The construction of molecular robotic-like objects that imitate living things is an important challenge for current chemists. Such molecular devices are expected to perform their duties robustly to carry out mechanical motion, process information, and make independent decisions. Dissipative self-organization plays an essential role in meeting these purposes. To produce a micro-robot that can perform the above tasks autonomously as a single entity, a function generator is required. Although many elegant review articles featuring chemical devices that mimic biological mechanical functions have been published recently, the dissipative structure, which is the minimum requirement, has not been sufficiently discussed. This article aims to show clearly that dissipative self-organization is a phenomenon involving autonomy, robustness, mechanical functions, and energy transformation. Moreover, the author details the recent experimental results of an autonomous light-driven molecular device that achieves all of these features. In addition, a chemical model of cell-amplification is also discussed to focus on the generation of hierarchical movement by dissipative self-organization. By reviewing this research, it may be perceived that mainstream approaches to synthetic chemistry have not always been appropriate. In summary, the author proposes that the integration of catalytic functions is a key issue for the creation of autonomous microarchitecture.

In this article we explore the limiting behavior of the universal prior distribution obtained when applied over multiple meta-level hierarchy of programs and output data of a computational automata model. We were motivated to alleviate the effect of Solomonoff's assumption that all computable functions or hypotheses of the same length are equally likely, by weighing each program in turn by the algorithmic probability of their description number encoding. In the limiting case, the set of all possible program strings of a fixed-length converges to a distribution of self-replicating quines and quine-relays - having the structure of a constructor. We discuss how experimental algorithmic information theory provides insights towards understanding the fundamental metrics proposed in this work and reflect on the significance of these result in digital physics and the constructor theory of life.

Two distinct isolates of the facultative parasite, Tetrahymena rostrata were compared, identifying and utilising markers that are useful for studying clonal variation within the species. The mitochondrial genomes and several nuclear genes were determined using Illumina short read sequencing. The two T. rostrata isolates had similar morphology and were pathogenic for Deroceras reticulatum slugs. The linear mitogenomes had the gene content and organisation typical of the Tetrahymena genus, comprising 8 tRNA genes, 6 ribosomal RNA genes and 45 protein coding sequences (CDS), twenty-two of which had known function. The two isolates had nucleotide identity within common nuclear markers encoded within the histone H3 and H4 and small subunit ribosomal RNA genes and differed by only 2-4 nucleotides in a region of the characterised actin genes. Variation was observed in several mitochondrial genes and was used to determine intraspecies variation and may reflect the natural history of T. rostrata from different hosts or the geographic origins of the isolates.

Over the last decade the blockchain technology has emerged to provide solutions to the complexity and privacy challenges of using distributed databases. It reduces the cost for customers by eliminating intermediaries and builds the trust in peer-to-peer communications. Over this time, the concept of blockchain has shifted greatly due to its potential in business growth for enterprises and the rapidly evolving applications in a collaborative smart cities' ecosystem, healthcare, and governance. Many platforms, with different architectures and consensus protocols, have been introduced. Consequently, it becomes challenging for an application developer to choose the right platform. Furthermore, blockchain has misaligned with the goals for efficient green collaborative digital ecosystem. Therefore, it becomes critical to address this gap and to build new frameworks to align blockchain with those goals. In this paper, we discuss the evolution of blockchain architecture and consensus protocols, bringing a retrospective analysis and discussing the rationale of the evolution of the various architectures and protocols, as well as capturing the assumptions conducting to their development and contributions to building collaborative applications. We introduce a classification of those architectures helping developers to choose a suitable platform for applications and providing insights for future research directions in the field to build new frameworks.

Covalent DNA protein crosslinks (DPCs) are common lesions that block replication. We examine here the consequence of DPCs on mutagenesis involving replicational template-switch reactions in Escherichia coli. 5-azacytidine (5azaC) is a potent mutagen for template-switching, dependent on DNA cytosine methylase (Dcm), implicating the trapped Dcm-DNA covalent complex as the initiator for mutagenesis. The leading strand of replication is more mutable than the lagging strand, explained by blocks to the replicative helicase and/or fork regression. We find that template-switch mutagenesis induced by 5-azaC does not require DSB repair via RecABCD. The ability to induce the SOS response is anti-mutagenic by an unknown mechanism. Mutants in recB, but not recA, exhibit high constitutive rates of template-switching and we suggest that RecBCD-mediated DNA degradation prevents template-switching associated with fork regression. A mutation in the DnaB fork helicase also promotes high levels of template-switching. We also find that other DPC-inducers, formaldehyde (a non-specific crosslinker) and ciprofloxacin (a topoisomerase II poison) are also strong mutagens for template-switching. Induction of mutations and genetic rearrangements that occur by template-switching may constitute a previously unrecognized component of the genotoxicity and genetic instability promoted by DPCs.

In E. coli DNA replication forks stall on average once per cell cycle. When this occurs, replisome components disengage from the DNA, exposing an intact, or nearly intact fork. Consequently, the fork structure must be regressed away from the initial impediment so repair can occur. Regression is catalyzed by the powerful, monomeric DNA helicase, RecG. During this reaction, the enzyme couples unwinding of fork arms to rewinding of duplex DNA resulting in the formation of a Holliday junction. RecG works against large opposing forces enabling it to clear the fork of bound proteins. Following subsequent processing of the extruded junction, the PriA helicase mediates reloading of the replicative helicase DnaB leading to the resumption of DNA replication. The single-strand binding protein (SSB) plays a key role in mediating PriA and RecG functions at forks. It binds to each enzyme via linker/OB-fold interactions and controls fork loading sites in a substrate-dependent manner that involves helicase remodeling. Finally, it is displaced by RecG during fork regression. The intimate and dynamic SSB-helicase interactions play key roles in ensuring fork regression and DNA replication restart.

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) proteins are a diverse and evolutionarily conserved family of cytidine deaminases that provide a variety of functions from tissue-specific gene expression and immunoglobulin diversity to control of viruses and retrotransposons. APOBEC family expansion has been documented among mammalian species, suggesting a powerful selection for their activity. Enzymes with a duplicated zinc-binding domain often have catalytically active and inactive domains, yet both have antiviral function. Although APOBEC antiviral function was discovered through hypermutation of HIV-1 genomes lacking an active Vif protein, much evidence indicates that APOBECs also inhibit virus replication through mechanisms other than mutagenesis. Multiple steps of the viral replication cycle may be affected, although nucleic acid replication is a primary target. Packaging of APOBECs into virions was first noted with HIV-1, yet is not a prerequisite for viral inhibition. APOBEC antagonism may occur in viral producer and recipient cells. Signatures of APOBEC activity include G-to-A and C-to-T mutations in a particular sequence context. The importance of APOBEC activity for viral inhibition is reflected in the identification of numerous viral factors, including Vif, which are dedicated to antagonism of these deaminases. Such viral antagonists often are only partially successful, leading to selection for viral variants.

The capsid precursor P1 constitutes the N-terminal part of the enterovirus poly-protein. It is processed into VP0, VP3, and VP1 by the viral proteases, and VP0 is cleaved autocatalytically into VP4 and VP2. We observed that poliovirus VP0 is recognized by an antibody against a cellular autophagy protein LC3A. The LC3A-like epitope overlapped the VP4/VP2 cleavage site. Individually expressed VP0-EGFP and P1 strongly colocalized with a marker of selective autophagy p62/SQSTM1. To assess the role of capsid proteins in autophagy development we infected different cells with poliovirus or encapsidated polio replicon coding for only the replication proteins. We analyzed the processing of LC3B and p62/SQSTM1, markers of the initiation and completion of the autophagy pathway, and systematically investigated the association of the viral antigens with these au-tophagy proteins in infected cells. We observed cell-type specific development of autophagy upon infection and found that only the virion signal strongly co-localized with p62/SQSTM1 early in infection. Collectively, our data suggest that activation of autophagy is an antiviral response, and that capsid proteins con-tain determinants targeting them to p62/SQSTM1-dependent sequestration. Such a strategy may control the level of capsid proteins so that viral RNAs are not re-moved from the replication/translation pool prematurely.

The infections caused by Chikungunya virus (CHIKV), genus Alphavirus, have become a health problem around the world, due to this virus’s widespread occurrence and high morbidity rate and the absence of vaccines or antiviral drugs. In this study, we analyzed a competitive inhibitor of ornithine decarboxylase—an enzyme that is key in the biosynthesis of polyamines (PAs), N-ω-chloroacetyl-L-ornithine (NCAO), which is a possible inhibitor of CHIKV replication because intracellular polyamines participate in the in vitro transcription and translation of CHIKV. NCAO does not have any cytotoxic effect on C6/36 cells even at 1000 μM at 72 h post-exposure. However, in Vero cells, a cytotoxic effect was present above 380 μM at 48 h post-exposure, which was considered when determining the inhibitory effect on viral replication. In this work, we demonstrate that NCAO inhibits the replication of CHIKV in Vero and C6/36 cells in a dose-dependent manner, causing a decrease in the PFU/mL of at least 4 logarithms (p <0.01) in both cell lines. Viral yields were restored by the addition of exogenous polyamines, mainly putrescine. The HPLC analyses showed that NCAO decreases the content of intracellular PAs, even though mainly spermidines and spermines are present in infected cells. NCAO inhibits CHIKV replication by depleting the intracellular polyamines in Vero and C6/36 cells, suggesting that this compound is a possible antiviral for CHIKV infections.

Zika virus (ZIKV) is an emerging human mosquito-transmitted pathogen of global concern, known to be associated with complications such as congenital defects and neurological disorders in adults. ZIKV infection is associated with induction of cell death. However, previous studies suggest that the virally-induced apoptosis occurs at a slower rate compared to the course of viral production. In this present study, we investigated the capacity of ZIKV to delay host cell apoptosis. We provide evidence that ZIKV has the ability to interfere with apoptosis whether it is intrinsically or extrinsically induced. In cells expressing viral replicon-type constructions, we show that this control is achieved through replication. Finally, our work highlights an important role for anti-apoptotic Bcl-2 family protein in the ability of ZIKV to control apoptotic pathways, avoiding premature cell death and thereby promoting virus replication in the host-cell.

The incidence of human papillomavirus-related head and neck squamous cell carcinoma (HPV+HNSCC) has reached epidemic levels in the last decade. While prophylactic vaccines will prevent future HPV infections, there are currently no HPV-specific antiviral drugs to treat current HPV infections or HPV+HNSCC. HPV replication and transcription are promising targets for anti-HPV therapeutics, as modulation of these processes can alter expression levels of HPV E6 and E7, which are required for maintenance of the transformed phenotype. This is a particularly attractive target in in HPV+HNSCC where the majority of tumors have episomal genomes replicating in an E1-E2 dependent manner. Here, we describe a model system to study HPV16 E1-E2 mediated DNA replication and HPV16 E2-mediated transcriptional activation and repression in multiple HNSCC cell lines. Our results demonstrate that low levels of IFIT1 are required for HPV16 replication in HNSCC cell lines and HPV16 E1 interacts with IFIT1. Restoration of IFIT1 expression in HNSCC cell lines partially inhibits HPV16 E1-E2 mediated replication. This system can be used to study replication and transcription by HPV16 E1 and E2 in HNSCC as well as be utilized to screen potential anti-HPV therapeutics that target HPV16 replication and transcription.

Vitrimers are covalent network materials, comparable in structure to classical thermosets. Unlike normal thermosets, they possess a chemical bond swap mechanism that makes their structure dynamic and suitable for activated welding and even autonomous self-healing. The central question in designing such materials is the trade-off between autonomy and material stability: The swap mechanism facilitates the healing but it also facilitates creep, which makes the perfectly stable self-healing solid a hard goal to reach. Here, we address this question for the case of self-healing vitrimers made from star polymers. Using coarse-grained molecular dynamics simulations, we study the adhesion of two vitrimer samples and find that they bond together on timescales that are much shorter than the stress relaxation time. We show that the swap mechanism allows the star polymers to diffuse through the material through coordinated swap events, but the healing process is much faster and does not depend on this mobility.

A vivid debate is ongoing in the scientific community about statistical malpractice and the related publication bias. No general consensus exists on the consequences and this is reflected in heterogeneous rules defined by scientific journals on the use and reporting of statistical inference. This paper aims at discussing how the debate is perceived by the agricultural economics community and implications for our roles as researchers, contributors to the scientific publication process, and teachers. We start by summarizing the current state of the p-value debate and the replication crisis, and commonly applied statistical practices in our community. This is followed by motivation, design, results and discussion of a survey on statistical knowledge and practice among the researchers in the agricultural economics community in Austria, Germany and Switzerland. We conclude that beyond short-term measures like changing rules of reporting in publications, a cultural change regarding empirical scientific practices is needed that stretches across all our roles in the scientific process. Acceptance of scientific work should largely be based on the theoretical and methodological rigor and where the perceived relevance arises from the questions asked, the methodology employed, and the data used but not from the results generated. Revised and clear journal guidelines, the creation of resources for teaching and research, and public recognition of good practice are suggested measures to move forward.

