ARTICLE | doi:10.20944/preprints201902.0172.v4
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: RNA-dependent amplification of mammalian mRNA; physiologically occurring intracellular PCR, iPCR; RNA-dependent RNA polymerase, RdRp; chimeric RNA; sense-strand RNA; antisense-strand RNA
Online: 12 June 2019 (12:21:59 CEST)
The transfer of protein-encoding genetic information from DNA to RNA to protein, a process formalized as the “Central Dogma of Molecular Biology”, has undergone a significant evolution since its inception. It was amended to account for the information flow from RNA to DNA, the reverse transcription, and for the information transfer from RNA to RNA, the RNA-dependent RNA synthesis. These processes, both potentially leading to protein production, were initially described only in viral systems, and although RNA-dependent RNA polymerase activity was shown to be present, and RNA-dependent RNA synthesisfound to occur, in mammalian cells, its function was presumed to be restricted to regulatory. However, recent results, obtained with multiple mRNA species in several mammalian systems, strongly indicate the occurrence of protein-encoding RNA to RNA information transfer in mammalian cells. It can result in the rapid production of the extraordinary quantities of specific proteins as was seen in cases of terminal cellular differentiation and during cellular deposition of extracellular matrix molecules. A malfunction of this process may be involved in pathologies associated either with the deficiency of a protein normally produced by this mechanism or with the abnormal abundanceof a protein or of its C-terminal fragment. It seems to be responsible for some types of familial thalassemia and may underlie the overproduction of beta amyloid in sporadic Alzheimer’s disease. The aim of the present article is to systematize the current knowledge and understanding of this pathway. The outlined framework introduces unexpected features of the mRNA amplification such as its ability to generate polypeptides non-contiguously encoded in the genome, its second Tier, a physiologically occurring intracellular polymerase chain reaction, iPCR, a Two-Tier Paradox and RNA Dark Matter. RNA-dependent mRNA amplification represents a new mode of genomic protein-encoding information transfer in mammalian cells. Its potential physiological impact is substantial, it appears relevant to multiple pathologies and its understanding opens new venues of therapeutic interference, it suggests powerful novel bioengineering approaches and its further rigorous investigations are highly warranted.
HYPOTHESIS | doi:10.20944/preprints202003.0021.v2
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: virus; population bottleneck; positive sense RNA virus; evolution
Online: 1 October 2020 (08:28:45 CEST)
Many positive sense RNA viruses, especially those infecting plants, are known to experience stringent, stochastic population bottlenecks inside the cells they invade, but exactly how and why these populations become bottlenecked are unclear. A model proposed ten years ago advocates that such bottlenecks are evolutionarily favored because they cause the isolation of individual viral variants in separate cells. Such isolation in turn allows the viral variants to manifest the phenotypic differences they encode. Recently published observations lend mechanistic support to this model, and prompt us to refine the model with novel molecular details. The refined model, designated Bottleneck, Isolate, Amplify, Select (BIAS), postulates that these viruses impose population bottlenecks on themselves by encoding bottleneck-enforcing proteins (BNEPs) that function in a concentration-dependent manner. In cells simultaneously invaded by numerous virions of the same virus, BNEPs reach the bottleneck-ready concentration sufficiently early to arrest nearly all internalized viral genomes. As a result, very few (as few as one) viral genomes stochastically escape to initiate reproduction. Repetition of this process in successively infected cells isolate viral genomes with different mutations in separate cells. This isolation prevents mutant viruses encoding defective viral proteins from hitchhiking on sister genome-encoded products, leading to the swift purging of such mutants. Importantly, genome isolation also ensures viral genomes harboring beneficial mutations accrue the cognate benefit exclusively to themselves, leading to the fixation of such beneficial mutations. Further interrogation of the BIAS hypothesis promises to deepen our understanding of virus evolution, and inspire new solutions to virus disease mitigation.
REVIEW | doi:10.20944/preprints201909.0212.v1
Subject: Biology And Life Sciences, Virology Keywords: positive-sense single-stranded rna viruses; innate immune evasion; type 1 interferon; viral pathogenesis; type 3 interferon
Online: 18 September 2019 (17:12:01 CEST)
Positive-sense single-stranded RNA (+ssRNA) viruses comprise many (re-)emerging human pathogens that pose a public health problem. Our innate immune system and in particular the interferon response form the important first line of defense against these viruses. Given their genetic flexibility, these viruses have therefore developed multiple strategies to evade the innate immune response in order to optimize their replication capacity. Already many molecular mechanisms of innate immune evasion by +ssRNA viruses have been identified. However, research addressing the effect of host innate immune evasion on the pathology caused by the viral infection is less prevalent in literature, though very relevant and interesting. Since interferons have been implicated in inflammatory diseases and immunopathology in addition to their protective role in infection, the influence of antagonizing the immune response may have an ambiguous effect on the clinical outcome of the viral disease. Therefore, this review discusses what is currently known about the role of interferons and host immune evasion in the pathogenesis of emerging viruses belonging to the coronaviruses, alphaviruses and flaviviruses.
ARTICLE | doi:10.20944/preprints202207.0358.v1
Subject: Biology And Life Sciences, Virology Keywords: Foot-and-mouth disease virus; safe sample transport; single-stranded positive-sense RNA; TRIzol extraction; naked RNA; infectivity; RNA transfection; lipofectamine; self-transfection; BHK cells
Online: 25 July 2022 (08:14:51 CEST)
Safe sample transport is of great importance for infectious diseases diagnostics. Various treatments and buffers are used to inactivate pathogens in diagnostic samples. At the same time, adequate sample preservation, particularly of nucleic acids, is essential to allow an accurate laboratory diagnosis. For viruses with single-stranded RNA genomes of positive polarity, such as foot-and-mouth disease virus (FMDV), however, naked full-length viral RNA can itself be infectious. In order to assess the risk of infection from inactivated FMDV samples, two animal experiments were performed. In the first trial, six cattle were injected with FMDV RNA (isolate A22/IRQ/24/64) into the tongue epithelium. All animals developed clinical disease within two days and FMDV was reisolated from serum and saliva samples. In the second trial, another group of six cattle was exposed to FMDV RNA by instilling it on the tongue and spraying it into the nose. The animals were observed for 10 days after exposure. All animals remained clinically unremarkable and virus isolation as well as FMDV genome detection in serum and saliva were negative. No transfection reagent was used for any of the animal inoculations. In conclusion, cattle can be infected by injection with naked FMDV RNA, but not by non-invasive exposure to the RNA. Inactivated FMDV samples that contain full-length viral RNA carry only a negligible risk of infecting animals.
