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In this paper, we propose an algorithm which approximates the Two-Sided Scaffold Filling problem to a performance ratio 1.4 + ε. This is achieved through a deep investigation of the optimal solution structure of Two-Sided Scaffold Filling. We make use of a relevant graph aiming at a solution of a Two-Sided Scaffold Filling instance, and evaluate the optimal solution value by the number of connected components in this graph. We show that an arbitrary optimal solution can be transformed into one whose relevant graph admits connected components that are available to compare with the solution of our algorithm in terms of their values. The performance ratio 1.4 + ε is obtained by comparing the bound of such an optimal solution with the solution of our algorithm. [ABSTRACT FROM AUTHOR]

Environmentally-friendly carbon-based materials possess the potential applications as general anode for alkali-ion batteries. However, the existing carbon-based materials cannot satisfy the increasing demand for high energy density and need further active exploration. Herein, nitrogen/oxygen co-doped graphene-like carbon nanocages (NOGCN) is synthesized from biomass cytidine on hydro-soluble sodium chloride nanocrystals by a one-step method as a general lithium and potassium-ion batteries anode. All reactants are completely renewable and readily available. The nitrogen/oxygen-doping, large interlayer spacing and robust self-supporting nanocage architecture greatly favour electrolyte penetration and improve the kinetics for ion and electron transport, resulting in extraordinary electrochemical performance. The synthesized NOGCN electrodes exhibit a high lithiation storage capacity of 620 mA h g−1 over 500 cycles at 500 mA g−1, with continuously magnifying capacity. Moreover, the impressive reversible potassiation capacity (355 mA h g−1 at 200 mA g−1) and rate capability (114 mA h g−1 at 1000 mA g−1) were achieved despite the large-sized potassium ions. Kinetic analysis and density functional theory calculations elaborately illustrate the Li/K-absorption properties of the N/O-doped graphene-like structure, further demonstrating the chemical affinity and superiority in Li/K storage. This study provides a facile and completely renewable method to prepare promising general anode material for alkali-ion batteries. Image 1 [ABSTRACT FROM AUTHOR]

Abstract SnSe is a promising anode material in sodium-ion batteries (SIBs) due to its high theoretical capacity (780 mA h g−1) and natural abundance. Herein, we report SnSe nanoplates vertically grown on nitrogen-doped carbon (SnSe/NC) with strong Sn-C bonding for high-performance anode in SIBs, which are synthesized by a facial cation-exchange strategy. The vertically grown SnSe nanoplates with large interplanar spacing (0.58 nm), strong electronic coupling of Sn-C bonding between SnSe and NC facilitate the fast electron/ion transfer, enabling high pseudocapacitive Na-ion storage and enhanced power capability. Density functional theory calculations demonstrate that the presence of N heteroatoms in NC matrix has a pivotal influence on the formation of Sn-C bonding to stabilize the SnSe/NC structure. Moreover, the SnSe nanoplates of SnSe/NC exhibits low interlayer Na+ diffusion barrier (0.1 eV) and low energy barrier (0.14 eV/uc) from discharged product to pristine SnSe/NC, implying the fast Na+ diffusion capability and good reversibility. Consequently, the SnSe/NC exhibits large capacities of 723 and 88 mA h g−1 at 0.025 and 20 A g−1, respectively, and 82% capacity retention for over 200 cycles at 2 A g−1, boosting promising applications in high-performance SIBs. Graphical abstract Vertical SnSe nanoplates riveting on nitrogen-doped carbon nanobelts via Sn-C bonding are synthesized by a facial cation-exchange strategy and provide a superior Na+ storage performance. fx1 Highlights • Cation-exchange synthesis of SnSe nanoplates vertically grown on nitrogen-doped carbon nanobelts. • The SnSe nanoplates are verified to have chemical coupling with nitrogen-doped carbon via Sn-C bonding. • Thin SnSe nanoplates display a low Na+ diffusion barrier (0.1 eV) and enhanced pseudocapacitive storage. • The hybrid has a large Na+ storage capacity, high rate performance and excellent cyclablity. [ABSTRACT FROM AUTHOR]

