Growth Algorithms for Lattice Heteropolymers at Low Temperatures

Two improved versions of the pruned-enriched-Rosenbluth method (PERM) are proposed and tested on simple models of lattice heteropolymers. Both are found to outperform not only the previous version of PERM, but also all other stochastic algorithms which have been employed on this problem, except for the core directed chain growth method (CG) of Beutler & Dill. In nearly all test cases they are faster in finding low-energy states, and in many cases they found new lowest energy states missed in previous papers. The CG method is superior to our method in some cases, but less efficient in others. On the other hand, the CG method uses heavily heuristics based on presumptions about the hydrophobic core and does not give thermodynamic properties, while the present method is a fully blind general purpose algorithm giving correct Boltzmann-Gibbs weights, and can be applied in principle to any stochastic sampling problem.Comment: 9 pages, 9 figures. J. Chem. Phys., in pres

The Impact of Food Viscosity on Eating Rate, Subjective Appetite, Glycemic Response and Gastric Emptying Rate

Understanding the impact of rheological properties of food on postprandial appetite and glycemic response helps to design novel functional products. It has been shown that solid foods have a stronger satiating effect than their liquid equivalent. However, whether a subtle change in viscosity of a semi-solid food would have a similar effect on appetite is unknown. Fifteen healthy males participated in the randomized cross-over study. Each participant consumed a 1690 kJ portion of a standard viscosity (SV) and a high viscosity (HV) semi-solid meal with 1000 mg acetaminophen in two separate sessions. At regular intervals during the three hours following the meal, subjective appetite ratings were measured and blood samples collected. The plasma samples were assayed for insulin, glucose-dependent insulinotropic peptide (GIP), glucose and acetaminophen. After three hours, the participants were provided with an ad libitum pasta meal. Compared with the SV meal, HV was consumed at a slower eating rate (P = 0.020), with postprandial hunger and desire to eat being lower (P = 0.019 and P,0.001 respectively) while fullness was higher (P,0.001). In addition, consuming the HV resulted in lower plasma concentration of GIP (P,0.001), higher plasma concentration of glucose (P,0.001) and delayed gastric emptying as revealed by the acetaminophen absorption test (P,0.001). However, there was no effect of food viscosity on insulin or food intake at the subsequent meal. In conclusion, increasing the viscosity of a semi-solid food modulates glycemic response and suppresses postprandial satiety, although the effect may be short-lived. A slower eating rate and a delayed gastric emptying rate can partly explain for the stronger satiating properties of high viscous semi-solid foods

Increasing the number of masticatory cycles is associated with reduced appetite and altered postprandial plasma concentrations of gut hormones, insulin and glucose

To determine the influence of masticatory efficiency on postprandial satiety and glycaemic response, twenty-one healthy males were recruited for this randomised cross-over trial. The participants consumed a fixed amount of pizza provided in equal-sized portions by chewing each portion either fifteen or forty times before swallowing. Subjective appetite was measured by appetite questionnaires at regular intervals for 3 h after the meal and plasma samples were collected for the measurement of selected satiety-related hormones, glucose, insulin and glucose-dependent insulinotropic peptide (GIP) concentrations. An ad libitum meal was provided shortly after the last blood sample was drawn and the amount eaten recorded. Compared with fifteen chews, chewing forty times per portion resulted in lower hunger (P¼0·009), preoccupation with food (P¼0·005) and desire to eat (P¼0·002). Meanwhile, plasma concentrations of glucose (P¼0·024), insulin (P,0·001) and GIP (P,0·001) were higher following the forty-chews meal. Chewing forty times before swallowing also resulted in a higher plasma cholecystokinin concentration (P¼0·045) and a trend towards a lower ghrelin concentration (P¼0·051). However, food intake at the subsequent test meal did not differ (P¼0·851). The results suggest that a higher number of masticatory cycles before swallowing may provide beneficial effects on satiety and facilitate glucose absorption

Violating conformal invariance: Two-dimensional clusters grafted to wedges, cones, and branch points of Riemann surfaces

We present simulations of 2-d site animals on square and triangular lattices in non-trivial geomeLattice animals are one of the few critical models in statistical mechanics violating conformal invariance. We present here simulations of 2-d site animals on square and triangular lattices in non-trivial geometries. The simulations are done with the newly developed PERM algorithm which gives very precise estimates of the partition sum, yielding precise values for the entropic exponent $\theta$ ($Z_N \sim \mu^N N^{-\theta}$). In particular, we studied animals grafted to the tips of wedges with a wide range of angles $\alpha$, to the tips of cones (wedges with the sides glued together), and to branching points of Riemann surfaces. The latter can either have $k$ sheets and no boundary, generalizing in this way cones to angles $\alpha > 360$ degrees, or can have boundaries, generalizing wedges. We find conformal invariance behavior, $\theta \sim 1/\alpha$, only for small angles ($\alpha \ll 2\pi$), while $\theta \approx const -\alpha/2\pi$ for $\alpha \gg 2\pi$. These scalings hold both for wedges and cones. A heuristic (non-conformal) argument for the behavior at large $\alpha$ is given, and comparison is made with critical percolation.Comment: 4 pages, includes 3 figure

