Exploring tradeoffs in pleiotropy and redundancy using evolutionary computing

Evolutionary computation algorithms are increasingly being used to solve optimization problems as they have many advantages over traditional optimization algorithms. In this paper we use evolutionary computation to study the trade-off between pleiotropy and redundancy in a client-server based network. Pleiotropy is a term used to describe components that perform multiple tasks, while redundancy refers to multiple components performing one same task. Pleiotropy reduces cost but lacks robustness, while redundancy increases network reliability but is more costly, as together, pleiotropy and redundancy build flexibility and robustness into systems. Therefore it is desirable to have a network that contains a balance between pleiotropy and redundancy. We explore how factors such as link failure probability, repair rates, and the size of the network influence the design choices that we explore using genetic algorithms.Comment: 10 pages, 6 figure

Two Weeks of Ischemic Conditioning Improves Walking Speed and Reduces Neuromuscular Fatigability in Chronic Stroke Survivors

This pilot study examined whether ischemic conditioning (IC), a noninvasive, cost-effective, and easy-to-administer intervention, could improve gait speed and paretic leg muscle function in stroke survivors. We hypothesized that 2 wk of IC training would increase self-selected walking speed, increase paretic muscle strength, and reduce neuromuscular fatigability in chronic stroke survivors. Twenty-two chronic stroke survivors received either IC or IC Sham on their paretic leg every other day for 2 wk (7 total sessions). IC involved 5-min bouts of ischemia, repeated five times, using a cuff inflated to 225 mmHg on the paretic thigh. For IC Sham, the cuff inflation pressure was 10 mmHg. Self-selected walking speed was assessed using the 10-m walk test, and paretic leg knee extensor strength and fatigability were assessed using a Biodex dynamometer. Self-selected walking speed increased in the IC group (0.86 ± 0.21 m/s pretest vs. 1.04 ± 0.22 m/s posttest, means ± SD; P\u3c 0.001) but not in the IC Sham group (0.92 ± 0.47 m/s pretest vs. 0.96 ± 0.46 m/s posttest; P= 0.25). Paretic leg maximum voluntary contractions were unchanged in both groups (103 ± 57 N·m pre-IC vs. 109 ± 65 N·m post-IC; 103 ± 59 N·m pre-IC Sham vs. 108 ± 67 N·m post-IC Sham; P = 0.81); however, participants in the IC group maintained a submaximal isometric contraction longer than participants in the IC Sham group (278 ± 163 s pre-IC vs. 496 ± 313 s post-IC, P = 0.004; 397 ± 203 s pre-IC Sham vs. 355 ± 195 s post-IC Sham; P = 0.46). The results from this pilot study thus indicate that IC training has the potential to improve walking speed and paretic muscle fatigue resistance poststroke

Transcranial optogenetic mapping revealed longitudinal changes in motor maps of ipsi-lesional and contra-lesional cortex following mild traumatic brain injury

poster abstractAbstract: Victims of traumatic brain injury (TBI) suffer short- and long-term physical, cognitive, behavioral and emotional impairments that depend on the severity of the injury. Mechanical and cellular alterations in mild TBI can cause global change in inhibition and excitation on the neuronal network level even in the absence of histologically significant cell injury. To understand functional changes of the motor cortex following closed-head mTBI, we applied an optogenetic stimulation method to map motor cortex activity in channelrhodopsins 2 (ChR2) transgenic mice. A closed-head mTBI was performed via a cortical impact device and longitudinal optogenetic mapping of the forelimb areas of the ipsilateral and contralateral motor cortex were done at multiple time points post injury. Optogenetically evoked responses were recorded with electromyography (EMG) in the bicep brachii of the forelimb and with electroencephalography (EEG) in the brain. The mapping revealed immediate suppression of EMG response of the injured ipsilateral motor cortex post mTBI, which was then followed by an enhanced response. The maps also showed a marked increased in the number of responsive spots in the contralateral motor cortex within the first 12 hours. In addition, rotarod behavioral test show a decrease in motor response within first two days after mTBI follows by recovery. In vitro calcium imaging of GCaMP6 cortical slice showed a decrease in intracellular calcium signal at 2 hours post in injury. These data suggest that excitable cortical neurons exhibit short-term impairment locally (epsilateral) as a result of the injury while long-term contralateral hyperexcitability may act as a functional compensatory mechanism. Our data suggests optogenetic mapping of the motor cortex is a valuable technique for longitudinal study of brain functions following mTBI, and that it revealed post-injury hyperexcitability may play an adaptive role in modifying the functional organization of the cortex in response to the short-term activity lost. These longitudinal sequelae may underlie posttraumatic neurological deficits and brain functional recovery

