The effect of elastic constants, cij, on the nature (easy or difficult) of a cleavage system in YBa2Cu3O7−δ is investigated, by employing a novel three-dimensional eigenfunction expansion technique, based in part on separation of the thickness-variable and partly a modified Frobenius type series expansion technique in conjunction with the Eshelby-Stroh formalism. Out of the available three complete sets of elastic constants, the first constitutes an estimate, while the second assumes tetragonal symmetry. This leaves only the experimental measurements by resonant ultrasound spectroscopy, despite reported values of c12 and to a lesser extent, c66, being excessively high. The present investigation considers six through-thickness crack systems weakening orthorhombic YBCO mon-crystalline plates. More important, the present approach predicts whether a crack would propagate in its original plane/direction or deflect to a different one. This fracture mechanics criterion is then employed for accurate determination of the full set of elastic constants of mono-crystalline YBCO. Finally, generally unavailable results, pertaining to the through-thickness variations of stress intensity factors and energy release rates for a crack corresponding to symmetric and skew-symmetric hyperbolic cosine loads that also satisfy the boundary conditions on the bounding surfaces of an orthorhombic monocrystalline plate bridge a longstanding gap in the field.

This paper explores ballot split by type and introduces universal measures of democratic power flow and accountable local representation. These measures allow definitive comparison of electoral systems between countries, and choice of a new electoral system within a country based on existing data and with minimum assumptions.

At INFN-LNS, and in collaboration with the ATOMKI laboratories, an innovative multi-diagnostic system with advanced analytical methods has been designed and implemented. This is based on several detectors and techniques (Optical Emission Spectroscopy, RF systems, Interfero-polarimetry, X-ray detectors) and here we focus on high resolution spatially-resolved X-ray spectroscopy, performed by means of a X-ray pin-hole camera setup operating in the 0.5−20 keV energy domain. The diagnostic system was installed at a 14 GHz Electron Cyclotron Resonance (ECR) ion source (ATOMKI, Debrecen), enabling high precision X-ray spectrally-resolved imaging of ECR plasmas heated by hundreds of Watts. The achieved spatial and energy resolution were 0.5 mm and 300 eV at 8 keV, respectively. We here present the innovative analysis algorithm that we properly developed for obtaining Single Photon-Counted (SPhC) images providing the local plasma emitted spectrum in a High-Dynamic-Range (HDR) mode, by distinguishing fluorescence lines of the materials of the plasma chamber (Ti, Ta) from plasma (Ar). This method allows a quantitative characterization of warm electrons population in the plasma (and its 2D distribution) which are the most important for ionization, and also to estimate local plasma density and spectral temperatures. The developed post-processing analysis is also able to remove the readout noise, that is often observable at very low exposure times (msec). The setup is now under update including fast shutters and trigger systems in order to allow simultaneously space and time-resolved plasma spectroscopy during transients, stable and turbulent regimes.

Quantitative trait loci (QTL) are genomic regions associated with phenotype variation of quantitative traits in a population. To date, a total of 267 QTL for 29 quantitative traits have been reported in 13 studies on flax. Of these, 200 QTL from 12 studies were identified based on genetic maps, scaffold sequences, or pre-released chromosome-scale pseudomolecules. Molecular markers for QTL identification differed across studies but were mainly based on simple sequence repeat (SSR) or single nucleotide polymorphism (SNP) markers. This article provides methods with software tools and database files to uniquely map SSR and SNP markers from different references onto the recently released chromosome-scale pseudomolecules. Using these methods, 195 QTL were successfully sorted onto the 15 flax chromosomes and grouped into 133 co-located QTL clusters. Mapping of QTL from different studies to the same reference enables comparisons and facilitates genome-wide QTL analysis, candidate gene scanning, and breeding applications.

Distributed deformation based on Fiber Bragg Grating sensors or other kinds of strain sensors can be used to evaluate safety in operating periods of bridges. However, most of the published researches about distributed deformation monitoring are focused on solid rectangular beam rather than box girder—a kind of typical hollow beam widely employed in actual bridges. Considering that the entire deformation of a single-cell box girder contains not only bending deflection but also two additional deformations respectively caused by shear lag and shearing action, this paper again revises the improved conjugated beam method (ICBM) based on the LFBG sensors to satisfy the requirements for monitoring two mentioned additional deformations. The best choice for the LFBG sensor placement in box gilder is also proposed in this paper due to strain fluctuation on flange caused by shear lag effect. Results from numerical simulations show that most of the theoretical monitoring errors of the revised ICBM are 0.3%~1.5%, and the maximum error is 2.4%. A loading experiment for a single-cell box gilder monitored by LFBG sensors show that most of the practical monitoring errors are 6%~8%, and the maximum error is 11%.

