The rapid advancements in gene therapy have opened up new possibilities for the treatment of genetic disorders, including Duchenne muscular dystrophy, Thalassemia, cystic fibrosis, Hemophilia, and Familial hypercholesterolemia. The utilization of the clustered regularly interspaced short palindromic repeats (CRISPR) - CRISPR-associated protein (Cas) system has revolutionized the field of gene therapy by enabling precise targeting of genes. In recent years, CRISPR/Cas9 has demonstrated remarkable efficacy in treating cancer and genetic diseases. However, the susceptibility of nucleic acid drugs to degradation by nucleic acid endonucleases, necessitates the development of functional vectors capable of protecting the nucleic acids from enzymatic degradation, while ensuring safety and effectiveness. This review aims to explore the biomedical potential of non-viral vector-explore CRISPR/Cas9 systems for the treatment of genetic diseases. Furthermore, it provides a comprehensive overview of recent research advances in viral and non-viral vector-based gene therapy for genetic disorders, including insights from preclinical and clinical studies. Additionally, the review analyzes the current limitations of these delivery systems and proposes avenues for the development of novel nano-delivery platforms.

Microplastics (plastic particles < 5 mm) are ubiquitous pollutants that pose the ability to carry microbiota, including pathogens. Microbial adhesion is usually a sign of pathogenicity, thus we investigated the adherent strains found on 4 mm nylon strips, which were ingested and excreted by wild fish specimens. Polymer analysis of the excreted samples shown no signs of degradation, nor have their controls, represented by the nylon strips submerged in the same water tanks. Both the ingested samples and controls presented pathogens in large numbers, revealing the fact that nylon microplastics can be physical carriers for pathogens in the aquatic environment.

Controllable, quantum-strong correlations of polarization states can be implemented with multi-photon independent states. Polarization-based photonic quantum correlations can be traced back to the overlap of the polarization Stokes vectors on the Poincaré sphere between two polarization filters. The quantum Rayleigh scattering prevents a single photon from propagating in a straight line inside a dielectric medium, and it also provides a mechanism for the projective measurement of polarization. Complexities associated with single-photon sources and detectors can be eliminated because the quantum Rayleigh scattering in a dielectric medium destroys entangled photons. Entanglement-free, identical sources and processing devices give rise to correlations rather than these being caused by “quantum nonlocality”. These analytic developments were prompted by the vanishing expectation values of the Pauli spin vector for a single photon of maximally entangled photonic Bell states.

A physical scrutiny of experimental results published in Physical Review Letters (December 2015, M. Giustina, et al., Phys. Rev. Lett. 115, 250401, and L. K. Shalm et al., Phys. Rev. Lett. 115, 250402) is undertaken. These articles reported that measured outcomes were fitted with quantum states possessing a dominant component of non-entangled photons, thereby contradicting their own claim of quantum nonlocality. With probabilities of photon detections lower than 0.1 %, the alleged quantum nonlocality cannot be classified as a resource for developing quantum computing devices, despite recent publicity. Experimental evidence of a feasible process for quantum-strong correlations has been identified (M. Iannuzzi, et al., Phys. Lett. A, 384 (9), 126200, 2020) in terms of correlations between independent and multi-photon states evaluated as Stokes vectors on the Poincaré sphere. As single-photon sources are not needed, the design and implementation of quantum computing operations will be significantly streamlined.

The Compact Midwave Imaging System (CMIS) is a wide field of view, multi-angle, multi-spectral pushframe imager that relies on the forward motion of the satellite to create a two-dimensional (2D) image swath. An airborne demonstration of CMIS was successfully completed in January-February 2021 on the NASA Langley Research Center Gulfstream III. The primary objective of the four-flight campaign was to demonstrate the capability of this unique instrument to perform stereo observations of clouds and other particulates (e.g. smoke) in the atmosphere. It is shown that the midwave infrared (MWIR) spectral bands of CMIS provide a unique 24/7 capability with high resolution for accurate stereo sensing. The instrument relies on new focal plane array (FPA) technology, which provides excellent sensitivity at much warmer detector temperatures than traditional technologies. This capability enabled a compact, low-cost design that can provide atmospheric motion vectors and cloud heights to support requirements for atmospheric winds in the 2017-2027 Earth Science Decadal Survey. Applications include day/night observations of the planetary boundary layer, severe weather, and wildfires. A comparison with current space-based earth science instruments demonstrates that the SWIR/MWIR multi-spectral capability of CMIS is competitive with larger, more expensive instrumentation. Imagery obtained over a controlled burn and operating nuclear power plant demonstrated the sensitivity of the instrument to temperature variations. The system relies on a mature stereoscopic imaging technique applied to the same scene from two independent platforms to unambiguously retrieve atmospheric motion vectors (AMVs) with accurate height assignment. This capability has been successfully applied to geostationary and low-earth orbit satellites to achieve excellent accuracy. When applied to a ground-point validation case, the accuracy for the CMIS aircraft observations was 20 m and 0.3 m/s for cloud heights and motion vectors, respectively. This result was confirmed by a detailed error analysis with analytical and covariance models. The results for CMIS cases with underflights of Aeolus, CALIPSO and Aqua provided a good validation of expected accuracies. The paper also showed the feasibility of accommodating CMIS on CubeSats to enable multiple instruments to be flown in a leader-follower mode.

For crystal periodic structure prediction, a new and concise approach based on the principles of statistical physics was employed to derive a new form of the equation to determine their period vectors (cell edge vectors), under general external stress. Then the new form is applicable to both classical physics and quantum physics. It also turned out to be the equation of state and the mechanical equilibrium condition for crystals under external stress and temperature. It should be helpful in piezoelectric and piezomagnetic studies, as the period vectors were changed by the external stress. For linear elastic crystals, it is actually also the microscopic but temperature-dependent form of the generalized Hooke's law, then can be used to calculate the corresponding elastic constants of the law, for given temperatures.

