Bronsted-Evans-Polanyi relation of multistep reactions and volcano curve in heterogeneous catalysis

Multistep surface processes involving a number of association reactions and desorption processes may be considered as hypothetical one-step desorption processes. Thus, heterogeneous catalytic reactions can be treated kinetically as consisting of two steps: adsorption and desorption. It is also illustrated that the hypothetical one-step desorption process follows the BEP relation. A volcano curve can be obtained from kinetic analysis by including both adsorption and desorption processes.

Ionic liquid-reconstituted cellulose composites as solid support matrices for biocatalyst immobilization

Preparation of cellulose-polyamine composite films and beads, which provide high loading of primary amines on the surface allowing direct one-step bioconjugation of active species, is reported using an ionic liquid (IL) dissolution and regeneration process. Films and bead architectures were prepared and used as immobilization supports for laccase as a model system demonstrating the applicability of this approach. Performance of these materials, compared to commercially available products, has been assessed using millimeter-sized beads of the composites and the lipase-catalyzed transesterification of ethyl butyrate.

USP17 Regulates Ras Activation and Cell Proliferation by Blocking RCE1 Activity

The proto-oncogene Ras undergoes a series of post-translational modifications at its carboxyl-terminal CAAX motif that are essential for its proper membrane localization and function. One step in this process is the cleavage of the CAAX motif by the enzyme Ras-converting enzyme 1 (RCE1). Here we show that the deubiquitinating enzyme USP17 negatively regulates the activity of RCE1. We demonstrate that USP17 expression blocks Ras membrane localization and activation, thereby inhibiting phosphorylation of the downstream kinases MEK and ERK. Furthermore, we show that this effect is caused by the loss of RCE1 catalytic activity as a result of its deubiquitination by USP17. We also show that USP17 and RCE1 co-localize at the endoplasmic reticulum and that USP17 cannot block proliferation or Ras membrane localization in RCE1 null cells. These studies demonstrate that USP17 modulates Ras processing and activation, at least in part, by regulating RCE1 activity.

Data mining approach identifies research priorities and data requirements for resolving the red algal tree of life

Background. The assembly of the tree of life has seen significant progress in recent years but algae and protists have been largely overlooked in this effort. Many groups of algae and protists have ancient roots and it is unclear how much data will be required to resolve their phylogenetic relationships for incorporation in the tree of life. The red algae, a group of primary photosynthetic eukaryotes of more than a billion years old, provide the earliest fossil evidence for eukaryotic multicellularity and sexual reproduction. Despite this evolutionary significance, their phylogenetic relationships are understudied. This study aims to infer a comprehensive red algal tree of life at the family level from a supermatrix containing data mined from GenBank. We aim to locate remaining regions of low support in the topology, evaluate their causes and estimate the amount of data required to resolve them. Results. Phylogenetic analysis of a supermatrix of 14 loci and 98 red algal families yielded the most complete red algal tree of life to date. Visualization of statistical support showed the presence of five poorly supported regions. Causes for low support were identified with statistics about the age of the region, data availability and node density, showing that poor support has different origins in different parts of the tree. Parametric simulation experiments yielded optimistic estimates of how much data will be needed to resolve the poorly supported regions (ca. 103 to ca. 104 nucleotides for the different regions). Nonparametric simulations gave a markedly more pessimistic image, some regions requiring more than 2.8 105 nucleotides or not achieving the desired level of support at all. The discrepancies between parametric and nonparametric simulations are discussed in light of our dataset and known attributes of both approaches. Conclusions. Our study takes the red algae one step closer to meaningful inclusion in the tree of life. In addition to the recovery of stable relationships, the recognition of five regions in need of further study is a significant outcome of this work. Based on our analyses of current availability and future requirements of data, we make clear recommendations for forthcoming research.

Rapid screening for monensin residues in poultry plasma by a dry reagent dissociation enhanced lanthanide fluoroimmunoassay.

