneous hyperintensity, no RM) to 4 (all dark, complete RM). Subjects with AN exhibited nearly twofold lower metaphyseal RM scores in both the femur (0.64 versus 1.22, p = .03) and tibia (0.54 versus 0.96, p = .08). In relaxometric measurements of four selected regions (femur and tibia amd epiphysis and metaphysis), subjects with AN showed higher mean epiphyseal but lower metaphyseal T1. The net AN-control difference between epiphysis and metaphysis was 70 ms in the femur (+31 versus −35 ms, p = .02) and of smaller magnitude in the tibia. In relaxometry data from the full width of the femur adjacent to the growth plate, AN subjects showed mean T1 consistently lower than in controls by 30 to 50 ms in virtually every part of the sampling region. These findings suggest that adolescents with AN exhibit premature conversion of hematopoietic to fat cells in the marrow of the peripheral skeleton potentially owing to adipocyte over osteoblast differentiation in the mesenchymal stem cell pool. © 2010 American Society for Bone and Mineral Researc

Perinatal mortality and its prevention in rural Swaziland

Perinatal mortality is defined as the number of stillbirths and deaths in the first week of life per thousand births. While diagnoses such as ‘prematurity’ or ‘intrapartum asphyxia’ are o f interest to midwives and doctors, they tell us very little about the basic reasons for these deaths. Of greater relevance to health workers in developing countries are what may be termed the ‘primary’ causes of mortality. These factors overlap and affec