Mayaro virus (MAYV) hijacks the host´s cell machinery to effectively replicate. The mitogen-activated protein kinases (MAPKs) p38, JNK and ERK1/2 have emerged as crucial cellular factors implicated in different stages of the viral cycle. However, whether MAYV uses these MAPKs to competently replicate has not yet been determined. The aim of this study was to evaluate the impact of MAPKs inhibition on MAYV replication using primary human dermal fibroblasts (HDFs) and HeLa cells. Viral yields in supernatants from MAYV-infected cells treated or untreated with inhibitors SB203580, SP600125, U0126 or Losmapimod were quantified using plaque assay. Also, viral protein expression was analyzed using immunoblot and immunofluorescence. Knockdown of p38⍺/p38β isoforms was performed in HDFs using the PROTACs molecule NR-7h. Our data demonstrated that HDFs are highly susceptible to MAYV infection. SB203580, a p38 inhibitor, reduced MAYV replication in a dose-dependent manner in both HDFs and HeLa cells. Additionally, SB203580 significantly decreased viral E1 protein expression. Similarly, knockdown or inhibition of p38⍺/p38β isoforms with NR-7h or Losmapimod, respectively, affected MAYV replication in a dose-dependent manner. Collectively, these findings suggest that p38 could play an important role in MAYV replication and could serve as a therapeutic target to control MAYV infection.

COVID19 is a current pandemic disease due to the novel coronavirus SARS-CoV-2. The scientific community mounted a strong response by accelerating research and innovation, and rapidly setting the basis to the understanding of molecular determinants of the disease for the development of targeted therapeutic interventions. The replication of the viral genome within the infected cells is a key step of SARS-CoV2 life cycle. It is a complex process involving the action of several viral and host proteins in order to perform RNA polymerization, proofreading and final capping. This review provides an update of structural and functional data on key actors of the replicatory machinery of SARS-CoV-2, filling the gaps in the current availability of structural data using homology modelling. Moreover, learning from similar viruses, we collect literature data to reconstruct the pattern of interactions among protein actors of the SARS-CoV-2 RNA polymerase machinery. In this pattern, an important role is played by co-factors, like Nsp8 and Nsp10, not only as allosteric activators but also as molecular connectors holding the entire machinery together to enhance the efficiency of RNA replication.

Self-assembly is a spontaneous process through which macroscopic structures are formed from basic microscopic constituents (e.g. molecules or colloids). By contrast, the formation of large biological molecules inside the cell (such as proteins or nucleic acids) is a process more akin to self-organization than to self-assembly, as it requires a constant supply of external energy. Recent studies have tried to merge self-assembly with self-organization by analyzing the assembly of self-propelled (or active) colloid-like particles whose motion is driven by a permanent source of energy. Here we present evidence that points to the fact that self-propulsion considerably enhances the assembly of polymers: self-propelled molecules are found to assemble into polymer-like structures, the average length of which increases towards a maximum as the self-propulsion force increases. Beyond this maximum, the average polymer length decreases due to the competition between bonding energy and disruptive forces that result from collisions. The assembly of active molecules might have promoted the formation of large pre-biotic polymers that could be the precursors of the informational polymers we observe nowadays.

In Escherichia coli, DNA replication termination is orchestrated by two clusters of Ter sites forming a DNA replication fork trap when bound by Tus proteins. The formation of a ‘locked’ Tus-Ter complex is essential for halting incoming DNA replication forks. However, the absence of replication fork arrest at some Ter sites raised questions about their significance. In this study, we examined the genome-wide distribution of Tus and found that only the six innermost Ter sites (TerA-E and G) were significantly bound by Tus. We also found that a single ectopic insertion of TerB in its non-permissive orientation could not be achieved, advocating against a need for ‘back-up’ Ter sites. Finally, examination of the genomes of a variety of Enterobacterales revealed a new replication fork trap architecture mostly found outside the Enterobacteriaceae family. Taken together, our data enabled the delineation of a narrow ancestral Tus-dependent DNA replication fork trap consisting of only two Ter sites.

Long noncoding RNAs (lncRNAs) of virus origin accumulate in cells infected by many positive strand (+) RNA viruses to bolster viral infectivity. Their biogenesis mostly utilizes exoribonucleases of host cells that degrade viral genomic or subgenomic RNAs in the 5’-to-3’ direction until being stalled by well-defined RNA structures. Here we report a viral lncRNA that is produced by a novel replication-dependent mechanism. This lncRNA corresponds to the last 283 nucleotides of the turnip crinkle virus (TCV) genome, hence is designated tiny TCV subgenomic RNA (ttsgR). ttsgR accumulated to high levels in TCV-infected Nicotiana benthamiana cells when the TCV-encoded RNA-dependent RNA polymerase (RdRp), also known as p88, was overexpressed. Both (+) and (-) strand forms of ttsgR were produced in these cells in a manner dependent on the RdRp functionality. Strikingly, templates as short as ttsgR itself were sufficient to program ttsgR amplification, as long as the TCV-encoded replication proteins, p28 and p88, were provided in trans. Consistent with its replicational origin, ttsgR accumulation required a 5’ terminal G₃(A/U)₄ motif shown by others to be crucial for the replication of a TCV satellite RNA. More importantly, introducing a new G₃(A/U)₄ motif elsewhere in the TCV genome was alone sufficient to cause the emergence of another lncRNA. Collectively our results unveil a replication-dependent mechanism for the biogenesis of viral lncRNAs, thus suggesting that multiple mechanisms, individually or in combination, may be responsible for viral lncRNA production.

The integrated stress response (ISR) is an adaptational signaling pathway that is induced in response to different stimuli, such as accumulation of unfolded and misfolded protein, hypoxia, amino acid deprivation, viral infection and ultraviolet light. It has been known that viral infection can activate ISR, but the role of ISR during viral infection is still unclear. In some cases, ISR is a protective mechanism of host cell against infection with virus whilst ISR may be hijacked by viruses for facilitating its replication. In this review, we highlighted recent advances on induction of ISR upon viral infection and the downstream responses involved such as autophagy, apoptosis, formation of stress granules and innate immunity response. We then discussed the molecular mechanism of ISR regulating viral replication and how viruses antagonize this cellular stress response resulting from ISR.

Maintenance of the human chromosomes stability requires a tight regulation of DNA replication to duplicate once and only once the entire genome of a single cell. In mammalians cells, origin activation is controlled in space and time by a cell specific and robust program called replication timing. About 100 000 of potential origins are loaded onto the chromatin at the G1 phase but only 20-30% are selected and active during the replication of a given cell. When the replication fork is slowed down by exogenous or endogenous sources, the cell need to activate more origins to complete the replication on time. Thus, the large choice of origins that can be activated may be a key player in the protection of the genome. The aim of this review is to discuss about the role of these dormant origins as housekeepers of the human genome in response to replicative stress.

A lack of data reproducibility (“reproducibility crisis”) is debated across many scientific and medical disciplines. A systematic analysis of the available evidence on the reliability of scientific data revealed that, although the existence of a reproducibility crisis is widely perceived, conclusive data on the scale of the problem are lacking. Most importantly we found that, although the debate is largely focused on methodological issues, researcher conduct defines research standards and in turn data reliability. The availability of reliable methods itself does not guarantee good practice. Moreover, research is typically characterised by a lack of established methods due to its immanent novelty. Despite the crucial importance of researcher conduct, research and conclusive data on the determinants of researcher behaviour are missing. In conclusion, meta-research is urgently needed that establishes an understanding of the factors that determine researcher behaviour. This knowledge can then be used to implement and iteratively improve measures, which incentivise researchers to apply the highest standards resulting in high quality data.

Self-enhancement (SE) is often overlooked as a fundamental cognitive ability mediated via the Pre-Frontal Cortex (PFC). Here we present research that establishes the relationship between the PFC, SE, and the potential evolved beneficial mechanisms. Specifically, we believe there is now enough evidence to speculate that SE exists to provide significant benefits and should be considered a normal aspect of the self. Whatever the metabolic or social cost, the upside of SE is great enough that it is a core and fundamental psychological construct. Furthermore, though entirely theoretical, we suggest that a critical reason the PFC has evolved so significantly in Homo sapien is to, in part, sustain SE. We therefore elaborate as to its proximate and ultimate mechanisms.

While the desire to uncover the neural correlates of consciousness has taken numerous directions, self-face recognition has been a constant in attempts to isolate aspects of self-awareness. The neuroimaging revolution of the 1990’s bought about systematic attempts to isolate the underlying neural basis self-face recognition. These studies, including some of the first fMRI (functional Magnetic Resonance Imaging) studies, revealed a right hemisphere bias for self-face recognition in a diverse set of regions including the insula, the Dorsal Frontal Lobe, the Temporal Parietal Junction and Medial Temporal Cortex. Confirmation of these data (which are correlational) was provided by TMS (Transcranial Magnetic Stimulation) and patients in which direct inhibition or ablation of right hemisphere regions leads to a disruption or absence of self-face recognition. These data are consistent with a number of theories including a right hemisphere dominance for self-awareness and/or a right hemisphere specialization for identifying significant social relationships including to oneself.

We report the development of an extrinsic self-healing coating system that shows no fluorescence from the intact coating, yellowish fluorescence in cracked regions, and greenish fluorescence in healed regions, thus allowing the separate monitoring of cracking and healing of coatings. This fluorescence monitoring self-healing system consisted of a top coating, an epoxy matrix resin containing mixed dye-loaded in single microcapsule. The dye-loaded microcapsules consisted of a poly(urea-formaldehyde) shell encapsulating a healing agent containing MAT-PDMS and styrene, a photo-initiator and a mixture of two dyes, one that fluoresces only in the solid state (DCM) and a second that fluoresces dramatically increased in the solid than solution state (4-TPAE). A mixture of the healing agent, photo-initiator and the two dyes was yellow due to fluorescence from DCM. On UV curing of this mixture, however, the color changed from yellow to green and the fluorescence intensity increased due to fluorescence from 4-TPAE in the solid state. When a self-healing coating embedded with microcapsules containing the DCM/4-TPAE dye mixture was scratched, the damaged region exhibited a yellowish color that changed to green after healing. Thus, the self-healing system reported here allows the separate monitoring of cracking and healing based on changes in fluorescence color.

Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8, is the causative agent of Kaposi’s sarcoma, Castleman’s disease, and primary effusion lymphoma. Although the functions of the viral thymidine kinases (vTK) of herpes simplex virus-1/2 and varicella zoster virus are well understood, that of KSHV ORF21 (an ortholog of vTK) is largely unknown. Here, we investigated the role of ORF21 in lytic replication and infection by generating two ORF21-mutated KSHV BAC clones: ORF21-kinase activity deficient-KSHV (21KD) and stop codon-induced ORF21-deleted-KSHV (21del). The results showed that both ORF21-mutations did not affect viral genome replication, lytic genes transcription, or the production of viral genome-encapsidated particles. ORF21 molecule-dependent function, other than the kinase function of ORF21, was involved in the infectivity of progeny virus. ORF21 was expressed at 36 h after induction of lytic replication, and endogenously expressed ORF21 was localized in the whole cytoplasm and decreased on the cell surface area. Moreover, the effects of ORF21 expression on signaling pathways and proliferation were analyzed. The results showed that ORF21 upregulated the MEK phosphorylation and anchorage-independent cell growth. These findings indicate that ORF21 plays key roles in both infection and oncogenesis of KSHV through the manipulation of cellular function.

Previously, we reported that MTH1 inhibitors TH588 and TH1579 selectively induce oxidative damage and kill Ras expressing or transforming cancer cells, as compared to non-transforming immortalized or primary cells. While this explains the impressive anti-cancer properties of the compounds, the molecular mechanism remains elusive. Oncogenes induce replication stress, re-sulting in under replicated DNA and replication continuing into mitosis, where TH588 and TH1579 treatment cause toxicity and incorporation of oxidative damage. Hence, we hypothesized that oncogene-induced replication stress explains the cancer selectivity. To test this, we overex-pressed c-Myc in human epithelial kidney cells (HA1EB), resulting in increased proliferation, polyploidy and replication stress. TH588 and TH1579 selectively kill c-Myc overexpressing clones, enforcing the cancer cell selective killing of these compounds. Moreover, the toxicity of TH588 and TH1579 in c-Myc overexpressing cells is rescued by transcription, proteasome or CDK1 inhibitors, but interestingly not by nucleoside supplementation. This suggest that cancer selectivity is unrelated oncogene-induced replication stress. We conclude that the molecular toxi-cological mechanisms how TH588 and TH1579 kill c-Myc overexpressing cells have several com-ponents and involves MTH1-independent proteosomal degradation of c-Myc itself, c-Myc driven transcription and CDK activation, and is likely unrelated to oncogene-induced replication stress.