Aiming at the classification identification problem of aeroengines, this paper adopts telemetry Fourier Transform Infrared Spectrometer to collect aeroengine hot jet infrared spectrum data, and proposes an aeroengine classification identification method based on spectral feature vectors. First, aeroengine hot jet infrared spectrum data are acquired and measured, meanwhile, the spectral feature vectors based on CO2 are constructed. Then, the feature vectors are combined with the seven mainstream classification algorithms to complete the training and prediction of the classification model. In the experiment, two Fourier transform infrared spectrometers, EM27 developed by Bruker and a self-developed telemetry FTIR, were used to telemeter the hot jet of three aeroengines to obtain infrared spectral data. The training data set and test data set were randomly divided in a ratio of 3:1. The model training of the training data set and the label prediction of the test data set were carried out by combining spectral feature vectors and classification algorithms. The classification evaluation indicators were accuracy, precision, recall, confusion matrix, and F1-score. The classification recognition accuracy of the algorithm was approximately 98%. This paper has great significance for the fault diagnosis of aeroengines and classification recognition of aircrafts.

Lyme disease is the most common tick-borne illness in the United States, Europe, and Asia. Borrelia burgdorferi, a spirochete bacterium transmitted by the tick vector Ixodes scapularis, causes Lyme disease in the U.S. If untreated, Lyme arthritis, carditis, and meningitis will occur. Given the absence of a human Lyme disease vaccine, we developed a vaccine using the rabies virus vaccine vector, BNSP333, and an outer surface borrelial protein BBI39. To incorporate BBI39 into the RABV virion, we generated a chimeric BBI39 antigen, BBI39RVG, by fusing it with the final amino acids of the RABV glycoprotein. Here we demonstrated that BBI39RVG antigen was incorporated into the RABV virion, and mice vaccinated with our RABV-BBI39RVG vaccine induced high amounts of BBI39-specific antibodies which are maintained long-term. The BBI39 antibodies neutralized Borrelia in vaccinated mice when challenged with Borrelia burgdorferi by either syringe injection or infected ticks, and reduced Lyme disease pathology.

After eight decades, the largest outbreak of sylvatic yellow fever virus (YFV) was recorded in Brazil between 2016-2018. Besides human and NHP surveillance, the entomo-virological approach is considered as a complementary tool. For this study, a total of 2904 mosquitoes of Aedes, Haemagogus and Sabethes genera from six Brazilian states (Bahia, Goiás, Mato Grosso, Minas Gerais, Pará, and Tocantins), were collected and grouped in 246 pools, which were tested for YFV using RT-qPCR. We detected 20 positive pools from Minas Gerais, 5 from Goiás, and 1 from Bahia, including 12 of Hg. janthinomys and 5 of Ae. albopictus. This is the first description of natural YFV infection in this species and warns of the likelihood of urban YFV re-emergence with the Ae. albopictus as a potential bridge vector. Three YFV sequences from Hg. janthinomys from Goiás and one from Minas Gerais, as well as one from Ae. albopictus from Minas Gerais clustered within the 2016-2018 outbreak clade, indicating YFV spread from Midwest and its infection in a main and in a likely-novel bridging vector species. Entomo-virological surveillance is critical in the YFV monitoring in Brazil, which could highlight the need to strengthen YFV surveillance, vaccination coverage, and vector control measures.

Gene therapy has seen major progress in recent years. Viral vectors have made a significant contribution through efficient engineering for improved delivery and safety. A large variety of indications such as cancer, cardiovascular, metabolic, hematological, neurological, muscular, ophthalmological, infectious diseases, and immunodeficiency have been targeted. Viral vectors based on adenoviruses, adeno-associated viruses, herpes simplex viruses, retroviruses including lentiviruses, alphaviruses, flaviviruses, measles viruses, rhabdoviruses, Newcastle disease virus, poxviruses, picornaviruses, reoviruses, and polyomaviruses have been used. Proof-of-concept has been demonstrated for different indications in animal models. Therapeutic efficacy has also been achieved in clinical trials. Several viral vector-based drugs have been approved for the treatment of cancer, and hematological, metabolic, and neurological diseases. Moreover, viral vector-based vaccines have been approved against COVID-19 and Ebola virus disease.

Lentiviral vectors (LVs) are a powerful tool for gene and cell therapy and human embryonic kidney cells (HEK293) have been extensively used as a platform for production of these vectors. Like most cells and cellular tissues, HEK293 cells release extracellular vesicles (EVs). EVs released by cells share similar size, biophysical characteristics and even a biogenesis pathway with cell-produced enveloped viruses, making it a challenge to efficiently separate EVs from LVs. Thus, EVs co-purify with LVs during downstream processing, becoming “impurities” in the context of cell therapy. To characterize EVs from an inducible lentivirus producing cell line, two conditions were studied: non-induced and induced. EVs’ identity was confirmed by transmission electron microscopy and western blot. Seven proteins were identified by mass spectrometry as potential EV markers. Lipid composition of EVs and LVs showed similar enrichment in phosphatidylserine. RNA cargos in EVs showed enrichment in genes involved in viral processes and binding functions. Flow virometry, GTA and ddPCR results also confirmed the heterogenic nature of EVs and LVs populations. These findings provide insights on the product profile of lentiviral preparation and could help develop separation strategies of co-produced EVs.

