The objective of this study was to apply simulation and computational intelligence techniques using artificial intelligence and genetic algorithm for economic and environmental optimization of the reverse network (manufacturers, waste managers and recyclers in São Paulo, Brazil) of waste electrical and electronic equipment (WEEE) to promote circular economy. For the economic evaluation, the reduction of: fuel, drivers, insurance, depreciation, maintenance and charges was considered and for the environmental evaluation, the environmental impact was measured in the abiotic, biotic, water, land, air and greenhouse gases compartments. It is concluded that the optimized structure of the WEEE reverse chain for São Paulo, Brazil reduced the number of collections, making the most of the cubage. It also generated economic and environmental gains, contributing to the strategic actions of the circular economy. Thus, the proposed simulation allows replication in organizational practice, mainly to meet the 2030 agenda on reducing the carbon footprint generated in transport in large cities. Thus, this study can guide companies on structuring the reverse WEEE chain in São Paulo, Brazil for economic and environmental optimization, a relevant aspect considering the exponential generation of WEEE, requiring the implementation of the national solid waste policy, and subsequently the signature of the electronics sector agreement in São Paulo.

According to data from the U.S FDA, the likelihood of a new drug progressing from Phase I clinical trials to market approval is only 8% (DiMasi et al., 2016). Furthermore, a significant attrition rate of 35% occurs during Phase II studies due to the failure to demonstrate clinical efficacy (Arrowsmith, 2011). These statistics underscore the urgent need to reassess the current research and development (R&D) paradigm. To address this challenge, a promising approach called reverse translational pharmacology (RTP) has emerged, aiming to enhance the predictive value of preclinical models used in biomedical research by leveraging animal models that spontaneously develop analogous diseases to humans (Schneider et al., 2018). The rationale behind RTP is that knowledge gained from clinical trials in canines can subsequently inform and guide human clinical trials, leading to improved outcomes for both species. Additionally, this approach capitalizes on the opportunity to stimulate veterinary drug development by leveraging pharmacokinetic (PK), efficacy, and safety data obtained from human clinical studies (Schneider et al., 2018). The application of reverse translational pharmacology holds immense potential for expediting drug development and advancing medical knowledge. By employing animal models that naturally develop diseases akin to those found in humans, researchers can enhance the predictive capacity of preclinical models, thereby mitigating the high attrition rates encountered in later stages of clinical trials. Moreover, the exchange of knowledge and data between human and veterinary medicine engenders a synergistic relationship, fostering progress in both domains (Schneider et al., 2018). As this innovative approach gains momentum, fostering collaborations between basic and clinician scientists, pharmaceutical companies, and veterinary professionals becomes increasingly imperative. By sharing resources, expertise, and findings, we can pave the way for groundbreaking discoveries and the development of safe and efficacious treatments for diverse diseases. Embracing reverse translational pharmacology offers an avenue to redefine the R&D paradigm, bringing us closer to a future where a higher proportion of drugs successfully traverse the arduous path from the laboratory to market approval, ultimately benefiting patients across species. In this brief commentary, we highlight four examples of diseases where reverse translational modeling has been used to support pharmaceutical research, including some applications developed in our research laboratory (SMART Pharmacology) at the Iowa State University College of Veterinary Medicine. In doing so, this report also seeks to provide a brief overview of the heuristic value of computational approaches in comparative research. To further illustrate the value of these in silico approaches, we deliberately chose to employ some features of ChatGPT to produce the present summary (OpenAI. (2023). GPT-3.5 [ChatGPT]. Retrieved from https://openai.com).

Vaccination has been one of the most successful and the most significant scientific advances in human health and life expectancy all around the globe. The World Health Organization considers that immunization should be recognized as the main component of human health right, due to the fact that vaccination prevents 2.5 million deaths annually (World Health Organization, 2011). The most successful vaccines have been developed using conventional methods that follow the paradigm established by Pasteur: "to isolate, inactivate and inject" the pathogen microorganism and mimic a natural infection. Recently, metagenomics have played an important role in the discovery of new immunogens for vaccine design and the selection of antigens based on genomic information. The main approach that has used this strategy has been called "reverse vaccinology". This promising and arising field allows the screening of the entire potential antigenic repertoire of an organism using predictive bioinformatic tools. Once the antigenic protein or proteins have been selected, they are expressed and purified using molecular cloning and in vitro expression techniques. Following the in vitro production step, they are probed in animal models to evaluate the in vivo protective strength of the immune response. The main aim of this in vivo approach is to evaluate the ability of the immune response to eliminate or neutralize the pathogen at the time of infection. Those antigens capable of generate a specific immune response with neutralizing activity for natural infections are the best candidate vaccines. In this review we summarize the evolution of vaccinology since its inception, with special emphasis on the development of VLPs as vaccine platforms and their future in preventive medicine and we introduce a new recombinant platform for antigen presentation based on Junin virus VLPs (JUNV-VLPs).

Liquid marbles are defined as hydrophilic liquid droplets that are coated with hydrophobic powdered materials. Till now, the behaviour of liquid marbles has been studied for triphasic systems comprising of the constituent hydrophilic phase, the hydrophobic coating and ambient air. In this article, we report the dynamics of aqueous droplets of varying pH (i.e. acidic, neutral and basic, respectively) moving under the influence of gravity in commonly available mustard oil. We find that the said dynamics could be divided into four parts: (i) formation of hanging aqueous droplets from the top surface of oil, (ii) oblate spheroid droplets moving at constant velocity due to viscous drag, (iii) distant repulsive interactions between two droplets due to “reverse Cheerios effect” and (iv) final impact between the two droplets explained by viscoelastic sliding friction over a compliant surface. This work would be of great interest to researchers working in the domain of interfacial phenomena like oil exploration, biomedical engineering, food technology and towards the realization of droplet-based microfluidic computational platforms for “more than Moore’s” paradigm in the domain of unconventional computation.

The increase in carbon dioxide emissions has a significant impact on human society and the global environment. As the most abundant and cheap C1 resource, the conversion and utilization of carbon dioxide has received extensive attention from researchers. In many methods of carbon dioxide conversion and utilization, the reverse water gas conversion reaction is considered to be one of the most effective ways. In this paper, the research progress of reverse water gas conversion reaction in recent years is introduced.

As hematite ores become lower in grade, finer in grain size, and more complex in compositions, their beneficiation by froth flotation to produce the high Fe grade concentrate has become increasingly more difficult. A systematic and in-depth process mineralogy study based on the multi-element chemical and MLA analysis combined with other characterization techniques was conducted to explore the fundamental reasons for difficulties in refractory hematite flotation separation. The results show that the valuable mineral in the sample was mainly hematite and gangue mineral was primarily quartz. Hematite had a fine particle size distributed over a range of 0~45 μm with a degree of mineral liberation of 90.19%. The particle size of quartz was relatively coarse and was mainly distributed in the range of 20~150 μm with a liberation degree of only 67.72%. Unliberated quartz was mainly associated with hematite and the composite particle content was 36.44%. The rougher flotation tests produced a flotation concentrate of 66.71% TFe grade at a recovery of 65.47%. The screening analysis results with rougher flotation products indicated that the main reasons for the poor performance of rougher flotation were the serious entrainment of fine hematite particles and the difficulty in effective collection of coarse low-grade composite particles. Possible approaches for improving hematite flotation performance have been proposed based on the results from this study.

One of the mechanisms used in the management and cure of atherosclerosis is reverse cholesterol transfer (RCT), which plays a vital role in the export of cholesterol from peripheral cells. Cholesterol efflux from macrophages in the subintima of the vessel wall is a critical part of RCT. ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) are involved in the transfer of cholesterol from arterial macrophages to extracellular high-density lipoprotein cholesterol (HDL). The HDL then transports esterified cholesterol to the liver for elimination. An important factor in the reverse cholesterol transport and excretion of extracellular cholesterol is HDL. Atherogenesis can be prevented by altering the processes of RCT and cholesterol efflux, and this might lead to novel treatment options for cardiovascular disease. Research of novel modifying variables for RCT and cholesterol efflux is necessary. A better understanding of RCT's molecular processes has been gained via research, allowing for the creation of new treatments that make use of RCT's potential for pharmacological improvement. The purpose of this review is to provoke discussion on the potential impact of selected flavonoids on cholesterol efflux on the progression of atherosclerosis (Fig. 1.).

Two major uses of linear perspective are in planar paintings - the flat canvas is incongruent with the painted 3-D scene - and in forced perspectives, such as theater stages that are concave truncated pyramids, where the physical geometry and the depicted scene are congruent. Patrick Hughes pioneered a third major art form, the reverse perspective, where the depicted scene opposes the physical geometry. Reverse perspectives comprise solid forms (truncated pyramids and prisms) jutting toward the viewer, thus forming concave spaces between the solids. The solids are painted in reverse perspective: as an example, the left and right trapezoids of a truncated pyramid are painted as rows of houses; the bottom trapezoid is painted as the road between them and the top forms the sky. This elicits the percept of a street receding away, even though it physically juts toward the viewer. Under this illusion, the concave void spaces between the solids are transformed into convex volumes. This depth-inversion creates a concomitant motion illusion: when a viewer moves in front of the art piece, the scene appears to move vividly. Two additional contributions by the artist are discussed, in which he combines reverse perspective parts with forced and planar perspective parts on the same art piece. The effect is spectacular, creating objects on the same planar surface that move in different directions, thus “breaking” the surface apart, demonstrating the superiority of objects over surfaces. We conclude with a discussion on the value of these art pieces in vision science.

