Jamming under tension in polymer crazes

Molecular dynamics simulations are used to study a unique expanded jammed state. Tension transforms many glassy polymers from a dense glass to a network of fibrils and voids called a craze. Entanglements between polymers and interchain friction jam the system after a fixed increase in volume. As in dense jammed systems, the distribution of forces is exponential, but they are tensile rather than compressive. The broad distribution of forces has important implications for fibril breakdown and the ultimate strength of crazes.Comment: 4 pages, 4 figure

Acute renal effects of the GLP-1 receptor agonist exenatide in overweight type 2 diabetes patients: a randomised, double-blind, placebo-controlled trial

Aims/hypothesis: This study aimed to investigate the acute renal effects of the glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide in type 2 diabetes patients. Methods: We included overweight (BMI 25–40 kg/m2) men and postmenopausal women, aged 35–75 years with type 2 diabetes (HbA1c 48–75 mmol/mol; 6.5–9.0%) and estimated GFR ≥ 60 ml min−1 1.73 m−2. Exenatide or placebo (NaCl solution, 154 mmol/l) was administrated intravenously in an acute, randomised, double-blind, placebo-controlled trial conducted at the Diabetes Center VU University Medical Center (VUMC). GFR (primary endpoint) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippurate clearance, respectively, based on timed urine sampling. Filtration fraction (FF) and effective renal vascular resistance (ERVR) were calculated, and glomerular hydrostatic pressure (PGLO) and vascular resistance of the afferent (RA) and efferent (RE) renal arteriole were estimated. Tubular function was assessed by absolute and fractional excretion of sodium (FENa), potassium (FEK) and urea (FEU), in addition to urine osmolality, pH and free water clearance. Renal damage markers, BP and plasma glucose were also determined. Results: Of the 57 patients randomised by computer, 52 were included in the final analyses. Exenatide (n = 24) did not affect GFR (mean difference +2 ± 3 ml min−1 1.73 m−2, p = 0.489), ERPF, FF, ERVR or PGLO, compared with placebo (n = 28). Exenatide increased RA (p < 0.05), but did not change RE. Exenatide increased FENa, FEK, urine osmolality and pH, while FEU, urinary flow and free water clearance were decreased (all p < 0.05). Osmolar clearance and renal damage makers were not affected. Diastolic BP and mean arterial pressure increased by 3 ± 1 and 6 ± 2 mmHg, respectively, whereas plasma glucose decreased by 1.4 ± 0.1 mmol/l (all p < 0.05). Conclusions/interpretation: Exenatide infusion does not acutely affect renal haemodynamics in overweight type 2 diabetes patients at normal filtration levels. Furthermore, acute GLP-1RA administration increases proximal sodium excretion in these patients. Trial registration: ClincialTrials.gov NCT01744236 Funding: The research leading to these results has been funded from: (1) the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 282521 – the SAFEGUARD project; and (2) the Dutch Kidney Foundation, under grant agreement IP12.87

Liraglutide and sitagliptin have no effect on intestinal microbiota composition : A 12-week randomized placebo-controlled trial in adults with type 2 diabetes

Aim: Preclinical data suggest that treatment with either glucagon-like peptide (GLP)-1 receptor agonists or dipeptidyl peptidase (DPP)-4 inhibitors could change the intestinal microbiome and thereby contribute to their beneficial (cardio)metabolic effects. Therefore, our study aimed to investigate the effects of these agents on microbiota composition in adults with type 2 diabetes (T2D). Methods: A total of 51 adults with T2D (mean +/- SD: age 62.8 +/- 6.9 years, BMI 31.8 +/- 4.1 kg/m(2), HbA(1c) 7.3 +/- 0.6%) treated with metformin and/or sulphonylureas were included in the 12-week randomized, double-blind trial. Patients were given the GLP-1 receptor agonist liraglutide (1.8 mg sc) or the DPP-4 inhibitor sitagliptin (100 mg), or matching placebos, once daily for 12 weeks. Faecal samples were collected at baseline and at 12 weeks after the start of the intervention. Microbiota analyses were performed by 16S rRNA gene-sequencing analysis. Bile acids were measured in faeces and plasma. Results: Liraglutide decreased HbA(1c) by 1.3% (95% CI: -1.7 to -0.9) and tended to reduce body weight (-1.7 kg, 95% CI: -3.6 to 0.3), but increased faecal secondary bile acid deoxycholic acid. Sitagliptin lowered HbA(1c) by 0.8% (95% CI: -1.4 to -0.4) while body weight remained stable (-0.8 kg, 95% CI: -2.7 to 1.0), but increased faecal levels of cholic acid, chenodeoxycholic acid and ursodeoxycholic acid. However, neither liraglutide nor sitagliptin affected either alpha or beta diversity of the intestinal microbiota, nor were changes in microbial composition related to clinical parameters. Conclusion: These data suggest that the beneficial effects of liraglutide and sitagliptin on glucose metabolism, body weight and bile acids, when used as add-on therapies to metformin or sulphonylureas, are not linked to changes in the intestinal microbiota (NCT01744236). (C) 2021 The Authors. Published by Elsevier Masson SAS.Peer reviewe

