Anabolic-androgenic steroid treatment induces behavioral disinhibition and downregulation of serotonin receptor messenger RNA in the prefrontal cortex and amygdala of male mice

Nandrolone is an anabolic-androgenic steroid (AAS) that is highly abused by individuals seeking enhanced physical strength or body appearance. Supraphysiological doses of this synthetic testosterone derivative have been associated with many physical and psychiatric adverse effects, particularly episodes of impulsiveness and overt aggressive behavior. As the neural mechanisms underlying AAS-induced behavioral disinhibition are unknown, we investigated the status of serotonergic system-related transcripts in several brain areas of mice receiving prolonged nandrolone administration. Male C57BL/6J mice received 15 mg/kg of nandrolone decanoate subcutaneously once daily for 28 days, and different sets of animals were used to investigate motor-related and emotion-related behaviors or 5-HT-related messenger RNA (mRNA) levels by real-time quantitative polymerase chain reaction. AAS-injected mice had increased body weight, were more active and displayed anxious-like behaviors in novel environments. They exhibited reduced immobility in the forced swim test, a higher probability of being aggressive and more readily attacked opponents. AAS treatment substantially reduced mRNA levels of most investigated postsynaptic 5-HT receptors in the amygdala and prefrontal cortex. Interestingly, the 5-HT(1B) mRNA level was further reduced in the hippocampus and hypothalamus. There was no alteration of 5-HT system transcript levels in the midbrain. In conclusion, high doses of AAS nandrolone in male mice recapitulate the behavioral disinhibition observed in abusers. Furthermore, these high doses downregulate 5-HT receptor mRNA levels in the amygdala and prefrontal cortex. Our combined findings suggest these areas as critical sites for AAS-induced effects and a possible role for the 5-HT(1B) receptor in the observed behavioral disinhibition.

TLR4/MYD88-dependent, LPS-induced synthesis of PGE(2) by macrophages or dendritic cells prevents anti-CD3-mediated CD95L upregulation in T cells

Antigen-presenting cells (APCs) control T-cell responses by multiple mechanisms, including the expression of co-stimulatory molecules and the production of cytokines and other mediators that control T-cell proliferation, survival and differentiation. Here, we demonstrate that soluble factor(s) produced by Toll-like receptor (TLR)-activated APCs suppress activation-induced cell death (AICD). This effect was observed in non-stimulated APCs, but it was significantly increased after lipopolysaccharide (LPS) treatment. Using different KO mice, we found that the LPS-induced protective factor is dependent on TLR4/MyD88. We identified the protective factor as prostaglandin E-2(PGE(2)) and showed that both APC-derived supernatants and PGE(2) prevented CD95L upregulation in T cells in response to TCR/CD3 stimulation, thereby avoiding both AICD and activated T cell killing of target macrophages. The PGE(2) receptors, EP2 and EP4, appear to be involved since pharmacological stimulation of these receptors mimics the protective effect on T cells and their respective antagonists interfere with the protection induced by either APCs derived or synthetic PGE(2). Finally, the engagement of EP2 and EP4 synergistically activates protein kinase A (PKA) and exchange protein directly activated by cAMP pathways to prevent AICD. Taken together, these results indicate that APCs can regulate T-cell levels of CD95L by releasing PGE2 in response to LPS through a TLR4/MyD88-dependent pathway, with consequences for both T cell and their own survival.

Combination Efficacy of Voriconazole and Amphotericin B in the Experimental Disease in Immunodeficient Mice Caused by Fluconazole-resistant Cryptococcus neoformans

The therapeutic efficacy of amphotericin B and voriconazole alone and in combination with one another were evaluated in immunodeficient mice (BALB/c-SCID) infected with a fluconazole-resistant strain of Cryptococcus neoformans var. grubii. The animals were infected intravenously with 3 x 10(5) cells and intraperitoneally treated with amphotericin B (1.5 mg/kg/day) in combination with voriconazole (40 mg/kg/days). Treatment began 1 day after inoculation and continued for 7 and 15 days post-inoculation. The treatments were evaluated by survival curves and yeast quantification (CFUs) in brain and lung tissues. Treatments for 15 days significantly promoted the survival of the animals compared to the control groups. Our results indicated that amphotericin B was effective in assuring longest-term survival of infected animals, but these animals still harbored the highest CFU of C. neoformans in lungs and brain at the end of the experiment. Voriconazole was not as effective alone, but in combination with amphotericin B, it prolonged survival for the second-longest time period and provided the lowest colonization of target organs by the fungus. None of the treatments were effective in complete eradication of the fungus in mice lungs and brain at the end of the experiment.