Understanding ecological interactions is a key in managing phytopathology. Although entomologists rely mostly on both traditional molecular methods and morphological characteristics to identify pests, next-generation sequencing is becoming the go-to avenue for scientists studying fungal and oomycete phytopathogens. These organisms sometimes infect plants together with insects. There are many relationships yet to be discovered and much to learn about how these organisms interact with one another. Considering the growing number of exotic insect introductions in Canada, a high-throughput strategy for screening those insects is already implemented by the Canadian Food Inspection Agency (CFIA). However, no plan is deployed to investigate the phytopathogenic fungal and oomycete species interacting with insects. Metagenomics analysis was performed on the preservation fluids from CFIA’s insect traps across Canada. Using the Ion Torrent PGM technology and fusion primers for multiplexing and indexing, community profiling was conducted on the different semiochemicals used in the insect traps and the various areas where these traps were placed. Internal transcribed spacer 1 (fungi and oomycetes) and adenosine triphosphate synthase subunit 9-nicotinamide adenine dinucleotide dehydrogenase subunit 9 spacer amplicons were generated. Although direct links between organisms could not be established, moderately phytopathogenic fungi (e.g., Leptographium spp. and Meria laricis) and oomycetes (mainly Peronospora spp. and Pythium spp.) unique to every type of semiochemical were discovered. The entomopathogenic yeast Candida michaelii was also detected. This project demonstrated our ability to screen for unwanted species faster and at a higher scale and throughput than traditional pathogen diagnostic techniques. Additionally, minimal modifications to this approach would allow it to be used in other phytopathology fields.

The new class of mRNA vaccines is studied extensively, leading to many novel prospects based on the pivotal success of vaccines against the SARS-Cov-2 virus. Many novel mechanisms of immune response discovered have led to the possibility of mutation-resistant vaccines by combining multiple conserved epitopes as antigens to manipulate the T-cell and B-cell responses; these antigens can also come from different organisms, providing protection against numerous diseases and of most tremendous significance is the utility of mRNA vaccines in preventing and treating more than 100 autoimmune disorders. This is a significant humanitarian breakthrough given the ease and faster and low cost of mRNA vaccines, being a chemical entity. This paper provides a prospective analysis of mRNA vaccines with much broader applications than anticipated when these vaccines entered treating SARS-Cov-2 infections.

Molecular therapies exploiting mRNA vectors embody enormous potential, as evidenced by the utility of this technology for the context of the COVID-19 pandemic. None-the-less, broad implementation of these promising strategies has been restricted by the limited repertoires of delivery vehicles capable of mRNA transport. On this basis, we explored a strategy based on exploiting the well characterized entry biology of adenovirus. To this end, we studied an adenovirus-polylysine (AdpL) that embodied “piggyback” transport of the mRNA on the capsid exterior of adenovirus. We hypothesized that the efficient steps of Ad binding, receptor-mediated entry, and capsid-mediated endosome escape could provide an effective pathway for transport of mRNA to the cellular cytosol for transgene expression. Our studies confirmed that AdpL could mediate effective gene transfer of mRNA vectors in vitro and in vivo. Facets of this method may offer key utilities to feasibilize the promise of mRNA-based therapeutics.

Pathological vessel growth harms vision and may finally lead to vision loss. Anti-angiogenic gene therapy with viral vectors for ocular neovascularization has shown great promise in pre-clinical studies. Most of the studies has conducted with different adeno-associate serotype vectors. In addition, Adeno and lentivirus vectors have been used. Therapy has targeted to block vascular endothelial growth factors or other pro-angiogenic factors. Clinical trials of intraocular gene therapy for neovascularization have shown the treatment to be safe without severe adverse events or systemic effects. Nevertheless, clinical studies have not proceeded phase 2 trials further.

Aedes aegypti mosquitoes are primary vectors of dengue, yellow fever, chikungunya and Zika viruses. Ae. aegypti is highly anthropophilic and relies nearly exclusively on human blood meals and habitats for reproduction. Socioeconomic factors may influence the spread of Ae. aegypti due to its close relationship with humans. This paper describes and summarizes the published literature on how socioeconomic variables influence the distribution of Ae. aegypti mosquitoes in the mainland United States. A comprehensive search of PubMed/Medline, Scopus, Web of Science, and EBSCO Academic Search Complete through June 12, 2019 was used to retrieve all articles published in English on the association of socioeconomic factors and the distribution of Ae. aegypti mosquitoes. Additionally, a hand search of mosquito control association websites was conducted in an attempt to identify relevant grey literature. Articles were screened for eligibility using the process described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Initially, 3,493 articles were identified through the database searches and previously known literature. After checking for duplicates, 2,145 articles remained. 570 additional records were identified through the grey literature search for a total of 2,715 articles. These articles were screened for eligibility using their titles and abstracts, and 2,677 articles were excluded for not meeting the eligibility criteria. Finally, the full text for each of the remaining articles (n = 38) was read to determine eligibility. Through this screening process, 11 articles were identified for inclusion in this review. The findings for these 11 studies revealed inconsistent relationships between the studied socioeconomic factors and the distribution and abundance of Ae. aegypti. The findings of this review suggest a gap in the literature and understanding of the influence of anthropogenic factors on the distribution of Ae. aegypti that could hinder efforts to implement effective public health prevention and control strategies should a disease outbreak occur.

Adeno-associated viral (AAV) vectors can be used for gene delivery. AAV.CAP-Mac was recently developed; it can cross the blood-brain barrier and transduce cells throughout the CNS. However, some brain regions were not transduced in adult rhesus monkeys. Additionally, AAV vectors can only package 5 kb of DNA. Also, AAV vectors may be genotoxic and cytotoxic, especially at high doses. Finally, AAV vectors are very expensive to produce at sufficiently high titers for treatment. Off-the-shelf cell-based delivery systems wherein the cells can infiltrate the target tissue and be hyper-motile would be ideal. Also, mRNA-based gene editing would be a transient treatment, and thus be much safer.

In the early 2000s, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) emerged as a performant and relevant tool for identifying micro-organisms. Since then, it has become practically essential for identifying bacteria in microbiological diagnostic laboratories. In the last decade, it was successfully applied for arthropod identification allowing to distinguish vectors from non-vectors of infectious diseases. However, identification failures are not rare, hampering it widely use. Failure is generally attributed either to the absence of respective counter species MS spectra in the database, or to the insufficient quality of query MS spectra (i.e. lower intensity and diversity of MS peaks detected). To avoid matching errors due to non-compliant spectra, the development of a strategy for detecting and excluding outlier MS profiles became compulsory. To this end, we created MSProfileR, an R package leading to a bioinformatics tool through a simple installation, integrating the control quality system of MS spectra and an analysis pipeline including peak detection and MS spectra comparisons. MSProfileR can also add metadata concerning the sample that the spectra are derived from. MSProfileR has been developed in the R environment and offers a user-friendly web interface using the R Shiny framework. It is available on Microsoft Windows as a web browser application by simply navigation using the link of the package on the Github. MSProfileR is therefore accessible to non-computer specialists and is freely available to the scientific community. We evaluated MSProfileR using two datasets including exclusively MS spectra from arthropods. In addition to coherent sample classification, outlier MS spectra were detected in each dataset confirming the value of MSProfileR.