Twelve week liraglutide or sitagliptin does not affect hepatic fat in type 2 diabetes: a randomised placebo-controlled trial

AIMS/HYPOTHESIS: Glucagon-like peptide (GLP)-1-based therapies have been suggested to improve hepatic steatosis. We assessed the effects of the GLP-1 receptor agonist liraglutide and the dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin on hepatic steatosis and fibrosis in patients with type 2 diabetes. METHODS: In this 12 week, parallel, randomised, placebo-controlled trial, performed at the VU University Medical Center between July 2013 and August 2015, 52 overweight patients with type 2 diabetes treated with metformin and/or sulphonylurea agent ([mean ± SD] age 62.7 ± 6.9 years, HbA1c 7.3 ± 0.7% or 56 ± 1 mmol/mol) were allocated to once daily liraglutide 1.8 mg (n = 17), sitagliptin 100 mg (n = 18) or matching placebos (n = 17) by computer generated numbers. Both participants and researchers were blinded to group assignment. Hepatic fat content was measured using proton magnetic resonance spectroscopy ((1)H-MRS). Hepatic fibrosis was estimated using three validated formulae. RESULTS: One patient dropped out in the sitagliptin group owing to dizziness, but no serious adverse events occurred. At week 12, no between-group differences in hepatic steatosis were found. Liraglutide reduced steatosis by 10% (20.9 ± 3.4% to 18.8 ± 3.3%), sitagliptin reduced steatosis by 12.1% (23.9 ± 3.0% to 21.0 ± 2.7%) and placebo lessened it by 9.5% (18.7 ± 2.7% to 16.9 ± 2.7%). Neither drug affected hepatic fibrosis scores compared with placebo. CONCLUSIONS/INTERPRETATION: Twelve-week liraglutide or sitagliptin treatment does not reduce hepatic steatosis or fibrosis in type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01744236 FUNDING : Funded by the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 282521 - the SAFEGUARD project

Leafy Spurge Biological Control Using Black Dot Flea Beetles and Deleterious Rhizobacteria: Final Report Submitted to South Dakota Department of Agriculture Weed and Pest Control

Size of leafy spurge (Euphorbia esula L) roots and their location in the soil profile are important factors relating to survival offirst-instar black dot flea beetle (Aphthona nigriscutis Foudras) larvae. First-instar larvae must find leafy spurge roots between 1 to 4 mm diam in the first 2 days after hatching from eggs for survival. In field studies, we ddermined that most flea beetle larvae reside within 7.6 em ofthe soil surface. Their location in the upper areas ofthe soil profile allows accessibility to desirable size roots, however the larvae are more susceptible to freezing temperatures in this region. Overall, there were fewer black dot flea beetle larvae in the soil at the Pollock site in 1997 compared to 1995 and 1996. In 1997, harsh winter weather conditions may have resulted in high mortality of larvae

Daily fluctuations of negative affect are only weakly associated with tremor symptoms in functional and organic tremor patients

BACKGROUND: There is a long-standing research history on the presumed psychological origin of functional movement disorders. Most studies do not address the heterogeneity in functional movement disorders and do not distinguish between risk factors, causes and consequences. We studied the associations between negative affect and objective as well as subjective symptom levels in patients with functional and organic tremor. METHODS: Thirty-three patients with a functional (14) or organic tremor (19) completed a web-based diary on subjective symptom burden and negative affect, five times a day for 30 days (total number of observations = 4759). During the same period, the participants wore an accelerometer to objectively record tremor. Vector autoregressive modelling was used to determine the time-lagged and contemporaneous associations between negative affect and objective/subjective tremor symptoms, both on an individual and a group level. RESULTS: In contrast to previous literature, patients with a functional or organic tremor showed a weak contemporaneous association between negative affect and objective/subjective tremor symptoms (on average r = 0.038 and 0.174 respectively). Time-lagged associations between negative affect and objective/subjective tremor symptoms were mixed in effect and direction and only present in a subset of patients, with no differences between patients with functional or organic tremor. CONCLUSIONS: Negative affect is only weakly associated with objective/subjective tremor symptoms, both on the contemporaneous and time-lagged associations, and these associations were mainly similar between patients with functional or organic tremor. These results argue against a strong influence of daily stress on tremor symptoms in patients with a functional or organic tremor