Enterovirus A71 (EV-A71) infection is a major cause of hand, foot and mouth disease (HFMD) which may be occasionally associated with severe neurological complications. There are currently a lack of treatment options for EV-A71 infection. The Raf-MEK-ERK signaling pathway, in addition to its critical importance in the regulation of cell growth, differentiation and survival, has been shown to be essential for virus replication. In this study, we investigated the anti-EV-A71 activity of vemurafenib, a clinically approved B-Raf inhibitor used in the treatment of late stage melanoma. Vemurafenib exhibits potent anti-EV-A71 effect in cytopathic effect inhibition and viral load reduction assays, with half maximal effective concentration (EC50) at nanomolar concentration. Mechanistically, vemurafenib interrupts both EV-A71 genome replication and assembly. These findings expand the list of potential antiviral candidates of anti-EV-A71 therapeutics.

Background: The presence of HIV residual replication markers was investigated among distinct subgroups of individuals on antiretroviral treatment (ART). Methods: One hundred sixteen patients were distributed into 5 treatment groups: first-line suppressive ART with a non-nucleoside analog reverse-transcriptase inhibitor (NNRTI) (n = 26), first-line suppressive ART with boosted protease inhibitors (PI-r) (n = 25), suppressive salvage therapy using PI-r (n = 27), suppressive salvage therapy with PI-r and raltegravir (n = 22) and virologic failure (n = 16). Episomal and total DNA quantitation was evaluated. HIV antibody and LPS quantitation was performed. Results: Episomal DNA was positive in 26% to 38% of individuals under suppressive ART, and it was higher among ART virologic failure group (p = 0.04). HIV proviral load was higher among patients with detectable episomal DNA (p = 0.01). Individuals receiving initial PI-r treatment presented lower HIV antibody (p = 0.027) and LPS (p = 0.029) levels than individuals receiving NNRTI. There was a negative correlation between episomal DNA quantitation and the duration of suppressive ART (p = 0.04), CD4+ T-cell count (p = 0.08), and CD8+ T-cell count (p = 0.07). Conclusions: Residual HIV replication has been inferred among individuals under suppressive ART according to episomal DNA detection. Residual replication may decrease with longer periods of suppressive ART and higher levels of CD4+ and CD8+ T cells. The relationship between episomal DNA and total DNA suggests there is a replenishment of the proviral reservoir. Lower antibody and LPS levels among patients with initial PI-r ART suggest these regimens may more effectively suppress HIV, more effectively decreasing HIV antigenic component.

As a universal pathogen leading to neonatal defects and transplant failure, Human cytomegalovirus (HCMV) has strict species specificity that the inability to using this virus in animals has hampered its pathogenesis study. However, the mechanism of cross-species barrier remains elusive that no non-human cell model has been established to fill this knowledge gap. We observed that primary dermis fibroblasts (TSDF) isolated from the Chinese tree shrew (Tupaia belangeri chinensis), a small laboratory animal with close affinity to primates, were permissive to HCMV replication. In TSDF infected with GFP-expressing HCMV, the green fluorescence and cytopathic effect were observed and the expression of 3 kinetic genes and replication of viral genome were detected. The cell-free viruses produced in TSDF reached 103 pfu/mL at 96 hpi, which were 10-fold lower than in primary human foreskin fibroblasts. Our results demonstrated that TSDF supported low level of lytic replication of HCMV. The TSDF model provides a useful platform for the mechanism study of species barrier of HCMV.

Purpose: To identify the impact of dealing with COVID-19 patients in clinical areas on nurses' professional self-concept and self-confidence. Background: Professional self-concept is considered a critical factor in the recruitment/retention process in nursing, nursing shortage, career satisfaction, and academic achievements. Professional self-confidence is also a crucial determinant in staff satisfaction, reducing turnover, and increasing work engagement. Design: Descriptive, comparative study. Methods: The study was conducted between February to May 2021 by utilizing a convenience sampling technique. A total of 170 nurses from two facilities were recruited from two COVID-19 and non-COVID-19 designated facilities. The level of professional self-concept and self-confidence was assessed by utilizing the Nurses' Self-Concept Instrument and Self-Confidence Scale. Results: The professional self-concept level among the exposed group to COVID-19 patients was lower than the comparison group, while the professional self-confidence level among the exposed group to COVID-19 patients was similar to the comparison group. On the other hand, the satisfied staff and those who received professional training in dealing with COVID-19 patients reported a higher level of professional self-concept. Conclusions: Dealing with COVID-19 patients has an impact on professional self-concept; the exposure group was lower than those who did not deal with COVID-19 patients, while the professional self-confidence level among the exposed group was similar to the comparison group. Getting professional training in dealing with COVID-19 patients and being satisfied at work were significant factors in improving the professional self-concept. Policymakers should create strategies that target the improvement of professional training in dealing with COVID-19 patients.

Background: Level of perceived competence as a basic psychological need could trigger achievement of diabetes self-management goals. Due to lack of a specific data collection tool to measure level of self-competence among Persian speaking patients with diabetes this study was conducted for cross-cultural adaptation and psychometric assessment of the Persian version of Perceived Competence Scale for Diabetes (PCSD-P). Methods: Standard translation/back-translation procedure was carried out to prepare a preliminary draft of the PCSD-P. Content and face validity of the early draft were checked by an expert panel including 15 scholars in the field of health education and promotion as well as nursing education with experience of working and research on diabetes. The final drafted questionnaire was completed by 177 randomly selected patients with type 2 diabetes. Based on the collected data structural validity of the contrived version was appraised using exploratory and confirmatory factor analysis (EFA, CFA). Cronbach's alpha and Intraclass Correlation coefficients (ICC) were used to check the scale’s reliability and internal consistency. ; (3) Results: The estimated measures of Content Validity Index (CVI= 0.95) and Content Validity Ratio (CVR= 0.8) were in the range of acceptable recommended limits. The EFA analysis results demonstrated a single factor solution according to the items’ loadings for the component. The model fit indices i.e. RMSEA= 0.000, CFI=1, TLI=1, GFI= 0.998, NFI= 0.999 RFI= 0.995 confirmed consistency of the hypothesized one-factor solution. Values of the internal consistency and reliability coefficients were also in the vicinity of acceptable range (α= 0.892, ICC=0. 886, P= 0.001). Conclusions: The study findings revealed good internal validity and applicability of the PCSD-P to measure degree of self-competence among Persian speaking type 2 diabetes patients to manage the chronic disease. Due to unrepresentativeness of the study sample future cross-cultural test of PCSD-P on diverse and broader Persian speaking populations is recommended.

This paper addresses the development of knowledge and assessment-centered learning approaches within a reflective learning framework in a first year physics class in a university faculty. The quality of students’ reflections was scored using a Self-reporting Reflective Learning Appraisal Questionnaire at the end of each learning approach. The results showed the differences between the approaches based on reflections on the learning control through self-knowledge, by connecting experience and knowledge, as well as through self-reflection and self-regulation. Assessment-centered activities fundamentally help students identify aspects of their attitudes towards, as well as regulate, their sustainability learning education.

Based on the sensitive sum frequency generation cross-correlation frequency-resolved optical gating (SFG-XFROG) measurement setup, besides the pulse broadening, blue shift, red shift and obvious pulse acceleration, we observed the soliton evolution when the low energy soliton pulse with wavelength of 1555nm transmit through the Si photonic crystal waveguide. The measurements were nicely matched with the simulation results, which are achieved with an optimized nonlinear Schrödinger equation (NLSE) modeling. The effects of various parameters of the silicon photonic crystal waveguides and the incident pulses on the pulse transmission were also analyzed, including the nonlinear effects and dispersion such as the self-phase modulation (SPM), self-steepening (SS) and intra-pulse Raman scattering(IRS). The results help us understand further the ultra-fast nonlinear dynamics of soliton in silicon-based waveguides, and even open a novel way for soliton-based functional elements in CMOS-compatible platforms.

Building on the Sustainable Happiness Model, this study examined how congruency between ideal self-image and brand image influence a sense of happiness. The findings show that when ideal self-image and ideal social self-image are congruent with brand image a sense of happiness can be enhanced through brand identification and positive emotions. This study contributes to literature as it reveals the mechanism of how congruency between ideal self-image and brand image positively affect happiness.

Viruses are obligate intracellular parasites that are dependent on host factors for their replication. One such host protein, p97 or the valosin-containing protein (VCP), is a highly conserved AAA ATPase that facilitates replication of diverse RNA- and DNA-containing viruses. The wide range of cellular functions attributed to this ATPase is consistent with its participation in multiple steps of the virus life cycle from entry and uncoating to viral egress. Studies of VCP/p97 interactions with viruses will provide important information about host processes and cell biology, but also viral strategies that take advantage of these host functions. The critical role of p97 in viral replication might be exploited as a target for development of pan-antiviral drugs that exceed the capability of virus-specific vaccines or therapeutics.

SARS-CoV-2 or COVID-19, a new seventh human corona virus, has out-broken in Wuhan, China since 31^st December 2019, and quickly escalated to take the form of pandemic which killed many human beings throughout almost all countries across continents. The rapidity of its transmission from human to human is far greater than all previous human corona viruses which came into existence like SARS-CoV, MERS-CoV, etc. The nucleotide sequence of SARS-CoV-2 (isolates Wuhan-Hu-1) is 29,875 bp in ss-RNA. Symptoms of SARS-CoV-2 infected pneumonia include from asymptomatic to high fever and/or respiratory illnesses. Coronavirus virion (spherical/round /elliptical in shape) consists of three parts- outer membrane or envelope, nucleocapsid and genome (RNA). SARS-CoV-2 was shown to use receptor, angiotensin converting enzyme 2 (ACE2) for attachment to the cells through its surface spike (S) protein (S1), and the virion enters into the host cell through two routes- direct membrane fusion and endocytotic pathway. The RNA of SARS-CoV acts directly as mRNA and here minus(-) 1 programmed ribosomal frameshift (-1PRF) is being operated by slippery sequence and pseudoknot, so it translates 16 nonstructural proteins including RNA dependent RNA replicase. Then genomic RNA replicated continuously on – strand RNA template and subgenomic RNA transcribed discontinuously on –RNA template to sgmRNA. Subgenomic RNAs/sgmRNAs synthesize all structural proteins. This article takes into consideration the details of established theories of viral structure, viral attachment, mode of entry into human cells, different models of replication and transcription of virus genome proposed by eminent scientists over the years, and makes an in depth examination highlighting meaningful points or important target cites of viral propagation or synthesis, which are conserved, for prompt development of potent drugs or vaccine to counter COVID-19 for which human race is anxiously and eagerly waiting.

Health self-tracking is an ongoing trend as software and hardware evolve, making the collection of personal data not only fun for users but also increasingly interesting for public health research. In a quantitative approach we studied German health self-trackers (N=919) for differences in their data disclosure behavior by comparing data showing and sharing behavior among peers and their willingness to donate data to research. In addition, we examined user characteristics that may positively influence willingness to make the self-tracked data available to research and propose a framework for structuring research related to self-measurement. Results show that users' willingness to disclose data as a "donation" more than doubled compared to their "sharing" behavior (willingness to donate= 4.5/10; sharing frequency= 2.09/10). Younger men (up to 34 years), who record their vital signs daily, are less concerned about privacy, regularly donate money, and share their data with third parties because they want to receive feedback, are most likely to donate data to research and are thus a promising target audience for health data donation appeals. The paper adds to qualitative accounts of self-tracking but also engages with discussions around data sharing and privacy.

