In Silico Synchronization of Cellular Populations Through Expression Data Deconvolution

Cellular populations are typically heterogenous collections of cells at different points in their respective cell cycles, each with a cell cycle time that varies from individual to individual. As a result, true single-cell behavior, particularly that which is cell-cycle--dependent, is often obscured in population-level (averaged) measurements. We have developed a simple deconvolution method that can be used to remove the effects of asynchronous variability from population-level time-series data. In this paper, we summarize some recent progress in the development and application of our approach, and provide technical updates that result in increased biological fidelity. We also explore several preliminary validation results and discuss several ongoing applications that highlight the method's usefulness for estimating parameters in differential equation models of single-cell gene regulation.Comment: accepted for the 48th ACM/IEEE Design Automation Conferenc

The Association Between Pelvic Discomfort and Erectile Dysfunction in Adult Male Bicyclists.

BackgroundBicycle riding's impact on erectile function remains a topic of great interest given cycling's popularity as a mode of transportation and exercise.AimWe evaluated risk factors for sexual dysfunction in male cyclists with the primary intention of determining if genital/pelvic pain and numbness are associated with erectile dysfunction (ED).MethodsWe surveyed male cyclists using an online anonymous questionnaire. Cyclists were queried on their demographics, cycling experience, and sexual function using the Sexual Health Inventory for Men (SHIM). ED was diagnosed when a completed SHIM score was <22. Regression analysis was used to evaluate the risk of ED in men with genital/pelvic pain or numbness after riding. The survey was designed in the United States.OutcomesQuantitative characterization of cycling habits, onset and timing of genital pain and numbness, and SHIM score.ResultsA total of 1635 participants completed the survey. A majority of men were over the age of 50 (58%, 934/1,607), Caucasian (88%, 1,437/1,635), had been active cyclists for over 10 years (63%, 1,025/1,635) and used road bikes (97%, 1,578/1,635). Overall, 22%, 30%, and 57% of men reported ED, genital pain, and genital numbness, respectively. While controlling for cohort demographics, body mass index, cycling intensity and equipment, and medical comorbidities, no saddle characteristics were associated with the risk of developing genital numbness. However, men reporting penile numbness were at higher risk of reporting ED (odds ratio [OR] = 1.453, P = .048). In addition, quicker onset of numbness and resolution of numbness within a day was associated with impaired erectile function. For example, numbness occurring less than 1 hour after cycling had greater odds of leading to ED than numbness after 5 hours (OR = 2.002, P = .032). Similarly, genital pain occurring less than 1 hour (OR = 2.466, P = .031) after cycling was associated with higher ED risk.Strengths & limitationsStrengths include a large sample size of high-intensity cyclists and validated questionnaire use. Limitations include reliance on anonymous self-reported survey data and minimal inquiry into the riding preferences and terrain traversed by cyclists.ConclusionsPelvic pain and numbness are common complaints among male riders in the United States. Men with such complaints are more likely to also report ED especially if it occurs earlier in the ride. Although direction of causality and temporality are uncertain, alleviation of factors resulting in pelvic discomfort may reduce cycling's impact on sexual function. Such interventions are critical given that cycling for both active travel and aerobic exercise confers numerous health benefits. Balasubramanian A, Yu J, Breyer BN, et al. The Association Between Pelvic Discomfort and Erectile Dysfunction in Adult Male Bicyclists. J Sex Med 2020;17:919-929

Linking Decision Theory and Quantitative Microbial Risk Assessment: Tradeoffs Between Compliance and Efficacy for Waterborne Disease Interventions

Achieving health gains from the U.N. Sustainable Development Goals of universal coverage for water and sanitation will require interventions that can be widely adopted and maintained. Effectiveness—how an intervention performs based on actual use—as opposed to efficacy will therefore be central to evaluations of new and existing interventions. Incomplete compliance—when people do not always use the intervention and are therefore exposed to contamination—is thought to be responsible for the lower‐than‐expected risk reductions observed from water, sanitation, and hygiene interventions based on their efficacy at removing pathogens. We explicitly incorporated decision theory into a quantitative microbial risk assessment model. Specifically, we assume that the usability of household water treatment (HWT) devices (filters and chlorine) decreases as they become more efficacious due to issues such as taste or flow rates. Simulations were run to examine the tradeoff between device efficacy and usability. For most situations, HWT interventions that trade lower efficacy (i.e., remove less pathogens) for higher compliance (i.e., better usability) contribute substantial reductions in diarrheal disease risk compared to devices meeting current World Health Organization efficacy guidelines. Recommendations that take into account both the behavioral and microbiological properties of treatment devices are likely to be more effective at reducing the burden of diarrheal disease than current standards that only consider efficacy.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151809/1/risa13381.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151809/2/risa13381-sup-0001-Appendix.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151809/3/risa13381_am.pd

Accountability in patenting of federally funded research

Bayh-Dole allows academic grantees to patent federally-funded research for purposes of promoting the commercialization of this research. To ensure commercialization goals are achieved, the Act requires grantees to report to funding agencies not only the existence of federally-funded patents but also utilization efforts they and their licensees/assignees are making. Although reporting is a cornerstone of accountability under Bayh-Dole, information about grantee compliance with reporting requirements is incomplete and dated. In fact, the last significant study of the question dates back to the late 1990s and analyzes only 633 patents. Since that time, concerns have emerged that federally-funded university patents are being asserted improperly against independent commercializers or even assigned to so-called “patent trolls.” This article provides fresh evidence indicating substantial under-reporting of the existence of federal funding in over 30,000 academic biomedical patents issued between 1980 to 2007. The article finds substantial under-reporting of federal funding even in the case of patents on FDA-approved drugs, which should presumably receive significant attention from universities. Grantees’ failure to report federal funding suggests similar, or even more significant, noncompliance with requirements to report utilization information. However, compliance with reporting requirements on utilization cannot be assessed because of secrecy associated with relevant government databases. Accordingly, the article makes a fresh argument that the Commerce Department, which has the requisite regulatory authority, work with funding agencies, to improve transparency. Greater transparency would not only motivate grantees to improve reporting but would also allow assessment of whether grantee patent management is actually achieving Bayh-Dole\u27s utilization goals

