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Morbidity and mortality from ischaemic heart disease (IHD) and heart failure (HF) remain significant in Europe and are increasing worldwide. Patients with IHD or HF might benefit from novel therapeutic strategies, such as cell-based therapies. We recently discussed the therapeutic potential of cell-based therapies and provided recommendations on how to improve the therapeutic translation of these novel strategies for effective cardiac regeneration and repair. Despite major advances in optimizing these strategies with respect to cell source and delivery method, the clinical outcome of cell-based therapy remains unsatisfactory. Major obstacles are the low engraftment and survival rate of transplanted cells in the harmful microenvironment of the host tissue, and the paucity or even lack of endogenous cells with repair capacity. Therefore, new ways of delivering cells and their derivatives are required in order to empower cell-based cardiac repair and regeneration in patients with IHD or HF. Strategies using tissue engineering (TE) combine cells with matrix materials to enhance cell retention or cell delivery in the transplanted area, and have recently received much attention for this purpose. Here, we summarize knowledge on novel approaches emerging from the TE scenario. In particular, we will discuss how combinations of cell/bio-materials (e.g. hydrogels, cell sheets, prefabricated matrices, microspheres, and injectable matrices) combinations might enhance cell retention or cell delivery in the transplantation areas, thereby increase the success rate of cell therapies for IHD and HF. We will not focus on the use of classical engineering approaches, employing fully synthetic materials, because of their unsatisfactory material properties which render them not clinically applicable. The overall aim of this Position Paper from the ESC Working Group Cellular Biology of the Heart is to provide recommendations on how to proceed in research with these novel TE strategies combined with cell-based therapies to boost cardiac repair in the clinical settings of IHD and HF. [ABSTRACT FROM AUTHOR]

Bouteloua gracilis (blue grama grass) is one of the most drought and grazing tolerant plants in the short-grass ecosystem. To obtain information on their photosystem activities, we measured the fast (< 1 s) chlorophyll a fluorescence transient (the OJIP curve) from their leaves, and isolated cells grown photoautotrophically in suspension in a culture medium, or with added sucrose. One of our goals was to study the effect of different sucrose concentrations (0, 0.15, 0.3, and 3%) on PSII activity in isolated cells. Our results on cells suspended in culture medium, using the JIP-test, showed a decrease in PSII activity at increasing sucrose concentrations, while the photoautotrophic cells showed an optimal PSII activity, close to that of the leaves. Further, our data on cells grown in 0, 0.15, and 0.3% sucrose, but with added CO2, and measured while the cells were deposited on filter paper, indicate that supplementary CO2 can increase the PSII activity in the presence of sucrose, although further research is necessary to understand these results. [ABSTRACT FROM AUTHOR]

In this issue we highlight three recent papers that demonstrate new strategies to extend the capabilities of paper microfluidics. Paper (a mesh of porous fibers) has a long history as a substrate to perform biomolecular assays. Traditional lateral flow immunoassays (LFAs) are widely used for rapid diagnostic tests, and perform well when a yes or no answer is required and the analyte of interest is at relatively high concentrations. High concentrations are required because usually only a small volume of analyte-containing fluid flows past the detection region, leading to a limited signal. Further, the small pores within paper matrices prevent the use of paper to control the flow of larger particles and cells, limiting the use of paper microfluidics for cell-based diagnostics. The work we highlight addresses these important unmet challenges in paper microfluidics: enriching low concentration analytes to a higher concentration in a smaller volume that can be processed effectively, and using paper to pump flows in larger channels amenable to cells. Applying these new approaches may allow diagnosis of disease states currently technically unachievable using current LFA systems, while maintaining many of the “un-instrumented” advantages of an assay on self-wicking paper. [ABSTRACT FROM AUTHOR]

Simple Summary: The paper describes the statistical analysis of the response of gastric cancer cells and normal cells to broadband terahertz radiation up to 4 THz, both with and without the use of nanostructured contrast agents. A statistical analysis was conducted towards multiple pairwise comparisons in order to identify the narrow THz frequency ranges where the contrast is enhanced and allows a clear identification of tumor cells in the presence of contrast agents. The paper describes the statistical analysis of the response of gastric cancer cells and normal cells to broadband terahertz radiation up to 4 THz, both with and without the use of nanostructured contrast agents. The THz spectroscopy analysis was comparatively performed under the ATR procedure and transmission measurement procedure. The statistical analysis was conducted towards multiple pairwise comparisons, including a support medium (without cells) versus a support medium with nanoparticles, normal cells versus normal cells with nanoparticles, and, respectively, tumor cells versus tumor cells with nanoparticles. When generally comparing the ATR procedure and transmission measurement procedure for a broader frequency domain, the differentiation between normal and tumor cells in the presence of contrast agents is superior when using the ATR procedure. THz contrast enhancement by using contrast agents derived from MRI-related contrast agents leads to only limited benefits and only for narrow THz frequency ranges, a disadvantage for THz medical imaging. [ABSTRACT FROM AUTHOR]

This paper explores a formal model of autopoiesis as presented by Maturana, Uribe and Varela, and analyzes this model and its implications through the lens of the notions of eigenforms (fixed points) and the intricacies of Goedelian coding. The paper discusses the connection between autopoiesis and eigenforms and a variety of different perspectives and examples. The paper puts forward original philosophical reflections and generalizations about its various conclusions concerning specific examples, with the aim of contributing to a unified way of understanding (formal models of) living systems within the context of natural sciences, and to see the role of such systems and the formation of information from the point of view of analogs of biological construction. To this end, we pay attention to models for fixed points, self-reference and self-replication in formal systems and in the description of biological systems. [ABSTRACT FROM AUTHOR]

In the current paper we provide a proof of NP-completeness for the Cell Formation Problem (CFP) with the fractional grouping efficacy objective function. First the CFP with a linear objective function is considered. Following the ideas of Pinheiro et al. (2016) we show that it is equivalent to the Bicluster Graph Editing Problem (BGEP), which is known to be NP-complete due to the reduction from the 3-Exact 3-Cover Problem – 3E3CP (Amit, 2004). Then we suggest a polynomial reduction of the CFP with the linear objective to the CFP with the grouping efficacy objective. It proves the NP-completeness of this fractional CFP formulation. Along with the NP-status our paper presents important connections of the CFP with the BGEP and 3E3CP. Such connections could be used for "transferring" of known theoretical properties, efficient algorithms, polynomial cases, and other features of well-studied graph editing and exact covering problems to the CFP. [ABSTRACT FROM AUTHOR]