The recommendations of the panel of experts on the further development of the ‘High-Tech Strategy’ of the Government of the Federal Republic of Germany designate the biologization of economic processes along with digitization as the central driver of societal change. Various fields such as the 'biologization of materials research' were then defined in the 'Bio-Agenda' in order to walk the path from biology to innovation. In view of this perspective, we describe how the use of biological materials and mechanisms can lead to resource conservation, the production of intelligent materials and new technological and medical applications. Our strategy, based on research on ‘Biointerfaces in Technology and Medicine’, aims at the development of modular biohybrid systems that could be used as 'biofactories of the future' for sustainable production processes. To achieve this goal, in a first phase already known technologies have to be further refined and integrated in order to obtain and apply compartmentalized reaction systems on different length and time scales. In a second phase, the resulting functional units will be employed to develop dissipative systems useful for biomedical applications and advanced production processes. From a technical point of view, future success in creating 'something entirely new' will depend crucially on robust and complementary research capabilities. Since the close connection of engineering and life sciences at KIT provides an excellent basis for this endeavor, we consider the above perspectives to be feasible.

Toby Walsh in “The Singularity May Never Be Near” gives six arguments to support his point of view that technological singularity may happen but that it is unlikely. In this paper, we provide analysis of each one of his arguments and arrive at similar conclusions, but with more weight given to the “likely to happen” probability.

Centromeres, the chromosomal loci where spindle fibers attach during cell division to segregate chromosomes, are typically found within satellite arrays in plants and animals. Satellite arrays have been difficult to analyze because they comprise megabases of tandem head-to-tail highly repeated DNA sequences. Much evidence suggests that centromeres are epigenetically defined by the location of nucleosomes containing the centromere-specific histone H3 variant cenH3, independently of the DNA sequences where they are located; however, the reason that cenH3 nucleosomes are generally found on rapidly evolving satellite arrays has remained unclear. Recently, long read sequencing technology has clarified the structures of satellite arrays and sparked rethinking of how they evolve, while new experiments and analyses have helped bring both understanding and further speculation about the role these highly repeated sequences play in centromere identification.

We use state-of-the-art computer-aided drug design (CADD) techniques to identify prospective inhibitors of the main protease enzyme, 3CLpro of the SARS-CoV-2 virus causing COVID-19. From our screening of over one million compounds including approved drugs, investigational drugs, natural products, and organic compounds, and a rescreening protocol incorporating enzyme dynamics via ensemble docking, we have been able to identify a range of prospective 3CLpro inhibitors. Importantly, some of the identified compounds had previously been reported to exhibit inhibitory activities against the 3CLpro enzyme of the closely related SARS-CoV virus. The top- ranking compounds are characterized by the presence of multiple bi- and monocyclic rings, many of them being heterocycles and aromatic, which are flexibly linked allowing the ligands to adapt to the geometry of the 3CLpro substrate site and involve a high amount of functional groups enabling hydrogen bond formation with surrounding amino acid residues, including the catalytic dyad residues H41 and C145. Among the top binding compounds we identified several tyrosine kinase inhibitors, which include a bioflavonoid, the group of natural products that binds best to 3CLpro. Another class of compounds that decently binds to the SARS-CoV-2 main protease are steroid hormones, which thus may be endogenous inhibitors and might provide an explanation for the age-dependent severity of COVID-19. Many of the compounds identified by our work show a considerably stronger binding than found for reference compounds with in vitro demonstrated 3CLpro inhibition and anticoronavirus activity. The compounds determined in this work thus represent a good starting point for the design of inhibitors of SARS-CoV-2 replication.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an etiologic agent of the respiratory disease in humans that is known as coronavirus disease 2019 (COVID19). The first outbreak of the disease was initially documented in Wuhan, Hubei Province, China in late December 2019 where people had experienced SARS pneumonia-like symptoms with unknown etiology. Since then it has been observed that COVID-19 positive patients have been showing mild to severe upper respiratory illness symptoms. The type of virus is known to make its transfer from animals to humans and for the concerned virus; researchers have claimed its origin from bat coronavirus at whole-genome level with a 96 % sequence identity. The COVID-19 virus is very contagious and communicable in nature and has been spread throughout the globe since its first outbreak in China. On March 9, 2020, WHO declared it as a Pandemic, and within a month it was already reported to have shown its presence in 213 countries and territories or areas. As of April 29, 2020, this novel virus infected 3,218,183 people and caused 228,029 mortalities worldwide with a variable mortality rate from 3-13 % across the planet and also varied by age and gender. Diagnosis of the disease is a key component in understanding and controlling the spread of the virus and several techniques have been devised including RT-PCR, ELISA, and sequencing-based approaches. To cure COVID-19 patients as of now we do not have proven to be a safe and effective treatment. Therapeutic options currently under investigation in various parts of the world. However, there are various effective therapeutic targets to repurpose the present antiviral therapy for developing potential interventions against SARS-CoV-2. Boosting the immune system can also help to prevent and spread of COVID-19 using various medication and exercises. In this review, our goal to summarize and discussed the present scientific advancements to fight against this novel pandemic.

Q-switched laser radiation at wavelengths of 355 nm, 532 nm, and 1064 nm from a Nd: YAG laser was used to generate plasma in laboratory air at the target surface made of compressed nano-silver particles of size 95 ± 10 nm. The emitted resonance spectra from the neutral silver at wavelengths of 327.9 nm and 338.2 nm indicate existence of self-reversal in addition to plasma self-absorption. Both lines were identified in emission spectra at different laser irradiation wavelengths with characteristic dips at the un-shifted central wavelengths. These dips are usually associated with self-reversal. Under similar conditions, plasmas at the corresponding bulk silver target were generated. The recorded emission spectra were compared to those obtained from the nano-material target. The comparisons confirm existence of self-reversal of resonance lines that emerge from plasmas produced at nano-material targets. This work suggests a method for recovery of the spectral line shapes and discusses practical examples. In addition, subsidiary calibration efforts that utilize the Balmer series Hα-line reveal that other Ag I lines at 827.35 nm and 768.7 nm are optically thin under variety of experimental conditions and are well-suited as reference lines for measurement of the laser plasma electron density.

Cyber Physical Systems (CPS) has been a popular research area in the last decade. The dependability of CPS is still a critical issue, and rare survey has been published in this domain. CPS is a dynamic complex system, which involves various multidisciplinary technologies. To avoid human error and to simplify management, self-management CPS (SCPS) is a wise choice. And to achieve dependable self-management, systematic solution is necessary to verify the design and to guarantee the safety of self-adaptation decision, as well as to maintain the health of SCPS. This survey first recalls the concepts of dependability, and proposes a generic environment-in-loop processing flow of self-management CPS, and then analyzes the error sources and challenges of self-management through the formal feedback flow. Focus on reducing the complexity, we first survey the self-adaptive architecture approaches and applied dependability means; then we introduce a hybrid multi-role self-adaptive architecture, and discuss the supporting technologies for dependable self-management at the architecture level. Focus on dependable environment-centered adaption, we investigate the verification and validation (V&V) methods for making safe self-adaptation decision and the solutions for processing decision dependably. For system-centered adaption, the comprehensive self-healing methods are summarized. Finally, we analyze the missing pieces of the technology puzzle and the future directions. In this survey, the technical trends for dependable CPS design and maintenance are discussed, an all-in-one solution is proposed to integrate these technologies and build a dependable organic SCPS. To the best of our knowledge, this is the first comprehensive survey on dependable SCPS building and evaluation.

Only by understanding the ability to take third-person perspective can we begin to elucidate the neural processes responsible for one’s inimitable conscious experience. The current study examined differences in hemispheric laterality during a first-person perspective (1PP) and third-person perspective (3PP) taking task, when using Transcranial Magnetic Stimulation (TMS). Participants were asked to take either the 1PP or 3PP when identifying the number of spheres in a virtual scene. During this task, single-pulse TMS was delivered to the motor cortex of both the left and right hemispheres of 10 healthy volunteers. Measures of TMS-induced motor-evoked potentials (MEPs) of the contralateral abductor pollicis brevis (APB) were employed as an indicator of lateralized cortical activation. The data suggest that the right hemisphere is more important in discriminating between 1PP and 3PP. These data add a novel method for determining perspective taking and add to the literature supporting the role of the right hemisphere in meta representation.

This study is a synthesis of 159 articles that were selected for their relevance to comprehend key aspects of the Massive Open Online Courses (MOOCs) phenomenon, from a discourse analysis perspective. Since 2011, MOOCs are expanding worldwide so that the number of subscribers outpointed 101 million at the end of 2018. This paper explores the question whether the MOOCs are the embodiment of the global one-world classroom or whether, instead, they represent a low-cost alternative tailored to a segment that doesn´t have enough time or resources to attend a brick-and-mortar college. In addition, the review tackles the link between motivation and low completion rates. Finally, we discuss the need to devise better methods to assess the pedagogical value of MOOCs.

Background: Nursing services provided by nurses are based on knowledge and competence in the field of nursing science developed in accordance with Client needs, scientific developments, and the demands of globalization. These health services include nursing services that are carried out responsibly, accountably, with quality, and safely by nurses who have obtained registration and permission to practice. Nursepreneur is innovation and courage to take risks and is ready to work hard to achieve goals with optimism. Which has important components namely: 1) quality, 2) role, 3) option and success. The post-pandemic new world, especially in the health care system, continues to grapple with the demands of costs to provide patient care and safety. By using the application of the nursing theory model. Purpose :. Assessing scientific studies on the application of evidence-based intervention in wound care using nursing theory, identifying the important role of telenursing in improving nursing services in Nerspreneurship, Method: literature study Conclusion: Telenursing in nursing focuses on providing nursing care through information technology, such as telephone, computers, and the Internet that can be used to improve treatment outcomes among older people, especially those with low literacy skills and low financial status (Esmaeilpour-BandBoni et al., 2020). The statement from the results of the study refutes that Telenursing is intended for patients who have higher education and middle and upper economic states.

Background: Indonesia is an archipelago with various cultured, will bee affects all aspects of people's lives, including beliefs related to health behavior and health care. One problem that needs serious attention is the elderly group because the elderly are a vulnerable group who have a high risk of experiencing health problems, such as anemia with hypertension, so they need good care management. The research objective was to determine self-management intervention for hypertensive elderly. Methods: This research is a literature review with five databases (Scopus, CINAHL, ScienceDirect, PubMed, Proquest), the study design used is an experimental, descriptive, cross-sectional, and review systematic, in March 2021. Guidelines for using JBI to measure quality and listing check out Prisma in this review guide. A feasibility study based on title, abstract, full text, and research methodology. The data analysis used narrative analysis based on the research findings. Results: Twelve articles met the predefined review inclusion criteria. The study found eight interventions for self-management in elderly hypertension, namely: 1) Knowledge of hypertension, 2) Regulation of physical activity, 3) Limitation of alcohol and cigarette consumption, 4) Sleep rest and stress management, 5) Diet and body weight management, 6) Blood pressure control, 7) Family and social support, 8) Adherence to therapy regimens. Conclusion: The conclusion of the study results obtained eight elderly self-management interventions, this done properly will affect compliance in optimizing the health of the elderly.

Background: Since the beginning of the 20th century, the importance of creating healthy work environments and promoting the health of workers in the healthcare sector to create Healthy and Resilient Organizations has been emphasized. In this context, self-esteem is an essential construct which influences health and healthy life styles, and therefore, the general wellbeing of nurses. The objective of this study was to analyze the mediating role of reasons for exercising in the effect that self-esteem has on uncontrolled eating by nursing professionals. Methods: The sample was made up of 1094 nurses who were administered the Rosenberg General Self-esteem Scale, the Goal Content for Exercise Questionnaire and the Three-Factor Eating Questionnaire-R18. Results: Bivariate correlation analysis and multiple mediation analysis showed that self-esteem has direct and indirect effects on uncontrolled eating. More so, self-esteem predicts doing physical exercise to improve one’s image, recognition and social affiliation, although the effects on uncontrolled eating were only significant through image. Conclusions: The results have important practical implications in the framework of Positive Occupational Health Psychology (POHP) as it emphasizes self-esteem, physical exercise and eating as essential aspects of the health and wellbeing of employees in the healthcare sector, highlighting the importance of creating organizations committed to promoting the psychosocial health of their workers.

We develop an optimized force-field for poly(3-hexylthiophene) (P3HT) and demonstrate its utility for predicting thermodynamic self-assembly. In particular, we consider short oligomer chains, model electrostatics and solvent implicitly, and coarsely model solvent evaporation. We quantify the performance of our model to determine what the optimal system sizes are for exploring self-assembly at combinations of state variables. We perform molecular dynamics simulations to predict the self-assembly of P3HT at ~350 combinations of temperature and solvent quality. Our structural calculations predict that the highest degrees of order are obtained with good solvents just below the melting temperature. We find our model produces the most accurate structural predictions to date, as measured by agreement with grazing incident X-ray scattering experiments.

