Analysis of metabolic pathways by the growth of cells in the presence of organic solvents.

A new approach to the analysis of metabolic pathways involving poorly water-soluble intermediates is proposed. It relies upon the ability of the hydrophobic intermediates formed by a sequence of intracellular reactions to cross the membrane(s) and partition between aqueous and organic phases, when cells are incubated in the presence of a nonpolar and nontoxic organic solvent. As a result of this thermodynamically driven efflux of the formed intermediates from the cell, they accumulate in the organic medium in sufficient quantities for GC-MS analysis and identification. This enables direct determination of the sequence of chemical reactions involved with no requirement for the isolation of each individual metabolite from a cell-free extract. The feasibility of the proposed methodology has been demonstrated by the elucidation of the biosynthesis of (R)-gamma-decalactone from (R)-ricinoleic acid catalyzed by the yeast Sporidiobolus ruinenii grown in the presence of decane. The corresponding 4-hydroxy-acid intermediates, formed in the course of beta-oxidation of (R)-ricinoleic acid, were simultaneously observed in a single experiment on the same chromatogram. Potential applications of this proposed methodology are briefly discussed.

Shigella flexneri surface protein IcsA is sufficient to direct actin-based motility.

Shigella flexneri is a Gram-negative bacterial pathogen that can grow directly in the cytoplasm of infected host cells and uses a form of actin-based motility for intra- and intercellular spread. Moving intracellular bacteria are associated with a polarized "comet tail" composed of actin filaments. IcsA, a 120-kDa outer membrane protein necessary for actin-based motility, is located at a single pole on the surface of the organism, at the junction with the actin tail. Here, we demonstrate that stable expression of IcsA on the surface of Escherichia coli is sufficient to allow actin-dependent movement of E. coli in cytoplasmic extracts, at rates comparable to the movement of S. flexneri in infected cells. Thus, IcsA is the sole Shigella-specific factor required for actin-based motility. Continuous protein synthesis and polarized distribution of the protein are not necessary for actin tail formation or movement. Listeria monocytogenes is an unrelated bacterial pathogen that exhibits similar actin-based intracytoplasmic motility. Actin filament dynamics in the comet tails associated with the two different organisms are essentially identical, which indicates that they have independently evolved mechanisms to interact with the same components of the host cytoskeleton.

Modelización de un proceso de elección secuencial en cuatro etapas del consumidor turista

El objetivo de este trabajo consiste en proponer un proceso de decisión secuencial y jerárquico que siguen los turistas vacacionales en cuatro etapas: 1) salir (o no) de vacaciones; 2) elección de un viaje nacional vs. internacional; 3) elección de determinadas áreas geográficas; y 4) elección de la modalidad del viaje -multidestino o de destino fijo- en estas áreas. Este análisis permite examinar las distintas fases que sigue un turista hasta seleccionar una determinada modalidad de viaje en un zona geográfica concreta, así como observar los factores que influyen en cada etapa. La aplicación empírica se realiza sobre una muestra de 3.781 individuos, y estima, mediante procedimientos bayesianos, un Modelo Logit de Coeficientes Aleatorios. Los resultados obtenidos revelan el carácter anidado y no independiente de las decisiones anteriores, lo que confirma el proceso secuencial y jerárquico propuesto.

Proceso cuatrietápico de elección del turista

El objetivo de este trabajo consiste en proponer y testar un proceso de decisión anidado y jerárquico que siguen los turistas vacacionales en cuatro etapas: 1) salir (o no) de vacaciones; 2) elección de un viaje nacional vs. internacional; 3) elección de determinadas áreas geográficas; y 4) elección de la modalidad del viaje –multidestino o de destino fijo– en estas áreas. Este análisis permite examinar las distintas fases que sigue un turista hasta seleccionar una determinada modalidad de viaje en un zona geográfica concreta, así como observar los factores que influyen en cada etapa. La aplicación empírica se realiza sobre una muestra de 3.781 individuos, y estima, mediante procedimientos bayesianos, un Modelo Logit de Coeficientes Aleatorios. Los resultados obtenidos revelan el carácter anidado y no independiente de las decisiones anteriores, lo que confirma el proceso anidado y jerárquico propuesto.