The blood-brain barrier (BBB) protects the brain by actively allowing the entry of ions and nutrients while limiting the passage of from toxins and pathogens. A healthy BBB has low permeability and high selectivity to maintain normal brain functions. Increased BBB permeability can result from neurological diseases and traumatic injuries. Modern engineering technologies such as microfluidics and fabrication techniques have advanced the development of BBB models to simulate the basic functions of BBB. However, the intrinsic BBB properties are difficult to replicate. Existing in vitro BBB models demonstrate inconsistent BBB permeability and selectivity due to variations in microfluidic design, cell types and arrangement, expression of tight junction (TJ) proteins, and use of shear stress. Specifically, microfluidic designs have flow channels of different sizes, complexity, topology, and modular structure. Different cell types are selected to mimic various physiological conditions. These factors make it challenging to compare results obtained using different experimental setups. This paper highlights key factors that play important roles in influencing microfluidic models and discusses how these factors contribute to permeability and selectivity of the BBB models. [ABSTRACT FROM AUTHOR]

In this paper, an automatic vision-guided micromanipulation approach to facilitate versatile deployment and portable setup is proposed. This paper is motivated by the importance of micromanipulation and the limitations in existing automation technology in micromanipulation. Despite significant advancements in micromanipulation techniques, there remain bottlenecks in integrating and adopting automation for this application. An underlying reason for the gaps is the difficulty in deploying and setting up such systems. To address this, we identified two important design requirements, namely, portability and versatility of the micromanipulation platform. A self-contained vision-guided approach requiring no complicated preparation or setup is proposed. This is achieved through an uncalibrated self-initializing workflow algorithm also capable of assisted targeting. The feasibility of the solution is demonstrated on a low-cost portable microscope camera and compact actuated microstages. Results suggest subpixel accuracy in localizing the tool tip during initialization steps. The self-focus mechanism could recover intentional blurring of the tip by autonomously manipulating it 95.3% closer to the focal plane. The average error in visual servo is less than a pixel with our depth compensation mechanism showing better maintaining of similarity score in tracking. Cell detection rate in a 1637-frame video stream is 97.7% with subpixels localization uncertainty. Our work addresses the gaps in existing automation technology in the application of robotic vision-guided micromanipulation and potentially contributes to the way cell manipulation is performed. Note to Practitioners—This paper introduces an automatic method for micromanipulation using visual information from microscopy. We design an automatic workflow, which consists of: 1) self-initialization; 2) vision-guided manipulation; and 3) assisted targeting, and demonstrate versatile deployment of the micromanipulator on a portable microscope camera setup. Unlike existing systems, our proposed method does not require any tedious calibration or expensive setup making it mobile and low cost. This overcomes the constraints of traditional practices that confine automated cell manipulation to a laboratory setting. By extending the application beyond the laboratory environment, automated micromanipulation technology can be made more ubiquitous and expands readily to facilitate field study. [ABSTRACT FROM AUTHOR]

This paper proposes a resonant switching cell model to analyze and design the single-ended resonant dc–dc converters. The single-ended zero-voltage switching (ZVS) converters such as the Class E converter are efficient for megahertz switching because they feature low turn-on and turn-off switching losses. Also, they use only a ground-referenced switch, allowing a simple gate drive circuit. In this paper, we investigate the single-ended resonant converter with the small input inductance, whereas the conventional Class E converter has a large input inductance. The main contribution of this paper is to propose the resonant switching cell as an analytic model that simplifies the analysis and the design of the resonant dc–dc converters. Furthermore, this paper presents the design method of the resonant switching cell model for minimizing the resonant current magnitude and conduction loss while the converter maintains ZVS property. The experimental results from a 10-MHz GaN-based prototype demonstrate the feasibility and effectiveness of the analysis and design based on the proposed resonant switching cell model. [ABSTRACT FROM AUTHOR]

This review is intended to contribute to the evidence of the effects of static magnetic field on cells and tissue, as well as to present research results that will elucidate the complex matters involved in the formation and remodeling of cells. The cell characteristics studied in the papers that are reviewed include cell viability and proliferation, aggregation and their differentiation, structure and membrane potential. A moderate static magnetic field in the most commonly used range of 2-80 mT has potential application in the formation and remodeling of plant and human cells. However, in the case of cancer cells, the range of fields commonly used was 0.2-9 T. Magnetism promotes changes in plant cell growth, which prompts the cell to proliferate, thereby ensuring an increased rate of biomass production. Some researches presented the enhancement of the differentiation of plant cells and skeletal muscle tissue by over 30% at 80 mT static magnetic field. Changes in the cell cycle and growth reflect directly on the cell number and viability and provide useful information to detect modifications in the cell machinery. Static magnetic field, depending on its intensity, enhances cell proliferation and thus may improve, among other processes, tissue regeneration, wound healing and the inhibition of cancer cell proliferation. Researchers showed, among other things, that cells under the influence of static magnetic field changed their shape, had a larger chloroplast, stiffer cell wall, density of the cytoskeleton and cytoplasm contained several mitochondria. Numerous studies also discussed the behavior of the cell membrane of plant and animal organisms, including humans, under the influence of an static magnetic field. The effects of static magnetic field on the cell membrane of plant and human cells were similar. The research results indicate that static magnetic fields can significantly change membrane depolarization and its potential that regulates ion movement and thus can have a significant impact on the properties and biological functionality of the cell. Studies have shown that continuous application of static magnetic field caused deformation and damage of cell membrane. Based on the theoretical analyses presented also in this review, it can be concluded that static magnetic field affects cells and tissue, giving them changes in properties and behaviors and modulates, e.g. in the activity of ion channels. Thus it may produce effects leading to changes in the functioning of the cell. It is possible to formulate directions for further research aimed at using static magnetic fields for the non-invasive remodeling and formation of plant and human cells. [ABSTRACT FROM AUTHOR]

