New methods for the synthesis of biologically active phenanthridine-based libraries

Small molecule libraries have become essential for the development of drug discovery campaigns and chemical genetics. The studies towards the synthesis of a small molecule library, based upon the cis-ring fused phenanthridine core I, will be described. The first section of this thesis examines the development and application of a novel intramolecular Heck cyclisation to the synthesis of core phenanthridine structure II, via precursor III (Chapter 2).The second section (Chapter 3) describes the extension of this methodology towards the development of a library of phenanthridines IV. This includes methodology designed to incorporate the key principles of diversity-oriented synthesis, namely appendage, stereochemical and skeletal diversity. The final part of this thesis (Chapter 4) describes the merging of these various methodologies to generate a small library of novel phenanthridine analogues. Preliminary biological evaluation of the phenanthridine library using whole organism zebrafish phenotyping, will also be discussed

USSR Space Life Sciences Digest, issue 16

This is the sixteenth issue of NASA's USSR Life Sciences Digest. It contains abstracts of 57 papers published in Russian language periodicals or presented at conferences and of 2 new Soviet monographs. Selected abstracts are illustrated with figures and tables from the original. An additional feature is the review of a book concerned with metabolic response to the stress of space flight. The abstracts included in this issue are relevant to 33 areas of space biology and medicine. These areas are: adaptation, biological rhythms, bionics, biospherics, body fluids, botany, cardiovascular and respiratory systems, developmental biology, endocrinology, enzymology, exobiology, gastrointestinal system, genetics, gravitational biology, habitability and environmental effects, hematology, human performance, immunology, life support systems, man-machine systems, mathematical modeling, metabolism, microbiology, musculoskeletal system, neurophysiology, nutrition, operational medicine, perception, personnel selection, psychology, radiobiology, reproductive biology, and space biology

First North American case of Hemoglobin Shepherds Bush (β 74[E18] Gly → Asp) in a central Pennsylvania family

BACKGROUND: Hemoglobin Shepherds Bush (Human Genome Variation Society name: HBB:c.224G > A) is an unstable hemoglobin variant resulting from a β 74 GGC to GAC mutation (Gly to Asp) that manifests clinically as hemolytic anemia or gall bladder disease due to chronic subclinical hemolysis. CASE PRESENTATION: We report a Pennsylvania family of English descent with this condition, first noticed in a 6-year-old female. The proband presented with splenomegaly, fatigue, dark urine and an elevated indirect bilirubin. Hemoglobin identification studies and subsequent genetic testing performed according to a systematic algorithm elucidated the diagnosis of Hb Shepherds Bush. CONCLUSIONS: This is the first case of this rare hemoglobin variant identified in North America to our knowledge. It was identified using a systematic algorithm of diagnostic tests that should be followed whenever considering a rare hemoglobinopathy as part of the differential diagnosis

Self-reported worst injuries in women's Australian football identify lower limb injuries as a prevention priority

BACKGROUND: Increasing participation by women in Australian football (AF) has made understanding their specific injury prevention needs a priority. In other sports, men and women have different injury profiles. This study aims to provide the first overview of self-reported injuries in women's AF. METHODS: Nationwide survey of women aged 17+ years who played in an AF competition was conducted following the 2014 playing season. The players' self-reported worst injury from the 2014 season is presented according to injury type, body part injured, treatment sought and games/training missed. RESULTS: Three-quarters of 553 respondents (n=431, 78%) reported at least 1 injury. Over half (n=235, 55%) of injuries were to the lower limb. Ankle ligament tears/sprains (n=50, 12% of all injuries) and knee ligament tears/sprains (n=45, 10%) were most frequent lower limb injuries reported. Two-thirds (65%) of all lower limb injuries led to at least 1 missed game. Of 111 (26% of all injuries) upper limb injuries reported, over half (n=57, 62%) were to the hand/fingers/thumb, including fractures (n=28, 6% of all injuries), ligament tears/sprains (n=18, 4%) and dislocations (n=11, 3%). Half of the upper limb injuries (51%) resulted in players missing matches/training. CONCLUSIONS: The most frequent self-reported worst injuries for women playing AF were joint damage to the ankle and knee. A prospective injury study is needed to confirm the causes and rate of these lower limb injuries to identify the most suitable prevention interventions

