Reconfiguration, contestation, and decline: conceptualizing mature large technical systems

Large technical systems (LTS) are integral to modern lifestyles but arduous to analyze. In this paper, we advance a conceptualization of LTS using the notion of mature “phases,” drawing from insights into innovation studies, science and technology studies, political science, the sociology of infra- structure, history of technology, and governance. We begin by defining LTS as a unit of analysis and explaining its conceptual utility and novelty, situating it among other prominent sociotechnical theories. Next, we argue that after LTS have moved through the (overlapping) phases proposed by Thomas Hughes of invention, expansion, growth, momentum, and style,mature LTS undergo the additional (overlapping) phases of reconfiguration, contestation (subject to pressures such as drift and crisis), and eventually stagnation and decline. We illustrate these analytical phases with historical case studies and the conceptual literature, and close by suggesting future research to refine and develop the LTS framework, particularly related to more refined typologies, temporal dimensions, and a broadening of system users. We aim to contribute to theoretical debates about the coevolution of LTS as well as empirical discussions about system-related use, socio- technical change, and policy-making

Expression of the ubiquitin-proteasome pathway and muscle loss in experimental cancer cachexia

Muscle protein degradation is thought to play a major role in muscle atrophy in cancer cachexia. To investigate the importance of the ubiquitin-proteasome pathway, which has been suggested to be the main degradative pathway mediating progressive protein loss in cachexia, the expression of mRNA for proteasome subunits C2 and C5 as well as the ubiquitin-conjugating enzyme, E214k, has been determined in gastrocnemius and pectoral muscles of mice bearing the MAC16 adenocarcinoma, using competitive quantitative reverse transcriptase polymerase chain reaction. Protein levels of proteasome subunits and E214k were determined by immunoblotting, to ensure changes in mRNA were reflected in changes in protein expression. Muscle weights correlated linearly with weight loss during the course of the study. There was a good correlation between expression of C2 and E214k mRNA and protein levels in gastrocnemius muscle with increases of 6–8-fold for C2 and two-fold for E214k between 12 and 20% weight loss, followed by a decrease in expression at weight losses of 25–27%, although loss of muscle protein continued. In contrast, expression of C5 mRNA only increased two-fold and was elevated similarly at all weight losses between 7.5 and 27%. Both proteasome functional activity, and proteasome-specific tyrosine release as a measure of total protein degradation was also maximal at 18–20% weight loss and decreased at higher weight loss. Proteasome expression in pectoral muscle followed a different pattern with increases in C2 and C5 and E214k mRNA only being seen at weight losses above 17%, although muscle loss increased progressively with increasing weight loss. These results suggest that activation of the ubiquitin-proteasome pathway plays a major role in protein loss in gastrocnemius muscle, up to 20% weight loss, but that other factors such as depression in protein synthesis may play a more important role at higher weight loss

‘Sub-Prime’ Water, Low-Security Entitlements and Policy Challenges in Over-Allocated River Basins: the Case of the Murray–Darling Basin

Environmental policy is often implemented using market instruments. In some cases, including carbon taxing, the links between financial products and the environmental objectives, are transparent. In other cases, including water markets, the links are less transparent. In Australia’s Murray–Darling Basin (MDB), financial water products are known as ‘entitlements’, and are similar to traditional financial products, such as shares. The Australian water market includes ‘Low Security’ entitlements, which are similar to ‘sub-prime’ mortgage bonds because they are unlikely to yield an amount equal to their financial worth. Nearly half the water purchased under the Murray–Darling Basin Plan for environmental purposes is ‘Low Security’. We suggest that the current portfolio of water held by the Australian Government for environmental purposes reflects the mortgage market in the lead-up to the global financial crisis. Banks assumed that the future value of the mortgage market would reflect past trends. Similarly, it is assumed that the future value of water products will reflect past trends, without considering climate change. Historic records of allocations to ‘Low Security’ entitlements in the MDB suggest that, in the context of climate change, the Basin Plan water portfolio may fall short of the target annual average yield of 2075 GL by 511 GL. We recommend adopting finance sector methods including ‘hedging’ ‘Low Security’ entitlements by purchasing an additional 322–2755 GL of ‘Low Security’, or 160–511 GL of ‘High Security’ entitlements. Securing reliable environmental water is a global problem. Finance economics present opportunities for increasing the reliability of environmental flows

Is eco-efficiency in greenhouse gas emissions converging among European Union countries?