Scientific knowledge evolves in small steps, with occasional backsteps to correct inaccuracies, all occurring within a competitive environment. This perspective for the first time looks at the history of latency-related RNA (LR-RNA) that was later renamed latency-associated transcript (LAT). At the 1986 International Herpesvirus Workshop (IHW) meeting in Leeds, England, Daniel L Rock and Anthony B Nesburn first reported the discovery of human herpes virus 1 (HSV-1) latency-related (LR)-RNA that is antisense to ICP0. Less than a month after the IHW meeting a paper was submitted to Science magazine and 8 months later appeared in print thanking “D. Rock for suggesting RNA complementary to the ICP0 message may be present in latently infected cells”. This perspective is not a review of LAT literature but intends to clarify the timeline of LAT discovery and subsequent breakthroughs such as reactivation, apoptosis, CD8+ T cell exhaustion, and LAT expression in different cell types detected during latency. While many review articles have been written about LAT since 1987, the most comprehensive and balanced review about LAT was written by Dr. David Bloom’s group (1). In this overview, I will discuss our original collaboration with Dr. Dan Rock and subsequent work that our group performed, which is still ongoing. Finally, I will discuss the controversies associated with LAT from its inception to current times.

Sodium phenyl dithiocarbamate (pl-dtc) as a ligand was prepared from the reaction of aniline (C6H5-NH2) and carbon(IV) sulfide (CS2) in the presence of sodium hydroxide via method of one-pot synthesis. Two coordination compounds ([VO(sfz)(pl-dtc)] and [Zn(sfz)(pl-dtc)]) from respective oxovanadium (IV) sulfate hydrate and zinc (II) chloride were prepared with mixed ligands involving sodium sulfadiazine (sfz) and the synthesized pl-dtc crystals, also via the method of one-pot synthesis. Structural analyses of the ligand and coordination compounds were assessed using characterization techniques involving physicochemical parameters and spectral analysis ( FT-IR, UV-Vis and NMR (1H NMR and 13C NMR) to confirm their synthenses and structures. Additionally, pl-dtc crystals which grew from the pl-dtc solution when refrigerated after five days, has its structure confirmed and revealed when subjected to single crystal x-ray crystallography technique. Differences in results of spectral analysis between ligands and their respective coordination compounds confirmed the coordination between ligands and coordination compounds. The in vitro antibacterial studies showed that the ligands had modest activity against Gram positive bacteria: Staphylococcus aureus, while, the coordination compounds had modest activities against the Gram negative bacteria: Escherichia coli when compared with ligand of pl-dtc.

Manganese porphyrins reportedly exhibit synergic effects when combined with irradiation. However, an in-depth understanding of intratumoral heterogeneity and immune pathways, as affected by Mn porphyrins, remains limited. Here, we explored the mechanisms underlying immunomodulation of a clinical candidate, MnTnBuOE-2-PyP5+ (BMX-001, MnBuOE), using single-cell analysis in murine carcinoma model. Mice bearing 4T1 tumors were divided into 4 groups: control, MnBuOE, radiotherapy (RT), combined MnBuOE and radiotherapy (MnBuOE/RT). In epithelial cells, epithelial-mesenchymal transition, TNF-α signaling via NF-кB, angiogenesis, and hypoxia-related genes were significantly downregulated in the MnBuOE/RT compared to the RT. All subtypes of cancer-associated fibroblasts (CAFs) were clearly reduced in MnBuOE and MnBuOE/RT. Inhibitory receptor-ligand interactions, in which epithelial cells and CAFs interacted with CD8+ T cells, were significantly lower in the MnBuOE/RT than in the RT. Trajectory analysis showed that DC maturation-associated markers were increased in MnBuOE/RT. M1 macrophages were significantly increased in the MnBuOE/RT compared to the RT, whereas myeloid-derived suppressor cells were decreased. CellChat analysis showed that the number of cell-cell communications was the lowest in the MnBuOE/RT. Our study is the first to provide evidence for the combined radiotherapy with a novel Mn porphyrin clinical candidate, BMX-001 from the perspective of each cell-type within the tumor microenvironment.