Pfs25, a Plasmodium falciparum surface protein expressed during zygote and ookinete stages in infected mosquitoes, is a lead transmission-blocking vaccine candidate against falciparum malaria. To enhance immunogenicity, recombinant Pfs25 was chemically conjugated to recombinant nontoxic Pseudomonas aeruginosa ExoProtein A (rEPA) in conformance with current good manufacturing practices (cGMP), and formulated with the alum adjuvant Alhydrogel. In order to meet the regulatory requirements for a phase 1 human clinical trial, the vaccine product was extensively evaluated for stability at an initial time point and through the clinical trial period annually. Because basic quality control methods to characterize alum-based vaccines remain unavailable, a thermal forced degradation study was performed prior to the initial evaluation to identify the methods suitable to detect the quality of vaccine formulations. Our results show that the vaccine product Pfs25-EPA formulated on Alhydrogel is in conformance with regulatory guidelines and suitable for human trials. [ABSTRACT FROM AUTHOR]

In order to run a dataflow with as low cost as possible, it is often faced with deciding which data-sets in a data-set sequence should be stored, with the rest regenerated. The Intermediate Data-set Storage problem arises from this situation. The current best algorithm for this problem takes O ( n 4 ) time. In this paper, we present two improved algorithms for this problem, the first of which can achieve a time complexity O ( n 2 ) , the second of which O ( r n ) , where n is the number of data-sets in a dataflow, r is a numerical number which indicates how large it is for the maximum storage cost to be divided by the minimum computation cost in the dataflow. [ABSTRACT FROM AUTHOR]

In-situ two-dimensional grazing incidence X-ray diffraction was applied in isothermal growth of graphene on nickel through chemical vapor deposition. The analyses showed that the graphene interlayer spacing decreases with the increasing number of graphene layers (growth time increase). Moreover, the as-deposited graphene can be gradually removed through in-situ Ar annealing treatment and inverse interlayer spacing change was also observed, i.e., the interlayer spacing of graphene increases with the number of graphene layers decrease. These results prove that there is a strong coupling effect between the interlayer spacing and the number of graphene layers. The weak interlayer interactions between graphene layers and the interface effects may contribute to this phenomenon. [ABSTRACT FROM AUTHOR]

Abstract: The present study reports a method to determine the total protein concentration or concentration of a protein of interest in a protein–protein conjugate using ultraviolet absorption, after determining the molar ratio of proteins in the conjugates, from which an extinction coefficient can be calculated. A Microsoft Excel solver-based template using amino acid analysis data was developed for determining the molar ratio. The percent mass of each protein in the conjugate is calculated from the amino acid composition data using the least squares method in the Microsoft Excel solver function, and the percent mass is converted to molar portion of each protein using corresponding molecular weight. A molar ratio is obtained by dividing the molar portion of protein 1 by the molar portion of protein 2. A weighted extinction coefficient is calculated using the molar ratio, and the total protein concentration is determined using ultraviolet absorption at 280nm. The accuracy of the method was verified using mixtures of known proteins. The present study provides a rapid, simple and accurate method for determining protein concentration in protein–protein conjugates. [Copyright &y& Elsevier]

Abstract: Efficient antigen extraction from vaccines formulated on aluminum hydroxide gels is a critical step for the evaluation of the quality of vaccines following formulation. It has been shown in our laboratory that the efficiency of antigen extraction from vaccines formulated on Alhydrogel decreased significantly with increased storage time. To increase antigen extraction efficiency, the present study determined the effect of surfactants on antigen recovery from vaccine formulations. The Plasmodium falciparum apical membrane antigen 1 (AMA1) formulated on Alhydrogel and stored at 2–8°C for 3 years was used as a model in this study. The AMA1 on Alhydrogel was extracted in the presence or absence of 30mM sodium dodecyl sulfate (SDS) or 20mM cetylpyridinium chloride in the extraction buffer (0.60M citrate, 0.55M phosphate, pH 8.5) using our standard antigen extraction protocols. Extracted AMA1 antigen was analyzed by 4–20% Tris–glycine SDS-PAGE followed by silver staining or western blotting. The results showed that inclusion of SDS or cetylpyridinium chloride in extraction buffer increased the antigen recovery dramatically and can be used for efficient characterization of Alhydrogel vaccines. [Copyright &y& Elsevier]