Partial differential representation of self-similarity feature has been derived from notion of the homogenous function in general sense. This representation allows consideration of stochastic self-similar systems. As well as the partial differential representation allows consideration of Stochastic Partial Differential Equation.

Though Cyber Physical Systems (CPS) become very popular in last the decade, dependability of CPS is still a critical issue and related survey is rare. We try to spell out the jigsaw of technologies and figure out the technical trends of dependable self-managing CPS. This survey first recalls the motivation and the similar concepts. By analyzing four generic architectures, we summarize the common characteristics and related assurance technologies, and propose a more generic environment-in-loop processing flow of CPS and a formal interaction flow between physical space and cyber space. Further, the similarity between correctness and dependability is formally analyzed and the new five research questions of dependable self-managing CPS are presented. Then we review the critical technologies and related correctness verification & validation (V&V) methods, the architectures for dependable self-managing CPS. Further, the detail dependability management and V&V technologies are surveyed, which covers the areas of running-time fault management methods and whole life cycle V&V technologies, maintenance and available tool sets. For holistic CPS development, Modeling techniques and MDE (model driven engineering) based V&V methods are analyzed in detail. Then we complete the jigsaw of technologies and figure out the missing part. Further, we propose the technical challenges and the further direction. To our best knowledge, this is the first comprehensive survey on dependable self-managing CPS development and evaluation.

This article is devoted to results of in-depth analysis of the system of binary-oppositional structures in DNA n-plet alphabets and their algebraic-matrix representations. These results show that the molecular complementary replication of DNA strands is accompanied by the presence of an algebraic version of the principle "like begets like" in matrix representations of DNA alphabets having internal structures. This algebraic version is based on binary-oppositional structures in the genetic molecular system, which can be represented by bynary numbers and corresponding matrices of DNA alphabets. The received results allow thinking that the phenomenon "like begets like" (or a complementary replication in a wide sense) is a systemic in the genetic organization and is connected with algebraic features of biological organization. Correspondingly, the biological principle "like begets like" can be additionally modeled by algebraic-matrix methods and approaches. Such algebraic-matrix modeling of the genetic coding system gives new ways for studying and understanding a key role of the named principle in genetic and other inherited physiological complexes. The author believes that further study of the algebraic relationships of the genetic system and inherited physiological complexes will be increasingly revealing the key biological role of the ancient principle "like begets like" at different levels of biological organization.

The generation of different types of defective viral genomes (DVG) is an unavoidable consequence of the error-prone replication of RNA viruses. In recent years, a particular class of DVGs, those containing long deletions or genome rearrangements, has gain interest due to their potential therapeutic and biotechnological applications. Identifying such DVGs in high-throughput sequencing data has become an interesting computational problem. Up to nowadays, several algorithms have been proposed, though all incur in false positives, a problem of practical interest if such DVGs have to be synthetized and tested in the laboratory. Here we develop a novel software, DVGfinder, that wraps the two most commonly used algorithms into a pipeline that predicts DVGs. Using a gradient boosting classifier machine learning algorithm, we evaluate the performance of DVGfinder compared to previous algorithms and found that it outcompetes their precision and sensitivity in simulated datasets. DVGfinder generates user-friendly output files in HTML format that can assist users to identify DVGs based on their associated probability of being true positives.

Human infections caused by the H5 highly pathogenic avian influenza virus (HPAIV) sporadically threaten public health. The susceptibility of HPAIVs to baloxavir acid (BXA), a new class of inhibitors for the influenza virus cap-dependent endonuclease, has been confirmed in vitro, but it has not yet been fully characterized. Here, the efficacy of BXA against HPAIVs, including recent H5N8 variants, was assessed in vitro. The antiviral efficacy of baloxavir marboxil (BXM) in H5N1 virus-infected mice was also investigated. BXA exhibited similar in vitro activities against H5N1, H5N6, and H5N8 variants tested in comparison with seasonal and other zoonotic strains. Compared with oseltamivir phosphate (OSP), BXM monotherapy in mice infected with the H5N1 HPAIV clinical isolate, the A/Hong Kong/483/1997 strain, also caused a significant reduction in viral titers in the lungs, brains, and kidneys, thereby preventing acute lung inflammation and reducing mortality. Furthermore, compared with BXM or OSP monotherapy, combination treatments with BXM and OSP using a 48-hour delayed treatment model showed a more potent effect on viral replication in the organs, accompanied by improved survival. In conclusion, BXM has a potent antiviral efficacy against H5 HPAIV infections.

The current article examined stoma self-care and health-related quality of life in patients with drainage enterostomy, describe clinical and sociodemographic variables and analyze the relations between all of them. Trained interviewers collected data using a standardized form that queried sociodemographic and clinical variables, collected from the electronic medical record, in addition to the Specific Self-Care for Ostomized Patients Questionnaire (CAESPO) and Stoma Quality of life (S-QoL) from January 2016 to January 2017. This was a multicenter, cross sectional study conducted in four hospitals of the province of Castellon (Spain) where 120 participants were studied. Significant differences were found in Self Care according to sex (p = .043); married participants show higher score (p < .01); also, significant differences according to work activity were observed (p < .01). Regarding the clinical variables, differences were observed according to the autonomy of care, the presence of complications in the stoma, the use of irrigation and the type of effluent (p < .01). We can highlight the importance of the skills related to self-care by ostomized patients has for a good level of quality of life related to health. In this learning process, the figure of the stoma therapist plays a very important role.

Research for novel vaccine adjuvants remains a critical need to improve the immune responses to a recombinant vaccine antigen. Emulsion adjuvants such as AS03 and MF59, particularly in the area of Influenza vaccines, have shown antigen dose sparing and allowed reduced immunizations. It was previously demonstrated that these emulsion adjuvants can be formulated using a simpler, low shear process of self-emulsification. The role of alpha tocopherol as an immunomodulator in emulsion adjuvants is evident from the success of AS03 in the on-going covid-19 pandemic. Although, it was a challenge to formulate alpha tocopherol with a low shear process to get closer to the AS03 composition, the self-emulsified version referred as self-emulsifying adjuvant systems (SE-AS) showed comparable immune responses to AS03 when co-administered with a Quadrivalent influenza virus (QIV) vaccine. In this paper, we first optimized the SE-AS with alpha tocopherol referred to as SE-AS44 to allow sterile filtration. We compared the in vitro cytokine profile with self-emulsifying adjuvant 160 (SEA160), a squalene-only self-emulsified adjuvant with composition similar to MF59. We compared SE-AS44 and SEA160 co-administered with a recombinant cytomegalovirus (CMV) pentamer antigen, which is a less immunogenic antigen, in vivo to compare the antibody and T-cell responses, in different adjuvanted groups, in C57BL/6 mice.

Self-healing is the capability of materials to repair themselves after damage has occurred, usually by interaction between molecules or chains. Physical and chemical processes are applied for the preparation of self-healing systems. There are different approaches for these systems such as heterogeneous systems, shape memory effects, hydrogen bonding or covalent-bond interaction, diffusion and flow dynamics. Self-healing mechanisms can occur in particular by heat and light exposure or by reconnection without direct effect. The applications of these systems display an increasing trend in both R&D and industry sectors. Moreover, self-healing systems and their energy storage applications are currently getting great importance. This review aims to provide general information on recent developments in self-healing materials and their energy applications in view of the critical importance of self-healing systems for lithium-ion batteries (LIBs). In the first part of the review, an introduction about self-healing mechanisms and design strategies of self-healing materials is given. Then, selected important healing materials in the literature for the anodes of LIBs are mentioned in the second part. The results and future perspectives are stated in the conclusion section.

Background: HIV self-testing (HIVST) is one of the recommended approaches for HIV testing services, particularly for helping reach populations who would not normally access facility-based HIV testing. HIVST must be tailored to different populations to ensure uptake. Objective: The main objective of this study was to develop an acceptable HIVST delivery strategy to help improve urban men’s engagement with HIV services. Methods: We invited key stakeholders for urban men’s HIV services to participate in a co-creation workshop aimed at developing HIVST delivery approaches for urban men, using eThekwini municipality as a study setting. We conducted purposive sampling to include health care users and health care providers, representing a range of views across the public sector and voluntary sector. We employed the Nominal Group Technique (NGT) method for data collection. The NGT workshop was conducted in two consecutive phases: phase one was focused on determining barriers for men’s engagement with the current/facility-based HIV testing services; phase two was aimed at determining HIVST delivery strategies. We used the results of the NGT to design a tailored HIVST strategy for urban men in eThekwini District. Results: Participants identified the following psychological factors as the most important barriers to uptake of HIV testing services by urban men: stigma, ignorance about the importance of testing and testing process as well as fear of positive test results. Key stakeholders suggested internal motivation strategies as a potentially effective approach to support HIVST delivery strategy. Guided by the NGT results, we designed a HIVST delivery strategy that is supported by a risk communication approach Conclusion: We designed an evidence-based risk communication mobile health (mHealth) strategy coupled with SARS COV-2 self-testing tailored to improve men’s uptake of HIVST. A follow-up study to evaluate the feasibility of implementing these approaches is recommended.

Our brains process information using a layered hierarchical network architecture, with abundant connections within each layer and sparse long-range connections between layers. As these long-range connections are mostly unchanged after development, each layer has to locally self-organize in response to new inputs to enable information routing between the sparse in- and output connections. Here we demonstrate that this can be achieved by a well-established model of cortical self-organization based on a well-orchestrated interplay between several plasticity processes. After this self-organization, stimuli conveyed by sparse inputs can be rapidly read out from a layer using only very few long-range connections. To achieve this information routing, the neurons that are stimulated form feed-forward projections into the unstimulated parts of the same layer and get more neurons to represent the stimulus. Hereby, the plasticity processes ensure that each neuron only receives projections from and responds to only one stimulus such that the network is partitioned into parts with different preferred stimuli. Along this line, we show that the relation between the network activity and connectivity self-organizes to a biologically plausible regime. Finally, we argue how the emerging connectivity may minimize the metabolic cost for maintaining a network structure under the above described constraints.

This proposal describes the design and development of an interoperable application that supports green open access with long-term sustainability and improved user experience of article deposit. Introduction: The lack of library resources and unfriendly repository user interface are two significant barriers that hinder green open access. Tasked to implement the open access mandate, librarians at an American research university developed a comprehensive system called Easy Deposit 2 to automate the support workflow of green open access. Implementation: Easy Deposit 2 is a web application that is able to harvest newly publications, outreach for manuscript on behalf of the library, and facilitate self-archiving to IR. It is developed and maintained by the library and integrated with the IR. Results and Discussion: The article deposit rate is about 25% with Easy Deposit 2, which increases significantly comparing to the previous period. It also serves as a local database for faculty publications with open access status. The lesson learned is that library cannot rely on a single commercial provider for publication data due to mismatched priorities. Conclusion: Recent IT developments provides new opportunities of innovation like Easy Deposit 2 in supporting open access. Academic librarians are vital in promoting "openness" in scholarly communication such as transparency and diversity in the sharing of publication data.

The study aimed to understand the experiences of adolescent smokers who participated in a smoking cessation program based on self-reflection, and to develop the theoretical basis for constructing similar programs. The participants, ten students from middle and high schools located in cities G and S, were interviewed after the program ended. Data were collected from August to November 2019 and analyzed using a phenomenological approach to understand participant experiences in depth. The analysis revealed five major themes: ‘Uniqueness of the Program,’ ‘Perception of Smoking Cessation,’ ‘Positive Reflection on Life,’ ‘Understanding Others,’ and ‘A Search for Hope and Vision in Life.’ The findings revealed that the smoking cessation program facilitated the development of self-identity and vision, which may indirectly strengthen the motivation for adolescent smokers to quit smoking. These findings suggest the need for a life-changing smoking cessation program that enhances self-concept and self-esteem. Moreover, it highlights the importance of follow-up research to ensure effectiveness, and the need to develop programs with creative content.

While some researchers have suggested that the self-employment (SE) sector is a haven during a financial Crisis, others believe that SE is not necessarily the desired outcome, but an indicator that the labor market is tightening for some groups. Few researchers have compared the SE sector before and after the occurrence of a significant financial Crisis, especially in developed countries. This paper analyzes the determinants of entry into self-employment during the 2008 Spanish Crisis. Using data from the Encuesta de Presupuesto Familiar (EPF), results show that although the rate of SE did not experience a significant change during this time the Crisis affected people differently based on gender, with being females more affected than males. Results also suggest differences between Comunidades Autonomas in how the self-employment sector behaved during the Crisis.