ARTICLE | doi:10.20944/preprints202303.0188.v1
Subject: Medicine And Pharmacology, Orthopedics And Sports Medicine Keywords: kinesiology tape; maximum isometric voluntary contraction; joint position sense; force sense; proprioception
Online: 10 March 2023 (08:50:49 CET)
(1) Background: Within the scope of prevention studies, many researchers have indicated the need to enhance knee proprioception. Kinesiology tape is one product that claims to enhance proprioception, however, its use has not been well researched in the healthy population before. The aim of the study was to investigate if kinesiology tape application on the quadriceps muscle enhances proprioception. (2) Methods: Twelve healthy and physically active volunteers (M=7, F=5, mean age= 20.75 ± 2.14, mean BMI=22.25 ±2.34) participated in the study. With computerized, custom-built isokinetic dynamometer, we recorded perceived joint position angles (small and large angles). For force sense, we recorded maximum voluntary isometric contractions (MVIC) and differences in torques (Nm) via force matching tasks both with vision and without vision on left leg. The absolute errors for joint position sense measurements and for force matching tasks and differences in MVIC both in untaped and taped conditions for left legs of all subjects were recorded. (3) Results: Two-way repeated measures ANOVA revealed that no significant interaction existed among small and large angle groups in both the conditions nor any main condition effect was observed in both the groups. (p>0.05). Similarly, no differences were accounted in force matching tasks between the taped and un-taped with vision and without vision (p=0.52 and 0.38 respectively.) Statistically insignificant increments were observed in mean torque post application. (p=0.67) (4) Conclusions: Present study suggests that immediate kinesiology tape application on quadriceps muscle offers no benefits on proprioception in terms of joint position sense and force sense hence other preventive measures to strengthen the proprioceptive system should be relied upon.
ARTICLE | doi:10.20944/preprints202111.0272.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: miR-155; FUBP1; strand selection; interleukin-10
Online: 15 November 2021 (19:24:40 CET)
MicroRNA-155 (miR-155) expression promotes inflammatory responses in macrophages. Activation of macrophages with lipopolysaccharide (LPS) elevates miR-155, while the anti-inflammatory cytokine interleukin-10 (IL10) reduces miR-155 levels. MiR-155 exists in two forms, miR-155-5p and miR-155-3p, produced from the precursor of miR-155 (pre-miR-155). MiR-155-5p is the most abundant strand in activated macrophages, but in response to LPS, the miR-155-3p level is upregulated first, followed by miR-155-5p later. We have previously identified CELF2 protein which interacts with pre-miR-155 and impairs miR-155-5p expression. We now show that CELF2 only regulates the miR-155-5p expression and that another protein FUBP1 controls miR-155-3p levels in response to LPS and IL10.
ARTICLE | doi:10.20944/preprints202201.0293.v2
Subject: Arts And Humanities, Philosophy Keywords: sense making analysis; critical phenomenology; sustainability transformations
Online: 13 October 2022 (09:26:33 CEST)
Transformation studies have been leaning towards the more practical aspects of change processes and have not yet dealt sufficiently with their personal and political dimensions. They are arguably constrained in doing so if they are either overly focussed on systems and how to control them or on individualistic values and behaviours. In this study we show how the actually-occurring societal transformations that people face can be usefully approached through the lenses of dialogical sense-making and critical phenomenology. While distinct, these approaches share a concern with aspects missed when transformation is abstracted and alienated from people’s lives; namely people’s lived experiences during times of change, and the conditions of possibility for these experiences. Dialogical sense-making explores how people create meaning around transformations, through interactions with other people, with different lines of arguments, and as part of broader public discourse. Critical phenomenology engages with subjectivity and lived experience, and with the role of foundational as well as socio-culturally dominant yet contingent structures in shaping our ways of perceiving, experiencing and knowing the world. Through a discussion of insights from these approaches, we show how they offer tools that enable new questions about transformative change as it is experienced and made sense of. Situating analyses of tranformation from within a focus on experience brings us closer to understanding the significance of change processes in people’s lives, and allows for an inquiry into the conditions of experience, including transformative experiences.
ARTICLE | doi:10.20944/preprints202310.0449.v1
Subject: Engineering, Civil Engineering Keywords: steel strand; GUW; signal denoising; VMD; SampEn-SVD
Online: 9 October 2023 (08:54:50 CEST)
The guided ultrasonic wave (GUW) is extensively employed in non-destructive testing (NDT) for the purpose of detecting defects in aerospace vehicles, oil pipelines and mechanical equipment. The filtration of GUW signals, which often contain substantial environmental noise, is a crucial procedure in signal processing. This paper presents a novel denoising approach that combines Variational Mode Decomposition (VMD) with an enhanced Singular Value Decomposition (SVD). The VMD method is employed to preprocess the initial signal, thereby segregating the signal component from the noise component. Subsequently, the SampEn-SVD (Sample Entropy-SVD) method is utilized to extract the effective component from the VMD-preprocessed noise component. Finally, the VMD-preprocessed signal component and the SampEn-SVD-processed effective component are combined to yield the resultant signal, which effectively filters out the noise. The efficacy of this integrated denoising approach is substantiated through the examination of experimental signals. Furthermore, a comparative analysis is conducted to evaluate the efficacy of this method in relation to other denoising techniques. The results indicate that the SampEn-SVD method yields a superior signal-to-noise ratio (SNR) when processing the GUW signal transmitted through the steel strand. Moreover, the denoising procedure significantly reduces the discretization of characteristic parameters in the signal waveform, thereby addressing the issue of inadequate reproducibility in testing outcomes. Consequently, the denoised signal exhibits high fidelity and demonstrates a strong correlation between its combined eigenvector and strand stress.
ARTICLE | doi:10.20944/preprints202106.0264.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: PEGDA Hydrogels; 3D recognition; diffusion; strand displacement assay.
Online: 9 June 2021 (11:45:54 CEST)
The control of the three-dimensional (3D) polymer network structure is important for permselective materials when specific biomolecules detection is needed. Here we investigate conditions to obtain a tailored hydrogel network that combine both molecular filtering and molecular capture capabilities for biosensing applications. Along this line short oligonucleotide detection in a displacement assay is set within PEGDA hydrogels synthetized by UV radical photopolymerization. To provide insights on the molecular filter capability, diffusion studies of several probes (sulforhodamine G and dextrans) with different hydrodynamic radii were carried out using NMR technique. Moreover, fluorometric analyses of hybridization of DNA oligonucleotides inside PEGDA-hydrogels shed light on the mechanisms of recognition in 3D, highlighting that mesh size and crowding effect greatly impact of hybridization mechanism onto polymer network. Finally, we found the best probe density and diffusion transport conditions to allow the specific oligonucleotide capture and detection inside PEGDA-hydrogels for oligonucleotide detection and the filtering out of higher molecular weight molecules.
ARTICLE | doi:10.20944/preprints201911.0292.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: NHEJ; double-strand breaks; mouse model; lymphocyte; neurodevelopment
Online: 24 November 2019 (15:57:38 CET)
Classical non-homologous end joining (NHEJ) is a molecular pathway that detects, processes and ligates DNA double-strand breaks (DSBs) throughout the cell cycle. Mutations in several NHEJ genes result in neurological abnormalities and immunodeficiency both in humans and mice. The NHEJ pathway is required for the V(D)J recombination in developing B and T lymphocytes, and for class switch recombination in mature B cells. Ku heterodimer formed by Ku70 and Ku80 recognizes DSBs and facilitates the recruitment of accessory factors (e.g., DNA-PKcs, Artemis, Paxx and Mri/Cyren) and downstream core factors subunits XLF, XRCC4 and Lig4. Accessory factors might be dispensable for the process depending on the genetic background and DNA lesion type. To determine the physiological role of Mri in DNA repair and development, we introduced frame-shift mutation in the Mri gene in mice. We then analyzed the development of Mri-deficient mice as well as wild type and immunodeficient controls. Mice lacking Mri possessed reduced levels of class switch recombination in B lymphocytes and slow proliferation of neuronal progenitors when compared to wild type littermates. Human cell lines lacking Mri were as sensitive to DSBs as WT controls. Overall, we concluded that Mri/Cyren is largely dispensable for DNA repair and mouse development.