Abstract: Plasmodium falciparum apical membrane antigen 1 (AMA1) is an asexual blood-stage vaccine candidate against the malaria parasite. AMA1-C1/ISA720 refers to a mixture of recombinant AMA1 proteins representing the FVO and 3D7 alleles in 1:1 mass ratio, formulated with Montanide® ISA 720 as a water-in oil emulsion. In order to develop the AMA1-C1/ISA720 vaccine for human use, it was important to determine the shelf life of this formulation. Previously it was found 267mM glycine stabilized the proteins in Montanide® ISA 720 formulations for a short period of time at 2–8°C . We now test the long term stability of AMA1-C1 at 10 and 40μg/mL formulated with Montanide® ISA 720 with 50mM glycine as a stabilizer. Stability of AMA1-C1/ISA720 at different time points following formulation (0, 5, 12 or 18 months) was evaluated by determining the mean particle size (diameter of the mean droplet volume), total protein content by a Modified Lowry assay, identity and integrity using western blot and SDS–PAGE. Our results showed that the mean particle size of these emulsions increased over time, whereas protein content, as determined by an ELISA method using a monoclonal antibody against penta-his, decreased over time. For the 10μg/mL AMA1-C1/ISA720 vaccine, the protein content was 6.5±2.2μg/mL, and for the 40μg/mL AMA1-C1/ISA720 vaccine, the protein content was only 8.2±2.3μg/mL after 18 months of storage at 2–8°C. These results suggest that the integrity of the protein was affected by long-term storage. The results of the present study indicate that the AMA1-C1/ISA720 emulsion was unstable after 12 months of storage, after which AMA1-C1 proteins were partially degraded. [Copyright &y& Elsevier]

Abstract: Aluminum based adjuvants (alum), including aluminum hydroxide (Alhydrogel®) and aluminum phosphate are the most commonly used adjuvant in the US. In order to ensure quality of vaccines, regulatory authorities require evaluation of antigen content in final vaccine products. Currently, there are no generic methods available for the determination of protein content in alum-based vaccines. Aluminum hydroxide gels exist as particles in solution, which interfere with direct quantitation of protein content in formulations using assays such as Lowry, BCA or Bradford protein assay. The present study adapts a simple fluorescent assay to directly (without the need for antigen extraction) determine antigen content on Alhydrogel® with accuracy and sensitivity using the o-phthalaldehyde (OPA) reagent. Malaria vaccine candidates AMA1-C1/Alhydrogel, AMA1-C2/Alhydrogel, MSP142-3D7/Alhydrogel, MSP142-C1/Alhydrogel or BSAM-2/Alhydrogel were used as model formulations. The results of the present study show that the OPA assay is highly accurate (87–100%), reproducible, and simple with a linear detection range of 25–400μg/mL for Alhydrogel® vaccines (except for MSP142-C1, which has a linear detection range of 31.25–500μg/mL). This assay has proven to be highly useful in our laboratory and been used in routine vaccine quality control processes. [Copyright &y& Elsevier]

Abstract: Alhydrogel® (aluminum hydroxide) is a widely used adjuvant in the US. Regulatory authorities require that vaccines be tested to determine the antigen content in the final vaccine product. The level of formulated antigen is currently determined in our laboratory by the o-Phthalaldehyde (OPA) fluorescent protein assay, and antigen identity and integrity are determined by Western blot and SDS–PAGE. However, OPA assay is non-specific and only limited to detection of total protein content, and it is often not sensitive enough to detect antigens in low dose formulations. Furthermore, antigens used in identity and integrity tests must be extracted from vaccines using an extraction procedure which is time-consuming and may not completely recover antigens for analysis or may alter the structures of antigens during extraction. The present study developed a Direct Alum Formulation Immunoassay (DAFIA) which was designed to directly (without antigen extraction), accurately, and sensitively determine the antigen content, identity and integrity on alum. The AMA1-C1/Alhydrogel formulation was used as a model vaccine in assay development and validation. The results showed that the DAFIA is highly antigen-specific, accurate (87–100%), sensitive (0.16 µg/ml), reproducible, and simple with a linear detection range of 0.16–10 µg/ml. These results demonstrate that DAFIA is an excellent assay to determine antigen content, identity and integrity of antigens bound to alum and may be used in routine vaccine quality control for testing antigens in Alhydrogel-based vaccines. [Copyright &y& Elsevier]

Abstract: Residual host cell protein impurities in recombinant proteins intended for human use must be accurately quantified to help establish their safety. We describe a novel means of host cell protein quantitation, in which a slot blot system was employed together with scanning laser densitometry to allow picogram level sensitivity in detection of residual host cell proteins in unpurified fermentation products and final purified bulk samples. Two allelic forms of merozoite surface protein 1, a promising malaria vaccine candidate antigen currently undergoing evaluation in clinical trials, were expressed in E. coli as clinical grade proteins, refolded, and carried through several chromatographic purification steps. Several lots of these proteins were analyzed with this generic quantitative assay that uses rat polyclonal antibodies generated against soluble and insoluble E. coli proteins. The assay had a detection range of 6.1–1562 ng/mL, with a detection limit of 6.1 ng/mL, comparable to reported ELISA-based methods. This assay proved simple yet very sensitive and accurate, giving highly reproducible results. Thus it is suitable for evaluating host cell protein levels in clinical grade recombinant proteins expressed in E. coli. [Copyright &y& Elsevier]