Volcanism powered by tidal forces inside celestial bodies can provide enough energy to keep important solvents for living systems in the liquid phase. Moreover, tidal forces and their environmental consequences may strongly influence habitability of planets and other celestial bodies and may result in special forms of live and living conditions. A prerequisite to calculate such tidal interactions and consequences is depending on simulations for tidal accelerations in a multi-body system. Unfortunately, from measurements in many extrasolar planetary systems only few physical and orbital parameters are well enough known for investigated celestial bodies. For calculating tidal acceleration vectors under missing most orbital parameter exactly, a simulation method is developed that is only based on a few basic parameters, easily measurable even in extrasolar planetary systems. Such a method as being presented here, allows finding a relation between the tidal acceleration vectors and potential heating inside celestial objects. Using values and results of our model approach to our solar system as a “gold standard” for feasibility allowed us to classify this heating in relation to different forms of volcanism. This “gold standard” approach gave us a classification measure for the relevance of tidal heating in other extrasolar systems with a reduced availability of exact physical parameters. We would help to estimate conditions for the identification of potential candidates for further sophisticated investigations by more complex established methods like viscoelastic multi-body theories. As a first example, we applied the procedures developed here to the extrasolar planetary system TRAPPIST-1 as an example to check our working hypothesis.

Atmospheric Motion Vectors (AMVs) calculated by six different institutions (Brazil Center for Weather Prediction and Climate Studies/CPTEC/INPE, European Organization for the Exploitation of Meteorological Satellites/EUMETSAT, Japan Meteorological Agency/JMA, Korea Meteorological Administration/KMA, Unites States National Oceanic and Atmospheric Administration/NOAA and the Satellite Application Facility on Support to Nowcasting/NWCSAF) with JMA’s Himawari-8 satellite data and other common input data are here compared. The comparison is based on two different AMV input datasets, calculated with two different image triplets for 21 July 2016, and the use of a prescribed and a specific configuration. The main results of the study are summarized as follows: (1) the differences in the AMV datasets depend very much on the “AMV height assignment” used and much less on the use of a prescribed or specific configuration; (2) the use of the “Common Quality Indicator (CQI)” has a quantified skill in filtering collocated AMVs for an improved statistical agreement between centers; (3) JMA AMV algorithm has the best overall performance considering all validation metrics, most likely due to its height assignment: “optimal estimation using observed radiance and NWP wind vertical profile”.

The increasing use of renewable energies as a source of electricity has led to a fundamental transition of the power supply system. The integration of fluctuating weather-dependent energy sources into the grid already has a major impact on the load flows of the grid. As a result, the interest in forecasting wind and solar radiation with a sufficient accuracy over short time horizons grew. In this study the short-term forecast of the effective cloud albedo based on optical flow estimation methods are investigated. The optical flow method utilized here is TV-L¹ from the open source library OpenCV. This method uses a multi-scale-approach to capture cloud motions on various spatial scales. After the clouds are displaced the solar surface radiation will be calculated with SPECMAGIC NOW which computes the global irradiation spectrally resolved from satellite imagery. Due to a high temporal and spatial resolution of satellite measurements the effective cloud albedo and thus solar radiation can be forecasted from 5 minutes up to 4 hours with a resolution of 0.05°. In the following there will be a brief description of the method for the short-term forecast of the effective cloud albedo. Subsequently evaluation results will be presented and discussed. Finally an outlook of further developments will be given.

Tularemia is a zoonotic disease caused by {\it Francisella tularensis} bacteria, a gram-negative coccobacillus-shaped bacterium. There are multiple transmission routes of the infection to humans such as consumption of contaminated food or water, handling of infected animals or bites from {\it haematophagous} arthropods (such as ticks, deer flies, or mosquitoes). In this study we focus on transmission via the bites of ticks and developed a deterministic model of ordinary and impulsive differential equations to gain insight in the differential effect of prescribed fire on {\it Demacenta variablis} and {\it Amblyomma americanum} ticks and the prevalence of tularemina. We found that prescribed fire differentially reduce the number of the two ticks with {\it A. americanum} reduced the least compare to {\it D. variablis} subsequently leading to differential increase of tularemia new infected cases in humans and rodents. Our result further indicates that the spatial arrangement of burn against unburn areas may not matter as either arrangement led to fewer ticks and reduction in tularemia transmission when prescribed fire was implemented. The results of this study provide important new understandings of the intricate effect of prescribed fire on tick species, and the dynamics of the tick-borne disease, tularemia disease in this study.

Interferon gamma (IFNg) is a pleiotropic cytokine that can potentially reprogramme the tumour microenvironment. However, the antitumour immunomodulatory properties of IFNg still need to be validated due to variable therapeutic outcomes in preclinical and clinical studies. We developed a replication-deficient Semliki Forest virus vector expressing IFNg (SFV/IFNg) and evaluated its immunomodulatory antitumour potential in vitro in a model of 3D spheroids and in vivo in immunocompetent 4T1 mouse breast cancer model. We demonstrated that SFV-derived IFN-g stimulated bone marrow macrophages to acquire the tumoricidal M1 phenotype in 3D nonattached conditions. Coculturing SFV/IFNg-infected 4T1 spheroids with BMDMs inhibited spheroid growth. In the orthotopic 4T1 mouse model, intratumoural administration of SFV/IFNg virus particles alone or in combination with the Pam3CSK4 TLR2/1 ligand led to significant inhibition of tumour growth compared to the administration of the control SFV/Luc virus particles. Analysis of the composition of intra-tumoural lymphoid cells isolated from tumours after SFV/IFNg treatment revealed an increase in CD4+ and CD8+ and a decrease in T-reg (CD4+/CD25+/FoxP3+) cell populations. Furthermore, a significant decrease in the populations of cells bearing myeloid cell markers CD11b, CD38 and CD206 was observed. In conclusion, the SFV/IFNg vector induces a therapeutic antitumour T-cell response and inhibits myeloid cell infiltration in treated tumours.

