Feasibility of Barley Straw Fibers as Reinforcement in Fully Biobased Polyethylene Composites: Macro and Micro Mechanics of the Flexural Strength.

Awareness on deforestation, forest degradation, and its impact on biodiversity and global warming, is giving rise to the use of alternative fiber sources in replacement of wood feedstock for some applications such as composite materials and energy production. In this category, barley straw is an important agricultural crop, due to its abundance and availability. In the current investigation, the residue was submitted to thermomechanical process for fiber extraction and individualization. The high content of holocellulose combined with their relatively high aspect ratio inspires the potential use of these fibers as reinforcement in plastic composites. Therefore, fully biobased composites were fabricated using barley fibers and a biobased polyethylene (BioPE) as polymer matrix. BioPE is completely biobased and 100% recyclable. As for material performance, the flexural properties of the materials were studied. A good dispersion of the reinforcement inside the plastic was achieved contributing to the elevate increments in the flexural strength. At a 45 wt.% of reinforcement, an increment in the flexural strength of about 147% was attained. The mean contribution of the fibers to the flexural strength was assessed by means of a fiber flexural strength factor, reaching a value of 91.4. The micromechanical analysis allowed the prediction of the intrinsic flexural strength of the fibers, arriving up to around 700 MPa, and coupling factors between 0.18 and 0.19, which are in line with other natural fiber composites. Overall, the investigation brightness on the potential use of barley straw residues as reinforcement in fully biobased polymer composites.

Advances in Rational Design and Materials of High-Performance Stretchable Electromechanical Sensors.

Stretchable and wearable sensor technology has attracted significant interests and created high technological impact on portable healthcare and smart human-machine interfaces. Wearable electromechanical systems are an important part of this technology that has recently witnessed tremendous progress toward high-performance devices for commercialization. Over the past few years, great attention has been paid to simultaneously enhance the sensitivity and stretchability of the electromechanical sensors toward high sensitivity, ultra-stretchability, low power consumption or self-power functionalities, miniaturisation as well as simplicity in design and fabrication. This work presents state-of-the-art advanced materials and rational designs of electromechanical sensors for wearable applications. Advances in various sensing concepts and structural designs for intrinsic stretchable conductive materials as well as advanced rational platforms are discussed. In addition, the practical applications and challenges in the development of stretchable electromechanical sensors are briefly mentioned and highlighted.

Cryopreservation timing is a critical process parameter in a thymic regulatory T-cell therapy manufacturing protocol.

Regulatory T cells (Tregs) are a promising therapy for several immune-mediated conditions but manufacturing a homogeneous and consistent product, especially one that includes cryopreservation, has been challenging. Discarded pediatric thymuses are an excellent source of therapeutic Tregs with advantages including cell quantity, homogeneity and stability. Here we report systematic testing of activation reagents, cell culture media, restimulation timing and cryopreservation to develop a Good Manufacturing Practice (GMP)-compatible method to expand and cryopreserve Tregs. By comparing activation reagents, including soluble antibody tetramers, antibody-conjugated beads and artificial antigen-presenting cells (aAPCs) and different media, we found that the combination of Dynabeads Treg Xpander and ImmunoCult-XF medium preserved FOXP3 expression and suppressive function and resulted in expansion that was comparable with a single stimulation with aAPCs. Cryopreservation tests revealed a critical timing effect: only cells cryopreserved 1-3 days, but not >3 days, after restimulation maintained high viability and FOXP3 expression upon thawing. Restimulation timing was a less critical process parameter than the time between restimulation and cryopreservation. This systematic testing of key variables provides increased certainty regarding methods for in vitro expansion and cryopreservation of Tregs. The ability to cryopreserve expanded Tregs will have broad-ranging applications including enabling centralized manufacturing and long-term storage of cell products.

Towards a common framework for defining ancillary material quality across the development spectrum.