The mechanism of action of a widely used drug gemfibrozil to reduce triglycerides (TG) and apolipoprotein B (apo B) is incompletely understood. Using human hepatoblastoma (HepG2) cells, we examined the effect of gemfibrozil on apo B secretion and TG synthesis catalyzed by diacylglycerol acyltransferase (DGAT), primary processes associated with the secretion of LDL. Gemfibrozil significantly decreased apo B secretion by HepG2 cells. It decreased oleate-induced stimulation of apo B secretion, suggesting that gemfibrozil-mediated inhibition of apo B secretion may be dependent on the synthesis of TG catalyzed by DGAT. Pre-incubation of HepG2 cells with gemfibrozil (200–400 μmol/l for 48 h) significantly inhibited microsomal DGAT activity. When added directly to the DGAT assay system containing control microsomes, gemfibrozil significantly inhibited the activity of DGAT by 14–25%. Gemfibrozil (200–400 μmol/l) inhibited TG synthesis by 47–50% as measured by the incorporation of 3H-oleic acid into TG. The data indicate that gemfibrozil inhibits DGAT activity resulting in decreased synthesis of TG and its availability for apo B lipidation rendering it susceptible to intracellular apo B degradation leading to the decreased secretion. These in-vitro data suggest a novel additional mechanism by which gemfibrozil lowers plasma TG and atherogenic apo B lipoproteins in dyslipidemic patients. [Copyright &y& Elsevier]

The Maximum Vertex Coverage problem (abbreviated as MVC) is to maximum the number of edges covered by a set of vertices of size exactly K on a graph. This problem is the dual of the vertex cover problem and has attracted a lot of interests in the literature of approximation algorithm. So far, the best approximation factor for the MVC problem is 3/4, which is obtained using an LP-rounding method. The main results of this paper are new approximation algorithms for MVC on cubic graphs and 3-bounded graphs (the vertex degrees are at most 3). The approximation factor on cubic graphs is 79/90 (≈0.878), which is tight by analyzing the existence of a feasible solution for a linear programming system. This algorithm can also be extended to 3-bounded graphs and guarantees an approximation factor of 19/24 (≈0.792). [ABSTRACT FROM AUTHOR]

