A document by Naomi Burns. Click on the document to view its contents.

The SARS-CoV-2 variants raise concerns about the effectiveness of vaccines. Safe and effective vaccines are urgently needed to combat the COVID-19 pandemic. As a SARS-CoV-2 antigen target, ORF8 strongly inhibits the IFN-β and NF-κB-responsive promoter, which is a potential antigen target for the development of SARS-CoV-2 vaccine. Adjuvants or delivery system were necessitated to improve the immunogenicity of ORF8. CRM197 was a carrier protein with the ability to activate T helper cells for antigens. Eight-arm PEG could conjugate multiple antigen molecules in one entity with inherent adjuvant effect. In the present study, ORF8 was conjugated with CRM197 and 8-arm PEG, respectively. The cellular and humoral immune responses to the conjugates (ORF8-CRM and ORF8-PEG) were evaluated in the BALB/c mice. As compared with ORF8-CRM and ORF8 administrated with aluminum adjuvant (ORF8/AL), ORF8-PEG induced a higher ORF8-specific IgG titer (2.6x104), higher levels of cytokines (IFN-γ, TNF-α, IFN-β, and IL-5), stronger splenocyte proliferation. Thus, conjugation with 8-arm PEG was an effective method to improve the immune response to ORF8. Moreover, ORF8-PEG did not lead to apparent toxicity to the cardiac, liver and renal functions. ORF8-PEG was expected to act as an effective vaccine to provide the immune protection against SARS-CoV-2.

The scale-up of bioprocesses is still one of the major obstacles in biotechnological industry. Scale-down bioreactors were identified as valuable tools to investigate the heterogeneities observed in large-scale tanks in laboratory-scale. Additionally, computational fluid dynamics (CFD) simulations can be used to gain information about fluid flow in tanks used for production. Here we present the rational design and comprehensive characterization of a scale-down setup, in which a flexible and modular plug-flow reactor is connected to a stirred tank bioreactor. With the help of CFD the mixing time difference between differently scaled bioreactors were evaluated and used as scale-down criterium. Additionally, it was used to characterize the setup at conditions were experiments could technically not be performed. This was the first time a scale-down setup was tested on high cell density Escherichia coli cultivations to produce industrial relevant antigen-binding fragments (Fab). Reduced biomass and product yields were observed during the scale-down cultivations. Additionally, the intracellular Fab fraction was increased by using the setup. The results show that including CFD in the design and characterization of a scale-down reactor can help to keep a connection to production scale and also gain intensive knowledge about the setup, which enhances usability.

This paper considers the analytical technique of element integral in the boundary element method with constant element for 3D Laplace and Stokes flow problems. For 3D Laplace problems, the analytical integral formulae, which are valid for an arbitrary source point, are derived. For 3D Stokes flow problems, analytical evaluation of the integrals, which the source point and the boundary element are in the same plane, are proposed. These analytical formulae are applicable for arbitrary convex polygonal planar elements. Numerical examples are given to validate the improvement on accuracy.

We use an analytical gravitational model that describes the local motion of stars near the central region of a barred galaxy. By integrating and classifying large sets of starting conditions of trajectories we manage to determine how the important parameters of the bar, such as its mass, strength, scale length, and angular velocity influence the motion of stars. For the orbit taxonomy, we combine traditional dynamical methods such as the classical Poincare surface of section along with modern chaos indicators such as the Smaller Alignment Index (SALI). Our results of the local galactic model are compared with previous studies using global gravitational models.

In this paper, we studied the existence of solution of p-Laplacian fractional differential equation with instantaneous and non-instantaneous impulses. Some new criteria guaranteeing the existence of solutions are established for the considered problem. Finally, an examples is given to illustrate our main result.

Global climate change is exposing intertidal organisms to increasing air and sea temperatures and changing ocean currents, affecting their ability to disperse, survive and reproduce, and resulting in shifts in their distribution and abundance. Improved understanding of these shifts requires characterization of population structure and local adaptation. We estimate the drivers of population structure in two intertidal gastropod species with contrasting life histories by assessing neutral and adaptive population structure and performing redundancy analyses in a seascape genomics framework. We show putative adaptive divergence between populations of the broadcast spawning topshell, Steromphala umbilicalis, despite high rates of neutral gene flow. This adaptive structure was best explained by geographic structure, separating sites in Wales from all other British and Irish sites. Larval dispersal, estimated from biophysical models, was also identified as a minor component explaining genetic connectivity in this species. For the direct developing dogwhelk, Nucella lapillus¸ neutral population structure was best explained by air and sea surface temperatures while putative adaptive population structure showed a greater influence of wave exposure. These results support the expected relationship between neutral population structure and reproductive mode (i.e., greater population structure in the direct developing N. lapillus compared with a lack of structure in the broadcast spawning S. umbilicalis) and highlight the interactive effects of geographic structure, larval dispersal and local environment on gene flow and adaptation of intertidal marine organisms.

