Ease Of Generation Research Articles

Cancer aneuploidies are shaped primarily by effects on tumour fitness.

Aneuploidies-whole-chromosome or whole-arm imbalances-are the most prevalent alteration in cancer genomes1,2. However, it is still debated whether their prevalence is due to selection or ease of generation as passenger events1,2. Here we developed a method, BISCUT, that identifies loci subject to fitness advantages or disadvantages by interrogating length distributions of telomere- or centromere-bounded copy-number events. These loci were significantly enriched for known cancer driver genes, including genes not detected through analysis of focal copy-number events, and were often lineage specific. BISCUT identified the helicase-encoding gene WRN as a haploinsufficient tumour-suppressor gene on chromosome 8p, which is supported by several lines of evidence. We also formally quantified the role of selection and mechanical biases in driving aneuploidy, finding that rates of arm-level copy-number alterations are most highly correlated with their effects on cellular fitness1,2. These results provide insight into the driving forces behind aneuploidy and its contribution to tumorigenesis.

Biohydrogen production through dark fermentation: Recent trends and advances in transition to a circular bioeconomy

Fossil fuel reserves have drastically decreased over the past two decades, contributing to a worldwide decline in energy sources. The volatility of energy prices and their serious ecological consequences have drawn the attention of researchers to alternative carbon-neutral renewable energy sources. Furthermore, ineffective waste management contributes to environmental contamination, harms human health, and negatively affects the global economy. Biohydrogen (Bio-H2) derived from waste biomass via dark fermentation is a valuable green fuel to solve the issues of clean energy production and waste management. Bio-H2 has several advantages over other biofuels, including carbon-neutral production, ease of generation, low carbon dioxide (CO2) emissions, and high energy efficiency. Besides, by using biowaste to produce bio-H2, global warming and CO2 emissions associated with biowaste incineration can be reduced. Although dark fermentation produces the most efficient and clean bio-H2, the yield and rate of production of the process are very low. This review article summarizes the recent developments in dark fermentation processes to enhance bio-H2 yield and productivity, including pre-treatment, additives inclusion, and integrated solutions. Additionally, this article highlights the metabolic pathways of Bio-H2 production and inhibitory substances that negatively affect dark fermentation. Challenges related to bio-H2 technology transfer from lab to industry are discussed, and prospects for future research to realize the technology transfer are briefed. Further, an integrated carbon-neutral approach by dark fermentation-assisted bio-H2 production is also discussed as a contribution to circular bioeconomy.

Cross-reactivity influences changes in human influenza A virus and Epstein Barr virus specific CD8 memory T cell receptor alpha and beta repertoires between young and old.

Older people have difficulty controlling infection with common viruses such as influenza A virus (IAV), RNA virus which causes recurrent infections due to a high rate of genetic mutation, and Epstein Barr virus (EBV), DNA virus which persists in B cells for life in the 95% of people that become acutely infected. We questioned whether changes in epitope-specific memory CD8 T cell receptor (TCR) repertoires to these two common viruses could occur with increasing age and contribute to waning immunity. We compared CD8 memory TCR alpha and beta repertoires in two HLA-A2+ EBV- and IAV-immune donors, young (Y) and older (O) donors to three immunodominant epitopes known to be cross-reactive, IAV-M158-66 (IAV-M1), EBV-BMLF1280-288 (EBV-BM), and EBV-BRLF1109-117 (EBV-BR). We, therefore, also designed these studies to examine if TCR cross-reactivity could contribute to changes in repertoire with increasing age. TCR high throughput sequencing showed a significant difference in the pattern of TRBV usage between Y and O. However, there were many more differences in AV and AJ usage, between the age groups suggesting that changes in TCRα usage may play a greater role in evolution of the TCR repertoire emphasizing the importance of studying TRAV repertoires. With increasing age there was a preferential retention of TCR for all three epitopes with features in their complementarity-determining region (CDR3) that increased their ease of generation, and their cross-reactive potential. Young and older donors differed in the patterns of AV/AJ and BV/BJ pairings and usage of dominant CDR3 motifs specific to all three epitopes. Both young and older donors had cross-reactive responses between these 3 epitopes, which were unique and differed from the cognate responses having features that suggested they could interact with either ligand. There was an increased tendency for the classic IAV-M1 specific clone BV19-IRSS-JB2.7/AV27-CAGGGSQGNLIF-AJ42 to appear among the cross-reactive clones, suggesting that the dominance of this clone may relate to its cross-reactivity with EBV. These results suggest that although young and older donors retain classic TCR features for each epitope their repertoires are gradually changing with age, maintaining TCRs that are cross-reactive between these two common human viruses, one with recurrent infections and the other a persistent virus which frequently reactivates.