Malaria transmission-blocking vaccines target mosquito-stage parasites and will support elimination programmes. Gamete vaccine Pfs230D1-EPA/Alhydrogel induced superior activity to zygote vaccine Pfs25-EPA/Alhydrogel in malaria-naive US adults. Here, we compared these vaccines in malaria-experienced Malians. We did a pilot safety study then double-blind, block-randomised, comparator-controlled main-phase trial in malaria-intense Bancoumana, Mali. 18–50-year-old healthy non-pregnant, non-breastfeeding consenting adult residents were randomly assigned (1:1:1:1) to receive four doses at months 0, 1, 4·5, and 16·5 of either 47 μg Pfs25, 40 μg Pfs230D1 or comparator (Twinrix or Menactra)—all co-administered with normal saline for blinding—or 47 μg Pfs25 plus 40 μg Pfs230D1 co-administered. We documented safety and tolerability (primary endpoint in the as-treated populations) and immunogenicity (secondary endpoint in the as-treated populations: ELISA, standard-membrane-feeding assay, and mosquito direct skin feed assay). This trial is registered at ClinicalTrials.gov , NCT02334462. Between March 19, and June 2, 2015, we screened 471 individuals. Of 225 enrolled for the pilot and main cohorts, we randomly assigned 25 participants to pilot safety cohort groups of five (20%) to receive a two-dose series of Pfs25-EPA/Alhydrogel (16 μg), Pfs230D1-EPA/Alhydrogel (15 μg) or comparator, followed by Pfs25-EPA/Alhydrogel (16 μg) plus Pfs230D1-EPA/Alhydrogel (15 μg) or comparator plus saline. For the main cohort, we enrolled 200 participants between May 11 and June 2, 2015, to receive a four-dose series of 47 μg Pfs25-EPA/Alhydrogel plus saline (n=50 [25%]; Pfs25), 40 μg Pfs230D1-EPA/Alhydrogel plus saline (n=49 [25%]; Pfs230D1), 47 μg Pfs25-EPA/Alhydrogel plus 40 μg Pfs230D1-EPA/Alhydrogel (n=50 [25%]; Pfs25 plus Pfs230D1), or comparator (Twinrix or Menactra) plus saline (n=51 [25%]). Vaccinations were well tolerated in the pilot safety and main phases. Most vaccinees became seropositive after two Pfs230D1 or three Pfs25 doses; peak titres increased with each dose thereafter (Pfs230D1 geometric mean: 77·8 [95% CI 56·9–106·3], 146·4 [108·3–198·0], and 410·2 [301·6–558·0]; Pfs25 geometric mean 177·7 [130·3–242·4] and 315·7 [209·9–474·6]). Functional activity (mean peak transmission-reducing activity) appeared for Pfs230D1 (74·5% [66·6–82·5]) and Pfs25 plus Pfs230D1 (68·6% [57·3–79·8]), after the third dose and after the fourth dose (88·9% [81·7–96·2] for Pfs230D1 and 85·0% [78·4–91·5] Pfs25 plus Pfs230D1) but not for Pfs25 (58·2% [49·1–67·3] after the third dose and 58·2% [48·5–67·9] after the fourth dose). Pfs230D1 transmission-reducing activity (73·7% [64·1–83·3]) persisted 10 weeks after the fourth dose. Transmission-reducing activity of 80% was estimated at 1659 ELISA units for Pfs25, 218 for Pfs230D1, and 223 for Pfs230D1 plus Pfs25. After 3850 direct skin feed assays, 35 participants (12 Pfs25, eight Pfs230D1, five Pfs25 plus Pfs230D1, and ten comparator) had transmitted parasites at least once. The proportion of positive assays in vaccine groups (Pfs25 33 [3%] of 982 [–0·013 to 0·014], Pfs230D1 22 [2%] of 954 [–0·005 to 0·027], and combination 11 [1%] of 940 [–0·024 to 0·002]) did not differ from that of the comparator (22 [2%] of 974), nor did Pfs230D1 and combination groups differ (–0·024 to 0·001). Pfs230D1 but not Pfs25 vaccine induces durable serum functional activity in Malian adults. Direct skin feed assays detect parasite transmission to mosquitoes but increased event rates are needed to assess vaccine effectiveness. Intramural Research Program of the National Institute of Allergy and Infectious Diseases and US National Institutes of Health. [ABSTRACT FROM AUTHOR]

Breakpoint graph has been widely used as a key data structure in algorithm design for genome rearrangements. The problem of breakpoint graph cycle decomposition, which asks for a largest collection of edge-disjoint cycles, is crucial in computing rearrangement distances between genomes. This problem is NP-hard, and can be approximated to 1.4193 + ϵ . It is still open for deciding whether a breakpoint graph can admit a cycle decomposition with none other than 2-cycles. In this paper, we present a linear time algorithm to detect whether a breakpoint graph can be decomposed into none other than 2-cycles. [ABSTRACT FROM AUTHOR]

The dehydration kinetics of graphene oxide (GO) were investigated by in-situ two-dimensional grazing incident X-ray diffraction. We found that the interlayer spacing of the GO membrane gradually decreased as the annealing temperature increased and as time elapsed. Surprisingly, we observed the formation of an intermediate “water-rich” GO layers at 25 °C with an interlayer spacing of approximately 15.2 Å, which was caused by the intercalation of two additional layers of water into the interlayers of the GO membrane. Moreover, three types of water trapped in GO were clearly distinguished upon isothermal annealing at various temperatures. Below 160 °C, the removal of “bulk water” and “confined water” resulted in a smaller interlayer spacing and the preservation of oxygen-containing functional groups. At 160 °C or higher, “bound water” was removed and oxygen-containing functional groups were lost, which contributed to the reduction of GO. The dehydration behaviour and structural evolution of GO investigated here is useful for understanding and controlling the properties of GO membranes for permeation, separation and electronic applications. [ABSTRACT FROM AUTHOR]

A clause is not-all-equal satisfied if it has at least one literal assigned with true and one literal assigned with false . Max NAE-SAT is given by a boolean variable set U and a clause set C , asks to find an assignment of U , such that the number of not-all-equal satisfied clauses in C is maximized. Max NAE-SAT turns into Max NAE- k -SAT if each clause contains exactly k literals. Local search has long been used in various SAT solvers. However, little has been done on local search to approximate Max NAE- k -SAT. Moreover, it is still open for what a quantitative bound could Max NAE- k -SAT be approximated to, at best. In this paper, we propose a local search algorithm which can approximate Max NAE- k -SAT to 2 k − 1 2 k − 1 − 1 for each fixed k ≥ 2 . Then we show that Max NAE- k -SAT cannot be approximated within 2 k − 1 2 k − 1 − 1 in polynomial time, if P ≠ NP . The algorithm for Max NAE- k -SAT can be extended to approximate Max NAE-SAT where each clause contains at least k literals to 2 k − 1 2 k − 1 − 1 . Using the algorithm for Max NAE-SAT where each clause contains at least k literals, we present a new algorithm to approximate Max-SAT where each clause contains at least k literals to 2 k 2 k − 1 . [ABSTRACT FROM AUTHOR]