A Short Antisense Oligonucleotide Ameliorates Symptoms of Severe Mouse Models of Spinal Muscular Atrophy

Recent reports underscore the unparalleled potential of antisense-oligonucleotide (ASO)-based approaches to ameliorate various pathological conditions. However, in vivo studies validating the effectiveness of a short ASO (survival motor neuron 1 (SMN1) gene. Correction of aberrant splicing of the remaining paralog, SMN2, can rescue mouse models of SMA. Here, we report the therapeutic efficacy of an 8-mer ASO (3UP8i) in two severe models of SMA. While 3UP8i modestly improved survival and function in the more severe Taiwanese SMA model, it dramatically increased survival, improved neuromuscular junction pathology, and tempered cardiac deficits in a new, less severe model of SMA. Our results expand the repertoire of ASO-based compounds for SMA therapy, and for the first time, demonstrate the in vivo efficacy of a short ASO in the context of a human disease

Effects of intravenous administration of polymyxin B in neonatal foals with experimental endotoxemia

Objective—To evaluate the effect of IV administration of polymyxin B on clinical and serum biochemical variables in foals with experimental endotoxemia. Design—Prospective experimental study. Animals—14 healthy neonatal foals. Procedures—Foals were randomly assigned to a treatment or control group and were administered a single dose of lipopolysaccharide (0.5 μg/kg [0.23 μg/lb]) IV over 30 minutes. The treatment group received polymyxin B (6,000 U/kg [2,727 U/lb], IV) immediately after completion of lipopolysaccharide infusion; the control group was administered an equal volume of saline (0.9% NaCl) solution. Subsequent doses of polymyxin B or saline solution were administered IV at 8 and 16 hours. Blood was collected at various time points, and outcome variables, including heart rate, respiratory rate, rectal temperature, attitude score, WBC count, neutrophil count, lymphocyte count, monocyte count, platelet count, Hct, blood lactate concentration, blood glucose concentration, serum tumor necrosis factor-α concentration, and plasma thromboxane B2 concentration, were measured. Urine was collected prior to and after experimentation to determine whether nephrotoxicosis was associated with treatment. Results—The treatment group had significantly lower blood lactate concentration and serum tumor necrosis factor-α and plasma thromboxane B2 concentrations and had higher blood glucose concentrations and better attitude scores, compared with the control group, at various time points during the study. No other significant differences and no evidence of overt nephrotoxicosis were detected. Conclusions and Clinical Relevance—Administration of polymyxin B IV in healthy neonatal foals challenged with lipopolysaccharide attenuated some clinical and serum biochemical derangements associated with endotoxemia

Somatostatin Receptors Signal through EFA6A-ARF6 to Activate Phospholipase D in Clonal β-Cells

Somatostatin (SS) is a peptide hormone that inhibits insulin secretion in β-cells by activating its Gi/o-coupled receptors. Our previous work indicated that a βγ-dimer of Gi/o coupled to SS receptors can activate phospholipase D1 (PLD1) (Cheng, H., Grodnitzky, J. A., Yibchok-anun, S., Ding, J., and Hsu, W. H. (2005) Mol. Pharmacol. 67, 2162–2172). The aim of the present study was to elucidate the mechanisms underlying SS-induced PLD activation. We demonstrated the presence of ADP-ribosylation factor Arf1 and Arf6 in clonal β-cells, HIT-T15. We also determined that the activation of PLD1 was mediated through Arf6. Overexpression of dominant-negative (dn) Arf6 mutant, Arf6(T27N), and suppression of mRNA levels using siRNA, both abolished SS-induced PLD activation, while overexpression of wild type Arf6 further enhanced this PLD activation. In contrast, overexpression of dn-Arf1 mutant Arf1(T31N) or dn-Arf5 mutant Arf5(T31N) failed to reduce SS-induced PLD activation. These findings suggested that Arf6, but not Arf1 or Arf5, mediates the effect of SS. We further determined the involvement of the Arf6 guanine nucleotide exchange factor (GEF) EFA6A, a GEF previously thought to be found predominantly in the brain, in the activation of PLD1 in HIT-T15 cells. Using Northern and Western blot analyses, both mRNA and protein of EFA6A were found in these cells. Overexpression of dn-EFA6A mutant, EFA6A(E242K), and suppression of mRNA levels using siRNA, both abolished SS-induced PLD activation, whereas overexpression of dn-EFA6B mutant, EFA6B(E651K), failed to reduce SS-induced PLD activation. In addition, overexpression of dn-ARNO mutant, ARNO(E156K), another GEF of Arf6, had no effect on SS-induced activation of PLD. Taken together, these results suggest that SS signals through EFA6A to activate Arf6-PLD cascade

Pressure-Induced Magnetism and Hidden Order in URu_2Si_2

We discuss the discovery of pressure-induced antiferromagnetism in URu_2Si_2, in the context of neutron, NMR and \mu SR results. The identification of a critical pressure separating mean-field and Ising phase transitions leads us to propose that the system lies close to a bicritical point associated with magnetic and (non-magnetic) hidden order. We conclude that the recent observation of an isotropic, field-independent component in the silicon NMR line-width implies that the hidden order parameter breaks time-reversal invariance and present a preliminary discussion of the underlying nature of the hidden order parameter.Comment: To appear in proceedings of SCES 200