The IkB–NF-kB Signaling Module: Temporal Control and Selective Gene Activation

Nuclear localization of the transcriptional activator NF-κB (nuclear factor κB) is controlled in mammalian cells by three isoforms of NF-κB inhibitor protein: IκBα, -β, and -ɛ. Based on simplifying reductions of the IκB–NF-κB signaling module in knockout cell lines, we present a computational model that describes the temporal control of NF-κB activation by the coordinated degradation and synthesis of IκB proteins. The model demonstrates that IκBα is responsible for strong negative feedback that allows for a fast turn-off of the NF-κB response, whereas IκBβ and -ɛ function to reduce the system's oscillatory potential and stabilize NF-κB responses during longer stimulations. Bimodal signal-processing characteristics with respect to stimulus duration are revealed by the model and are shown to generate specificity in gene expression

Effective Conformal Theory and the Flat-Space Limit of AdS

We develop the idea of an effective conformal theory describing the low-lying spectrum of the dilatation operator in a CFT. Such an effective theory is useful when the spectrum contains a hierarchy in the dimension of operators, and a small parameter whose role is similar to that of 1/N in a large N gauge theory. These criteria insure that there is a regime where the dilatation operator is modified perturbatively. Global AdS is the natural framework for perturbations of the dilatation operator respecting conformal invariance, much as Minkowski space naturally describes Lorentz invariant perturbations of the Hamiltonian. Assuming that the lowest-dimension single-trace operator is a scalar, O, we consider the anomalous dimensions, gamma(n,l), of the double-trace operators of the form O (del^2)^n (del)^l O. Purely from the CFT we find that perturbative unitarity places a bound on these dimensions of |gamma(n,l)|<4. Non-renormalizable AdS interactions lead to violations of the bound at large values of n. We also consider the case that these interactions are generated by integrating out a heavy scalar field in AdS. We show that the presence of the heavy field "unitarizes" the growth in the anomalous dimensions, and leads to a resonance-like behavior in gamma(n,l) when n is close to the dimension of the CFT operator dual to the heavy field. Finally, we demonstrate that bulk flat-space S-matrix elements can be extracted from the large n behavior of the anomalous dimensions. This leads to a direct connection between the spectrum of anomalous dimensions in d-dimensional CFTs and flat-space S-matrix elements in d+1 dimensions. We comment on the emergence of flat-space locality from the CFT perspective.Comment: 46 pages, 2 figures. v2: JHEP published versio

Feasibility and acceptability of telehealth coaching to promote healthy eating in chronic kidney disease: A mixed-methods process evaluation

Objective To evaluate the feasibility and acceptability of a personalised telehealth intervention to support dietary self-management in adults with stage 3-4 chronic kidney disease (CKD). Design Mixed-methods process evaluation embedded in a randomised controlled trial. Participants People with stage 3-4 CKD (estimated glomerular filtration rate [eGFR]15-60 mL/min/1.73 m 2). Setting Participants were recruited from three hospitals in Australia and completed the intervention in ambulatory community settings. Intervention The intervention group received one telephone call per fortnight and 2-8 tailored text messages for 3 months, and then 4-12 tailored text messages for 3 months without telephone calls. The control group received usual care for 3 months then non-tailored education-only text messages for 3 months. Main outcome measures Feasibility (recruitment, non-participation and retention rates, intervention fidelity and participant adherence) and acceptability (questionnaire and semistructured interviews). Statistical analyses performed Descriptive statistics and qualitative content analysis. Results Overall, 80/230 (35%) eligible patients who were approached consented to participate (mean±SD age 61.5±12.6 years). Retention was 93% and 98% in the intervention and control groups, respectively, and 96% of all planned intervention calls were completed. All participants in the intervention arm identified the tailored text messages as useful in supporting dietary self-management. In the control group, 27 (69%) reported the non-tailored text messages were useful in supporting change. Intervention group participants reported that the telehealth programme delivery methods were practical and able to be integrated into their lifestyle. Participants viewed the intervention as an acceptable, personalised alternative to face-face clinic consultations, and were satisfied with the frequency of contact. Conclusions This telehealth-delivered dietary coaching programme is an acceptable intervention which appears feasible for supporting dietary self-management in stage 3-4 CKD. A larger-scale randomised controlled trial is needed to evaluate the efficacy of the coaching programme on clinical and patient-reported outcomes. Trial registration number ACTRN12616001212448; Results

