Predicting the effectiveness of hepatitis C virus neutralizing antibodies by bioinformatic analysis of conserved epitope residues using public sequence data

Hepatitis C virus (HCV) is a global health issue. Although direct-acting antivirals are available to target HCV, there is currently no vaccine. The diversity of the virus is a major obstacle to HCV vaccine development. One approach toward a vaccine is to utilize a strategy to elicit broadly neutralizing antibodies (bNAbs) that target highly-conserved epitopes. The conserved epitopes of bNAbs have been mapped almost exclusively to the E2 glycoprotein. In this study, we have used HCV-GLUE, a bioinformatics resource for HCV sequence data, to investigate the major epitopes targeted by well-characterized bNAbs. Here, we analyze the level of conservation of each epitope by genotype and subtype and consider the most promising bNAbs identified to date for further study as potential vaccine leads. For the most conserved epitopes, we also identify the most prevalent sequence variants in the circulating HCV population. We examine the distribution of E2 sequence data from across the globe and highlight regions with no coverage. Genotype 1 is the most prevalent genotype worldwide, but in many regions, it is not the dominant genotype. We find that the sequence conservation data is very encouraging; several bNAbs have a high level of conservation across all genotypes suggesting that it may be unnecessary to tailor vaccines according to the geographical distribution of genotypes

Recombinant Flag-tagged E1E2 glycoproteins from three hepatitis C virus genotypes are biologically functional and elicit cross-reactive neutralizing antibodies in mice

Hepatitis C virus (HCV) is a globally disseminated human pathogen for which no vaccine is currently available. HCV is highly diverse genetically and can be classified into 7 genotypes and multiple sub-types. Due to this antigenic variation, the induction of cross-reactive and at the same time neutralizing antibodies is a challenge in vaccine production. Here we report the analysis of immunogenicity of recombinant HCV envelope glycoproteins from genotypes 1a, 1b and 2a, with a Flag tag inserted in the hypervariable region 1 of E2. This modification did not affect protein expression or conformation or its capacity to bind the crucial virus entry factor, CD81. Importantly, in immunogenicity studies on mice, the purified E2-Flag mutants elicited high-titer, cross-reactive antibodies that were able to neutralize HCV infectious particles from two genotypes tested (1a and 2a). These findings indicate that E1E2-Flag envelope glycoproteins could be important immunogen candidates for vaccine aiming to induce broad HCV-neutralizing responses

Spatial Numerical Range in Non-unital, Normed algebras and their Unitizations

Let $(A, \|\cdot\|)$ be any normed algebra (not necessarily complete nor unital). Let $a \in A$ and let $V_A(a)$ denote the spatial numerical range of $a$ in $(A, \|\cdot\|)$. Let $A_e = A + {\mathbb C} 1$ be the unitization of $A$. If $A$ is faithful, then we get two norms on $A_e$; namely, the operator norm $\|\cdot\|_{op}$ and the $\ell^1$-norm $\|\cdot\|_1$. Let $A^{op} = (A, \|\cdot\|_{op})$, $A_e^{op} = (A_e, \|\cdot\|_{op})$, and $A_e^1 = (A_e, \|\cdot\|_1)$. We can calculate the spatial numerical range of $a$ in all these three normed algebras. Because the spatial numerical range highly depend on the identity as well as on the completeness and the regularity of the norm, they are different. In this paper, we study the relations among them. Most of the results proved in \cite{BoDu:71, BoDu:73} will become corollaries of our results. We shall also show that the completeness and regularity of the norm is not required in \cite[Theorem 2.3]{GaHu:89}.Comment: 8 page

On the convexity of spatial numetical range in normed algebras

In this article, we address the following question: Is it true that the spatial numerical range (SNR) $V_A(a)$ of an element $a$ in a normed algebra $(A, \|\cdot\|)$ is always convex? If the normed algebra is unital, then it is convex \cite[Theorem 3, P.16]{BoDu:71}. In non-unital case, we believe that the problem is still open and its answer seems to be negative. In search of such a normed algebra, we have proved that the SNR $V_A(a)$ is convex in several non-unital Banach algebras.Comment: 9 page