Slovakia: the Eurogroup’s enfant terrible. OSW Commentary No. 63, 2011-10-14

When Slovakia’s parliament rejected the European Financial Stability Facility (EFSF) reform on 11 October it undermined Slovakia’s reputation as a credible partner within the EU. Moreover, Prime Minister Iveta Radicova combined the vote on the strengthening of the EFSF – a key anti-crisis mechanism in the Eurozone – with a vote of confidence for her cabinet. This eventually led to the collapse of the government. Before Slovakia’s decision, the strengthening of the EFSF had been endorsed by the national parliaments of all the eurozone countries. Slovakia, which had opted to be the last one to carry out the ratification procedure, adopted the EFSF reform only in a re-vote on 13 October, due to the support of the opposition left-wing party. However, problems with ratification have cast a shadow over the achievements of Slovakia which as one of the freshest members of the eurozone had been actively seeking to influence the creation of EU mechanisms for dealing with the debt crisis. For the past eighteen months the Slovak government, formed by conservative and liberal parties, has consistently called for the controlled bankruptcy of Greece, a tightening of the rules of the Stability and Growth Pact, and for the private sector’s participation in financing the rescue packages for indebted states. It was in part down to Slovakia that these proposals, previously regarded as extreme, were introduced into the mainstream EU debate. The constructive position presented by Slovakia’s diplomacy in recent months has brought Bratislava tangible results, such as the reduction of its contribution to the permanent anti-crisis fund, the European Stabilisation Mechanism (ESM). Thus Slovakia, which adopted the single currency on 1 January 2009, has become an informal spokesman for the new, poorer members of the eurozone.

Growth and carbon metabolism of the seaweed Fucus vesiculosus in the western Baltic Sea ("Kiel Outdoor Benthocosms")

Warming and acidification of the oceans as a consequence of increasing CO2-concentrations occur at large scales. Numerous studies have shown the impact of single stressors on individual species. However, studies on the combined effect of multiple stressors on a multi-species assemblage, which is ecologically much more realistic and relevant, are still scarce. Therefore, we orthogonally crossed the two factors warming and acidification in mesocosm experiments and studied their single and combined impact on the brown alga Fucus vesiculosus associated with its natural community (epiphytes and mesograzers) in the Baltic Sea in all seasons (from April 2013 to April 2014). We superimposed our treatment factors onto the natural fluctuations of all environmental variables present in the Benthocosms in so-called delta-treatments. Thereby we compared the physiological responses of F. vesiculosus (growth and metabolites) to the single and combined effects of natural Kiel Fjord temperatures and pCO2 conditions with a 5 °C temperature increase and/or pCO2 increase treatment (1100 ppm in the headspace above the mesocosms). Responses were also related to the factor photoperiod which changes over the course of the year. Our results demonstrate complex seasonal pattern. Elevated pCO2 positively affected growth of F. vesiculosus alone and/or interactively with warming. The response direction (additive, synergistic or antagonistic), however, depended on season and daylength. The effects were most obvious when plants were actively growing during spring and early summer. Our study revealed for the first time that it is crucial to always consider the impact of variable environmental conditions throughout all seasons. In summary, our study indicates that in future F. vesiculosus will be more affected by detrimental summer heat-waves than by ocean acidification although the latter consequently enhances growth throughout the year. The mainly negative influence of rising temperatures on the physiology of this keystone macroalga may alter and/or hamper its ecological functions in the shallow coastal ecosystem of the Baltic Sea.

