Safety profile of a multi-antigenic DNA vaccine against hepatitis C virus

Despite direct acting antivirals (DAAs) curing >95% of individuals infected with hepatitis C (HCV), in order to achieve the World Health Organization HCV Global Elimination Goals by 2030 there are still major challenges that need to be overcome. DAAs alone are unlikely to eliminate HCV in the absence of a vaccine that can limit viral transmission. Consequently, a prophylactic HCV vaccine is necessary to relieve the worldwide burden of HCV disease. DNA vaccines are a promising vaccine platform due to their commercial viability and ability to elicit robust T-cell-mediated immunity (CMI). We have developed a novel cytolytic DNA vaccine that encodes non-structural HCV proteins and a truncated mouse perforin (PRF), which is more immunogenic than the respective canonical DNA vaccine lacking PRF. Initially we assessed the ability of the HCV pNS3-PRF and pNS4/5-PRF DNA vaccines to elicit robust long-term CMI without any adverse side-effects in mice. Interferon-γ (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assay was used to evaluate CMI against NS3, NS4 and NS5B in a dose-dependent manner. This analysis showed a dose-dependent bell-curve of HCV-specific responses in vaccinated animals. We then thoroughly examined the effects associated with reactogenicity of cytolytic DNA vaccination with the multi-antigenic HCV DNA vaccine (pNS3/4/5B). Hematological, biochemical and histological studies were performed in male Sprague Dawley rats with a relative vaccine dose 10–20-fold higher than the proposed dose in Phase I clinical studies. The vaccine was well tolerated, and no toxicity was observed. Thus, the cytolytic multi-antigenic DNA vaccine is safe and elicits broad memory CMI.Jason Gummow, Makutiro G. Masavuli, Zelalem A. Mekonnen, Yanrui Li, Danushka K. Wijesundara, Ashish C. Shrestha, Ilia Voskoboinik, Eric J. Gowans and Branka Grubor-Bau

Pteridophyte flora of Udawattakele forest the past, present and future

Pteridophytes represent an important group in the plant kingdom. Approximately 11,300 Pteridophytespecies have been described worldwide, ofwhich about 360 species have been recorded in Sri Lanka.Most of Sri Lankan Pteridophyte species is concentrated in the understory of the rainforests ofCentral Highlands. Udawattakele forest with 132 ha was one of such highlands (510 m above sealevel) which received special attention by European Pteridologists, even during the colonial era. It hasbeen reported that 13 species are already extinct from Sri Lanka mainly because of various threatsfaced by Pteridophytes. Thus, the objective of this study was to compare the diversity of Pteridophyteflora at present with the previous records and identify possible conservation issues.Species diversity of Pteridophytes at Udawattakele forest in the past was obtained from reviewing ofliterature (Karunarathne, 1986; Sledge, 1950-1981) and observations of preserved specimens at theNational Herbarium. Two line transects (10m x 4000 m) on both side of Lady Horton's Walk wereassessed to identify the present level of Pteridophyte diversity. Almost all Pteridophyte species wereidentified at species level through morphological observations and subsequently with the help of keys.The Lady Horton's Walk was selected for the study, because the majority of Pteridophytes atUdawattakele was concentrated in this area and previous assessments of Pteridophytic diversityhave been conducted in the area. At the selected locations species were counted to identify dominantspecies.According to literature, 25 Ptridophytic species and 4 hybrids (29 taxa) have been collected fromLady Horton '5 Walk in Udawattakele forest. Chronologically 7, 17,2 and 3 taxa have been recordedfrom 1888-1900, 1950-1954, 1973 and 1993, respectively. Out of 29 taxa collected by foreignPteridologists, only preserved specimens of27 taxa have been deposited in the British Museum andthe Kew Herbarium. Karunarathne (1986) recorded 23 Pteridophyte species from the forest. Thepresent study was able to identify 36 Pteridophyte species belong to 9 families and 20 genera from theforest, of which 29 species are common and usually grow on harsh environment in the disturbed areasand roadside banks. Seven species occur in relatively high moist and shaded areas of the forest. Thepresent study was able to record 13 additional species compared to Karaunarathne (1986). However,out of 29 taxa recorded in the literature, 9 species were recorded during the present study. Further, 7species iArthropteris palisotti, Christella hispidula x C. parasitica, Diplazium sylvasticum,Microlepia speluncae, Pronephrium articulatum, Teetaria subtriphylla and T trimenii) had notbeen recorded even in the other parts ofthe country during the last 50 years. The present study wasalso unable to record such species from Udawattakele forest. Out of the above 7 species, two rarespecies namely, Pronephrium artieulatum and Christella hispidula x C. parasitiea had beenrecorded only once over the last century. Such records were also found from Lady Horton's Walk inUdawattakele forest before 50 years.However, at present the Lady Horton's walk has severely been invaded by Myroxylon balsamumsuppressing its native biodiversity. Further, roadside banks of the Lady Horton's walk have very dryconditions. Few wet and shaded areas are also invaded by a naturalized fern species such as Adiantumpulverulent um and it has become dominant species in the area. Such causes may have contributedfor loss of some Pteridophyts species from Udawattakele forest. It is well known that Pteridophytesare very sensitive to changes of environmental conditions and human activities. This raises the issueof necessity of continuous monitoring ofPteridophytic biodiversity for their conservation even withintheir natural habitats.