ARTICLE | doi:10.20944/preprints202209.0110.v1
Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: ADHD; Antisocial Behavior; Sense of Coherence; Protective Factors
Online: 7 September 2022 (11:03:25 CEST)
Numerous studies have established the link between ADHD and antisocial behavior, one of the most serious functional impairments caused by the disorder. However, research on protective factors that mitigate this link is still lacking. The Salutogenic Model of Health offers the “Sense of Coherence” (SOC), establishing that individuals who see their lives as logical, meaningful, and manageable are more resistant to various risk factors and diseases. The present study examines for the first time whether SOC is also a protective factor against ADHD-related different types of antisocial behaviors (severe/mild violent behavior, verbal violence, property crimes, public disorder, and drug abuse). 2260 participants aged 15-50 completed online questionnaires assessing the level of ADHD symptoms, antisocial behaviors, and SOC. An interaction between ADHD and SOC was found in predicting each type of antisocial behavior. The link between ADHD and antisocial behavior was significantly weaker for high than low SOC participants, regardless of age group. The current study found that people with high SOC are protected against the effect of ADHD on one of the most serious functional impairments, antisocial behavior. These findings suggest that SOC is a protective factor from the adverse effects of ADHD, justifying further prospective and intervention studies.
ARTICLE | doi:10.20944/preprints201802.0167.v1
Subject: Social Sciences, Safety Research Keywords: CBD; planning and design policies; sense of safety
Online: 26 February 2018 (12:07:42 CET)
Planning, development and design policies influence sense of safety of people touse the City centre or Central Business District (CBD) and therefore city centres can becomeactive and vibrant during the day and night. This paper reviews past and present planningpolicies relevant for feeling of personal safety in the context of housing, retail, amenities,street infrastructure, building design and transportation aspects. The past development trendsshow that insignificant attention has been paid to people's sense of safety when using publicspaces, particularly at night, a factor identified important in creating attractive city centressince 1960s. Local plans primarily refer to safety in relation to roads, accessibility andworkability. Local policies also show the dominance of CCTV since the 1990s has becomeubiquitous, but changes to sense of safety in urban spaces now may actually be a betterreflection of planning and design decisions made over the past 20 years.
ARTICLE | doi:10.20944/preprints202308.1216.v1
Subject: Chemistry And Materials Science, Analytical Chemistry Keywords: Voltammetry, bio current, feeling sense, in vivo, brain wave
Online: 16 August 2023 (13:48:36 CEST)
As the human-body controls depend on the brain neuro current, here assay is related to thinking nerve detection. For this purpose, the brain current was analyzed by electrochemical three-electrode systems using 0.1-mm micro wire in vivo probe, which probe was made by using carbon nanotube paste coated needle type. Here working electrode was inserted in the rat brain’s muscle core with a 0.3-mm-diameter needle type Ag/AgCl Cl-coated Ag wire reference, and counter electrode of 0.1-mm-diameter Pt micro needle was inserted 5 mm deep into the in vivo muscle skin, under anesthesia with 2.0 ~ -2.0 V potential windows, 50 mv/s cyclic scan and 1.0x10-5A chrono amperometric sensitivity on the body systems. Under the optimum conditions, diagnostic application was performed to such as smell signal, muscular strength, five sense assay and thinking neuro current.
ARTICLE | doi:10.20944/preprints202105.0749.v1
Subject: Social Sciences, Psychology Keywords: psychological distress; loneliness; sense of mastery; adolescents; young adults
Online: 31 May 2021 (11:35:42 CEST)
Background and aims Loneliness and a low sense of mastery have been associated with excessive gambling, but the underlying processes of these relationships remain unstudied. Because psychological distress can increase vulnerability to excessive gambling, we investigated its mediating role in these relationships among young people. To meet the need for cross-country research, we also observed how these relationships occur in four countries with different cultures. Design, setting and participants Demographically balanced cross-sectional survey data were collected for 15–25-year-olds in Finland (n=1200; 50% male), the United States (n=1212; 49.8% male), South Korea (n=1192; 49.6% male) and Spain (n=1212; 51.2% male). Measurements Excessive gambling was measured with the South Oaks Gambling Screen, psychological distress was assessed with the 12-Item General Health Questionnaire, loneliness was measured with the Three-Item Loneliness Scale and low sense of mastery was assessed with the Pearlin Mastery Scale. Associations were examined first using zero-inflated negative binomial regression analyses with excessive gambling as the outcome. In addition, path analyses were performed to study how loneliness and low sense of mastery relate to excessive gambling, with psychological distress as the mediating variable. Findings Loneliness and low sense of mastery were associated indirectly with excessive gambling via psychological distress in all country samples. Low sense of mastery was also directly associated with excessive gambling. There was a direct association between loneliness and excessive gambling only in samples from South Korea and Spain. Conclusions Psychological distress is an important factor in understanding how loneliness and sense of mastery relate to gambling.
ARTICLE | doi:10.20944/preprints201801.0281.v1
Subject: Arts And Humanities, Humanities Keywords: migrants; sense of belonging; small town; stranger; South Sudanese
Online: 30 January 2018 (10:35:53 CET)
Australian regional areas are now receiving significant numbers of migrants from the African continent. Predominantly Anglo-Saxon communities perceive these ‘newcomers’ as physically and culturally different. Asking, however, how African migrants themselves construct relationships with local communities and build a sense of belonging in regional and rural areas is a very different question. This paper explores South Sudanese migrants’experiences conceptualising their sense of belonging in a small county town: Castlemaine, Victoria. Focus group discussions show that even with the welcoming atmosphere and support from the local community, South Sudanese migrants are still attracted to metropolitan environments that have greater diversity, feeling more at home in such settings. Using the theoretical background of a stranger, this paper argues the cities allow strangers be un-noticed letting them feel at ‘home’. Findings from the study show settings with greater diversity encourage negotiating difference openly and easing power imbalances among different groups.Finally, the locality of Castlemaine, within easy commuting distance to metropolitan Melbourne and suburbs, is considered in relation to hypermobility reducing the capacity to construct ‘bridging capital’ within such local communities.
ARTICLE | doi:10.20944/preprints202311.1638.v1
Subject: Chemistry And Materials Science, Physical Chemistry Keywords: Smoke Toxicity; Large-Scale; Oriented Strand Board; ISO 9705; Flammability
Online: 28 November 2023 (01:40:57 CET)
As smoke toxicity is unregulated outside of the mass transport industry, there is no set methodology for assessing smoke toxicity of construction products, like OSB, on a large-scale. This research aims to assess the novel design of a modified ISO 9705 room corner test designed for smoke toxicity quantification. Three tests conditions will be assessed to determine if restriction of ventilation is enough to force a fire to transition to under-ventilated flaming, or if the fuel loading is much more important in affecting the fire severity and fire condition. The research found that fuel loading and test geometry has more significant impact on the fire condition than restricting the ventilation. While imposing restrictions on the test rooms ventilation did increase the equivalence ratio, it was not sufficient enough to force the transition into under-ventilated flaming. The addition of a door to the test room did not force the fire to transition to under-ventilated flaming. When doubling the fuel loading, there was sufficient fuel for the fire to transition to under-ventilated flaming. This research has provided the experimental methodologies to assess smoke toxicity at a range of ventilation conditions on a large-scale.
