Evolutionary and molecular foundations of multiple contemporary functions of the nitroreductase superfamily.

Insight regarding how diverse enzymatic functions and reactions have evolved from ancestral scaffolds is fundamental to understanding chemical and evolutionary biology, and for the exploitation of enzymes for biotechnology. We undertook an extensive computational analysis using a unique and comprehensive combination of tools that include large-scale phylogenetic reconstruction to determine the sequence, structural, and functional relationships of the functionally diverse flavin mononucleotide-dependent nitroreductase (NTR) superfamily (>24,000 sequences from all domains of life, 54 structures, and >10 enzymatic functions). Our results suggest an evolutionary model in which contemporary subgroups of the superfamily have diverged in a radial manner from a minimal flavin-binding scaffold. We identified the structural design principle for this divergence: Insertions at key positions in the minimal scaffold that, combined with the fixation of key residues, have led to functional specialization. These results will aid future efforts to delineate the emergence of functional diversity in enzyme superfamilies, provide clues for functional inference for superfamily members of unknown function, and facilitate rational redesign of the NTR scaffold

Adherence to Nutrition and Physical Activity Cancer Prevention Guidelines and Development of Colorectal Adenoma.

Adherence to the American Cancer Society's (ACS) Nutrition and Physical Activity Cancer Prevention Guidelines is associated with reductions in overall cancer incidence and mortality, including site-specific cancers such as colorectal cancer. We examined the relationship between baseline adherence to the ACS guidelines and (1) baseline adenoma characteristics and (2) odds of recurrent colorectal adenomas over 3 years of follow-up. Cross-sectional and prospective analyses with a pooled sample of participants from the Wheat Bran Fiber (n = 503) and Ursodeoxycholic Acid (n = 854) trials were performed. A cumulative adherence score was constructed using baseline self-reported data regarding body size, diet, physical activity and alcohol consumption. Multivariable logistic regression demonstrated significantly reduced odds of having three or more adenomas at baseline for moderately adherent (odds ratio [OR] = 0.67, 95% confidence intervals [CI]: 0.46⁻0.99) and highly adherent (OR = 0.50, 95% CI: 0.31⁻0.81) participants compared to low adherers (p-trend = 0.005). Conversely, guideline adherence was not associated with development of recurrent colorectal adenoma (moderate adherence OR = 1.16, 95% CI: 0.85⁻1.59, high adherence OR = 1.23, 95% CI: 0.85⁻1.79)

B-factory Signals for a Warped Extra Dimension

We study predictions for B-physics in a class of models, recently introduced, with a non-supersymmetric warped extra dimension. In these models few ($\sim 3$) TeV Kaluza-Klein masses are consistent with electroweak data due to bulk custodial symmetry. Furthermore, there is an analog of GIM mechanism which is violated by the heavy top quark (just as in SM) leading to striking signals at $B$-factories:(i) New Physics (NP) contributions to $\Delta F= 2$ transitions are comparable to SM. This implies that, within this NP framework, the success of SM unitarity triangle fit is a ``coincidence'' Thus, clean extractions of unitarity angles via e.g. $B \to \pi \pi,\rho \pi, \rho \rho, DK$ are likely to be affected, in addition to O(1) deviation from SM prediction in $B_s$ mixing. (ii) O(1) deviation from SM predictions for $B \to X_s l^+ l^-$ in rate as well as in forward-backward and direct CP asymmetry. (iii) Large mixing-induced CP asymmetry in radiative B decays, wherein the SM unamibgously predicts very small asymmetries. Also with KK masses 3 TeV or less, and with anarchic Yukawa masses, contributions to electric dipole moments of the neutron are roughly 20 times larger than the current experimental bound so that this framework has a "CP problem".Comment: On further consideration, we found that our framework does have a "CP problem" in that though contributions to neutron's electric dipole moment from CKM-like phases vanish at the one-loop level, sizeable contributions are induced by Majorana-like phases. Last sentence of abstract is changed along with para #3 and 4 on page

Integral constraints on the monodromy group of the hyperkahler resolution of a symmetric product of a K3 surface