An experimental test of deviant modeling

Objectives: Test the effect of deviant peer modeling on theft as conditioned by verbal support for theft and number of deviant models. Methods: Two related randomized experiments in which participants were given a chance to steal a gift card (ostensibly worth $15) from the table in front of them. Each experiment had a control group, a verbal prompting group in which confederate(s) endorsed stealing, a behavioral modeling group in which confederate(s) committed theft, and a verbal prompting plus behavioral modeling group in which confederate(s) did both. The first experiment used one confederate; the second experiment used two. The pooled sample consisted of 335 undergraduate students. Results: Participants in the verbal prompting plus behavioral modeling group were most likely to steal followed by the behavioral modeling group. Interestingly, behavioral modeling was only influential when two confederates were present. There were no thefts in either the control or verbal prompting groups regardless of the number of confederates. Conclusions: Behavioral modeling appears to be the key mechanism, though verbal support can strengthen the effect of behavioral modeling.UW/SSHRC Seed Gran

Gamma ray production in inelastic scattering of neutrons produced by cosmic muons in 56^{56}Fe

We report on the study of the intensities of several gamma lines emitted after the inelastic scattering of neutrons in $^{56}$Fe. Neutrons were produced by cosmic muons passing the 20t massive iron cube placed at the Earth's surface and used as a passive shield for the HPGe detector. Relative intensities of detected gamma lines are compared with the results collected in the same iron shield by the use of $^{252}$Cf neutrons. Assessment against the published data from neutron scattering experiments at energies up to 14 MeV is also provided

Promoting Community Health Research Partnerships Through a Small Grants Program: Processes and Lessons Learned

While there are multiple ways to engage communities in health research, one approach is through partnership-based research in which community representatives are involved as intentional partners in the research process, from conceptualization and co-creation to implementation, analysis, interpretation, and dissemination. However, there remain numerous challenges to supporting and sustaining such partnerships. Since its launch in 2019, the integrated Translational Health Research Institute of Virginia (iTHRIV) has sought to foster community engaged health research among its four research/clinical institutions through a community partnership-based grant program. Over five funding cycles, iTHRIV has awarded 14 one-year research grants addressing topics such as opioid use disorder, cancer, hepatitis C and autism. Each funding cycle has provided valuable experience and feedback toward iterative program refinements. Key lessons have included: 1) the Request For Proposals (RFP) must be very clear and community-vetted; 2) transparency regarding administrative burden required for compliance is critical to inform cost-benefit decisions; 3) giving different modes of communication, adequate and creative marketing of the RFP is necessary; 4) establishing a centralized program officer for all grantees facilitated post-award procedural navigation; 5) one year is insufficient to carry out most studies involving human subjects. Additionally, while the program anecdotally promoted collaborative partnerships, the true impact may be difficult to evaluate

Culturally adaptive storytelling intervention versus didactic intervention to improve hypertension control in Vietnam- 12 month follow up results: A cluster randomized controlled feasibility trial

