Improving Electro-Weak Fits with TeV-scale Sterile Neutrinos

We study the impact of TeV-scale sterile neutrinos on electro-weak precision observables and lepton number and flavour violating decays in the framework of a type-I see-saw extension of the Standard Model. At tree level sterile neutrinos manifest themselves via non-unitarity of the PMNS matrix and at one-loop level they modify the oblique radiative corrections. We derive explicit formulae for the S,T,U parameters in terms of the neutrino masses and mixings and perform a numerical fit to the electro-weak observables. We find regions of parameter space with a sizable active-sterile mixing which provide a better over-all fit compared to the case where the mixing is negligible. Specifically we find improvements of the invisible Z-decay width, the charged-to-neutral-current ratio for neutrino scattering experiments and of the deviation of the W boson mass from the theoretical expectation.Comment: 16 pages, 17 figures, Journal accepted versio

Pleiotropy of FRIGIDA enhances the potential for multivariate adaptation.

An evolutionary response to selection requires genetic variation; however, even if it exists, then the genetic details of the variation can constrain adaptation. In the simplest case, unlinked loci and uncorrelated phenotypes respond directly to multivariate selection and permit unrestricted paths to adaptive peaks. By contrast, 'antagonistic' pleiotropic loci may constrain adaptation by affecting variation of many traits and limiting the direction of trait correlations to vectors that are not favoured by selection. However, certain pleiotropic configurations may improve the conditions for adaptive evolution. Here, we present evidence that the Arabidopsis thaliana gene FRI (FRIGIDA) exhibits 'adaptive' pleiotropy, producing trait correlations along an axis that results in two adaptive strategies. Derived, low expression FRI alleles confer a 'drought escape' strategy owing to fast growth, low water use efficiency and early flowering. By contrast, a dehydration avoidance strategy is conferred by the ancestral phenotype of late flowering, slow growth and efficient water use during photosynthesis. The dehydration avoidant phenotype was recovered when genotypes with null FRI alleles were transformed with functional alleles. Our findings indicate that the well-documented effects of FRI on phenology result from differences in physiology, not only a simple developmental switch

The use of a cap-mounted tri-axial accelerometer for measurement of distance, lap times and stroke rates in swim training

This paper will report some of the findings from a trial which recorded accelerometer data from six elite level swimmers (three female and three male, varying primary event stroke and distance) over the course of a regular 15 week training block. Measurements from a headmounted accelerometer are used to determine when the athlete is swimming, marking of turning points (and therefore distance and lap-time measurements), and is processed by frequency analysis to determine stroke-rate. Comparison with video where available, and with training plans and literature where not, have proven this method to be accurate and reliable for determining these performance metrics. The primary objective of this project was to develop a low-cost, simple and highly usable system for use in swim coaching, feedback from elite coaches has indicated that development of this could be an extremely useful addition to their training regime

Selling Your Self in the United States

In the contemporary U.S. workplace, corporate personhood is increasingly becoming the metaphor structuring how job seekers are supposed to present themselves as employable. If one takes oneself to be a business, one should also take oneself to be an entity that requires a brand. Some ethnographic questions arise when job seekers try to embody corporate personhood. How does one transform oneself into a brand? What are the obstacles that a person encounters adopting a form of corporate personhood? How does one foster relationships or networks that will lead to a job, not just a circulation of one’s brand identity? Based on research in Indiana and northern California, this article explores the conundrums of marketing oneself as a desirable employee on Facebook, LinkedIn, Twitter, email, and so on. I address the reasons why the increased use of social media contributes to popularizing a notion of self-branding. I also discuss the quandaries people face when using social media to create this self-brand. In sum, this article investigates the obstacles people face when they try to embody a form of corporate personhood across media, a form of self putatively based on the individual, but one that has been transformed into a corporate form that people can not easily inhabit

195 - Targeting Telomeric and c-MYC G4 DNA as an Anticancer Approach

G-quadruplex (G4) DNA are non-canonical higher order DNA structures formed from guanine rich sequences, made up of stacked G-tetrads stabilized by non-Watson-Crick (Hoogsteen) base pairing and K+ ions. Early interests in G4 DNA were spurred on by the revelation that G4 was formed in telomeric DNA sequences at the end of our chromosomes. This was particularly promising given that G4 structures formed in telomeric DNA were also found to inhibit an enzyme known as telomerase, which is overexpressed (\u3e90%) in cancer cells. Cancer cells require telomerase activity for survival and immortality , therefore stabilization of telomeric G4 can inhibit telomerase activity and prevent the survival of cancer cells. More recently, G4 DNA has also been shown to be overrepresented in the promoter regions of oncogenes (e.g., c-myc and ras genes) and the 5\u27UTR of mRNA. As a result, G4 DNA represents a viable target for possible anti-cancer therapeutic agents to treat previously undruggable sites such as the c-myc and ras oncogenes. In this work, G4 structures formed at both telomeric and c-myc G4 sequences were investigated, with an emphasis on c-myc G4. This was done by probing the G4 structures with a variety of known and novel compounds such as quinacrine, TMPyP4 and NDI derivatives. Using the biophysical techniques of isothermal titration calorimetry (ITC), fluorescent displacement, thermal melting, and circular dichroism (CD) spectroscopy, the binding characteristics of these compounds to G4 DNA were investigated

Universality of filamentous aggregation phenomena.