RO membrane fouling is one of the main challenges that membrane manufactures, the scientific community and industry professionals have to deal with. The consequences of this inevitable phenomenon have a negative effect on the performance of the desalination system. Predicting fouling in RO systems is key to evaluating the long-term operating conditions and costs. Much research has been done on fouling indices, methods, techniques and prediction models to estimate the influence of fouling on the performance of RO systems. This paper offers a critical review evaluating the state of industry knowledge in the development of fouling indices and models in membrane systems for desalination in terms of use and applicability. Despite major efforts in this field, there are gaps in terms of effective methods and models for the estimation of fouling in full-scale RO desalination plants. In existing models applied to full-scale RO desalination plants, neither the spacer geometry of membranes nor the efficiency and frequency of chemical cleanings - which play an important role in the performance of this process - are considered.

Since the first published genome sequence of Trypanosoma cruzi in 2005, there has been tremendous technological advance in genomics, reverse genetics, and assay development for this elusive pathogen. However, there is still an unmet need for new and better drugs to treat Chagas disease. Here we introduce a T. cruzi assay strain that is useful for drug research as well as basic studies in host-pathogen interaction. Trypanosoma cruzi STIB980 is a strain of discrete typing unit TcI that grows well in culture as axenic epimastigotes or intracellular amastigotes. We have evaluated the optimal parameters for genetic transfection and constructed derivatives of T. cruzi STIB980 that express reporter genes for fluorescence- or bioluminescence-based drug efficacy testing, as well as a Cas9-expressing line for CRISPR/Cas9-mediated gene editing. The genome of T. cruzi STIB980 was sequenced by combining short-read Illumina with long-read Oxford Nanopore technologies. The latter served for the primary assembly, the former to correct mistakes and fill the gaps. This resulted in a high-quality nuclear haplotype assembly of 28 Mb in 400 contigs, containing 10,043 open-reading frames with a median length of 1077 bp. We believe that T. cruzi STIB980 is a useful addition to the antichagasic toolbox, and propose that it can serve as a DTU TcI reference strain for drug efficacy testing.

An HPLC method for indicating stability was developed, created, and confirmed for the quantification measurement of recombinant human erythropoietin in large quantities as well as dosage forms. An isocratic separation was accomplished using a Thermo Biobasic C18 (250 mm 4.6 mm i.d., 300Ao, 5 m) column with a flow rate of 1.0 mL min-1 as well as a UV detector to monitor the eluate at 278 nm. Acetonitrile, 0.05 mM potassium dihydrogen phosphate (80:20 v/v), and orthophosphoric acid adjusted to 4.0 made up the mobile phase. The drug was exposed to oxidative stress, hydrolysis, and photodegradation to simulate stress conditionsRecombinant Human Erythropoietin, the parent compound, was eluted at roughly 6.675 minutes, as well as all byproducts have been entirely disconnected inside an overall analytical run time of about 15 minutes. To identify quantification limits of 0.05 and 0.2 g mL-1, respectively, the method was linear over a concentration range of 1-6 g mL-1 (r = 0.9989). Recombinant Human Erythropoietin can be measured accurately, selectively, sensitively, and precisely using this method both in dosage form and in bulk. Stress-induced degradation products did not interact with the identification of Recombinant Human Erythropoietin, indicating that the assay is stable.

Sparkling wine producing and consumption are in constant increase in the last decade and show no sign of slowing. Prior consumption, origin, grape variety, occasion, price and sensorial perception are factors that typically influence wine consumers’ purchasing and consumption behavior. The presence of volatile compounds in sparkling wines, with direct impact on their organoleptic characteristics, is influenced by several factors, such as the base-wine characteristics, grapes cultivar conditions, the used yeasts, the aging stage or wine-making practices. For this study, five sparkling wines variants from Muscat Ottonel grape variety were obtained. For the experimental samples, the grapes were processed by applying secondary fermentation in bottles. The base-wine was obtained through reverse osmosis and had a predetermined alcoholic concentration (10.5 % vol.). This study aimed to analyze the influence of different commercial yeasts (IOC FIZZ™, IOC DIVINE™, LEVULIA CRISTAL™, IOC 18-2007™) on the volatile composition of experimental sparkling wines. The obtained sparkling wines were characterized by the physical-chemical parameters (according to OIV methods of analysis) and volatile fraction (using gas-chromatography). Data showed an important impact on the concentration of the volatile compounds (p < 0.05), depending on the type of inoculated yeast for the second fermentation and only a minor influence on the physical-chemical parameters was registered.

Phosphorus is essential and non-substitutable chemical element required for the cellular processes of all living organisms. The main source of phosphorus in the biosphere is phosphate rock. With more than 700 Mt P2O5, Estonia holds the largest sedimentary phosphate rock deposits in European Union. Estonian phosphate rock is principally sandstone that holds abundant remains of phosphatic brachiopod shells and compared to other sedimentary rocks, is particularly outstanding by its remarkably low content of hazardous heavy metals such as Cd and saturated by valuable elements present in the rock such as rear earth elements (REEs).

As freshwater sources of drinking water become limited cities and urban areas must consider higher-salinity waters as potential sources of drinking water. The Salton Sea in the Imperial Valley of California has a very high salinity (43 ppt), total dissolved solids (70,000 mg/L) and color (1440 CU). Proposals to desalinate the Salton Sea are expected to lower the equilibrium salinity from 45 ppt to 3 ppt yielding significant benefits for ecological restoration. High salinity eutrophic waters such as the Salton Sea are difficult to treat yet more desirable sources of drinking water are not always available. Jar tests were performed to evaluate the treatability of Salton Sea water for potential urban water use by coagulation using aluminum chlorohydrate, ferric chloride and alum. Coagulation-sedimentation proved to be relatively ineffective for lowering turbidity with no clear optimum dose for any of the coagulants tested. Alum was most effective for color removal (28 percent) at a dose of 40 mg/L. Turbidity was removed effectively with 0.45 m and 0.1 m microfiltration. Bench tests of Salton Sea water using Sea Water Reverse Osmosis (SWRO) achieved rejections of 99 percent salinity, 97.7 percent conductivity, 98.6 percent total dissolved solids, 98.7 percent chloride, 65 percent sulfate, and 99.3 percent turbidity.

Pyrolysis is a thermochemical conversion process designed for biomass decomposition in an oxygen-free environment. It typically operates within a temperature window of 200 to 800°C and generates various byproducts, including gases, liquid fractions (both aqueous and organic) such as bio-oil, and solids like char. Bio-oil is a significant product of pyrolysis. It is characterised by a complex blend of organic compounds. The acidic nature of bio-oil primarily originates from volatile acids, such as acetic acid. The recovery of acetic acid from bio-oil facilitates the use of the extracted substance as a precious resource, hence enhancing its significance in the framework of a circular bioeconomy. Acetic acid finds widespread application in manufacturing commercially important chemicals like vinyl acetate monomers and formulating phytosanitary products due to its inherent herbicidal and antifungal properties. However, to be used, acetic acid has to be separate from the raw bio-oil. Separation methodologies, including nanofiltration and reverse osmosis, demonstrate potential in recovering acidic constituents from bio-oil due to their high selectivity and effective system management. This article offers a concise review about acetic production from lignocellulosic biomass from pyrolysis and its recovery through various membrane separation processes.

Cerebrovascular and airway structures are tubular structures used for transporting blood and gases, respectively, providing essential support for the normal activities of the human body. Accurately segmenting these tubular structures is the basis of morphology research and patho-logical detection. Nevertheless, accurately segmenting these structures from images presents great challenges due to their complex morphological and topological characteristics. To address this challenge, this paper proposes a framework UARAI based on the U-Net multi-scale reverse at-tention network and sparse convolution network. The framework utilizes a multi-scale structure to effectively extract the global and deep detail features of vessels and airways. Further, it enhances the extraction ability of fine-edge features by a joint reverse attention module. In addition, the sparse convolution structure is introduced to improve the features' expression ability without increasing the model's complexity. Finally, the proposed training sample cropping strategy re-duces the influence of block boundaries on the accuracy of tubular structure segmentation. The experimental findings demonstrate that the UARAI-based metrics, namely Dice and IoU, achieve impressive scores of 90.31% and 82.33% for cerebrovascular segmentation and 93.34% and 87.51% for airway segmentation, respectively. Compared to commonly employed segmentation tech-niques, the proposed method exhibits remarkable accuracy and robustness in delineating tubular structures such as cerebrovascular and airway. These results hold significant promise in facilitating medical image analysis and clinical diagnosis, offering invaluable support to healthcare profes-sionals.

The reverse transcription quantitative polymerase chain reaction (RT-qPCR) is an established tool for the diagnosis of RNA pathogens. Its potential for automation has caused it to be used as a presence/absence diagnostic tool even when RNA quantification is not required. This technology has been pushed to the forefront of public awareness by the COVID-19 pandemic, as its global application has enabled rapid and analytically sensitive mass testing, with the first test targeting three viral genes published within days of the publication of the SARS-CoV-2 genomic sequence. One of those, targeting the RNA-dependent RNA polymerase gene, has been heavily criticised for supposed scientific flaws at the molecular and methodological level and this criticism has been extrapolated to doubts about the validity of RT-qPCR for COVID-19 testing in general. We have analysed this assay in detail and our findings reveal some limitations, but also highlight the robustness of the RT-qPCR methodology for SARS-CoV-2 detection. Whilst our data show that some errors can be tolerated, it is always prudent to confirm that primer and probe sequences complement their intended target, since when errors do occur, they may result in a reduction in the analytical sensitivity. However, in this case it is unlikely that a mismatch will result in poor specificity or significant number of false positive SARS-CoV-2 diagnoses, especially as this is routinely checked by diagnostic laboratories as part of their quality assurance.