Ancillary materials (AMs) play a critical role in the manufacture of cell and gene therapies, and best practices for their quality management are the subject of ongoing discussion. Given that the final product cannot be sterilized, AM quality becomes increasingly critical to the clinical advancement of cell and gene therapies. Despite a lack of direct legislative direction regarding AM quality, internationally harmonized guidance is available from several industry-standard bodies that describe the principles and application of a risk-based approach to AM qualification and related supply-chain risk management. According to a best-practice risk-based approach, AMs must be adequately qualified to a degree that reflects the level of risk the material presents to patient safety and the drug product's specification. This general approach can be implemented in different ways, and balancing quality with cost of goods is critical to the cost-effective manufacture of advanced therapy medicinal products. In some cases, it may be preferable or necessary to use AMs that are produced in compliance with current Good Manufacturing Practice. However, developers may be able to suppress manufacturing costs without undermining safety or regulatory compliance in the case that a material presents a lower risk profile. Despite a great deal of attention and interest in the quality of AMs in the cell and gene therapy space, there is still a need for greater harmonization to create a shared understanding of what constitutes a risk-based approach to AM production and sourcing. In this article, we propose a staged approach to AM quality that achieves a balance between the competing demands of risk mitigation and cost of goods containment at the various stages of AM quality development. Our novel, heuristic framework for communication among AM suppliers, users and regulators aims to bring down development and manufacturing costs and lessen the workload around regulatory compliance.

Automated Good Manufacturing Practice-compliant generation of human monocyte-derived dendritic cells from a complete apheresis product using a hollow-fiber bioreactor system overcomes a major hurdle in the manufacture of dendritic cells for cancer vaccines.

BACKGROUND: Although dendritic cell (DC)-based cancer vaccines represent a promising treatment strategy, its exploration in the clinic is hampered due to the need for Good Manufacturing Practice (GMP) facilities and associated trained staff for the generation of large numbers of DCs. The Quantum bioreactor system offered by Terumo BCT represents a hollow-fiber platform integrating GMP-compliant manufacturing steps in a closed system for automated cultivation of cellular products. In the respective established protocols, the hollow fibers are coated with fibronectin and trypsin is used to harvest the final cell product, which in the case of DCs allows processing of only one tenth of an apheresis product. MATERIALS AND RESULTS: We successfully developed a new protocol that circumvents the need for fibronectin coating and trypsin digestion, and makes the Quantum bioreactor system now suitable for generating large numbers of mature human monocyte-derived DCs (Mo-DCs) by processing a complete apheresis product at once. To achieve that, it needed a step-by-step optimization of DC-differentiation, e.g., the varying of media exchange rates and cytokine concentration until the total yield (% of input CD14+ monocytes), as well as the phenotype and functionality of mature Mo-DCs, became equivalent to those generated by our established standard production of Mo-DCs in cell culture bags. CONCLUSIONS: By using this new protocol for the Food and Drug Administration-approved Quantum system, it is now possible for the first time to process one complete apheresis to automatically generate large numbers of human Mo-DCs, making it much more feasible to exploit the potential of individualized DC-based immunotherapy.

Computational modeling of fatigue crack propagation in butt welded joints subjected to axial load.

This article addresses the study of crack behavior elicited on axial fatigue in specimens joined by butt weld made of steel ASTM A36 by using fracture mechanics and simulation software of finite elements (Ansys APDL, Franc3D). The computational model was initially to define the geometry model by using CAD software. Specimens with Weld Reinforcement of 2 mm and 3mm were simulated. Subsequently, the type of element for the mesh, the information inclusion concerning material mechanical properties and load conditions were selected. By using Franc3D software, the crack propagation phenomenon is analyzed, and its growth parameters have been established. In this way, it is possible to calculate the magnitude of stress intensity factor (SIF) along the crack front. It is concluded that the stress located in the weld toe is maximized proportionately to the size of the weld reinforcement due to the concentration effect of geometric stress. In addition, it is observed that the propagation rate obtained from Paris law has a similar behavior for the studied weld reinforcements; the latter as there were short cracks.

Not all artificial structures are created equal: Pilings linked to greater ecological and environmental change in sediment communities than seawalls.