Outline of Fungi and fungus-like taxa

This article provides an outline of the classification of the kingdom Fungi (including fossil fungi. i.e. dispersed spores, mycelia, sporophores, mycorrhizas). We treat 19 phyla of fungi. These are Aphelidiomycota, Ascomycota, Basidiobolomycota, Basidiomycota, Blastocladiomycota, Calcarisporiellomycota, Caulochytriomycota, Chytridiomycota, Entomophthoromycota, Entorrhizomycota, Glomeromycota, Kickxellomycota, Monoblepharomycota, Mortierellomycota, Mucoromycota, Neocallimastigomycota, Olpidiomycota, Rozellomycota and Zoopagomycota. The placement of all fungal genera is provided at the class-, order- and family-level. The described number of species per genus is also given. Notes are provided of taxa for which recent changes or disagreements have been presented. Fungus-like taxa that were traditionally treated as fungi are also incorporated in this outline (i.e. Eumycetozoa, Dictyosteliomycetes, Ceratiomyxomycetes and Myxomycetes). Four new taxa are introduced: Amblyosporida ord. nov. Neopereziida ord. nov. and Ovavesiculida ord. nov. in Rozellomycota, and Protosporangiaceae fam. nov. in Dictyosteliomycetes. Two different classifications (in outline section and in discussion) are provided for Glomeromycota and Leotiomycetes based on recent studies. The phylogenetic reconstruction of a four-gene dataset (18S and 28S rRNA, RPB1, RPB2) of 433 taxa is presented, including all currently described orders of fungi

Notes for genera: basal clades of Fungi (including Aphelidiomycota, Basidiobolomycota, Blastocladiomycota, Calcarisporiellomycota, Caulochytriomycota, Chytridiomycota, Entomophthoromycota, Glomeromycota, Kickxellomycota, Monoblepharomycota, Mortierellomycota, Mucoromycota, Neocallimastigomycota, Olpidiomycota, Rozellomycota and Zoopagomycota)

Compared to the higher fungi (Dikarya), taxonomic and evolutionary studies on the basal clades of fungi are fewer in number. Thus, the generic boundaries and higher ranks in the basal clades of fungi are poorly known. Recent DNA based taxonomic studies have provided reliable and accurate information. It is therefore necessary to compile all available information since basal clades genera lack updated checklists or outlines. Recently, Tedersoo et al. (MycoKeys 13:1--20, 2016) accepted Aphelidiomycota and Rozellomycota in Fungal clade. Thus, we regard both these phyla as members in Kingdom Fungi. We accept 16 phyla in basal clades viz. Aphelidiomycota, Basidiobolomycota, Blastocladiomycota, Calcarisporiellomycota, Caulochytriomycota, Chytridiomycota, Entomophthoromycota, Glomeromycota, Kickxellomycota, Monoblepharomycota, Mortierellomycota, Mucoromycota, Neocallimastigomycota, Olpidiomycota, Rozellomycota and Zoopagomycota. Thus, 611 genera in 153 families, 43 orders and 18 classes are provided with details of classification, synonyms, life modes, distribution, recent literature and genomic data. Moreover, Catenariaceae Couch is proposed to be conserved, Cladochytriales Mozl.-Standr. is emended and the family Nephridiophagaceae is introduced

