Youth at risk, social exclusion, and intergenerational poverty dynamics : A new survey instrument with application to Brazil

This paper addresses the underlying causes of problems and risks faced by poor and excluded youth of 10-24 years of age. The authors develop a survey instrument that addresses poverty in a broad sense, including hunger, early pregnancy and fatherhood, violence, crime, drug use, low levels of social capital, and low educational attainment. The authors also shed light on intergenerational transfer of risks that are considered to induce poverty. They document findings based on the survey data gathered in three poor urban neighborhoods in Fortaleza in Northeast Brazil. Their main findings show that: (i) Poor youth are at considerable risk of growing up without their father. Only 7 percent grow up with their father present in the household. (ii) The intergenerational transmission of low education attainment is at play, but it is diminishing. (iii) The risk of early pregnancy and fatherhood is large among poor and excluded youth-31 percent of the youth had their first child before age 16, triple that of the adult population. (iv) The risk of sexual abuse and violence within the household exists-6 percent of the youth answered that they had their first sexual relationship with a family member, and 13 percent grow up in households with violence. (v) The social capital levels are low-only 5 percent of the youth and 9 percent of the adults have measurable social capital. (vi) The risk of growing up in a violent neighborhood is large-59 percent of the youth claim that they live in a violent neighborhood, 80 percent feel unsafe in their neighborhood, and 50 percent feel unsafe at home.Health Monitoring&Evaluation,Housing&Human Habitats,Children and Youth,Public Health Promotion,Gender and Social Development,Health Monitoring&Evaluation,Housing&Human Habitats,Gender and Social Development,Adolescent Health,Youth and Governance

Prolonged and tunable residence time using reversible covalent kinase inhibitors.

Drugs with prolonged on-target residence times often show superior efficacy, yet general strategies for optimizing drug-target residence time are lacking. Here we made progress toward this elusive goal by targeting a noncatalytic cysteine in Bruton's tyrosine kinase (BTK) with reversible covalent inhibitors. Using an inverted orientation of the cysteine-reactive cyanoacrylamide electrophile, we identified potent and selective BTK inhibitors that demonstrated biochemical residence times spanning from minutes to 7 d. An inverted cyanoacrylamide with prolonged residence time in vivo remained bound to BTK for more than 18 h after clearance from the circulation. The inverted cyanoacrylamide strategy was further used to discover fibroblast growth factor receptor (FGFR) kinase inhibitors with residence times of several days, demonstrating the generalizability of the approach. Targeting of noncatalytic cysteines with inverted cyanoacrylamides may serve as a broadly applicable platform that facilitates 'residence time by design', the ability to modulate and improve the duration of target engagement in vivo

Samferdsel og miljø 2007 : Utvalgte indikatorer for samferdselssektoren

Rapporten inneholder utvalgt statistikk og indikatorer for samferdselssektoren med hovedvekt på sammenhenger mellom samferdsel og miljø. I den grad det har vært mulig, er norske data sammenlignet med definerte indikatorer i EUs TERMprosjekt (Transport and Environment Reporting Mechanism) og med andre internasjonale datakilder. I tillegg presenteres utdypende statistikk for Norge

New Species in the Old World: Europe as a Frontier in Biodiversity Exploration, a Test Bed for 21st Century Taxonomy

The number of described species on the planet is about 1.9 million, with ca. 17,000 new species described annually, mostly from the tropics. However, taxonomy is usually described as a science in crisis, lacking manpower and funding, a politically acknowledged problem known as the Taxonomic Impediment. Using data from the Fauna Europaea database and the Zoological Record, we show that contrary to general belief, developed and heavily-studied parts of the world are important reservoirs of unknown species. In Europe, new species of multicellular terrestrial and freshwater animals are being discovered and named at an unprecedented rate: since the 1950s, more than 770 new species are on average described each year from Europe, which add to the 125,000 terrestrial and freshwater multicellular species already known in this region. There is no sign of having reached a plateau that would allow for the assessment of the magnitude of European biodiversity. More remarkably, over 60% of these new species are described by non-professional taxonomists. Amateurs are recognized as an essential part of the workforce in ecology and astronomy, but the magnitude of non-professional taxonomist contributions to alpha-taxonomy has not been fully realized until now. Our results stress the importance of developing a system that better supports and guides this formidable workforce, as we seek to overcome the Taxonomic Impediment and speed up the process of describing the planetary biodiversity before it is too late

Cosmological Radiative Transfer Codes Comparison Project I: The Static Density Field Tests

Radiative transfer simulations are now at the forefront of numerical astrophysics. They are becoming crucial for an increasing number of astrophysical and cosmological problems; at the same time their computational cost has come to the reach of currently available computational power. Further progress is retarded by the considerable number of different algorithms (including various flavours of ray-tracing and moment schemes) developed, which makes the selection of the most suitable technique for a given problem a non-trivial task. Assessing the validity ranges, accuracy and performances of these schemes is the main aim of this paper, for which we have compared 11 independent RT codes on 5 test problems: (0) basic physics, (1) isothermal H II region expansion and (2) H II region expansion with evolving temperature, (3) I-front trapping and shadowing by a dense clump, (4) multiple sources in a cosmological density field. The outputs of these tests have been compared and differences analyzed. The agreement between the various codes is satisfactory although not perfect. The main source of discrepancy appears to reside in the multi-frequency treatment approach, resulting in different thicknesses of the ionized-neutral transition regions and different temperature structure. The present results and tests represent the most complete benchmark available for the development of new codes and improvement of existing ones. To this aim all test inputs and outputs are made publicly available in digital form.Comment: 32 pages, 39 figures (all color), comments welcom