ARTICLE | doi:10.20944/preprints202103.0077.v1
Subject: Engineering, Automotive Engineering Keywords: multi-strand cable lines; ampacity; coupled electromagnetic and thermal phenomena
Online: 2 March 2021 (11:16:25 CET)
The paper is focused on numerical modeling of multi-strand cable lines placed in free air. Modeling is carried out within the framework of the so-called multi-physics approach using commercial software. The paper describes in detail the steps undertaken to develop realistic, reliable numerical models of power engineering cables, taking into account their geometries and heat exchange conditions. The results might be of interest to the designers of multi-strand cable systems.
ARTICLE | doi:10.20944/preprints202009.0627.v1
Subject: Engineering, Automotive Engineering Keywords: multi-strand cable lines; ampacity; skin and proximity effects; symmetry
Online: 26 September 2020 (12:17:53 CEST)
Skin and proximity effects have a considerable impact on current distribution in multi-strand cable lines. Under unfavorable heat exchange conditions some strands may be subject to excessive overheating, what may lead to serious malfunctions or even fires of the installation. The paper proposes a new criterion for a quick choice of spatial configurations, for which the effect might be minimized. A comprehensive analysis of literature cases is provided, including the recommendations of the U.S. National Code and the Canadian standard.
ARTICLE | doi:10.20944/preprints202310.1899.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: motor recovery; neurorehabilitation; proprioceptive impairment; position sense; thumb localizing test
Online: 30 October 2023 (10:32:01 CET)
Proprioceptive deficits accompanied with motor paresis after stroke, namely sensory ataxic motor paresis has a poorer prognosis of recovery than pure motor deficit. We aimed to investigate the effects of repetitive peripheral magnetic stimulation (rPMS) on sensory ataxic upper extremity (UE) paresis at acute stroke. Eighteen stroke participants with sensory ataxic UE paresis were randomized. rPMS group received five sessions of intervention per week, where 20 minutes of rPMS prior to 20 minutes of physical therapy (PT) every other day, alternating with 40 minutes of PT. The control group received five sessions of 40 minutes of PT/week. Outcome measures were Wolf motor function test (WMFT), UE motor section of Fugl-Meyer Motor Assessment Scale (FMA-UE), and Thumb localizing test (TLT). All assessments were compared before and after intervention. rPMS group received mean 6.5 sessions and the control group received 12.8 sessions, showing significantly imbalanced intervention due to different timing of hospital discharge. The imbalance was corrected by calculating gains of motor scores divided by sessions as Progress Rate (PR). Corrected gains (PR) of rPMS group was more significantly enhanced in WMFT and FMA-UE than control groups. rPMS group tended to improve TLT more than control one. rPMS might improve sensory ataxic UE paresis after stroke and proprioceptive deficit.
ARTICLE | doi:10.20944/preprints202107.0626.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: tilapia; negative-sense RNA virus; Tilapia lake virus; DNA vaccine
Online: 28 July 2021 (11:11:37 CEST)
Tilapia lake virus (TiLV) is the main tilapia-infecting virus worldwide, causing serious economic losses. However, there is no vaccine for this viral disease. Here, TiLV ORF10 (TiLV-ORF10) encoding a protein with abundant epitopes was constructed into the eukaryotic expression vector pcDNA3.1, and used to evaluate the immune protective effects in Nile tilapia (Oreochromis niloticus). RT-PCR and western blot analyses conﬁrmed vaccine plasmid expression in tilapia muscle tissues. Moreover, the transcription levels of immunoglobulin M, toll-like receptor 2, myeloid differentiation factor 88, interleukin 8, tumor necrosis factor alpha, gamma-IFN, and nuclear factor κB immune-related genes were statistically signiﬁcantly upregulated in the spleen, liver, and kidney of vaccinated tilapias (P < 0.05). TiLV challenge experiments showed that relative percent survival (RPS) was signiﬁcantly enhanced in ﬁsh by this DNA vaccine. Moreover, RPS was enhanced further when using a higher amount of the DNA vaccine (85.72% RPS at a DNA dose of 45 μg pcDNA3.1–ORF10). Vaccination with pcDNA3.1–ORF10 signiﬁcantly reduced virus replication, as evidenced by the low amount of virus in the spleen, liver, and kidney of vaccinated tilapias after TiLV challenge. Thus, pcDNA3.1–ORF10 could induce protective immunity in tilapia and may be a potential vaccine candidate for controlling diseases caused by TiLV.
ARTICLE | doi:10.20944/preprints202202.0071.v1
Subject: Physical Sciences, Particle And Field Physics Keywords: quantum electrodynamics; electron mass; fine structure constant; strand conjecture; tangle model.
Online: 4 February 2022 (10:50:03 CET)
A geometric Planck-scale model of quantum electrodynamics is tested against observations. Based on Dirac’s proposal to describe spin 1/2 particles as tethered objects, elementary fermions are conjectured to be fluctuating rational tangles with unobservable tethers. As Battey-Pratt and Racey showed, when such tangles propagate, they obey the free Dirac equation. Classifying rational tangles yields the observed spectrum of elementary fermions. Classifying deformations of tangle cores yields exactly three types of gauge interactions. They exchange three types of elementary gauge bosons and have the symmetry groups U(1), broken SU(2) and SU(3). The possible rational tangles for fermions, Higgs and gauge bosons allow only the observed Feynman diagrams. The complete Lagrangian of the standard model arises, including the Lagrangian of quantum electrodynamics. Over 50 tests of the tangle model are deduced. They include details on the perturbation expansion of the g-factor and the existence of limit values for electric and magnetic fields. Measurements agree with most tests, though this could change in the future. Some tests are genuine predictions that still need to be checked. In particular, the geometry of the process occurring at QED interaction vertices suggests an ab-initio estimate for the fine structure constant. In addition, the average geometric shapes of the elementary particle tangles suggest ab-initio lower and upper limits for the mass values of the electron and the other leptons.
ARTICLE | doi:10.20944/preprints202103.0621.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Auger electron; cisplatin; 191Pt; 189Pt; radio-drug; DNA double-strand break; γH2AX
Online: 25 March 2021 (14:30:14 CET)
Due to their short range (2–500 nm), Auger electrons (Auger e-) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Au-ger e-, it remains challenging to maximize the interaction between Auger e- and DNA. To assess the DNA-damaging effect of Auger e- released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [189, 191Pt]cisplatin and evaluated both its in vitro properties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by im-munofluorescence staining of γH2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio-Pt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a. radio-cisplatin was low (0.6% incubated dose after 25-h incuba-tion), resulting in the frequency of cells with γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by release of Auger e- very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger e-.
ARTICLE | doi:10.20944/preprints202310.1895.v1
Subject: Computer Science And Mathematics, Mathematics Keywords: limited number; different physical spaces; mathematics sense; number belongs to space
Online: 30 October 2023 (10:11:09 CET)
Bounded number theory says that number is not infinite; that is, the number is limited. To come to a conclusion about limited number, one needs to understand the meaning of math and varying spaces, so one needs to understand that math and spaces interact. A matemática tem a função de descrever com precisão o mundo, onde os números representam elementos ou fatos que racionalmente elementos ou fatos pertencem ao espaço, e os espaços têm propriedades que os diferenciem de outros espaços; portanto, não há nenhum elemento ou fato infinito devido a diferenças nas propriedades dos espaços não permite o elemento ou fato em todos os espaços.
