Synthesis and screening of potential antimicrobial compounds

Tuberculosis (TB), an infection caused by human pathogen Mycobacterium tuberculosis, continues to kill millions each year and is as prevalent as it was in the pre-antimicrobial era. With the emergence of continuously-evolving multi-drug resistant strains (MDR) and the implications of the HIV epidemic, it is crucial that new drugs with better efficacy and affordable cost are developed to treat TB. With this in mind, the first part of this thesis discusses the synthesis of libraries of derivatives of pyridine carboxamidrazones, along with cyclised (1,2,4-triazole and 1,2,4-oxadiazole) and fluorinated analogues. Microbiological screening against M. tuberculosis was carried out at the TAACF, NIAID and IDRI (USA). This confirmed the earlier findings that 2-pyridyl-substituted carboxamidrazones were more active than the 4-pyridyl-substituted carboxamidrazones. Another important observation was that upon cyclisation of these carboxamidrazones, a small number of the triazoles retained their activity while in most of the remaining compounds the activity was diminished. This might be attributed to the significant increase in logP value caused by cyclisation of these linear carboxamidrazones, resulting in high lipophilicity and decreased permeability. Another reason might be that the rigidity conferred upon the compound due to cyclisation, results in failure of the compound to fit into the active site of the putative target enzyme. In order to investigate the potential change to the compounds’ metabolism in the organism and/or host, the most active compounds were selected and a fluorine atom was introduced in the pyridine ring. The microbiological results shows a drastic improvement in the activity of the fluorinated carboxamidrazone amides as compared to their non fluorinated counterpart. This improvement in the activity could possibly be the result of the increased cell permeability caused by the fluorine. In a subsidiary strand, a selection of long-chain , -unsaturated carboxylic esters, -keto, -hydroxy carboxylic esters and -keto, -hydroxy carboxylic esters, structurally similar to mycolic acids, were synthesised. The microbiological data revealed that one of the open chain compound was active against the Mycobacterium tuberculosis H37Rv strain and some resistant isolates. The possible compound activity could be its potential to disrupt mycobacterial cell wall synthesis by interfering with the FAS-II pathway.

A gyenge hazai innovációs teljesítmény intézményi magyarázatához. Vitaírás a nemzetközi innovációs versenyben való részvétel akadályairól (Towards an institutional explanation of the country's weak innovation performance)

Miért van a magyar gazdaság hasonlóan kritikus helyzetben, mint a rendszerváltást megelőző időkben? Miért nem sikerül az eladósodást megállítani, a gazdaságot konszolidálni, és fenntartható növekedési pályára állítani? Ennek közvetlen okát a szerzők a fejlődés féloldalasságában és a duális gazdasági szerkezetben látják. A piacgazdasági intézmények bevezetése ugyanis nem járt együtt az egész gazdaságot (vagy legalábbis annak nagy részét) átfogó, a tudásvezérelt információgazdaság felé mutató, gyors fejlődéssel. Számos indikátor azt jelzi, hogy az ország lemaradt a nemzetközi innovációs versenyben. Az innovációk elégtelensége azonban nem véletlen, nem exogén adottság, hanem a formális piaci intézmények mögött meghúzódó valós intézményi berendezkedéssel, a gazdaságban ténylegesen észlelhető magatartásmintákkal magyarázható. A piacgazdasági intézmények és jogi keretek, amelyek elvileg lehetőséget adnak az erőforrásokhoz való szabad és nyílt hozzáférésre, csak részben töltődtek meg tartalommal. Az országban még mindig meglehetősen korlátozott a sikeres belépés lehetősége a piaci és a politikai arénába, azaz a magyar társadalom - a north-i terminológiával élve - "korlátozott hozzáférésre alapozott társadalomként" írható le. Az a tény, hogy a piaci szereplők esélyei az államhoz és intézményeihez fűződő kapcsolatoktól függően nagyban különböznek egymástól, és a gazdasági szereplők rendszerszerűen használják e kapcsolatokat járadékszerzésre, lefojtja az innovációt, és újra és újra megakasztja a fejlődést. / === / Why is Hungary's economy still in a critical state similar to the one before the change of system? Why is the indebtedness not being halted, the economy consolidated or vital structural reforms performed? The authors see the direct cause in lopsided development and a dual economic structure. The introduction of market economic institutions was not followed by rapid, overall development towards a knowledge-led, information economy. Several indicators show how Hungary has fallen behind in competition for international innovation. The inadequacy is not a fortuitous, exogenous attribute, but explicable in terms of a real institutional setup underlying the formal market institutions, and of actual behaviour patterns found in the economy. Only in part has substance been gained by the institutions and legal frames of a market economy that theoretically would provide free and open access to resources. The scope for successful entry into the market or political arena remains very narrow, so that in Douglass North's terms, Hungary's is still "a society based on restricted access." Innovation is stifled and development repeatedly impeded by the fact that market players' chances differ widely depending on their connections with the state and its institutions and such connections are used regularly in rent-seeking.

