The effect of temperature on single-polypeptide adsorption

The hydrophobic attraction (HA) is believed to be one of the main driving forces for protein folding. Understanding its temperature dependence promises a deeper understanding of protein folding. Herein, we present an approach to investigate the HA with a combined experimental and simulation approach, which is complementary to previous studies on the temperature dependence of the solvation of small hydrophobic spherical particles. We determine the temperature dependence of the free-energy change and detachment length upon desorption of single polypeptides from hydrophobic substrates in aqueous environment. Both the atomic force microscopy (AFM) based experiments and the molecular dynamics (MD) simulations show only a weak dependence of the free energy change on temperature. In fact, depending on the substrate, we find a maximum or a minimum in the temperature-dependent free energy change, meaning that the entropy increases or decreases with temperature for different substrates. These observations are in contrast to the solvation of small hydrophobic particles and can be rationalized by a compensation mechanism between the various contributions to the desorption force. On the one hand this is reminiscent of the protein folding process, where large entropic and enthalpic contributions compensate each other to result in a small free energy difference between the folded and unfolded state. On the other hand, the protein folding process shows much stronger temperature dependence, pointing to a fundamental difference between protein folding and adsorption. Nevertheless such temperature dependent single molecule desorption studies open large possibilities to study equilibrium and non-equilibrium processes dominated by the hydrophobic attraction

CoCStom trial: study protocol for a randomised trial comparing completeness of adjuvant chemotherapy after early versus late diverting stoma closure in low anterior resection for rectal cancer

Background: Current evidence supports a diverting stoma in patients undergoing low anterior resection with total mesorectal excision for rectal cancer as it reduces clinical severity of anastomotic leakage. However, relevant stoma morbidity after rectal cancer surgery exists and has a significant impact on quality of life. Moreover, a diverting stoma has an influence on completeness of chemotherapy but it remains unclear in which way. There is no evidence regarding optimal timing for stoma closure in relation to adjuvant chemotherapy. Two randomised controlled trials have studied early stoma closure after low anterior resection in patients with rectal cancer, one of them showing that early closure around day 8 after resection is possible without increasing morbidity. Methods/Design: CoCStom is a randomised multicentre trial comparing completeness of adjuvant chemotherapy as primary endpoint after early (8–10 days after resection, before starting adjuvant therapy) versus late (~26 weeks after resection and completion of adjuvant therapy) stoma closure in patients with locally advanced rectal cancer undergoing low anterior resection after neoadjuvant therapy. After exclusion of post-operative anastomotic leakage 257 patients from 30 German hospitals are planned to be included in order to assure a power of 80 % for the confirmatory analysis of at least 214 evaluable cases. An absolute increase of 20 % for the rate of completely administered adjuvant chemotherapy is regarded as a clinically meaningful step forward and serves as basis for sample size calculation. Quality of life, stoma-related complications, individual completeness of chemotherapy rate, percentage of patients stopping adjuvant therapy or undergoing dose modifications or delay, oncological outcomes, cumulative days of hospitalisation and number of readmissions, rate of symptomatic anastomotic leaks after stoma closure, mortality, post-operative complications and toxicity of adjuvant chemotherapy are secondary endpoints. Discussion: The CoCStom trial aims to clarify optimal timing of stoma closure in the context of adjuvant chemotherapy. Depending on the results of the trial, patients could benefit either from early or late stoma closure in regard to long term oncological survival due to a higher rate of completeness of adjuvant chemotherapy treatment and thus better effectiveness. Trial registration: German Clinical Trials Register, DRKS00005113 . Registered 28 August 201

Additive Manufacturing as a Means of Gas Sensor Development for Battery Health Monitoring

Lithium-ion batteries (LIBs) still need continuous safety monitoring based on their intrinsic properties, as well as due to the increase in their sizes and device requirements. The main causes of fires and explosions in LIBs are heat leakage and the presence of highly inflammable components. Therefore, it is necessary to improve the safety of the batteries by preventing the generation of these gases and/or their early detection with sensors. The improvement of such safety sensors requires new approaches in their manufacturing. There is a growing role for research of nanostructured sensor’s durability in the field of ionizing radiation that also can induce structural changes in the LIB’s component materials, thus contributing to the elucidation of fundamental physicochemical processes; catalytic reactions or inhibitions of the chemical reactions on which the work of the sensors is based. A current method widely used in various fields, Direct Ink Writing (DIW), has been used to manufacture heterostructures of Al2O3/CuO and CuO:Fe2O3, followed by an additional ALD and thermal annealing step. The detection properties of these 3D-DIW printed heterostructures showed responses to 1,3-dioxolan (DOL), 1,2-dimethoxyethane (DME) vapors, as well as to typically used LIB electrolytes containing LiTFSI and LiNO3 salts in a mixture of DOL:DME, as well also to LiPF6 salts in a mixture of ethylene carbonate (EC) and dimethyl carbonate (DMC) at operating temperatures of 200 °C–350 °C with relatively high responses. The combination of the possibility to detect electrolyte vapors used in LIBs and size control by the 3D-DIW printing method makes these heterostructures extremely attractive in controlling the safety of batteries