Changes in Legislation of Civic Associations and Societies and Analysis of the Selected Society Funding

Import 04/11/2015Tato diplomová práce sleduje jeden z dopadů nedávné rekodifikace soukromého práva v českém právním řádu. Díky tomu dochází k představení transformačních možností občanského sdružení na nové právní formy. Následně je vybrána nejvhodnější varianta a tato zvolená přeměna je představena na konkrétní organizaci. Nakonec dochází k analýze hospodaření zvolené organizace a zobrazení návrhů na zlepšení její finanční situace.This thesis follows one of the impact od recent recodification od civil law in the czech legal order. Due to that show possibilities of transformations of the civic association to the new legal form. Subsequently, the best option is selected and the selected transformation is introduced to a specific organization. Finally, there is a financial analysis of the selected organization and display of proposals to improve its financial situation.117 - Katedra účetnictvídobř

Visualizing Recreational Trails: Montgomery County, Maryland

Final project for URSP 688M (Spring 2018). University of Maryland, College Park.At the request of the Montgomery County Department of Parks, eight county recreation trails were visualized via 360° photos and video, to help develop a state-of-the-art bike stress index tailored toward mountain bike trails. Using the Google Street View platform to publish photos online as well as several GIS open-source datasets and analytic tools, approximately 60 miles of trail were successfully visualized, and four mountain biking trails were stress-indexed. With the images and stress analysis methodology in hand, the department has the opportunity to lead the nation in visualizing recreation trails by integrating the data products into their online trail web-map. The project deliverables also provide a resource for trail planners and managers who strive to convey variable trail conditions to new and local trail users from anywhere in the world.Montgomery Count

SB04-22/23: Resolution Authorizing Approval of Staff Senate Signature of Bear Necessities Statement to University Administration

Passed during May 10, 2023 Staff Senate meeting. Documents from the May 10, 2023 meeting of the University of Montana S by University of Montana--Missoula. Staff Senate (umt.edu) Resolution authorizing approval of Staff Senate to sign support to the ASUM Bear Necessities statement to the University of Montana Administration. Resolution Authored by Kat Cowley. Additional Authors, including Cowley, listed for letter. Letter discusses concerns regarding the status of marginalized and vulnerable student populations and offers suggestions on some ways the University of Montana can support students at a basic human level. These include continued advocacy for increase support from the State of Montana, increased housing availability, meal plan affordability, open education resources, campus accessibility, and addressing staffing issues

Vijana Vijiweni II: A cluster-randomized trial to evaluate the efficacy of a microfinance and peer health leadership intervention for HIV and intimate partner violence prevention among social networks of young men in Dar es Salaam Global health