The effect of climate change on the population of sycamore lace bug (Corythuca ciliata, Say) based on a simulation model with phenological response

Climate change affects on insect populations in many ways: it can cause a shift in geographical spread, abundance, or diversity, it can change the location, the timing and the magnitude of outbreaks of pests and it can define the phenological or even the genetic properties of the species. Long-time investigations of special insect populations, simulation models and scenario studies give us very important information about the response of the insects far away and near to our century. Getting to know the potential responses of insect populations to climate change makes us possible to evaluate the adaptation of pest management alternatives as well as to formulate our future management policy. In this paper we apply two simple models, in order to introduce a complex case study for a Sycamore lace bug population. We test how the model works in case the whether conditions are very different from those in our days. Thus, besides we can understand the processes that happen in present, we can analyze the effects of a possible climate change, as well.

Data compilation on the biological response to ocean acidification: environmental and experimental context of data sets and related literature

The exponential growth of studies on the biological response to ocean acidification over the last few decades has generated a large amount of data. To facilitate data comparison, a data compilation hosted at the data publisher PANGAEA was initiated in 2008 and is updated on a regular basis (doi:10.1594/PANGAEA.149999). By January 2015, a total of 581 data sets (over 4 000 000 data points) from 539 papers had been archived. Here we present the developments of this data compilation five years since its first description by Nisumaa et al. (2010). Most of study sites from which data archived are still in the Northern Hemisphere and the number of archived data from studies from the Southern Hemisphere and polar oceans are still relatively low. Data from 60 studies that investigated the response of a mix of organisms or natural communities were all added after 2010, indicating a welcomed shift from the study of individual organisms to communities and ecosystems. The initial imbalance of considerably more data archived on calcification and primary production than on other processes has improved. There is also a clear tendency towards more data archived from multifactorial studies after 2010. For easier and more effective access to ocean acidification data, the ocean acidification community is strongly encouraged to contribute to the data archiving effort, and help develop standard vocabularies describing the variables and define best practices for archiving ocean acidification data.

Experimental detection of sudden stiffness change in a structural system employing Laser Doppler Vibrometry

Sudden changes in the stiffness of a structure are often indicators of structural damage. Detection of such sudden stiffness change from the vibrations of structures is important for Structural Health Monitoring (SHM) and damage detection. Non-contact measurement of these vibrations is a quick and efficient way for successful detection of sudden stiffness change of a structure. In this paper, we demonstrate the capability of Laser Doppler Vibrometry to detect sudden stiffness change in a Single Degree Of Freedom (SDOF) oscillator within a laboratory environment. The dynamic response of the SDOF system was measured using a Polytec RSV-150 Remote Sensing Vibrometer. This instrument employs Laser Doppler Vibrometry for measuring dynamic response. Additionally, the vibration response of the SDOF system was measured through a MicroStrain G-Link Wireless Accelerometer mounted on the SDOF system. The stiffness of the SDOF system was experimentally determined through calibrated linear springs. The sudden change of stiffness was simulated by introducing the failure of a spring at a certain instant in time during a given period of forced vibration. The forced vibration on the SDOF system was in the form of a white noise input. The sudden change in stiffness was successfully detected through the measurements using Laser Doppler Vibrometry. This detection from optically obtained data was compared with a detection using data obtained from the wireless accelerometer. The potential of this technique is deemed important for a wide range of applications. The method is observed to be particularly suitable for rapid damage detection and health monitoring of structures under a model-free condition or where information related to the structure is not sufficient.

Remote Sensing of Vegetation Change Across a Latitudinal Gradient in the Canadian Arctic