There has been observational evidence about spin axes of quasars in large quasar groups correlated over hundreds of Mpc. This is seen in the radio spectrum as well as in the optical range. There is not yet a satisfactory explanation of this "spooky" alignment. This alignment cannot be explained by mutual interaction at the time that quasars manifest themselves optically. A cosmological explanation could be possible in the formation of superconducting vortices (cosmic strings) in the early universe, just after the symmetry-breaking phase of the universe. We gathered from the NASA/IPAC and SIMBAD extragalactic databases the right ascension, declination, inclination, position angle and eccentricity of the host galaxies of 3 large quasar groups to obtain the azimuthal and polar angle of the spin vectors. The alignment of the azimuthal angle of the spin vectors of quasars in their host galaxy is confirmed in the large quasar group U1.27 and compared with two other groups in the vicinity, i.e., U1.11 and U1.28. It is well possible that the azimuthal angle alignment fits the predicted azimuthal angle dependency in the theoretical model of the formation of general relativistic superconducting vortices, where the initial axially symmetry is broken just after the symmetry breaking of the scalar-gauge field.} \keyword{quasar groups; alignment spin vectors; host galaxy; cosmic strings; symmetry breaking; scalar-gauge field.

The “NWCSAF High Resolution Winds (NWC/GEO-HRW)” software is developed by the EUMETSAT’s “Satellite Application Facility on support to Nowcasting and very short range forecasting (NWCSAF)”, inside its stand-alone software package for calculation of meteorological products with geostationary satellite data (NWC/GEO). The whole NWC/GEO software package can be obtained after registration at the NWCSAF Helpdesk, www.nwcsaf.org. It is easy to get, install and use. The code is easy to read and fully documented. And in the NWCSAF Helpdesk, users find support and help for its use. “NWCSAF High Resolution Winds” provides a detailed calculation of Atmospheric Motion Vectors (AMVs) and Trajectories, locally and in near real time, using as input NWP model data and geostationary satellite image data. The latest version of the software, v2018, is able to process MSG, Himawari-8/9, GOES-N and GOES-R satellite series images, so that AMVs and Trajectories can be calculated all throughout the planet Earth with the same algorithm and quality. In the “2014 and 2018 AMV Intercomparison Studies”, “NWCSAF High Resolution Winds” has shown to be one of the two best AMV algorithms for both MSG and Himawari-8/9 satellites. And the “Coordination Group for Meteorological Satellites (CGMS)” has recognized in its “2012 Meeting Report”: 1. “NWCSAF High Resolution Winds” fulfills the requirements to be a portable stand-alone AMV calculation software due to its easy installation and usability. 2. It has been successfully adapted by some CGMS members and serves as an important tool for development. It is modular, well documented, and well suited as stand-alone AMV software. 3. Although alternatives exist as portable stand-alone AMV calculation software, they are not as advanced in terms of documentation and do not have an existing Helpdesk. Considering this, a full description and validation of the “NWCSAF/High Resolution Winds” is shown here for the first time in a peer-reviewed paper. The procedure to obtain the software for operational meteorology and research is also explained.

Ebola Virus Disease (EVD) is one of the most lethal transmissible infections characterized by a high fatality rate, and caused by members of the Filoviridae family. The recent large outbreak of EVD in West Africa (2013-2016), highlighted the worldwide danger of this disease and its impact on global public health and economy. The development of highly needed anti-Filoviridae antivirals has been so far hampered by the shortage of tools to study their life cycle in vitro, and therefore screen for potential active compounds outside a biosafety level-4 (BSL-4) containment. Importantly, the development of surrogate models to in vitro study of Filoviridae entry in a BSL-2 setting, such as viral pseudotypes and Ebola virus like particles, tremendously boosted both our knowledge on viral life cycle and the identification of promising anti-Filoviridae compounds interfering with viral entry. In this context, the combination of such surrogate systems with large-scale small molecule compounds and haploid genetic screenings, as well as rational drug design and drug repurposing approaches will prove priceless in our quest for the development of a treatment for EVD.

Persistent human papillomavirus (HPV) infection is responsible for practically all cervical and a high proportion of anogenital and oropharyngeal cancers. Therapeutic HPV vaccines in clinical development show great promise in improving outcomes for patients who mount an anti-HPV T cell response, but far from all patients elicit a sufficient immunological response. This witnesses a translational gap between animal models and human patients. Here, we investigated the potential of a new assay consisting of co-culturing vaccine-transduced dendritic cells (DCs) with syngeneic healthy human peripheral blood mononuclear cells (PBMCs) to mimic a human in vivo immunization. This new promising human ex vivo PBMC assay was evaluated using an innovative therapeutic adenovirus (Adv)-based HPV vaccine encoding the E1, E2, E6, and E7 HPV16 genes. This new method allowed us to show that vaccine-transduced DCs yielded functional effector T cells and unveiled information on immunohierarchy showing E1-specific T cell immunodominance over time. We suggest that this assay can be a valuable translational tool to complement the known animal models, not only for HPV therapeutic vaccines, and supports the use of E1 as an immunotherapeutic target. Nevertheless, the findings reported here need to be validated in a larger number of donors, and preferably in patient samples.