Purpose: The COVID 2019 has had been going pandemic as per WHO situation reports. The major differentiating point in this virus is the presence of a unique furin cleavage site. Our insilico study points out to the effectiveness of a potent plant origin furin inhibitor. We exploited the aspect of the cleavage machinery of furin subunits which is critical and indispensible to the entry of SARS-CoV-2 in human cells and subsequent massive contagion. Methods: In-silico analysis was done to observe the interactions of proposed analogs of protease inhibitor of plant origin against furin protein as well as the furin spike glycoprotein binding machinery. This was done by docking protocols using Hex 6.0 software followed by molecular Dynamic simulation (MDS) analysis in 100ns scale using Amber94. Further, the images were analysed with PyMol software. Results: The analogs I, II and III included in our study showed strong interactivity against furin individually, as well as the furin-Spike Glycoprotein 1 binding machinery. The findings were confirmed using molecular dynamic simulation analysis which indicated good structural stability and ability to neutralise furin and furin-spike glycoprotein 1. Analog II was found to be the best interactive molecule against furin, showing the least deviation (1.484 ± 0.0064). Also, it was the most effective against furin + Spike glycoprotein I (SGP I) machinery [1.575± 0.01]. Major conclusions: We report the first of its kind of natural furin inhibitor(s) which would disrupt the furin machinery of SARS CoV2 and help in controlling the CoViD 19 contagion.

The phytohormone abscisic acid (ABA) is synthesized by plants during drought to close stomata and regulate desiccation tolerance pathways. In conifers and a few angiosperms with embolism resistant xylem a peaking-type (p-type) response in ABA levels has been observed, in which ABA levels increase early in drought then decrease as drought progresses, declining to pre-stressed levels. The mechanism behind this dynamic remains unknown. Here we sought to characterize the mechanism driving p-type ABA dynamics in the conifer Callitris rhomboidea and the highly drought resistant angiosperm Umbellularia californica. We measured leaf water potentials (Ψ l), stomatal conductance, ABA, conjugates and phaseic acid (PA) levels in potted plants during a prolonged but non-fatal drought. Both species displayed a p-type ABA dynamic during prolonged drought. Measuring ABA levels in bench dried, rehydrated branches collected before and after the peak in ABA levels revelated that in both species ABA biosynthesis is deactivated in leaves that have been dehydrated beyond leaf turgor loss point. Considerable conversion of ABA to conjugates was found to occur during drought, but not catabolism to PA. The mechanism driving the decline in ABA levels in p-type species appears to be conserved across seed plants and is mediated by sustained conjugation of ABA and the deactivation of ABA biosynthesis as Ψ l becomes more negative than turgor loss.

A 75-year-old man was admitted with a diagnosis of diabetic ketoacidosis and hyperkalemia. During the treatment, he developed refractory hyperkalemia. Following our review, diagnosis of pseudohyperkalaemia secondary to thrombocytosis was made. We report this case to remind the importance of clinical suspicion of this phenomenon to prevent its serious consequences.

Second generation (2G) ethanol is produced using lignocellulosic biomass. However, the pre-treatment processes generate a variety of molecules (furan derivatives, phenolic compounds, and organic acids) that act as inhibitors of microbial metabolism, and thus reduce the efficiency of the fermentation step in this process. In this context, the present study aimed to investigate the effect of furan derivatives on the physiology of lactic acid bacteria (LAB) strains that are potential contaminants of ethanol production. Homofermentative and heterofermentative strains of laboratory LAB and isolated from first generation ethanol fermentation were used. LAB strains were challenged to grow in the presence of furfural and hydroxymethyylfurfural (HMF). We found that the effect of HMF and furfural on the growth rate of LAB is dependent of the metabolic type, and growth kinetics in the presence of these compounds is enhanced for heterofermentative LAB, whereas is inhibitory to homofermentative LAB. Sugar consumption and product formation were also enhanced in the presence of furaldehydes in heterofermentative LAB, that displayed effective detoxification kinetics when compared to the homofermentative LAB. This knowledge is important because lactic acid bacteria can be explored within the scope of bio-detoxification, as well as to guide metabolic engineering strategies to yeast biocatalysts based on the mechanisms used by these bacteria.