Monensin, a carboxylic acid ionophore, is commonly fed to poultry to control coccidiosis. A method for rapid analysis of unextracted poultry plasma samples has been developed based on a novel immunoassay format: one-step all-in-one dry reagent time resolved fluorimetry. All assay specific components were pre-dried onto microtitration plate wells. Only addition of the serum sample diluted in assay buffer was required to perform analysis. Results were available one hour after sample addition. The limit of detection (mean + 3s) of the assay calculated from the analysis of 23 known negative samples was 14.2 ng ml(-1). Intra- and inter-assay RSD were determined as 15.2 and 7.4%, respectively, using a plasma sample fortified with 50 ng ml(-1) monensin. Eight broiler chickens were fed monensin at a dose rate of 120 mg kg(-1) feed for one week, blood sampled then slaughtered without drug withdrawal. Plasma monensin concentrations, as determined by the fluoroimmunoassay ranged from 101-297 ng ml(-1). This compared with monensin liver concentrations, determined by LC-MS, which ranged fi om 13-41 ng g(-1). The fluoroimmunoassay described is extremely user friendly, gives particularly rapid results and is suitable for the detection and quantification of plasma monensin residues. Data from medicated poultry suggest that analysis of plasma may be useful in predicting the extent of monensin liver residues.

Synergistic phage-antibiotic combinations for the control of Escherichia coli biofilms in vitro.

The potential application of phage therapy for the control of bacterial biofilms has received increasing attention as resistance to conventional antibiotic agents continues to increase. The present study identifies antimicrobial synergy between bacteriophage T4 and a conventional antibiotic, cefotaxime, via standard plaque assay and, importantly, in the in vitro eradication of biofilms of the T4 host strain Escherichia coli 11303. Phage-antibiotic synergy (PAS) is defined as the phenomenon whereby sub-lethal concentrations of certain antibiotics can substantially stimulate the host bacteria's production of virulent phage. Increasing sub-lethal concentrations of cefotaxime resulted in an observed increase in T4 plaque size and T4 concentration. The application of PAS to the T4 one-step growth curve also resulted in an increased burst size and reduced latent period. Combinations of T4 bacteriophage and cefotaxime significantly enhanced the eradication of bacterial biofilms when compared to treatment with cefotaxime alone. The addition of medium (10(4) PFU mL(-1) ) and high (10(7) PFU mL(-1) ) phage titres reduced the minimum biofilm eradication concentration value of cefotaxime against E. coli ATCC 11303 biofilms from 256 to 128 and 32 µg mL(-1) , respectively. Although further investigation is needed to confirm PAS, this study demonstrates, for the first time, that synergy between bacteriophage and conventional antibiotics can significantly improve biofilm control in vitro.

Numbered-up gas-liquid micro/milli channels reactor with modular flow distributor

Gas-liquid processing in microreactors remains mostly restricted to the laboratory scale due to the complexity and expenditure needed for an adequate numbering-up with a uniform flow distribution. Here, the numbering-up is presented for multi-phase (gas-liquid) flow in microreactor suitable for a production capacity of kg/h. Based on the barrier channels concept, the barrier-based micro/milli reactor (BMMR) is designed and fabricated to deliver flow non-uniformity of less than 10%. The BMMR consists of eight parallel channels all operated in the Taylor flow regime and with a liquid flow rate up to 150. mL/min. The quality of the flow distribution is reported by studying two aspects. The first aspect is the influence of different viscosities, surface tensions and flow rates. The second aspect is the influence of modularity by testing three different reaction channels type: (1) square channels fabricated in a stainless steel plate, (2) square channels fabricated in a glass plate, and (3) circular channels (capillaries) made of stainless steel. Additionally, the BMMR is compared to that of a single channel regard the slug and bubble lengths and bubble generation frequency. The results pave the ground for bringing multi-phase flow in microreactor one step closer for large scale production via numbering-up. © 2012 Elsevier B.V.

The Dimensions of Expatriate Adjustment

A narrow and partial theoretical base has limited current concepts of expatriate adjustment and the research based upon them. This conceptual article explores one of the less theorized aspects of expatriate adjustment: the fact that it has multiple dimensions. We conceive of adjustment as a person-environment relationship that takes place in the three dimensions of cognitions, feelings, and behaviors. Combining these elements takes us one step closer to a comprehensive and more realistic understanding of the nature of expatriate adjustment. We include suggestions for future research that follow from our reconceptualization.

Mesoporous SSZ-13 zeolite prepared by a dual-template method with improved performance in the methanol-to-olefins reaction

Hierarchical SSZ-13 zeolites were synthesized by combining N,N,N-trimethyl-1-adamantanammonium hydroxide (TMAdOH) as the structure-directing agent for chabazite formation with mono- and diquaternary ammonium-type and organosilane mesoporogens and extensively characterized for their structural, textural, and catalytic properties. Mesoporous SSZ-13 zeolites can be synthesized in one step by combining TMAdOH and the diquaternary ammonium-type surfactant C22-4-4Br2. The mesopore volume increases with the mesoporogen/SDA ratio. The hierarchical zeolites are highly crystalline and exhibit similar Brønsted acidity as SSZ-13. Hierarchical SSZ-13 zeolites display increased lifetime in packed-bed MTO experiments than conventional SSZ-13 at similar light olefins yield. The increased lifetime is due to better utilization of the micropore space. With increasing mesoporosity, the micropore space is used more efficiently, but also the rate of coke formation at the crystal periphery increases. Accordingly, the most stable zeolite is obtained at a relatively low C22-4-4Br2/SDA ratio. These zeolite catalysts can be regenerated without substantial loss of activity.

