Lipid and carbohydrate based adjuvant/carriers in immunology

This review discusses various issues regarding vaccines:what are they and how they work, safety aspects, the role of adjuvants and carriers in vaccination, synthetic peptides as immunogens, and new technologies for vaccine development and delivery including the identification of novel adjuvants for mucosal vaccine delivery. There has been a recent increase of interest, in the use of lipids and carbohydrates as adjuvants, and so a particular emphasis is placed on adjuvants derived from lipids or carbohydrates, or from both. Copyright (C) 2003 European Peptide Society and John Wiley Sons, Ltd.

Pacific Carriers Ltd v BNP Paribas

High Court decision in Pacific Carriers v BNP Paribas, that BNP Paribas was estopped from denying the authority of its manager to sign the documents on its behalf will be a relief to third parties who rely on documents signed for and on behalf of financial institutions - particularly to those involved in the shipping industry who seek letters of indemnity relating to discharge of cargo without production of bills of lading.

Using DEM to model ore breakage within a pilot scale SAG mill

The best accepted method for design of autogenous and semi-autogenous (AG/SAG) mills is to carry out pilot scale test work using a 1.8 m diameter by 0.6 m long pilot scale test mill. The load in such a mill typically contains 250,000-450,000 particles larger than 6 mm, allowing correct representation of more than 90% of the charge in Discrete Element Method (DEM) simulations. Most AG/SAG mills use discharge grate slots which are 15 mm or more in width. The mass in each size fraction usually decreases rapidly below grate size. This scale of DEM model is now within the possible range of standard workstations running an efficient DEM code. This paper describes various ways of extracting collision data front the DEM model and translating it into breakage estimates. Account is taken of the different breakage mechanisms (impact and abrasion) and of the specific impact histories of the particles in order to assess the breakage rates for various size fractions in the mills. At some future time, the integration of smoothed particle hydrodynamics with DEM will allow for the inclusion of slurry within the pilot mill simulation. (C) 2004 Elsevier Ltd. All rights reserved.

E-cadherin transport from the trans-Golgi network in tubulovesicular carriers is selectively regulated by Golgin-97

E-cadherin is a cell-cell adhesion protein that is trafficked and delivered to the basolateral cell surface. Membrane-bound carriers for the post-Golgi exocytosis of E-cadherin have not been characterized. Green fluorescent protein (GFP)-tagged E-cadherin (Ecad-GFP) is transported from the trans-Golgi network (TGN) to the recycling endosome on its way to the cell surface in tubulovesicular carriers that resemble TGN tubules labeled by members of the golgin family of tethering proteins. Here, we examine the association of golgins with tubular carriers containing E-cadherin as cargo. Fluorescent GRIP domains from golgin proteins replicate the membrane binding of the full-length proteins and were coexpressed with Ecad-GFP. The GRIP domains of p230/golgin-245 and golgin-97 had overlapping but nonidentical distributions on the TGN; both domains were on TGN-derived tubules but only the golgin-97 GRIP domain coincided with Ecad-GFP tubules in live cells. When the Arl1-binding endogenous golgins, p230/golgin-245 and golgin-97 were displaced from Golgi membranes by overexpression of the p230 GRIP domain, trafficking of Ecad-GFP was inhibited. siRNA knockdown of golgin-97 also inhibited trafficking of Ecad-GFP. Thus, the GRIP domains of p230/golgin-245 and golgin-97 bind discriminately to distinct membrane subdomains of the TGN. Golgin-97 is identified as a selective and essential component of the tubulovesicular carriers transporting E-cadherin out of the TGN.

Clathrin-independent endocytosis: New insights into caveolae and non-caveolar lipid raft carriers

A number of recent studies have provided new insights into the complexity of the endocytic pathways originating at the plasma membrane of mammalian cells. Many of the molecules involved in clathrin coated pit internalization are now well understood but other pathways are less well defined. Caveolae appear to represent a low capacity but highly regulated pathway in a restricted set of tissues in vivo. A third pathway, which is both clathrin- and caveolae-independent, may constitute a specialized high capacity endocytic pathway for lipids and fluid. The relationship of this pathway, if any, to macropinocytosis or to the endocytic pathways of lower eukaryotes remains an interesting open question. Our understanding of the regulatory mechanisms and molecular components involved in this pathway are at a relatively primitive stage. In this review, we will consider some of the characteristics of different endocytic pathways in high and lower eukaryotes and consider some of the common themes in endocytosis. One theme which becomes apparent from comparison of these pathways is that apparently different pathways can share common molecular machinery and that pathways considered to be distinct actually represent similar basic pathways to which additional levels of regulatory complexity have been added. (c) 2005 Elsevier B.V. All rights reserved.