Artificial structures are agents of change in marine ecosystems. They add novel habitat for hard-substrate organisms and modify the surrounding environment. Most research to date has focused on the communities living directly on artificial structures, and more research is needed on the potential impacts these structures have on nearby communities and the surrounding environment. We compared the sedimentary habitat surrounding two types of artificial structures (pilings and seawalls) to sediments adjacent to rocky reefs using a combination of traditional sediment analyses, stable isotope analysis, and environmental DNA. Artificial and natural shore sediments were best differentiated by sediment variables strongly associated with flow speed. Pilings sediments had significantly finer grain size, higher organic content, and generally lower C:N ratios than sediments adjacent to the other habitat types, suggesting flow is reduced by pilings. Sedimentary assemblages near pilings were also consistent with those predicted under low-flow conditions, with elevated bacterial colonization and increased relative abundances of small deposit feeders compared with other habitat types. Additionally, lumbrinerid polychaetes in pilings sediments had reduced δ15N values, suggesting different detrital resources and fewer trophic linkages compared with lumbrinerids in other habitats. Woody detritus was greater adjacent to seawalls than to natural rocky shores or pilings. Our findings suggest that artificial structures have the potential to influence adjacent soft sediments through changes to sediment properties that affect infaunal and microbial communities, as well as trophic linkages for some consumers. We hypothesize that this is due to a combination of altered flow, differing detrital subsidies, and differing adjacent land-use among habitat types. Managers should consider the potential for changed sediment properties and ecology when deciding where to build different types of artificial structures. Further manipulative experiments are needed to understand mechanisms of change and help manage the impacts of artificial structures on the seafloor.

A Decision-Making Method with Grey Multi-Source Heterogeneous Data and Its Application in Green Supplier Selection.

In view of the multi-attribute decision-making problem that the attribute values are grey multi-source heterogeneous data, a decision-making method based on kernel and greyness degree is proposed. The definitions of kernel and greyness degree of an extended grey number in a grey multi-source heterogeneous data sequence are given. On this basis, we construct the kernel vector and greyness degree vector of the sequence to whiten the multi-source heterogeneous information, then a grey relational bi-directional projection ranking method is presented. Considering the multi-attribute multi-level decision structure and the causalities between attributes in decision-making problem, the HG-DEMATEL method is proposed to determine the hierarchical attribute weights. A green supplier selection example is provided to demonstrate the rationality and validity of the proposed method.

Membrane Innovation in Dialysis.

Despite advances in renal replacement therapy, the adequate removal of uremic toxins over a broad molecular weight range remains one of the unmet needs in hemodialysis. Therefore, membrane innovation is currently directed towards enhanced removal of uremic toxins and increased membrane permeability. This chapter presents a variety of opportunities where innovation is brought into dialysis membranes. It covers the membrane formation from solution, describing different approaches to control the phase inversion process through additives that either swell in the polymer solution or influence the pore shrinkage during the membrane drying process. Additionally, large-scale manufacturing is described, and the influence of raw materials, spinning, and drying processes on membrane selectivity are presented. Finally, new characterization methods developed for the latest innovations around the application of membranes in dialysis are discussed, which allow the membrane performance for removal of a broad range of uremic toxins and the expected albumin loss in clinical use.

Medical Gas Containers and Closures; Current Good Manufacturing Practice Requirements. Final rule.

The Food and Drug Administration (FDA or the Agency) is amending its current good manufacturing practice (CGMP) and labeling regulations regarding medical gases. FDA is requiring that portable cryogenic medical gas containers not manufactured with permanent gas use outlet connections have gas-specific use outlet connections that cannot be readily removed or replaced except by the manufacturer. FDA is also requiring that portable cryogenic medical gas containers and high-pressure medical gas cylinders meet certain labeling, naming, and color requirements. These requirements are intended to increase the likelihood that the contents of medical gas containers are accurately identified and reduce the likelihood of the wrong gas being connected to a gas supply system or container. FDA is also revising an existing regulation that conditionally exempts certain medical gases from certain otherwise-applicable labeling requirements in order to add oxygen and nitrogen to the list of gases subject to the exemption, and to remove cyclopropane and ethylene from the list.

Quality Control Assays for Clinical-Grade Human Mesenchymal Stromal Cells: Methods for ATMP Release.

Mesenchymal stromal/stem cells (MSC) are promising candidates for the development of cell-based therapies for various diseases and are currently being evaluated in a number of clinical trials (Sharma et al., Transfusion 54:1418-1437, 2014; Ikebe and Suzuki, Biomed Res Int 2014:951512, 2014). MSC for therapeutic applications are classified as advanced therapy medicinal products (ATMP) (Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004) and must be prepared according to good manufacturing practices ( http://ec.europa.eu/health/documents/eudralex/vol-4 ). They may be derived from different starting materials (mainly bone marrow (BM), adipose tissue, or cord blood) and applied as fresh or cryopreserved products, in the autologous as well as an allogeneic context (Sharma et al., Transfusion 54:1418-1437, 2014; Ikebe and Suzuki, Biomed Res Int 2014:951512, 2014; Sensebé and Bourin, Transplantation 87(9 Suppl):S49-S53, 2009). In any case, they require an approved and well-defined panel of assays in order to be released for clinical use.This chapter describes analytical methods implemented and performed in our cell factory as part of the release strategy for an ATMP consisting of frozen autologous BM-derived MSC. Such methods are designed to assess the safety (sterility, endotoxin, and mycoplasma assays) and identity/potency (cell count and viability, immunophenotype and clonogenic assay) of the final product. Some assays are also applied to the biological starting material (sterility) or carried out as in-process controls (sterility, cell count and viability, immunophenotype, clonogenic assay).The validation strategy for each analytical method is described in the accompanying Chapter 20 .