The COVID-19 pandemic has underscored the importance of swift responses and the necessity of dependable technologies for vaccine development. Our team previously developed a fast cloning system for the modified vaccinia virus Ankara (MVA) vaccine platform. In this study, we report the construction and preclinical testing of a recombinant MVA vaccine obtained using this system. We obtained recombinant MVA expressing the unmodified full-length SARS-CoV-2 spike (S) protein containing the D614G amino acid substitution (MVA-Sdg) and a version expressing a modified S protein containing amino acid substitutions designed to stabilize the protein a in a pre-fusion conformation (MVA-Spf). S protein expressed by MVA-Sdg was found to be expressed and correctly processed and transported to the cell surface, where it efficiently produced cell-cell fusion. Version Spf, however, was not proteolytically processed and despite being transported to the plasma membrane, it failed to induce cell-cell fusion. We assessed both vaccine candidates in prime-boost regimens in the susceptible transgenic K18-human angiotensin converting enzyme 2 (K18-hACE2) mice and in golden Syrian hamsters. Robust immunity and protection from disease was induced with either vaccine in both animal models. Remarkably, the MVA-Spf vaccine candidate produced higher levels of antibodies, a stronger T cell response, and a higher degree of protection from challenge. In addition, the levels of SARS-CoV-2 in the brain of MVA-Spf inoculated mice was decreased to undetectable levels. Those results add to our current experience and range of vaccine vectors and technologies for developing a safe and effective COVID-19 vaccine

Most existing cancer therapies negatively affect normal tissue as well as cancerous tissue. A potentially effective strategy for treating cancer that precludes off-target damage and could be an option for most patients would involve targeting one or more mutations that are ubiquitous in the given patient’s tumor(s). To effect this strategy, one would employ multi-region sequencing of a patient’s primary tumor and metastases to seek out mutations that are shared between all or at least most regions. Once the target or targets are known, one would ideally rapidly generate a molecular switch for at least one of said ubiquitous mutations that can distinguish the mutated DNA, RNA, or protein from the wild-type version and subsequently trigger a therapeutic response. I propose that the therapeutic response involve the replication of an oncolytic virus or intracellular bacterium, as any mutation can theoretically be detected by a vector that enters the cell - and automatic propagation could be very helpful. Moreover, the mutation “signal” can be easily enhanced through transcriptional and translational (if the target is an intracellular protein) enhancement. Importantly, RNA may make the best target for the molecular switches in terms of amplification of the signal and ease of targeting.

Analysis of the demographic, temporal and seasonal distribution of hantavirus infections in Barbados was conducted using national surveillance data for 861 laboratory confirmed cases during 2008-2016. The crude incidence rate of hantavirus infections varied from 5.05 to 100.16 per 100,000 persons per year. One major hantavirus epidemic occurred in Barbados during 2010. Hantavirus cases occurred throughout the year with low level transmission during the dry season (December to June) with increased transmission during rainy season (July to November) and a seasonal peak in August. Hantavirus incidence rates were significantly higher in females than males every year during the study period. More than 50% of hantavirus cases were 30 years of age or less. The highest incidence rate (63.36 cases per 100,000 population) was observed among patients 0–4 years of age. This represents the first epidemiological data for hantavirus disease among an entire population in the English-speaking Caribbean.

Many protein expression systems are primary utilised to produce a single, specific recombinant protein. In contrast, most biological processes such as virus assembly rely upon a complex of several interacting proteins rather than the activity of a sole protein. The high complexity of the baculovirus genome, coupled with a multiphase replication cycle incorporating distinct transcriptional steps, made it the ideal system to manipulate for high-level expression of a single or co-expression of multiple foreign proteins within a single cell. We have developed and utilised a series of recombinant baculovirus systems to unravel the sequential assembly process of a complex non-enveloped model virus, Bluetongue virus (BTV). The high protein yields expressed by the baculovirus system not only facilitated structure-function analysis of each viral proteins but were also advantageous to crystallography studies and supported the first atomic level resolution of a recombinant viral protein, the major BTV capsid protein. Further, the formation of recombinant double-shelled virus-like particles (VLPs) provided insights into the structure-function relationships among the four major structural proteins of the BTV whilst also representing a potential candidate for a viral vaccine. The baculovirus multi-gene expression system facilitated the study of structurally complex viruses (both non-enveloped and enveloped viruses) and heralded in a new generation of viral vaccines.

Keywords: Porcine reproductive and respiratory syndrome virus, baculovirus surface display vectors, neutralizing antibody, IFN-γ, IL-4.

The research and development of non-viral gene therapy has been extensive over the past decade and has received a big push thanks to the successful approval of non-viral gene therapy products in recent times. Despite these developments, gene therapy applications in cancer have been limited. One of the main causes of this has been the imbalance in development of delivery vectors as compared to nucleic acid payloads. This paper reviews non-viral vectors that can be used to deliver nucleic acids for cancer treatment. It discusses various types of vectors and highlights their current applications. Additionally, it also discusses perspective on regulatory landscape to facilitate commercial translation of gene therapy.

miRNAs have recently attracted investigators' interest as regulators of valvular diseases pathogenesis, diagnostic biomarkers, and therapeutical targets. Evidence from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse development, aortic leaflet fusion, and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes of different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address miRNAs over or under-representation and thus, their impact on pathogeneses. In this review, we discuss the fundamental intra- and intercellular signals regulated by miRNAs leading to defects in mitral and aortic valves, congenital heart diseases, and the possible therapeutic strategies targeting them. These miRNAs inhibitors comprise of antisense oligonucleotides and sponge vectors. The miRNA mimics, miRNA expression vectors, and small molecules are instead possible practical strategies to increase specific miRNA activity. Advantages and technical limitations of these new drugs, including instability and complex pharmacokinetics, are also presented. Novel delivery strategies, such as nanoparticles and liposomes, are described to improve knowledge on future personalized treatment directions.

