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With its excellent biocompatibility, biodegradability, and antimicrobial activity, chitosan is a promising scaffold material for hard-tissue engineering. Yet, pristine chitosan foams typically lack the strength and porosity required for such use. Here we present a simple emulsion-templating approach to fabricate pristine chitosan foams with optimized strength and porosity. Sodium dodecyl sulfate (SDS), a widely used biocompatible anionic surfactant, was employed at trace levels to aid polymerization. The foams display a dual-scale pore morphology. Cavities of 150–300 μm are separated by around 50 μm thick chitosan walls containing large interconnecting openings. The walls are further populated with meso- and macropores of 50–500 nm. This architecture should support cell attachment and growth, facilitate proliferation, and enhance nutrient transport and metabolic exchange. The structure yields high surface area (up to 10 m2 g−1). Mechanically, the thick-walled cavities impart both elastic recovery and high compressive resistance (255 kPa at 40% strain from foams polymerized with 4% chitosan). A preliminary drug-release study using vancomycin confirmed excellent loading and sustained release.

Logistics planning in emergency situations involves dispatching commodities (e.g., medical materials and personnel, specialised rescue equipment and rescue teams, food, etc.) to distribution centres in affected areas as soon as possible so that relief operations are accelerated. In this study, a planning model that is to be integrated into a natural disaster logistics Decision Support System is developed. The model addresses the dynamic time-dependent transportation problem that needs to be solved repetitively at given time intervals during ongoing aid delivery. The model regenerates plans incorporating new requests for aid materials, new supplies and transportation means that become available during the current planning time horizon. The plan indicates the optimal mixed pick up and delivery schedules for vehicles within the considered planning time horizon as well as the optimal quantities and types of loads picked up and delivered on these routes.

This article investigates whether campaign speeches during the US presidential elections can help predict foreign policy behavior. We use speeches made by Donald J. Trump during his bid for president in 2016. We compare the analysis from 2016 with his actual foreign policy decisions during his tenure, 2017-2020. Operational code analysis and leadership traits analysis approaches are used to analyze candidate Trump's foreign policy beliefs and strategies associated with them. We use Profiler Plus software to conduct content analysis which produces OCA and LTA results. We use three separate datasets to analyze Trump's beliefs and traits focusing on his general foreign policy speeches, the MENA region, and a third one only about Islamic State and Syria. Our results show that Trump's profile indicates a foreign policy orientation that avoids involvement in affairs that are perceived as beyond immediate interests. The consistency between his beliefs and traits during the 2016 campaign and his actual foreign policy behavior leads us to conclude that individual level analysis, and specifically OCA and LTA approaches, are useful tools to analyze, explain and predict foreign policy.

The hydration performance of GCL can be influenced from several factors one of which is bentonite mass per unit area (MPUA). This study reports the hydration and hydraulic conductivity of a GCL over a wide range of MPUA. GCLs were hydrated over a compacted silty sand for 7 and 30 days and water contents were determined. It was found that water content linearly decreased from 74 to 61% as the MPUA increased. Subsequent to hydration, GCLs were cut in 100 mm in diameter to determine the hydraulic conductivity. To reexamine the bentonite MPUAs in 100 mm diameter GCLs, the water-holding capacity of geotextile components was determined. It was found that water content of non-woven geotextiles increased from 12 to 45%, while that of woven geotextile remained constant at 2% when the bentonite MPUA increased. Finally, hydraulic conductivity tests were carried out on the samples with varying MPUAs. The results showed that the hydraulic conductivity of GCL ranged between 5.2 × 10–12 and 2.6 × 10–11 m/s. The hydraulic conductivity was still low (i.e., 9.2 × 10–12 m/s) when the bentonite MPUA was decreased further to 1.8 kg/m2.

Defined and semi-defined medium-based feeding strategies were developed to enhance recombinant human growth hormone (rhGH) production by Bacillus subtilis BGSC-1A178 (scoC ⁻) strain carrying pMK4::pre(subC)::hGH. Defined medium-based feeding strategies were designed by exponential feeding of glucose and (NH₄)₂HPO₄ at two pre-determined specific growth rates, µ ₀ = 0.10 and 0.17 h⁻¹. Semi-defined medium-based feeding strategies were designed by exponential feeding of substrate solution consisting of glucose, (NH₄)₂HPO₄, peptone, and trace salt solution (PTM1) at three pre-determined specific growth rates, µ ₀ = 0.10, 0.17, and 0.25 h⁻¹. At all the strategies applied, transition cultivation time from batch to fed-batch operation was t T = 4 h. The highest rhGH concentration was obtained as C ᵣₕGH = 0.5 g L⁻¹ with semi-defined medium-based feeding strategy designed with µ ₀ = 0.25 h⁻¹ using feed substrate stock solution containing 200 g L⁻¹ glucose, 117 g L⁻¹ (NH₄)₂HPO₄, 100 g L⁻¹ peptone, and 5 mL L⁻¹ PTM1 at t = 22 h when the cell concentration reached to C X = 8.29 g L⁻¹. The overall product and cell yields on glucose were obtained as [Formula: see text] = 7.21 mg g⁻¹ and [Formula: see text] = 0.12 g g⁻¹, respectively. The results indicate the requirement of designing continuous feed stream in fed-batch production to enhance rhGH production by r-B. subtilis.

