A Powerful New Quantitative Genetics Platform, Combining Caenorhabditis elegans High-Throughput Fitness Assays with a Large Collection of Recombinant Strains.

The genetic variants underlying complex traits are often elusive even in powerful model organisms such as Caenorhabditis elegans with controlled genetic backgrounds and environmental conditions. Two major contributing factors are: (1) the lack of statistical power from measuring the phenotypes of small numbers of individuals, and (2) the use of phenotyping platforms that do not scale to hundreds of individuals and are prone to noisy measurements. Here, we generated a new resource of 359 recombinant inbred strains that augments the existing C. elegans N2xCB4856 recombinant inbred advanced intercross line population. This new strain collection removes variation in the neuropeptide receptor gene npr-1, known to have large physiological and behavioral effects on C. elegans and mitigates the hybrid strain incompatibility caused by zeel-1 and peel-1, allowing for identification of quantitative trait loci that otherwise would have been masked by those effects. Additionally, we optimized highly scalable and accurate high-throughput assays of fecundity and body size using the COPAS BIOSORT large particle nematode sorter. Using these assays, we identified quantitative trait loci involved in fecundity and growth under normal growth conditions and after exposure to the herbicide paraquat, including independent genetic loci that regulate different stages of larval growth. Our results offer a powerful platform for the discovery of the genetic variants that control differences in responses to drugs, other aqueous compounds, bacterial foods, and pathogenic stresses

Physics of thick polymers

We present the results of analytic calculations and numerical simulations of the behaviour of a new class of chain molecules which we call thick polymers. The concept of the thickness of such a polymer, viewed as a tube, is encapsulated by a special three body interaction and impacts on the behaviour both locally and non-locally. When thick polymers undergo compaction due to an attractive self-interaction, we find a new type of phase transition between a compact phase and a swollen phase at zero temperature on increasing the thickness. In the vicinity of this transition, short tubes form space filling helices and sheets as observed in protein native state structures. Upon increasing the chain length, or the number of chains, we numerically find a crossover from secondary structure motifs to a quite distinct class of structures akin to the semi-crystalline phase of polymers or amyloid fibers in polypeptides.Comment: 41 pages, 20 figures. Accepted for publication in J. Pol. Sci.

Streaming Verification for Graph Problems: Optimal Tradeoffs and Nonlinear Sketches

We study graph computations in an enhanced data streaming setting, where a space-bounded client reading the edge stream of a massive graph may delegate some of its work to a cloud service. We seek algorithms that allow the client to verify a purported proof sent by the cloud service that the work done in the cloud is correct. A line of work starting with Chakrabarti et al. (ICALP 2009) has provided such algorithms, which we call schemes, for several statistical and graph-theoretic problems, many of which exhibit a tradeoff between the length of the proof and the space used by the streaming verifier. This work designs new schemes for a number of basic graph problems---including triangle counting, maximum matching, topological sorting, and single-source shortest paths---where past work had either failed to obtain smooth tradeoffs between these two key complexity measures or only obtained suboptimal tradeoffs. Our key innovation is having the verifier compute certain nonlinear sketches of the input stream, leading to either new or improved tradeoffs. In many cases, our schemes in fact provide optimal tradeoffs up to logarithmic factors. Specifically, for most graph problems that we study, it is known that the product of the verifier's space cost $v$ and the proof length $h$ must be at least $\Omega(n^2)$ for $n$-vertex graphs. However, matching upper bounds are only known for a handful of settings of $h$ and $v$ on the curve $h \cdot v=\tilde{\Theta}(n^2)$. For example, for counting triangles and maximum matching, schemes with costs lying on this curve are only known for $(h=\tilde{O}(n^2), v=\tilde{O}(1))$, $(h=\tilde{O}(n), v=\tilde{O}(n))$, and the trivial $(h=\tilde{O}(1), v=\tilde{O}(n^2))$. A major message of this work is that by exploiting nonlinear sketches, a significant ``portion'' of costs on the tradeoff curve $h \cdot v = n^2$ can be achieved

Local scale-invariance and ageing in noisy systems

The influence of the noise on the long-time ageing dynamics of a quenched ferromagnetic spin system with a non-conserved order parameter and described through a Langevin equation with a thermal noise term and a disordered initial state is studied. If the noiseless part of the system is Galilei-invariant and scale-invariant with dynamical exponent z=2, the two-time linear response function is independent of the noise and therefore has exactly the form predicted from the local scale-invariance of the noiseless part. The two-time correlation function is exactly given in terms of certain noiseless three- and four-point response functions. An explicit scaling form of the two-time autocorrelation function follows. For disordered initial states, local scale-invariance is sufficient for the equality of the autocorrelation and autoresponse exponents in phase-ordering kinetics. The results for the scaling functions are confirmed through tests in the kinetic spherical model, the spin-wave approximation of the XY model, the critical voter model and the free random walk.Comment: Latex2e, 45 pages, no figures, final for

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Subcutaneous furosemide in advanced heart failure: service improvement project

Objectives: In severe heart disease, parenteral administration of loop diuretic is often needed. We present clinical outcomes from episodes of care using subcutaneous continuous infusion of furosemide (CSCI-furosemide).Methods: Retrospective review of service improvement data. The heart failure nurse specialist, supported by the heart failure-palliative care multi-disciplinary team, works with the community or hospice staff who administer the CSCI-furosemide. Data collected for consecutive patients receiving CSCI-furosemide included: age, sex, New York Heart Association (NYHA) class, preferred place of care, goal of treatment, infusion-site reactions, and signs and symptoms of fluid retention (including weight and self-reported breathlessness).Results: 116 people (men 86 [66%]; mean age 79 years, 49 to 97; NYHA class 3 [36/116, 31%] or 4 heart failure [80/116, 69%]) received 130 episodes of CSCI-furosemide (average duration 10 days, 1 to 49), over half in the patient’s own home/care home (80/129,; 61%) aiming to prevent hospital admission. 40/129 (31%) were managed in the hospice, and 9 (7.0%) in a community hospital. Average daily furosemide dose was 125 mg (40 to 300mg). The goal of treatment was achieved in (119/130, 91.5%) episodes.The median reduction in weight was 4kg (interquartiles -7 kg to -2 kgs, -22 to +9 kgs). Self-reported breathlessness reduced from 8.2 (+/-1.9) to 5.2 (+/-1.8). Adverse events occurred in 31/130 (24%) episodes; all but 4/130 (3%, localised skin infection) were mild.Conclusions: These preliminary data indicate that CSCI-furosemide is safe and effective for people with severe heart failure. An adequately powered randomised controlled trial is indicated