Disulfide bonds maintain the proper structural conformation and stability of the protein. Introduction of new disulfide bonds or disulfide bonds engineering is a promising strategy of rational protein designing that has been applied to improve the stability of various proteins. In this work, we have applied this approach to an industrially important enzyme Glycoside Hydrolase family GH 7 cellobiohydrolase (GH7 CBHs) or Cel7A of our locally isolated strain of thermophilic fungus Aspergillus fumigatus ( AfCel7A). Disulfide by Design 2.0 (DbD2), a web-based tool for mutation site detection in proteins, used and created four mutations (T416C-I432C, G460C-G465C, D276C-G279C, and D322C-G327C) in the peripheral loops but outside of the catalytic region. The disulfide bond (T416C-I432C) formed between the A2 and A4 loop showed higher thermostability (70% activity at 70 0C), higher substrate affinity (K m= 0.081mM) and higher catalytic activity (Kcat =9.75 min -1; Kcat/Km = 120.37 mM min -1) than wild type AfCel7A (50% activity at 70 0C; K m= 0.128mM; Kcat = 4.833 min -1; Kcat/Km = 37.75 mM min -1). Whereas the other three mutants with high B factor showed the loss of thermostability and loss of catalytic activity compared to the wild type. This is the first report of the gain of function of both thermostability and enzyme activity of cellobiohydrolase Cel7A by disulfide bond engineering. Further, comparative molecular dynamics simulations revealed that the variant T416C-I432C is comparatively less flexible (RMSD) than both wild type and other variants at 300K, 325K. However, increased flexibility at tunnel entrance (RMSF at 300K and 325K) may responsible for the gain of catalytic activity and the formation of more hydrogen bonds while binding with cellobiose may responsible for the increase of substrate affinity.

The maxillary first molars vary in root canal morphology and configuration, making them both diagnostic and technical challenges. cone beam computed tomographyic (CBCT) examination is an excellent tool for identifying and managing these complex root canal systems.

Pulmonary arteriovenous fistula (PAVF) is a rare clinical disorder characterized anatomically by an abnormal right-to-left shunt (RLS) at the pulmonary vascular level. RLS was detected by right-heart contrast echocardiography (RHCE), and a large number of contrast microbubbles were detected entering the left atrium and ventricle from the left and right pulmonary veins, Intuitively prompt bilateral pulmonary arteriovenous fistula. Computed tomography angiography confirmed the diagnosis. We report a case of a patient with PAVF complicated with pulmonary hypertension, RHCE with high-frequency transthoracic ultrasound showed the typical signs of pulmonary arteriovenous fistula. We used this method for the first time to diagnose pulmonary arteriovenous fistula.

Psychogenic nonepileptic seizures (PNES) are a common and highly disabling form of Functional Neurological Disorder (FND). The diagnosis of PNES could be missed or delayed in various clinical scenarios, including where patients present with concurrent musculoskeletal/neurological findings. This case report examines these pitfalls and their prevention.

The Equilibrium Theory of Island Biogeography (ETIB) is a widely applied dynamic theory proposed to explain why islands have coherent differences in species richness. The development of the ETIB was temporarily challenged by the alternative static Theory of Ecological Impoverishment (TEI), which suggests that the number of species on an island is determined by its number of niches or habitats. With no clear evidence relating species richness to the number of niches, the TEI was almost abandoned in favour of the ETIB. Here, we show that the number of climatic niches on islands is an important predictor of the species richness of plants, herpetofauna and land birds, and we propose a new model called the General Theory of Island Biogeography (GTIB) that merges the ETIB and TEI theories. When we test our GTIB for resident land birds in Krakatau Islands it reveals a good correspondence with observed species richness, immigration and extinction rates.

Background Understanding the long-term psychosocial impact of pediatric hematopoietic stem cell transplantation (HSCT) for non-malignant diseases is needed in order to optimize pre-HSCT counseling, supportive care, and long-term follow up programs after HSCT for this group of patients and caregivers. Procedure This qualitative study included 14 patients transplanted for a non-malignant disease during childhood. In-depth interviews were held online to explore patients’ perspectives on the long-term psychosocial impact of HSCT on their lives. Results were analyzed based on the Grounded Theory approach. Results Patients’ median age at the time of interview was 19 years (range 14-49) and median years after HSCT was 12 years (range 3-33). Four main themes were identified: (1) Doing okay, (2) Experiencing persistent involvement with healthcare services, (3) Influence on relationships with loved ones, and (4) Impact on patient’s life course. Subthemes extracted were doing okay, feeling of being cured, health limitations, sense of vulnerability, ongoing connection to the hospital, acceptance, friendship, family relations, development of own identity, not taking life for granted, social development, impact on (school) career, and thinking about the future. Conclusions Patients reported active coping strategies and resilience after this high-impact treatment. The data highlight the need for patient-adjusted supportive care, indicating more need of supportive care in the long-term outpatient clinic.

A wideband filtering phase shifter is proposed based on vertically installed planar (VIP) circuit structures, where the VIP circuit is used to realize a tight coupling. The even-odd mode analysis is adopted to analyze the whole structure. Then, a 45° filtering phase shifter is designed to verify the design methodology. The simulated and measured results demonstrate that the proposed phase shifter has low insertion losses (<0.5 dB) and excellent return losses (< -15 dB) in the frequency band of 1.12 ~ 2.23 GH. The 3°-phase shift bandwidth is more than 64.31%.