Human Retinal Organoids Provide a Suitable Tool for Toxicological Investigations: A Comprehensive Validation Using Drugs and Compounds Affecting the Retina.

Retinal drug toxicity screening is essential for the development of safe treatment strategies for a large number of diseases. To this end, retinal organoids derived from human pluripotent stem cells (hPSCs) provide a suitable screening platform due to their similarity to the human retina and the ease of generation in large-scale formats. In this study, two hPSC cell lines were differentiated to retinal organoids, which comprised all key retinal cell types in multiple nuclear and synaptic layers. Single-cell RNA-Seq of retinal organoids indicated the maintenance of retinal ganglion cells and development of bipolar cells: both cell types segregated into several subtypes. Ketorolac, digoxin, thioridazine, sildenafil, ethanol, and methanol were selected as key compounds to screen on retinal organoids because of their well-known retinal toxicity profile described in the literature. Exposure of the hPSC-derived retinal organoids to digoxin, thioridazine, and sildenafil resulted in photoreceptor cell death, while digoxin and thioridazine additionally affected all other cell types, including Müller glia cells. All drug treatments caused activation of astrocytes, indicated by dendrites sprouting into neuroepithelium. The ability to respond to light was preserved in organoids although the number of responsive retinal ganglion cells decreased after drug exposure. These data indicate similar drug effects in organoids to those reported in in vivo models and/or in humans, thus providing the first robust experimental evidence of their suitability for toxicological studies.

Genetically Engineered Hamster Models of Dyslipidemia and Atherosclerosis.

Animal models of human diseases play an extremely important role in biomedical research. Among them, mice are widely used animal models for translational research, especially because of ease of generation of genetically engineered mice. However, because of the great differences in biology between mice and humans, translation of findings to humans remains a major issue. Therefore, the exploration of models with biological and metabolic characteristics closer to those of humans has never stopped.Although pig and nonhuman primates are biologically similar to humans, their genetic engineering is technically difficult, the cost of breeding is high, and the experimental time is long. As a result, the application of these species as model animals, especially genetically engineered model animals, in biomedical research is greatly limited.In terms of lipid metabolism and cardiovascular diseases, hamsters have several characteristics different from rats and mice, but similar to those in humans. The hamster is therefore an ideal animal model for studying lipid metabolism and cardiovascular disease because of its small size and short reproduction period. However, the phenomenon of zygote division, which was unexpectedly blocked during the manipulation of hamster embryos for some unknown reasons, had plagued researchers for decades and no genetically engineered hamsters have therefore been generated as animal models of human diseases for a long time. After solving the problem of in vitro development of hamster zygotes, we successfully prepared enhanced green fluorescent protein (eGFP) transgenic hamsters by microinjection of lentiviral vectors into the zona pellucida space of zygotes. On this basis, we started the development of cardiovascular disease models using the hamster embryo culture system combined with the novel genome editing technique of clustered regularly interspaced short palindromic repeats (CRISPR )/CRISPR associated protein 9 (Cas9). In this chapter, we will introduce some of the genetically engineered hamster models with dyslipidemia and the corresponding characteristics of these models. We hope that the genetically engineered hamster models can be further recognized and complement other genetically engineered animal models such as mice, rats, and rabbits. This will lead to new avenues and pathways for the study of lipid metabolism and its related diseases.