This note addresses a fundamental problem in matrix theory on establishing and characterizing range equalities for matrix expressions that involve generalized inverses. We first establish a group of necessary and sufficient conditions for the matrix range equality ${\rm range}(D_1 - C_1A_1^{\dag}B_1) = {\rm range}(D_2 - C_2A_2^{\dag}B_2)$ to hold, where $(\cdot)^{\dag}$ denotes the Moore--Penrose inverse of matrix. We then give several groups of range equalities with extrusion properties for multiple matrix products associated with two matrices and their conjugate transposes and Moore--Penrose inverses.

This note shows that the well-known reverse order law $(AB)^{\dag} = B^{\dag}A^{\dag}$ for the Moore--Penrose inverse of matrix product is equivalent to many other equalities for that are composed of multiple products $(AB)^{\dag}$ and $B^{\dag}A^{\dag}$ by means of the definition of the Moore--Penrose inverse and orthogonal projector theory.

The high mutation rate of human immunodeficiency virus type 1 (HIV-1) plays a major role in treatment resistance from the development of vaccines to long-lasting drugs. In addressing the crux of the issue, various attempts to estimate the mutation rate of HIV-1 resulted in a large range of 10-5 - 10-3 errors/bp/cycle due to the use of different types of investigation methods. In this review, we discuss the different assay methods, their findings on the mutation rates of HIV-1 and how the location of these mutations can be further analyzed for their potential allosteric effects to reveal potentially new inhibitors with different pharmacodynamics that can be used to circumvent fast occurring HIV drug resistance. Given that HIV is one of the fastest mutating viruses, it is a good model for comprehensive study of its mutations that can give rise to much horizontal understanding towards overall viral drug resistance as well as emerging viral diseases.

This paper presents an overview of the principal structural and dynamics characteristics of reverse micelles (RMs) in order to highlight their structural flexibility and versatility, along with the possibility to modulate their parameters in a controlled-manner. The multifunctionality in a large range of different scientific fields is exemplified in two distinct directions: a theoretical model for mimicry of biological microenvironment and practical application in the field of nanotechnology and nano-based sensors. RMs represents a convenient experimental approach that limits the drawbacks of the conventionally biological studies in vitro, while the particular structure confers them the status of simplified mimics of cells by reproducing a complex supramolecular organization in an artificial system. The biological relevance of RMs is discussed in some particular cases referring to the confinement and crowding environment, molecular dynamics of water and cell membrane structure. The use of RMs in different range of applications seems to be more promising due to their structural and compositional flexibility, a high efficiency and selectivity being achieved. The advance in nanotechnology is based on developing new methods of nanomaterials synthesis and deposition. This review highlighting the advantages of using RMs in synthesis of nanoparticles with specific properties and in nano (bio)sensors design.

Proper management of water is a challenge for every individual but especially for companies. Nowadays also legislation obliges companies to clean the wastewater before being discharged into municipal public sewer especially if they use some chemicals or oily elements in their production process. Construction of the wastewater cleaner depends directly on the way of pollution, the amount of contaminated water and the energy demand of the cleaning process. The paper deals with the construction of the wastewater cleaner, which is based on the technology of electro-flotation for the treatment of water contaminated with disperse colorants. The experimental work as well as the modelling using the statistical methods proved the suitability of the chosen technology. Also, each colour combination requires a specific time period for the water treatment. The authors determined the time interval for cleaning the wastewater that was polluted with yellow colour to 33 minutes. Finally, the wastewater cleaner that is based on the electro-flotation technology was included in the company’s reverse logistics system.

Hybrid reverse osmosis electrodialysis systems make it possible to obtain solutions with a higher concentration of components compared to single electrodialysis treatment, i.e. more efficient separation of brine and pure water. The article proposes experimental and pilot-industrial studies of a hybrid membrane system operation using industrial wastewater for the disposal of liquid waste from an ion-exchange chemical-desalting water treatment plant of a thermal power plant, followed by a calculation of economic efficiency and an analysis of the environmental feasibility of their use. The developed technological scheme offers separate processing of acidic and alkaline waste regeneration solutions using calcium carbonate reagent and desalination on baromembrane and electromembrane units to obtain clean water and dry residue. The hybrid system includes a booster filter press and an evaporator. The hybrid system makes it possible to provide a thermal power plant with a "zero discharge" with a minimum consumption of reagents and electricity, as well as return all water from wastewater to the power plant cycle.

In the context of food packaging design, customization enhances the value of a product by meeting the needs of the consumer. Personalization is also linked to adaptation. This makes it possible to improve the properties of the packaging from various points of view: functional, aesthetic, economic and ecological. Currently the functional and formal properties of packaging are not investigated among themselves, however the study of both properties are the basis for creating a new concept of personalized and sustainable product. In accordance with this approach, the conceptual design procedure of packaging with personalized and adapted geometries based on the digitization of fresh food is proposed in this work. This study is based on the application of advanced technologies for the design and development of food packaging, in this case apples, in order to improve the quality of the packaging. The results obtained show that it is possible to use advanced technologies in the early stages of product design in order to obtain competitive products adapted to new emerging needs.

Given a square matrix $A$, we are able to construct numerous equalities that involve reasonable mixed operations of $A$ and its conjugate transpose $A^{\ast}$, Moore--Penrose inverse $A^{\dag}$, and group inverse $A^{\#}$. Such kind of equalities can be generally represented in the equation form $f(A, \, A^{\ast}, A^{\dag}, A^{\#}) =0$. In this article, the author constructs a series of simple or complicated matrix equalities, as well as matrix rank equalities involving the mixed operations of the four matrices. As applications, we give a sequence of necessary and sufficient conditions for a square matrix to be range-Hermitian.

It is a classic topic in algebras to construct and verify equalities that are composed of various algebraic operations of elements and their inverses or generalized inverses. In this note, the author constructs a matrix equality $(AB)^{\dag} = B^{\ast}(A^{\ast}ABB^{\ast})^{\#}A^{\ast}$ (called a mixed reverse-order law), where $A$ and $B$ are two matrices of appropriate sizes, $(\cdot)^{\ast}$, $(\cdot)^{\dag}$, and $(\cdot)^{\#}$ denote the conjugate transpose, the Moore--Penrose inverse, and the group inverse of a matrix, respectively, and shows that the mixed reverse-order law always holds. A list of variation forms of this matrix equality are also given, and necessary and sufficient conditions are obtained for them to hold. Especially, we show a remarkable fact that the two reverse-order laws $(AB)^{\dag} = B^{\dag}A^{\dag}$ and $(A^{\ast}ABB^{\ast})^{\#} = (BB^{\ast})^{\#}(A^{\ast}A)^{\#}$ are equivalent.

In humans and animal models, intermittent fasting (IF) interventions promote body weight loss, improve metabolic health, and are thought to lower cardiovascular disease risk. However, there is a paucity of reports on the relevancy of such nutritional interventions in the context of dyslipidemia and atherosclerotic cardiovascular diseases. The present study assessed the metabolic and atheroprotective effects of intermittent fasting intervention (IF) in atherosclerosis-prone apolipoprotein E-deficient (Apoe-/-) mice. Groups of male and female Apoe-/- mice were fed a regular (chow) or atherogenic (high-fat, high-cholesterol, HFCD) diet for 4 months, either ad libitum or in an alternate-day fasting manner. The results show that IF intervention improved glucose and lipid metabolism independently of sex. However, IF only decreased body weight gain in males fed chow diet and differentially modulated adipose tissue parameters and liver steatosis in a diet composition-dependent manner. Finally, IF prevented spontaneous aortic atherosclerotic lesions formation in mice fed chow diet, irrespective of sex but failed to reduce HFCD-diet-induced atherosclerosis. Overall, the current work indicates that IF interventions can efficiently improve glucose homeostasis and treat atherogenic dyslipidemia, but a degree of caution is warranted with regard to the individual sex and the composition of the dietary regimen.

Pseudomonas aeruginosa is a critical healthcare challenge due to its ability to cause persistent infections and the acquisition of antibiotic resistance mechanisms. Lack of preventive vaccines and rampant drug resistance phenomenon has rendered patients vulnerable. As new antimicrobials are in the preclinical stages of development, mining for the unexploited drug targets is also crucial. Here, we designed a chimeric vaccine against P. aeruginosa using a subtractive proteomics approach and identified nine unique enzymes as novel drug targets in PAO1 proteome. A total of five unique proteins were selected as potential vaccine candidates based on essentiality, extracellular localization, virulence, antigenicity, pathway association, protein-protein interaction analysis, hydrophilicity, and low molecular weight. These include two outer membrane porins OprF (P13794) and OprD (P32722), a protein activator precursor pra (G3XDA9), a probable outer membrane protein precursor PA1288 (Q9I456), and a conserved hypothetical protein PA4874 (Q9HUT9). These proteins were further analyzed using a reverse vaccinology approach to identify immunogenic and antigenic T cell and B cell epitopes. The best scoring epitopes qualifying for all set criteria were then further subjected to the construction of a polypeptide multi-epitope vaccine construct with cholera toxin B (CtxB) subunit as an adjuvant. The identified drug targets qualifying the screening criteria were: UDP-2-acetamido-2-deoxy-d-glucuronic acid 3-dehydrogenase WbpB (G3XD23), aspartate semialdehyde dehydrogenase (Q51344), 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase (Q9HV71), 3-deoxy-D-manno-octulosonic-acid transferase (Q9HUH7), glycyl-tRNA synthetase alpha chain (Q9I7B7), riboflavin kinase/FAD synthase (Q9HVM3), aconitate hydratase 2 (Q9I2V5), probable glycosyltransferase WbpH (G3XD85) and UDP-3-O-[3-hydroxylauroyl] glucosamine N-acyltransferase (Q9HXY6). For druggability and pocketome analysis crystal and homology structures of these proteins were retrieved and developed. A sequence-based search was performed in different databases (ChEMBL, Drug Bank, PubChem and Pseudomonas database) for the availability of reported ligands and tested drugs for the screened targets. These predicted targets may provide a basis for the development of reliable antibacterial preventive and therapeutic options against P. aeruginosa.