Sorting permutations by block moves is a fundamental combinatorial problem in genome rearrangements. The classic block move operation is called transposition, which switches two adjacent blocks, or equivalently, moves a block to some other position. But large blocks movement rarely occurs during real evolutionary events. A natural restriction of transposition is to bound the length of the blocks to be switched. In this paper, we investigate the problem called sorting by bounded singleton moves, where one of the switched blocks is exactly a singleton while the other is of length at most c. This problem generalizes the sorting by short block moves problem proposed by Heath and Vergara [11] , which requires the total length of blocks switched bounded by 3. When c = 3 , we devise a 9 5 -approximation algorithm for an arbitrary permutation, and a 12 7 -approximation algorithm for a woven double-strip permutation. Our algorithms can be slightly extended to solve the sorting by c -bounded singleton moves problem for any constant c ≥ 3 , guaranteeing an approximation factor of 3 c 5 and 4 c 7 for arbitrary permutations and woven double-strip permutations respectively, just by exploiting a new lower bound of sorting by c -bounded singleton moves. • Sorting a lone dome, mushroom or rainbow needs a 1-move and a 2-move. • Sorting a lone double-mushroom, right-mushroom, left-mushroom or bridge needs a 1-move and two 2-moves. • If no correcting 2-move can be performed, then there exist lone arcs or mushrooms. • A permutation is a woven double-strip permutation if and only if its longest decreasing subsequence has length at most 2. [ABSTRACT FROM AUTHOR]

Abstract: Neospora caninum is the causal agent of bovine neosporosis which results in high levels of abortion. The present study determined the protective efficacy of two Neospora antigens –Neospora cyclophilin (NcCyP) and NcSRS2. The ability of native NcCyP to upregulate mouse IFN-γ was also confirmed in this study. Recombinant NcCyP or NcSRS2 were tested either alone or in combination and formulated with adjuvant ImmuMax-SR and CpG. Female BALB/c mice (n =15) of 10–12 weeks of age were immunized s.c. twice over a 2-week interval with vaccines containing either NcCyP (20μg/dose) alone, NcSRS2 (20μg/dose) alone, NcCyP plus NcSRS2, or non-recombinant bacterial antigen (NR) in 2 separate trials. All mice were challenge-infected 3 weeks following the booster immunization and necropsied 3 weeks after the challenge infection. Brain and serum were collected and Nc-specific DNA sequence in brain tissue and antibodies in serum were analyzed by PCR or ELISA/Western blotting. Results showed that mice vaccinated with rNcCyP, rNcSRS2, or both rNcCyP and rNcSRS2 responded with high levels of NcCyP or NcSRS2 specific antibodies. Overall, mice received vaccines formulated with either rNcCyP or rNcCyP and rNcSRS2 had a higher (p <0.01) percent protection when compared to the mock- or non-vaccinated mice. The group immunized with rNcSRS2 alone exhibited slightly lower levels of protection, which was higher (p <0.05) than that of the non-vaccinated group but did not differ (p =0.06) from that of the mock-vaccinated group. The results of the present study indicate that NcCyP is a highly efficacious vaccine candidate which may be useful in protection against Neospora infection. [Copyright &y& Elsevier]

