Abstract:
To determine whether trientine treatment could improve in vivo outcome, we measured cardiac function in groups of trientine-treated diabetic (TETA-DIA), non-drug-treated diabetic (DIA) and sham-treated control (SHAM) rats, by using in vivo high-field cardiac magnetic-resonance imaging (cMRI) and an ex-vivo isolated-perfused working heart method. Forty age-matched animals underwent a cMRI scan after which 12 were randomized to the SHAM group and 28 underwent streptozotocin-injection; of these, 25 developed stable diabetes, and 12 were then randomized to receive no treatment for 16 weeks (DIA) and the other 13 to undergo 8-weeks' untreated diabetes followed by 8-weeks' drug treatment (TETA-DIA). Animals were studied again by cMRI at 8 and 16 weeks following disease induction, and finally by measurement of ex vivo cardiac function.After eight weeks diabetes, rats (DIA/TETA-DIA) had developed significant impairment of LV function, as judged by impairment of ejection fraction (LVEF), cardiac output (CO), and LV mass (LVM)/body-mass (all P < 0.001), as well as other functional indexes. LVEF, CO (both P < 0.001) and the other indexes deteriorated further at 16 weeks in DIA, whereas trientine (TETA-DIA) improved cardiac function by elevating LVEF and CO (both P < 0.001), and also partially reversed the increase in LVM/body-mass (P < 0.05). In ex vivo hearts from DIA, the CO response to increasing preload pressure was deficient compared with SHAM (P < 0.001) whereas the preload-CO relationship was significantly improved in TETA-DIA animals (P < 0.001).Trientine treatment significantly improved cardiac function in diabetic rats with substantive LV impairment. These results implicate impaired copper regulation in the pathogenesis of impaired cardiac function caused by diabetic cardiomyopathy, and support ongoing studies of trientine treatment in patients with heart failure.

Abstract:
A mathematically and culturally natural modification of Evart Bruins' explanation of the genesis of the numbers on the Old Babylonian tablet Plimpton 322 gives an economical accounting for the "missing pairs" in his reconstruction. When the new scheme is used to predict the numbers that would follow those on Plimpton 322, the results add five new rows to those listed by Price and Friberg in their hypothetical extension of the content of Plimpton 322 to rows covering the edges and back.

Abstract:
The minimum number of self-intersection points for members of a free homotopy class of curves on the punctured torus is bounded above in terms of the number L of letters required for a minimal description of the class in terms of the generators of the fundamental group and their inverses: it is less than or equal to (L-2)^2/4 if L is even, and (L-1)(L-3)/4 if L is odd. The classes attaining this bound are explicitly described in terms of the generators; there are (L-2)^2 + 4 of them if L is even, and 2(L-1)(L-3) + 8 if L is odd; similar descriptions and totals are given for classes with self-intersection number equal to one less than the maximum. Proofs use both combinatorial calculations and topological operations on representative curves. Computer-generated data are tabulated counting, for each non-negative integer, how many length-L classes have that self-intersection number, for each length L less than or equal to 12. Experimental data are also presented for the pair-of-pants surface.

Abstract:
We address the problem of computing bounds for the self-intersection number (the minimum number of self-intersection points) of members of a free homotopy class of curves in the doubly-punctured plane as a function of their combinatorial length L; this is the number of letters required for a minimal description of the class in terms of the standard generators of the fundamental group and their inverses. We prove that the self-intersection number is bounded above by L^2/4 + L/2 - 1, and that when L is even, this bound is sharp; in that case there are exactly four distinct classes attaining that bound. When L is odd, we establish a smaller, conjectured upper bound ((L^2 - 1)/4)) in certain cases; and there we show it is sharp. Furthermore, for the doubly-punctured plane, these self-intersection numbers are bounded below, by L/2 - 1 if L is even, (L - 1)/2 if L is odd; these bounds are sharp.

Abstract:
We show explicitly how a strongly coupled fixed point can be constructed in scalar $g\varphi^4$ theory from the solutions to a non-linear eigenvalue problem. The fixed point exists only for $d< 4$, is unstable and characterized by $\nu=2/d$ (correlation length exponent), $\eta=1/2-d/8$ (anomalous dimension). For $d=2$, these exponents reproduce to those of the Ising model which can be understood from the codimension of the critical point. At this fixed point, $\varphi^{2i}$ terms with $i>2$ are all irrelevant. The testable prediction of this fixed point is that the specific heat exponent vanishes. 2d critical Mott systems are well described by this new fixed point.