ARTICLE | doi:10.20944/preprints202305.1736.v1
Subject: Public Health And Healthcare, Public, Environmental And Occupational Health Keywords: Urban Garden; Perceived Restorativeness; Resillience; Sense of Community; Stress; Salivary cortisol
Online: 25 May 2023 (05:10:25 CEST)
This study aimed to investigate the influence of urban garden activities on participants' Perceived restorativeness, resilience, sense of community, and stress reduction. Ninety individuals who agreed to participate to the experiment were divided into experimental and control groups. To collect data 16 sessions of urban garden activities were conducted every two weeks from May to November of 2022. Perceived Restorativeness Scale, Conner-Davidson Resilience Scale, Sense of Community Index, and Brief Encounter Psychosocial Instrument were employed to measure participants’ psychological effects. To evaluate physiological effect salivary cortisol tests were performed. The results of the study revealed that urban gardening activities influenced on participants' physiological and psychological reactions in positive ways.
ARTICLE | doi:10.20944/preprints202105.0322.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Virus; plant virus; long noncoding RNA; replication; positive sense RNA virus
Online: 14 May 2021 (11:01:56 CEST)
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.
COMMUNICATION | doi:10.20944/preprints201911.0386.v1
Subject: Social Sciences, Area Studies Keywords: multi-stakeholder processes; sustainability transformations; sense-making; strategy; theory of change
Online: 30 November 2019 (09:52:47 CET)
The commonly used words ‘transformation’ and ‘transition’ tend to lose their edge when used for any significant change process as is rather often the case. Partners and wider stakeholders in initiatives related to ‘sustainability transitions’ therefore often entertain different perspectives on what the strategic orientation of an initiative is or is meant to be. Common planning and design processes such as situation analysis and theories of change, however, often do not sufficiently cater to this dynamic. As a result, different actors may be pulling the initiative in different directions, undermining the overall partnership efforts. In this short contribution a strategic scoping canvas and an associated facilitation process are presented as a way of addressing such situations. Illustrations are provided of initial application in three cases related to food system transitions in Peru, Ethiopia, and Bangladesh, exploring the connectivity with approaches commonly used in the context of system transformations, including the Multi-Level Perspective on sustainability transitions, the Leverage Points approach, Capability Approach, and the theory of Large System Change. We conclude that the canvas and associated facilitation approach has proved useful in different contexts, offering opportunities for complementing existing methodologies, and potentially enhancing their efficacy in facilitated multi-stakeholder processes.
ARTICLE | doi:10.20944/preprints201801.0282.v1
Subject: Social Sciences, Safety Research Keywords: environmental cues; fear of crime spots; sense of safety; social cues
Online: 1 February 2018 (07:59:02 CET)
Streets are primary elements through which the character of urban neighborhoods are experienced and expressed. The “sense of safety” in neighborhood streets is paramount to social and psychological wellbeing of its residents and visitors. The intention of this study was to explore environmental and social cues of a neighborhood, which evoke fear of crime, which will help designers to prevent the generation of such negative feelings and promote more safe and comfortable spaces in our cities. This study used interviews, group discussions and observations to identify fear-generating factors with a sample of participants in the multi ethnic neighborhood of Kotahena in Colombo, Sri Lanka. Field data was analyzed through visual documentation and photographic surveys. Moreover, group discussions, interviews and personal observations were used to synergize the study objectives. The findings inform that fear of crime on streets is influenced by both environmental and social cues to varying degrees. Feelings of fear were associated with gender, ethnicity and less familiarity with the place as participants were from an ethnic minority within the community. Literature has emphasized that fear of crime has a connection to actual crime locations. The research findings, however, indicate that fear of crime spots identified by the residents do not have a direct relationship to the actual crime locations.
ARTICLE | doi:10.20944/preprints202307.2156.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: DNA double-strand breaks; ionizing radiation; DNA repair pathways; homologous recombination; mathematical modeling
Online: 1 August 2023 (10:30:28 CEST)
Relative contribution of different repair pathways to the radiation-induced DNA damage responses remains a challenging issue of studying the radiation injury endpoints. Comparative manifestation of homologous recombination (HR) after application of different radiation doses greatly determines an overall effectiveness of recovery in dividing cell after irradiation, since HR is an error-free mechanism intended for repair of DNA double strand breaks (DSB) during S/G2 phases of cell cycle. In this article, we present an experimentally observed evidence of dose-dependent shift in relative contribution of HR in human fibroblasts after X-ray exposure at doses 20-1000 mGy, which is also supported by quantitative modeling of DNA DSB repair. Our findings indicate that the radiation dose increase leads to dose-dependent decrease in relative contribution of HR into the entire repair process.
ARTICLE | doi:10.20944/preprints202311.0053.v1
Subject: Computer Science And Mathematics, Mathematics Keywords: relationships between spaces; numerical knowledge; sense of mathematics; odd and even numbers
Online: 1 November 2023 (09:46:00 CET)
A teoria diz que o número interage com os espaços com base no significado da matemática, desta forma é possível obter conhecimento numérico. A teoria mostra a possibilidade de usar espaços relacionados entre si para explicar as razões pelas quais dois números pares formam um par, dois números ímpares formam um par, um número par e um ímpar formam um número ímpar, três números ímpares formam um número ímpar, três números pares formam um número ímpar. um par, um ímpar e dois pares formam um ímpar, dois ímpares e um par formam um par.
ARTICLE | doi:10.20944/preprints202304.0674.v1
Subject: Biology And Life Sciences, Toxicology Keywords: oocyte; oxidative stress; DNA double strand break, hexavalent chromium, RAD51, microtubule, polar body extrusion
Online: 21 April 2023 (05:42:55 CEST)
Environmental and occupational exposure to hexavalent chromium, Cr(VI), causes female reproductive failures and infertility. Cr(VI) is used in more than 50 industries and is a group-A carcinogen, mutagenic and teratogenic, and a male and female reproductive toxicant. Our previous findings indicate that Cr(VI) causes follicular atresia, trophoblast cell apoptosis, and mitochondrial dysfunction in metaphase II (MII) oocytes. However, the integrated molecular mechanism of Cr(VI)-induced oocyte defects are not understood. The current study investigates the mechanism of Cr(VI) in causing meiotic disruption of MII oocytes, leading to infertility in superovulated rats. Postnatal day (PND)-22 rats were treated with potassium dichromate (1 and 5 ppm) in drinking water from PND 22-29 and superovulated. MII oocytes were analyzed by immunofluorescence, and images were captured by confocal microscopy and quantified by Image Pro Plus software. Our data showed that Cr(VI) increased microtubule misalignment, missegregation of chromosomes, a bulged and folded actin cap, oxidative DNA and protein damage, increased DNA double-strand break, and DNA repair protein RAD51. Cr(VI) also induced incomplete cytokinesis and delayed polar body extrusion. Our study indicates that exposure to environmentally relevant doses of Cr(VI) caused severe DNA damage, distorted oocyte cytoskeletal proteins, and caused oxidative DNA and protein damage leading to infertility.