Pompe disease is a rare, progressive neuromuscular disorder caused by deficiency of acid α-glucosidase (GAA) and accumulation of lysosomal glycogen. We assessed the safety and efficacy of avalglucosidase alfa, a recombinant human GAA enzyme replacement therapy specifically designed for enhanced mannose-6-phosphate-receptor targeting and enzyme uptake aimed at increased glycogen clearance, compared with the current approved standard of care, alglucosidase alfa, in patients with late-onset Pompe disease. We did a randomised, double-blind, phase 3 trial at 55 sites in 20 countries. We enrolled individuals (aged ≥3 years) with enzymatically confirmed late-onset Pompe disease who had never received treatment. We used a centralised treatment allocation system to randomly allocate participants to either avalglucosidase alfa or alglucosidase alfa. Participants and investigators were unaware of their treatment allocation. The primary outcome measure was change from baseline to week 49 in upright forced vital capacity percent (FVC%) predicted. We used a hierarchical fixed sequential testing strategy, whereby non-inferiority of avalglucosidase alfa compared with alglucosidase alfa was assessed first, with a non-inferiority margin of 1·1. If non-inferiority was seen, then superiority was tested with a 5% significance level. The key secondary objective was effect on functional endurance, measured by the 6-minute walk test (6MWT). Safety was assessed, including treatment-emergent adverse events and infusion-associated reactions. The modified intent-to-treat population was the primary analysis population for all efficacy analyses. The safety population was the analysis population for safety analyses. This trial is registered with ClinicalTrials.gov, NCT02782741. We report results of the 49-week primary analysis period. Between Nov 2, 2016, and March 29, 2019, 100 participants were randomly allocated avalglucosidase alfa (n=51) or alglucosidase alfa (n=49). Treatment with avalglucosidase alfa resulted in a least-squares mean improvement in upright FVC% predicted of 2·89% (SE 0·88) compared with 0·46% (0·93) with alglucosidase alfa at week 49 (difference 2·43% [95% CI −0·13 to 4·99]). Non-inferiority was shown because the lower bound of the 95% CI for the difference far exceeded the predefined non-inferiority margin but did not exclude 0 (p=0·0074). Superiority was not reached (p=0·063), so formal testing was stopped, as per the testing hierarchy. Improvements were also seen in the 6MWT with avalglucosidase alfa compared with alglucosidase alfa, with greater increases in distance covered (difference 30·01 m [95% CI 1·33 to 58·69]) and percent predicted (4·71% [0·25 to 9·17]). Treatment-emergent adverse events potentially related to treatment were reported in 23 (45%) of 51 participants in the avalglucosidase alfa group and in 24 (49%) of 49 in the alglucosidase alfa group, and infusion-associated reactions were reported in 13 (26%) participants in the avalglucosidase alfa group and 16 (33%) in the alglucosidase alfa group. Of the five trial withdrawals, all in the alglucosidase alfa group, four were due to adverse events, including two infusion-associated reactions. Serious treatment-emergent adverse events were reported in eight (16%) participants who received avalglucosidase alfa and in 12 (25%) who received alglucosidase alfa. One participant treated with alglucosidase alfa died because of acute myocardial infarction determined to be unrelated to treatment. Antidrug antibody responses were similar in both groups. High and persistent titres (≥12 800) and neutralising antibodies were more common with alglucosidase alfa (in 16 [33%] participants) than with avalglucosidase alfa (ten [20%]). We consider that this study provides evidence of clinically meaningful improvement with avalglucosidase alfa therapy over alglucosidase alfa in respiratory function, ambulation, and functional endurance, with no new safety signals reported. An open-label extended-treatment period is ongoing to confirm the long-term safety and efficacy of avalglucosidase alfa, with the aim for this therapy to become the new standard treatment in late-onset Pompe disease. Sanofi Genzyme.

The recent Arab uprisings have forced many actors to reconsider their positions regarding Middle Eastern politics. Role theory provides a viable tool to explain changes in actors’ foreign policy behaviors, presuming that states’ foreign policies are shaped by the ruling elites’ foreign policy role conceptions. This article analyzes Turkish foreign policy roles with regard to the Middle East and North Africa before and since the Arab uprisings that began in December 2010. We argue that these uprisings caused Turkey to change its emphasis from roles built on soft power instruments to harder roles requiring material capabilities. We also discuss the implications of this change with reference to theories of international politics.

The transition of cells from an epithelial to a mesenchymal phenotype is a critical event during morphogenesis in multicellular organisms and underlies the pathology of many diseases, including the invasive phenotype associated with metastatic carcinomas. Transforming growth factor β (TGFβ) is a key regulator of epithelial-to-mesenchymal transition (EMT). However, the molecular mechanisms that control the dissolution of tight junctions, an early event in EMT, remain elusive. We demonstrate that Par6, a regulator of epithelial cell polarity and tight-junction assembly, interacts with TGFβ receptors and is a substrate of the type II receptor, TβRII. Phosphorylation of Par6 is required for TGFβ-dependent EMT in mammary gland epithelial cells and controls the interaction of Par6 with the E3 ubiquitin ligase Smurf1. Smurf1, in turn, targets the guanosine triphosphatase RhoA for degradation, thereby leading to a loss of tight junctions. These studies define how an extracellular cue signals to the polarity machinery to control epithelial cell morphology.

Signaling pathways transmit information through protein interaction networks that are dynamically regulated by complex extracellular cues. We developed LUMIER (for luminescence-based mammalian interactome mapping), an automated high-throughput technology, to map protein-protein interaction networks systematically in mammalian cells and applied it to the transforming growth factor-{szligbeta} (TGF{szligbeta}) pathway. Analysis using self-organizing maps and k-means clustering identified links of the TGF{szligbeta} pathway to the p21-activated kinase (PAK) network, to the polarity complex, and to Occludin, a structural component of tight junctions. We show that Occludin regulates TGF{szligbeta} type I receptor localization for efficient TGF{szligbeta}-dependent dissolution of tight junctions during epithelial-to-mesenchymal transitions.