Obesity in adolescents combined with the increased exposure time to electronic devices, enhances a sedentary lifestyle and is linked to the risk of developing musculoskeletal injuries. The aim of this study was to identify possible correlations between anthropometric characteristics, body composition, exposure time to electronic devices or screen time (ST) and physical activity (PA) level along with muscle power and dynamic knee valgus (DKV) in young athletes to avoid future injuries. A total of 125 adolescent basketball athletes (66.4% boys), 12 to 17 years old (13.94±1.58 years) participated. Anthropometric and demographic characteristics were recorded. PA level was assessed through IPAQ and ST through a single question from the HELENA study. The Counter Movement Jump test was used for the evaluation of the lower limb muscle power, while the Single Leg Drop Jump test was used for the evaluation of the dynamic knee valgus via two-dimensional (2D) kinematic analysis. The Pearson index showed a statistically significant positive correlation between muscle power and height (r=0.788, p<0.001), while the Spearman index showed a smaller but equally statistically significant positive correlation with BMI (rs =0.651, p<0.001) and age (rs=0.579, p<0.001). The ST (rs= -0.194, p=0.03) showed a weak negative correlation with DKV, while PA (r=0.85, p<0.001) showed a high, statistically significant, positive correlation. The anthropometric characteristics of adolescent athletes can determine their ability to produce muscle power. A high level of physical activity could play a key role in compensating and thus reducing the negative effects of high exposure to screen time on the dynamic knee valgus

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.

Abstract: Beetroot (Beta vulgaris L) has been known for being a rich source of phytochemicals, minerals and vitamins. This study presents a model system for how the combination of extrac-tion/chromatography/mass spectrometry and NMR offers an efficient way to profile metabolites in the extracts of a natural product, beetroot . Such combination may lead to the identification of more nutritional or medicinal compounds in natural products, and it is essential for our ongoing investigation to study the selective adsorption/desorption of these metabolites on nanoparticles. The aqueous and organic extracts underwent analyses using UV-vis spectroscopy; GC-MS; LC-MS; 1H, 13C, TOCSY, HSQC, and selective TOCSY NMR experiments. Polar Extract: The two forms of betalain pigment were identified by UV-vis and LC MS. Fourteen amino acids, sucrose, and other compounds among which is riboflavin, were identified by LC-MS. 2D TOCSY showed the spin coupling correlations corresponding to some of these compounds. The HSQC spectrum showed 1H/13C spin correlation in sucrose confirming the high abundance of sucrose in beetroot. Organic Extract: GC-MS data enabled the identification of several compounds including six fatty acid methyl esters (FAME) with higher than, on average, 90% similarity score. Selective TOCSY NMR data showed the spin coupling pattern corresponding to oleic, linoleic, and linolenic fatty acids. 31P NMR spectra indicate that phospholipids exist in both the organic and aqueous phases. Keywords: Beetroot (Beta vulgaris L); Total Correlation Spectroscopy (TOCSY); Gas Chromatog-raphy-Mass Spectrometry (GC-MS); selective TOCSY, Homonuclear single quantum correlation (HSQC); fatty acid methyl esters (FAME).

Ribosome assembly is one of the most fundamental processes in gene expression and has served as a playground to investigate the molecular mechanisms of how protein-RNA complexes (RNPs) assemble. The bacterial ribosome is composed of around 50 ribosomal proteins several of which are co-transcriptionally assembled on a ~4,500 nucleotides long pre-rRNA transcript that is further processed and modified during transcription, the entire process taking around 2 minutes in vivo and assisted by dozens of assembly factors. How this complex molecular process works so efficiently to produce an active ribosome has been investigated over decades and has resulted in the development of a plethora of novel approaches that can also be used to study the assembly of other RNPs. Here we review biochemical, structural and biophysical methods that have been developed and integrated to provide a detailed and quantitative understanding of this complex and intricate molecular process of assembly. We also discuss emerging cutting-edge approaches that could be used in the future to study how transcription, rRNA processing, cellular factors and the native cellular environment shape ribosome assembly and RNP assembly at large.