Most of the existing influence maximization algorithms are not suitable for large-scale social networks due to their high time complexity or limited influence propagation range. Therefore, a D-RIS influence maximization algorithm is proposed based on the independent cascade model and combined with the reverse reachable set sampling. Under the premise that the influence propagation function satisfies monotonicity and submodularity, the D-RIS algorithm uses automatic debugging method to determine the critical value of the number of reverse reachable sets, which not only obtains a better influence propagation range, and greatly reduce the time complexity. The experimental results on the two real data sets of Slashdot and Epinions show that D-RIS algorithm is close to the CELF algorithm and higher than RIS algorithm, HighDegree algorithm, LIR algorithm and pBmH algorithm in influence propagation range. At the same time, it is significantly better than the CELF algorithm and RIS algorithm in running time, which indicates that D-RIS algorithm is more suitable for large scale social network.

Reverse order laws for generalized inverses of matrix products is a classic object of study in the theory of generalized inverses. One of the well-known reverse order laws for a matrix product $AB$ is $(AB)^{(i,\ldots,j)} = B^{(s_2,\ldots,t_2)}A^{(s_1,\ldots,t_1)}$, where $(\cdot)^{(i,\ldots,j)}$ denotes an $\{i,\ldots, j\}$-generalized inverse of matrix. Because $\{i,\ldots, j\}$-generalized inverse of a singular matrix is unique, the relationships between both sides of the reverse order law can be divided into four situations for consideration. This paper provides a thorough coverage of the reverse order laws for $\{i,\ldots, j\}$-generalized inverses of $AB$, from the development of background and preliminary tools to the collection of miscellaneous formulas and facts on the reverse order laws in one place with cogent introduction and references for further study. We begin with the introduction of a linear mixed model $y = AB\beta + A\gamma + \epsilon$ and the presentation of two least-squares methodologies to estimate the fixed parameter vector $\beta$ in the model, and the description of connections between the two types of least-squares estimators and the reverse order laws for generalized inverses of $AB$. We then prepare some valued matrix analysis tools, including a general theory on linear or nonlinear matrix identities, a group of expansion formulas for calculating ranks of block matrices, two groups of explicit formulas for calculating the maximum and minimum ranks of $B^{(s_2,\ldots,t_2)}A^{(s_1,\ldots,t_1)}$, as well as necessary and sufficient conditions for $B^{(s_2,\ldots,t_2)}A^{(s_1,\ldots,t_1)}$ to be invariant with respect to the choice of $B^{(s_2,\ldots,t_2)}A^{(s_1,\ldots,t_1)}$. We then present a unified approach to the 512 matrix set inclusion problems associated with the above reverse order laws for the eight commonly-used types of generalized inverses of $A$, $B$, and $AB$ through use of the definitions of generalized inverses, the block matrix method (BMM), the matrix rank method (MRM), the matrix equation method (MEM), and various algebraic calculations of matrices.

Base on the sequence of S genes, which encode spike proteins, we previously identified three different types (North American, S INDEL and S large-DEL types) of porcine epidemic diarrhea virus (PEDV) that have re-emerged in Japan since 2013. Base on experimental infections with the North American and S large-DEL types, we also hypothesized that PEDV virulence may be linked to the S1 subunit of the S protein. To test this hypothesis, we have now assayed in gnotobiotic piglets various recombinant PEDVs generated by reverse genetics. Piglets inoculated with CV777 maintained in National Institute of Animal Health, along with piglets infected with a recombinant form of the same virus, developed subclinical to mild diarrhea. In contrast, severe watery diarrhea, dehydration, weight loss, astasia, and high mortality were observed in piglets inoculated with recombinant strains in which the S gene was partially or fully replaced with corresponding sequences from the highly virulent Japanese PEDV isolate OKN-1/JPN/2013. Indeed, symptoms resembled those in piglets inoculated with the OKN-1/JPN/2013, and were especially pronounced in younger piglets. Collectively, the data demonstrate that the S1 subunit of the S protein is an important determinant of PEDV virulence, and advance development of new vaccine candidate.

Consumption of coffee by women early in their pregnancy has been viewed as potentially increasing the risk of miscarriage, low birth weight, and childhood leukemias. Many of these reports of epidemiologic studies have not acknowledged the potential biases inherent in studying the relationship between early-pregnancy-coffee consumption and subsequent events. I discuss five of these biases, recall bias, misclassification, residual confounding, reverse causation, and publication bias. Each might account for claims that attribute adversities to early-pregnancy-coffee consumption. To what extent these biases can be avoided remains to be determined. At a minimum, they need to be acknowledged wherever they might account for what is reported.

This study investigated the removal characteristics of N-nitrosamines and their precursors at three pilot-scale water reclamation plants. These plants applies different integrated membrane systems: (1) microfiltration (MF) / nanofiltration (NF) / RO; (2) sand filtration/three-step RO; and (3) ultrafiltration (UF) / NF and UF / RO. Variable removal of N-nitrosodimethylamine (NDMA) by the RO membrane processes could be attributable to membrane fouling and feed water temperature. The effect of membrane fouling on N-nitrosamines removal was extensively evaluated at one of the plants by conducting one month of operation and chemical cleaning of the RO membrane element. Membrane fouling enhanced N-nitrosamines removal by the pilot-scale RO membrane process. This finding contributes to better understanding of variable removal of NDMA by RO membrane processes. This study also investigated the removal characteristics of N-nitrosamines precursors. The NF and RO membrane processes greatly reduced NDMA formation potential (FP), but the UF process had little effect. The contributions of MF, NF, and RO membrane processes for reducing FPs of NDMA, N-nitrosopyrrolidine (NPYR) and N-nitrosodiethylamine (NDEA) were different, suggesting different size distributions of their precursors.

In this paper, a two-stage stochastic programming modelling is proposed to design a multi-period, multistage, and single-commodity integrated forward/reverse logistics network design problem under uncertainty. The problem involves both strategic and tactical decision levels. The first stage deals with strategic decisions, which are the number, capacity, and location of forward and reverse facilities. At the second stage tactical decisions such as base stock level as an inventory policy is determined. The generic introduced model consists of suppliers, manufactures, and distribution centers in forward logistic and collection centers, remanufactures, redistribution, and disposal centers in reverse logistic. The strength of proposed model is its applicability to various industries. The problem is formulated as a mixed-integer linear programming model and is solved by using Benders’ Decomposition (BD) approach. In order to accelerate the Benders’ decomposition, a number of valid inequalities are added to the master problem. The proposed accelerated BD is evaluated through small-, medium-, and large-sized test problems. Numerical results reveal that proposed solution algorithm increases convergence of lower bound and upper bound of BD and is able to reach an acceptable optimality gap in a convenient CPU time.

Benzylsuccinate is generated in anaerobic toluene degradation by radical addition of toluene to fumarate and further degraded to benzoyl-CoA by a beta-oxidation pathway. Using metabolic modules for benzoate transport and activation to benzoyl-CoA and the enzymes of benzylsuccinate beta-oxidation, we established an artificial pathway for benzylsuccinate production in Escherichia coli, which is based of its degradation pathway running in reverse. Benzoate is supplied to the medium, but needs to be converted to benzoyl-CoA by an uptake transporter and a benzoate-CoA ligase or CoA-transferase. In contrast, the second substrate succinate is endogenously produced from glucose under anaerobic conditions, and the constructed pathway includes a succinyl-CoA:benzylsuccinate CoA-transferase that activates it to the CoA-thioester. We present first evidence for the feasibility of this pathway and explore product yields under different growth conditions. Compared to aerobic cultures, the product yield increased more than 1000-fold in anaerobic glucose-fermenting cultures and showed further improvement under fumarate-respiring conditions. An important bottleneck to overcome appears to be product excretion, based on much higher recorded intracellular concentrations of benzylsuccinate, compared to those excreted. While no export system is known for benzylsuccinate, we observed an increased product yield after adding an unspecific mechanosensitive channel to the constructed pathway.

With an estimated 10 million people infected, the deltaretrovirus human T-cell lymphotropic virus type 1 (HTLV-1) is the second most prevalent pathogenic retrovirus in humans after HIV-1. Like HIV-1, HTLV-1 overwhelmingly persists in a host via a reservoir of latently infected CD4+ T cells. Although most patients are asymptomatic, HTLV-1-associated pathologies are often debilitating and include childhood infective dermatitis and adult T-cell leukaemia/lymphoma (ATLL), which presents in mature adulthood and is associated with poor prognosis with short overall survival despite treatment. Curiously, the strongest indicator for the development of ATLL is the acquisition of HTLV-1 through breastfeeding. There are no therapeutic or preventative regimens for HTLV-1. However, antiretrovirals (ARVs), which target the essential retrovirus enzymes, have been developed for and transformed HIV therapy. Since the architectures of retroviral enzyme active sites are highly conserved, some HIV-specific compounds may be active against HTLV-1. Here, we expand on our work showing that integrase strand transfer inhibitors (INSTIs) and some nucleoside reverse transcriptase inhibitors (NRTIs) block HTLV-1 transmission in cell culture. Specifically, we find that dolutegravir, the INSTI currently recommended as the basis of all new combination antiretroviral therapy prescriptions, and the latest prodrug formulation of the NRTI tenofovir, tenofovir alafenamide, also potently inhibit HTLV-1 infection in cell culture. Our results, if replicated in a clinical setting, could see transmission rates of HTLV-1 and future caseloads of HTLV-1-associated pathologies like ATLL dramatically cut via the simple redistribution of already widely available HIV pills to HTLV-1 endemic areas. Considering our findings with the old medical saying ‘it’s better to prevent than cure’, we highly recommend the inclusion of INSTIs and tenofovir prodrugs in upcoming HTLV-1 clinical trials as potential prophylactics.