Global air surface temperatures and precipitation have increased over the last several decades resulting in a trend of greening across the Circumpolar Arctic. The spatial variability of warming and the inherent effects on plant communities has not proven to be uniform or homogeneous on global or local scales. We can apply remote sensing vegetation indices such as the Normalized Difference Vegetation Index (NDVI) to map and monitor vegetation change (e.g., phenology, greening, percent cover, and biomass) over time. It is important to document how Arctic vegetation is changing, as it will have large implications related to global carbon and surface energy budgets. The research reported here examined vegetation greening across different spatial and temporal scales at two disparate Arctic sites: Apex River Watershed (ARW), Baffin Island, and Cape Bounty Arctic Watershed Observatory (CBAWO), Melville Island, NU. To characterize the vegetation in the ARW, high spatial resolution WorldView-2 data were processed to create a supervised land-cover classification and model percent vegetation cover (PVC) (a similar process had been completed in a previous study for the CBAWO). Meanwhile, NDVI data spanning the past 30 years were derived from intermediate resolution Landsat data at the two Arctic sites. The land-cover classifications at both sites were used to examine the Landsat NDVI time series by vegetation class. Climate variables (i.e., temperature, precipitation and growing season length (GSL) were examined to explore the potential relationships of NDVI to climate warming. PVC was successfully modeled using high resolution data in the ARW. PVC and plant communities appear to reside along a moisture and altitudinal gradient. The NDVI time series demonstrated an overall significant increase in greening at the CBAWO (High Arctic site), specifically in the dry and mesic vegetation type. However, similar overall greening was not observed for the ARW (Low Arctic site). The overall increase in NDVI at the CBAWO was attributed to a significant increase in July temperatures, precipitation and GSL.

Nursing and medical students as agents of change in health care: impact of schools core values and culture-a discussion paper

Within the UK the quality of care delivered in some hospitals, nursing homes and caring facilities has been the subject of significant enquiry, challenge and concern in recent years. There was need for a change in the culture of patient and client care. Traditionally a change in culture is seen as moving from an organisational head through to the organisation and in this case through to front-line care. This hasn’t necessarily achieved the desired effect and impact in terms of quality of care within the UK. Historically, certainly nurses have acted more as recipients of change, rather than agents of change
This paper suggests that schools of nursing and medicine with robust core values and a more consistently enacted culture of care, are better able and more likely to transfer this to nursing and medical students within their professional socialisation. In addition, and rather than the newly qualified nurse or doctor being absorbed into existing cultures of care delivery (which are not necessarily always reflecting high qualities of care), schools of nursing and medicine could better facilitate the development of more `agency’ within students and better equipping the students on qualification and stepping into practice, with a role and function as potential agents of change. Effective leadership within schools of nursing and medicine can both translate to quality and consistency, and enactment of organisational core values and working culture. The working culture of schools is intrinsic to developing students as agents of change

History of Premenstrual Mood Change and Postpartum Episodes are Associated with Perimenopausal Episodes in Women with Bipolar Disorder

Background and Aims: Reproductive life events are potential triggers of mood episodes in women with bipolar disorder. We aimed to establish whether a history of premenstrual mood change and postpartum episodes are associated with perimenopausal episodes in women who have bipolar disorder. Methods: Participants were 339 post-menopausal women with DSM-IV bipolar disorder recruited into the Bipolar Disorder Research Network (www.bdrn.org). Women self-reported presence (N = 200) or absence (N = 139) of an illness episode during the perimenopausal period. History of premenstrual mood change was measured using the self-report Premenstrual Symptoms Screening Tool (PSST), and history of postpartum episodes was measured via semi-structured interview (Schedules for Clinical Assessment in Neuropsychiatry, SCAN) and inspection of case-notes. Results: History of a postpartum episode within 6 months of delivery (OR = 2.13, p = 0.03) and history of moderate/severe premenstrual syndrome (OR = 6.33, p < 0.001) were significant predictors of the presence of a perimenopausal episode, even after controlling for demographic factors. When we narrowed the definition of premenstrual mood change to premenstrual dysphoric disorder, it remained significant (OR = 2.68, p = 0.007). Conclusions: Some women who have bipolar disorder may be particularly sensitive to reproductive life events. Previous mood episodes in relation to the female reproductive lifecycle may help clinicians predict individual risk for women with bipolar disorder approaching the menopause. There is a need for prospective longitudinal studies of women with bipolar disorder providing frequent contemporaneous ratings of their mood to overcome the limitations of retrospective self-report data.

Energy systems analysis of transboundary river basins in a nexus approach: the Sava river basin study case