Discrete interband mutual focusing in nonlinear photonic lattices

We study nonlinear coupling of mutually incoherent beams associated with different Floquet-Bloch waves in a one-dimensional optically-induced photonic lattice. We demonstrate experimentally how such interactions lead to asymmetric mutual focusing and, for waves with opposite diffraction properties, to simultaneous focusing and defocusing as well as discreteness-induced beam localization and reshaping effects.Comment: 8 pages, 6 figures. To download the associated .avi movie, go to http://www.rsphysse.anu.edu.au/~crr124/mut_focus

The Index Of Narrative Microstructure: A Clinical Tool For Analyzing School-Age Children's Narrative Performances

Purpose: This research was conducted to develop a clinical tool-the Index of Narrative Microstructure (INMIS)-that would parsimoniously account for important microstructural aspects of narrative production for school-age children. The study provides field test age- and grade-based INMIS values to aid clinicians in making normative judgments about microstructural aspects of pupils' narrative performance. Method: Narrative samples using a single-picture elicitation context were collected from 250 children age 5-12 years and then transcribed and segmented into T-units. A T-unit consists of a single main clause and any dependent constituents. The narrative transcripts were then coded and analyzed to document a comprehensive set of microstructural indices. Results: Factor analysis indicated that narrative microstructure consisted of 2 moderately related factors. The Productivity factor primarily comprised measures of word output, lexical diversity, and T-unit output. The Complexity factor comprised measures of syntactic organization, with mean length of T-units in words and proportion of complex T-units loading most strongly. Principal components analysis was used to provide a linear combination of 8 variables to approximate the 2 factors. Formulas for calculating a student's performance on the 2 factors using 8 narrative measures are provided. Conclusions: This study provided a method for professionals to calculate INMIS scores for narrative Productivity and Complexity for comparison against field test data for age (5- to 12-year-old) or grade (kindergarten to Grade 6) groupings. INMIS scores complement other tools in evaluating a child's narrative performance specifically and language abilities more generally.Communication Sciences and Disorder

Deformation Energy Minima at Finite Mass Asymmetry

A very general saddle point nuclear shape may be found as a solution of an integro-differential equation without giving apriori any shape parametrization. By introducing phenomenological shell corrections one obtains minima of deformation energy for binary fission of parent nuclei at a finite (non-zero) mass asymmetry. Results are presented for reflection asymmetric saddle point shapes of thorium and uranium even-mass isotopes with A=226-238 and A=230-238 respectively.Comment: 5 pages, 2 Postscript figures, REVTeX, Version 4.

Fomite-mediated transmission as a sufficient pathway: a comparative analysis across three viral pathogens

Abstract Background Fomite mediated transmission can be an important pathway causing significant disease transmission in number of settings such as schools, daycare centers, and long-term care facilities. The importance of these pathways relative to other transmission pathways such as direct person-person or airborne will depend on the characteristics of the particular pathogen and the venue in which transmission occurs. Here we analyze fomite mediated transmission through a comparative analysis across multiple pathogens and venues. Methods We developed and analyzed a compartmental model that explicitly accounts for fomite transmission by including pathogen transfer between hands and surfaces. We consider two sub-types of fomite-mediated transmission: direct fomite (e.g., shedding onto fomites) and hand-fomite (e.g., shedding onto hands and then contacting fomites). We use this model to examine three pathogens with distinct environmental characteristics (influenza, rhinovirus, and norovirus) in four venue types. To parameterize the model for each pathogen we conducted a thorough literature search. Results Based on parameter estimates from the literature the reproductive number ( R 0 $\mathcal {R}_{0}$ ) for the fomite route for rhinovirus and norovirus is greater than 1 in nearly all venues considered, suggesting that this route can sustain transmission. For influenza, on the other hand, R 0 $\mathcal {R}_{0}$ for the fomite route is smaller suggesting many conditions in which the pathway may not sustain transmission. Additionally, the direct fomite route is more relevant than the hand-fomite route for influenza and rhinovirus, compared to norovirus. The relative importance of the hand-fomite vs. direct fomite route for norovirus is strongly dependent on the fraction of pathogens initially shed to hands. Sensitivity analysis stresses the need for accurate measurements of environmental inactivation rates, transfer efficiencies, and pathogen shedding. Conclusions Fomite-mediated transmission is an important pathway for the three pathogens examined. The effectiveness of environmental interventions differs significantly both by pathogen and venue. While fomite-based interventions may be able to lower R 0 $\mathcal {R}_{0}$ for fomites below 1 and interrupt transmission, rhinovirus and norovirus are so infectious ( R 0 > > 1 $\mathcal {R}_{0}>>1$ ) that single environmental interventions are unlikely to interrupt fomite transmission for these pathogens.https://deepblue.lib.umich.edu/bitstream/2027.42/146145/1/12879_2018_Article_3425.pd