Due to limitation of the binding energy of a self-gravitating matter, the radius of a body is at least twice larger than the Schwarzschild radius. The total energy is adsorbed at the body surface, giving rise of a size-dependent surface tension. Since the Hawking temperature appears to be the critical one, the black holes possess zero surface tension. Microscopic neutrino stars are also introduced.

This study aimed to know the conditioning factors of the transition process to the self-care of women diagnosed with HIV/AIDS. This qualitative study was carried out from June to September 2015 with seven seropositive women, users of a specialized service in sexually transmitted diseases in the municipality of Imperatriz, Maranhão State, Brazil. For the data collection, an individual interview was used, and data analysis was performed by content analysis delineated by Hsieh and Shannon (2005). The resources that influence the self-care in the transition process of women with HIV/AIDS are represented by personal conditioning factors, such as the meaning they attribute to the living with the disease, personal attitudes and cultural beliefs, socioeconomic status, preparation and knowledge about the disease, and by conditioning factors found in the community and society. The transition theory can provide important insights about the resources present in the adaptation process of women diagnosed with HIV so that they can perform their self-care satisfactorily.

To better understand the shape memory materials and self-healing materials, a new series of liquid-crystalline shape memory polyurethane (LC-SMPU) composites, named SMPU-OOBAm, were successfully prepared by incorporating 4-octyldecyloxybenzoic acid (OOBA) into the PEG-based SMPU. The effect of OOBA on the structure, morphology and properties has been carefully investigated. The results demonstrate that SMPU-OOBAm have liquid crystalline properties, triple-shape memory properties and self-healing properties. The incorporated OOBA promotes the crystallizability of both soft and hard segments of SMPU, and the crystallization rate of the hard segment of SMPU decreases when the OOBA-content increases. Additionally, the SMPU-OOBAm forms a two-phase separated structure (SMPU phase and OOBA phase), and it shows two-step modulus changes upon heating. Therefore, the SMPU-OOBAm shows triple-shape memory behavior, and the shape recovery ratio decreases with an increase in the OOBA content. Finally, SMPU-OOBAm shows self-healing properties. The new mechanism can be ascribed to the heating-induced “bleeding” of OOBA in the liquid crystalline state and the subsequent re-crystallization upon cooling. This successful combination of liquid crystalline properties, triple-shape memory properties and self-healing properties make the SMPU-OOBAm composites with many promise applications in smart optical devices, smart electronic devices and smart sensors.

In 2015, the Self-Action Leadership Theory—a qualitative, nomological expansion of self-leadership theory rooted in atmospheric and astronomical metaphor aimed at expanding the personal freedom of individuals, organizations, and nations by bolstering the existential growth of individuals through a series of Maslow-esque stages of holistic, personal development. This article introduces an accompanying, practitioner-based Model of Self-Action Leadership (SAL) aimed at the implicit enhancement of a holistic range of administrative processes through explicit training, mentoring, and coaching in the model’s general and universally-applicable principles and practices. The SAL model produces an original construct of personal leadership practice that builds upon the extant self-leadership academic canon, which dates back to 1983 (Manz, 1983). It also provides an analogue to four of the five core processes of Project Management by positioning a self-action leader (an individual) as the ongoing “project” at hand. The SAL Model is rooted in action research and was developed through a variety of self-oriented, action research projects in conjunction with a comprehensive, qualitative, analytical autoethnographic study of a scholar’s life experiences.

In this study, a structural profiling of equid alphaherpesvirus 1 (EHV-1) transcriptome was carried out using next-generation (Illumina) and third-generation (Oxford Nanopore Technologies) sequencing platforms. We annotated the canonical mRNA molecules and their isoforms, including transcript start and end site isoforms, and splice variants. Additionally, a number of putative 5′-truncated mRNAs containing shorter in-frame ORFs were detected. We also demonstrated that EHV-1 produces a high number of non-coding transcripts, including antisense and intergenic RNAs. One of the most remarkable features of the EHV-1 is the generation of abundant fusion transcripts some of which encoding chimeric polypeptides. We observed a higher number of splicing and transcriptional overlaps than in related viruses. Additionally, we found that many upstream genes of tandem gene clusters have their own transcript end sites (TESs) besides the co-terminal TESs, which is rare in other alphaherpesviruses. We show here that the replication origins (OriS and OriL) of the virus are co-localized with promoter sequences and overlap with specific RNA molecules. Furthermore, we discovered a novel non-coding RNA (designated as NOIR) that overlaps the 5′-ends of the longer transcript variants encoded by the two main transactivator genes ORF64 and 65 bracketing the OriL. These all suggest the existence of a central regulatory system which controls the genome-wide transcription and the replication through a mechanism based on the interference between the machineries carrying out the synthesis of DNA and RNA.

Enterovirus 71 (EV71) infection hand-foot-mouth disease (HFMD), meningoencephalitis, neonatal sepsis, and even fatal encephalitis in children, thereby representing a serious public health hazard. It is important to determine the mechanisms underlying the regulation of EV71 infection. In this study, we initially reveal that the interleukin enhancer binding factor 2 (ILF2) down-regulates EV71 50% tissue culture infective dose (TCID50), attenuates EV71 plaque formation unit (PFU), thereby repressing EV71 infection. Moreover, we reveal a distinct mechanism by which EV71 antagonizes ILF2-mediated antiviral effects. Chip data analyses show that ILF2 mRNA is reduced upon EV71 infection. Cellular studies indicate that EV71 infection represses ILF2 mRNA expression and protein production in human leukemic monocytes (THP-1) differentiated macrophages and in human rhabdomyosarcoma (RD) cells. Additionally, EV71 non-structural protein 2B interacts with ILF2 in human embryonic kidney (HEK293T) cells. Interestingly, in the presence of EV71 2B, ILF2 is translocated from the nucleus to the cytoplasm and co-localizes with 2B in the cytoplasm. Therefore, we reveal a distinct mechanism by which EV71 antagonizes ILF2-mediated antiviral effects by inhibiting ILF2 expression and promoting ILF2 translocation from the nucleus to cytoplasm through its 2B protein.

Nanometer-curved surfaces are abundant in biological systems as well as in nano-sized technologies. Properly functionalized polymer-grafted nanoparticles (PGNs) adhere to surfaces with different geometries and curvatures. This work explores some of the energetic and mechanical characteristics of the adhesion of PGNs to surfaces with positive, negative and zero curvatures using Coarse-Grained Molecular Dynamics (CGMD) simulations. Our calculated free energies of binding of the PGN to the curved and flat surfaces as a function of separation distance show that curvature of the surfaces critically impacts the adhesion strength. We find that the flat surface is the most adhesive, and the concave surface is the least adhesive surface. This somewhat counterintuitive finding suggests that while a bare nanoparticle is more likely to adhere to a positively curved surface than a flat surface, grafting polymer chains to the nanoparticle surface inverts this behavior. Moreover, we studied the rheological behavior of PGN upon separation from the flat and curved surfaces under external pulling force. The results presented herein can be exploited in drug delivery and self-assembly applications.

The goal of this work is to show that the underlying symmetries of effective field theory can be traced to the onset of self-similarity. In particular, we argue that the scale-free structure of fractal geometry lies at the heart of invariance principles in classical and Quantum Field Theory.

This paper, which is one of the few in the world dealing with this topic, presented the psychologist's work based on the concepts of mentalization and internal working models (IWMs) of attachment, with an adolescent girl who was prone to nonsuicidal self-injury. Gaga, a student in the first grade of high school, had visible scars from cutting her hands on the inner sides of both forearms. Gaga told the psychologist that her mother believes that this is an attempt to draw attention to her problems, and even a suicide attempt. Together with Gaga, the psychologist made a formulation of her mental difficulties. The main aim of the psychologist's work with Gaga was to control unpleasant impulses and emotions, so as to eliminate self-injury. This aim has been achieved through three global tasks: 1) that Gaga, in the relationship with the psychologist, builds her IWMs as positive, so that she can see herself as a person who is worthy of the love and support of close people; 2) to develop a stable capacity for mentalization; 3) to apply this acquired skills in the interpretation of her affective experiences. The mentalizing approach in working with Gaga was based on an attitude of emotional warmth, acceptance and authentic interest in her inner world. The psychologist's work with Gaga led to her better self-control, which resulted in the cessation of her self-injury. In her work with a psychologist, Gaga acquired positive IWMs, which she transferred into other significant interpersonal relationships.

Consciousness is usually perceived as a state of being aware of one’s environment as well as self. Despite its omnipresence in our life, understanding this concept is challenging. This has given rise to several theories attempting to explain the nature of consciousness, as well as hard and soft problems of consciousness. In fact, the boundaries of consciousness defined by these theories are a topic of continued discussion, particularly in light of the recent advances in artificial intelligence (AI). Some of these theories consider consciousness as a simple integration of information while others purport the need for an agency in the process of integration for an entity to be considered conscious. Some theories consider consciousness as a graded entity and some equate consciousness with content of awareness. In this work, major theories of consciousness are reviewed and compared, focusing on awareness, attention, and sense of self. These findings are interpreted in relation to AI in order to ascertain what makes AI distinct from natural intelligence.

Consciousness is usually interpreted as a state of being aware of one’s environment as well as self, while awareness is understood as knowledge of something. Despite their semantic differences, in philosophy, these terms are often used interchangeably, as is the case of the hard problem of consciousness proposed by Chalmers, which in fact is the hard problem of awareness. Trilogy paradigm of consciousness (or simply “trilogy”) offers a new paradigm where consciousness is the result of a unique interaction between awareness and the decision-making process. By conferring the input of awareness to the decision-making process, a new mental function of awareness-based choice selection (ABCS) or true free will emerges. Likewise, application of the power of decision-making to the process of awareness gives rise to discretionary selection of information for awareness (DSIA) or intentional attention. The intertwined actions of ABCS and DSIA comprise “I” which is the faculty of our consciousness and is what sets natural intelligence (NI) apart from artificial intelligence (AI). Based on trilogy, mind is an unconscious compilation of all mental function excluding ABCS and DSIA that are the essence of consciousness. As humans, we are a union of “I,” our minds, and our bodies.

Peru has one of the highest informal employment rates in Latin America (73%). Previous studies have shown higher prevalence of poor self-perceived health (P-SPH) in informal workers compared to formal. The study’s aim is to analyse the role of working conditions in the association between informality and SPH in urban working population in Peru. We conducted a cross-sectional study based on 3098 workers from the working conditions survey of Peru 2017. Prevalence of P-SPH and exposure to poor working conditions were calculated separated by formal and informal employment and stratified by sex. Poisson regression models were used to assess the association between P-SPH and informal employment, with its prevalence ratios (PR) crude and adjusted for working conditions. Informal employment was 76% in women and 66% in men. Informal workers were more exposed to poor working conditions than formals and reported worse SPH. Workers in informal employment showed higher risk of P-SPH than formals: PR 1.38 [95% CI: 1.16 – 1.64] in women and PR 1.27 [95% CI: 1.08 – 1.49] in men. Adjustment by working conditions weakened the association in both sexes. In women, this association was only partially explained by worse working conditions 1.23 [95% CI: 1.04 – 1.46]. The negative effect on informal workers’ health is partially explained by poor working conditions. However, there is a part of the effect explained by informality per se.

Background: This study consists of a brief psychological intervention, which uses the Self-Regulation Therapy (SRT, procedure based on suggestion and classical conditioning), to improve coping with stress and emotionality by reproducing the positive effects of illegal drugs: cannabis, cocaine, ecstasy. Method: 15 volunteers (8 males, 7 females), with a mean age of 24.67 (SD = 4.43), underwent intervention to improve their coping with stress and emotionality using SRT. They carried out pre- and post-intervention scores for 10 days and during a 4-week fol-low-up. The employed instruments were: COPE (Coping Skills Inventory) and PNAS (Positive and Negative Affect Schedule). Results: SRT was superior to non-intervention for the 4 coping strategies (2= .829, .453, .411 and .606) and for positive (2= .371) and negative emotionality (2= .419). An improvement in scores was evidenced in the follow-up scores compared to the pre-intervention measures. Conclusions: This study shows for the first time that it is possible to use illegal drugs, considered harmful to public health, to improve young people’s coping capacity and emotionality by reproducing their positive effects with SRT.