Species detection using eDNA is revolutionizing the global capacity to monitor biodiversity. However, the lack of regional, vouchered, genomic sequence information—especially sequence information that includes intraspecific variation—creates a bottleneck for management agencies wanting to harness the complete power of eDNA to monitor taxa and implement eDNA analyses. eDNA studies depend upon regional databases of complete mitogenomic sequence information to evaluate the effectiveness of such data to differentiate, identify and detect taxa. We created the Oregon Biodiversity Genome Project working group to utilize recent advances in sequencing technology to create a database of complete, near error-free mitogenomic sequences for all of Oregon’s resident freshwater fishes. So far, we have successfully assembled the complete mitogenomes of 313 specimens of freshwater fish representing 7 families, 55 genera, and 129 (88%) of the 146 resident species and lineages. Our comparative analyses of these sequences illustrate that the short (~150 bp) mitochondrial “barcode” regions typically used for eDNA assays are not consistently diagnostic for species-level identification and that no single region is best for metabarcoding Oregon’s fishes. However, often-overlooked intergenic regions of the mitogenome such as the D-loop have the potential to reliably diagnose and differentiate species. This project provides a blueprint for other researchers to follow as they build regional databases. It also illustrates the taxonomic value and limits of complete mitogenomic sequences, and how current eDNA assays and the “PCR-free” environmental genomics methods of the future can best leverage this information.

Aim Determine seasonal, annual and decadal patterns of abundance in reptile populations and assemblages occupying an isolated urban bushland remnant Location Bold Park (~338 ha), Perth, Southwestern Australia Time period 1986-2021 Major taxa studied: Squamate reptiles Methods Fenced pitfall trapping in four sampling sites representing different habitats and fire history over the primary reptile activity period and 35 consecutive years; trapping regime was modified for the last 28 years. Results The location occurs in one of 35 global biodiversity hotspots and has a Mediterranean climate experiencing a 15% decline from the century average rainfall over the last 50 years. Twenty-nine species were recorded, with 16 captured in 32 or more years and accounting for nearly 97% of all captures; the six most common for 81%. Three taxa became locally extinct. Activity predominates in warmer and dryer months (October to April), peaking in November December. Species richness remained relatively constant between years with around 73% of known taxa captured annually. Assemblage structure didn’t change when analysing presence/absence data but shifted through five statistically significantly assemblages analysing relative abundance data. Over the last 28 years relative abundance was significantly and positively correlated with annual rainfall residuals for the three years preceding annual sampling, resulting in significant changes in total assemblage structure and significantly similar patterns in four sample sites; presence/absence data indicated minor assemblage structure changes. Main conclusions Annual species number remained relatively constant but relative abundance illustrated significant temporal changes in assemblage structure over decades; presence/absence did not. The modeled relationship between relative abundance and annual rainfall residuals for the three years preceding annual sampling is supported by known ecological responses and reptile demographics within this Mediterranean climate. Maintenance of urban biodiversity should consider impacts of a significantly drying climate exacerbating the extinction debt already inherent in isolated bushland populations.

The transportation system using the Long-stator linear motor propulsion system has the advantage of directly transmitting propulsion force to the vehicle regardless of adhesive friction at high speed, and is used for high speed maglev. However, the initial installation cost is high and as the length of the segmented stator increases, the operating efficiency and power factor are low, resulting in an increase in the capacity of the propulsion inverter and in operating costs. The paper proposes a section switching method using BCT (Bi-directional Controlled Thyristors) in order to minimize the length of the segmented stator. And in order to verify the excellence of section switching method using BCT, a small scale circular test-bed based on a linear motor was manufactured. The experimental result showed that the output current of the inverter fluctuates by motor impedance change when the vehicle moves between stator blocks, and a current ripple occurs due to a position error of the discontinuous position detection signal. In order to solve these problems, a position estimator using full-state observer was presented and the excellence was verified through a test using the test-bed.

Covid 19 pandemic has shocked the world over the last 2 years. Thankfully with the use of covid mass vaccination life is returning back to normal . Here we describe a case of suspected acute ST elevation anterior wall myocardial infarction and LAD artery thrombus in two hours of vaccination

A patient with polycystic kidney disease had flank and back pain lasting for a month. We considered that her cysts led to the pain, which is a common symptom of polycystic kidney disease. However, a cancer hidden in large and multiple cysts caused the pain.

The paper is concerned with the following Schr\”{o}dinger-Poisson system $$ \left\{\begin{array}{ll} -\Delta u+u+\phi u=|u|^{p-1}u+|u|^4u, &x\in \mathbb{R}^3, \\[0.25cm] -\Delta\phi=u^2, &x\in \mathbb{R}^3, \end{array} \right. $$ where $3