PHOTO (COLOR): Voluntary declarations in submitted manuscripts can describe gender balance in study samples, for example. "These [manuscript] statements might arguably only be done by those who already understand the importance of equity, diversity, and inclusion", Roessler said. [Extracted from the article]

We demonstrate, for the first time, resistive RAM (RRAM) arrays where each cell can store 3 bits. Such full array-level demonstration is possible through special techniques (e.g., that exploit RRAM-specific characteristics of variations in cell resistances), presented in this paper, which efficiently allocate resistance range corresponding to each bit combination (required for proper write operation) while maintaining appropriate sensing margin (required for proper read operation). Our techniques are not restricted to 3 bits-per-cell only (and, in this paper, we demonstrate 2 bits-per-cell at the array level as well). Our measured results are based on multiple 4 Kbit arrays of 1T1R HfOx-based RRAM integrated in the back end of the line of 130-nm silicon CMOS technology. We achieve 3 bits-per-cell (2 bits-per-cell) RRAM with 11 (3) programing iterations on average. [ABSTRACT FROM AUTHOR]

Many people find the manipulation of the human germline—editing the DNA of sperm or egg cells such that these genetic changes are passed to the resulting offspring—to be morally impermissible. In this paper, I argue for the claim that editing the human germline is morally permissible. My argument starts with the claim that outcome uncertainty regarding the effects of germline editing shows that the duty to not harm cannot ground the prohibition of germline editing. Instead, if germline editing is wrong, it is wrong because it violates a duty to protect. However, we also have an epistemic duty to gather evidence regarding the effects of editing the human germline which overrides any moral duty to protect future generations. Thus, we have a duty to gather evidence regarding the effects of editing the human germline, which is to say that we have a duty to edit the human germline. [ABSTRACT FROM AUTHOR]

Simple Summary: This scoping review of systematic reviews aims to accurately assess the degree of existing scientific evidence on the cancer hallmarks proposed in 2011 by Hanahan and Weinberg, in the form of systematic reviews and meta-analyses, applied to oral potentially malignant disorders, oral cavity and oropharyngeal squamous cell carcinomas, in order to point out gaps in evidence and lines of research that should be implemented in the future to improve the malignant transformation prediction, diagnosis and/or prognosis of these diseases. In 2000 and 2011, Hanahan and Weinberg published two papers in which they defined the characteristics that cells must fulfil in order to be considered neoplastic cells in all types of tumours that affect humans, which the authors called "hallmarks of cancer". These papers have represented a milestone in our understanding of the biology of many types of cancers and have made it possible to reach high levels of scientific evidence in relation to the prognostic impact that these hallmarks have on different tumour types. However, to date, there is no study that globally analyses evidence-based knowledge on the importance of these hallmarks in oral and oropharyngeal squamous cell carcinomas. For this reason, we set out to conduct this scoping review of systematic reviews with the aim of detecting evidence gaps in relation to the relevance of the cancer hallmarks proposed by Hanahan and Weinberg in oral and oropharyngeal cancer, and oral potentially malignant disorders, and to point out future lines of research in this field. [ABSTRACT FROM AUTHOR]

In this paper were analyzed the scientific bibliographic sources regarding the physiological and biochemical role of zinc on the tissues and organs of the organism of breeding roosters. In addition, in laboratory conditions, our researchers studied hematological, biochemical indices as well as glycine, glutamate and cysteine content in blood serum, seminal plasma and reproductive cells of breeding roosters. It is established that this element has a beneficial action on the organism of breeding roosters, maintaining and stabilizing the indices listed above at the level of physiological norms, compared to the roosters from the control group, and at the same time participating in the antioxidant protection of cells and maintaining cell homeostasis by balancing transmembrane metabolism. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer’s disease (AD) and Type 2 diabetes (T2D) are both ageassociated diseases. Identification of shared genes could help develop early diagnosis and preventive strategies. Although genetic background plays a crucial role in these diseases, we noticed an underrepresentation tendency of North African populations in omics studies. Materials and methods: First, we conducted a comprehensive review of genes and pathways shared between T2D and AD through PubMed. Then, the function of the identified genes and variants was investigated using annotation tools including PolyPhen2, RegulomeDB, and miRdSNP. Pathways enrichment analyses were performed with g:Profiler and EnrichmentMap. Next, we analyzed variant distributions in 16 worldwide populations using PLINK2, R, and STRUCTURE software. Finally, we performed an inter-ethnic comparison based on the minor allele frequency of T2D-AD common variants. Results: A total of 59 eligible papers were included in our study. We found 231 variants and 363 genes shared between T2D and AD. Variant annotation revealed six single nucleotide polymorphisms (SNP) with a high pathogenic score, three SNPs with regulatory effects on the brain, and six SNPs with potential effects on miRNA-binding sites. The miRNAs affected were implicated in T2D, insulin signaling pathways, and AD. Moreover, replicated genes were significantly enriched in pathways related to plasma protein binding, positive regulation of amyloid fibril deposition, microglia activation, and cholesterol metabolism. Multidimensional screening performed based on the 363 shared genes showed that main North African populations are clustered together and are divergent from other worldwide populations. Interestingly, our results showed that 49 SNP associated with T2D and AD were present in North African populations. Among them, 11 variants located in DNM3, CFH, PPARG, ROHA, AGER, CLU, BDNF1, CST9, and PLCG1 genes display significant differences in risk allele frequencies between North African and other populations. Conclusion: Our study highlighted the complexity and the unique molecular architecture of North African populations regarding T2D-AD shared genes. In conclusion, we emphasize the importance of T2D-AD shared genes and ethnicity-specific investigation studies for a better understanding of the link behind these diseases and to develop accurate diagnoses using personalized genetic biomarkers. [ABSTRACT FROM AUTHOR]