Abstract:
Objective To investigate, using accelerometers, the levels of physical activity being undertaken by individuals with intellectual disabilities with and without Down's syndrome. Methods One hundred and fifty two individuals with intellectual disabilities aged 12–70 years from East and South-East England. Physical activity levels in counts per minute (counts/min), steps per day (steps/day), and minutes of sedentary, light, moderate, vigorous, and moderate to vigorous physical activity (MVPA) measured with a uni-axial accelerometer (Actigraph GT1M) for seven days. Results No individuals with intellectual disabilities met current physical activity recommendations. Males were more active than females. There was a trend for physical activity to decline and sedentary behaviour to increase with age, and for those with more severe levels of intellectual disability to be more sedentary and less physically active, however any relationship was not significant when adjusted for confounding variables. Participants with Down's syndrome engaged in significantly less physical activity than those with intellectual disabilities without Down's syndrome and levels of activity declined significantly with age. Conclusions Individuals with intellectual disabilities, especially those with Down's syndrome may be at risk of developing diseases associated with physical inactivity. There is a need for well-designed, accessible, preventive health promotion strategies and interventions designed to raise the levels of physical activity for individuals with intellectual disabilities. We propose that there are physiological reasons why individuals with Down's syndrome have particularly low levels of physical activity that also decline markedly with age.

Abstract:
Many ceramic and hybrid metal-organic framework materials show negative thermal expansion (NTE): they \textit{contract} instead of expanding on heating \cite{Barrera_Miller_Lind_Romao 2005}. Their structures are invariably characterised as a network of polyhedral groups of atoms that are connected through sharing of corner atoms or by shared ligands. Empirically, NTE materials tend to show pressure-induced softening, pressure enhancement of NTE, and the reduction of NTE on heating. But such effects have only been investigated in a small number of materials \cite{Pantea 2006,Chapman 2005,Chapman 2007,Fangexp 2013}, and as yet there is no general framework for understanding the whole suite of properties together. By studying models with Hamiltonians chosen to reflect the physical picture generally accepted as responsible for NTE in framework materials, we demonstrate that NTE, pressure-enhanced NTE, and pressure-induced softening naturally emerge together. We then show how anharmonic interactions lead to structural warm hardening---something that has only previously been seen in laser-excited warm-dense matter \cite{Ernstorfer 2009}---as well as to the transition from NTE to positive thermal expansion and the disappearing of the pressure-induced softening at high temperatures.

Abstract:
We study the square-lattice Bose-Hubbard model with bounded random on-site energies at zero temperature. Starting from a dual representation obtained from a strong-coupling expansion around the atomic limit, we employ a real-space block decimation scheme. This approach is non-perturbative in the disorder and enables us to study the renormalization-group flow of the induced random-mass distribution. In both insulating phases, the Mott insulator and the Bose glass, the average mass diverges, signaling short range superfluid correlations. The relative variance of the mass distribution distinguishes the two phases, renormalizing to zero in the Mott insulator and diverging in the Bose glass. Negative mass values in the tail of the distribution indicate the presence of rare superfluid regions in the Bose glass. The breakdown of self-averaging is evidenced by the divergent relative variance and increasingly non-Gaussian distributions. We determine an explicit phase boundary between the Mott insulator and Bose glass.

Abstract:
Mycobacterium tuberculosis (strain Mtb72) rifamycin resistant mutants were selected in vitro with either rifampicin or rifabutin. One mutant R190 (rpoB S522L) selected with rifampicin had a rifampicin MIC of 32 μg/ml but remained sensitive to rifabutin (MIC<0.8 μg/ml). This mutant was subjected to a second round of selection with rifabutin.All 105 first round resistant mutants derived from the parent strain (Mtb72) screened acquired mutations within the 81 bp rpoB hotspot. When the rifampicin resistant but rifabutin sensitive S522L mutant was subjected to a second round of selection, single additional rpoB mutations were identified in 24 (92%) of 26 second round mutants studied, but 14 (54%) of these strains contained mutations outside the 81 bp hotspot (codons 144, 146, 148, 505). Additionally, spontaneous rifabutin resistant mutants were produced at >10 times the frequency by the S522L mutant than the parent strain.First round selection of mutation S522L with rifampicin increased the frequency and changed the spectrum of mutations identified after selection with rifabutin.It has been estimated that one third of the World's population is infected with Mycobacterium tuberculosis (MTB) resulting in 2 million deaths annually. In uncomplicated cases short course therapy (6 months) using a multiple-drug regimen is highly effective. An essential component of this regimen is rifampicin (RIF). In MTB resistance to antimicrobial agents appears to be solely due to spontaneous mutation, as no horizontal transfer of genetic elements carrying a resistance genotype has been described. For this reason MTB strains or sub-populations with an unusual spectrum or rate of mutations are of considerable interest [1-3] as potentially they are more prone to develop resistance to antimicrobial drugs.Mutations within an 81-bp locus of MTB rpoB have been seen in almost all (> = 95%) rifamycin resistant isolates, whether they be clinical [4] or laboratory generated mutants [5]. These mutation