BackgroundIntimate partner violence (IPV) and sexually transmitted infections (STIs), including HIV, remain important public health problems with devastating health effects for men and women in sub-Saharan Africa. There have been calls to engage men in prevention efforts, however, we lack effective approaches to reach and engage them. Social network approaches have demonstrated effective and sustained outcomes on changing risk behaviors in the U.S. Our team has identified and engaged naturally occurring social networks comprised mostly of young men in Dar es Salaam in an intervention designed to jointly reduce STI incidence and the perpetration of IPV. These stable networks are locally referred to as “camps.” In a pilot study we demonstrated the feasibility and acceptability of a combined microfinance and peer health leadership intervention within these camp-based peer networks.Methods designWe are implementing a cluster-randomized trial to evaluate the efficacy of an intervention combining microfinance with health leadership training in 60 camps in Dar es Salaam, Tanzania. Half of the camps have been randomized to the intervention arm, and half to a control arm. The camps in the intervention arm will receive a combined microfinance and health leadership intervention for a period of two years. The camps in the control arm will receive a delayed intervention. We have enrolled 1,258 men across the 60 study camps. Behavioral surveys will be conducted at baseline, 12-months post intervention launch and 30-month post intervention launch and biological samples will be drawn to test for Neisseria gonorrhea (NG), Chlamydia trachomatis (CT), and Trichomonas vaginalis (TV) at baseline and 30-months. The primary endpoints for assessing intervention impact are IPV perpetration and STI incidence.DiscussionThis is the first cluster-randomized trial targeting social networks of men in sub-Saharan Africa that jointly addresses HIV and IPV perpetration and has both biological and behavioral endpoints. Effective approaches to engage men in HIV and IPV prevention are needed in low resource, high prevalence settings like Tanzania. If we determine that this approach is effective, we will examine how to adapt and scale up this approach to other urban, sub-Saharan African settings.Trial registrationClinical Trials.gov: NCT01865383. Registration date: May 24, 2013

Development and Reporting of Prediction Models: Guidance for Authors From Editors of Respiratory, Sleep, and Critical Care Journals

Prediction models aim to use available data to predict a health state or outcome that has not yet been observed. Prediction is primarily relevant to clinical practice, but is also used in research, and administration. While prediction modeling involves estimating the relationship between patient factors and outcomes, it is distinct from casual inference. Prediction modeling thus requires unique considerations for development, validation, and updating. This document represents an effort from editors at 31 respiratory, sleep, and critical care medicine journals to consolidate contemporary best practices and recommendations related to prediction study design, conduct, and reporting. Herein, we address issues commonly encountered in submissions to our various journals. Key topics include considerations for selecting predictor variables, operationalizing variables, dealing with missing data, the importance of appropriate validation, model performance measures and their interpretation, and good reporting practices. Supplemental discussion covers emerging topics such as model fairness, competing risks, pitfalls of “modifiable risk factors”, measurement error, and risk for bias. This guidance is not meant to be overly prescriptive; we acknowledge that every study is different, and no set of rules will fit all cases. Additional best practices can be found in the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines, to which we refer readers for further details

Alphacoronaviruses in New World Bats: Prevalence, Persistence, Phylogeny, and Potential for Interaction with Humans

Bats are reservoirs for many different coronaviruses (CoVs) as well as many other important zoonotic viruses. We sampled feces and/or anal swabs of 1,044 insectivorous bats of 2 families and 17 species from 21 different locations within Colorado from 2007 to 2009. We detected alphacoronavirus RNA in bats of 4 species: big brown bats (Eptesicus fuscus), 10% prevalence; long-legged bats (Myotis volans), 8% prevalence; little brown bats (Myotis lucifugus), 3% prevalence; and western long-eared bats (Myotis evotis), 2% prevalence. Overall, juvenile bats were twice as likely to be positive for CoV RNA as adult bats. At two of the rural sampling sites, CoV RNAs were detected in big brown and long-legged bats during the three sequential summers of this study. CoV RNA was detected in big brown bats in all five of the urban maternity roosts sampled throughout each of the periods tested. Individually tagged big brown bats that were positive for CoV RNA and later sampled again all became CoV RNA negative. Nucleotide sequences in the RdRp gene fell into 3 main clusters, all distinct from those of Old World bats. Similar nucleotide sequences were found in amplicons from gene 1b and the spike gene in both a big-brown and a long-legged bat, indicating that a CoV may be capable of infecting bats of different genera. These data suggest that ongoing evolution of CoVs in bats creates the possibility of a continued threat for emergence into hosts of other species. Alphacoronavirus RNA was detected at a high prevalence in big brown bats in roosts in close proximity to human habitations (10%) and known to have direct contact with people (19%), suggesting that significant potential opportunities exist for cross-species transmission of these viruses. Further CoV surveillance studies in bats throughout the Americas are warranted