Resource management policies are frequently designed and planned to target specific needs of particular sectors, without taking into account the interests of other sectors who share the same resources. In a climate of resource depletion, population growth, increase in energy demand and climate change awareness, it is of great importance to promote the assessment of intersectoral linkages and, by doing so, understand their effects and implications. This need is further augmented when common use of resources might not be solely relevant at national level, but also when the distribution of resources ranges over different nations. This dissertation focuses on the study of the energy systems of five south eastern European countries, which share the Sava River Basin, using a water-food(agriculture)-energy nexus approach. In the case of the electricity generation sector, the use of water is essential for the integrity of the energy systems, as the electricity production in the riparian countries relies on two major technologies dependent on water resources: hydro and thermal power plants. For example, in 2012, an average of 37% of the electricity production in the SRB countries was generated by hydropower and 61% in thermal power plants. Focusing on the SRB, in terms of existing installed capacities, the basin accommodates close to a tenth of all hydropower capacity while providing water for cooling to 42% of the net capacity of thermal power currently in operation in the basin. This energy-oriented nexus study explores the dependency on the basin’s water resources of the energy systems in the region for the period between 2015 and 2030. To do so, a multi-country electricity model was developed to provide a quantification ground to the analysis, using the open-source software modelling tool OSeMOSYS. Three main areas are subject to analysis: first, the impact of energy efficiency and renewable energy strategies in the electricity generation mix; secondly, the potential impacts of climate change under a moderate climate change projection scenario; and finally, deriving from the latter point, the cumulative impact of an increase in water demand in the agriculture sector, for irrigation. Additionally, electricity trade dynamics are compared across the different scenarios under scrutiny, as an effort to investigate the implications of the aforementioned factors in the electricity markets in the region.

The families and friends of heavy drinkers: Caught in the cross-fire of policy change?

INTRODUCTION AND AIMS: Research highlights the need to better understand the impact of alcohol-related harm on families and communities. Scottish policy initiatives to reduce alcohol consumption and alcohol-related harm include the planned introduction of a minimum unit price for alcohol. We aimed to explore existing and proposed changes in alcohol policy, from the standpoint of heavy drinkers, through accounts of their involvement and repercussions for family and friends. DESIGN AND METHODS: Interviews were conducted with 20 heavy drinkers, recruited from hospital alcohol treatment centres in Scotland's two largest cities. Participants were part of a larger longitudinal mixed methods study. Interviews explored experiences of alcohol-related harm and the impact, or potential impact, of alcohol policy changes on drinking patterns, risk-taking, consumption and wellbeing. Data coded for 'family and friends' were thematically analysed using a constant comparison method. RESULTS: Family and friends were portrayed as important for aiding moderation and abstinence, but more often for sustaining continued heavy drinking. Heavy drinkers with complex needs and those living in deprived communities suggested that increased alcohol prices could exacerbate the detrimental effect on their health and social circumstances, and that of their family, should their consumption remain excessive. DISCUSSION AND CONCLUSIONS: Population level policy initiatives to reduce alcohol consumption, such as minimum unit pricing, will impact on the families and social networks of heavy drinkers in addition to the drinker. The most vulnerable may be affected disproportionately. Alcohol policy changes and evaluations need to consider consequences for drinkers, families and communities. [O'May F, Whittaker A, Black H, Gill J. The families and friends of heavy drinkers: Caught in the cross-fire of policy change?

Perceptions of climate change, environmental variability and the role of agricultural adaptation strategies by small-scale farmers in Africa: the case of Mwanga district in Northern Tanzania

Abstract The potential impacts of climate change and environmental variability are already evident in most parts of the world, which is witnessing increasing temperature rates and prolonged flood or drought conditions that affect agriculture activities and nature-dependent livelihoods. This study was conducted in Mwanga District in the Kilimanjaro region of Tanzania to assess the nature and impacts of climate change and environmental variability on agriculture-dependent livelihoods and the adaptation strategies adopted by small-scale rural farmers. To attain its objective, the study employed a mixed methods approach in which both qualitative and quantitative techniques were used. The study shows that farmers are highly aware of their local environment and are conscious of the ways environmental changes affect their livelihoods. Farmers perceived that changes in climatic variables such as rainfall and temperature had occurred in their area over the period of three decades, and associated these changes with climate change and environmental variability. Farmers’ perceptions were confirmed by the evidence from rainfall and temperature data obtained from local and national weather stations, which showed that temperature and rainfall in the study area had become more variable over the past three decades. Farmers’ knowledge and perceptions of climate change vary depending on the location, age and gender of the respondents. The findings show that the farmers have limited understanding of the causes of climatic conditions and environmental variability, as some respondents associated climate change and environmental variability with social, cultural and religious factors. This study suggests that, despite the changing climatic conditions and environmental variability, farmers have developed and implemented a number of agriculture adaptation strategies that enable them to reduce their vulnerability to the changing conditions. The findings show that agriculture adaptation strategies employ both planned and autonomous adaptation strategies. However, the study shows that increasing drought conditions, rainfall variability, declining soil fertility and use of cheap farming technology are among the challenges that limit effective implementation of agriculture adaptation strategies. This study recommends further research on the varieties of drought-resilient crops, the development of small-scale irrigation schemes to reduce dependence on rain-fed agriculture, and the improvement of crop production in a given plot of land. In respect of the development of adaptation strategies, the study recommends the involvement of the local farmers and consideration of their knowledge and experience in the farming activities as well as the conditions of their local environment. Thus, the findings of this study may be helpful at various levels of decision making with regard to the development of climate change and environmental variability policies and strategies towards reducing farmers’ vulnerability to current and expected future changes.