This paper details the content and structure of the folk concept of life, and discusses its relevance for scientific research on life. In four empirical studies, we investigate which features of life are considered salient, universal, central, and necessary. Functionings, such as nutrition and reproduction, but not material composition, turn out to be salient features commonly associated with living beings (Study 1). By contrast, being made of cells is considered a universal feature of living species (Study 2), a central aspect of life (Study 3), and our best candidate for being necessary for life (Study 4). These results are best explained by the hypothesis that people take life to be a natural kind subject to scientific scrutiny. [ABSTRACT FROM AUTHOR]

Summary: With the commercialization of the electric vehicles, the large‐scale lithium‐ion cells as the power of electric vehicles are to be retired. The second‐use of retired cells is of great significance to improve the battery economy. A fast classification and regroup evaluation method of the retired lithium‐ion cells are proposed in this paper to improve the classification efficiency of retired lithium‐ion cells and adapt to the regroup under different conditions. The lithium‐ion cells after being balanced in parallel are charged in series with a constant current. A support vector regression (SVR) model with the parameters optimized by the particle swarm optimization (PSO) algorithm is built for the fast capacity estimation and the error will not exceed 0.3%. Different cells regrouped means different performance. In order to improve the consistency of retired cells and satisfy different using conditions, a Weighted‐K‐means algorithm is proposed in this paper to regroup the cells with the known capacity and internal resistance. The classification method is evaluated by the voltage consistency of cells using different working conditions, which indicates capacity occupied a large proportion can meet the requirement of energy condition meanwhile keep a good consistency. But the resistance will dominate in algorithm under conditions which have requirement for instantaneous power. [ABSTRACT FROM AUTHOR]

Low power cache memory in a system on chip is in high demand today. With the lowering of MOSFET's channel length, low-power SRAM design has become a more challenging task. This paper presents differential 8T SRAM cell with minimum power utilization. The proposed cell has one pair of transmission gate as access switches. Due to use of TG instead of pass gate access transistor its write access time (TWA) is short. The low power consumption of the cell is due to stacking effect. This paper compares design metrics of the proposed cell with conventional 6T (CON6T) and ZIGZAG 8T (ZG8T) SRAM cells. The proposed 8T SRAM cell shows 1.15×/1.17× improvement in TWA as compared to CON6T/ZG8T at a penalty of 2.65×/2× in read access time (TRA). The proposed cell consumes 3.22× less hold power compared to both CON6T and ZG8T SRAM cells. And the proposed cell consumes 4.41× (4.44×) less write power as compared to CON6T (ZG8T) SRAM cell. Our proposed cell takes 1.37× lower chip area as compared to ZG8T cell at the expense of 1.49× higher area as compared to CON6T SRAM cell. The proposed cell also achieves 1.5×/3× higher stability during write operation as compared to CON6T/ZG8T SRAM cell, respectively. Read static margin of the proposed cell is same as CON6T but 3.2× lower than ZG8T SRAM cell. [ABSTRACT FROM AUTHOR]

Molecular dynamics simulations require barostats to be performed at a constant pressure. The usual recipe is to employ the Berendsen barostat first, which displays a first-order volume relaxation efficient in equilibration but results in incorrect volume fluctuations, followed by a second-order or a Monte Carlo barostat for production runs. In this paper, we introduce stochastic cell rescaling, a first-order barostat that samples the correct volume fluctuations by including a suitable noise term. The algorithm is shown to report volume fluctuations compatible with the isobaric ensemble and its anisotropic variant is tested on a membrane simulation. Stochastic cell rescaling can be straightforwardly implemented in the existing codes and can be used effectively in both equilibration and production phases. [ABSTRACT FROM AUTHOR]

Cell penetration is a typical micromanipulation technique widely utilized in many cell biological applications. The significant cell deformation generated during penetration can mechanically damage the cell and even cause the death of the cell. Measuring the intracellular displacement resulting from cell deformation can provide a quantitative evaluation of the mechanical harm done to cells during penetration. The existing labeled intracellular displacement measurement approaches have limitations in spatial resolution and must introduce markers, which cause further harm to the cell. Moreover, label-free methods, such as traditional optical flow methods, are not suitable for measuring the inconsistent intracellular displacement distribution due to cell penetration. This paper presents a label-free noncontact method for measuring the intracellular displacements during penetration. First, based on a finite element simulation, the uneven distribution of intracellular displacements due to penetration was modeled by a quadratic model. Then, by combining the obtained displacement model with the Farnebäck dense optical flow method, a model-based optical flow method was developed to measure intracellular displacements. Finally, the method was used to ascertain the intracellular displacement in porcine oocyte penetration experiments. The forward-backward error of the proposed detection method is less than 0.5 pixels, lower by 49.3% and 26.1%, respectively, compared with two typical Farnebäck optical flow methods. This method could be used to analyze cell damage during penetration. With an appropriate extension, the method may be suitable for measuring the intracellular displacement due to cell manipulations other than penetration. [ABSTRACT FROM AUTHOR]

Background: The effects of laser therapy on normal cells are well known and accepted, but the impact of this therapy on malignant cells are not yet fully understood. This review aims to map and outline what the scientific literature addresses on the effects of laser therapy on malignant cells. Methods: This review article followed the guidelines of the PRISMA‐ScR protocol, being all the search, analysis, and selection of articles based on it. Results: After all application of the predetermined criteria, five studies were included, dated between the years 2013 and 2021. With the complete reading of the selected studies, 100% of the articles were classified as category III of the Agency for Healthcare as Research and Quality classification. Similar themes among the papers included were investigated and compared. In these five studies, the visible red and near infrared wavelengths were used, and energy densities varied between 1 and 5 J/cm2. It was observed that low‐level laser could alter the expression of cell proliferation and migration proteins, such as cyclin D1, E‐cadherin, and β‐catenin. In addition, changes related to increased cell viability and metabolism were also identified. Conclusion: The low‐level laser seems to positively regulate the proliferative, migratory, and viability capacity of neoplastic cells, depending on the protocol used. All these studies included in the review are equivalent to in vitro studies; the cells are not in such a complex environment as is an organized tissue, making it necessary to carry out more complex tests, such as in vivo research. [ABSTRACT FROM AUTHOR]

