Photopolymerized thermosensitive poly(HPMAlactate)-PEG-based hydrogels : effect of network design on mechanical properties, degradation, and release behavior

Photopolymerized thermosensitive A-B-A triblock copolymer hydrogels composed of poly(N-(2-hydroxypropyl)-methacrylamide lactate) A-blocks, partly derivatizal with methacrylate groups to different extents (10, 20, and 30%) and hydrophilic poly(ethylene glycol) B-blocks of different molecular weights (4, 10, and 20 kDa) were synthesized. The aim of the present study was to correlate the polymer architecture with the hydrogel properties, particularly rheological, swelling, degradation properties and release behavior. It was found that an increasing methacrylation extent and a decreasing PEG molecular weight resulted in increasing gel strength and cross-link density, which tailored the degradation profiles from 25 to more than 300 days. Polymers having small PEG blocks showed a remarkable phase separation into polymer- and water-rich domains, as demonstrated by confocal microscopy. Depending on the hydrophobic domain density, the loaded protein resides in the hydrophilic pores or is partitioned into hydrophilic and hydrophobic domains, and its release from these compartments is tailored by the extent of methacrylation and by PEG length, respectively. As the mechanical properties, degradation, and release profiles can be fully controlled by polymer design and concentration, these hydrogels are suitable for controlled protein release

Discourse analysis and role performance

Language Use in Past and Presen

Alpha-helical destabilization of the Bcl-2-BH4-domain peptide abolishes its ability to inhibit the IP3 receptor

The anti-apoptotic Bcl-2 protein is the founding member and namesake of the Bcl-2-protein family. It has recently been demonstrated that Bcl-2, apart from its anti-apoptotic role at mitochondrial membranes, can also directly interact with the inositol 1,4,5-trisphosphate receptor (IP3R), the primary Ca2+-release channel in the endoplasmic reticulum (ER). Bcl-2 can thereby reduce pro-apoptotic IP3R-mediated Ca2+ release from the ER. Moreover, the Bcl-2 homology domain 4 (Bcl-2-BH4) has been identified as essential and sufficient for this IP3R-mediated anti-apoptotic activity. In the present study, we investigated whether the reported inhibitory effect of a Bcl-2-BH4 peptide on the IP (3)R1 was related to the distinctive alpha-helical conformation of the BH4 domain peptide. We therefore designed a peptide with two glycine "hinges" replacing residues I14 and V15, of the wild-type Bcl-2-BH4 domain (Bcl-2-BH4-IV/GG). By comparing the structural and functional properties of the Bcl-2-BH4-IV/GG peptide with its native counterpart, we found that the variant contained reduced alpha-helicity, neither bound nor inhibited the IP (3)R1 channel, and in turn lost its anti-apoptotic effect. Similar results were obtained with other substitutions in Bcl-2-BH4 that destabilized the alpha-helix with concomitant loss of IP3R inhibition. These results provide new insights for the further development of Bcl-2-BH4-derived peptides as specific inhibitors of the IP3R with significant pharmacological implications

Unveiling the prehistoric landscape at Stonehenge through multi-receiver EMI

YesArchaeological research at Stonehenge (UK) is increasingly aimed at understanding the dynamic of the wider archaeological landscape. Through the application of state-of-the-art geophysical techniques, unprecedented insight is being gathered into the buried archaeological features of the area. However, applied survey techniques have rarely targeted natural soil variation, and the detailed knowledge of the palaeotopography is consequently less complete. In addition, metallic topsoil debris, scattered over different parts of the Stonehenge landscape, often impacts the interpretation of geophysical datasets. The research presented here demonstrates how a single multi-receiver electromagnetic induction (EMI) survey, conducted over a 22 ha area within the Stonehenge landscape, offers detailed insight into natural and anthropogenic soil variation at Stonehenge. The soil variations that were detected through recording the electrical and magnetic soil variability, shed light on the genesis of the landscape, and allow for a better definition of potential palaeoenvironmental and archaeological sampling locations. Based on the multi-layered dataset, a procedure was developed to remove the influence of topsoil metal from the survey data, which enabled a more straightforward identification of the detected archaeology. The results provide a robust basis for further geoarchaeological research, while potential to differentiate between modern soil disturbances and the underlying sub-surface variations can help in solving conservation and management issues. Through expanding this approach over the wider area, we aim at a fuller understanding of the human–landscape interactions that have shaped the Stonehenge landscape

The orbits of subdwarf B + main-sequence binaries. I: The sdB+G0 system PG 1104+243