Potential Mechanisms Underlying Response to Effects of the Fungicide Pyrimethanil from Gene Expression Profiling inSaccharomyces cerevisiae

Pyrimethanil is a fungicide mostly applied in vineyards. When misused, residue levels detected in grape must or in the environment may be of concern. The present work aimed to analyze mechanisms underlying response to deleterious effects of pyrimethanil in the eukaryotic model Saccharomyces cerevisiae. Pyrimethanil concentration-dependent effects at phenotypic (inhibition of growth) and transcriptomic levels were examined. For transcriptional profiling, analysis focused on two sublethal exposure conditions that inhibited yeast growth by 20% or 50% compared with control cells not exposed to the fungicide. Gene expression modifications increased with the magnitude of growth inhibition, in numbers and fold-change of differentially expressed genes and in diversity of over-represented functional categories. These included mostly biosynthesis of arginine and sulfur amino acids metabolism, as well as energy conservation, antioxidant response, and multidrug transport. Several pyrimethanil-responsive genes encoded proteins sharing significant homology with proteins from phytopathogenic fungi and ecologically relevant higher eukaryotes.

Climate change adaptation solutions for the green sectors of selected zones in the MENA region

In this paper, we propose climate adaptation solutions for the green sectors in three different zones of MENA: Egypt’s Delta (irrigated), Karak, in the highlands of Jordan (rainfed), and Lebanon’s Orontes basin (mixed: rainfed-irrigated). We analysed land use and crop intensification, and calculated the economic productivity of water – a critical scarce resource in MENA. By integrating the results with evidence from literature on the potential impacts of climate change and socio-economic factors, we could identify vulnerability levels of the three regions and propose adaptation measures relying of the concept of the “food-water-energy nexus.” While the vulnerability levels are found to be high in the Delta (Egypt) and Karak (Jordan), mainly due to water scarcity and poor adaptive capacity, the vulnerability level is moderate in the Orontes zone (Lebanon) due to a diversified agricultural sector and good market development, coupled with moderate water scarcity. Proposed adaptation solutions range from measures to improve technical efficiency, to measures that encourage economically efficient allocation by use of market forces. For both cases, the development of market opportunities is emphasized to make the proposed measures attractive to farmers.

Two dimensional analysis of inflatable structures by the positional FEM

This paper presents a, simple two dimensional frame formulation to deal with structures undergoing large motions due to dynamic actions including very thin inflatable structures, balloons. The proposed methodology is based on the minimum potential energy theorem written regarding nodal positions. Velocity, acceleration and strain are achieved directly from positions, not. displacements, characterizing the novelty of the proposed technique. A non-dimensional space is created and the deformation function (change of configuration) is written following two independent mappings from which the strain energy function is written. The classical New-mark equations are used to integrate time. Dumping and non-conservative forces are introduced into the mechanical system by a rheonomic energy function. The final formulation has the advantage of being simple and easy to teach, when compared to classical Counterparts. The behavior of a bench-mark problem (spin-up maneuver) is solved to prove the formulation regarding high circumferential speed applications. Other examples are dedicated to inflatable and very thin structures, in order to test the formulation for further analysis of three dimensional balloons.

Unconstrained Finite Element for Geometrical Nonlinear Dynamics of Shells

This paper presents a positional FEM formulation to deal with geometrical nonlinear dynamics of shells. The main objective is to develop a new FEM methodology based on the minimum potential energy theorem written regarding nodal positions and generalized unconstrained vectors not displacements and rotations. These characteristics are the novelty of the present work and avoid the use of large rotation approximations. A nondimensional auxiliary coordinate system is created, and the change of configuration function is written following two independent mappings from which the strain energy function is derived. This methodology is called positional and, as far as the authors' knowledge goes, is a new procedure to approximated geometrical nonlinear structures. In this paper a proof for the linear and angular momentum conservation property of the Newmark beta algorithm is provided for total Lagrangian description. The proposed shell element is locking free for elastic stress-strain relations due to the presence of linear strain variation along the shell thickness. The curved, high-order element together with an implicit procedure to solve nonlinear equations guarantees precision in calculations. The momentum conserving, the locking free behavior, and the frame invariance of the adopted mapping are numerically confirmed by examples. Copyright (C) 2009 H. B. Coda and R. R. Paccola.