Experiments to measure a single molecule/particle, i.e. an individual molecule/particle, at room temperature or under physiological conditions without immobilization, for example on a surface, or without significant hydrodynamic flow have so far failed. This failure has given impetus to the underlying theory of Brownian molecular motion towards its stochastics due to diffusion. Quantifying the thermodynamic jitter of molecules/particles inspires many and forms the theoretical basis of single-molecule/single-particle biophysics and biochemistry. For the first time, our simulation results for a live cell (cytoplasm) show that the tracks of individual single molecules are localized in Brownian motion, while there is fanning out in fractal diffusion (anomalous diffusion).

Ankle sprains are the most frequently occurring musculoskeletal injuries among recreational athletes. Ankle support through bandages following the initial orthotic treatment might be beneficial for rehabilitation purposes. Since hardly any study has investigated the impact of bandages in the acute phase of ankle sprains, our study examined the immediate effects of wearing an ankle bandage on fine coordination, proprioception, and motor performance in subjects five weeks after an acute ankle injury. In total, 70 subjects with acute unilateral supination trauma were tested. All subjects completed several rating questionnaires and biomechanical investigations, including a fine coordination and proprioception test, single leg stances, the Y-Balance test and gait analysis. All biomechanical investigations were conducted for the subject's injured leg with and without a bandage (MalleoTrain® Bauerfeind AG) and the healthy leg. Subjects reported moderate to strong improvements in ankle stability and pain when wearing the bandage. Wearing the bandage significantly normalized subjects’ single leg stance performance, as well as the stance phase duration, and the vertical ground reaction forces during walking. However, the bandage did not have a clear effect on fine coordination and proprioception. Wearing a bandage in the acute phase of an ankle sprain may immediately improve motor performance, including standing and walking.

The study evaluated the immune response to the Janssen Ad26.COV2.S COVID-19 vaccine in a Ugandan cohort, focusing on spike (S) and nucleocapsid (N) protein-directed antibodies. The aim was to assess the longevity and robustness of the elicited antibodies, aligning with breakthrough infections and prior exposure to SARS-CoV-2. The study involved 319 specimens collected over 12 months from 60 vaccinees aged 18 to 64. Binding antibodies were quantified using a validated ELISA method to measure SARS-CoV-2-specific IgG, IgM, and IgA levels against the S and N proteins. The results showed that baseline seropositivity for S-IgG was high at 67%, increasing to 98% by day 14 and consistently stayed above 95% for up to 12 months. However, S-IgM responses remained suboptimal. An increased S-IgA serpositivity rate doubled from 40% at baseline to 86% just two weeks following the initial vaccine dose, indicating sustained and robust mucosal immunity. An increase in N-IgG levels at nine months post-vaccination suggested breakthrough infections in eight cases. Baseline cross-reactivity influenced spike-directed antibody responses, with those with pre-existing S-IgG antibodies showing higher responses. The vaccine demonstrated robust and long-lasting immune responses, with significant implications for regions where administering follow-up doses is challenging.

Does cell clustering influence intrinsic and acquired multi-drug resistance (MDR) differently? To address this question, we studied cultured monolayers (representing individual cells) and cultured spheroids (representing clusters) formed by drug-naïve (intrinsic MDR) and drug-exposed (acquired MDR) lines of ovarian cancer A2780 cells by cytometry of reaction rate constant (CRRC). MDR efflux was characterized by accurate and robust “cell number vs. MDR efflux rate constant (kMDR)” histograms. Both drug-naïve and drug-exposed monolayer cells presented unimodal histograms; the histogram of drug-exposed cells was shifted towards higher kMDR value suggesting greater MDR activity. Spheroids of drug-naïve cells presented a bimodal histogram indicating the presence of two subpopulations with different MDR activity. In contrast, spheroids of drug-exposed cells presented a unimodal histogram qualitatively similar to that of the monolayers of drug-exposed cells but with a moderate shift towards greater MDR activity. The observed greater effect of cell clustering on intrinsic than on acquired MDR can help guide the development of new therapeutic strategies targeting clusters of circulating tumor cells.