Fortune Favours the Bold: An Agent-Based Model Reveals Adaptive Advantages of Overconfidence in War

Overconfidence has long been considered a cause of war. Like other decision-making biases, overconfidence seems detrimental because it increases the frequency and costs of fighting. However, evolutionary biologists have proposed that overconfidence may also confer adaptive advantages: increasing ambition, resolve, persistence, bluffing opponents, and winning net payoffs from risky opportunities despite occasional failures. We report the results of an agent-based model of inter-state conflict, which allows us to evaluate the performance of different strategies in competition with each other. Counter-intuitively, we find that overconfident states predominate in the population at the expense of unbiased or underconfident states. Overconfident states win because: (1) they are more likely to accumulate resources from frequent attempts at conquest; (2) they are more likely to gang up on weak states, forcing victims to split their defences; and (3) when the decision threshold for attacking requires an overwhelming asymmetry of power, unbiased and underconfident states shirk many conflicts they are actually likely to win. These “adaptive advantages” of overconfidence may, via selection effects, learning, or evolved psychology, have spread and become entrenched among modern states, organizations and decision-makers. This would help to explain the frequent association of overconfidence and war, even if it no longer brings benefits today

The European union’s 2010 target: Putting rare species in focus

P. 167-185The European Union has adopted the ambitious target of halting the loss of biodiversity by 2010. Several indicators have been proposed to assess progress towards the 2010 target, two of them addressing directly the issue of species decline. In Europe, the Fauna Europaea database gives an insight into the patterns of distribution of a total dataset of 130,000 terrestrial and freshwater species without taxonomic bias, and provide a unique opportunity to assess the feasibility of the 2010 target. It shows that the vast majority of European species are rare, in the sense that they have a restricted range. Considering this, the paper discusses whether the 2010 target indicators really cover the species most at risk of extinction. The analysis of a list of 62 globally extinct European taxa shows that most contemporary extinctions have affected narrow-range taxa or taxa with strict ecological requirements. Indeed, most European species listed as threatened in the IUCN Red List are narrow-range species. Conversely, there are as many wide-range species as narrow-range endemics in the list of protected species in Europe (Bird and Habitat Directives). The subset of biodiversity captured by the 2010 target indicators should be representative of the whole biodiversity in terms of patterns of distribution and abundance. Indicators should not overlook a core characteristic of biodiversity, i.e. the large number of narrow-range species and their intrinsic vulnerability. With ill-selected indicator species, the extinction of narrowrange endemics would go unnoticedS

Investigating orphan cytochromes P450 from Mycobacterium tuberculosis : the search for potential drug targets

Tuberculosis (TB) is a disease that the World Health Organisation (WHO) regards as a global pandemic. There is a great need for new drugs to combat this threat. Drug resistant strains of the causative agent, Mycobacterium tuberculosis (Mtb), have increased the urgency of this quest for novel anti-mycobacterial medicines. Publication of the Mtb genome sequence revealed a large number of cytochrome P450 (CYP) enzymes [Cole, S. T. et al. 1998]. These mono-oxygenase enzymes have been studied for many years and are responsible for metabolic functions in every kingdom of life. Research on the Mtb P450s to date has highlighted several of them as having critcal roles within the organism. CYP121 and CYP128 have been implicated as essential through gene knockout studies. It has been demonstrated that CYP125 is not essential for viability. However, it is part of a gene cluster highly important for Mtb infectivity and virulence. Due to the prospective importance of P450s to Mtb, this group of enzymes is under investigation as a source of novel drug targets. CYP142 was discovered as a potential drug target after it was located to a gene cluster involved in cholesterol catabolism during Mtb dormancy. As part of this PhD project, it was demonstrated that CYP142 performs an almost identical role to that reported for CYP125. These enzymes both perform C27 hydroxylation and carboxylation of the cholesterol side chain. However, variations in the level of oxidation have been identified, dependent upon the redox system with which these P450s are associated. A crystal structure of CYP142 showing high similarity in active site architecture to CYP125 supports the physiological role of CYP142 in cholesterol catabolism. Combining this with in vitro data which demonstrates that CYP142 possesses high affinity for a range of azole anti-fungal agents [Ahmad, Z. et al. 2005, 2006] supports the suggestion that it is a candidate target for the next generation of anti-mycobacterial drugs. CYP144 was highlighted as being important during the latent phase of Mtb growth, a phase that is not targeted by any of the current antimycobacterials. Work performed as part of this PhD has shown that many characteristics of CYP144 are highly comparable to those reported for other MtbP450s. CYP144 shows high affinity and specificity towards many azole molecules. Econazole, clotrimazole and miconazole have repeatedly been shown to bind to MtbP450s, including CYP144 and CYP142, with high affinity and are excellent potential candidates as novel anti-mycobacterial agents. An N-terminally truncated form of CYP144, CYP144-T, has been investigated in the pursuit of a CYP144 crystal structure. It is hoped that this will enable the elucidation of a physiological role for CYP144. Both CYP142 and CYP144 have demonstrated biochemical and biophysical characteristics that contribute to our knowledge of P450 enzymes. This PhD has established that CYP142 exhibits an equilibrium between P450 and P420 species in its CO-bound, ferrous form. A conversion from P420, and stabilisation of P450, upon substrate binding was also demonstrated. CYP144 displays unusual azole coordination characteristics when examined by EPR and removal of the CYP144 gene from Mtb increased sensitivity of the strain to clotrimazole. Studies of these enzymes has advanced knowledge of P450 and Mtb redox chemistry, established roles for the MtbP450 cohort and identified the potential of anti-mycobacterial drugs and associated targets.EThOS - Electronic Theses Online ServiceGBUnited Kingdo