On ""Schwinger mechanism for gluon pair production in the presence of arbitrary time dependent chromo-electric field""

Recently the paper ""Schwinger mechanism for gluon pair production in the presence of arbitrary time dependent chromo-electric field"" by G. C. Nayak was published [Eur. Phys. J. C 59: 715, 2009; arXiv:0708.2430]. Its aim is to obtain an exact expression for the probability of non-perturbative gluon pair production per unit time per unit volume and per unit transverse momentum in an arbitrary time-dependent chromo-electric background field. We believe that the obtained expression is open to question. We demonstrate its inconsistency on some well-known examples. We think that this is a consequence of using the socalled ""shift theorem""[arXiv:hep-th/0609192] in deriving the expression for the probability. We make some critical comments on the theorem and its applicability to the problem in question.

On the effects of geographical constraints on task execution in complex

In the present work, the effects of spatial constraints on the efficiency of task execution in systems underlain by geographical complex networks are investigated, where the probability of connection decreases with the distance between the nodes. The investigation considers several configurations of the parameters defining the network connectivity, and the Barabasi-Albert network model is also considered for comparisons. The results show that the effect of connectivity is significant only for shorter tasks, the locality of connection simplied by the spatial constraints reduces efficiency, and the addition of edges can improve the efficiency of the execution, although with increasing locality of the connections the improvement is small.

Ligand induced interaction of thyroid hormone receptor beta with its coregulators

Thyroid hormones exert most of their physiological effects through two thyroid hormone receptor (TR) subtypes, TR alpha and TR beta, which associate with many transcriptional coregulators to mediate activation or repression of target genes. The search for selective TR beta ligands has been stimulated by the finding that several pharmacological actions mediated by TR beta might be beneficial in medical conditions such as obesity, hypercholesterolemia and diabetes. Here, we present a new methodology which employs surface plasmon resonance to investigate the interactions between TR beta ligand binding domain (LBD) complexes and peptides derived from the nuclear receptor interaction motifs of two of its coregulators, SRC2 and DAX1. The effect of several TR beta ligands, including the TR beta selective agonist GC-I and the TR beta selective antagonist NH-3, were investigated. We also determined the kinetic rate constants for the interaction of TR beta-T3 with both coregulators, and accessed the thermodynamic parameters for the interaction with DAX1. Our findings Suggest that flexibility plays an important role in the interaction between the receptor and its coregulators. and point out important aspects of experimental design that should be addressed when using TR beta LBD and its agonists. Furthermore, the methodology described here may be useful for the identification of new TR beta ligands. (C) 2008 Elsevier Ltd. All rights reserved.

Missing data mechanisms and their implications on the analysis of categorical data

We review some issues related to the implications of different missing data mechanisms on statistical inference for contingency tables and consider simulation studies to compare the results obtained under such models to those where the units with missing data are disregarded. We confirm that although, in general, analyses under the correct missing at random and missing completely at random models are more efficient even for small sample sizes, there are exceptions where they may not improve the results obtained by ignoring the partially classified data. We show that under the missing not at random (MNAR) model, estimates on the boundary of the parameter space as well as lack of identifiability of the parameters of saturated models may be associated with undesirable asymptotic properties of maximum likelihood estimators and likelihood ratio tests; even in standard cases the bias of the estimators may be low only for very large samples. We also show that the probability of a boundary solution obtained under the correct MNAR model may be large even for large samples and that, consequently, we may not always conclude that a MNAR model is misspecified because the estimate is on the boundary of the parameter space.

Obsessive-compulsive disorder: Influence of age at onset on comorbidity patterns

Purpose. - This study investigates the influence of age at onset of OCS on psychiatric comorbidities, and tries to establish a cut-off point for age at onset. Methods. - Three hundred and thirty OCD patients were consecutively recruited and interviewed using the following structured interviews: Yale-Brown Obsessive Compulsive Scale; Yale Global Tic Severity Scale and the Structured Clinical Interview for DSM-IV. Data were analyzed with regression and cluster analysis. Results. - Lower age at onset was associated with a higher probability of having comorbidity with tic, anxiety, somatoform, eating and impulse-control disorders. Longer illness duration was associated with lower chance of having tics. Female gender was associated with anxiety, eating and impulse-control disorders. Tic disorders were associated with anxiety disorders and attention-deficit/hyperactivity disorder. No cutoff age at onset was found to clearly divide the sample in homogeneous subgroups. However, cluster analyses revealed that differences started to emerge at the age of 10 and were more pronounced at the age of 17, suggesting that these were the best cut-off points on this sample. Conclusions. - Age at onset is associated with specific comorbidity patterns in OCD patients. More prominent differences are obtained when analyzing age at onset as an absolute value. (C) 2008 Elsevier Masson SAS. All rights reserved.

Risk of Giardia infection for drinking water and bathing in a peri-urban area in Sao Paulo, Brazil

A high incidence of waterborne diseases is observed worldwide and in order to address contamination problems prior to an outbreak, quantitative microbial risk assessment is a useful tool for estimating the risk of infection. The objective of this paper was to assess the probability of Giardia infection from consuming water from shallow wells in a peri-urban area. Giardia has been described as an important waterborne pathogen and reported in several water sources, including ground waters. Sixteen water samples were collected and examined according to the US EPA (1623, 2005). A Monte Carlo method was used to address the potential risk as described by the exponential dose response model. Giardia cysts occurred in 62.5% of the samples (0.1-36.1 cysts/l). A median risk of 10-1 for the population was estimated and the adult ingestion was the highest risk driver. This study illustrates the vulnerability of shallow well water supply systems in peri-urban areas.