INTRODUCTION: Vietnam is experiencing an epidemiologic transition with an increased prevalence of non-communicable diseases. The country needs novel, large-scale, and sustainable interventions to improve hypertension control. We report the 12 month follow-up results of a cluster randomized feasibility trial in Hung Yen province, Vietnam, which evaluated the feasibility and acceptability of two community-based interventions to improve hypertension control: a storytelling and a didactic intervention. METHODS: The storytelling intervention included stories in the patients\u27 own words about coping with hypertension and didactic content about the importance of healthy lifestyle behaviors in controlling elevated blood pressure levels. The didactic intervention included only didactic content, which were general recommendations for managing several important risk factors for hypertension and other non-communicable diseases. The storytelling intervention was delivered by two DVDs three months apart; the didactic intervention included only one DVD. The trial was conducted in patients with poorly controlled hypertension from 4 communes (communities), which were equally randomized to the two interventions. RESULTS: The mean age of the 160 patients was 66 years and 54% were men. Between baseline enrollment and the 12 month follow-up, mean systolic blood pressure declined by 10.8 mmHg (95% CI: 6.5-14.9) in the storytelling group and by 5.8 mmHg (95% CI: 1.6-10.0) in the didactic content group. The storytelling group also experienced more improvement in several health behaviors, including increased levels of physical activity and reduced consumption of salt and alcohol. CONCLUSIONS: We observed considerable long-term beneficial effects of both interventions, especially of our storytelling intervention, among patients with inadequately controlled hypertension. A large scale randomized trial should more systematically compare the short and long-term effectiveness of the two interventions in controlling hypertension. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02483780

Functional plasticity of antibacterial EndoU toxins.

Bacteria use several different secretion systems to deliver toxic EndoU ribonucleases into neighboring cells. Here, we present the first structure of a prokaryotic EndoU toxin in complex with its cognate immunity protein. The contact-dependent growth inhibition toxin CdiA-CTSTECO31 from Escherichia coli STEC_O31 adopts the eukaryotic EndoU fold and shares greatest structural homology with the nuclease domain of coronavirus Nsp15. The toxin contains a canonical His-His-Lys catalytic triad in the same arrangement as eukaryotic EndoU domains, but lacks the uridylate-specific ribonuclease activity that characterizes the superfamily. Comparative sequence analysis indicates that bacterial EndoU domains segregate into at least three major clades based on structural variations in the N-terminal subdomain. Representative EndoU nucleases from clades I and II degrade tRNA molecules with little specificity. In contrast, CdiA-CTSTECO31 and other clade III toxins are specific anticodon nucleases that cleave tRNAGlu between nucleotides C37 and m2 A38. These findings suggest that the EndoU fold is a versatile scaffold for the evolution of novel substrate specificities. Such functional plasticity may account for the widespread use of EndoU effectors by diverse inter-bacterial toxin delivery systems

Cognition and education benefits of increased hemoglobin and blood oxygenation in children with sickle cell disease

BACKGROUND: Among individuals with sickle cell disease (SCD), decreased hemoglobin is associated with lower oxygen saturation (SpO2) and increased risk of stroke, both of which are associated with lower intelligence quotient (IQ) scores. Thus, increasing hemoglobin and SpO2 in individuals with SCD may increase IQ and educational attainment. METHODS: A cohort simulation model was built to determine academic performance and educational attainment based on cognitive function (measured by IQ) of a pediatric SCD cohort randomly assigned to treatment and control groups. The model contained two key stages: childhood (\u3c10 years) and adolescence (≥10 years). In stage 1, increased hemoglobin and increased SpO2 (assigned to the treatment group) were determinants of higher IQ, prevention of IQ deterioration over time. Increased hemoglobin was also a determinant of decreased stroke risk. In stage 2, improvement in adolescent IQ as a result of treatment was a determinant of academic performance. RESULTS: In a simulated cohort of 2000 children and adolescents with SCD (52.5% female, 50% treated), stroke incidence was predicted to be 44.4% lower among the treated group than the untreated group (4.5% versus 8.1%, respectively). The average IQ among the treated group was estimated to be 91.1 compared with 82.9 in the untreated group (a 9.9% difference; P\u3c0.001). Finally, high school (≥12 years of education) completion rates were estimated to be 64.7% higher among the treated group: 76.1% of the treated group was projected to complete high school compared with 46.2% of the untreated group. CONCLUSIONS: Our model predicts that an average improvement in hemoglobin of 1.1 g/dL (11 g/L) among individuals with SCD may be associated with improved neurocognition and educational outcomes. These improvements may also generate benefits not captured by our model, including improved quality of life, employment, and income