Background & Aims: Globally, liver diseases account for 2 million deaths per year. For those with advanced liver disease the only curative approach is liver transplantation. However, less than 10% of those in need get a liver transplant due to limited organ availability. To circumvent this challenge, there has been a great focus in generating a bioengineered liver. Despite its essential role in liver functions, a functional biliary system has not yet been developed. In this framework, exploration of epithelial cell self-organogenesis and microengineering-driven geometrical cell confinement allow to envision the bioengineering of a functional biomimetic intrahepatic biliary tract. Approach: Three-dimensional (3D) bile ducts were built in vitro by restricting cell adhesion to two-dimensional (2D) patterns to guide cell self-organization. Tree shapes mimicking the configuration of the human biliary system were micropatterned on glass slides, restricting cell attachment to these areas. Different tree geometries and culture conditions were explored to stimulate self-organogenesis of normal rat cholangiocytes (NRCs) used as a biliary cell model, either alone or in coculture with human umbilical endothelial cells (HUVECs). Results: Pre-seeding the micropatterns with HUVECs promoted luminogenesis with higher efficiency to yield functional branched biliary tubes. Lumen formation, apico-basal polarity, and preservation of the cholangiocyte phenotype were confirmed. Moreover, intact and functional biliary structures were detached from the micropatterns for further manipulation. Conclusion: This study presents physiologically relevant 3D biliary duct networks built in vitro from 2D micropatterns. This opens opportunities for investigating bile duct organogenesis, physiopathology, and drug testing.

(1)Background: This report was an effective evaluation of using multimedia educational program for self-care and quality of life in patients with a stoma at postoperative and established a simple threshold for enterostomy self-care skills.(2)Methods:108 patients with enterostomy were randomly assigned to receive either the intervention multimedia education program (including information about preparation for enterostomy care, cleaning method, manual bag replacement steps and precautions). The primary outcome was self-care ability and quality of life (defined as overall enterostomy self-care ability and overall quality of life), which was assessed at 2 weeks after intervention via an interview.(3)Results: Compared with those who in the conventional stoma education program, patients received the multimedia education program significantly improved their overall self-care ability and quality of life in statistically. The threshold of the enterostomy self-care skill scale was 20 points, and its corresponding sensitivity was 77.8%, and the specificity was 75.7%.(4)Conclusions: According to our study, the multimedia education program could enhance self-care ability of home care and quality of life in patients with enterostomy.

The advancement of bioconcrete over cementitious composites has brought us to the application of microbes in the field of construction materials. Certain microbes like bacteria, algae, and fungi have been discussed in the review. The purpose of applying these microbes in the matrix is mainly to enhance the concrete’s strength and other properties such as durability, resistance, and self-healing ability. As these microbes are able to induce calcite biomineralizations, the process is also known as Microbiologically Induced Calcite Precipitation (MICP). Some known microorganisms with their mentioned ability are Bacillus subtilis and Bacillus cohnii (bacteria), Chlorella vulgaris and Spirulina platensis (algae), and Trichoderma reesei, Aspergillus niger, and Neurospora crassa (fungi). The paper provides a “state-of-the-art” review of research into the effects of bioconcrete and discusses the overall methodologies of every medium with their physiological, physicochemical and bioengineering properties in the light of recent researches done so far in the same field.

There is growing evidence on the relevance of self-efficacy for well-being and functioning among individuals with psychotic disorders, but specific self-efficacy for coping with stress has rarely been investigated. This study explored the outcomes of an intervention for the improvement of coping resources based on a training in coping skills and coping with stress self-efficacy (CSSE). Fourteen adult volunteers who were diagnosed with schizophrenia (n=12) or schizoaffective disorder (n=2) were matched in clinical and sociodemographic characteristics and randomly assigned to the study groups. The intervention group received the training along with their pharmacological therapy; the control group received their prescribed drug therapy. Participants completed self-reports on CSSE, perceived successful daily functioning based on coping skills, and clinical status (BPRS-E). Trained patients showed a significant increase in CSSE and reported greater successful functioning status, and significant improvements in their clinical status were also observed. All these enhancements remained at 3-month and 6-month follow-ups. Control participants showed no significant changes. Moreover, the intervention condition interacted with CSSE and perceived coping functioning in explaining improvements in clinical status: in the treatment group, greater CSSE translated into enhanced daily functioning, and this improvement predicted better clinical status. These findings stress the relevance of promoting coping resources in psychotic disorders and provide preliminary evidence for the potential benefits of CSSE.

Proteins and DNA exhibit key physical chemical properties that make them advantageous for building nanostructures with outstanding features. Both DNA and protein nanotechnology have growth notably and proved to be fertile disciplines. The combination of both types of nanotechnologies is helpful to overcome the individual weaknesses and limitations of each one, paving the way for the continuing diversification of the structural nanotechnologies. Recent studies have implemented a synergistic combination of both biomolecules to assemble unique and sophisticate protein-DNA nanostructures. These hybrid nanostructures are highly programmable and display remarkable features that create new opportunities to build in the nanoscale. This review focuses on the strategies deployed to create hybrid protein-DNA nanostructures. Here, we will discuss strategies such as polymerization, spatial directing and organizing, coating, rigidizing or folding DNA into particular shapes or moving parts. The enrichment of structural DNA nanotechnology by incorporating protein nanotechnology has been clearly demonstrated and still shows a large potential to create useful and advanced materials with cell-like properties or dynamic systems. It can be expected that structural protein-DNA nanotechnology will open new avenues in the fabrication of nano-assemblies with unique functional applications and enrich the toolbox of bionanotechnology.

Transition from primary to secondary school is more successful when students’ learning is consistent. Students are also more likely to enjoy the school, engage with learning, and have a high academic achievement in the secondary school when they feel motivated. This is a critical aspect especially in cases when global pandemics situations allow only the online schooling opportunity. Students that are away from school lack the traditional sources of motivation and self-regulated learning skills, thus research is needed to identify other important factors that can be developed in remote settings. The aim of this study was to find out how students perceive their experience with the transition from primary to secondary school and how such a transition influences students’ self-regulated learning (SRL) and motivation. Self-reported data were collected during the COVID-19 breakout from a total of N=80, 6th and 7th grade students aged 12-14 years old. Results showed that students had a successful transition, especially when they are supported by their parents and teachers. Next, Bivariate Pearson Correlation analysis indicated that students’ perceptions about their experience with the transition from primary to secondary school and their self-regulated learning and motivation are significantly correlated. No gender differences were found among all main study variables.

Background and Objectives: In Libya, prescription medicines can easily be dispensed without a prescription, as self-medication with the subsequent of potential misuse and unnecessary risk for patients. This systematic review and meta-analysis explored the prevalence of self-medication among citizens in Libya. Methods: We systematically searched PubMed, ISI Web of Knowledge, EMBASE, Medline, Scopus, google scholar and ResearchGate databases for studies published in Libya reporting the prevalence of non-prescription use of medicines in community pharmacies, targeting studies published from Jan 2008 until Dec 2019. A random meta-analysis was performed to analyze pooled estimates of non-prescription usage of medicines. Results: Out of 63 articles identified, a total of 13 papers from 7 cities were met the inclusion criteria and involved a total of 4741 subjects. The overall pooled proportion of self-medication of drugs was 53.6% (95% CI: 0.93% - 1.08%), with low heterogeneity and the P-value of the whole population tasted was found to be = 1.000 (df = 12). Seven out of the 13 studies reported data on self-medication for antibiotics without prescription. The records ranged from 15.3% (95% CI 0.61–1.65) in Misurata to 76.6% (95% CI 0.80–1.25) in Tripoli. Conclusion: Self-medication use of medicines among Libyan population is a common phenomenon involving a high proportion use of antibiotics. This misuse of medications could enhance the development and spread of antibiotic resistance.

The Photovoltaic modules are usually installed on the ground which exposes it to surface deposition of foreign particles. In the Middle East and North Africa region, the primary culprit is dust and sand. They form an insulating and opaque layer on the surface of the glass, which obstructs its heat transfer and optical properties, thereby reducing the overall yield efficiency of the solar panel. Cleaning of this layer is critical to the operation of the solar panel and often requires great effort and energy on a large-scale solar array. In this paper, we propose a novel self-cleaning mechanism for solar panels, with an understanding of the structural integrity of the Photovoltaic laminate and application of external mechanical vibration. By applying an external source of vibration, the solar panels vibrate, excites its fundamental frequencies and cleans by its own. The method is analyzed using finite element analysis method and tested using experiments. Our simulation results based on IEC 61215 show that the maximum principal stress and deformation in the critical layers is within limits. Our experimental results prove the proposed theory is feasible and can be extended to large scale solar arrays. Our proposed method is retrofittable and could save money, energy and effort in cleaning the solar arrays, which can replace current techniques.

Nanoparticle (NP)–surfactants formed by the self-assembly of NPs and end-functionalized polymers at the hydrophilic/hydrophobic interface have a wide range of applications in many fields. In this study, the influence of density of amino groups, NPs dimension and pH on the interaction between end-functionalized polymers and NPs were extensively investigated. Single amino-terminated polystyrene (PS-NH2, Mw ≈ 0.6k, 2.5k, 3.5k, 3.9k) and diamino-terminated polystyrene (H2N-PS-NH2, Mw ≈ 1.1k, 2.8k) were prepared using reversible addition–fragmentation chain transfer polymerization and atom transfer radical polymerization. NPs with different dimensions (zero-dimensional carbon dots with sulfonate groups, one-dimensional cellulose nanocrystals with sulfate groups and two-dimensional graphene with sulfonate groups) in the aqueous phase were added into the toluene phase containing the aminated PS. The influence of pH and the molecular weight of amino-terminated PS on the interfacial tension between two phases were investigated. The results indicate that aminated PS exhibited the strongest interfacial activity after compounding with sulfonated NPs at a pH of 3. Terminating PS with amino groups on both ends leads to better performance in in reducing the water/toluene interfacial tension than modifying the molecular structure of PS on a single end. The dimension of sulfonated NPs also contributed significantly to the reduction of the water/toluene interfacial tension. The minimal interfacial tension was 4.49 mN/m after compounding PS-NH2 with sulfonated zero-dimensional carbon dots. Molecular dynamics simulation on the evolution of the water/toluene interface in the presence of sulfonated carbon dots and H2N-PS-NH2 revealed that these opposite charged substances moved towards the interface in an extreme short time and orderly assembled in a thermodynamic equilibrium.

In this paper, first the Self-Written Waveguide (SWW) process in wet photopolymer media (liquid solutions), are examined for three examples: single-, counter-, and co-fibers exposure. Then the SWWs formed inside solid material are examined including the effects of manipulating the alignment of the fibers. In all cases high precision measurements are used to position the fiber optic cables (FOCs) before exposure using a microscope. The self-writing process is indirectly monitored by observing (imaging) the light emerging from the side of the material sample during SWW formation. In this way the optical waveguide trajectories formed in an Acrylamide/Polyvinyl Alcohol (AA/PVA) a photopolymer material (sensitized at 532 nm) are examined. First the transmission of light by this material is characterized. Then the bending and merging of the waveguides which occur are investigated. The predictions of our model are shown to qualitatively agree with the observed trajectories. The largest index changes taking place at any time during the exposure, i.e. during SWW formation, are shown to take place at the positions where the largest exposure light intensity is present. Typically, such maxima exist close to the input face and the first maximum is referred to as the location of the Primary Eye. Other local maxima also appear further along the SWW and are referred to as Secondary Eyes, i.e. deeper within the material.

The work shows a single case intervention based on the motivational coaching model the “Cantón’s Giraffe”, theoretically and experimentally proven in a 20-years-old dancesport practitioner, who considered improving her execution with her dance partner. Methodological triangulation was used [34], combining a test-retest quantitative measure (Using Ryff Psychological Wellbeing Scales; the Rosenberg Self-Esteem Questionnaire and an ad-hoc instrument for the motivational force assessment) and subjective analysis of the responses from the interviews conducted. A three-phase intervention protocol was used [33]: identification, intervention, and follow-up. The results show an improvement in reevaluation scores, an increase in the subjective evaluation, and participant satisfaction and perceived resources raised at the end of the intervention. These results are in line with previous similar studies.

Hydrogels incorporated with hydrophobic motifs have received considerable attention to recapitulate the cellular microenvironments, specifically for the bio-mineralization of a 3D matrix. Introduction of hydrophobic motifs into a hydrogel often results in irregular arrangement of the motifs, and further phase separation of hydrophobic domains, but limited efforts have been made to resolve this challenge in the hydrophobically-modified hydrogel. Therefore, this study presents an advanced integrative strategy to incorporate hydrophobic domains regularly in a hydrogel by self-assembling of polymer cross-linkers, building blocks of a hydrogel. Self-assemblies between polymer cross-linkers were examined as micro-domains to incorporate hydrophobic motifs in a hydrogel. The self-assembled structures in a pre-gelled solution were confirmed with the fluorescence analysis and the hydrophobicity of a hydrogel could be tuned by incorporating the motifs in a controlled manner. Overall, the results of this study would greatly serve to tuning performance of a wide array of hydrophobically-modified hydrogels in drug delivery, cell therapies and tissue engineering.