Cell regulatory networks are the determinants of cellular homeostasis. Any alteration to these networks results in the disturbance of cellular homeostasis and induces cells towards different fates. Myocyte enhancer factor 2A (MEF2A) is one of four members of the MEF2 family of transcription factors (MEF2A-D). MEF2A is highly expressed in all tissues and is involved in many cell regulatory networks including growth, differentiation, survival and death. It is also necessary for heart development, myogenesis, neuronal development and differentiation. In addition, many other important functions of MEF2A have been reported. Recent studies have shown that MEF2A can regulate different, and sometimes even mutually exclusive cellular events. How MEF2A regulates opposing cellular life processes is an interesting topic and worthy of further exploration. Here, we reviewed almost all MEF2A research papers published in English and summarized them into three main sections: 1) the association of genetic variants in MEF2A with cardiovascular disease, 2) the physiopathological functions of MEF2A, and 3) the regulation of MEF2A activity and its regulatory targets. In summary, multiple regulatory patterns for MEF2A activity and a variety of co-factors cause its transcriptional activity to switch to different target genes, thereby regulating opposing cell life processes. The association of MEF2A with numerous signaling molecules establishes a central role for MEF2A in the regulatory network of cellular physiopathology. [ABSTRACT FROM AUTHOR]

Atomic Force Microscopy (AFM) is a powerful tool enabling the mechanical characterization of biological materials at the nanoscale. Since biological materials are highly heterogeneous, their mechanical characterization is still considered to be a challenging procedure. In this paper, a new approach that leads to a 3-dimensional (3D) nanomechanical characterization is presented based on the average Young's modulus and the AFM indentation method. The proposed method can contribute to the clarification of the variability of the mechanical properties of biological samples in the 3-dimensional space (variability at the x–y plane and depth-dependent behavior). The method was applied to agarose gels, fibroblasts, and breast cancer cells. Moreover, new mathematical methods towards a quantitative mechanical characterization are also proposed. The presented approach is a step forward to a more accurate and complete characterization of biological materials and could contribute to an accurate user-independent diagnosis of various diseases such as cancer in the future. [ABSTRACT FROM AUTHOR]

We consider the energy-efficient mobility-aware content caching problem with clustered small cells (SCs) in ultra-dense networks (UDNs). The UDN is regarded as one of the key solutions to overcome the explosive growth of mobile data traffic and consequential energy consumption. In addition, caching the popular contents at the edge of UDNs can further mitigate the challenges of traffic and energy. In this paper, we group the SCs into disjoint clusters and model the mobility of users between clusters as a Markov chain. We formulate the caching problem aimed at minimizing the overall energy consumption for content delivery to the moving users. Then we decompose the complicated task of energy consumption optimization in cache-enabled UDNs into two sub-problems. In the first sub-problem, we formulate the inter-cluster caching problem as minimizing the energy consumption for serving a user request by the macro base station. We show that the first sub-problem is NP-hard, and develop a polynomial-heuristic algorithm. Further, we define the mobility-oblivious version of the sub-problem, and provide a ${\textstyle {1 \over {2k }}}$ -approximation solution for the mobility-aware based on this mobility-oblivious version. In the second sub-problem, we consider the heterogeneity of small cells and define the intra-cluster caching problem. The aim of this sub-problem is the placement of content in different SCs within the cluster so that the energy consumption for the content delivery in that cluster is minimized. In particular, the second sub-problem fits the general framework of the generalized assignment problem, which allows us to exploit its rich literature, to determine the optimal solution for our problem. Through extensive simulations based on real wireless data and human mobility patterns, we demonstrate the benefits of our approach that is even up to 56% better compared to the conventional caching schemes. [ABSTRACT FROM AUTHOR]

The quantum-dot cellular automata (QCA) were highly regarded due to its high operating frequency and significantly low power consumption. One of the most useful circuits in processors architecture is counter. This paper presents effective designs and arrangement of QCA based counter-circuits. In this study new counter circuits in QCA technology are designed and precise simulation are done using the QCADesigner. Three, four and five bits counters are proposed in this paper in QCA technology. A comparison is made between the past and recent designs to illustrate which method is better and more efficient in terms of area, complexity, number of cells, and delay. For example, the proposed three bit shift register has 174 quantum cells, 0.2μm2 occupied area and three QCA clock cycles delay. [ABSTRACT FROM AUTHOR]

Summary: In situ growing conductive polyaniline (PANi) has been regarded as a functional binder to enhance the performance of silicon based anodes in half cells, while few papers discussing the influence of Mn2+ from cathode on full cells. In this paper, the effects of Mn2+ on NSi@PANi electrodes in both half and full cells are investigated, and the mechanism for the fast capacity fade of LiMn2O4/NSi@PANi full cell is elucidated. Results reveal that the full cell will significant accelerate the capacity fade of NSi@PANi anode, and the extra consumption of active Li+ and electrolytes caused by the deposited Mn2+ on silicon anodes in lithium manganate (LMO)/NSi@PANi full cells is confirmed as the main reason of the capacity fade and lower coulombic efficiency for the excessive growth of solid electrolyte interphase. [ABSTRACT FROM AUTHOR]

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This paper presents a review of the space exploration for life signature search with a special focus on the fluorescence microscope we developed for the life signature search on Mars and in other sites. Considering where, what, and how to search for life signature is essential. Life signature search exploration can be performed on the Mars surface and underground, on Venus' cloud, moon, asteroids, icy bodies (e.g., moons of Jupiter and Saturn), and so on. It is a useful strategy to consider the targeted characteristics that may be similar to those of terrestrial microorganisms, which are microorganisms with uniform spherical or rod structures with approximately 1 μm diameter surrounded by a membrane having a metabolic activity and mainly made of carbon-based molecules. These characteristics can be analyzed by using a fluorescence microscope and a combination of fluorescence pigments with specific staining characteristics to distinguish the microorganism characteristics. Section 1 introduces the space exploration for life signature search. Section 2 reviews the scientific instruments and achievements of past and ongoing Mars exploration missions closely related to astrobiology. Section 3 presents the search targets and analysis of astrobiology. Section 4 discusses the extraterrestrial life exploration methods that use a microscope together with other methods (based on mass spectrometry, morphology, detection of growth, movement, and death, etc. for microscopic and macroscopic organism). Section 5 expounds on the life signature detection fluorescence microscope, for which we have manufactured a bread board model and tested for extraterrestrial life exploration. [ABSTRACT FROM AUTHOR]

