Endovascular occlusion with a new mechanical detachable coil

OBJECTIVE: Metallic coils have been used for vascular embolization for many years but controlled-release coils have only recently become commercially available. Most of these devices are microcoils that were manufactured primarily for the packing of intracerebral aneurysms; therefore, they lack radial force and are not ideal agents for the occlusion of high-flow lesions such as pulmonary arteriovenous malformations (PAVMs). The objective of this study was to review our experience with a new detachable coil based on the conventional Gianturco-Wallace coil. SUBJECTS AND METHODS: The new detachable coil was initially used for the treatment of varicocele in 20 patients. Subsequently, the coil was used in 48 patients during 90 procedures for the treatment of PAVMs. RESULTS: A total of 548 coils were used. Complete occlusion of the testicular vein was achieved in all patients with varicocele. Successful occlusion of the PAVM being treated was achieved in all patients, and no instances of recanalization were documented in any of the patients who returned for follow-up angiography. Forty-one coils had to be removed completely from the catheter before detachment because of inappropriate size or position. Eight coils failed to detach easily, and six of these had to be removed. Most of these device failures were associated with kinking of the screw thread mechanism between the coil and the delivery wire. CONCLUSION: The Jackson detachable coil allows safer, more accurate, and more distal embolization of PAVMs than is possible with nondetachable coils. Complications associated with its use have been few.     

Kinetics of Silicothermic Reduction of Manganese Oxide for Advanced High-Strength Steel Production

The kinetics of silicothermic reduction of manganese oxide from MnO–SiO₂–CaO–Al₂O₃ slags reacting with Fe-Si droplets were studied in the temperature range of 1823 K to 1923 K (1550 °C to 1650 °C). The effects of initial droplet mass, initial droplet silicon content, and initial slag manganese oxide content were studied. Data obtained for 15 pct silicon showed agreement with control by mass transport of MnO in the slag with a mass transfer coefficient (k _s) of 4.0 × 10^?5 m/s at 1873 K (1600 °C). However, when this rate-determining step was tested at different initial silicon contents, the agreement was lost, suggesting mixed control between silicon transport in the metal and manganese oxide transport in the slag. Increasing the temperature resulted in a decrease in the rate of reaction because of an increase in the favorability of SiO as a product. Significant gas generation was found during all experiments, as a result of silicon monoxide production. The ratio of silicon monoxide to silica formation was increased by factors favoring silicon transport over that of manganese, further supporting the conclusion that the reaction is under mixed control by transports of both silicon and manganese oxide.     

Analysing experiences and issues in self-built shelters in Bangladesh using transdisciplinary approach

There are currently 70.8 million forcibly displaced people, globally. Bangladesh hosts the largest refugee camp in the world. Much effort has gone into the research, design and delivery of mass-produced shelters. Yet most refugees live in self-built shelters using simple shelter materials. This paper aims to demonstrate the benefits of using a transdisciplinary approach for holistic data collection in such shelters. A total of 1594 households were surveyed in refugee camps in Bangladesh using diverse methods—e.g. surveys, semi-structured interviews, physical measurements. It was only because of the use of various methods that the reasons behind identified issues were discovered or quantified. For example, household surveys uncovered the issue of poor ventilation, but only the semi-structured interviews exposed the reasons behind it, while physical measurements assessed the implications of this—annual particulate exposure 13 times the recommended limit. Furthermore, several methods pointed to issues with materials, but only the focus groups discussions exposed the need for gender-sensitive technical training tailored for women on the correct use of the materials. This study demonstrates that a diverse team (humanitarian staff, building physicists, and anthropologists) using several approaches to data-gathering and working in a transdisciplinary manner has much to offer the sector, and by including quantitative physical measurements allows costed improvement plans to be developed, targets to be set and general, rather than case specific, knowledge to be generated. The findings of this study have resulted in new shelter interventions by the aid sector that were rolled out in over 70,000 shelters.

     

Rapid and precise epitope mapping of monoclonal antibodies against Plasmodium falciparum AMA1 by combined phage display of fragments and random peptides

We describe an approach for the rapid mapping of epitopes withina malaria antigen using a combination of phage display techniques.Phage display of antigen fragments identifies the location ofthe epitopes, then random peptide libraries displayed on phageare employed to identify accurately amino acids involved inthe epitope. Finally, phage display of mutant fragments confirmsthe role of each residue in the epitope. This approach was appliedto the apical membrane antigen-1 (AMA1), which is a leadingcandidate for inclusion in a vaccine directed against the asexualblood stages of Plasmodium falciparum. As part of the effortboth to understand the function of AMA1 in the parasite lifecycle and to define the specificity of protective immune responses,a panel of monoclonal antibodies (MAbs) was generated to obtainbinding reagents to the various domains within the molecule.There is a pressing need to determine rapidly the regions recognizedby these antibodies and the structural requirements requiredwithin AMA1 for high affinity binding of the MAbs. Using phagedisplaying random AMA1 fragments, it was shown that MAb5G8 recognizesa short linear epitope within the pro-domain of AMA1 whereasthe epitope recognized by MAb 1F9 is reduction sensitive andresides within a disulphide-bonded 57 amino acid sub-domainof domain-1. Phage displaying random peptide libraries and mutantAMA1 fragments were employed for fine mapping of the MAb5G8core epitope to a three-residue sequence in the AMA1 prodomain.     