The generation of isogenic induced pluripotent stem cell (iPSC) lines using CRISPR-Cas9 technology is a technically challenging, time-consuming process with variable efficiency. Here we use fluorescence-activated cell sorting (FACS) to sort biallelic CRISPR-Cas9 edited single-cell iPS clones into high-throughput 96-well microtiter plates. We used high-content screening (HCS) technology and generated an in-house developed algorithm to select the correctly edited isogenic clones for continued expansion and validation. In our model we have gene-corrected the iPSCs of a Parkinson’s disease (PD) patient carrying the autosomal dominantly inherited heterozygous c.88G>C mutation in the SNCA gene, which leads to the pathogenic p.A30P form of the alpha-synuclein protein. Undertaking a PCR restriction-digest mediated clonal selection strategy prior to sequencing, we were able to post-sort validate each isogenic clone using a quadruple screening strategy. Subsequent transfection with mRNA encoding excision-only transposase allows for the generation of footprint-free isogenic iPSC lines. These monoclonal isogenic iPSC lines retain a normal molecular genotype, express pluripotency markers and have the ability to differentiate into the three germ layers. This combinatory approach of FACS, HCS and post-sorted restriction digestion facilitates the generation of isogenic cell lines for disease modelling to be scaled-up on an automated platform.

A genome-wide association study (GWAS) was performed on a set of 260 lines which belong to three different bi-parental flax mapping populations. These lines were sequenced to an averaged genome coverage of 19× using the Illumina Hi-Seq platform. Phenotypic data for 11 seed yield and oil quality traits were collected in eight year/location environments. A total of 17,288 single nucleotide polymorphisms were identified, which explained more than 80% of the phenotypic variation for days to maturity (DTM), iodine value (IOD), palmitic (PAL), stearic, linoleic (LIO) and linolenic (LIN) acid contents. Twenty-three unique genomic regions associated with 33 QTL for the studied traits were detected, thereby validating four genomic regions previously identified. The 33 QTL explained 48-73% of the phenotypic variation for oil content, IOD, PAL, LIO and LIN but only 8-14% for plant height, DTM and seed yield. A genome-wide selective sweep scan for selection signatures detected 114 genomic regions that accounted for 7.82% of the flax pseudomolecule and overlapped with the 11 GWAS-detected genomic regions associated with 18 QTL for 11 traits. The results demonstrate the utility of GWAS combined with selection signatures for dissection of the genetic structure of traits and for pinpointing genomic regions for breeding improvement.

Pathogenicity is unknown for the majority of human gene variants. For prioritization of sequenced somatic and germline mutation variants, in silico approaches can be utilized. In this study, 84 million non-synonymous Single Nucleotide Variants (SNVs) in the human coding genome were annotated using consensus Variant Effect Prediction (cVEP) method. An algorithm, implemented as a stacked ensemble of supervised learners, performed combination of the 39 functional, conservation mutation impact scores from dbNSFP4.0. Adding gene indispensability score, accounting for differences in the pathogenicities of the variants in the essential and the mutation-tolerant genes, improved the predictions. For each SNV the consensus combination gives either a continuous-value pathogenicity score, or a categorical score in five classes: pathogenic, likely pathogenic, uncertain significance, likely benign, benign. The provided class database is aimed for direct use in clinical practice. The trained prediction models were 5-fold cross-validated on the evidence-based categorical annotations from the ClinVar database. The rankings of the scores based on their ability to predict pathogenicity were obtained. A two-step strategy using the rankings, scores and class annotations is suggested for filtering and prioritization of the human exome mutations in clinical and biological applications of NGS technology.

Vanadium(IV) chalcogenide materials are of increasing interest for use in catalysis and energy conversion-related applications. Since no ternary compounds are yet known in the V–Se–Te system, we studied ternary VwSeyTe2–y (w = 1.10, 1.13; y = 0.42, 0.72) phases crystallizing in space group P3m1 (no. 164). Two single-crystal specimens with differing compositions of a solid solution were obtained using the ceramic method. All products were characterized by either single-crystal or powder X-ray diffraction. The lattice parameters increase with rising tellurium content in accordance to the larger ionic radius of the tellurium anion compared to selenium. The chemical compositions were confirmed by energy dispersive X-ray spectroscopy. Further, magnetic measurements revealed mostly antiferromagnetic properties. Simultaneous differential scanning calorimetry/thermogravimetric analyses in nitrogen atmosphere showed endothermic decomposition accompanied by the formation of VN. The results of this work can serve as a basis for the synthesis of new phases in the V–Se–Te and related vanadium chalcogenide systems.