Eco-efficiency refers to the ability to produce more goods and services with less impact on the environment and less consumption of natural resources. This issue has become a matter of concern that is receiving increasing attention from politicians, scientists and researchers. Furthermore, greenhouse gases emitted as a result of production processes have a marked impact on the environment and are also the foremost culprit of global warming and climate change. This paper assesses convergence in eco-efficiency in greenhouse gas emissions in the European Union. Eco-efficiency is assessed at both country and greenhouse-gas-specific levels using Data Envelopment Analysis techniques and directional distance functions, as recently proposed by Picazo-Tadeo et al. (Eur J Oper Res, 220:798–809, 2012). Convergence is then evaluated using the Phillips and Sul (Econometrica, 75:1771–1855, 2007) approach that allows testing for the existence of convergence groups. Although the results point to the existence of different convergence clubs depending on the specific pollutant considered, they signal the existence of at least four clear groups of countries. The first two groups are core European Union high-income countries (Benelux, Germany, Italy, Austria, the United Kingdom and Scandinavian countries). A third club is made up of peripheral countries (Spain, Ireland, Portugal and Greece) together with some Eastern countries (Latvia and Slovenia), while the remaining clubs consist of groups containing Eastern European countries

Use of Cross-Taxon Congruence for Hotspot Identification at a Regional Scale

One of the most debated problems in conservation biology is the use of indicator (surrogate) taxa to predict spatial patterns in other taxa. Cross-taxon congruence in species richness patterns is of paramount importance at regional scales to disclose areas of high conservation value that are significant in a broader biogeographical context but yet placed in the finer, more practical, political context of decision making. We analysed spatial patterns of diversity in six arthropod taxa from the Turkish fauna as a regional case study relevant to global conservation of the Mediterranean basin. Although we found high congruence in cross-taxon comparisons of species richness (0.241<r<0.645), hotspots of different groups show limited overlap, generally less than 50 per cent. The ability of a given taxon to capture diversity of other taxa was usually modest (on average, 50 percent of diversity of non-target taxa), limiting the use of hotspots for effective conservation of non-target groups. Nevertheless, our study demonstrates that a given group may partially stand in for another with similar ecological needs and biogeographical histories. We therefore advocate the use of multiple sets of taxa, chosen so as to be representative of animals with different ecological needs and biogeographical histories

Structural Insights into the Evolution of a Non-Biological Protein: Importance of Surface Residues in Protein Fold Optimization

Phylogenetic profiling of amino acid substitution patterns in proteins has led many to conclude that most structural information is carried by interior core residues that are solvent inaccessible. This conclusion is based on the observation that buried residues generally tolerate only conserved sequence changes, while surface residues allow more diverse chemical substitutions. This notion is now changing as it has become apparent that both core and surface residues play important roles in protein folding and stability. Unfortunately, the ability to identify specific mutations that will lead to enhanced stability remains a challenging problem. Here we discuss two mutations that emerged from an in vitro selection experiment designed to improve the folding stability of a non-biological ATP binding protein. These mutations alter two solvent accessible residues, and dramatically enhance the expression, solubility, thermal stability, and ligand binding affinity of the protein. The significance of both mutations was investigated individually and together, and the X-ray crystal structures of the parent sequence and double mutant protein were solved to a resolution limit of 2.8 and 1.65 Å, respectively. Comparative structural analysis of the evolved protein to proteins found in nature reveals that our non-biological protein evolved certain structural features shared by many thermophilic proteins. This experimental result suggests that protein fold optimization by in vitro selection offers a viable approach to generating stable variants of many naturally occurring proteins whose structures and functions are otherwise difficult to study

Do teachers have more health problems? Results from a French cross-sectional survey

BACKGROUND: Although only a few studies have been published on teachers' health, certain ideas are widely accepted, such as for example, the preconceived notion that teachers suffer from an excessively high rate of mental health problems. The objective of this study is to compare teachers' mental and physical health to that of a control group. METHODS: A cross-sectional postal survey was conducted among a sample of 3,679 teachers and 1,817 non-teachers aged 20 to 60 years old. RESULTS: No lifetime prevalence of any psychiatric disorder (with the exception of undifferentiated somatoform disorder in men) or mean scores of psychological distress were found to be significantly higher in teachers. However, multiple analyses, adjusted for all confounding variables, revealed a higher risk of lifetime anxiety disorders in male teachers. On the other hand, significant differences were observed for some physical ailments: a higher lifetime prevalence of rhinopharyngitis/laryngitis in both male and female teachers, of conjunctivitis and lower urinary tract infection in male teachers and of bronchitis, eczema/dermatitis and varicose veins in female teachers. No significant difference was found for chronic pain between the two groups. CONCLUSION: Teachers do not seem to have poorer mental health. However, their physical condition is characterized by a higher prevalence of health problems related to the ENT tract, and to a lesser extent, depending on the gender, to skin, eyes, legs and lower urinary tract

Airway sizes and proportions in children quantified by a video-bronchoscopic technique