A pilot study on the design and validation of a hybrid exoskeleton robotic device for hand rehabilitation

Study Design: An iterative design process was used to obtain design parameters that satisfy both kinematic and dynamic requirements for the hand exoskeleton. This design was validated through experimental studies. Introduction: The success of hand rehabilitation after impairments depends on the timing, intensity, repetition, and frequency, as well as task-specific training. Considering the continuing constraints placed on therapist-led rehabilitation and need for better outcomes, robot-assisted rehabilitation has been explored. Soft robotic approaches have been implemented for a hand rehabilitation exoskeleton as they have more tolerance for alignment with biological joints than those of hard exoskeletons. Purpose of the Study: The purpose of the study was to design, develop, and validate a soft robotic exoskeleton for hand rehabilitation. Methods: A motion capture system validated the kinematics of the soft robotic digit attached on top of a human index finger. A pneumatic control system and algorithms were developed to operate the exoskeleton based on three therapeutic modes: continuous passive, active assistive, and active resistive motion. Pilot studies were carried out on one healthy and one poststroke participant using continuous passive motion and bilateral/bimanual therapy modes. Results: The soft robotic digits were able to produce required range of motion and accommodate for dorsal lengthening, with trajectories of the center of rotation of the soft robotic joints in close agreement with the center of rotation of the human finger joints. Discussion: The exoskeleton showed the robust performance of the robot in applying continuous passive motion and bilateral/bimanual therapy. Conclusions: This soft robotic exoskeleton is promising for assisting in the rehabilitation of the hand

Soft Robotic Rehabilitation Exoskeleton (REHAB Glove) for Hand Therapy

This paper presents the design, control, and validation of a soft robotic exoskeleton system, the REHAB Glove, for hand rehabilitation. The system is comprised of five hybrid soft-andrigid robotic digits that apply controlled flexion and extension motion to fingers. The previous actuator design of the soft robotic digit was improved for kinematic compatibility with anatomical motions of the hand in relation to range of motion, center of rotation, and dorsal skin lengthening. The design was validated using motion capture and analysis. A position control algorithm, which controls finger angular trajectories (angular position and velocity), was developed based on motion sensor feedback. The operation of this algorithm was verified using a 90° digit tip trajectory with two angular velocities of 15°/sec and 30°/sec. A pilot study was carried out with five healthy individuals to evaluate the performance of the REHAB Glove in providing therapeutic schemes. The results show that the REHAB Glove is able to provide controlled motion compatible with the kinematics and dynamics of the human

Kinematic Study of a Soft-and-Rigid Robotic Digit for Rehabilitation and Assistive Applications

This paper presents the kinematic study of a pneumatically actuated soft-and-rigid robotic digit designed to be used in exoskeleton-based hand rehabilitation and assistive applications. The soft-and-rigid robotic digit is comprised of three inflatable bellow-shaped structure sections (soft sections) and four semirigid sections in an alternating order which correspond to the anatomy of a human finger. The forward and backward bending motions at each soft section (joint) are generated by pressure and vacuum actuation, respectively. The goal here is to investigate the compatibility of the soft robotic digit\u27s kinematic parameters such as range of motion, center of rotation, and lengthening at the joints with the required anatomical motion of the human finger to ensure proper function and safe interaction. The soft robotic digits were fabricated using silicone rubber materials in a compression molding process for the experimental study. The kinematic parameters of both a human and soft robotic index finger were measured using a motion capture system. The obtained results show that the robotic digit was able to provide the required range of motion: 0-90° at the metacarpophalangeal (MCP) joint, 0-100° at the proximal interphalangeal (PIP) joint, and 0-70° at the distal interphalangeal (DIP) joint. Furthermore, the data show the center of rotation of each soft section (robotic joint) was remotely coincident with that of the corresponding index finger. The lengthening of the three soft sections of the robotic digit were measured to be 7mm, 7mm, and 2mm for the MCP, PIP, and DIP, respectively. The corresponding values for the dorsal skin lengthening of a human index finger is 11mm, 15mm, and 5mm and are longer than the achieved lengthening in the robotic digit

Mesoporous SiC with Potential Catalytic Application by Electrochemical Dissolution of Polycrystalline 3C-SiC

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