Hydrogen peroxide (H 2 O 2) is a reactive oxygen species (ROS) that can be used as a marker for the occurrence of oxidative stress in the organism. Lysosomes serve as intracellular digestive sites, and when the concentration of H 2 O 2 in them is abnormal, lysosomal function is often impaired, leading to the development of diseases. Hydrogen sulfide (H 2 S) acts as a gaseous signaling molecule that scavenges H 2 O 2 from cells and tissues, thereby maintaining the redox environment of the body. However, most of the reported hydrogen peroxide fluorescent probes so far can only detect H 2 O 2 , but cannot maintain the intracellular redox environment. In this paper, an H 2 O 2 fluorescent probe LN-HOD with lysosomal targeting properties was designed and synthesized by combining the H 2 O 2 recognition site with a naphthylamine fluorophore via a thiocarbamate moiety. The probe has the advantages of large Stokes shift (110 nm), high sensitivity and good H 2 S release capability. The probe LN-HOD can be used to detect H 2 O 2 in cells, zebrafish and plant roots. In addition, LN-HOD detects changes in the concentration of H 2 O 2 in plant roots when Arabidopsis is stressed by cadmium ion (Cd2+). And through its ability to release H 2 S, it can help to remove excess H 2 O 2 and maintain the redox environment in cells, zebrafish and plant roots. The present work provides new ideas for the detection and assisted removal of H 2 O 2 , which contributes to the in-depth study of the cellular microenvironment in organisms. In this paper, we designed and synthesized LN-HOD , a fluorescent probe targeting the detection of H 2 O 2 in lysosomes, by combining the H 2 O 2 recognition site with a naphthalimide fluorophore via a thiocarbamate moiety. The probe has the advantages of large Stokes displacement, high sensitivity and good H 2 S release capability. The probe LN-HOD can be used to detect H 2 O 2 in cells, zebrafish and plant roots. In addition, LN-HOD detects changes in the concentration of H 2 O 2 in plant roots when Arabidopsis is stressed by cadmium ion (Cd2+). And through its ability to release H 2 S, it can help to remove excess H 2 O 2 and maintain the redox environment in cells, zebrafish and plant roots. The present work provides new ideas for the detection and assisted removal of H 2 O 2 , which contributes to the in-depth study of the cellular microenvironment in organisms. [Display omitted] • The probe LN-HOD not only detects H 2 O 2 but also releases H 2 S. • LN-HOD has the ability to release H 2 S in cells, zebrafish and Arabidopsis. • LN-HOD has a good ability to maintain the redox environment in cells. • LN-HOD can detect changes in H 2 O 2 concentration in plants induced by Cd2+ ion stress effects. [ABSTRACT FROM AUTHOR]

In this paper, a new mobile robot mapping algorithm inspired from the functionality of hippocampus cells is presented. Place cells in hippocampus can store a map of the environment. This model fuses odometry and vision data based on dimensionality reduction technique, hierarchically. These two types of data are first fused and then considered as inputs to the place cell model. Place cells do the clustering of places. The proposed Place cell model has two types of inputs: Grid cells input and input from the lateral entorhinal cortex (LEC). The LEC is modelled based on the dimension reduction technique. Therefore, the data that causes locations different to be inserted into the place cell from this layer. Another contribution is proposing a new unsupervised dimension reduction method based on k-means. The method can find perpendicular independent dimensions. Also, the distance of cluster centres found in these dimensions is maximised. The method was compared with LDA and PCA in standard functions. Although LDA is a supervised method, the result showed that the proposed unsupervised method outperformed. To evaluate the place cells model, sequences of images collected by a mobile robot was used and similar results to real place cells achieved. [ABSTRACT FROM AUTHOR]

CircZNF609 (cZNF609) is previously revealed as an essential mediator in oxidative stress. This paper determined the role of cZNF609 in skin oxidative damage to evaluate its importance in pressure ulcer. HaCaT cells treated by H2O2 were considered as a cell model of pressure ulcer. The role of cZNF609 in the model was checked by conducting CCK-8 assay, FITC-PI double-staining, ROS detection and Western blot. The downstream gene and signalling of cZNF609 were studied by utilizing qRT-PCR and Western blot. HaCaT cells were remarkably damaged by H2O2, as evidenced by the viability loss, apoptosis and ROS generation. It was coupled with the elevated expression of p53, p16, Bax and the activated forms of caspase-3 and PARP. Meanwhile, cZNF609 was high-expressed in response to H2O2. The oxidative stress driven by H2O2 was alleviated by transfection with cZNF609 specific siRNA. Further, the anti-antioxidant impacts of cZNF609 silence were impeded by miR-145 silence. The inhibition of JNK and p38MAPK pathways induced by cZNF609 silence was impeded by miR-145 silence. The protective function of cZNF609 silence in H2O2-injured HaCaT cells was revealed in vitro. Silence of cZNF609 exhibited its impact possibly through regulating miR-145, and JNK and p38MAPK pathways. [ABSTRACT FROM AUTHOR]