Peptides specific for Mycobacterium avium subspecies paratuberculosis infection: diagnostic potential

Mycobacterium avium subspecies paratuberculosis (Map) is the causative agent of Johne's disease (JD). Current serological diagnostic tests for JD are limited by their sensitivity when used in sub-clinical stages of the disease. Our objective was to identify peptides that mimic diagnostically important Map epitopes that might be incorporated into a new-generation JD diagnostic. Four peptides were isolated from a phage-displayed random peptide library by screening on antibodies derived from Map-infected goats. The peptides were recognised by antibodies from Map-infected goats but not by antibodies from uninfected goats. The peptides elicited immune responses in rabbits, which reacted strongly with bona fide Map antigens proving the peptides were true epitope mimics. To assess the diagnostic value a panel of goat sera was screened for reactivity's with peptides. The peptides were recognised by antibodies from a proportion of goats infected with Map compared with control animals with a diagnostic specificity of 100% and the sensitivity ranged from 50 to 75%. Combinations of any two peptides improved sensitivity 62.5-87.5% and 100% sensitivity was achieved with three of the four peptides in combination. These data suggest peptides representing diagnostically important Map epitopes could be incorporated into a sensitive diagnostic test.     

Optimising DNA binding to carbon nanotubes by non-covalent methods

The use of carbon nanotubes as a gene delivery system has been extensively studied in recent years owing to its potential advantages over viral vectors. To achieve this goal, carbon nanotubes have to be functionalized to become compatible with aqueous media and to bind the genetic material. To establish the best conditions for plasmid DNA binding, we compare the dispersion properties of single-, double- and multi-walled carbon nanotubes (SWCNTs, DWCNTs and MWCNTs, respectively) functionalized with a variety of surfactants by non-covalent attachment. The DNA binding properties of the functionalized carbon nanotubes were studied and compared by electrophoresis. Furthermore, a bilayer functionalization method for DNA binding on SWCNTs was developed that utilized RNA-wrapping to solubilize the nanotubes and cationic polymers as a bridge between nanotubes and DNA.     

Computer-aided evaluation and exploration of chemical spaces constrained by reaction pathways

The processes of molecular design and synthetic route selection are necessarily intertwined during discovery. Computational tools have been developed to facilitate synthesis planning, but in a discovery setting, finding a single route to a single molecule of interest may be less important than finding a route that enables rapid access to a library of analogs. Here, we demonstrate how we can estimate route “diversifiability” and use it as a criterion during route selection. We illustrate how the chemical space of synthetically accessible analogs is influenced by properties of alternative starting materials or constraints on their cost. Finally, we integrate these analyses with a synthesizability-constrained hit expansion workflow in a virtual screening pipeline for focused library expansion around putative hits to support molecular optimization. As medicinal chemistry and adjacent fields shift toward more autonomous design and synthesis of new molecules, it will be increasingly important to embed considerations of synthesizability into molecular design to ensure that computational recommendations are actionable.     

Cellular localization,accumulation and trafficking of double-walled carbon nanotubes in human prostate cancer cells

Carbon nanotubes (CNTs) are at present being considered as potential nanovectors with the ability to deliver therapeutic cargoes into living cells. Previous studies established the ability of CNTs to enter cells and their therapeutic utility, but an appreciation of global intracellular trafficking associated with their cellular distribution has yet to be described. Despite the many aspects of the uptake mechanism of CNTs being studied, only a few studies have investigated internalization and fate of CNTs inside cells in detail. In the present study, intracellular localization and trafficking of RNA-wrapped, oxidized double-walled CNTs (oxDWNT-RNA) is presented. Fixed cells, previously exposed to oxDWNT-RNA, were subjected to immunocytochemical analysis using antibodies specific to proteins implicated in endocytosis; moreover cell compartment markers and pharmacological inhibitory conditions were also employed in this study. Our results revealed that an endocytic pathway is involved in the internalization of oxDWNT-RNA. The nanotubes were found in clathrin-coated vesicles, after which they appear to be sorted in early endosomes, followed by vesicular maturation, become located in lysosomes. Furthermore, we observed co-localization of oxDWNT-RNA with the small GTP-binding protein (Rab 11), involved in their recycling back to the plasma membrane via endosomes from the trans-golgi network.      

Corrosion of nickel-containing stainless steel in concentrated sulphuric acid

The corrosion of UNS S30403 stainless steel was investigated in 93.5 wt% sulphuric acid at temperatures from 40 to 100 °C. Time-dependent free corrosion potential measurements demonstrate that the steel is subject to spontaneous active-passive oscillation. Studies on the effect of temperature and electrode rotation speed indicate that the oscillation is activation and transport controlled over different segments of the oscillations. It is concluded that the oscillation is caused by reversible changes in the exchange current for the cathodic reduction of sulphuric acid, depending on the presence or absence of nickel sulphide on the steel surface.     

A Model to Compute Phase Diagrams in Oxides with Empirical or First-Principles Energy Methods and Application to the Solubility Limits in the CaO–MgO System

The CaO–MgO system is used as a prototype system to evaluate the accuracy of several energy and entropy approximations for predicting solid-state phase diagrams in ionic materials. Configurational disorder between the cations is parameterized with the cluster expansion technique. The vibrational contribution to the free energy is incorporated with a harmonic model that accounts for the dependence of the vibrational density of states on the cation configuration. The CaO–MgO phase diagram can be predicted very accurately with quantum mechanical energy methods, without the use of any adjustable parameters. Published empirical potential parameters for the CaO–MgO system reproduce the qualitative features of the phase diagram but significantly underestimate the solubility limits. Parameters that reasonably reproduce the quantum mechanical results are presented.