Nanosensors Based on a Single ZnO:Eu Nanowire for Hydrogen Gas Sensing

Fast detection of hydrogen gas leakage or its release in different environments, especially in large electric vehicle batteries, is a major challenge for sensing applications. In this study, the morphological, structural, chemical, optical, and electronic characterizations of ZnO:Eu nanowire arrays are reported and discussed in detail. In particular, the influence of different Eu concentrations during electrochemical deposition was investigated together with the sensing properties and mechanism. Surprisingly, by using only 10 μM Eu ions during deposition, the value of the gas response increased by a factor of nearly 130 compared to an undoped ZnO nanowire and we found an H2gas response of ∼7860 for a single ZnO:Eu nanowire device. Further, the synthesized nanowire sensors were tested with ultraviolet (UV) light and a range of test gases, showing a UV responsiveness of ∼12.8 and a good selectivity to 100 ppm H2gas. A dual-mode nanosensor is shown to detect UV/H2gas simultaneously for selective detection of H2during UV irradiation and its effect on the sensing mechanism. The nanowire sensing approach here demonstrates the feasibility of using such small devices to detect hydrogen leaks in harsh, small-scale environments, for example, stacked battery packs in mobile applications. In addition, the results obtained are supported through density functional theory-based simulations, which highlight the importance of rare earth nanoparticles on the oxide surface for improved sensitivity and selectivity of gas sensors, even at room temperature, thereby allowing, for instance, lower power consumption and denser deployment

Influence of complete administration of adjuvant chemotherapy cycles on overall and disease-free survival in locally advanced rectal cancer: post hoc analysis of a randomized, multicenter, non-inferiority, phase 3 trial

Abstract Background A randomized trial demonstrated that capecitabine is at least as effective as fluorouracil in the adjuvant treatment of patients with locally advanced rectal cancer. However, not all patients receive all planned cycles of chemotherapy. Therefore it is of interest how complete or partial administration of chemotherapy influences oncological outcome. Methods A post hoc analysis of a trial with 401 randomized patients, nine being excluded because of missing data, was performed. 392 patients (197 - capecitabine, 195 - fluorouracil) could be analyzed regarding the number of administered adjuvant chemotherapy cycles. In the subgroup of 361 patients with an overall survival of at least six months, five-year overall and disease-free survival were analyzed in respect to completion (complete vs. incomplete) of chemotherapy cycles. Survival rates and curves were calculated and compared using the log-rank test. The effect of completion of chemotherapy was adjusted for relevant confounding factors. Results Two hundred fifty-one (64.0%) of analyzed patients received all postoperative scheduled cycles. Five-year overall survival was significantly better in these patients compared to the incomplete group (76.0 vs. 60.6%, p < 0.0001). Of 361 patients with an overall survival of at least six months, 251(69.5%) patients received all cycles. Five-year overall survival was also significantly better than in the incomplete group (76.0 vs. 66.4%, p = 0.0073). Five-year disease free survival was numerically better (64.9 vs. 58.7%, p = 0.0646; HR [not all cycles vs. all cycles] = 1.42 95% CI: [0.98, 2.07]). Cox regression models show a non-significant better OS (p = 0.061) and DFS (p = 0.083), if chemotherapy cycles were administered completely. Conclusion Complete administration of chemotherapy cycles was associated with improved five-year overall and disease-free survival in patients with locally advanced rectal cancer

Additional file 1: of Influence of complete administration of adjuvant chemotherapy cycles on overall and disease-free survival in locally advanced rectal cancer: post hoc analysis of a randomized, multicenter, non-inferiority, phase 3 trial

Uni- and multivariate analyses for OS and DFS. Univariate Cox regression models for CoC and baseline characteristics of the study population as well as adjustment of CoC effect for relevant confounding factors. (DOCX 45 kb

Stick-Slip Mechanisms at the Nanoscale

<div><p>When two surfaces slide past each other, energy is mainly dissipated by stick-slip events. Macroscopic stick-slip is usually explained by asperities that come in and out of contact. Herein, we probe stick-slip at the nanoscale at interfaces and polymer coated interfaces by pulling single polymers covalently attached to an AFM cantilever tip laterally over solid substrates in liquid environment. We find two different stick mechanisms, namely desorption stick (DS) and cooperative stick (CS). While DS-slip resembles the velocity dependence of macroscopic stick-slip, CS-slip shows an increase in friction with velocity. For various reasons we anticipate that both stick mechanisms are necessary for a molecular understanding of stick-slip at the interface and interphase. </p></div

Flexible endoscopy is enough diagnostic prior to loop ileostomy reversal

Purpose!#!This study investigates whether contrast enema (CE) and flexible endoscopy (FE) should be performed routinely after low anterior resection (LAR) before ileostomy reversal. Additionally, the impact of previous anastomotic leakage (AL) on diagnostic test accuracy (DTA) was assessed.!##!Methods!#!This is a retrospective analysis of prospectively collected tertiary care data of two centers. Consecutive rectal cancer patients undergoing LAR with loop ileostomy formation were included. Before ileostomy reversal, all patients were assessed by CE and FE. DTA of FE and CE for asymptomatic AL in patients who had previously suffered from clinically relevant AL (group 1) compared with those without apparent AL after LAR (group 0) were assessed separately.!##!Results!#!Two hundred ninety-three patients were included in the analysis, 86 in group 1 and 207 in group 0. Overall sensitivity for detection of asymptomatic AL was 76% (FE) and 60% (CE). Specificity was 100% for both tests. DTA of FE was equal or superior to CE in all subgroups. Prevalence of asymptomatic AL at the time of testing was 1.4% in group 0 and 25.6% in group 1.!##!Conclusion!#!Flexible endoscopy is the more accurate diagnostic test for the detection of asymptomatic anastomotic leaks prior to ileostomy reversal. Contrast enema showed no gain of information. In the group without complications after the initial rectal resection, 104 must be tested to find one leak prior to reversal. In those patients, routine diagnostic testing additional to digital rectal examination may be questioned