The predicted orbital period histogram of an sdB population is bimodal with a peak at short ( 250 days) periods. Observationally, there are many short-period sdB systems known, but only very few long-period sdB binaries are identified. As these predictions are based on poorly understood binary interaction processes, it is of prime importance to confront the predictions to observational data. In this contribution we aim to determine the absolute dimensions of the long-period sdB+MS binary system PG1104+243. High-resolution spectroscopy time-series were obtained with HERMES at the Mercator telescope at La Palma, and analyzed to obtain radial velocities of both components. Photometry from the literature was used to construct the spectral energy distribution (SED) of the binary. Atmosphere models were used to fit this SED and determine the surface gravity and temperature of both components. The gravitational redshift provided an independent confirmation of the surface gravity of the sdB component. An orbital period of 753 +- 3 d and a mass ratio of q = 0.637 +- 0.015 were found from the RV-curves. The sdB component has an effective temperature of Teff = 33500 +- 1200 K and a surface gravity of logg = 5.84 +- 0.08 dex, while the cool companion is found to be a G-type star with Teff = 5930 +- 160 K and logg = 4.29 +- 0.05 dex. Assuming a canonical mass of Msdb = 0.47 Msun, the MS component has a mass of 0.74 +- 0.07 Msun, and its Teff corresponds to what is expected for a terminal age main-sequence star with sub-solar metalicity. PG1104+243 is the first long-period sdB binary in which accurate physical parameters of both components could be determined, and the first sdB binary in which the gravitational redshift is measured. Furthermore, PG1104+243 is the first sdB+MS system that shows consistent evidence for being formed through stable Roche-lobe overflow.Comment: Accepted by A&A on 05-10-201

Physical Activity Status in Patients With Coronary Heart Disease: Results From the Cross-Sectional EUROASPIRE Surveys.

BACKGROUND: The study aim was to assess the physical activity levels as well as the intention to become physically active in patients with stable coronary heart disease (CHD) with a special focus on the association with their risk profile. METHODS: Analyses are based on the cross-sectional EUROASPIRE IV surveys. Information was available on 8966 patients in EUROASPIRE III and on 7998 patients in EUROASPIRE IV. Physical activity level according to patients risk profile and their medical management was assessed, the intention to become physically active was investigated and a time trend analysis was performed. RESULTS: A better cardiovascular risk profile as well as receiving physical activity advice or weight loss advice was associated with better physical activity levels. The physical activity status improved significantly over time, the proportion of patients reporting vigorous physical activity for at least 20 minutes ≥ 3 times/week increased from 14.1% to 20.2% (P < .001). Similarly, a significantly greater proportion of patients are in the maintenance stage (36.6% vs. 27.4%) and a smaller proportion in the precontemplation stage (43.2% vs. 52.3%). CONCLUSION: Although an increase was seen in the proportion of patients being adequately physical active, physical activity levels remain suboptimal in many CHD patients

Perceived Adverse Drug Events in Heart Failure Patients' Perception and Related Factors

Background: Patients with heart failure (HF) often perceive adverse drug events (ADEs), affecting quality of life. For weighing the benefits and burden of medication in HF care, knowledge on patients' perception of ADEs is needed. Our aim was to assess these ADE perceptions and to identify factors related to these perceptions. Methods: A cross-sectional study was performed including HF patients recruited from primary care and outpatient clinics. Patients were included in the analysis if they perceived an ADE in the past 4 weeks. This information was collected using an open-ended question and a symptom checklist. Data on ADE perception were obtained using a modified version of the Revised Illness Perception Questionnaire. Demographic, clinical, and ADE characteristics were collected by self-administered questionnaire and chart review. The relations between these factors and ADE perceptions were analyzed using regression analyses. Results: In total, 261 HF patients perceived an ADE and completed the questionnaire. Patients reported 814 ADEs, of which 26% of the patients reported dizziness and 24% reported dry mouth as being the most prevalent. Almost half of the patients (46%) perceived their ADE as something serious, with major consequences for their daily life (40%) and reported to be worried (36%) about the ADE. Patients perceived the ADE as a chronic problem (91%), and the majority believed more in the ability of the health care provider to control the ADE (61%) than in their own ability (46%). Demographic and clinical variables had a limited contribution to the explained variance of ADE perceptions after adjusting for ADE characteristics, such as perceived severity. Conclusion: Patients with HF perceive particular negative consequences and emotional distress of symptomatic ADE. Open communication between patients and providers with attention for patients ADE perceptions would be valuable during the decision process of ADE management and may result in a regimen aligned with patients' preferences and needs