Systematic Engineering of Uniform, Highly Efficient, Targeted and Shielded Viral-Mimetic Nanoparticles

In the past decades, numerous types of nanomedicines have been developed for the efficient and safe delivery of nucleic acid-based drugs for cancer therapy. Given that the destination sites for nucleic acid-based drugs are inside cancer cells, delivery systems need to be both targeted and shielded in order to overcome the extracellular and intracellular barriers. One of the major obstacles that has hindered the translation of nanotechnology-based gene-delivery systems into the clinic has been the complexity of the design and assembly processes, resulting in non-uniform nanocarriers with unpredictable surface properties and efficiencies. Consequently, no product has reached the clinic yet. In order to address this shortcoming, a multifunctional targeted biopolymer is genetically engineered in one step, eliminating the need for multiple chemical conjugations. Then, by systematic modulation of the ratios of the targeted recombinant vector to PEGylated peptides of different sizes, a library of targeted-shielded viral-mimetic nanoparticles (VMNs) with diverse surface properties are assembled. Through the use of physicochemical and biological assays, targeted-shielded VMNs with remarkably high transfection efficiencies (>95%) are screened. In addition, the batch-to-batch variability of the assembled targeted-shielded VMNs in terms of uniformity and efficiency is examined and, in both cases, the coefficient of variation is calculated to be below 20%, indicating a highly reproducible and uniform system. These results provide design parameters for engineering uniform, targeted-shielded VMNs with very high cell transfection rates that exhibit the important characteristics for in vivo translation. These design parameters and principles could be used to tailor-make and assemble targeted-shielded VMNs that could deliver any nucleic acid payload to any mammalian cell type.

Microneedle-Iontophoresis Combinations for Enhanced Transdermal Drug Delivery

It has recently been proposed that the combination of skin barrier impairment using microneedles (MNs) coupled with iontophoresis (ITP) may broaden the range of drugs suitable for transdermal delivery as well as enabling the rate of delivery to be achieved with precise electronic control. However, few reports exist on the combination of ITP with in situ drug-loaded polymeric MN delivery systems. Our in vitro permeation studies revealed that MN enhances transdermal drug delivery. The combination of dissolving MN and ITP did not further enhance the extent of delivery of the low molecular weight drug ibuprofen sodium after short application periods. However, the extent of peptide/protein delivery was significantly enhanced when ITP was used in combination with hydrogel-forming MN arrays. As such, hydrogel-forming MN arrays show promise for the electrically controlled transdermal delivery of biomacromolecules in a simple, one-step approach, though further technical developments will be necessary before patient benefit is realized.

Human B cell colony growth from pre-B cells in vitro

We describe a simple one-step technique for the growth of human B cell colonies in semi-solid agar in vitro. This method used conditioned medium from the human plasmacytoma cell line LICR-LON-H My 2 as a source of stimulating activity. A linear relationship exists between the number of B cells seeded and the number of colonies formed (r = 0.95). Most colony forming cells, approximately 1 in 500 of B cells seeded, lack surface immunoglobulin, possess Fc receptors and mark with the Leu 12 monoclonal antibody. Cells within developing colonies are found to have cytoplasmic IgM, IgA and IgG depending on the length of time in culture.