REVIEW | doi:10.20944/preprints201810.0500.v3
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: DNA repair; long non-coding RNA; microRNA; DNA damage; double-strand breaks; NHEJ; HR
Online: 26 October 2018 (10:22:45 CEST)
DNA double-strand breaks (DSBs) are deleterious lesions that are generated in response to ionizing radiation or replication fork collapse that can lead to genomic instability and cancer. Eukaryotes have evolved two major pathways, namely homologous recombination (HR) and non-homologous end joining (NHEJ) to repair DSBs. Whereas the roles of protein-DNA interactions in HR and NHEJ have been fairly well defined, the functions of small and long non-coding RNAs and RNA-DNA hybrids in the DNA damage response is just beginning to be elucidated. This review summarizes recent discoveries on the identification of non-coding RNAs and RNA-mediated regulation of DSB repair
ARTICLE | doi:10.20944/preprints202308.1056.v1
Subject: Environmental And Earth Sciences, Geography Keywords: sense of place; dyke; flood protection embankment; flood collective memory; suballuvial bedrock protrussion
Online: 15 August 2023 (08:42:34 CEST)
The origin and dynamics of a- 2010 pluvial flood in the valley of a large European river are described. In order to study how local people perceive this catastrophic event a small administrative unit (rural municipality) within Holocene floodplain (thus flooded to 90%) was chosen. Using a questionnaire a human-research survey was performed in the field among 287 people living on flood-prone area. Almost half of the interviewees feel safe and do not expect a flood recurrence (interpreted as a levee effect). 17% believe the levee was intentionally breached due to political issues. 6% of interviewees link the breach with small mammals using leeves as a habitat, eg. beavers, moles, foxes. Spatial distribution of the survey results are analyzed. Maps presenting: inundation height, economic loss, attitude to geohazards and perception of possible flood recurrence were drawn. Causes of the flood as viewed by local inhabitants and in the context of the riverine geological setting and its processes are discussed. Particular attention is paid to processes linking the levee breach location with specific geomorpic features of the Holocene floodplain. A wide perspective of fluvial geomorphology where erosive landforms of crevasse channels (and associated depositional crevasse splays) are indicators of geohazards was adopted. This distinct geomorphological imprint left by overbank flow is considered as natural flood marks. Such an approach is completely neglected by interviewees who overestimate a role of hydraulic structures.
ARTICLE | doi:10.20944/preprints202104.0790.v1
Subject: Business, Economics And Management, Accounting And Taxation Keywords: Cognitive style; Spatial Cognition; Sense of Direction; Spatial Orientation; Mental Rotation; Individual Differences
Online: 30 April 2021 (15:23:16 CEST)
Background: Military pilots show high visuo-spatial skills. Previous studies demonstrate that they are better in mental rotating a target, in taking different perspectives, in estimating distances, in travel planning and in topographic memory. Here, we compared navigational cognitive styles between military pilots and people without flight experience. Pilots were expected to be more survey users than non-pilots, showing higher navigational strategies. Method: 106 jet military pilots of Italian Air Force and 92 non-pilots were enrolled in order to investigate group differences in navigational styles. Participants were asked to perform a reduced version of the Spatial Cognitive Style Test – SCST, consisting of six tasks that allow to distinguish individuals in landmark (people orient themselves by using a figurative memory for environmental objects), route (people use an egocentric representation of the space) and survey (people have a map-like representation of the space) users. Results: In line with our hypothesis, military pilots mainly adopt a survey style, whereas non-pilots mainly adopt the route style. In addition, pilots outperformed non pilots in both the 3D-Rotation task and Map Description Task. Conclusion: Military flight expertise influences some aspects of the spatial ability, leading to enhance human navigation. Although, it must be considered that they are a population whose navigational skills were already high at the time of selection at the academy before formal training began.
ARTICLE | doi:10.20944/preprints202112.0054.v1
Subject: Social Sciences, Education Keywords: dropout intention; perceived social isolation; perceived social support; engagement; sense of belonging; higher education
Online: 3 December 2021 (13:08:34 CET)
Social and academic integration variables have shown to be relevant for the understanding of university dropout. However, there is less evidence regarding the influence of these variables on dropout intention, as well as predictive models that explain their relationships. Improvements in this topic become relevant considering that dropout intention stands as a useful measure to anticipate and intervene on this phenomenon. The objective of the present study was to evaluate a predictive model for the university dropout intention that considers the relationships between social and academic variables, during the first university semester of 2020. The research was carried out using a cross-sectional associative-predictive design, with a convenience sampling (n=711) due the restrictions of pandemic period. The results showed a good fit of the proposed hypothetical model that explains 38.7% of dropout intention. Both social support and perceived social isolation predicted the sense of belonging, and through it, engagement. Previous academic performance predicted early academic performance, and through it, engagement. The set of variables predicted the intention to quit, through engagement. These results are a contribution both to the understanding of the phenomenon and to guide potential interventions in the early stages of the university experience.
CASE REPORT | doi:10.20944/preprints202103.0466.v1
Subject: Social Sciences, Psychology Keywords: anarchic hand syndrome; DTI; white matter disconnection; lesion mapping; sense of agency; posterior lesions.
Online: 18 March 2021 (10:09:37 CET)
The anarchic hand syndrome refers to an inability to control the movements of one’s own hand which acts as if it had a will of its own. The symptoms may differ depending on whether the brain lesion is anterior, posterior, callosal or subcortical, but the relative classifications are not conclusive. This study investigates the role of white matter disconnections in a patient whose symptoms are inconsistent with the mapping of the lesion site. A repeated neuropsychological investigation was associated with a review of the literature on the topic to identify the frequency of various different symptoms relating to this syndrome. Furthermore, an analysis of the neuroimaging regarding structural connectivity allowed us to investigate the grey matter lesions and white matter disconnections. The results indicated that some of the patient’s symptoms were associated with structures that, although not directly damaged, were dysfunctional due to a disconnection in their networks. This suggests that the anarchic hand may be considered as a disconnection syndrome involving the integration of multiple antero-posterior, insular and interhemispheric networks. In order to comprehend this rare syndrome better, the clinical and neuroimaging data need to be integrated with the clinical reports available in the literature on the topic.
ARTICLE | doi:10.20944/preprints202103.0288.v1
Subject: Business, Economics And Management, Accounting And Taxation Keywords: eHealth Literacy; digital health literacy; sense of coherence; COVID-19; COVID-HL-Q; Pakistan.
Online: 10 March 2021 (15:07:22 CET)
Amid to the COVID-19 pandemic, digital health literacy (DHL) has become a significant public health concern. This research aims to assess information seeking behavior, as well as the ability to find relevant information and deal with DHL among university students in Pakistan. An online-based cross-sectional survey, using a web-based interviewing technique, was conducted to collect data on DHL. Simple bivariate and multivariate linear regression was performed to assess the association of key characteristics with DHL. The results show a high DHL related to COVID-19 in 54.3% of students. Most of the Pakistani students demonstrated ~50% DHL in all dimensions, except of reliability. Multivariate findings showed that gender, sense of coherence and importance of information were found to be significantly associated with DHL. However, a negative association was observed with students’ satisfaction with information. This led to the conclusion that critical operational and navigations skills are essential to achieve COVID-19 DHL and cope with stress, particularly to promote both personal and community health. Focused interventions and strategies should be designed to enhance DHL amongst university students to combat the pandemic.
