Clinically Applicable Assessment of Tisagenlecleucel CAR T Cell Treatment by Digital Droplet PCR for Copy Number Variant Assessment

Chimeric antigen receptor (CAR) T cell therapy is an innovative immunotherapy for treating cancers in both children and adults with proven utility in numerous clinical trials. Significantly, some CAR T cell therapies have now been approved by relevant national regulatory bodies across numerous countries for clinical therapeutic use outside of clinical trials. One such recently licensed product is tisagenlecleucel, a CAR T therapy approved for the treatment of B-cell acute lymphoblastic leukemia (B-ALL) using autologous T cells from the patient. The genetically engineered T cells target a protein called CD19, common to B cells, through a CAR incorporating a 4-1BB costimulatory domain to improve response. Since tisagenlecleucel is now a standard of care treatment for B-ALL, it is clinically essential to be able to accurately monitor these CAR T cells in patients. Assessment of the copy number variant (CNV) of the CAR T cell products allows this within a clinically acceptable timeframe for optimal patient benefit. However, no standardized method with high reproducibility and efficiency has been described within a routine clinical laboratory setting. Here, we demonstrated a novel digital droplet PCR (ddPCR)-based methodology for the study of CNV (ddPCR-CNV) in 4-1BB CD19-specific CAR T cells with universal applicability across clinical diagnostic laboratories.     

Energy‐efficient management using a traffic‐oriented routing scheme for cognitive radio networks

This paper elaborates on a traffic manipulation routing scheme that associates the moments of the traffic, targeting the maximization of the energy conservation, as well as the effective resource management of the network nodes. The energy conservation is achieved through the data flow coordination, in association with the data traffic volume and the resource exchange, between the nodes that exploit radio spectrum access in cognitive radio networking architectures. The routing scheme that is proposed in this paper interrelates the backward difference of traffic moments for each node based on a series model, together with the sleep‐time period, towards reflecting this measurement to the minimization of the nodes activity durations to achieve energy conservation. The effective operation of the routing scheme is achieved by exploiting a signalling mechanism that was adopted for the proper communication of the nodes over the available radio spectrum parts, such as the television white spaces. Simulation tests were conducted towards examining the validity of the proposed routing scheme via multiple performance evaluation experiments. Simulation results have shown the offered reliability and the efficiency of the proposed traffic‐aware scheme, in reference to the efficient energy consumption of the networking nodes and the minimization of the delays. Copyright © 2015 John Wiley & Sons, Ltd.     

intGuide: A platform for context-aware services featuring augmented-reality, based on the outcome of European Research Projects

As people become increasingly acquainted with information technology, they demand continuous availability of services related to their work or leisure. The era of ubiquitous computing announced long ago is currently turning into an everyday reality at an ever-increasing pace. Alongside the evolution of ubiquitous and nomadic computing, the need of people to access vast amounts of information in a comprehensive and efficient way gives rise to the areas of information visualization and augmented-reality. Such technologies allow for the comprehensive presentation of visual information equally addressing the needs of different categories of people.

In the past 5 years, we have been active in a set of European Research Projects addressing the above-mentioned research directions, with the long-term goal to develop a software platform that will enable context-aware services deploying advanced visualization technology in a series of application domains, such as cultural heritage dissemination, interactive television and retail industry. The multitude of the application domains addressed, as well as the multidisciplinary expertise necessary to create a generic platform was successfully addressed in complementary research activities. In this paper, we present the idea of a platform for context-aware services by exploiting advanced visualization technology and subsequently we briefly review the research projects that delivered valuable pieces in the overall puzzle. Emphasis is put on the practical issues of the implementation and deployment in different application scenarios.     

Effects of Drying and Extraction Methods on the Quality and Antioxidant Activity of Sea Buckthorn (Hippophae rhamnoides) Berries and Leaves

Sea buckthorn is a promising source of bioactive compounds. However, there is limited information on the effect of post harvest drying and extraction of sea buckthorn on its antioxidant capacity. The effect of freeze, air, and solar dryingon the extraction yield of sea buckthorn berries and leaves was evaluated with respect to their bioactive content. Sequential extraction with solvents of different polarity and solvent-free microwave-assisted extraction were applied. Freeze-drying has better performance in the berries’ extracts, while air-drying has better performance in the leaves’ extracts. All data were analyzed by Multi Factor Analysis of Variance (ANOVA) and Duncan's post-hoc tests at a level of α = .05. Although the extraction yield in the sequential extraction of sea buckthorn berries is significantly better, the leaves’ extracts exhibit superior radical scavenging ability. Accelerated solar drying appears to preserve sea buckthorn leaves without degrading their antioxidant content. The components responsible for the high antioxidant activity of leaves’ extracts were found to be several flavonoids and polyphenols. The extract obtained by the microwave extraction of fresh berries exhibits moderate antioxidant activity compared to the polar extracts of freeze-dried berries.     