Mapping loss of heterozygosity in normal human breast cells from BRCA1/2 carriers

We have studied loss of heterozygosity at the BRCA1 and BRCA2 loci in 992 normal cell clones derived from topographically defined areas of normal tissue in four samples from BRCA1/BRCA2 mutation carriers. The frequency of loss of heterozygosity in the clones was low ( 1.01%), but it was found in all four samples, whether or not a tumour was present. Topographical mapping revealed that the genetic changes were clustered in some breast samples. Our study confirms the previous finding that a field of genetic instability can exist around a tumour, suggesting that sufficient tissue must be removed at surgery to avoid local recurrence. We also demonstrate that such a field of genetic change can exist in morphologically normal tissue before a tumour develops and, for the first time, we demonstrate that the field is of a size greater than one terminal duct-lobular unit. The genetic changes are not identical, however, which suggests that genetic instability in these regions may play an early role in tumour development. We also confirm and extend our original observation of loss of the wild-type BRCA1 allele in some clones, and loss of the mutant allele in others, demonstrating that loss of either allele is a stochastic event.

Inorganic nanoparticles as carriers for efficient cellular delivery

Cellular delivery involving the transfer of various drugs and bio-active molecules (peptides, proteins and DNAs, etc.) through the cell membrane into cells has attracted increasing attention because of its importance in medicine and drug delivery. This topic has been extensively reviewed. The direct delivery of drugs and biomolecules, however, is generally inefficient and suffering from problems such as enzymic degradation of DNAs. Therefore, searching for efficient and safe transport vehicles (carriers) to delivery genes or drugs into cells has been challenging yet exciting area of research. In past decades, many carriers have been developed and investigated extensively which can be generally classified into four major groups: viral carriers, organic cationic compounds, recombinant protiens and inorganic nanoparticles. Many inorganic materials, such as calcium phosphate, gold, carbon materials, silicon oxide, iron oxide and layered double hydroxide (LDH), have been studied. Inorganic nanoparticles show low toxicity and promise for controlled delivery properties, thus presenting a new alternative to viral carriers and cationic carriers. Inorganic nanoparticles generally possess versatile properties suitable for cellular delivery, including wide availability, rich functionality, good biocompatibility, potential capability of targeted delivery (e.g. selectively destroying cancer cells but sparing normal tissues) and controlled release of carried drugs. This paper reviews the latest advances in inorganic nanoparticle applications as cellular delivery carriers and highlights some key issues in efficient cellular delivery using inorganic nanoparticles. Critical proper-ties of inorganic nanoparticles, surface functionalisation (modification), uptake of biomolecules, the driving forces for delivery, and release of biomolecules will be reviewed systematically. Selected examples of promising inorganic nanoparticle delivery systems, including gold, fullerences and carbon nanotubes, LDH and various oxide nanoparticles in particular their applications for gene delivery will be discussed. The fundamental understanding of properties of inorganic nanoparticles in relation to cellular delivery efficiency as the most paramount issue will be highlighted. (c) 2005 Elsevier Ltd. All rights reserved.

Dating paleochannel iron ore by (U-Th)/He analysis of supergene goethite, Hamersley province, Australia

(U-Th)/He dating of late-stage authigenic goethite, combined with corrections for diffusive loss of He-4 by the He-4/He-3 methodology, reveals strong correlation between a sample's age and its depth in ferruginized channel sediments from the Yandicoogina deposit, Western Australia. Corrected ages, ranging from ca. 18 Ma near the surface to ca. 5 Ma at the bottom of the profile, indicate that ferruginization of the aggraded channels becomes progressively younger with depth. This trend is consistent with goethite precipitation at the groundwater-atmosphere interface during water table drawdown driven by the aridification of Western Australia during the Neogene. The results demonstrate that the (U-Th)/He system is ideal for dating goethite if diffusive loss corrections are applied. The approach is suitable for dating weathering reactions on Earth and should also be suitable for dating Fe oxyhydroxides in the Martian regolith.