Organoid and Spheroid Tumor Models: Techniques and Applications.

Simple SummaryCell cultures can be carried out in three dimensions (3D). Organoids and spheroids are different 3D cell culture models that can be cultured with different techniques. These 3D cell culture units established from a patient tumor have several similarities to the original tumor tissue and possess several advantages in conducting basic and clinical cancer research. Organoids prepared from a patient tissue can be preserved in a living biobank. Testing chemo-, radio- and immuno-therapies on these organoids has the potential to predict the patient responses and these models have incredible promise for personalized medicine. This review presents different organoid models, the techniques to prepare them and recent advances in their applications.Techniques to develop three-dimensional cell culture models are rapidly expanding to bridge the gap between conventional cell culture and animal models. Organoid and spheroid cultures have distinct and overlapping purposes and differ in cellular sources and protocol for establishment. Spheroids are of lower complexity structurally but are simple and popular models for drug screening. Organoids histologically and genetically resemble the original tumor from which they were derived. Ease of generation, ability for long-term culture and cryopreservation make organoids suitable for a wide range of applications. Organoids-on-chip models combine organoid methods with powerful designing and fabrication of micro-chip technology. Organoid-chip models can emulate the dynamic microenvironment of tumor pathophysiology as well as tissue–tissue interactions. In this review, we outline different tumor spheroid and organoid models and techniques to establish them. We also discuss the recent advances and applications of tumor organoids with an emphasis on tumor modeling, drug screening, personalized medicine and immunotherapy.

Induced Pluripotent Stem Cells in Dental and Nondental Tissue Regeneration: A Review of an Unexploited Potential.

Cell-based therapies currently represent the state of art for tissue regenerative treatment approaches for various diseases and disorders. Induced pluripotent stem cells (iPSCs), reprogrammed from adult somatic cells, using vectors carrying definite transcription factors, have manifested a breakthrough in regenerative medicine, relying on their pluripotent nature and ease of generation in large amounts from various dental and nondental tissues. In addition to their potential applications in regenerative medicine and dentistry, iPSCs can also be used in disease modeling and drug testing for personalized medicine. The current review discusses various techniques for the production of iPSC-derived osteogenic and odontogenic progenitors, the therapeutic applications of iPSCs, and their regenerative potential in vivo and in vitro. Through the present review, we aim to explore the potential applications of iPSCs in dental and nondental tissue regeneration and to highlight different protocols used for the generation of different tissues and cell lines from iPSCs.

Electrochemical Engineering in the Core of the Dye-Sensitized Solar Cells (DSSCs)

Dye-sensitized solar cells (DSSCs) are classed in the category of thin-film solar cells, which have been under thorough investigation during the last thirty years thanks to their low price, easy fabrication procedure, low toxicity and ease of generation. Even now, there are great efforts to substitute the present DSSC materials because of their elevated price, less abundance, and long-term stability. The performance of present DSSCs attains 12%, employing Ru(II) dyes via regulating material and structural features, which remains less than the performance given by first- and second-generation solar cells, i.e., other thin-film solar cells and Si-based solar cells which provide ~20% - 30% performance. This work focuses on the main findings of Sharma et al. [1] which presented an in-depth review on DSSC fabrication, running principle, fundamental issues (low efficiency, low scalability, and low stability), prospective efficient materials, and finally a brief insight to commercialization.