Strain Hardening of Polymer Glasses: Entanglements, Energetics, and Plasticity

Simulations are used to examine the microscopic origins of strain hardening in polymer glasses. While stress-strain curves for a wide range of temperature can be fit to the functional form predicted by entropic network models, many other results are fundamentally inconsistent with the physical picture underlying these models. Stresses are too large to be entropic and have the wrong trend with temperature. The most dramatic hardening at large strains reflects increases in energy as chains are pulled taut between entanglements rather than a change in entropy. A weak entropic stress is only observed in shape recovery of deformed samples when heated above the glass transition. While short chains do not form an entangled network, they exhibit partial shape recovery, orientation, and strain hardening. Stresses for all chain lengths collapse when plotted against a microscopic measure of chain stretching rather than the macroscopic stretch. The thermal contribution to the stress is directly proportional to the rate of plasticity as measured by breaking and reforming of interchain bonds. These observations suggest that the correct microscopic theory of strain hardening should be based on glassy state physics rather than rubber elasticity.Comment: 15 pages, 12 figures: significant revision

Precision timing of PSR J1012+5307 and strong-field GR tests

We report on the high precision timing analysis of the pulsar-white dwarf binary PSR J1012+5307. Using 15 years of multi-telescope data from the European Pulsar Timing Array (EPTA) network, a significant measurement of the variation of the orbital period is obtained. Using this ideal strong-field gravity laboratory we derive theory independent limits for both the dipole radiation and the variation of the gravitational constant.Comment: 3 pages, Proceedings of the 12th Marcel Grossmann Meeting on General Relativity (MG 12

Acute renal effects of the GLP-1 receptor agonist exenatide in overweight type 2 diabetes patients: a randomised, double-blind, placebo-controlled trial

Aims/hypothesis: This study aimed to investigate the acute renal effects of the glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide in type 2 diabetes patients. Methods: We included overweight (BMI 25–40 kg/m2) men and postmenopausal women, aged 35–75 years with type 2 diabetes (HbA1c 48–75 mmol/mol; 6.5–9.0%) and estimated GFR ≥ 60 ml min−1 1.73 m−2. Exenatide or placebo (NaCl solution, 154 mmol/l) was administrated intravenously in an acute, randomised, double-blind, placebo-controlled trial conducted at the Diabetes Center VU University Medical Center (VUMC). GFR (primary endpoint) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippurate clearance, respectively, based on timed urine sampling. Filtration fraction (FF) and effective renal vascular resistance (ERVR) were calculated, and glomerular hydrostatic pressure (PGLO) and vascular resistance of the afferent (RA) and efferent (RE) renal arteriole were estimated. Tubular function was assessed by absolute and fractional excretion of sodium (FENa), potassium (FEK) and urea (FEU), in addition to urine osmolality, pH and free water clearance. Renal damage markers, BP and plasma glucose were also determined. Results: Of the 57 patients randomised by computer, 52 were included in the final analyses. Exenatide (n = 24) did not affect GFR (mean difference +2 ± 3 ml min−1 1.73 m−2, p = 0.489), ERPF, FF, ERVR or PGLO, compared with placebo (n = 28). Exenatide increased RA (p < 0.05), but did not change RE. Exenatide increased FENa, FEK, urine osmolality and pH, while FEU, urinary flow and free water clearance were decreased (all p < 0.05). Osmolar clearance and renal damage makers were not affected. Diastolic BP and mean arterial pressure increased by 3 ± 1 and 6 ± 2 mmHg, respectively, whereas plasma glucose decreased by 1.4 ± 0.1 mmol/l (all p < 0.05). Conclusions/interpretation: Exenatide infusion does not acutely affect renal haemodynamics in overweight type 2 diabetes patients at normal filtration levels. Furthermore, acute GLP-1RA administration increases proximal sodium excretion in these patients. Trial registration: ClincialTrials.gov NCT01744236 Funding: The research leading to these results has been funded from: (1) the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 282521 – the SAFEGUARD project; and (2) the Dutch Kidney Foundation, under grant agreement IP12.87