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cess timepoints, providing cost and time savings. This study suggests that data-driven models and machine learning techniques can be employed using existing data for understanding and improving production of a specific cell type, which is potentially applicable to other lineages and critical for realization of their therapeutic applications.The juxta-anastomotic stenosis of an arteriovenous fistula (AVF) is a significant clinical problem in hemodialysis patients with no effective treatment. Previous studies of AV anastomotic angles on hemodynamics and vascular wall injury were based on computational fluid dynamics (CFD) simulations using standardized AVF geometry, not the real-world patient images. The present study is the first CFD study to use angiographic images with patient-specific outcome information, i.e., the exact location of the AVF stenotic lesion. We conducted the CFD analysis utilizing patient-specific AVF geometric models to investigate hemodynamic parameters at different locations of an AVF, and the association between hemodynamic parameters and the anastomotic angle, particularly at the stenotic location. We analyzed 27 patients who used radio-cephalic AVF for hemodialysis and received an angiographic examination for juxta-anastomotic stenosis. The three-dimensional geometrical model of each patient's AVF was built using the angiographic images, in which the shape and the anastomotic angle of the AVF were depicted. CFD simulations of AVF hemodynamics were conducted to obtain blood flow parameters at different locations of an AVF. We found that at the location of the stenotic lesion, the AV angle was significantly correlated with access flow disturbance (r = 0.739; p less then 0.001) and flow velocity (r = 0.563; p = 0.002). Furthermore, the receiver operating characteristic (ROC) curve analysis revealed that the AV angle determines the lesion's flow disturbance with a high area under the curve value of 0.878. The ROC analysis also identified a cut-off value of the AV angle as 46.5°, above or below which the access flow disturbance was significantly different. By applying CFD analysis to real-world patient images, the present study provides evidence that an anastomotic angle wider than 46.5° might lead to disturbed flow generation, demonstrating a reference angle to adopt during the anastomosis surgery.Tooth loss is a common consequence of a huge number of causes and can decrease the quality of humans' life. Tooth is a complex organ composed of soft connective tissues and mineralized tissues of which dentin is the most voluminous component whose formation is regulated by a very complex process displaying several similarities with osteogenesis. Calcium phosphates, in particular hydroxyapatite (HA), is the phase present in higher amount into the structure of dentin, characterized by microscopic longitudinal dentinal tubules. To address the challenge of dental tissue regeneration, here we propose a novel biomimetic approach, to design hybrid scaffolds resembling the physico-chemical features of the natural mineralized tissues, suitable to recreate an appropriate microenvironment that stimulates cell colonization and proliferation, therefore effective for improving regenerative approach in dental applications. Biomineralization is the adopted synthesis as a nature inspired process consisting in the nucleation of magnesium-doped-hydroxyapatite (MgHA) nanocrystals on the gelatin (Gel) matrix generating hybrid flakes (Gel/MgHA) featured by a GelMgHA weight ratio close to 2080 and size of 50-70 μm. Chemical and topotactic constrains affect the formation of MgHA mineral phase on the organic template, generating quasi-amorphous MgHA as revealed by XRD analysis and Ca/P ratio lower than 1.67, resembling the chemical and biological features of the natural apatite. The Gel/MgHA was then merged into the polymeric blend made of chitosan (Chit) and Gel to obtain a 3D porous scaffold with polymers MgHA weight ratio of 4060 and featured by an aligned porous structure as obtained by controlled freeze-drying process. The overall composite shows a swelling ratio of about 15 times after 6 h in PBS. The chemical stability was assured by means of a dehydrothermal cross-linking treatment (DHT) keeping the degradation lower than 20% after 28 days, while cell adhesion and proliferation were evaluated using a mouse fibroblast cell line.A distributed biological system can be defined as a system whose components are located in different subpopulations, which communicate and coordinate their actions through interpopulation messages and interactions. We see that distributed systems are pervasive in nature, performing computation across all scales, from microbial communities to a flock of birds. We often observe that information processing within communities exhibits a complexity far greater than any single organism. Synthetic biology is an area of research which aims to design and build synthetic biological machines from biological parts to perform a defined function, in a manner similar to the engineering disciplines. However, the field has reached a bottleneck in the complexity of the genetic networks that we can implement using monocultures, facing constraints from metabolic burden and genetic interference. This makes building distributed biological systems an attractive prospect for synthetic biology that would alleviate these constraints an the design of microbial communities and identify areas where we lack the necessary tools.Stress resistance is an important trait expected of lactic acid bacteria used in food manufacturing. Among the various sources of stress, high temperature is a key factor that interrupts bacterial growth. In this regards, constant efforts are made for the development of heat-resistant strains, but few studies were done accompanying genomic analysis