Clinical-Grade Manufacturing of Therapeutic Human Mesenchymal Stem/Stromal Cells in Microcarrier-Based Culture Systems.

The therapeutic potential of mesenchymal stem/stromal cells (MSC) has triggered the need for high cell doses in a vast number of clinical applications. This demand requires the development of good manufacturing practices (GMP)-compliant ex vivo expansion protocols that should be effective to deliver a robust and reproducible supply of clinical-grade cells in a safe and cost-effective manner. Controlled stirred-tank bioreactor systems under xenogeneic (xeno)-free culture conditions offer ideal settings to develop and optimize cell manufacturing to meet the standards and needs of human MSC for cellular therapies. Herein we describe two microcarrier-based stirred culture systems using spinner flasks and controlled stirred-tank bioreactors under xeno-free conditions for the efficient ex vivo expansion of human bone marrow and adipose tissue-derived MSC.

GMP-Compliant Expansion of Clinical-Grade Human Mesenchymal Stromal/Stem Cells Using a Closed Hollow Fiber Bioreactor.

This chapter describes a method for GMP-compliant expansion of human mesenchymal stromal/stem cells (hMSC) from bone marrow aspirates, using the Quantum(®) Cell Expansion System from Terumo BCT. The Quantum system is a functionally closed, automated hollow fiber bioreactor system designed to reproducibly grow cells in either GMP or research laboratory environments. The chapter includes protocols for preparation of media, setup of the Quantum system, coating of the hollow fiber bioreactor, as well as loading, feeding, and harvesting of cells. We suggest a panel of quality controls for the starting material, the interim product, as well as the final product.

The pharmaceutical vial capping process: Container closure systems, capping equipment, regulatory framework, and seal quality tests.

Parenteral drug products are protected by appropriate primary packaging to protect against environmental factors, including potential microbial contamination during shelf life duration. The most commonly used CCS configuration for parenteral drug products is the glass vial, sealed with a rubber stopper and an aluminum crimp cap. In combination with an adequately designed and controlled aseptic fill/finish processes, a well-designed and characterized capping process is indispensable to ensure product quality and integrity and to minimize rejections during the manufacturing process. In this review, the health authority requirements and expectations related to container closure system quality and container closure integrity are summarized. The pharmaceutical vial, the rubber stopper, and the crimp cap are described. Different capping techniques are critically compared: The most common capping equipment with a rotating capping plate produces the lowest amount of particle. The strength and challenges of methods to control the capping process are discussed. The residual seal force method can characterize the capping process independent of the used capping equipment or CCS. We analyze the root causes of several cosmetic defects associated with the vial capping process.

Multidisciplinary Testing of Floor Pads on Stability, Energy Absorption, and Ease of Hospital Use for Enhanced Patient Safety.

OBJECTIVES: A major improvement in hospital safety could be realized if serious injury did not accompany falls. We studied several commercially available floor pads made of different materials to determine which (if any) would be practical in a hospital room and reduce injury without posing a threat to the balance of patients. METHODS: A multidisciplinary approach was undertaken to (1) measure upper and lower body motion in 17 young (<50 years) and 17 older (>55 years) adults during an instrumented sit to stand test from a hospital bed onto the different floor pads, (2) predict the energy dissipation available in floor pads by quantifying the relative mechanical properties, and (3) obtain professional feedback from hospital nurses via a questionnaire (8 questions) following a period of working on the different floor pads. Five floor pads, composed of foam, gel, and/or rubber were tested. All pads were compared with a typical hospital floor (concrete covered with linoleum tiles, considered the control). RESULTS: All of the pads subject to mechanical testing showed at least 3 times more energy absorption compared with the control. Balance testing showed that three of the pads resulted in minimal or no significant increases in body motion during sit-to-stand. Nursing feedback revealed that only 2 of these 3 pads may be feasible for hospital room use: one made primarily of firm rubber and one made of foam. CONCLUSIONS: Floor pads do exist that show promise for hospital use that absorbing energy without major impacts on balance during sit-to-stand. Although only commercially available pads were investigated, results may inform the design and multidisciplinary testing of other floor surfaces.