Prolyl hydroxylase domain proteins (PHD2) is an oxygen sensor that is able to induce hypoxia-inducible factor-α (HIF-α) degradation under normoxic condition. The present paper designed to reveal the function of PHD2 in hepatocellular carcinoma (HCC) cells proliferation, migration and invasion. qRT-PCR and Western blot were carried out to see the expression of PHD2 in HCC tissues and cell lines. PHD2 expression in Huh7 and HepG3B cells was overexpressed or suppressed by transfection and then the changes of cell proliferation, migration and invasion were detected by CCK-8 assay, transwell assay and Western blot. PHD2 was highly expressed in HCC tissues and cell lines (Huh7, Hep3B, SK-HEP-1, HCCLM3 and MHCC97) as relative to para-cancerous non-tumour tissues and a normal hepatocyte line MIHA. PHD2 overexpression promoted Huh7 and Hep3B cells viability, migration and invasion. Meanwhile, CyclinD1, c-Myc, MMP-2, MMP-9 and Vimentin were up-regulated, while p53 was down-regulated by PHD2 overexpression. PHD2 silence led to a contrary impact. Further, PHD2 overexpression up-regulated Ras and Raf expression and induced phosphorylation of MEK, ERK, JAK1 and STAT3. PHD2 exhibited pro-tumour functions in HCC cells. PHD2 promoted HCC possibly through Ras/Raf/MEK/ERK and JAK1/STAT3 pathways. PHD2 is highly expressed in HCC tissue and cell lines; PHD2 promotes the proliferation of Huh7 and HepG3B cells; PHD2 enhances Huh7 and HepG3B cells migration and invasion; PHD2 activates Ras/Raf/MEK/ERK and JAK1/STAT3 signalling. [ABSTRACT FROM AUTHOR]

Based on the Dual cell structure display, this paper proposes an effective contrast enhancement scheme. By using the lower cell to control the backlight brightness, local dimming is realized at the pixel level. Combined with spatial filtering, the ghosting problem of the Dual cell structure display is solved. [ABSTRACT FROM AUTHOR]

As a key reactive oxygen species (ROS), hypochlorous acid (HClO) plays a vital role in living systems. Ratiometric and endoplasmic reticulum-targeting probes for highly sensitive detection of hypochlorous acid are in demand. In this paper, we constructed a novel reticulum-targeting and ratiometric fluorescent probe for determining hypochlorous acid. The probe applied 4-aminonaphthalimide as the fluorescent group, employed the (2-aminoethyl)thiourea group as a specific recognition unit, and used the p-toluenesulfonamide group as the localization group of the endoplasmic reticulum. When HClO is absent, the probe underwent an intramolecular charge transfer (ICT) process and displayed green emission. In the presence of HClO, the ICT process was inhibited, which induced a 49 nm blue-shift of fluorescence emission from 533 nm to 484 nm. The ratiometric fluorescent probe exhibited high sensitivity and selectivity for HClO. Furthermore, the ratiometric fluorescent probe could work in a wide pH range. The fluorescence intensity ratios (I484nm/I533nm) exhibited a linear response to the concentration of HClO from 5.0 × 10−7 to 1.0 × 10−5 mol L−1. The detection limit was evaluated to be 1.0 × 10−7 mol L−1 for HClO. In addition, the probe displayed an excellent endoplasmic reticulum-targeting ability, and has been successfully applied for the confocal imaging of HClO in the endoplasmic reticulum of PC-12 cells with almost no cell toxicity. All of such outstanding properties demonstrated that it could be employed to sense HClO in the endoplasmic reticulum of living cells. [ABSTRACT FROM AUTHOR]

This paper investigates subchannel allocation based on clustered interference alignment in dense small cell networks when all small cell user equipments (SUEs) have differentiated requirements for data streams. By imposing the condition that each cluster has a size not exceeding the maximum value achieved when each SUE needs only one data stream, we maximize the number of SUEs with guaranteed requirements for data streams, which is NP-hard. Hence, we propose a two-phase efficient solution with much lower complexity and reduced feedback overhead. First, similarity clustering is performed by graph partition, and then, subchannel allocation is done through a coloring algorithm. Numerical results show that the proposed solution offers a performance better than the related schemes and close to the approximate optimal solution. [ABSTRACT FROM AUTHOR]

Characterization of circadian systems at the organism level—a top-down approach—has led to definition of unifying properties, a hallmark of the science of chronobiology. The next challenge is to use a bottom-up approach to show how the molecular workings of the cellular circadian clock work as building blocks of those properties. We review new studies, including a recently published PLOS Biology paper by Nikhil and colleagues, that show how programmed but also stochastic generation of variation in cellular circadian period explain important adaptive features of entrained circadian phase. A recent PLOS Biology paper shows that clonal cell populations are themselves a collection heterogeneous cellular circadian clocks; this Primer explores the implications, proposing that the phase of entrainment of biological clocks (to time of day or to season) is granular, built from the contributions of individual cells. [ABSTRACT FROM AUTHOR]

The rooms of each building can be interpreted as three-dimensional cells. Borders (sides, edges) of rooms can be identified as the two-, one-, or zero-dimensional boundary cells of the three dimensional cell. The building structures identified as two-, one-, or zero-dimensional cells can be modeled by distinguished geometrical forms, surface-, line-, and point-like bodies. In accordance with the latter, building materials (finished products) can also be considered as surface-, line-, and point-like bodies. The aim of the study is to create compliance between the cell elements and the building structures. It will be done at different levels: – interpretation of relationship between building construction and cells, – interpretation of relationship between building construction and selected bodies, – interpretation the loadbearing's structure using cells, – structure of the surface-construction and the cells, – interpretation building types using cells. In this paper (as part I) the first two items will be studied. The other three cases will be studied in another paper (as part II). [ABSTRACT FROM AUTHOR]

Summary: In this paper, a dynamic and location‐based power allocation mechanism is proposed which could be adopted at both macrocell (MC) and overlaid fixed/mobile small cells (SCs) to mitigate inter‐cell interference (ICI) effects in heterogeneous cellular networks (HetCNs). The proposed Dynamic Power Allocation based on User Location (DPAUL) mechanism allows both MCs and deployed fixed/mobile SCs to dynamically allocate transmit power to its serving base stations (BSs) based on the location of a user in the cell. The paper illustrates the mitigation of dynamic downlink interferences occurring due to the mobility of SCs and users. The mobility of cell and its users is analyzed by introducing the Cell‐User mobility (CUM) model in the network. The proposed DPAUL mechanism is compared with the authors' other ICI mitigation techniques: Dynamic Fixed Region Cooperation (DFRC) and Dynamic Power Allocation Mechanism (DPAM). The network metrics Sumrate, User throughput, Energy‐efficiency, and Outage probability are investigated with allocation of sub 6 GHz and mmWave spectrums at MCs and fSCs/mSCs, respectively. [ABSTRACT FROM AUTHOR]