Multibeam radar based on linear frequency modulated waveform diversity

Multibeam radar (MBR) systems based on waveform diversity require a set of orthogonal waveforms in order to generate multiple channels in transmission and extract them efficiently at the receiver with digital signal processing. Linear frequency modulated (LFM) signals are extensively used in radar systems due to their pulse compression properties, Doppler tolerance, and ease of generation. Here, the authors investigate the level of isolation between MBR channels based on LFM chirps with rectangular and Gaussian amplitude envelopes. The orthogonal properties and the mathematical expressions of the isolation are derived as a function of the chirp design diversity, and specifically for diverse frequency slopes and frequency offsets. The analytical expressions are validated with a set of simulations as well as with experiments at C-band using a rotating target.

Predicting the spectrum of TCR repertoire sharing with a data-driven model of recombination.

SummaryDespite the extreme diversity of T‐cell repertoires, many identical T‐cell receptor (TCR) sequences are found in a large number of individual mice and humans. These widely shared sequences, often referred to as “public,” have been suggested to be over‐represented due to their potential immune functionality or their ease of generation by V(D)J recombination. Here, we show that even for large cohorts, the observed degree of sharing of TCR sequences between individuals is well predicted by a model accounting for the known quantitative statistical biases in the generation process, together with a simple model of thymic selection. Whether a sequence is shared by many individuals is predicted to depend on the number of queried individuals and the sampling depth, as well as on the sequence itself, in agreement with the data. We introduce the degree of publicness conditional on the queried cohort size and the size of the sampled repertoires. Based on these observations, we propose a public/private sequence classifier, “PUBLIC” (Public Universal Binary Likelihood Inference Classifier), based on the generation probability, which performs very well even for small cohort sizes.

Analysis of aptamer discovery and technology

Aptamers are nucleic acid molecules that mimic antibodies by folding into complex 3D shapes that bind to specific targets. Although some aptamers exist naturally as the ligand-binding elements of riboswitches, most are generated in vitro and can be tailored for a specific target. Relative to antibodies, aptamers benefit from their ease of generation, low production cost, low batch-to-batch variability, reversible folding properties and low immunogenicity. However, the true value of aptamers lies in the simplicity by which these molecules can be engineered into sensors, actuators and other devices that are often central to emerging technologies. This Review examines changing trends in aptamer technology by analysing the first quarter century of aptamer data that is available in the scientific literature (1990–2015). We highlight specific examples that showcase the use of aptamers in key applications, discuss challenges that have impeded the success of aptamers in practical applications, provide suggestions for choosing chemical modifications that can lead to enhanced activity or stability, and propose standards for the characterization of aptamers in the scientific literature. Aptamers are nucleic acid molecules that can be evolved to bind to specific molecular targets and have found applications in technologies such as sensors and actuators. This Review provides a critical analysis of the first 25 years of aptamer research.

Full-Optical TOAD based Walsh-Hadamard code generation

Transmission of information takes place simultaneously over the same available channel bandwidth in Code Division Multiple Access (CDMA) technique. The spread spectrum (SS) technique is used in CDMA systems for transmission of information by employing spreading codes. A unique spreading code, acts as a signature code, is assigned for each individual user. The signal occupies a bandwidth much larger than the minimum necessary to send the information in SS modulation technique. A synchronized reception with the code at the receiver is applied for dispreading the information before the data recovery. From a long-term, Walsh-Hadamard codes have been employed as spread spectrum codes in CDMA communications due to their ease of generation. Walsh-Hadamard codes are absolutely orthogonal binary user codes which have so many favourite applications in synchronous multicarrier communications. However, the optical application of Walsh-Hadamard codes turns important for optical CDMA to solve the above problem. For this, the designs need the use of nonlinear optics capable of controlling multi-valued signals. To achieve this goal all-optical terahertz optical asymmetric Demultiplexer based design of Walsh-Hadamard codes is explored in this paper.