Evolving to the optoelectronic mouse for phycotoxin analysis in shellfish

Despite ethical and technical concerns, the in vivo method, or more commonly referred to mouse bioassay (MBA), is employed globally as a reference method for phycotoxin analysis in shellfish. This is particularly the case for paralytic shellfish poisoning (PSP) and emerging toxin monitoring. A high-performance liquid chromatography method (HPLC-FLD) has been developed for PSP toxin analysis, but due to difficulties and limitations in the method, this procedure has not been fully implemented as a replacement. Detection of the diarrhetic shellfish poisoning (DSP) toxins has moved towards LC-mass spectrometry (MS) analysis, whereas the analysis of the amnesic shellfish poisoning (ASP) toxin domoic acid is performed by HPLC. Although alternative methods of detection to the MBA have been described, each procedure is specific for a particular toxin and its analogues, with each group of toxins requiring separate analysis utilising different extraction procedures and analytical equipment. In addition, consideration towards the detection of unregulated and emerging toxins on the replacement of the MBA must be given. The ideal scenario for the monitoring of phycotoxins in shellfish and seafood would be to evolve to multiple toxin detection on a single bioanalytical sensing platform, i.e. 'an artificial mouse'. Immunologically based techniques and in particular surface plasmon resonance technology have been shown as a highly promising bioanalytical tool offering rapid, real-time detection requiring minimal quantities of toxin standards. A Biacore Q and a prototype multiplex SPR biosensor have been evaluated for their ability to be fit for purpose for the simultaneous detection of key regulated phycotoxin groups and the emerging toxin palytoxin. Deemed more applicable due to the separate flow channels, the prototype performance for domoic acid, okadaic acid, saxitoxin, and palytoxin calibration curves in shellfish achieved detection limits (IC20) of 4,000, 36, 144 and 46 μg/kg of mussel, respectively. A one-step extraction procedure demonstrated recoveries greater than 80 % for all toxins. For validation of the method at the 95 % confidence limit, the decision limits (CCα) determined from an extracted matrix curve were calculated to be 450, 36 and 24 μg/kg, and the detection capability (CCβ) as a screening method is ≤10 mg/kg, ≤160 μg/kg and ≤400 μg/kg for domoic acid, okadaic acid and saxitoxin, respectively.

Controlling Surface Topology and Functionality of Electrospun Fibers on the Nanoscale using Amphiphilic Block Copolymers To Direct Mesenchymal Progenitor Cell Adhesion

Surface patterning in three dimensions is of great importance in biomaterials design for controlling cell behavior. A facile one-step functionalization of biodegradable PDLLA fibers using amphiphilic diblock copolymers is demonstrated here to systematically vary the fiber surface composition. The copolymers comprise a hydrophilic poly[oligo(ethylene glycol) methacrylate] (POEGMA), poly[(2-methacryloyloxy)ethyl phosphorylcholine] (PMPC), or poly[2-(dimethylamino)ethyl methacrylate)] (PDMAEMA) block and a hydrophobic poly(l-lactide) (PLA) block. The block copolymer-modified fibers have increased surface hydrophilicity compared to that of PDLLA fibers. Mixtures of PLAPMPC and PLAPOEGMA copolymers are utilized to exploit microphase separation of the incompatible hydrophilic PMPC and POEGMA blocks at the fiber surface. Conjugation of an RGD cell-adhesive peptide to one hydrophilic block (POEGMA) using thiol-ene chemistry produces fibers with domains of cell-adhesive (POEGMA) and cell-inert (PMPC) sites, mimicking the adhesive properties of the extracellular matrix (ECM). Human mesenchymal progenitor cells (hES-MPs) showed much better adhesion to the fibers with surface-adhesive heterogeneity compared to that to fibers with only adhesive or only inert surface chemistries.

The emergence of bone technologies at the end of the pleistocene in Southeast Asia:Regional and evolutionary implications

For many decades Palaeolithic research viewed the development of early modern human behaviour as largely one of progress down a path towards the modernity of the present. The European Palaeolithic sequence the most extensively studied was for a long time the yard-stick against which records from other regions were judged. Recent work undertaken in Africa and increasingly Asia, however, now suggests that the European evidence may tell a story that is more parochial and less universal than previously thought. While tracking developments at the large scale (the grand narrative) remains important, there is growing appreciation that to achieve a comprehensive understanding of human behavioural evolution requires an archaeologically regional perspective to balance this. One of the apparent markers of human modernity that has been sought in the global Palaeolithic record, prompted by finds in the European sequence, is innovation in bonebased technologies. As one step in the process of re-evaluating and contextualizing such innovations, in this article we explore the role of prehistoric bone technologies within the Southeast Asian sequence, where they have at least comparable antiquity to Europe and other parts of Asia. We observe a shift in the technological usage of bone from a minor component to a medium of choice during the second half of the Last Termination and into the Holocene. We suggest that this is consistent with it becoming a focus of the kinds of inventive behaviour demanded of foraging communities as they adapted to the far-reaching environmental and demographic changes that were reshaping this region at that time. This record represents one small element of a much wider, much longerterm adaptive process, which we would argue is not confined to the earliest instances of a particular technology or behaviour, but which forms part of an on-going story of our behavioural evolution. © 2012 The McDonald Institute for Archaeological Research.