Global wind observations are fundamental for studying weather and climate dynamics. Most wind measurements come from atmospheric motion vectors (AMVs) by tracking the displacement of cloud or water vapor features. These AMVs generally rely on thermal infrared (IR) techniques for their height assignments, which are subject to large uncertainties in the presence of weak or reversed vertical temperature gradients around the planetary boundary layer (PBL) and with tropopause folding. Stereo imaging can overcome the height assignment problem using geometric parallax for feature height determination. In this study we develop a stereo 3D-Wind algorithm to simultaneously retrieve AMV and height from geostationary (GEO) and low Earth orbit (LEO) satellite imagery and apply it to collocated Geostationary Operational Environmental Satellite (GOES) and Multi-angle Imaging SpectroRadiometer (MISR) imagery. The new algorithm improves AMV and height relative to products from GOES or MISR alone, with an estimated accuracy of <0.5 m/s in AMV and <200 m in height with 2.2 km sampling. The algorithm can be generalized to other LEO-GEO or GEO-GEO combinations for greater spatiotemporal coverage. The technique demonstrated with MISR and GOES has important implications for future high-quality AMV observations, for which a low-cost constellation of CubeSats can play a vital role.

In electric circuits, energy is delivered by electromagnetic fields through the space, as suggested by Kraus and Carver. They provide insights by showing electric/magnetic fields and Poynting vector directions around a DC circuit. In this work, the energy flow mechanism by Kraus and Carver is further studied theoretically for arbitrary terminal potentials of a DC power source.

In crystal structure prediction, Newton's second law can always be applied to particles (atoms or ions) in a cell to determine their positions. However the values of the period vectors (crystal cell edge vectors) should be determined as well. Here we applied the dynamical equations of period vectors derived recently based on Newton's laws (doi:/10.1139/cjp-2014-0518) for that purpose, where the period vectors are driven by the imbalance between the internal and external pressures/stresses. For equilibrium states, they became equations of state, which essentially turn out the equilibrium conditions of crystals from mechanical point of view. For external pressure, by ignoring some effects, they reduced to the Mie-Gruneisen equation. Since the internal stress has both a full kinetic energy term and a full interaction term, the influences of both external temperature and stress/pressure on crystal structures can be calculated, then thermodynamical properties and processes were presented. Contrary to usual ideas, the equations show that pure harmonic vibrating phonons can result in thermal expansion in crystals when the external temperature is changed. Finally, crystal system collapse due to temperature and/or stress/pressure change was discussed.

Since crystals are made of periodic structures in space, predicting their three period vectors starting from any values based on the inside interactions is a basic theoretical physics problem. For the general situation where crystals are under constant external stress, we derived dynamical equations of the period vectors in the framework of Newtonian dynamics, for pair potentials recently (doi:/10.1139/cjp-2014-0518). The derived dynamical equations show that the period vectors are driven by the imbalance between the internal and external stresses. This presents a physical process where when the external stress changes, the crystal structure changes accordingly, since the original internal stress can not balance the external stress. The internal stress has both a full kinetic energy term and a full interaction term. It is extended to many-body interactions in this paper. As a result, all conclusions in the pair-potential case also apply for many-body potentials.

Xylella fastidiosa (Xf) is classified as a quarantine pest due to its consequences on economically significant crops. Its main form of transmission in Europe is through the insect Philaenus spumarius. Due to climate change, populations of insect vectors became more extensive, resulting in the dissemination of the bacteria through longer periods, but destruction of these insects raises issues, due to their role in nature. Upon infection, Xf causes the occlusion of xylem vessels by bacterial aggregates, and tylosis production by the plant as a response to infection. Although symptomatic manifestations of Xf are often linked to water stress, a variety of plant species have been found to carry the pathogen without symptoms, making it all too easy to evade detection when relying on visual inspections. Beyond water stress, other conditions (individual plant resistance/tolerance, bacterial concentrations, transpiration rates, and interactions between subspecies) may be implicated in symptom development. A thorough understanding of how this disease develops, especially its capacity to spread from the initial focus and establish a systemic infection, is imperative. This review focuses on the Xf infection process, the development of symptoms, its spread within Portugal, and the actions that have been taken to counter it.

This survey reports on the DNA identification and occurrence of Culex torrentium and Cx. pipiens s.s. in Belgium. These native disease vector mosquito species are morphologically difficult to separate and the biotypes of Cx. pipiens s.s. are morphologically indistinguishable. Culex torrentium and Cx. pipiens s.s. were identified using the COI and ACE2 loci. We recorded 1,248 Cx. pipiens s.s. and 401 Cx. torrentium specimens from 24 locations in Belgium (collected between 2017 and 2019). Culex pipiens biotypes pipiens and molestus, and their hybrids, were differentiated by fragment size analysis of the CQ11 locus (956 pipiens and 227 molestus biotype specimens, 29 hybrids). Hybrids were observed at 13 out of 16 sympatric sites. These results confirm that both species are widespread in Belgium, but while Cx. torrentium revealed many COI haplotypes, Cx. pipiens s.s. showed only one abundant haplotype. This latter observation may either reflect a recent population-wide demographic or range expansion, or a recent bottleneck, possibly linked to a Wolbachia infection. Finally, new evidence is provided for the asymmetric but limited introgression of the molestus biotype into the pipiens biotype.

Height assignment is an important problem for satellite measurements of Atmospheric Motion Vectors (AMVs) that are interpreted as winds by forecast and assimilation systems. Stereo methods assign heights to AMVs from the parallax observed between observations from different vantage points in orbit while tracking cloud or moisture features. In this paper, we fully develop the stereo method to jointly retrieve wind vectors with their geometric heights from geostationary satellite pairs. Synchronization of observations between observing systems is not required. NASA and NOAA stereo-winds codes have implemented this method and we have processed large datasets from GOES-16, -17, and Himawari-8. Our retrievals are validated against rawinsonde observations and demonstrate the potential to improve forecast skill. Stereo winds also offer an important mitigation for the loop heat pipe anomaly on GOES-17 during times when warm focal plane temperatures cause infra-red channels that are needed for operational height assignments to fail. We also examine several application areas, including deep convection in tropical cyclones, planetary boundary layer dynamics, and fire smoke plumes, where stereo methods provide insights into atmospheric processes. The stereo method is broadly applicable across the geostationary ring where systems offering similar Image Navigation and Registration (INR) performance as GOES-R are deployed.