Experiments to measure a single molecule/particle, i.e. an individual molecule/particle, at room temperature or under physiological conditions without immobilization, for example on a surface, or without significant hydrodynamic flow have so far failed. This failure has given impetus to the underlying theory of Brownian molecular motion towards its stochastics due to diffusion. Quantifying the thermodynamic jitter of molecules/particles inspires many and forms the theoretical basis of single-molecule/single-particle biophysics and biochemistry. For the first time, our simulation results for a live cell (cytoplasm) show that the tracks of individual single molecules are localized in Brownian motion, while there is fanning out in fractal diffusion (anomalous diffusion).

Let $f\left(1\right)=1$ , and let $f(n+1)=2^{2^{f\left(n\right)}}$ for every positive integer n. We consider the following hypothesis: if a system S ⊆ {x_i · x_j = x_k : i, j, k ∈ {1, . . . , n}} ∪ {x_i + 1 = x_k : i, k ∈{1, . . . , n}} has only finitely many solutions in non-negative integers x₁, . . . , x_n, then each such solution (x₁, . . . , x_n) satisfies x₁, . . . , x_n ≤ f (2n). We prove: (1) the hypothesisimplies that there exists an algorithm which takes as input a Diophantine equation, returns an integer, and this integer is greater than the heights of integer (non-negative integer, positive integer, rational) solutions, if the solution set is finite; (2) the hypothesis implies that there exists an algorithm for listing the Diophantine equations with infinitely many solutions in non-negative integers; (3) the hypothesis implies that the question whether or not a given Diophantine equation has only finitely many rational solutions is decidable by a single query to an oracle that decides whether or not a given Diophantine equation has a rational solution; (4) the hypothesis implies that the question whether or not a given Diophantine equation has only finitely many integer solutions is decidable by a single query to an oracle that decides whether or not a given Diophantine equation has an integer solution; (5) the hypothesis implies that if a set $\mathfrak{M}$ ⊆ has a finite-fold Diophantine representation, then $\mathfrak{M}$ is computable.

Despite being a rare disease worldwide, rabies has the highest morbidity and mortality rates, with nearly all symptomatic cases leading to coma and death. Rabies represents an infectious disease caused by the Rabies virus (RABV), which is part of the Lyssavirus group and the Rhabdoviridae family, and it mainly spreads through the bite and scratch of an infected mammal, but particularly of wild animals, such as bats, foxes, wolves and racoons, and of domestic animals, such as dogs and cats, in rabies-prone areas of the world. Airborne transmission has been deemed as extremely rare, and no clinical case as such has been recorded worldwide yet, except in the enclosed environment, such as research laboratories and caves where infected bats are present. Domestic mammals, such as dogs and ferrets, represent other important reservoirs of disease transmission, and the human cases of Asia and Africa amount approximately 95% of all human cases worldwide. Infected animals most commonly start transmitting the virus once the first symptoms have occurred, and if they experience disease aggravation and death within 10 days, a case of rabies is registered, more easily if the incidence occurred in the urban area and then, any person or animal that had been potentially exposed are strongly recommended to receive the inoculation. It is rare for asymptomatic mammals to transmit the illness. Most First-World and several Second-World countries have recently been declared dog rabies-free by the World Health Organization. The disease can only be treated prophylactically, with three doses of a vaccine containing an inactivated form of RABV, or with five doses of the vaccine and two doses of anti-RABV immunoglobulins within 28 days if the patient is believed to have been exposed to the virus beforehand. It has been projected that, once the viral load reaches elements of the central nervous system, prophylactic approaches are no longer effective, even if symptoms have not begun yet, and this highlights the urgent trait of the medical condition, strongly recommending exposed people to receive the prophylactic doses immediately after the potential exposure to the virus. The pathogen first infects the bodily fluids, before reaching the peripheral nervous system, from where it will gradually move toward the spinal cord or the encephalon, at a speed of movement ranging from 1 to 40 cm per day. It was also found, in extremely rare circumstances, to infect the nasopharyngeal cavity and the lungs. The primary cause of a successful, gradual advance of the viral load toward the point of clinical no-return for the patient - the CNS - is a complex mechanism of induced innate immune evasion, with the interferon system being heavily targeted and silenced by RABV proteins. The ‘Milwaukee’ protocol is locally believed to decrease the mortality rate of the clinical illness to approximately 80%, although significantly more research is required in this sense. First-line immune evasion represents the central mechanism developed by viruses during their evolutionary process to gain control over human immunity, so it could be the development and adjustment of a counter-offensive to this evolutionary operating system that could address the core elements of the problem. Human recombinant Type I and Type III Interferons were found to be significant vaccine adjuvants and to considerably delay the clinical onset of the disease. Despite their central role in natural immunity-based prophylaxis, vaccine support and, in often cases, vaccination per se, a local administration of IFNs as such may not be enough to tackle the core problem of the endemic disease, and a specific and systemic treatment of potential host cells with IFN I and III, as well as IFN-stimulating proteins, may constitute a major research requirement in the coming years of disease investigation, as the inoculation efforts with the inactivated virus and immunoglobulin administration continue. The administration of a relatively low dosage of somatic Natural Killer cells, gamma-interferon and perhaps, of somatic helper CD4+ and somatic cytotoxic CD8+ T-lymphocytes treated with alpha-, beta- and lambda-interferon could be merged with the administration of a similar dosage of alpha-, beta- and lambda-interferon during the efforts to develop an effective and less costly prophylactic vaccine against rabies. A combination of a nasal substance containing a low dosage of IFN I and III with a reduced concentration of neutralized RABV copies, and/or with a low dose of anti-RABV IgA antibodies, could also be tested for humans for the purposes of pre- and post-exposure prophylaxis.