Negroes - Detroit

Sign on Back of building at 16626 East Warren

Inhibition of protein interactions with the beta(2) sliding clamp of Escherichia coli DNA polymerase III by peptides from beta(2)-binding proteins

The sliding clamp of the Escherichia coli replisome is now understood to interact with many proteins involved in DNA synthesis and repair. A universal interaction motif is proposed to be one mechanism by which those proteins bind the E. coli sliding clamp, a homodimer of the beta subunit, at a single site on the dimer. The numerous beta(2)-binding proteins have various versions of the consensus interaction motif, including a related hexameric sequence. To determine if the variants of the motif could contribute to the competition of the beta-binding proteins for the beta(2) site, synthetic peptides derived from the putative beta(2)-binding motifs were assessed for their abilities to inhibit protein-beta(2) interactions, to bind directly to beta(2), and to inhibit DNA synthesis in vitro. A hierarchy emerged, which was consistent with sequence similarity to the pentameric consensus motif, QL(S/D)LF, and peptides containing proposed hexameric motifs were shown to have activities comparable to those containing the consensus sequence. The hierarchy of peptide binding may be indicative of a competitive hierarchy for the binding of proteins to beta(2) in various stages or circumstances of DNA replication and repair.

Labor force activity among Australians with musculoskeletal disorders comorbid with depression and anxiety disorders

Aim: Musculoskeletal disorders (MSD) are a leading cause of work-related disability. This investigation explored the impact of MSD comorbid with depression and anxiety disorders, on labor force activity. Methods: The Australian Bureau of Statistics provided confidentialized data files collected from a household sample of 37,580 people. MSD, affective, and anxiety disorders were identified and employment restrictions were assessed at four levels of severity. Results: Anxiety and depression of six months duration was present in 12.1% of people with MSD. Comorbidity magnified the negative impacts of single conditions on labor force activity. Most at risk were people with back problems and comorbid depression, people with arthritis or other MSD and comorbid anxiety, males with MSD and comorbid depression, and females with MSD and comorbid anxiety. Conclusions: The results suggest that the occupational rehabilitation needs of people with MSD comorbid with depression or anxiety may currently be underestimated.

West (side) and south (front) elevations, public housing, Cotton Tree Housing Estate, Maroochydore

This pilot project at Cotton Tree, Maroochydore, on two adjacent, linear parcels of land has one of the properties privately owned while the other is owned by the public housing authority. Both owners commissioned Lindsay and Kerry Clare to design housing for their separate needs which enabled the two projects to be governed by a single planning and design strategy. This entailed the realignment of the dividing boundary to form two approximately square blocks which made possible the retention of an important stand of mature paperbark trees and gave each block a more useful street frontage. The scheme provides seven two-bedroom units and one single-bedroom unit as the private component, with six single-bedroom units, three two-bedroom units and two three-bedroom units forming the public housing. The dwellings are deployed as an interlaced mat of freestanding blocks, car courts, courtyard gardens, patios and decks. The key distinction between the public and private parts of the scheme is the pooling of the car parking spaces in the public housing to create a shared courtyard. The housing climbs to three storeys on its southern edge and falls to a single storey on the north-western corner. This enables all units and the principal private outdoor spaces to have a northern orientation. The interiors of both the public and private units are skilfully arranged to take full advantage of views, light and breeze.

The role of texture in shape from shading: are humans biased towards seeing relief textures?