Multiphysics modelling and experimental investigations of the filling and curing phases of bi-injection moulding of thermoplastic polymer/liquid silicone rubbers

Liquid silicone rubber (LSR) is a family of high-technology elastomer materials. The member of this family has been identified as being very promising for development in the coming decades due to their unique properties and ease of generation in large series by the injection moulding process. In particular, the over-moulding of LSR on other materials, such as thermoplastic polymers, metals and ceramics, is possible today, which leads to the possibility of obtaining multi-material, functional multi-colour and newly featured components. The work presented in this paper focuses on the transformation of liquid silicone rubber to better understand the phenomena involved to improve production processes and to optimize the processing conditions for bi-material components in well-defined geometry and functional properties. The rheological, rheo-kinetic and thermal behaviours of silicone elastomers were investigated and characterized under real conditions of manufacture with different combined methods. A thermo-rheo-kinetic model was then developed and implemented using the moulding simulation software Cadmould® 3D to simulate two-component injection moulding of silicone rubber into a thermoplastic polymer. For the validation of the models chosen and the parameters identified, bi-material injection moulding tests of a two-component standard peel test specimen (polyamide thermoplastic polymer/liquid silicone rubber) were performed and compared to numerical results.

The behavioural assessment of savouring in schizotypal anhedonia: The Verbal Fluency Test of Enjoyable Experiences (VFTEE)

Hedonic response is abnormal in negative schizotypy. Using self-report methods, Applegate, El-Deredy, and Bentall (2009) reported that schizotypal anhedonia was associated with a poor capacity to savour, where savouring is the ability to mentally rehearse past, present and future pleasant experiences. A behavioural measure of savouring, the Verbal Fluency Test of Enjoyable Experiences (VFTEE), was developed, and reliability and validity were assessed. The VFTEE elicits memories and predictions of positive experiences, using ease of generation as an index of savouring ability.Sixty-seven students, who scored high and low on measures of negative schizotypy and hypomania, completed questionnaire measures of hedonic functioning. Evoked affect was assessed on four trials of the VFTEE and an incentivised card-sorting task. The VFTEE demonstrated good internal reliability. Correlation and regression analyses revealed stylistically different abnormalities in how hypomanic and negatively schizotypal groups savour behaviourally.

QAM Constellation Design for Complex Field Network Coding in Multi-Way Relay Channels

Complex field network coding has been shown to achieve a throughput of 1/2 symbol per user per channel use in a multi-way relay channel. To achieve this throughput, a superimposed combination of user symbols must be distinguishable at the relay. Rectangular QAM constellations are commonly employed in communication systems due to their ease of generation, demodulation, and near optimal performance in AWGN channels. In this paper, an algorithm is presented to provide precoding vectors that guarantee every superposed combination of user symbols at the relay is distinguishable and QAM constellations are received at the relay. The performance in AWGN channels is derived. The algorithm allows users to employ different signal constellations, and also has the flexibility to allow users to join or leave the network at any time.

English

This paper shows the combustion of biogas in rural households’ appliances. Biogas has been known since 1800s as an odourless and colourless gas with high combustion rate. Its use is beginning to gain ground in most developing countries like Nigeria due to its availability, ease of generation and environmental friendliness. Developing countries are characterized by poor infrastructural development, inadequate energy and water supply, poor health delivery system, etc. which hinders economic and social development. Most sources of rural households’ energy are firewood, animal dung, crop residue and kerosene which are associated with negative environmental impacts. The study was carried-out by articulation of past literatures on biogas combustion and consumption in household’s appliances and internal combustion engines. The study ascertains from the past studies high efficiency of biogas compared with natural gas andliquid petroleum gas (LPG) on stove-top burner, oven and two panel flue heater. It was observed that, biogas consumption is higher in all the appliances under investigation as compared to natural gas and LPG. The study recommended public enlightenment on biogas technology and its associate benefits to rural areas. The government and NGOs should encourage the application of this technology through financing of pilot projects in community leaders’ households which will extend to the populace. The technology should also be embraced because it is associated with environmental hygiene. Key words: Efficiency, hygiene, sustainability, developing countries, biogas.