We use perturbative renormalization group theory to study the kinetics of protein aggregation phenomena in a unified manner across multiple timescales. Using this approach, we find that, irrespective of the specific molecular details or experimental conditions, filamentous assembly systems display universal behavior in time. Moreover, we show that the universality classes for protein aggregation correspond to simple autocatalytic processes and that the diversity of behavior in these systems is determined solely by the reaction order for secondary nucleation with respect to the protein concentration, which labels all possible universality classes. We validate these predictions on experimental data for the aggregation of several different proteins at several different initial concentrations, which by appropriate coordinate transformations we are able to collapse onto universal kinetic growth curves. These results establish the power of the perturbative renormalization group in distilling the ultimately simple temporal behavior of complex protein aggregation systems, creating the possibility to study the kinetics of general self-assembly phenomena in a unified fashion

Solving mixed-integer nonlinear optimization problems using simultaneous convexification : a case study for gas networks

Solving mixed-integer nonlinear optimization problems (MINLPs) to global optimality is extremely challenging. An important step for enabling their solution consists in the design of convex relaxations of the feasible set. Known solution approaches based on spatial branch-and-bound become more effective the tighter the used relaxations are. Relaxations are commonly established by convex underestimators, where each constraint function is considered separately. Instead, a considerably tighter relaxation can be found via so-called simultaneous convexification, where convex underestimators are derived for more than one constraint function at a time. In this work, we present a global solution approach for solving mixed-integer nonlinear problems that uses simultaneous convexification. We introduce a separation method that relies on determining the convex envelope of linear combinations of the constraint functions and on solving a nonsmooth convex problem. In particular, we apply the method to quadratic absolute value functions and derive their convex envelopes. The practicality of the proposed solution approach is demonstrated on several test instances from gas network optimization, where the method outperforms standard approaches that use separate convex relaxations.Projekt DEAL 202

Opposing effects of final population density and stress on Escherichia coli mutation rate

Evolution depends on mutations. For an individual genotype, the rate at which mutations arise is known to increase with various stressors (stress-induced mutagenesis-SIM) and decrease at high final population density (density-associated mutation-rate plasticity-DAMP). We hypothesised that these two forms of mutation-rate plasticity would have opposing effects across a nutrient gradient. Here we test this hypothesis, culturing Escherichia coli in increasingly rich media. We distinguish an increase in mutation rate with added nutrients through SIM (dependent on error-prone polymerases Pol IV and Pol V) and an opposing effect of DAMP (dependent on MutT, which removes oxidised G nucleotides). The combination of DAMP and SIM results in a mutation rate minimum at intermediate nutrient levels (which can support 7 × 10  cells ml ). These findings demonstrate a strikingly close and nuanced relationship of ecological factors-stress and population density-with mutation, the fuel of all evolution

Lipid vesicles trigger α-synuclein aggregation by stimulating primary nucleation.

α-Synuclein (α-syn) is a 140-residue intrinsically disordered protein that is involved in neuronal and synaptic vesicle plasticity, but its aggregation to form amyloid fibrils is the hallmark of Parkinson's disease (PD). The interaction between α-syn and lipid surfaces is believed to be a key feature for mediation of its normal function, but under other circumstances it is able to modulate amyloid fibril formation. Using a combination of experimental and theoretical approaches, we identify the mechanism through which facile aggregation of α-syn is induced under conditions where it binds a lipid bilayer, and we show that the rate of primary nucleation can be enhanced by three orders of magnitude or more under such conditions. These results reveal the key role that membrane interactions can have in triggering conversion of α-syn from its soluble state to the aggregated state that is associated with neurodegeneration and to its associated disease states.This work was supported by the UK BBSRC and the Wellcome Trust (CMD, TPJK, MV), the Frances and Augustus Newman Foundation (TPJK), Magdalene College, Cambridge (AKB) , St John’s College, Cambridge (TCTM), the Cambridge Home and EU Scholarship Scheme (GM), Elan Pharmaceuticals (CMD, TPJK, MV, CG) and the Leverhulme Trust (AKB).This is the accepted manuscript. The final version is available from NPG at http://www.nature.com/nchembio/journal/v11/n3/abs/nchembio.1750.htm