We study two fundamental linguistic channels ‒ the Sentences and the Interpunctions channels ‒ and show they can reveal deeper connections between texts. The theory applied does not follow the actual paradigm of linguistic studies. As study‒case, we consider the Greek New Testament, with the purpose of determining mathematical connections between its texts and possible differences in writing style (mathematically defined) of writers, and in reading skill required to their readers. The analysis is based on deep‒language parameters and communication/information theory. To set the New Testament texts in the larger Greek Classical Literature, we consider texts written by Aesop, Polybius, Flavius Josephus and Plutarch. The results largely confirm what scholars have found about the New Testament texts giving, therefore, credibility to the theory. The gospel according to John is very similar to Fables written by Aesop. Surprisingly, the Epistle to the Hebrews and Apocalypse, are each other “photocopy” in the two linguistic channels, and not linked to all other texts. These two texts deserve further study by historians of the early Christian Church Literature at the level of meaning, readers and possible Old Testament texts which might have influenced them. The theory can guide scholars to study any literary corpus.

In this non-exhaustive review, we discuss the importance of invariant vectors in atomic physics, such as the Laplace-Runge-Lenz vector, the Redmond vector in the presence of an electric field, the Landau-Avron-Sivardière vector when the system is subject to a magnetic field, and the supergeneralized Runge-Lenz vector for the two-center problem. Application to Stark and Zeeman effects are outlined. The existence of constants of motion in the charge-dyon system is also briefly mentioned.

While it is well known that 98-99% of the human genome do not encode proteins, but are nevertheless transcriptionally active and give rise to a broad spectrum of noncoding RNAs (ncRNAs) with complex regulatory and structural functions, specific functions have so far been assigned to only a tiny fraction of all known transcripts. On the other hand, the striking observation of an overwhelmingly growing fraction of ncRNAs, in contrast to an only modest increase in the number of protein-coding genes, during evolution from simple organisms to humans, strongly suggests critical but so far essentially unexplored roles of the noncoding genome for human health and disease pathogenesis. Research into the vast realm of the noncoding genome during the past decades thus lead to a profoundly enhanced appreciation of the multi-level complexity of the human genome. Here, we address a few of the many huge remaining knowledge gaps and consider some newly emerging questions and concepts of research. We attempt to provide an up-to-date assessment of recent insights obtained by molecular and cell biological methods, and by the application of systems biology approaches. Specifically, we discuss current data regarding two questions: (1) By which mechanisms could evolutionary recent ncRNAs with critical regulatory functions in a broad spectrum of cell types (neural, immune, cardiovascular) constitute novel thera-peutic targets in human diseases ? (2) Since noncoding genome evolution is causally linked to brain evolution, and given the pro-found interactions between brain and immune system, could human-specific brain-expressed ncRNAs play a direct or indirect (immune-mediated) role in human diseases? Synergistic with the remarkable recent progress regarding delivery, efficacy, and safety of nu-cleic acid-based therapies, the ongoing large-scale exploration of the noncoding genome for human-specific therapeutic targets is encouraging to proceed with the development and clinical evaluation of novel therapeutic pathways suggested by these research fields.

Advances in biological sciences have been applied in medicine, agriculture and industry with great benefit. Some recent trends in society, governance structures and communications, however, appear to be hampering the use of new scientific findings for controlling infectious diseases. These limitations are illustrated with examples related to (i) the adaptation of fresh water mosquito vectors of major arboviral diseases to salinity in coastal areas with consequences for disease transmission, (ii) understanding the implications of reduced dengue transmission during the COVID-19 lockdown for dengue control, (iii) causes underlying the rapid spread of the malaria vector Anopheles stephensi in South Asia and Africa, (iv) the application of serodiagnostic techniques for Lyme disease and tick-borne relapsing fever caused by tick-borne bacteria of the genus Borrelia, and (v) COVID-19 prevention.

Spinors are used for the computation of probability in quantum mechanics. They are treated as elements of a complex vector space in contrast to a real vector space. Spinor theory is abstract mathematics with an ambiguous interpretation. The overall phase of spinors does not affect the computation of probability in quantum mechanics. If two spinors have an overall phase of imaginary number i, then they can be treated like vectors in a real vector space. The square of the magnitude of the number, which is the sum of dot product and the term having basis vector i of cross product of two such vectors, is equal to the probability computed using the corresponding spinors. Therefore, the geometry of such spinors can be easily depicted in a three-dimensional space like vectors in a real vector space. Spinors are not isotropic vectors in Hilbert space. The sum of dot product and cross product of two complex numbers is equivalent to the quotient of the division of one complex number by another. Similarly, the sum of dot product and cross product of two vectors is the quotient of the division of one vector by another. Using the rules of division of vectors, we can find the rules of multiplication of vectors. The rules of multiplication and division of basis vector i match the rules of multiplication and division of imaginary number i. Therefore, basis vector i is nothing but imaginary number i. Multiplication of dot and cross product of two vectors to the second vector will give us the components of the first vector that are parallel and orthogonal to the second vector. Vectors are also made up of complex numbers like spinors. The reason for finding dot product of complex numbers in the process of computing the probability is to ignore the overall phase in contrast to the phase difference. This is misconstrued as complex vector space in quantum mechanics. 3-D number which is nothing but a spinor with new notation is an extension of vector algebra. It can have a real number as a term in addition to the terms i, j and k. In all other respects, it is a vector. 3-D numbers are part of the number system like real numbers and complex numbers. The real numbers are one dimensional numbers, the complex numbers are two-dimensional numbers and the 3-D numbers as well as vectors and spinors are three-dimensional numbers. As polarisation and spin are one and the same, we can straight away apply 3-D numbers to polarisation of light. 3-D numbers will greatly simplify the study of areas of science where three-dimensional space is involved.