Simplified signal processing for impedance spectroscopy with spectrally sparse sequences

Classical method for measurement of the electrical bio-impedance involves excitation with sinusoidal waveform. Sinusoidal excitation at fixed frequency points enables wide variety of signal processing options, most general of them being Fourier transform. Multiplication with two quadrature waveforms at desired frequency could be easily accomplished both in analogue and in digital domains, even simplest quadrature square waves can be considered, which reduces signal processing task in analogue domain to synchronous switching followed by low pass filter, and in digital domain requires only additions. So called spectrally sparse excitation sequences (SSS), which have been recently introduced into bio-impedance measurement domain, are very reasonable choice when simultaneous multifrequency excitation is required. They have many good properties, such as ease of generation and good crest factor compared to similar multisinusoids. Typically, the usage of discrete or fast Fourier transform in signal processing step is considered so far. Usage of simplified methods nevertheless would reduce computational burden, and enable simpler, less costly and less energy hungry signal processing platforms. Accuracy of the measurement with SSS excitation when using different waveforms for quadrature demodulation will be compared in order to evaluate the feasibility of the simplified signal processing. Sigma delta modulated sinusoid (binary signal) is considered to be a good alternative for a synchronous demodulation.

Analysis of intracellular reducing levels in human hepatocytes on three‐dimensional focusing microchip

A novel three-dimensional hydrodynamic focusing microfluidic device integrated with high-throughput cell sampling and detection of intracellular contents is presented. It has a pivotal role in maintaining the reducing environment in cells. Intracellular reducing species such as vitamin C and glutathione in normal and tumor cells were labeled by a newly synthesized 2,2,6,6-tetramethyl-piperidine-1-oxyl-based fluorescent probe. Hepatocytes are adherent cells, which are prone to attaching to the channel surface. To avoid the attachment of cells on the channel surface, a single channel microchip with three sheath-flow channels located on both sides of and below the sampling channel was developed. Hydrostatic pressure generated by emptying the sample waste reservoir was used as driving force of fluid on the microchip. Owing to the difference between the liquid levels of the reservoirs, the labeled cells were three-dimensional hydrodynamically focused and transported from the sample reservoir to the sample waste reservoir. Hydrostatic pressure takes advantage of its ease of generation on a microfluidic chip without any external pressure pump, which drives three sheath-flow streams to constrain a sample flow stream into a narrow stream to avoid blockage of the sampling channel by adhered cells. The intracellular reducing levels of HepG2 cells and L02 cells were detected by home-built laser-induced fluorescence detector. The analysis throughput achieved in this microfluidic system was about 59-68 cells/min.

Neutralization of Human Papillomavirus by Specific Nanobodies Against Major Capsid Protein L1

The human papillomavirus (HPV) is the main cause of cervical cancer in developing countries. Rapid diagnosis and initiation of treatment of the HPV infection are critical. Various methods have been employed to reduce the immunogenicity of antibodies targeting HPV serotypes. Nanobodies are the smallest fragments of naturally occurring single-domain antibodies with their antigenbinding site compromised into a single domain. Nanobodies have remarkable properties such as high stability, solubility, and high homology to the human VH3 domain. In this study, a phagemid library was employed to enrich for nanobodies against the L1 protein of the human papilloma virus. Binding reactivity of the selected clones was evaluated using phage enzyme-linked immunosorbent assay (phage-ELISA). Finally, two nanobodies (sm5 and sm8) with the best reactivity against the Gardasil vaccine and the purified HPV-16 L1 protein were expressed and purified using a Ni(+)-NTA column. The accuracy of expression and purification of the nanobodies was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting assays. In vitro studies demonstrated that neutralization was achieved by the selected nanobodies. The ease of generation and unique features of these molecules make nanobodies promising molecules for the new generation of HPV diagnosis and therapy.

Hexazamacrocycle assisted sensing of silver ion through facile synthesis of silver nanoparticles

The ease of generation of silver nanoparticles by using hexazamacrocycle ligand, L1 is utilized for the visual detection of the presence of silver ions at lower concentrations.