When a textured surface is modulated in depth and illuminated, the level of illumination varies across the surface, producing coarse-scale luminance modulations (LM) and amplitude modulation (AM) of the fine-scale texture. If the surface has an albedo texture (reflectance variation) then the LM and AM components are always in-phase, but if the surface has a relief texture the phase relation between LM and AM varies with the direction and nature of the illuminant. We showed observers sinusoidal luminance and amplitude modulations of a binary noise texture, in various phase relationships, in a paired-comparisons design. In the first experiment, the combinations under test were presented in different temporal intervals. Observers indicated which interval contained the more depthy stimulus. LM and AM in-phase were seen as more depthy than LM alone which was in turn more depthy than LM and AM in anti-phase, but the differences were weak. In the second experiment the combinations under test were presented in a single interval on opposite obliques of a plaid pattern. Observers were asked to indicate the more depthy oblique. Observers produced the same depth rankings as before, but now the effects were more robust and significant. Intermediate LM/AM phase relationships were also tested: phase differences less than 90 deg were seen as more depthy than LM-only, while those greater than 90 deg were seen as less depthy. We conjecture that the visual system construes phase offsets between LM and AM as indicating relief texture and thus perceives these combinations as depthy even when their phase relationship is other than zero. However, when different LM/AM pairs are combined in a plaid, the signals on the obliques are unlikely to indicate corrugations of the same texture, and in this case the out-of-phase pairing is seen as flat. [Supported by the Engineering and Physical Sciences Research Council (EPSRC)].

The characterisation of clean metal surfaces

The most perfectly structured metal surface observed in practice is that of a field evaporated field-ion microscope specimen. This surface has been characterised by adopting various optical analogue techniques. Hence a relationship has been determined between the structure of a single plane on the surface of a field-ion emitter and the geometry of a binary zone plate. By relating the known focussing properties of such a zone plate to those obtained from the projected images of such planes in a field-ion micrograph, it is possible to extract new information regarding the local magnification of the image. Further to this, it has been shown that the entire system of planes comprising the field-ion imaging surface may be regarded as a moire pattern formed between over-lapping zone plates. The properties of such moire zone plates are first established in an analysis of the moire pattern formed between zone plates on a flat surface. When these ideas are applied to the field-ion image it becomes possible to deduce further information regarding the precise topography of the emitter. It has also become possible to simulate differently proJected field-ion images by overlapping suitably aberrated zone plates. Low-energy ion bombardment is an essential preliminary to much surface research as a means of producing chemically clean surfaces. Hence it is important to know the nature and distribution of the resultant lattice damage, and the extent to which it may be removed by annealing. The field-ion microscope has been used to investigate such damage because its characterisation lies on the atomic scale. The present study is concerned with the in situ sputtering of tungsten emitters using helium, neon, argon and xenon ions with energies in the range 100eV to 1keV, together with observations of the effect of annealing. The relevance of these results to surface cleaning schedules is discussed.

New drugs for type 2 diabetes mellitus:what is their place in therapy?

Oral therapy for type 2 diabetes mellitus, when used appropriately, can safely assist patients to achieve glycaemic targets in the short to medium term. However, the progressive nature of type 2 diabetes usually requires a combination of two or more oral agents in the longer term, often as a prelude to insulin therapy. Issues of safety and tolerability, notably weight gain, often limit the optimal application of anti-diabetic drugs such as sulforylureas and thiazolidinediones. Moreover, the impact of different drugs, even within a single class, on the risk of long-term vascular complications has come under scrutiny. For example, recent publication of evidence suggesting potential detrimental effects of rosiglitazone on myocardial events generated a heated debate and led to a reduction in use of this drug. In contrast, current evidence supports the view that pioglitazone has vasculoprotective properties. Both drugs are contraindicated in patients who are at risk of heart failure. An additional recently identified safety concern is an increased risk of fractures, especially in postmenopausal women. Several new drugs with glucose-lowering efficacy that may offer certain advantages have recently become available. These include (i) injectable glucagonlike peptide-1 (GLP-1) receptor agonists and oral dipeptidyl peptidase-4 (DPP-4) inhibitors; (ii) the amylin analogue pramlintide; and (iii) selective cannabinoid receptor-1 (CB1) antagonists. GLP-1 receptor agonists, such as exenatide, stimulate nutrient-induced insulin secretion and reduce inappropriate glucagon secretion while delaying gastric emptying and reducing appetite. These agents offer a low risk of hypoglycaemia combined with sustained weight loss. The DPP-4 inhibitors sitagliptin and vildagliptin are generally weight neutral, with less marked gastrointestinal adverse effects than the GLP-1 receptor agonists. Potential benefits of GLP-1 receptor stimulation on P cell neogenesis are under investigation. Pancreatitis has been reported in exenatide-treated patients. Pramlintide, an injected peptide used in combination with insulin, can reduce insulin dose and bodyweight. The CB1 receptor antagonist rimonabant promotes weight loss and has favourable effects on aspects of the metabolic syndrome, including the hyperglycaemia of type 2 diabetes. However, in 2007 the US FDA declined approval of rimonabant, requiring more data on adverse effects, notably depression. The future of dual peroxisome proliferator-activated receptor-alpha/gamma agonists, or glitazars, is presently uncertain following concerns about their safety. In conclusion, several new classes of drugs have recently become available in some countries that offer new options for treating type 2 diabetes. Beneficial or neutral effects on bodyweight are an attractive feature of the new drugs. However, the higher cost of these agents, coupled with an absence of long-term safety and clinical outcome data, need to be taken into consideration by clinicians and healthcare organizations.