Thermal evolution of the ore-hosting Isa Superbasin: Central and Northern Lawn Hill Platform

Hydrocarbon migration pathways and organic mineral matter associations were used to identify brine pathways in Paleoproterozic to early Mesoproterozoic rocks from the Lawn Hill platform, Mount Isa. Several types of organic matter are identified, and their thermal imprints are used to reconstruct the thermal history of the northern to central parts of the Isa superbasin. Three major thermal hydrothermal episodes are recognized from the organic maturation studies. Isotherm plots on a 175-km-long structural-sedimentological north-south section of the Isa superbasin highlight specific fault systems that acted as hot fluid conduits during the geologic history of the basin. Some of these systems indicate continuing activity into the south Nicholson basin, supported by the presence of low reflectance (type B) bitumen. This bitumen has not been overprinted by later hydrothermal episodes and therefore represents the latest thermal event. Along the north-south profile a general southward increase in temperature is evident. The lowest temperatures are recorded in proximity to the basin margin on the southern flank of the Murphy inlier. Thermal processes and their sequence of events in the basin are recorded by organic maturation, subsequent hydrocarbon generation, its migration and destruction coincident with transport and precipitation of minerals. As some timing and trapping mechanisms for minerals may have analogues with hydrocarbon entrapment, relative timing of processes leading to organic maturation, hydrocarbon generation and migration are utilized in this study to enhance understanding of ore-grade mineralization. In the Proterozoic successions of the Mount Isa basin multiple hydrocarbon generation events are recognized. These events record the transient passage of potential metal-bearing fluids rather than background conductive heat flow from the basement. Such hydrothermal fluids are responsible for inverse maturation profiles in the vicinity of the Termite Range fault and extreme maturation (reflectance values) up to 6 percent Ro at the Grevillea prospect. At Century, intermediate Ro values of

Wills' mineral processing technology: an introduction to the practical aspects of ore treatment and mineral recovery

"Wills' Mineral Processing Technology" provides practising engineers and students of mineral processing, metallurgy and mining with a review of all of the common ore-processing techniques utilized in modern processing installations. Now in its Seventh Edition, this renowned book is a standard reference for the mineral processing industry. Chapters deal with each of the major processing techniques, and coverage includes the latest technical developments in the processing of increasingly complex refractory ores, new equipment and process routes. This new edition has been prepared by the prestigious J K Minerals Research Centre of Australia, which contributes its world-class expertise and ensures that this will continue to be the book of choice for professionals and students in this field. This latest edition highlights the developments and the challenges facing the mineral processor, particularly with regard to the environmental problems posed in improving the efficiency of the existing processes and also in dealing with the waste created. The work is fully indexed and referenced. -The classic mineral processing text, revised and updated by a prestigious new team -Provides a clear exposition of the principles and practice of mineral processing, with examples taken from practice -Covers the latest technological developments and highlights the challenges facing the mineral processor -New sections on environmental problems, improving the efficiency of existing processes and dealing with waste.

40Ar/39Ar dating of Mn-iron ore of the Sapecado Mine, Qadrilatero Ferrifero, Brazil

The SW region of Amazonian craton presents policyclic evolution between 1.80-1.00 Ga and is comprised of the Rio Negro-Juruena, Rondoniana and Sunsas Provinces. The evolution of this region has being characterized by four orogens: Alto Jauru (1.79-1.74 Ga), Cachoeirinha (1.58-1.52 Ga), Suíte Santa Helena (1.45-1.42 Ga) e Sunsas/Aguapeí (1.0-0.9 Ga). The Alto Jauru orogen consists of TTG gneissic associations, greenstone sequences and intrusive granitoids origined in volcanic arc setting. Eight 40Ar/39Ar step-heating analyses were carried out in minerals (biotiteand hornblende) to investigate the thermal history and crustal evolution of this region. From the Alto Jauru orogen was sampled the gneiss banded and two biotite grains provide large dispersion of apparent ages, suggesting heterogenity in reservoir of the argon. Apparent age diagram yielded integrated ages of 1472 ± 6 Ma, interpreted as minimum ages of regional cooling episode. Three analyses of hornblende present ages varing from 1310 to 1400 Ma, possibly because smaller grain size become more susceptible to argon loss. 40Ar/39Ar step-heating methodology applied on biotite of pyroclastic tuff (U-Pb age about 1758 ± 7 Ma) presented integrated age of 1507 ± 7 Ma. The results found for this terrane demonstrated a geochronological correlation with metamorphic process linked Cachoeirinha orogen. Biotite and hornblende grains separates from granite and a tonalite origined during Cachoeirinha orogen were analyzed and the apparent age diagrams indicated well-defined plateau ages of 1520-1540 Ma. Biotite grains from a granitic sample were analized, and integrated ages about 1526 ± 2 Ma were obtained due argon loss in the initial steps. Thermochronologic history of SW region Amazonian craton is coherent with regional policyclic events and 40Ar/39Ar ages here presented probably correspond to regional cooling period of Cachoeirinha orogen.