ARTICLE | doi:10.20944/preprints202305.1857.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: γH2AX; Actinomycin D; Akt; DNA damage response; DNA double-strand break; DNA-PK; Etoposide; p95/NBS1
Online: 26 May 2023 (05:11:01 CEST)
DNA double-strand breakage is the most lethal damage to chromosomal DNA. It activates a series of cellular DNA damage response pathways, including DNA damage sensing, control of cell cycle arrest and apoptosis, and DNA repair. DNA damage response pathways are regulated by complex signaling machineries. Of the intracellular signaling cascades, diacylglycerol kinase (DGK) phosphorylates diacylglycerol (DG) to generate phosphatidic acid (PA). Because both DG and PA serve as second messengers, DGK activity induces a shift of signaling pathways from DG-mediated to PA-mediated cascades, thereby implicating DGK in the regulation of widely various functions. Reportedly, one member of the DGK family, DGKζ, is intimately involved in the regulation of stress responses through p53 and NF-κB. Stresses such as ischemia and infarction cause DGKζ downregulation. Experimental DGKζ depletion renders cells and mice vulnerable to various stressors such as chemotherapeutic agents and ionizing irradiation. Nevertheless, how DGKζ is involved in DNA repair, a critical event of DNA damage response for survival remains unknown. For this study, we examined how DGKζ depletion affects DNA repair mechanisms. We demonstrated that DGKζ depletion causes attenuation of Akt activation and DNA-PK protein expression upon DNA damage, which might engender downregulated BRCA1 protein synthesis and stability. Results suggest that DGKζ depletion attenuates BRCA1-mediated DNA repair machinery, thereby conferring vulnerability to DNA damage.
ARTICLE | doi:10.20944/preprints202308.1525.v1
Subject: Social Sciences, Media Studies Keywords: Fan community platform; Mental well-being; Sense of virtual community; Fan interaction; Parasocial relationship; Weverse
Online: 22 August 2023 (07:15:51 CEST)
Activities in the digital economy driven by information technology have rapidly increased in scope and speed in the aftermath of COVID-19. Meanwhile, social isolation accelerated by quarantine measures has increased concerns about individuals’ mental health. However, little is known about the specific consequences of online interactions, especially when applied in online fan community-based relationships where loyal community members are prevalent. Therefore, we examined whether a sense of virtual community (SOVC) can link fans’ online activities with their mental well-being and behavioral loyalty to the platform. For this purpose, we focus on BTS fandom “Adorable Representative MC for Youth” (ARMY) behaviors and attitudes on the fan community platform Weverse. With 202 valid data samples acquired from global ARMY, this study conducted a partial least squares–structural equation modeling analysis. The empirical findings reveal that SOVC in Weverse is significantly influenced by the intensity of online interactions with other fans and parasocial relationships with celebrities. SOVC is found to be the direct predictor of fans’ behavioral loyalty and mental well-being. When considering fans’ perceptions of other social media platforms, dissatisfaction with previous online fan communities enhances the intensity of online interactions with other fans in Weverse.
HYPOTHESIS | doi:10.20944/preprints202305.0607.v2
Subject: Biology And Life Sciences, Biophysics Keywords: Hox gene collinearity; temporal collinearity; Noether theory; self similarity; double strand break; split Ηox cluster; limb growth
Online: 11 May 2023 (04:34:03 CEST)
Abstract: Hox gene clusters are crucial in Embryogenesis. It was observed that some Hox genes were located in order along the telomeric to centromeric direction of the DNA sequence: Hox1, Hox2, Hox3…. These genes were expressed in the same order in the ontogenetic units of the Drosophila embryo along the Anterior-Posterior axis. The two entities (genome and embryo) differ significantly in linear size and in-between distance. This strange phenomenon was named Spatial Collinearity (SP). Later, it was observed that, particularly in the Vertebrates, a Temporal Collinearity (TC) coexists: first is Hox1 expressed, later Hox2 and even later Hox3,…,. Hox clusters are irreversibly elongated along the force direction. According to a Biophysical Model (BM), pulling forces act at the anterior end of the cluster while a cluster fastening applies at the posterior end. During Evolution, the elongated Hox clusters are broken at variable lengths thus split clusters may be created. An Empirical Rule was formulated distinguishing development due to a complete Hox cluster from development due to split Hox clusters. BM can explain this Empirical Rule. In an accidental mutation where the cluster fastening is dismantled, a minimal pulling force can automatically shift the cluster inside the Hox activation domain. This cluster translocation can probably explain the absence of temporal collinearity in Drosophila.
ARTICLE | doi:10.20944/preprints201908.0220.v1
Subject: Chemistry And Materials Science, Metals, Alloys And Metallurgy Keywords: high nitrogen austenitic stainless steel; multi-strand composite welding wire; EBSD; welding thermal cycle; mechanical property; microstructure
Online: 21 August 2019 (03:34:18 CEST)
A multi-strand composite welding wire was applied to join high nitrogen austenitic stainless steel, and microstructures and mechanical properties were investigated. The electrical signals demonstrate that the welding process using a multi-strand composite welding wire is highly stable. The welded joints are composed of columnar austenite and dendritic ferrite and welded joints obtained under high heat input and cooling rate have a noticeable coarse-grained heat-affected zone and larger columnar austenite in weld seam. Compared with welded joints obtained under the high heat input and cooling rate, welded joints have the higher fractions of deformed grains, high angle grain boundaries, Schmid factor and the lower dislocation density under the low heat input and cooling rate, which indicate a lower tensile strength and higher yield strength. The rotated goss (GRD) orientation of a thin plate and the cube (C) orientation of a thick plate are obvious after welding, but the S orientation at 65° sections of Euler’s space is weak. The δ-ferrite was studied based on the primary ferrite solidification mode. It is observed that low heat input and high cooing rate result in the increasing of δ-ferrite and high dislocation density was obtained in grain boundaries of δ-ferrite. M23C6 precipitates due to low cooling rate and heat input in weld seam and deteriorates the elongation of welded joints. The engineering stress-strain curves also show the low elongation and tensile strength of welded joints under low heat input and cooling rate, which is mainly caused by the high fraction of δ-ferrite and the precipitation of M23C6.
ARTICLE | doi:10.20944/preprints202307.0877.v1
Subject: Physical Sciences, Other Keywords: Ouroboros Model; Analogical Algorithms; AI-Challenge; Large Language Models; Cybernetics; Synergetics; Understanding; Common Sense; Consciousness; Free Will.
Online: 13 July 2023 (12:28:07 CEST)
A topical challenge for algorithms in general and for automatic image categorization and generation in particular is presented with the aim of highlighting strengths and deficiencies of current Artificial Intelligence approaches while sketching a way forward. A general lack of encompassing symbol-embedding and (not only) -grounding in some bodily basis is made responsible for current deficiencies. A concomitant dearth of hierarchical organization of concepts follows suite. As a remedy for these shortcomings, it is proposed to take a wide step back and to newly incorporate aspects of cybernetics and analog control processes. It is claimed that a promising overarching perspective is provided by the Ouroboros Model with a valid and versatile algorithmic backbone for general cognition at all accessible levels of abstraction and capabilities.