Background: A quantitative understanding of airway sizes and proportions and a reference point for comparisons are important to a bronchoscopist. The aims of this study were to measure large airway areas, and define proportions and predictors of airway size in children. Methods: A validated videobronchoscope technique was used to measure in-vivo airway cross-sectional areas (cricoid, right (RMS) and left (LMS) main stem and major lobar bronchi) of 125 children. Airway proportions were calculated as ratios of airways to cricoid areas and to endotracheal tube (ETT) areas. Mann Whitney U, T-tests, and one-way ANOVA were used for comparisons and standard univariate and backwards, stepwise multivariate regression analyses were used to define airway size predictors. Results: Airways size increased progressively with increasing age but proportions remained constant. The LMS was 21% smaller than the RMS. Gender differences in airways' size were not significant in any age group or airway site. Cricoid area related best to body length (BL): cricoid area (mm2) = 26.782 + 0.254*BL (cm) while the RMS and LMS area related best to weight: RMS area (mm2) = 23.938 + 0.394*Wt (kg) and LMS area (mm2) = 20.055 + 0.263*Wt (kg) respectively. Airways to cricoid ratios were larger than airway to ETT ratios (p=0.0001). Conclusions: The cricoid and large airways progressively increase in size but maintain constant proportional relationships to the cricoid across childhood. The cricoid area correlates with body length while the RMS and LMS are best predicted by weight. These data provide for quantitative comparisons of airway lesions

Vitamin C Enhances Vitamin E Status and Reduces Oxidative Stress Indicators in Sea Bass Larvae Fed High DHA Microdiets

Docosahexaenoic acid (DHA) is an essential fatty acid necessary for many biochemical, cellular and physiological functions in fish. However, high dietary levels of DHA increase free radical injury in sea bass (Dicentrarchus labrax) larvae muscle, even when vitamin E (&alpha;-tocopherol, &alpha;-TOH) is increased. Therefore, the inclusion of other nutrients with complementary antioxidant functions, such as vitamin C (ascorbic acid, vitC), could further contribute to prevent these lesions. The objective of the present study was to determine the effect of vitC inclusion (3,600 mg/kg) in high DHA (5 % DW) and &alpha;-TOH (3,000 mg/kg) microdiets (diets 5/3,000 and 5/3,000 + vitC) in comparison to a control diet (1 % DHA DW and 1,500 mg/kg of &alpha;-TOH; diet 1/1,500) on sea bass larvae growth, survival, whole body biochemical composition and thiobarbituric acid reactive substances (TBARS) content, muscle morphology, skeletal deformities and antioxidant enzymes, insulin-like growth factors (IGFs) and myosin expression (MyHC). Larvae fed diet 1/1,500 showed the best performance in terms of total length, incidence of muscular lesions and ossification degree. IGFs gene expression was elevated in 5/3,000 diet larvae, suggesting an increased muscle mitogenesis that was confirmed by the increase in the mRNA copies of MyHC. vitC effectively controlled oxidative damages in muscle, increased &alpha;-TOH larval contents and reduced TBARS content and the occurrence of skull deformities. The results of the present study showed the antioxidant synergism between vitamins E and C when high contents of DHA are included in sea bass larvae diets

Host-parasite co-metabolic activation of antitrypanosomal aminomethyl-benzoxaboroles

<div><p>Recent development of benzoxaborole-based chemistry gave rise to a collection of compounds with great potential in targeting diverse infectious diseases, including human African Trypanosomiasis (HAT), a devastating neglected tropical disease. However, further medicinal development is largely restricted by a lack of insight into mechanism of action (MoA) in pathogenic kinetoplastids. We adopted a multidisciplinary approach, combining a high-throughput forward genetic screen with functional group focused chemical biological, structural biology and biochemical analyses, to tackle the complex MoAs of benzoxaboroles in <i>Trypanosoma brucei</i>. We describe an oxidative enzymatic pathway composed of host semicarbazide-sensitive amine oxidase and a trypanosomal aldehyde dehydrogenase TbALDH3. Two sequential reactions through this pathway serve as the key underlying mechanism for activating a series of 4-aminomethylphenoxy-benzoxaboroles as potent trypanocides; the methylamine parental compounds as pro-drugs are transformed first into intermediate aldehyde metabolites, and further into the carboxylate metabolites as effective forms. Moreover, comparative biochemical and crystallographic analyses elucidated the catalytic specificity of TbALDH3 towards the benzaldehyde benzoxaborole metabolites as xenogeneic substrates. Overall, this work proposes a novel drug activation mechanism dependent on both host and parasite metabolism of primary amine containing molecules, which contributes a new perspective to our understanding of the benzoxaborole MoA, and could be further exploited to improve the therapeutic index of antimicrobial compounds.</p></div