Combined natural antimicrobial treatments (EDTA,lysozyme, rosemary and oregano oil) on semi cooked coated chicken meat stored in vacuum packages at 4 °C: Microbiological and sensory evaluation

The present study examined the effect of natural antimicrobials: Ethylenediaminetetraacetate (EDTA), lysozyme, rosemary and oregano oil and their combinations, on the shelf-life of semi cooked coated chicken fillets stored under vacuum packaging (VP), at 4 ± 0.5 °C for a period of 18 days. The treatments of semi cooked coated chicken fillets examined in the present study were the following: Air-packaged (A, control samples), vacuum-packaged (VP), VP with EDTA–lysozyme solution 1.50% w/w, (VP + EL), VP with rosemary oil 0.20% v/w, (VP + R), VP with oregano oil 0.20% v/w, (VP + O), VP with EDTA–lysozyme solution and rosemary oil (VP + EL + R) and finally VP with EDTA–lysozyme and oregano oil (VP + EL + O). The shelf-life of the samples was determined using both microbiological and sensory analyses. Among the antimicrobial combinations examined in the present study, the treatments VP + EL + R and VP + EL + O were the most effective against the growth of Gram-negative, Gram-positive bacteria, and to a lesser extent on yeasts. Based on both microbiological (TVC data) and sensory (taste attribute) analyses, treatments: VP and VP + O gave a shelf life extension of 6 days, whereas treatments VP + EL + R and VP + EL + O produced a shelf-life extension of 7–8 days, as compared to the control samples.Industrial RelevanceThe present research has highlighted the use of natural antimicrobial treatment combinations, including: EDTA, lysozyme, rosemary and oregano oil and their combinations, in the extension of shelf-life of semi cooked coated chicken fillets stored under vacuum packaging at 4 °C for a period of 18 days. Establishing, the determination of the shelf-life of fresh poultry and products represents a challenge for food companies as poultry meat has a short shelf-life, which causes substantial practical problems for its distribution. Therefore, knowledge of natural preservatives, that can be used as alternatives to chemical additives, that could extend the products' shelf life can have an important economic feedback by reducing losses attributed to spoilage and by allowing the products to reach distant and new markets. This study has shown that combinations of natural antimicrobials can extend the shelf-life of the product.     

The Marine Polysaccharide Ulvan Confers Potent Osteoinductive Capacity to PCL-Based Scaffolds for Bone Tissue Engineering Applications

Hybrid composites of synthetic and natural polymers represent materials of choice for bone tissue engineering. Ulvan, a biologically active marine sulfated polysaccharide, is attracting great interest in the development of novel biomedical scaffolds due to recent reports on its osteoinductive properties. Herein, a series of hybrid polycaprolactone scaffolds containing ulvan either alone or in blends with κ-carrageenan and chondroitin sulfate was prepared and characterized. The impact of the preparation methodology and the polysaccharide composition on their morphology, as well as on their mechanical, thermal, water uptake and porosity properties was determined, while their osteoinductive potential was investigated through the evaluation of cell adhesion, viability, and osteogenic differentiation of seeded human adipose-derived mesenchymal stem cells. The results verified the osteoinductive ability of ulvan, showing that its incorporation into the polycaprolactone matrix efficiently promoted cell attachment and viability, thus confirming its potential in the development of biomedical scaffolds for bone tissue regeneration applications.     

Hierarchical Reliable Multicast: Performance Analysis and Optimal Placement of Proxies

This paper studies the use of multicast together with proxy nodes for reliably disseminating data from a single source to a large number of receivers. In order to achieve reliability, data must be retransmitted in case of loss either by the source or by special network nodes, called proxies. Each proxy is responsible for reliably delivering the data to a subgroup it is assigned. The multicast tree is partitioned into subgroups that form a hierarchy rooted at the source, hence the term hierarchical reliable multicast. The performance of this approach strongly depends on the topology and the loss characteristics of the underlying tree and the location of proxies. In the first part of the paper, we study the processing and bandwidth performance of such a reliable multicast dissemination given the tree and the placement of proxies. In the second part of the paper, we develop dynamic programming algorithms that give a placement of a fixed number of proxies on an arbitrary tree that minimizes the bandwidth used for reliable transfer. The first algorithm provides an optimal solution to the multicast proxies location problem in polynomial time, in the number of nodes and proxies. The second is an approximation algorithm that gives a solution with cost within a chosen precision from the optimal, in an improved running time. An optimal and an approximate solution are also provided for the proxies location problem if unicast is used for transmissions. Applications of this dynamic programming approach to related problems are discussed.     

Constant round group key agreement protocols: A comparative study

The scope of this paper is to review and evaluate all constant round Group Key Agreement (GKA) protocols proposed so far in the literature. We have gathered all GKA protocols that require 1,2,3,4 and 5 rounds and examined their efficiency. In particular, we calculated each protocol’s computation and communication complexity and using proper assessments we compared their total energy cost. The evaluation of all protocols, interesting on its own, can also serve as a reference point for future works and contribute to the establishment of new, more efficient constant round protocols.     

Textural properties of legume protein isolate and polysaccharide gels

The influence of legume proteins from lupin, pea and fababean on the formation of gels prepared by heat treatment in the absence or presence of xanthan gum, locust bean gum and NaCl was investigated. The resulting fracture and texture properties of gels not only are associated with the heating process used to form the gel but also depend on the conformational aspects of xanthan–locust bean gum in admixture with legume proteins, which after 10 days of aging reinforce the system. The fracture and textural properties are explained in terms of the effect of the protein–polysaccharide molecular structure and physicochemical conditions applied in the gel system during the gel preparation and measurements. Copyright © 2006 Society of Chemical Industry