Age-Dependence of Femoral Strength in White Women and Men

Although age-related variations in areal bone mineral density (aBMD) and the prevalence of osteoporosis have been well characterized, there is a paucity of data on femoral strength in the population. Addressing this issue, we used finite-element analysis of quantitative computed tomographic scans to assess femoral strength in an age-stratified cohort of 362 women and 317 men, aged 21 to 89 years, randomly sampled from the population of Rochester, MN, and compared femoral strength with femoral neck aBMD. Percent reductions over adulthood were much greater for femoral strength (55% in women, 39% in men) than for femoral neck aBMD (26% in women, 21% in men), an effect that was accentuated in women. Notable declines in strength started in the mid-40s for women and one decade later for men. At advanced age, most of the strength deficit for women compared with men was a result of this decade-earlier onset of strength loss for women, this factor being more important than sex-related differences in peak bone strength and annual rates of bone loss. For both sexes, the prevalence of “low femoral strength” (<3000 N) was much higher than the prevalence of osteoporosis (femoral neck aBMD T-score of −2.5 or less). We conclude that age-related declines in femoral strength are much greater than suggested by age-related declines in femoral neck aBMD. Further, far more of the elderly may be at high risk of hip fracture because of low femoral strength than previously assumed based on the traditional classification of osteoporosis. © 2010 American Society for Bone and Mineral Research

Novel Barriers to Prevent Dogwood Borer (Lepidoptera: Sesiidae) and Rodent Damage in Apple Plantings

We evaluated a combination of noninsecticidal alternatives to control trunk-damaging dogwood borer, Synanthedon scitula (Harris), consisting of novel barrier technologies, used alone or in combination with mating disruption. Barrier formulations evaluated included fibrous barriers of nonwoven ethylene vinyl acetate (EVA) and nonfibrous barriers of rubberized paint (elastomer) used in building coatings. To examine efficacy of dogwood borer control in orchards, all barrier trials were replicated in field tests, both in combination with mating disruption and without it. Trunk inspections to determine whether mating disruption and barriers effectively reduced actual tree infestation showed pheromone disruption significantly reduced infestation compared with the untreated check, but was not as effective as trunk handgun sprays of chlorpyrifos. EVA trunk barriers were effective in preventing borer infestation compared with untreated trees. The elastomer did not differ from the check or the EVA treatment. There was no interaction between disruption and barrier treatments. Barrier field life and durability was assessed over 2 yr by comparing degradation over time due to weathering and other environmental effects including animal damage. The EVA persisted and remained more intact than the elastomer, but was in need of reapplication after 2 yr. Barriers were also screened for efficacy against voles in small-plot trials in nonorchard locations with known high vole pressure; they were tested either alone, combined with a repellent (thiram), or, in the case of the elastomer only, combined with an abrasive (sand). Only the EVA significantly lowered vole chewing damage relative to the untreated check

Fostering Physics Content and Pedagogy Learning by Future Physics Teachers via Student Authored YouTube Video Projects

We describe a curricular innovation for STEM teacher preparation -- the use of video projects in undergraduate and graduate physics courses for future physics teachers at SUNY Buffalo State. US courses were adapted under the guidance of our colleagues’ similar work at Universität zu Köln [1]. Our students prepared end of course short “proof of concept” rough video vignettes of 5-10min addressing both physics content and physics pedagogical topics. YouTube [2] example videos are provided, and insights are shared

Adding Student Video Projects to Physics Courses

Physics students have traditionally prepared many kinds of reports—laboratory, activity, project, and even book or article reports. Smartphones and YouTube videos are familiar cultural objects to current students, and our students use smartphone cameras to include photographs of apparatus, phenomena, hand-sketched figures, graphs, and mathematical equations in their physics reports. Here we present basic techniques for physics students to use smartphones and tablets to create short (\u3c 5 min) end-of-semester video projects. Our students mainly use Apple Computer’s iPad1 tablets, but also other tablets and various smartphones. Finally we discuss appropriate instructor expectations and grading. Similar non-physics student video reporting efforts were reported using video cameras by Kearney,2 and Hechter and Guy.

CRANKITE: a fast polypeptide backbone conformation sampler

Background: CRANKITE is a suite of programs for simulating backbone conformations of polypeptides and proteins. The core of the suite is an efficient Metropolis Monte Carlo sampler of backbone conformations in continuous three-dimensional space in atomic details. Methods: In contrast to other programs relying on local Metropolis moves in the space of dihedral angles, our sampler utilizes local crankshaft rotations of rigid peptide bonds in Cartesian space. Results: The sampler allows fast simulation and analysis of secondary structure formation and conformational changes for proteins of average length