The Spectral extension property in the unitization of Banach Algebras

Let $A$ be a non-unital Banach algebra and let $A_e = A \oplus {\mathbb C}1$ be the unitization of $A$. It is true that if $A_e$ has the spectral extension property (SEP), then $A$ has the same. Does the converse hold? In this paper, we give some necessary as well as some equivalent conditions.Comment: 8 page

DEVELOPMENT AND VALIDATION OF STABILITY INDICATING HPTLC METHOD FOR ESTIMATION OF SWERTIAMARIN IN BULK AND DOSAGE FORM

Objective: In the present study a novel stability-indicating high-performance thin-layer chromatography (HPTLC) method for quantitative determination of Swertiamarin (SW) in bulk drug and formulation has been developed and validated as per ICH guideline Q2 (R1) for global acceptance of standardized herbal formulations. Methods: HPTLC method is developed and validated using solvent ethyl acetate: ethanol: chloroform (3:2.5:4.5 v/v/v) (Rf of SW 0.65±0.04) in the absorbance mode at 243 nm. Various forced degradation conditions were used to check degradation of drug. Results: The method showed a good linear relationship (r2 = 0.9990) in the concentration range 200-700 ng per spot. It was found to be linear, accurate, precise and specific. Conclusion: It can be applied for quality control as well as for stability testing of different dosage forms containing swertiamarin. The developed method is validated as per ICH guideline Q2(R1) for global acceptance of standardized herbal formulations

Global Management Effectiveness Study: Integrated Social and Ecological Report for Non-node and Node Sites

The purpose of this study is to provide a critical assessment of the implementation, impact, and performance of Marine Managed Area (MMA) projects to serve as a basis for improved planning and implementation of new MMA projects worldwide. The specific objectives of the study are (1) to determine the socioeconomic, governance and ecological effects of MMAs; (2) to determine the critical factors influencing MMA effects, as well as the impact of the timing of those factors on the effects of the MMA; and (3) to provide tools for predicting MMA effects based on ecological, socioeconomic and governance variable

On the motion of hairy black holes in Einstein-Maxwell-dilaton theories

Starting from the static, spherically symmetric black hole solutions in massless Einstein-Maxwell-dilaton (EMD) theories, we build a "skeleton" action, that is, we phenomenologically replace black holes by an appropriate effective point particle action, which is well suited to the formal treatment of the many-body problem in EMD theories. We find that, depending crucially on the value of their scalar cosmological environment, black holes can undergo steep "scalarization" transitions, inducing large deviations to the general relativistic two-body dynamics, as shown, for example, when computing the first post-Keplerian Lagrangian of EMD theories

A multifaceted hospital-wide intervention increases hand hygiene compliance

Background. Hand hygiene is an important and basic practice that should be used by all healthcare staff to protect both themselves and their patients against infection. Unfortunately hand hygiene compliance remains poor.Objective. To show an improvement in hand hygiene compliance using a multifaceted approach.Methods. This was a quasiexperimental pre-post intervention study design with a number of standardised interventions to promote hand hygiene. The World Health Organization hand hygiene multimodal (five-step) intervention approach was used. The study ran from June 2015 to August 2015 in 11 selected wards of a 975-bed tertiary and quaternary care public hospital (Groote Schuur Hospital, Cape Town, South Africa). The outcome was to assess improvement in hand hygiene compliance monthly over the 3 months, compared with nonintervention wards and compared with the wards’ own performance measured in 2014. The study included both descriptive and analytical components.Results. Post intervention, hand hygiene compliance showed a statistically significant improvement for before patient contact from 34% in 2014 to 76% in 2015 (p<0.05) and for after patient contact from 47% in 2014 to 82% in 2015 (p<0.05).Conclusion. The intervention improved hand hygiene compliance and can easily be replicated in other wards, resulting in sustaining a culture of hand hygiene improvement and behavioural change throughout the hospital