Network equilibrium models represent a versatile tool for the analysis of interconnected objects and their relationships. They have been widely employed in both science and engineering to study the behaviour of complex systems under various conditions, including external perturbations and damage. In this paper, network equilibrium models are revisited through graph-theory laws and attributes with special focus on systems that can sustain equilibrium in the absence of external perturbations (self-equilibrium). A new approach for the analysis of self-equilibrated networks is proposed; they are modelled as a collection of cells, predefined elementary network units that have been mathematically shown to compose any self-equilibrated network. Consequently, the equilibrium state of complex self-equilibrated systems can be obtained through the study of individual cell equilibria and their interactions. A series of examples that highlight the flexibility of network equilibrium models are included in the paper. The examples attest how the proposed approach, which combines topological as well as geometrical considerations, can be used to decipher the state of complex systems. [ABSTRACT FROM AUTHOR]

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This paper presents the design, fabrication and experimental characterization of an electro-thermally actuated microgripper suitable for single-cell manipulation. The analysis of the mechanical properties of cells is of great interest both in medicine and biology because the study of the cellular mechanical behaviour and resistance is necessary in these fields. Microgrippers (Bio-MEMS) have an important role in the manipulation of biological tissues and cells. In recent works, the research group simulated the mechanical behavior of grippers and the different actuation strategies. Considering the dimensional specifications and targets imposed by actuation and biocompatibility, in this paper, a microgripper based on electro-thermal actuation is studied. Starting from previous numerical results, a novel SU8 structure is designed and realized according to the micro-fabrication constraints and then the structure is simulated using the finite element method (FEM)-based thermo-structural simulations in ANSYS. Therefore, the fabrication method and steps are presented and the gripper has been developed and tested. Finally, the tip displacements of the gripper, electro-thermally actuated in different operating conditions, are compared with those obtained by means of numerical FEM simulations. A good agreement is obtained between simulations and experimental results. [ABSTRACT FROM AUTHOR]

This is a broad overview and critical review of a particular group of closely related ex vivo and in vitro metabolic NMR spectroscopic methods. The scope of interest comprises studies of cultured cells and excised tissue, either intact or after physicochemical extraction of metabolites. Our detailed discussion includes pitfalls that have led to erroneous statements in the published literature, some of which may cause serious problems in metabolic and biological interpretation of results. To cover a wide range of work from relevant research areas, we consider not only the most recent achievements in the field, but also techniques that proved to be valid and successful in the past, although they may not have generated a very significant number of papers more recently. Thus, this comparative review also aims at providing background information useful for judiciously choosing between the metabolic ex vivo/in vitro NMR methods presented. Finally, the methods of interest are discussed in the context of, and in relation to, other metabolic analysis protocols such as HR-MAS and cell perfusion NMR, as well as the mass spectrometry approach. [ABSTRACT FROM AUTHOR]

Cardiac remodelling refers to changes in left ventricular structure and function over time, with a progressive deterioration that may lead to heart failure (HF) development (adverse remodelling) or vice versa a recovery (reverse remodelling) in response to HF treatment. Adverse remodelling predicts a worse outcome, whilst reverse remodelling predicts a better prognosis. The geometry, systolic and diastolic function and electric activity of the left ventricle are affected, as well as the left atrium and on the long term even right heart chambers. At a cellular and molecular level, remodelling involves all components of cardiac tissue: cardiomyocytes, fibroblasts, endothelial cells and leucocytes. The molecular, cellular and histological signatures of remodelling may differ according to the cause and severity of cardiac damage, and clearly to the global trend toward worsening or recovery. These processes cannot be routinely evaluated through endomyocardial biopsies, but may be reflected by circulating levels of several biomarkers. Different classes of biomarkers (e.g. proteins, non‐coding RNAs, metabolites and/or epigenetic modifications) and several biomarkers of each class might inform on some aspects on HF development, progression and long‐term outcomes, but most have failed to enter clinical practice. This may be due to the biological complexity of remodelling, so that no single biomarker could provide great insight on remodelling when assessed alone. Another possible reason is a still incomplete understanding of the role of biomarkers in the pathophysiology of cardiac remodelling. Such role will be investigated in the first part of this review paper on biomarkers of cardiac remodelling. [ABSTRACT FROM AUTHOR]

In this paper, an isolated single-ended primary-inductive converter (ISEPIC) with a softswitching cell for implementing features of zero-voltage switching (ZVS) and zero-current switching (ZCS) is proposed. The ISEPIC has the following advantages: (1) By changing the inductor element of the ISEPIC into a transformer element, the features of electrical isolation can be achieved. (2) By incorporating a soft-switching cell, the power switches (MOSFETs) of the ISEPIC can achieve ZVS and ZCS features during turn-on conditions. Therefore, the power losses of the power switches can be reduced during the turn-on transient, and the overall efficiency of the ISEPIC can be increased significantly. Finally, a prototype of the ISEPIC with a soft-switching cell is built. Experimental results are presented to verify the performance and feasibility of the proposed ISEPIC for implementing features of ZVS and ZCS. [ABSTRACT FROM AUTHOR]

Grid cells and place cells are important neurons in the animal brain. The information transmission between them provides the basis for the spatial representation and navigation of animals and also provides reference for the research on the autonomous navigation mechanism of intelligent agents. Grid cells are important information source of place cells. The supervised learning and unsupervised learning models can be used to simulate the generation of place cells from grid cell inputs. However, the existing models preset the firing characteristics of grid cell. In this paper, we propose a united generation model of grid cells and place cells. First, the visual place cells with nonuniform distribution generate the visual grid cells with regional firing field through feedforward network. Second, the visual grid cells and the self-motion information generate the united grid cells whose firing fields extend to the whole space through genetic algorithm. Finally, the visual place cells and the united grid cells generate the united place cells with uniform distribution through supervised fuzzy adaptive resonance theory (ART) network. Simulation results show that this model has stronger environmental adaptability and can provide reference for the research on spatial representation model and brain-inspired navigation mechanism of intelligent agents under the condition of nonuniform environmental information. [ABSTRACT FROM AUTHOR]