Connecting social media to e-commerce:cold-start product recommendation using microblogging information

In recent years, the boundaries between e-commerce and social networking have become increasingly blurred. Many e-commerce websites support the mechanism of social login where users can sign on the websites using their social network identities such as their Facebook or Twitter accounts. Users can also post their newly purchased products on microblogs with links to the e-commerce product web pages. In this paper, we propose a novel solution for cross-site cold-start product recommendation, which aims to recommend products from e-commerce websites to users at social networking sites in 'cold-start' situations, a problem which has rarely been explored before. A major challenge is how to leverage knowledge extracted from social networking sites for cross-site cold-start product recommendation. We propose to use the linked users across social networking sites and e-commerce websites (users who have social networking accounts and have made purchases on e-commerce websites) as a bridge to map users' social networking features to another feature representation for product recommendation. In specific, we propose learning both users' and products' feature representations (called user embeddings and product embeddings, respectively) from data collected from e-commerce websites using recurrent neural networks and then apply a modified gradient boosting trees method to transform users' social networking features into user embeddings. We then develop a feature-based matrix factorization approach which can leverage the learnt user embeddings for cold-start product recommendation. Experimental results on a large dataset constructed from the largest Chinese microblogging service Sina Weibo and the largest Chinese B2C e-commerce website JingDong have shown the effectiveness of our proposed framework.

Visual driver support system for traffic signs

It has been well documented that traffic accidents that can be avoided occur when the motorists miss or ignore traffic signs. With the attention of drivers getting diverted due to distractions like cell phone conversations, missing traffic signs has become more prevalent. Also, poor weather and other unfriendly driving conditions sometimes makes the motorists not to be alert all the time and see every traffic sign on the road. Besides, most cars do not have any form of traffic assistance. Because of heavy traffic and proliferation of traffic signs on the roads, there is a need for a system that assists the driver not to miss a traffic sign to reduce the probability of an accident. Since visual information is critical for driving, processed video signals from cameras have been chosen to assist drivers. These inexpensive cameras can be easily mounted on the automobile. The objective of the present investigation and the traffic system development is to recognize the traffic signs electronically and alert drivers. For the case study and the system development, five important and critical traffic signs have been selected. They are: STOP, NO ENTER, NO RIGHT TURN, NO LEFT TURN, and YIELD. The system was evaluated processing still pictures taken from the public roads, and the recognition results were presented in an analysis table to indicate the correct identifications and the false ones. The system reached the acceptable recognition rate of 80% for all five traffic signs. The processing rate was about three seconds. The capabilities of MATLAB, VLSI design platforms and coding have been used to generate a visual warning to complement the visual driver support system with a Field Programmable Gate Array (FPGA) on a XUP Virtex-II Pro Development System.