The interactions between metal ions and graphene oxide (GO) nanosheets were investigated by in situ two-dimensional grazing incidence X-ray diffraction (GIXRD). We found that metal cations (Mn2+, Co2+, Cu2+, Fe3+) and GO can self-assemble into a hydroxide/GO superlattice by drop-casting a metal chloride and GO solution due to the electrostatic interactions between the positively charged hydroxide and the negatively charged GO nanosheets and the interlayer spacing of the superlattice can be controlled by the cation species. Moreover, based on this superlattice template, graphene-based metal oxide nanosheets can be facilely obtained by subsequent annealing. The growth mechanism and structural evolution of the GO/cation systems can be described in four stages: (1) hydrated cation intercalation of the GO interlayer in an aqueous solution; (2) metal hydroxide growth between the GO layers during annealing, with the formation of a superlattice structure at approximately 250 °C; (3) metal oxide nucleation between the reduced GO (rGO) interlayers with increasing temperature; and (4) complete graphene layer decomposition at a temperature of 600 °C, along with metal oxide nanosheet formation. This work gives a new perspective for understanding the interactions between and growth behaviour of metal cations and GO. We employed the in situ two-dimensional grazing incidence X-ray diffraction (GIXRD) technique to understand the interaction between and growth behaviour of metal cations (Mn2+, Co2+, Cu2+, Fe3+) and GO layers. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Pfs25H-EPA is a protein-protein conjugate transmission-blocking vaccine against Plasmodium falciparum that is safe and induces functional antibodies in malaria-naive individuals. In this field trial, we assessed Pfs25H-EPA/Alhydrogel for safety and functional immunogenicity in Malian adults.Methods: This double-blind, randomised, comparator-controlled, dose-escalation trial in Bancoumana, Mali, was done in two staggered phases, an initial pilot safety assessment and a subsequent main phase. Healthy village residents aged 18-45 years were eligible if they had normal laboratory results (including HIV, hepatitis B, hepatitis C tests) and had not received a previous malaria vaccine or recent immunosuppressive drugs, vaccines, or blood products. Participants in the pilot safety cohort and the main cohort were assigned (1:1) by block randomisation to a study vaccine group. Participants in the pilot safety cohort received two doses of Pfs25H-EPA/Alhydrogel 16 μg or Euvax B (comparator vaccine), and participants in the main cohort received Pfs25H-EPA/Alhydrogel 47 μg or comparator vaccine (Euvax B for the first, second, and third vaccinations and Menactra for the fourth vaccination). Participants and investigators were masked to group assignment, and randomisation codes in sealed envelopes held by a site pharmacist. Vials with study drug for injection were covered by opaque tape and labelled with a study identification number. Group assignments were unmasked at final study visit. The primary outcomes were safety and tolerability for all vaccinees. The secondary outcome measure was immunogenicity 14 days after vaccination in the per-protocol population, as confirmed by the presence of antibodies against Pfs25H measured by ELISA IgG and antibody functionality assessed by standard membrane feeding assays and by direct skin feeding assays. This trial is registered with ClinicalTrials.gov, number NCT01867463.Findings: Between May 15, and Jun 16, 2013, 230 individuals were screened for eligibility. 20 individuals were enrolled in the pilot safety cohort; ten participants were assigned to receive Pfs25H-EPA/Alhydrogel 16 μg, and ten participants were assigned to receive comparator vaccine. 100 individuals were enrolled in the main cohort; 50 participants were assigned to receive Pfs25H-EPA/Alhydrogel 47 μg, and 50 participants were assigned to receive comparator vaccine. Compared with comparator vaccinees, Pfs25H vaccinees had more solicited adverse events (137 events vs 86 events; p=0·022) and treatment-related adverse events (191 events vs 126 events, p=0·034), but the number of other adverse events did not differ between study vaccine groups (792 vs 683). Pfs25H antibody titres increased with each dose, with a peak geometric mean of 422·3 ELISA units (95% CI 290-615) after the fourth dose, but decreased relatively rapidly thereafter, with a half-life of 42 days for anti-Pfs25H and 59 days for anti-EPA (median ratio of titres at day 600 to peak, 0·19 for anti-Pfs25H vs 0·29 for anti-EPA; p=0·009). Serum transmission-reducing activity was greater for Pfs25H than for comparator vaccine after the fourth vaccine dose (p<0·001) but not after the third dose (p=0·09). Repeated direct skin feeds were well tolerated, but the number of participants who infected at least one mosquito did not differ between Pfs25H and comparator vaccinees after the fourth dose (p=1, conditional exact).Interpretation: Pfs25H-EPA/Alhydrogel was well tolerated and induced significant serum activity by standard membrane feeding assays but transmission blocking activity was not confirmed by weekly direct skin feed. This activity required four doses, and titres decreased rapidly after the fourth dose. Alternative antigens or combinations should be assessed to improve activity.Funding: Division of Intramural Research, National Institute of Allergy and Infectious Diseases. [ABSTRACT FROM AUTHOR]