This study investigates the effects of the antiperspirant aluminum chlorohydrate on the development of antibiotic resistance in commensal Staphylococcus epidermidis isolates. The isolates were exposed to aluminum chlorohydrate for 30 days, respectively. The bacteria that developed resistance to oxacillin, and ciprofloxacin were isolated, and the expression levels of some antibiotic resistance genes were determined by quantitative reverse transcriptase-PCR. Before and after the exposure, the minimum inhibitory concentration (MIC) values of the bacteria were determined by the microdilution method. A time-dependent increase was observed in the number of bacteria that developed resistance and increased the MIC value. Consistent with the ciprofloxacin resistance observed after exposure, an increase in the norA, norB/C, gyrA, gyrB, parC, and parE gene expressions was observed. In addition to aluminum chlorohydrate exposure, oxacillin resistance was observed in all test bacteria in the group subcultured only in the medium, suggesting that phenotypic resistance cannot be correlated with chemical exposure in the light of these data. The increase in mecA gene expressions of selected test bacteria that acquired resistance to oxacillin after exposure compared with control groups suggests that the observed resistance may be related to aluminum chlorohydrate exposure. To our knowledge, this is the first time in the literature that the effects of aluminum chlorohydrate as an antiperspirant on the development of antibiotic resistance in Staphylococcus epidermidis have been reported.

A Water demand per capita will rise in the Arab world as a result of climate change and population expansion. One of the most important aims in coping with population increase around the world is to conserve water supplies. As a result, the Kingdom of Saudi Arabia constructed Al Wajeed Water Treatment System to meet the demands of the southern population. This research aims to assess the drinking water quality produced from the AlWajeed Water Treatment System. Monthly water samples were collected (January 2018 to January 2021) from the Al Wajeed Water Treatment Framework (4sites), extending to governorates; Bishah`s distribution system (5sites) and Tathleeth`s distribution system (7sites). Water quality criteria, such as physical, chemical, and microbiological parameters, revealed that the majority of water samples collected from the Al Wajeed Water Framework and its environs are of a good quality matched the national and international standards. Few sites showed water quality criteria, such turbidity, fluoride and total coliform did not comply with national and global standards. The obtained results explained the importance of monitoring and follow-up programs for drinking water criteria. In addition, they can help the authorities and stakeholders in the sustainable development.

Flood routing in flood forecasting issue, calculation the height of flood bands, determining the river boundaries, and estimation of protective facilities for flood –exposed building is applicable. In many cases, due to the lack of measuring stations, the status of the upstream flood generating hydrograph is not known. The purpose of this study is to present an integrated method comprising of an optimization model and a hydrodynamic numerical model for flood modeling to determine the upstream hydrograph using the provided hydrograph at the downstream measuring station of a river. The routing procedure consists of three steps: (1) generating a hypothetical upstream hydrograph using genetic algorithm method; (2) hydrodynamic modeling using a numerical simulation model for flood routing according to the hypothetical hydrograph which is generated in the first step; (3) compare the calculated and observed hydrograph in downstream by using a fitness function. This recommended procedure was named as Reverse Flood Routing Method (RFRM) and was then applied to Karun River, the largest river in Iran. Comparing the generated upstream hydrograph by the RFRM model with the corresponding measured hydrograph at Ahvaz hydrometric station, as an ungauged river location, shows the high accuracy of the recommended model in this study.

Systemic lupus erythematosus (SLE) is a heterogenous autoimmune disease. While its etiology remains elusive, current understanding suggests a multifactorial process with contributions by genetic, immunologic, hormonal, and environmental factors. A hypothesis that combines several of these factors proposes that genomic elements, the L1 retrotransposons, are instrumental in SLE pathogenesis. L1 retroelements are transcriptionally activated in SLE and produce two proteins, ORF1p and ORF2p, which are immunogenic and can drive type I interferon (IFN) production by producing DNA species that activate cytosolic DNA sensors. In addition, these two proteins reside in RNA-rich macromolecular assemblies that also contain well-known SLE autoantigens like Ro60. We surmise that cells expressing L1 will exhibit all the hallmarks of cells infected by a virus, resulting in a cellular and humoral immune response similar to those in chronic viral infections. However, unlike exogenous viruses, L1 retroelements cannot be eliminated from the host genome. Hence, dysregulated L1 will cause a chronic, but perhaps episodic, challenge for the immune system. The clinical and immunological features of SLE can be largely explained by this model. Here we review the support for, and the gaps in, this hypothesis of SLE and its potential for new diagnostic, prognostic, and therapeutic options in SLE.

This note reconsiders a matrix equality $A_1A_2^{-}A_3A_4^{-}A_5 = A$ composed by six matrices of appropriate sizes, where $A_2^{-}$ and $A_4^{-}$ are generalized inverses of $A_2$ and $A_4$, respectively, and solves a selection of matrix set inclusion problems associated with various mixed reverse order laws for generalized inverses of products of two, three, and four matrices by means of this equality and its variations.

The active layer thickness (ALT) is affected by local soil material and surface vegetation coverage in Tibetan plateau permafrost region. The human activities and engineering construction along the Qinghai-Tibet Highway (QTH) destroyed the surface vegetation coverage, which have seriously influenced the ALT and heat exchange balance. Meanwhile, the changes of the detailed internal structure in the active layer will affect the stability of engineering infrastructure. Ground-penetrating radar (GPR) was used to detect the ALT in the permafrost region. However, researches on the detailed structure of the active layer and spatial variation information of ALT are rare, the main reason given for this is that the lack of advanced imaging techniques to enhance the GPR images. In this paper, the researchers focus on solving this problem by applying the reverse time migration (RTM) method to GPR field data acquired in the Beiluhe region. Analyses of the results led to conclusions as follows: a) The RTM algorithm is proved to be accurate for imaging the characteristics of the active layer through the dielectric constant model obtained by common midpoint and GPR data velocity analysis. b) The result of RTM profiles show the loose structure and graben-like fine internal structure. Combining with drill data and soil materials information, the researchers deduce the graben-like structure might be coarse gravel layer, which may be related to subgrade settlements in some local area. c) The 2D contour maps not only show the spatial variation feature of ALT at two sides of the highway, but also can compensate the defect of the research for single 2D survey line. The ALT is about 0.6~0.8 m in most areas, and about 0.8~0.9 m near the highway at west side of the QTH on the 2D contour maps. From the RTM interpretation profile, the closer to the plash, the deeper thawed active layer. The detailed internal structure of the active layer and 2D contour maps of ALT have great significance for the study of fine internal structure and the characteristic of ALT spatial variation in the Tibetan plateau under the background of climatic change.

The effective treatment of human immunodeficiency virus (HIV), also known as acquired immunodeficiency syndrome (AIDS), has transformed a highly lethal disease into a chronic and manageable condition. However, better methods need to be developed for eliminating the virus from reservoirs, enhancing patient access and adherence to therapy, and improving treatment in the long term to reduce adverse effects. From the perspective of drug discovery, one promising strategy is the development of anti-HIV prodrugs. This approach aims to enhance the efficacy and safety of treatment, promoting the development of more appropriate and convenient systems for patients. In this review, we discussed the use of the prodrug approach for HIV antiviral agents and emphasized nucleoside reverse transcriptase inhibitors. We comprehensively described various strategies that are used to enhance factors such as water solubility, bioavailability, pharmacokinetic parameters, permeability across biological membranes, chemical stability, drug delivery to specific sites/organs, and tolerability. These strategies might help researchers conduct better studies in this field. We also reported successful examples from the primary therapeutic classes while discussing the advantages and limitations. In this review, we highlighted the key trends in the application of the prodrug approach for treating HIV/AIDS..

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly to most parts of the world, causing high numbers of deaths and significant social and economic impacts. SARS-CoV-2 is a novel coronavirus with a suggested zoonotic origin and with the potential for cross-species transmission among animals. Antarctica can be considered the only continent free of SARS-CoV-2 although at the end of the 2019-2020 tourist season, at least one SARS-CoV-2 positive tourist visited the Antarctic Peninsula. Therefore, concerns have been expressed regarding the potential human introduction of this virus to the continent through the activities of research or tourism with potential effects including those related to human health, but also the potential for virus transmission to Antarctic wildlife. This reverse-zoonotic transmission risk to Antarctic wildlife is assessed considering the available information on host susceptibility, dynamics of the infection in humans, and contact interactions between humans and Antarctic wildlife. Measures to reduce the risk are proposed as well as the identification of knowledge gaps related to this issue.

Fast neutron (FN) radiation mediated mutagenesis is a unique approach among the several induced mutagenesis methods being used in plant science in terms of impacted mutations. The FN mutagenesis usually creates deletions from a few bases to several million bases (Mb). A library of random deletion generated using FN mutagenesis lines can provide indispensable resources for the reverse genetic approaches. In this review, information from several efforts made using FN mutagenesis has been compiled to understand the type of induced mutations, frequency, and genetic stability. Concerns regarding the utilization of FN mutagenesis technique for a plant with different level of ploidy and genome complexity are discussed. We have highlighted the utility of next-generation sequencing techniques which can be efficiently utilized for the characterization of mutant lines as well as for the mapping of causal mutations. Pros and cons of Mut-map, MutChromSeq, exon capture, whole genome sequencing, MutRen-Seq, and different tilling approaches can be used for the detection of FN-induced mutation has also been discussed. Genomic resources developed using the FN mutagenesis have been catalogued wooing to meaningful utilization of the available resources. The information provided here will be helpful for the efficient exploration for the crop improvement programs and for better understanding of genetic regulations.