In recent decades, organizational research has given special attention to the mechanisms promoting the health and wellbeing of nursing professionals. In this context, self-esteem is a personal resource which influences wellbeing at work and psychological wellbeing of nurses. The purpose of this study was to analyze the mediating role of eating in the effect of sleep quality on self-esteem in nursing professionals. The sample of 1073 nurses were administered the Rosenberg General Self-Esteem Scale, the Pittsburgh Sleep Quality Index and the Three-Factor Eating Questionnaire-R18. The results show that poor sleep quality and type of eating directly and indirectly affect self-esteem. More so, poor sleep quality deteriorated self-esteem through emotional eating, and even though emotional eating facilitated disinhibited eating, this relationship had no significant effects on self-esteem. The findings of this study suggest that hospital management should implement employee health awareness programs on the importance of healthy sleep and design educational interventions for improving the quality of their diet.

Positive Occupational Health Psychology (POHP) examines the mechanisms that promote workers’ health and wellbeing, in addition to risk factors arising from work activity. The aim of this study was to analyze the mediating role of perceived stress in the effect that self-efficacy has on engagement in nurses. The sample comprised 1777 currently working nurses. We administered the Utrecht Work Engagement Scale (UWES), the Perceived Stress Questionnaire and the General Self-Efficacy Scale. Following bivariate correlational analysis, multiple linear regression analysis, and simple and multiple mediation analysis the results showed Self-efficacy to be a powerful personal resource that positively predicts employees’ engagement, although the effect diminishes when there are mediating variables of stress. We found differences in the way the different aspects of stress mediated the relationship between Self-efficacy and the engagement dimensions. “Energy–joy” was the strongest mediating variable for all of the engagement dimensions, and this, together with “harassment–social acceptance” dampened the effect of Self-efficacy on vigor and dedication, whereas “Overload” was only a mediator for dedication. Because nurses work in a stressful environment, risk factor arising from work activity, hospital management should design interventions to enhance their workers’ personal resources and improve personal and organizational wellbeing.

Theoretical studies propose an association between family violence and low self-control in adolescence, yet empirical findings of this association are inconclusive. The aim of the present research was to systematically summarize available findings on the relation between family violence and self-control across adolescence. We included 27 studies with 143 effect sizes, representing more than 25,000 participants of eight countries from early to late adolescence. Applying a multi-level meta-analyses, taking dependency between effect sizes into account while retaining statistical power, we examined the magnitude and direction of the overall effect size. Additionally, we investigated whether theoretical moderators (e.g., age, gender, country), and methodological moderators (cross-sectional/longitudinal, informant) influenced the magnitude of the association between family violence and self-control. Our results revealed that family violence and self-control have a small to moderate significant negative association (r = -.191). This association did not vary across gender, country, and informants. The strength of the association, however, decreased with age and in longitudinal studies. This finding provides evidence that researchers and clinicians may expect low self-control in the wake of family violence, especially in early adolescence. Recommendations for future research in the area are discussed.

Controlling surface-protein interaction during wastewater treatment is the key motivation for developing functionally modified membranes. A new biocatalytic thermo-responsive poly(vinylidene fluoride)(PVDF)/nylon-6,6/poly(N-isopropylacrylamide)(PNIPAAm) ultrafiltration membrane was fabricated to achieve dual functionality of protein-digestion and thermo-responsive self-cleaning. The PVDF/nylon-6,6/PNIPAAm composite membranes were constructed by integrating a hydrophobic PVDF cast layer and hydrophilic nylon-6,6/PNIPAAm nanofiber layer where trypsin enzymes were covalently immobilized. The immobilization density of enzymes on the membrane surface decreased with increasing PNIPAAm concentration, due to the decreased number of amine functional sites. Through a ultrafiltration study using a model solution containing BSA/NaCl/CaCl₂, the PNIPAAm containing biocatalytic membranes demonstrated a combined effect of enzymatic and thermo-switchable self-cleaning. The membrane without PNIPAAm revealed superior fouling resistance and self-cleaning with an R_PD of 22%, compared to membranes with 2 and 4 wt% PNIPAAm with 26% and 33% R_PD, respectively, after an intermediate temperature cleaning at 50°C, indicating that higher enzyme density offers more efficient self-cleaning than the combined effect of enzyme and PNIPAAm at low concentration. The conformational volume phase transition of PNIPAAm did not affect the stability of immobilized trypsin on membrane surface. Such novel surface engineering design offer a promising route to severe surface-protein contamination remediation in food and wastewater applications.

This paper presents a study of different types of parametric signals with application to underwater acoustic communications. In all the signals, the carrier frequency is 200 kHz, which corresponds to the resonance frequency of the transducer under study and different modulations are presented and compared. In this sense, we study modulations with parametric sine sweeps (4 to 40 kHz) that represent binary codes (zeros and ones), getting closer to the application in acoustic communications. The different properties of the transmitting signals in terms of bit rate, directivity, efficiency and power needed are discussed as well.

The threat of antimicrobial resistance to society is compounded by a relative lack of new clinically effective licensed therapies reaching patients over the past three decades. This has been particularly problematic within antifungal drug development leading to a rise in fungal infection rates and associated mortality. This paper highlights the potential of an ultrashort peptide, (naphthalene-2-ly)-acetyl-diphenylalanine-dilysine-OH (NapFFKK-OH), encompassing hydrogel-forming and antifungal properties within a single peptide motif, thus overcoming formulation (e.g. solubility, drug loading) issues associated with many current employed highly hydrophobic antifungals. A range of fungal susceptibility (colony counts) and cell cytotoxicity (MTS cell viability, LIVE/DEAD staining® with fluorescent microscopy, haemolysis) assays were employed. Scanning electron microscopy confirmed the nanofibrous architecture of our self-assembling peptide, existing as a hydrogel at concentrations of 1% w/v and above. Broad-spectrum activity was demonstrated against a range of fungi clinically relevant to infection (Aspergillus niger, Candida glabrata, Candida albicans, Candida parapsilosis and Candida dubliniensis) with greater than 4 log10 CFU/mL reduction at concentrations of 0.5% w/v and above. We hypothesise antifungal activity is due to targeting of anionic components present within fungal cell membranes resulting in membrane disruption and cell lysis. NapFFKK-OH demonstrated reduced toxicity against mammalian cells (NCTC 929, ARPE-19) suggesting increased selectivity for fungal cells. However, further studies relating to safety for systemic administration is required, given the challenges toxicity has presented in the wider context of antimicrobial peptide drug development. Overall this study highlights the promise of NapFFKK-OH hydrogels, particularly as a topical formulation for the treatment of fungal infections relating to the skin and eyes, or as a hydrogel coating for the prevention of biomaterial related infection.

The critical changes in physical appearance during adolescence can considerably influence the self-appraisal of body image. The purpose of this study is to analyze body self-image gender differences in Mediterranean adolescents, and his relationships to the anthropometric characteristics of this population in different phases of the adolescence. Participants were 809 Mediterranean teenagers (396 females) aged 11 to 17. A relative low prevalence of dissatisfaction with body image was observed among healthy urban Mediterranean adolescents (boys 17.3%; girls 22.7%). Girls showed statistically significantly higher mean BSQ scores than boys (M = 61.7, SD = 26.6 versus M = 56.3, SD = 27.1; p < 0.001). Girls in the late adolescence were more often classified as being dissatisfied (31%) in comparison to those in the early adolescent group (19.1%; p < 0.05). There was a good correlation of BSQ scores with all the anthropometric variables in males but not in females.

Personal health data is acquired, processed, stored, and accessed using a variety of different devices, applications, and services. These are often complex and highly connected. Therefore, use or misuse of the data is hard to detect for people, if they are not capable to understand the trace (i.e., the provenance) of that data. We present a visualization technique for personal health data provenance using comics strips. Each strip of the comic represents a certain activity, such as entering data using a smartphone application, storing or retrieving data on a cloud service, or generating a diagram from the data. The comic strips are generated automatically using recorded provenance graphs. The easy-to-understand comics enable all people to notice crucial points regarding their data such as, for example, privacy violations.

This article will examine the ambivalence in the views of Jewish authorities towards suicide. There are Jewish rulings which forbid the taking of one's own life, including requested euthanasia. There are seemingly contrary rulings which tolerate and sometimes admire suicide, particularly under conditions of religious persecution. The article will attempt an overview of suicide rates in Jewish communities, indicating variations in different circumstances. The question of whether religiosity affects suicide will be raised and examined. These variations—and of course other factors—may offer some clues to the precursors of suicide, and the processes which may be involved. The causal and risk factors in self-harm among Jews will also be examined. The article then turns to post-suicide events, behaviours and attitudes in Jewish communities.

Medically underserved communities have limited access to effective disease management resources in the U.S. Mobile health applications (mHealth apps) offer patients a cost-effective way to monitor and self-manage their condition and to communicate with providers; however, current diabetes self-management apps have rarely included end-users from underserved communities in the design process. This research documents key stakeholder-driven design requirements for a diabetes self-management app for medically underserved patients. Semi-structured survey-interviews were carried out with 97 patients with diabetes and 11 healthcare providers from medically underserved counties in South Texas to elicit perspectives and preferences regarding a diabetes self-management app, and their beliefs regarding such an app’s usage and utility. Patients emphasized the need for accessible educational content and for quick access to guidance on regulating blood sugar, diet, and exercise and physical activity using multimedia rather than textual form. Healthcare providers indicated that glucose monitoring, educational content, and graphical visualization of diabetes data were among the top-rated app features. These findings suggest that specific design requirements for the underserved may improve the adoption, usability, and sustainability of such interventions. Designers should consider health literacy and numeracy, linguistic barriers, data visualization, data entry complexity, and information exchange capabilities.

This review focuses on the regulation and modulation of human DNA polymerase δ (Pol δ). The emphasis is on mechanisms that regulate the activity and properties of Pol δ in DNA repair and replication. The areas covered are the degradation of the p12 subunit of Pol δ, which converts it from a heterotetramer (Pol δ4) to a heterotrimer (Pol δ3), in response to DNA damage and also during the cell cycle. The biochemical mechanisms that lead to degradation of p12 are reviewed, as well as the properties of Pol δ4 and Pol δ3 that provide insights into their functions in DNA replication and repair. The second focus of the review involves the functions of two Pol δ binding proteins, PDIP46 and PDIP38, both of which are multi-functional proteins. PDIP46 is a novel activator of Pol δ4, and the impact of this function is discussed in relation to its potential roles in DNA replication. Several new models for the roles of Pol δ3 and Pol δ4 in leading and lagging strand DNA synthesis that integrate a role for PDIP46 are presented. PDIP38 has multiple cellular localizations including the mitochondria, the splicesosomes and the nucleus. It has been implicated in a number of cellular functions, including the regulation of specialized DNA polymerases, mitosis, the DNA damage response, Mdm2 alternative splicing and the regulation of the Nox4 NADPH oxidase.

Abstract Introduction There is a clear link between self-medication practice and ongoing pandemic diseases like COVID-19, According to studies conducted globally and the general Ethiopian population turned to self-medication and symptomatic treatment as a result of inadequate COVID-19 treatment and also about 80% of the population amassed drugs for pandemic use. Objective: The objective of this study was to assess self-medication practice for treatment of Covid-19 and reason to use self- medication among residents in Bedelle city and its surrounding, Southwest Oromia, Ethiopia. Methodology: A cross sectional study design was employed and the standardized questionnaire was developed by reviewing relevant literatures then the data was collected using face to face interview. Final data was analyzed by using SPSS version 23. Result: The final study contained 415 respondents in total, with a response rate of 98.5%. The majority of responses were females and between the ages of 18 - 25 Category. In this study population, the use of self-medication since the onset of the Covid-19 epidemic was reported by participants were around 50.6%. Analgesics (42.4%) and cold medicines (29.5%) were the most frequently used medications for treatment of COVID-19. Also the reported uses of these drugs included treatment of Covid-19 symptoms like the Headache (22.2%), Fever (13.2%), respiratory infective (14.3%), and cold (21.4%) were the most frequently reported symptoms for self-medication. Self-medication methods were used more frequently by women than Men. Conclusion: According to this study, analgesics and cold medications are commonly self- medicated drugs used for Covid-19 therapy. It is a serious health concern, particularly when COVID-19 symptoms are present, and high consumption of self-medication has been linked to COVID-19 prevention or treatment. Key words: Covid-19, Medicine, Practice, Bedelle city, Self-Medication