The development of effective vaccines against difficult disease targets will require the identification of new subunit vaccination strategies that can induce and maintain effective immune responses in humans. Here we report on a phase 1a clinical trial using the AMA1 antigen from the blood-stage Plasmodium falciparum malaria parasite delivered either as recombinant protein formulated with Alhydrogel adjuvant with and without CPG 7909, or using recombinant vectored vaccines-chimpanzee adenovirus ChAd63 and the orthopoxvirus MVA. A variety of promising 'mixed-modality' regimens were tested. All volunteers were primed with ChAd63, and then subsequently boosted with MVA and/or protein-in-adjuvant using either an 8- or 16-week prime-boost interval. We report on the safety of these regimens, as well as the T cell, B cell, and serum antibody responses. Notably, IgG antibody responses primed by ChAd63 were comparably boosted by AMA1 protein vaccine, irrespective of whether CPG 7909 was included in the Alhydrogel adjuvant. The ability to improve the potency of a relatively weak aluminium-based adjuvant in humans, by previously priming with an adenoviral vaccine vector encoding the same antigen, thus offers a novel vaccination strategy for difficult or neglected disease targets when access to more potent adjuvants is not possible. [ABSTRACT FROM AUTHOR]

Abstract: A Phase 1 trial was conducted in malaria-naïve adults to evaluate the recombinant protein vaccine apical membrane antigen 1-Combination 1 (AMA1-C1) formulated in Montanide® ISA 720 (SEPPIC, France), a water-in-oil adjuvant. Vaccinations were halted early due to a formulation issue unrelated to stability or potency. Twenty-four subjects (12 in each group) were enrolled and received 5 or 20μg protein at 0 and 3 months and four subjects were enrolled and received one vaccination of 80μg protein. After first vaccination, nearly all subjects experienced mild to moderate local reactions and six experienced delayed local reactions occurring at Day 9 or later. After the second vaccination, three subjects experienced transient grade 3 (severe) local reactions; the remainder experienced grade 1 or 2 local reactions. All related systemic reactogenicity was grade 1 or 2, except one instance of grade 3 malaise. Anti-AMA1-C1 antibody responses were dose dependent and seen following each vaccination, with mean antibody levels 2–3 fold higher in the 20μg group compared to the 5μg group at most time points. In vitro growth-inhibitory activity was a function of the anti-AMA1 antibody titer. AMA1-C1 formulated in ISA 720 is immunogenic in malaria-naïve Australian adults. It is reasonably tolerated, though some transient, severe, and late local reactions are seen. [Copyright &y& Elsevier]

Abstract: In this paper we report our efforts to enhance the immunogenicity of Pfs28, a transmission blocking vaccine candidate of Plasmodium falciparum, using a strategy of chemical conjugation. With an improved procedure, Pfs28 was covalently coupled to the mutant and non-toxic ExoProtein A of Pseudomonas aeruginosa by the reaction between thiolated antigen and maleimide modified carrier protein. The optimized process resulted in a higher antigen-carrier conjugation ratio, and the conjugation product could be purified using single-step size-exclusion chromatography. A significant increase in immunogenicity measured by ELISA was observed in mice immunized with conjugated Pfs28 as compared to unconjugated Pfs28. [Copyright &y& Elsevier]

Abstract: Due to their low cost, flexibility, and convenience for long distance data transfer, plastic scintillating fibers (PSFs) have been increasingly used in building detectors or sensors for detecting various radiations and imaging. In this work, the possibility of using PSF coupled with charge-coupled devices (CCD) to build area detectors for X-ray imaging is studied using a Monte Carlo simulation. The focus is on X-ray imaging with energy from a few 100keV to about 20MeV. It is found that the efficiency of PSF in detecting X-ray in this energy range is low. The performance can be improved by coating a PSF with X-ray absorption layers and the MTF of the system is presented. It seems possible to build such area detectors with PSFs for imaging hard X-rays under certain environment. [Copyright &y& Elsevier]

Abstract: Montanide® ISA 720 is an experimental adjuvant, formulated as water-in-oil emulsions, that induces high antibody titers in several animal species. It has been used in human vaccine trials with malaria and HIV vaccines. The heightened response is likely due, in part, to the formation of a depot at the injection site. However, post-formulation modifications were seen with seven proteins tested during storage of ISA 720 formulations at 37°C for 1 week and two proteins stored longer at 4°C. Potency studies in mice, in which the stored vaccines were diluted into placebo emulsions for appropriate dosing, indicated that this instability could lead to loss of immunogenicity in the post-injection depot, limiting the allowable storage time of preformed vaccines. We describe point-of-injection formulation for ISA 720 vaccines that meets the requirement for in vitro stability. For preformed vaccines, addition of glycine or glycylglycine prevented antigen modification on storage at 37°C, providing a potential way of stabilizing antigen/ISA 720 formulations for in vitro storage and the post-injection depot. [Copyright &y& Elsevier]