This article aims to solve the problem of robust supervision of a reverse osmosis desalination system (RO-DS) with two models, external model and bond graph model. The structure of an industrial system from the point of view of the external model operates according to several modes of operation (degraded and normal). For this external model, we cannot locate the faults since we are talking about a global operation of the system. The possible solution for the development of research was to use the multidisciplinary model called bond graph. This model by its graphic nature and using a unified language makes it possible to model the industrial system element by element from where it helps the user not only to detect the faults but also to locate them when they appear in the system. The results suggest that the use of the bond graph model for alarm 02 is a reverse osmosis error (RO1); these phenomena are readable on the bond graph model and can be quantified by equations. The equation of the model of this reverse osmosis (RO1) is found in the residual equations (r5, r6 and r7), so that these residues will be sensitive to this rupture. The possible solution during research development was to use the bond graph model to supplement information with physical knowledge and to locate faults. This article also describes the operating safety (by minimizing false alarms and non-detections as well as delays in fault detection) of the desalination system by using the bond graph model described in Linear Fractional Transformation (LFT) form for enable it to manage the robust supervision of a desalination system. An approach based on (LFT-BG) is developed to monitor tank leakage (Cu) and reverse osmosis (RO1 and RO2) faults or valve level (V1 and V2) closures and membrane clogging reverse osmosis (Rm1 and Rm2) that can occur in the reverse osmosis desalination system (RO-DS).

In this paper we introduce the hypo-q-operator norm and hypo-q-numerical radius on a Cartesian product of algebras of bounded linear operators on Banach spaces. A representation of these norms in terms of semi-inner products, the equivalence with the q-norms on a Cartesian product and some reverse inequalities obtained via the scalar reverses of Cauchy-Buniakowski-Schwarz inequality are also given.

This paper addresses the Collatz Conjecture, an open question in mathematics that postulates all positive integers will eventually reach one when a pair of specific operations are repeatedly applied. Despite its apparent simplicity, the conjecture lacks a formal proof. To tackle this enigma, we introduce Algebraic Inverse Trees (AITs), data structures that trace inverse operations of the Collatz sequence. This new approach not only elaborates our unique methodology but also sheds light on the underlying complexities of the Collatz Conjecture.

Due to the fact that to date, the question of the origin of SARS-CoV-2 has not been resolved yet, the author analyzed the main advances in the development of genetic engineering of viruses that took place before the onset of the COVID-19 pandemic. The first artificial genetically modified viruses could appear in nature in the mid-1950s. The technique of nucleic acid hybridization was developed by the end-1960s. In the late 1970s, a method called the "reverse genetics" emerged to synthesize RNA and DNA molecules. In the early 1980-s, it became possible to combine the genes of different viruses and insert the genes of one virus into the genome of another virus. Since that time, the production of vector vaccines began. Currently, by modern technologies one can assemble any virus based on the nucleotide sequence available in the virus database or designed by a computer as a virtual model.Scientists around the world are invited to answer the call of Neil Harrison and Jeffrey Sachs of Columbia University, for a thorough and independent investigation into the origin of SARS-CoV-2. Only a full understanding of the origin of the new virus can minimize the likelihood of a similar pandemic in the future.

Hepatitis B virus (HBV) is known to cause severe liver diseases such as acute or chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Chronic hepatitis B (CHB) infection is a major health problem with nearly 300 million individuals infected worldwide. Currently, nucleos(t)ide analogs (NAs) and interferon alpha are clinically approved treatments for HBV infection. NAs are potent antiviral agents that bind to HBV polymerase and block viral reverse transcription and replication. Besifovir dipivoxil maleate (BSV) is a newly developed NA against HBV in the form of acyclic nucleotide phosphonate that is available for oral administration similar to adefovir and tenofovir. Until now, resistance to BSV treatment has not been reported. In this study, we found a CHB patient who showed viral breakthrough after long-term treatment with BSV. The isolated HBV DNA from patient’s serum were cloned into the replication-competent HBV 1.2mer and the sequence of reverse transcriptase (RT) domain of HBV polymerase were analyzed. We also examined the drug susceptibility of generated clones in vitro. Several mutations were identified in HBV RT domain. A particular mutant harboring ten RT mutations showed resistance to BSV treatment in vitro. The ten mutations include rtV23I (I), rtH55R (R), rtY124H (H), rtD134E (E), rtN139K (K), rtL180M (M), rtM204V (V), rtQ267L (L), rtL269I (I) and rtL336M (M). To further identify the responsible mutations for BSV resistance, we performed in vitro drug susceptibility assay on several artificial clones. As a result, our study revealed that rtL180M (M) and rtM204V (V) mutations, already known as lamivudine-resistant mutations, confer resistance to BSV in the CHB patient.

Short chain quinones (SCQs) have been identified as potential drug candidates against mitochondrial dysfunction, which is largely dependent on their reversible redox characteristics of the active quinone core. We recently synthesized a SCQ library of > 148 naphthoquinone derivatives and identified 16 compounds with enhanced cytoprotection compared to the clinically used benzoquinone idebenone. One of the major drawbacks of idebenone is its high metabolic conversion in the liver, which significantly restricts is therapeutic activity. Therefore, this study assessed the metabolic stability of the 16 identified naphthoquinone derivatives 1-16 using hepatocarcinoma cells in combination with an optimized reverse-phase liquid chromatography (RP-LC) method. Most of the derivatives showed significantly better stability than idebenone over 6 hours (p < 0.001). By extending the side-chain of SCQs, increased stability for some compounds was observed. Metabolic conversion from the derivative 3 to 5 and reduced idebenone metabolism in the presence of 5 were also observed. These results highlight the therapeutic potential of naphthoquinone-based SCQs and provide essential insights for future drug design, prodrug therapy and polytherapy, respectively.

Low-cost RGB-D cameras are increasingly used in several research fields including human-machine interaction, safety, robotics, biomedical engineering and even Reverse Engineering applications. Among the plethora of commercial devices, the Intel RealSense cameras proved to be among the best suitable devices, providing a good compromise between cost, ease of use, compactness and precision. Released on the market in January 2018, the new Intel model RealSense D415 has a wide acquisition range (i.e. ~160-10000 mm) and a narrow field of view to capture objects in rapid motion. Given the unexplored potential of this new device, especially when used as a 3D scanner, the present work aims to characterize and to provide metrological considerations on the RealSense D415. In particular, tests are carried out to assess the device performances in the near range (i.e. 100-1000 mm). Characterization is performed by integrating the guidelines of the existing standard (i.e. the German VDI/VDE 2634 part 2 normative) with a number of literature-based strategies. Performance analysis is finally compared against latest close-range sensors, thus providing a useful guidance for researchers and practitioners aiming to use RGB-D cameras in Reverse Engineering applications.

Cell-penetrating peptides (CPPs), a group of small peptides capable of promoting the transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular uptake of exogenously delivered macromolecules. GV1001, a peptide derived from a reverse-transcriptase subunit of telomerase (hTERT) and developed as a vaccine against various cancers, reportedly has unexpected CPP properties. Unlike typical CPPs, such as the HIV-1 TAT peptide, GV1001 enabled the cytosolic delivery of macromolecules such as proteins, DNA and siRNA via extracellular heat shock protein 90 (eHSP90) and 70 (eHSP70) complexes. The eHSP-GV1001 interaction may have biological effects in addition to its cytosolic delivery function. GV1001 was originally designed as a MHC class II-binding cancer epitope, but its CPP properties may contribute to its strong anti-cancer immune response relative to other telomerase peptide-based vaccines. Cell signaling via eHSP-GV1001 binding may lead to unexpected biological effects, such as direct anticancer or antiviral effects. In this review, we focus on the CPP effects of GV1001 bound to eHSP90 and ehsp70.

The resistance of Candida spp to fluconazole is a serious problem; Therefore, it must be investigated to expand the understanding of the phenomenon with a view to its clinical applicability. The aim was to evaluate the expression of ERG3, ERG11, CDR1, and SNQ2 genes involving computational analysis. Relative expression was quantified by RT-qPCR. Metrics were obtained by molecular docking and through Fisher's discriminant functions, a predictive classification against susceptibility to fluconazole was performed. The expression of ERG3, CDR1, and SNQ2 genes was higher in resistant strains than in dose-dependent sensitive strains. The gene with the highest expression in strains exposed to fluconazole was CDR1 and, in both resistant and dose-dependent sensitive strains exposed to fluconazole, the ERG11 gene had lower expression. The molecular docking model generated lower median fluconazole-ERG11 contacts than the median fluconazole-ERG3, -CDR1, and -SNQ2 contacts. The predicted classification through the multivariate model for fluconazole sensitivity obtained an accuracy of 73.5%. Resistant strains had a significant expression of CDR1, SNQ2 and ERG3 genes, compared to a comparatively low expression of ERG11. Molecular analysis identified a low affinity between fluconazole and its drug target, which may explain a lower intrinsic susceptibility of the fungus.