ARTICLE | doi:10.20944/preprints202008.0176.v1
Subject: Public Health And Healthcare, Nursing Keywords: COVID-19; nurses; posttraumatic stress disorder; perceived social support; changes in outlook; sense of security; meaning in life
Online: 7 August 2020 (08:10:28 CEST)
The COVID-19 pandemic affects not only physical health but also deteriorates mental health resulting in sleep problems, depression, and traumatic stress. Our research investigates the level of posttraumatic stress, perceived social support, opinions on positive and negative consequences of the pandemic, sense of security, and sense of meaning among nurses in the face of new and not fully understood global epidemiological phenomena. For this purpose, computer-assisted web interviewing methods were conducted between May 1 and May 15, 2020. Participating nurses completed the following research tools: The Impact Event Scale-Revised (IES-R), The Multidimensional Scale of Perceived Social Support (MSPSS), The Changes in Outlook Questionnaire (CIOQ), The Safety Experience Questionnaire (SEQ) and The Meaning in Life Questionnaire (MLQ). Three hundred and twenty-five nurses working throughout Poland joined the study of an average age of 39.18 ± 11.16 years. The average overall IES-R score in the study group was 1.78 ± 0.65. Among the dimensions of traumatic stress, the highest score was obtained in the dimension Avoidance 1.86 ± 0.73, then in the dimensions Hyperarousal 1.8 ± 0.78 and Intrusion 1.74 ± 0.83. Amongst studied nurses, the highest support rates were provided by significant others (22.58 ± 5.22), then from friends (21.91 ± 5) and family (21.45 ± 4.4). Among the surveyed nurses, higher average scores were noted in the subscale measuring positive psychological changes (18.56 ± 4.04). In contrast, a higher average level of assessment was noted on the Reflection on the safety dimension (4.21 ± 0.49). The mean MLQ score was 5.33 ± 0.87. A slightly higher result was observed in the subscale Presence (5.35 ± 1.14). The results of the research implemented during the period of severe psychological pressure associated with the COVID-19 pandemic provided information on symptoms of traumatic stress in the examined group of nurses. Their sense of security has been lowered and accompanied by an intensified reflection on issues concerning security. However, the sense of meaning (currently felt) in life remains higher than the tendency to searching for it. The surveyed nurses perceive individual support from the so-called significant others (apart from family and friends). They see positive changes resulting from painful experiences related to the COVID-19 pandemic, which can be characterized by adaptation in the form of posttraumatic growth.
ARTICLE | doi:10.20944/preprints202311.1987.v1
Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: Hox gene collinearity; temporal collinearity; Noether Theory; self similarity; double strand break; split Hox clusters; chicken limb growth
Online: 1 December 2023 (03:12:17 CET)
Hox gene clusters are crucial in Embryogenesis. It was observed that some Hox genes are located in order along the telomeric to centromeric direction of the DNA sequence: Hox1, Hox2, Hox3…. These genes are expressed in the same order in the ontogenetic units of the Drosophila embryo along the Anterior-Posterior axis. The two entities (genome and embryo) differ significantly in linear size and in-between distance. This strange phenomenon was named Spatial Collinearity (SP). Later, it was observed that, particularly in the Vertebrates, a Temporal Collinearity (TC) coexists: first is Hox1 expressed, later Hox2 and even later Hox3,…,. According to a Biophysical Model (BM), pulling forces act at the anterior end of the cluster while a cluster fastening applies at the posterior end. Hox clusters are irreversibly elongated along the force direction. During Evolution, the elongated Hox clusters are broken at variable lengths thus split clusters may be created. An Empirical Rule was formulated distinguishing development due to a complete Hox cluster from development due to split Hox clusters. BM can ‘explain’ this Empirical Rule. In a spontaneous mutation where the cluster fastening is dismantled, a minimal pulling force can automatically shift the cluster inside the Hox activation domain. This cluster translocation can probably explain the absence of Temporal Collinearity in Drosophila.
REVIEW | doi:10.20944/preprints202304.0143.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Genome stability; DNA replication; DNA repair; lagging strand DNA synthesis; Okazaki fragments; initiation; DNA polymerase α; DNA primase; CTC1-STN1-TEN1 complex; SV40 T antigen; CMG complex
Online: 10 April 2023 (04:20:27 CEST)
The term ‘Hallmarks of Cancer’ was coined by Hanahan and Weinberg in their influential reviews and they described genome instability as a property of cells enabling cancer development [1, 2]. Accurate DNA replication of genomes is central to diminish genome instability. Here, the understanding of the initiation of DNA synthesis in origins of DNA replication to start leading strand synthesis and the initiation of Okazaki fragment on the lagging strand are crucial to control genome instability. Recent findings have provided new insights into the mechanism of the remodelling of the prime initiation enzyme, DNA polymerase α-primase, during primer synthesis, how the enzyme complex achieves lagging strand synthesis, and how it is linked to replication forks to achieve optimal initiation of Okazaki fragments. Moreover, the central roles of RNA primer synthesis by Pol-prim in multiple genome stability pathways such as replication fork restart and protection of DNA against degradation by exonucleases during double-strand break repair is discussed.
REVIEW | doi:10.20944/preprints202001.0353.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: chromothripsis; structural variants; DNA-repair; DNA-repair disorders; DNA-double strand breaks (DSBs); ataxia telangiectasia mutated (ATM); ataxia-telangiectasia and Rad3-related (ATR); TP53; micronuclei; chromosome pulverization.
Online: 29 January 2020 (11:58:58 CET)
Chromothripsis is a mutational mechanism leading to complex and relatively clustered chromosomal rearrangements resulting in diverse phenotypic outcomes depending on the involved genomic landscapes. It may occur both in the germ and the somatic cells resulting in congenital and developmental disorders and cancer, respectively. Asymptomatic individuals may be carriers of chromotriptic rearrangements and experience recurrent reproductive failures when two or more chromosomes are involved. Several mechanisms are postulated to underly chromothripsis. The most attractive hypothesis involves chromosome pulverization in micronuclei followed by incorrect reassembly of fragments through DNA repair to explain the clustered nature of the observed complex rearrangements. Moreover, exogenous or endogenous DNA damage induction and dicentric bridge formation may be involved. Chromosome instability is commonly observed in the cells of patients with DNA-repair disorders, such as ataxia telangiectasia, Nijmegen breakage syndrome and Bloom syndrome. In addition, germline variations of TP53 have been associated with chromothripsis in Sonic-Hedgehog medulloblastoma and acute myeloid leukemia. In the present review, we focus on the underlying mechanisms of chromothripsis and the involvement of defective DNA-repair genes resulting in chromosome instability and chromothripsis-like rearrangements.
ARTICLE | doi:10.20944/preprints202307.1233.v1
Subject: Computer Science And Mathematics, Information Systems Keywords: SPARSAR = Specialized NLP system for English Poetry organized into ten feeding modules and over twenty dictionaries; Automatic Analysis of English Poems; Visualization of Linguistic and Poetic Content; Creating Clusters of Boxes of Different Dimension one for each poem according to linguistic content and positioning each box in a space; Computing Sound-Sense Harmony; Comparing Phonetic and Phonological Features with Meaning; Automatic Lexical and Semantic Sentiment Analysis of Poetry; Appraisal Theory Framework.
Online: 18 July 2023 (12:24:24 CEST)
We assume that poetic devices have an implicit goal: producing an overall sound scheme that will induce the reader to associate intended and expressed meaning to the sound of the poem. Sounds may be organized into categories and assigned presumed meaning as suggested by traditional literary studies. In my work, I have extracted automatically the sound grids of all the sonnets by William Shakespeare and have combined them with the themes expressed by their contents. In a first experiment I have computed lexically and semantically based sentiment analysis obtaining an 80% of agreement. In a second experiment sentiment analysis has been substituted by Appraisal Theory thus obtaining a more fine-grained interpretation which in some cases contradicts the first one. The computation for the second poet - regarded by many critics the best of last century - includes both vowels and consonants. In addition, it combines automatic semantically and lexically based sentiment analysis with sound grids. The results produce visual maps that clearly separate poems into three clusters: negative harmony, positive harmony and disharmony where the latter instantiates the need by the poet to encompass the opposites in a desperate attempt to reconcile them.