Let M be a 2n-dimensional Kahler manifold deformation equivalent to the Hilbert scheme of length n subschemes of a K3 surface S. Let Mon be the group of automorphisms of the cohomology ring of M, which are induced by monodromy operators. The second integral cohomology of M is endowed with the Beauville-Bogomolov bilinear form. We prove that the restriction homomorphism from Mon to the isometry group O[H^2(M)] is injective, for infinitely many n, and its kernel has order at most 2, in the remaining cases. For all n, the image of Mon in O[H^2(M)] is the subgroup generated by reflections with respect to +2 and -2 classes. As a consequence, we get counter examples to a version of the weight 2 Torelli question, when n-1 is not a prime power.Comment: Version 3: Latex, 54 pages. Expository change

Dephasing due to Intermode Coupling in Superconducting Stripline Resonators

The nonlinearity exhibited by the kinetic inductance of a superconducting stripline couples stripline resonator modes together in a manner suitable for quantum non-demolition measurement of the number of photons in a given resonator mode. Quantum non-demolition measurement is accomplished by coherently driving another resonator mode, referred to as the detector mode, and measuring its response. We show that the sensitivity of such a detection scheme is directly related to the dephasing rate induced by such an intermode coupling. We show that high sensitivity is expected when the detector mode is driven into the nonlinear regime and operated close to a point where critical slowing down occurs

Deriving the Golden Ratio using a Scientific Calculator

In this article, we illustrate the use of a scientific calculator for exploring the Fibonacci sequence and the Golden Ratio. The calculator, equipped with a feature for setting up iterations, enables the process of creating a sequence which rapidly converges to the Golden Ratio

Game On? Smoking Cessation Through the Gamification of mHealth: A Longitudinal Qualitative Study

BACKGROUND: Finding ways to increase and sustain engagement with mHealth interventions has become a challenge during application development. While gamification shows promise and has proven effective in many fields, critical questions remain concerning how to use gamification to modify health behavior. OBJECTIVE: The objective of this study is to investigate how the gamification of mHealth interventions leads to a change in health behavior, specifically with respect to smoking cessation. METHODS: We conducted a qualitative longitudinal study using a sample of 16 smokers divided into 2 cohorts (one used a gamified intervention and the other used a nongamified intervention). Each participant underwent 4 semistructured interviews over a period of 5 weeks. Semistructured interviews were also conducted with 4 experts in gamification, mHealth, and smoking cessation. Interviews were transcribed verbatim and thematic analysis undertaken. RESULTS: Results indicated perceived behavioral control and intrinsic motivation acted as positive drivers to game engagement and consequently positive health behavior. Importantly, external social influences exerted a negative effect. We identified 3 critical factors, whose presence was necessary for game engagement: purpose (explicit purpose known by the user), user alignment (congruency of game and user objectives), and functional utility (a well-designed game). We summarize these findings in a framework to guide the future development of gamified mHealth interventions. CONCLUSIONS: Gamification holds the potential for a low-cost, highly effective mHealth solution that may replace or supplement the behavioral support component found in current smoking cessation programs. The framework reported here has been built on evidence specific to smoking cessation, however it can be adapted to health interventions in other disease categories. Future research is required to evaluate the generalizability and effectiveness of the framework, directly against current behavioral support therapy interventions in smoking cessation and beyond

Large Charge Four-Dimensional Extremal N=2 Black Holes with R^2-Terms

We consider N=2 supergravity in four dimensions with small R^2 curvature corrections. We construct large charge extremal supersymmetric and non-supersymmetric black hole solutions in all space, and analyze their thermodynamic properties.Comment: 18 pages. v2,3: minor fixe

Neutrino Parameters, Abelian Flavor Symmetries, and Charged Lepton Flavor Violation

Neutrino masses and mixings have important implications for models of fermion masses, and, most directly, for the charged lepton sector. We consider supersymmetric Abelian flavor models, where neutrino mass parameters are related to those of charged leptons and sleptons. We show that processes such as \tau to \mu\gamma, \mu to e\gamma and \mu-e conversion provide interesting probes. In particular, some existing models are excluded by current bounds, while many others predict rates within reach of proposed near future experiments. We also construct models in which the predicted rates for charged lepton flavor violation are below even the proposed experimental sensitivities, but argue that such models necessarily involve loss of predictive power.Comment: 27 pages, refs added, published versio