Visual Inspection Reliability for Precision Manufactured Parts.

OBJECTIVE: Sandia National Laboratories conducted an experiment for the National Nuclear Security Administration to determine the reliability of visual inspection of precision manufactured parts used in nuclear weapons. BACKGROUND: Visual inspection has been extensively researched since the early 20th century; however, the reliability of visual inspection for nuclear weapons parts has not been addressed. In addition, the efficacy of using inspector confidence ratings to guide multiple inspections in an effort to improve overall performance accuracy is unknown. Further, the workload associated with inspection has not been documented, and newer measures of stress have not been applied. METHOD: Eighty-two inspectors in the U.S. Nuclear Security Enterprise inspected 140 parts for eight different defects. RESULTS: Inspectors correctly rejected 85% of defective items and incorrectly rejected 35% of acceptable parts. Use of a phased inspection approach based on inspector confidence ratings was not an effective or efficient technique to improve the overall accuracy of the process. Results did verify that inspection is a workload-intensive task, dominated by mental demand and effort. CONCLUSION: Hits for Nuclear Security Enterprise inspection were not vastly superior to the industry average of 80%, and they were achieved at the expense of a high scrap rate not typically observed during visual inspection tasks. APPLICATION: This study provides the first empirical data to address the reliability of visual inspection for precision manufactured parts used in nuclear weapons. Results enhance current understanding of the process of visual inspection and can be applied to improve reliability for precision manufactured parts.

Correlation between hierarchical structure of crystal networks and macroscopic performance of mesoscopic soft materials and engineering principles.

This review examines how the concepts and ideas of crystallization can be extended further and applied to the field of mesoscopic soft materials. It concerns the structural characteristics vs. the macroscopic performance, and the formation mechanism of crystal networks. Although this subject can be discussed in a broad sense across the area of mesoscopic soft materials, our main focus is on supramolecular materials, spider and silkworm silks, and biominerals. First, the occurrence of a hierarchical structure, i.e. crystal network and domain network structures, will facilitate the formation kinetics of mesoscopic phases and boost up the macroscopic performance of materials in some cases (i.e. spider silk fibres). Second, the structure and performance of materials can be correlated in some way by the four factors: topology, correlation length, symmetry/ordering, and strength of association of crystal networks. Moreover, four different kinetic paths of crystal network formation are identified, namely, one-step process of assembly, two-step process of assembly, mixed mode of assembly and foreign molecule mediated assembly. Based on the basic mechanisms of crystal nucleation and growth, the formation of crystal networks, such as crystallographic mismatch (or noncrystallographic) branching (tip branching and fibre side branching) and fibre/polymeric side merging, are reviewed. This facilitates the rational design and construction of crystal networks in supramolecular materials. In this context, the (re-)construction of a hierarchical crystal network structure can be implemented by thermal, precipitate, chemical, and sonication stimuli. As another important class of soft materials, the unusual mechanical performance of spider and silkworm silk fibres are reviewed in comparison with the regenerated silk protein derivatives. It follows that the considerably larger breaking stress and unusual breaking strain of spider silk fibres vs. silkworm silk fibres can be interpreted according to the synergistically correlated hierarchical structures of the domain and crystal networks, which can be quantified by the hierarchical structural correlation and the four structural parameters. Based on the concept of crystal networks, the new understanding acquired will transfer the research and engineering of mesoscopic materials, particularly, soft functional materials, to a new phase.

Survey of perfluoroalkyl acids (PFAAs) and their precursors present in Japanese consumer products.

Perfluoroalkyl acids (PFAAs) and their precursors have been used in various consumer products. However, limited information regarding their occurrence and concentration levels in products is available. In this study, we investigated 18 PFAAs and 14 PFAA precursors in various categories of consumer products purchased in Japan. Relatively high total concentrations of PFAAs and their precursors were found in sprays for fabrics and textiles (