This study describes the development of an automated bag valve mask (BVM) compression system, which, during acute shortages and supply chain disruptions can serve as a temporary emergency ventilator. The resuscitation system is based on the Arduino controller with a real-time operating system installed on a largely RepRap 3-D printable parametric component-based structure. The cost of the system is under $170, which makes it affordable for replication by makers around the world. The device provides a controlled breathing mode with tidal volumes from 100 to 800 milliliters, breathing rates from 5 to 40 breaths/minute, and inspiratory-to-expiratory ratio from 1:1 to 1:4. The system is designed for reliability and scalability of measurement circuits through the use of the serial peripheral interface and has the ability to connect additional hardware due to the object-oriented algorithmic approach. Experimental results demonstrate repeatability and accuracy exceeding human capabilities in BVM-based manual ventilation. Future work is necessary to further develop and test the system to make it acceptable for deployment outside of emergencies in clinical environments, however, the nature of the design is such that desired features are relatively easy to add with the test using protocols and parametric design files provided.

The SARS-CoV-2-induced acute COVID-19 pandemic disorder seems to have begun all of the sudden in 2020, with very little data available regarding prior times in which people experienced mysterious flu-like illness symptoms characteristic of the pandemic disease. The scientific community seems to be divided into a few parts with regards to the belief of the kind of viral origins. A significant number of scientists believe that the virus solely has natural origins and that it underwent a thorough process of zoonosis, independent of laboratory research-based research that would only catalyse zoonosis due to helping the virus gain additional function of transmission and virulence. Many other scientists believe that the virus has wide origins characteristic of “gain-of-function” laboratory research, whilst many other scientists believe that most of the viral genome has natural origins, with the zoonotic process having been artificially catalysed only in its latter part of transmission to humans. Considerable extent of scientific evidence suggests that the virus underwent a restricted, but considerable extent of “gain-of-function” research, prior to having been accidentally leaked into the nearby environment, whilst its process of zoonotic spillover into humans was influenced by such events, given for example the multidimensional pathogenetic process displayed by the virus and its main antigen of action, the spike glycoprotein, causing all kinds of immune pathophysiology - including transient immunosuppression. Investigations into the origins of the novel coronavirus have been lasting for years, seemingly with no concrete end in sight, and the available molecular testing methods to detect SARS-CoV-2 infection displaying less than perfect results have not significantly helped the process. Evidence even started pointing toward the existence of artificial, laboratory research-based viral origins, exposing a probable accidentally-induced artificial process of “accelerated viral evolution”, which could be particularly dangerous because of the nature of the SARS-CoV-2 pathogenic agent. Likewise, it is possible that the prevention of distribution of scientific data regarding scenarios as such in fact constitutes censorship, rather than regulation of data that may be considered not to be significantly evidence based. Simultaneously, it is important not to regard all hypotheses and preliminary reports of scientific research as evidence-based, but to ensure that due diligence is performed in all cases. The integrity of scientific research and ultimately of the innovation process of medical solutions depends on the integrity of democracy and the rule of law, as well as on regulating partnerships with scientific companies from world nations where autocracy rules their society.