The genetic diversity of coronavirus (CoV) is high, and its infection in animals has not yet been fully revealed. By RT-PCR detection of partial RNA dependent RNA polymerase (RdRp) gene of CoV, we screened a total of 502 small mammals belonging to 18 species in 12 genera and 4 orders collected in Dali and Nujiang Prefecture of Western Yunnan Province, China. The prevalence of β-CoV in Chevrieri's field mouse (Apodemus chevrieri) and Lancangjiang field mouse (A. ilex) were 3.54% (4/113) and 6.67% (6/90), respectively; the prevalence of α-CoV in White-footed Indochinese rat (Rattus nitidus) and long-tailed red-toothed shrew (Episoriculus leucops) was 75% (3/4) and 5.88% (1/17), respectively. The co-infection rates of β-CoV and α-CoV in Kachin red-backed vole (Eothenomys cachinus), Norway rat (R. norvegicus) were 2.22% (2/90), 3.85% (1/26) respectively. The identity of the partial RdRp genes obtained of 13 strains of β-CoV was 83.42%-99.23% at nucleotide level, and it is worth noting that the two strains from Kachin red-backed vole showed highly homology to BOV-36/IND/2015 from Indian bovine and DcCoV-HKU23 from one-humped camel (Camelus dromedarius) in Morocco, the nucleotide similarity between 97.86%-98.33%. Similarly, the identity of the 7 strains of α-CoV among the partial RdRp sequences was 94.00%-99.18% at nucleotide levels. The viral load in different tissues was measured by quantitative RT-PCR (qRT-PCR). The average CoV viral load in small mammalian intestinal tissue was 1.25×106copies/g, differently, the mean CoV viral load in liver, heart, lung, spleen and kidney tissue was from 1.29×103 to 4.02×103copies/g, which revealed that CoV has extensive tropism of intestinal tissue in small mammals (P &lt; 0.0001). This result revealed the genetic diversity, epidemiology, and infective tropism of α-CoV and β-CoV in small mammals from Dali and Nujiang, which deepens the comprehending of the retention and infection of coronavirus in natural hosts.

Purpose: Inflammation of various degrees is common among humans. There are associated side effects with orthodox delivery systems and anti-inflammatory agents hence the study investigated the characteristics of herbal lipospheres and the anti-inflammatory potency of the lipospheres formulated from Pentaclethra macrophylla with the view to having a drug with a better delivery system and lesser side effects.Methods: Herbal lipospheres were formulated using solidified reverse micellar solutions (SRMS) of P90H and goat fat and characterized for particle size and morphology, pH – time dependent analysis, encapsulation efficiency (EE%) and Fourier Transform infrared spectroscopy. The in vitro antinociceptive and anti-inflammatory study were carried out using membrane stabilization by hypotonicity induced haemolysis and determination of anti-platelet aggregatory activity models. The in-vivo anti-nociceptive and anti-inflammatory studies on egg albumin and formaldehyde induced arthritis models were done. Total white blood cell count and differential blood count were carried out on the rats. Results: The results showed that there was no change in pH for the PM unloaded lipospheres and 2.5g of PM-loaded lipospheres from Day 1 to Day 7, but mild variation in the rest of the formulations. The EE ranged from 35.2% to 94% increasing according to the drug concentration. The photomicrographs of the lipospheres showed that the particles were spherical in shape. The particle sizes were within the acceptable range for lipospheres. FTIR showed no interaction. In the arthritis study, PM-loaded lipospheres inhibited edema consistently throughout the duration of observation. Inhibition of membrane increased steadily with an increase in concentration of PM in the lipospheres and the standard drug. The platelet aggregatory inhibition decreased steadily with an increase in concentration of the PM in the lipospheres as well as the standard. The T50 dose of PM had the highest percentage of WBC and it decreased as the treatment doses increased from T100 to T200. There was no significant differences among the Neutrophil counts of the different groups.Conclusion: The study, therefore, showed that the methanol extract of Pentaclethra macrophylla formed efficient herbal lipospheres with antinociceptive and anti-inflammatory activities.

The mathematical modelling of reverse logistics inventory systems ignores that returned items may arrive out of sequence, i.e. with different number of remanufacturing times. Moreover, such modelling assumes that the retuned items may retain the same quality upon recovery regardless of how many times they have been previously remanufactured. This paper develops a new mathematical expression of the percentage of retuned items that can be remanufactured a finite number of times. The proposed expression is modelled as a function of the expected number of times an item can be remanufactured on its life cycle and the number of times an item can be technologically (or optimally) remanufactured based on its quality upon recovery. The model developed in this paper considers joint production and remanufacturing options. The return rate is a varying demand dependent rate, which is a decision variable with demand, product deterioration, manufacturing and remanufacturing rates being arbitrary functions of time. The model considers the initial inventory of returned items in the mathematical formulation, which enables decision makers to adjust all functions and input parameters for subsequent cycles. Illustrative examples indicate that dependent purchasing price of recovery items and the incorporation of remanufacturing investment cost significantly impact on the optimal remanufacturing policy.

Load transfer through orthopaedic joint implants is poorly understood. The longer-term outcomes of these implants are just starting to be studied, making it imperative to monitor contact loads across the entire joint implant interface to elucidate the force transmission and distribution mechanisms exhibited by these implants in service. This study proposes and demonstrates the design, implementation, and characterization of a 3D-printed smart polymer sensor array using conductive polyaniline (PANI) structures embedded within a polymeric parent phase. The piezoresistive characteristics of PANI were studied to characterize the sensing behaviours inherent to these embedded pressure sensor arrays. PANI's stable response to a continuous load, its stability throughout loading and unloading cycles, and its repeatable and linear response to incremental loading cycles together with the accuracy of these measurements were investigated. It is demonstrated that this specially developed multi-material additive manufacturing process for polyaniline is an attractive approach for the fabrication of implant components having embedded smart-polymer sensors for the measurement and analysis of joint loads in orthopaedic implants.

People have long had a problem: the equations of motion that reflect the laws of physics are invariance under time inversion, while there always are irreversible processes for gases compose of microscopic particles. This article solves this problem. The point is that we should distinguish between the concepts of the equation of motion and motion. We also need to distinguish between the concepts of time-inverse motion and reverse motion. The former is anticlockwise, which is a frictional motion, while the latter is clockwise. For the single-particle motions in classical mechanics and in quantum mechanics, we present mathematical expressions for time-inversion motion and reverse motion, respectively. We demonstrate that single-particle motion is irreversible. The definition of the reversibility of two-particle collisions is given. According to the definition, the two-particle collision as a microscopic motion processes is irreversible. Consequently, for a gas consisting of a large number of particles colliding with each other, its movement should be irreversible, unless the condition of detailed balance is met. We give a physical explanation for the detailed balance, which does not concern the meaning of microscopic reversibility. The detailed balance means that after a pair of reciprocal collisions occur, the distribution function of the particles remains unchanged. Therefore, microscopic two-particle collision events are irreversible, but the statistical average of a large number of collision events makes it possible for the macroscopic process of a gas to be reversible. Conclusively, we clarify the microscopic mechanism of the irreversible process of gases.

Although domestic cats are susceptible to infection with SARS-CoV-2, the role of the virus in causing feline disease is less well defined. We conducted a large-scale study to identify SARS-CoV-2 infections in UK pet cats, using active and passive surveillance. Remnant feline respiratory swab samples, submitted for other pathogen testing between May 2021 and February 2023, were screened using RT-qPCR. In addition, we appealed to veterinarians for swab samples from cats suspected of having clinical SARS-CoV-2 infections. Bespoke testing for SARS-CoV-2 neutralising antibodies was also performed, on request, in suspected cases. One RT-qPCR-positive cat was identified from the active surveillance (1/549, 0.18 %), during the Delta wave (1/175, 0.57 %). Passive surveillance detected one cat infected with the Alpha variant, and two of ten cats tested RT-qPCR-positive during the Delta wave. No cats tested RT-qPCR-positive after the emergence of Omicron BA.1 and its descendants although 374 were tested by active and eleven by passive surveillance. We describe four cases of SARS-CoV-2 infection in pet cats, identified by RT-qPCR and/or serology, that presented with a range of clinical signs, as well as their SARS-CoV-2 genome sequences. Our results demonstrate that, although uncommon, clinical infections in cats can and do occur.

Desalination accounts for 1% of the total global water consumption and is an energy-intensive process, with the majority of operational expenses attributed to energy consumption. Moreover, at present, a significant portion of the power comes from traditional fossil fuel-fired power plants and the greenhouse gas emissions associated with power production along with concentrated brine discharge from the process, pose a severe threat to the environment. Due to the dramatic impact of climate change, there is a major opportunity to develop sustainable desalination processes to combat the issues of brine discharge, greenhouse gas emissions along with a reduction in energy consumption per unit of freshwater produced. Nanotechnology can play a vital role to achieve specific energy consumption reduction as nanofluids application increases the overall heat transfer coefficient enabling the production of more water for the same size desalination plant. Furthermore, concentrated brine discharge harms the marine ecosystems, and hence, this problem must also be solved to support the objective of sustainable desalination. Several studies have been carried out in the past several years in the field of nanotechnology applications for desalination, brine treatment and the role of renewable energy in desalination. This paper aims to review the major advances in this field of nanotechnology for desalination. Furthermore, a hypothesis for developing an integrated solar thermal and nanofluid sustainable desalination system, based on the cyclic economy model is proposed.

The demand of high data rate and ubiquitous coverage in heterogeneous cellular (HetNets) is increasing progressively. In order to meet this demand, sophisticated model having applied interference reduction scheme and cell association technique is needed. The small base station (sBS)are deployed inside the broadcasting area of macro base station (mBS), in heterogeneous cellular networks (HetNets). Since mBS has high transmission power therefore a large number of users get connected with mBS. This causes disproportion of load distribution across the HetNets. For load balancing users from high power mBS are migrated to low power sBS to increase network capacity and to decrease the load from mBS. This results in interference in the communication signal because of strong mBS Interference. Hence, we need interference management technique to mitigate interference and user association and to efficiently use sBSs’ resources. Inter-cell interference (ICI) limit the HetNets’ performance. Additionally, there exist deliberate jamming interference which depends on jammers transmission power and its proximity with the target, which notably degrades the network performance. In this paper, we employ reverse frequency allocation scheme (RFA) to reduce inter cell interference, deliberate jamming interference and to accomplish load balancing. The proposed setup is analyzed inquisitively and with the help of simulations. The result shows reduction in interferences as well as balance of load distribution in the network achieved by employing RFA scheme together with cell association.