to identify the causal factors of the resistance mechanisms. Furthermore, it is also thought that tolerance to multiple stresses are equally important. Herein, we isolated one Enterococcus faecium strain named BIOPOP-3 and completed a full-length genome sequence. Using this strain, a two-step adaptive laboratory evolution (ALE) method was applied to obtain a heat-resistant strain, BIOPOP-3 ALE. After sequencing the whole genome, we compared the two full-length sequences and identified one non-synonymous variant and four indel variants that could potentially confer heat resistance, which were technically validated by resequencing. We experimentally verified that the evolved strain was significantly enhanced in not only heat resistance but also acid and bile resistance. We demonstrated that the developed heat-resistant strain can be applied in animal feed manufacturing processes. The multi-stress-resistant BIOPOP-3 ALE strain developed in this study and the two-step ALE method are expected to be widely applied in industrial and academic fields. In addition, we expect that the identified variants which occurred specifically in heat-resistant strain will enhance molecular biological understanding and be broadly applied to the biological engineering field.IgG, the main serum immunoglobulin isotype, exists in four subclasses which selectively appear with distinctive glycosylation profiles. find more However, very little is known about the biological consequences mainly due to the difficulties in the generation of distinct IgG subtypes with targeted glycosylation. Here, we show a comprehensive expression and glycan modulation profiling of IgG variants in planta that are identical in their antigen binding domain but differ in their subclass appearance. While IgG1, 2, and 4 exhibit similar expression levels and purification yields, IgG3 is generated only at low levels due to the in planta degradation of the heavy chain. All IgG subtypes are produced with four distinct N-glycosylation profiles, differing in sugar residues previously shown to impact IgG activities, i.e., galactosylation, sialylation and core fucosylation. Affinity purified IgG variants are shown to be fully assembled to heterodimers but display different biochemical/physical features. All subtypes are equally well amenable to targeted glycosylation, except sialylated IgG4 which frequently accumulates substantial fractions of unusual oligo-mannosidic structures. IgG variants show significant differences in aggregate formation and endotoxin contamination which are eliminated by additional polishing steps (size exclusion chromatography, endotoxin removal treatments). Collectively we demonstrate the generation of 16 IgG variants at high purity and large glycan homogeneity which constitute an excellent toolbox to further study the biological impact of the two main Fc features, subclass and glycosylation.The organ-on-a-chip (OOC) technology has been utilized in a lot of biomedical fields such as fundamental physiological and pharmacological researches. Various materials have been introduced in OOC and can be broadly classified into inorganic, organic, and hybrid materials. Although PDMS continues to be the preferred material for laboratory research, materials for OOC are constantly evolving and progressing, and have promoted the development of OOC. This mini review provides a summary of the various type of materials for OOC systems, focusing on the progress of materials and related fabrication technologies within the last 5 years. The advantages and drawbacks of these materials in particular applications are discussed. In addition, future perspectives and challenges are also discussed.The increasing interest toward biocompatible nanotechnologies in medicine, combined with electric fields stimulation, is leading to the development of electro-sensitive smart systems for drug delivery applications. To this regard, recently the use of pulsed electric fields to trigger release across phospholipid membranes of liposomes has been numerically studied, for a deeper understanding of the phenomena at the molecular scale. Aim of this work is to give an experimental validation of the feasibility to control the release from liposome vesicles, using nanosecond pulsed electric fields characterized by a 10 ns duration and intensity in the order of MV/m. The results are supported by multiphysics simulations which consider the coupling of three physics (electromagnetics, thermal and pore kinetics) in order to explain the occurring physical interactions at the microscopic level and provide useful information on the characteristics of the train of pulses needed to obtain quantitative results in terms of liposome electropermeabilization. Finally, a complete characterization of the exposure system is also provided to support the reliability and validity of the study.The study of the liver progenitor cell microenvironment has demonstrated the important roles of both biochemical and biomechanical signals in regulating the progenitor cell functions that underlie liver morphogenesis and regeneration. While controllable two-dimensional in vitro culture systems have provided key insights into the effects of growth factors and extracellular matrix composition and mechanics on liver differentiation, it remains unclear how microenvironmental signals may differentially affect liver progenitor cell responses in a three-dimensional (3D) culture context. In addition, there have only been limited efforts to engineer 3D culture models of liver progenitor cells through the tunable presentation of microenvironmental stimuli. We present an in vitro model of 3D liver progenitor spheroidal cultures with integrated polyethylene glycol hydrogel microparticles for the internal presentation of modular microenvironmental cues and the examination of the combinatorial effects with an exogenous soluble factor.