Barley is an important crop grown on almost 49 Mha worldwide in 2021 and is particu-larly significant in Europe where powdery mildew is the most frequent disease on sus-ceptible varieties. The most suitable way for protecting crops is exploiting genetic re-sistance. However, the causal agent Blumeria hordei is an extremely adaptable pathogen. The aims of this research were to increase our knowledge of the rapidly changing path-ogen population and detect rare virulences. Random samples of the pathogen were ob-tained from the air by means of a mobile spore sampler. Spores were collected by driv-ing across the Czech Republic in 2019, 2021 and 2023 and 299 isolates were analyzed on 121 host varieties. No infection occurred on 35 differentials, rare virulence was recorded on 31 varieties and a higher virulence frequency was found on 55 differentials. A core set of differentials along with four additional varieties distinguish 295 pathotypes (Simple Index = 0.987) and virulence complexity of isolates varied from 4 to 19 with an average 10.39. The detection of new virulences, the increasing frequency of previously rare viru-lences and high pathotype diversity as well as high virulence complexity confirm that using nonspecific durable resistance is crucial for successfully breeding commercial va-rieties.

Recent years have seen a rapid uptake in distributed energy resources (DER). Such technologies pose a number of challenges to network operators, which can ultimately limit the amount of rooftop solar photovoltaics (PV) systems that can be connected to a network. The objective of this industry-based research was to determine the potential network effects of forecast levels of customer owned rooftop solar PV on Energy Queensland’s distribution network and formulate functions that can be used to determine such effects without the requirement for detailed network modeling and analysis. In this research, many of Energy Queensland’s distribution feeders were modelled using DIgSILENT PowerFactory and analyzed with forecast levels of solar PV and customer load. Python scripts were used to automate this process and quasi dynamic simulation (QDSL) models were used to represent the dynamic volt-watt and volt-var response of inverters, as mandated by the Australian Standard AS/NZS 4777. In analyzing the results, linear regression was used to form trend equations that represent various network characteristics against the number of PV connections. The trend equations provide a way of approximating network characteristics for other feeders under various levels of customer owned rooftop solar PV without the need for detail modeling.

We suggest that despite McLuhan’s claim not to have a theory of communication that in fact the body of his work does indeed constitute a theory of media and their effects which I have called his General Theory of Media (GToM) that also includes his Laws of Media (LoM). Both McLuhan’s GToM and his LoM are described. A comparison is made of three notions of law: i. McLuhan’s notion of law as used in his Laws of Media; ii. the notions of the Law in the legal sense and iii. the notion of law as formulated in scientific laws. McLuhan’s understanding of media is used to analyze some of the negative effects of social media suggesting that laws need to be formulated to prevent the misuse of social media that are antithetical to democracy and the invasion of the privacy of the individual users of these apps. McLuhan’s Laws of Media are then used to provide insights into the nature of scientific laws, the Law in the legal sense and his own Laws of Media.

We investigated the radioclinical outcomes of naviculectomy and limited/tailored soft-tissue releases in a short series of ambulatory children with complex/intractable congenital vertical talus subsets namely neglected, multiple operated and recurrent patients. We postulated that this technique will yield satisfactory radioclinical outcomes and minimal complications because it avoids extensive surgical release/trauma that is otherwise classically recommended for complex congenital vertical talus (CVT). The cohort consisted of five -four boys, one girl- complex CVT children with neglected, multiple operated and/or recurrent subsets. Patients were included if manipulative casting techniques were deemed unlikely to produce a plantigrade foot. Patients underwent naviculectomy with variable on-demand limited soft tissue releases. Two patients had bilateral affection and two had a non-idiopathic aetiology. The mean age was 5.2 years (4 to 6.25) and mean follow-up was 2.3 years (1 to 3). We reported satisfactory outcomes as per foot posture, function, overall parent satisfaction including pain and radiography per lateral views of talar-axis-first metatarsal base angle on the short/intermediate term. Whereas manipulative casting is unlikely to yield lasting outcomes in ambulatory children with complex subsets of CVT, extensive surgical soft-tissue releases have unfavourable long-term complications. As a substitute, naviculectomy as a form of resection arthroplasty created a practical and affordable third way between manipulative casting with minimally invasive surgery and the extensive surgical soft tissue releases on the short/intermediate term.

The current study applied a new approach for the interpolation and regionalization of observed precipitation series to a smaller spatial scale (0.125° by 0.125° grid) across the Upper Indus Basin (UIB), with appropriate adjustments for the orographic effect and changes in glacier storage. The approach is evaluated and validated through reverse hydrology, guided by observed flows and available knowledge base. More specifically, the generated corrected precipitation data is validated by means of SWAT-modelled responses of the observed flows to the different input precipitation series (original and corrected ones). The results show that the SWAT- simulated flows using the corrected, regionalized precipitation series as input are much more in line with the observed flows than those using the uncorrected observed precipitation input for which significant underestimations are obtained.

Interference fits are a very common shaft-hub connection due to their low manufacturing cost and excellent technical properties. Plastic Conditioning of this machine element is a new and not very well known method. By exploiting residual stresses and the associated increase in the yield point, these components can absorb operating loads such as rotating bending moments, torsion, temperature changes and centrifugal forces purely elastically and avoid plastic deformation during operation. Compared to conventionally joined interference fits, the load bearing capacity in the elastic range can be increased by almost 200% and a specifically defined additional safety against plastic deformation in the elastic-plastic range can be ensured. This paper examines the effects of Reverse Yielding on the technology of Plastic Conditioning of Interference Fits in Power Transmission Engineering. Based on the Shear Stress Hypothesis (SH), the Plane Stress State (PSS) and the ideal plastic behavior of materials, the stress-mechanical relationships are explained, the influencing parameters are examined and conclusions are drawn for the plastic conditioning process. Taking into account the theoretical knowledge according to the state of the art, modified material behavior assumptions (isotropic hardening) and the Von Mises Yield Criterion (VMYC) are also considered. In addition, the method of plastic conditioning of interference fits is introduced and its basic principles are briefly explained. Along with computational suggestions to avoid Reverse Yielding, open issues requiring further research are identified.

Mobile devices have become tools we spend our free time where we carry them with us every moment, they allow us to interact with the environment, we immortalize the moment when necessary. These devices which we spend most of our daily life become very common in recent years and even there are unique business areas emerged. It was announced that the number of people using smartphones is over than 2.5 billion in the first quarter of 2016. As people become more addicted to mobile technology, they become the target of malevolent people. A huge increase in the number of mobile malware is observed as the number of the users increase. Billions of users at risk day by day due to the development of the methods. We have addressed the recent methods used and the types of malware that target mobile devices in our study. We have mentioned the proxy server and reverse proxy server operation logic. We discuss the method of turning mobile devices into reverse proxy servers, risks involved and protection methods.

Chronic HCV infection and associated liver cancer impose a heavy burden on the healthcare system. Direct acting antivirals eliminate HCV, unless it is drug resistant, and partially reverse liver disease, but they cannot cure HCV-related cancer. Possible remedy could be a multi-component immunotherapeutic vaccine targeting both HCV-infected and malignant cells, also those not infected with HCV. To meet this need we developed a two-component DNA vaccine based on the highly conserved core protein of HCV to target HCV-infected cells, and a renowned tumor associated antigen telomerase reverse transcriptase (TERT) based on the rat TERT, to target malignant cells. Their synthetic genes were expression-optimized, and HCV core was truncated after aa 152 (Core152opt) to delete the domain interfering with immunogenicity. Core152opt and TERT DNA were highly immunogenic in BALB/c mice, inducing IFN-γ/IL-2/TNF-α response of CD4+ and CD8+ T cells. Also, DNA-immunization with TERT enhanced cellular immune response against luciferase encoded by a co-delivered plasmid (Luc DNA). However, DNA-immunization with Core152opt and TERT mix resulted in abrogation of immune response against both components. A loss of bioluminescent signal after co-delivery of TERT and Luc DNA into mice indicated that TERT affects the in vivo expression of luciferase directed by the immediate early cytomegalovirus and interferon-β promoters. Panel of mutant TERT variants was created and tested for their expression effects. TERT with deleted N-terminal nucleoli localization signal and mutations abrogating telomerase activity still suppressed the IFN-β driven Luc expression, while the inactivated reverse transcriptase domain of TERT and its analogue, enzymatically active HIV-1 reverse transcriptase, exerted only weak suppressive effects, implying that suppression relied on the presence of the full-length/nearly full-length TERT, but not its enzymatic activity. The effect(s) could be due to interference of the ectopically expressed xenogeneic rat TERT with biogenesis of mRNA, ribosomes and protein translation in murine cells, affecting the expression of immunogens. HCV core can aggravate this effect, leading to early apoptosis of co-expressing cells, preventing the induction of immune response.

Human oncoviruses are able to subvert telomerase function in cancer cells through multiple strategies. The activity of the catalytic subunit of telomerase (TERT) is commonly enhanced in virus-related cancers. Viral oncoproteins, such as high-risk human papillomavirus (HPV) E6, Epstein-Barr virus (EBV) LMP1, Kaposi sarcoma-associated herpesvirus (HHV-8) LANA, hepatitis B virus (HBV) HBVx, hepatitis C virus (HCV) core protein and human T-cell leukemia virus-1 (HTLV-1) tax protein, interact with regulatory elements in the infected cells and contribute to the transcriptional activation of TERT gene. Specifically, viral oncoproteins have been shown to bind TERT promoter, to induce post-transcriptional alterations of TERT mRNA and to cause epigenetic modifications, which have important effects on the regulation of telomeric and extra-telomeric functions of the telomerase. Other viruses, such as herpesviruses, operate by integrating their genomes within the telomeres or by inducing alternative lengthening of telomeres (ALT) in non-ALT cells. In this review, we recapitulate recent findings on virus-telomerase/telomeres interplay and the importance of TERT-related oncogenic pathways activated by cancer causing viruses.