A quantum chemical study on the formation of phosphorus mononitride

The chemical mechanism of the (1)PN formation was successfully studied by using the CCSD(T)/6-311++G(3df,3pd) level of theory. The (1)NH(3) + (3)PH and (4)P + NH(3) reaction paths are not energetically favorable to form the (1)PN molecule. However, the (3)NH + (3)PH, (4)N + (3)PH(3), (4)N + (3)PH, (4)P + (3)NH, and (4)P + (2)NH(2) reaction paths to form the (1)PN molecule are only energetically favorable by taking place through specific transition states to form the (1)PN molecule. The NH(3) + (3)PH, (4)N + (1)PH(3), NH(3) + (4)P, and (4)N + (2)PH(2) reactions are spin-forbidden and the probability of hopping for these reactions was estimated to be 0 by the Landau-Zener theory. This is the first detailed study on the chemical mechanism for the (1)PN formation. (C) 2009 Elsevier B.V. All rights reserved.

The impact of big-boxes on local retail : What happens when IKEA comes to town?

The development of large discount retailers, or big-boxes as they are sometimes referred to, are often subject to heated debate and their entry on a market is greeted with either great enthusiasm or dread. For instance, the world’s largest retailer Wal-Mart (Forbes 2014) has a number of anti- and pro-groups dedicated to its being and the event of a Wal-Mart entry tends to be met with protests and campaigns (Decamme 2013) but also welcomed by, for instance, consumers (Davis & DeBonis 2013). Also in Sweden, the entry of a big box is a hot topic and before IKEA’s opening i Borlänge 2013, the first in Sweden in more than five years, great expectations were mixed with worry (Västerbottens-Kuriren 2011).The presence of large scale discount retailers is not, however, a novel phenomenon but a part of a long-term change in retailing that has taken place globally over the past couple of decades (Taylor & Smalling, 2005). As noted by Dawson (2006), the trend in Europe has over the past few decades gone towards an increasing concentration of large firms along with a decrease of smaller firms.This trend is also detectable in the Swedish retail industry. Over the past decade, the retailing industry in Sweden has increased by around 190 Billion SEK, and its share of GDP has risen from 2,7% to 2,9%, while the number of employees have increased from 200 000 to 250 000 (HUI 2013). This growth, however, has not been distributed evenly but rather it has been oriented mainly towards out-of-town retail clusters. Parallel to this development, the number of large retailers has risen at the expense of market shares of smaller independent firms (Rämme et al 2010). Thereby, the presence of large scale retailers is simply part of a changing retail landscape.The effects of this development, where large scale retailing agents relocate shopping to out-of-town shopping areas, have been heavily debated. On the one hand, the big-boxes are accused of displacing independent small retail businesses in the city-centers and the residential areas, resulting in, to some extent, reduced employment opportunities and less availability for the consumers - especially the elderly (Ljungberg et al 2006). In addition, as access to shopping now tends to require some sort of a motorized vehicle, environmental aspects to the discussion have emerged. Ultimately these types of concerns have resulted in calls for regulations against this development (Olsson 2010). On the other hand, the proponents of the new shopping landscape argue that this evolution implies productivity gains, the benefits of lower prices and an increased variety of products (Maican & Orth 2012). Moreover it is argued that it leads to, for instance, better services (such as longer opening hours) and a creative destruction transformation pressure on retailers, which brings about a renewal of city-centerIIretail and services, increasing their attractivity (Bergström 2010). The belief in benefits of a big box entry can be exemplified by the attractivity of IKEA, and the fact that municipalities are prepared to commit to expenses amounting up to hundreds of millions in order to attract the entry of this big-box. Borlänge municipality, for instance, agreed to expenses of about 350 million SEK in order to secure the entry of IKEA, which opened in 2013 (Blomgren 2009).Against this backdrop, the overall effects of large discount retailers become important: Are the economic benefits enough to warrant subsidies or are there, on the contrary, some very compelling grounds for regulations against these types of establishments? In other words; how is overall retail in a region where a store like IKEA enters affected? And how are local retail firms affected?In order to answer these questions, the purpose of this thesis is to study how entry of a big-box retailer affects the entry region. The object of this study is IKEA - one of the world’s largest retailers, with 345 stores, active in over 40 countries and with profits of about 3.3 billion (IKEA 2013; IKEA 2014). By studying the effects of IKEA-entry, both on an aggregated level and on firm level, this thesis intends to find indications of how large discount retail establishments in general can be expected to affect the economic development both in a region overall, but also on the local firm level, something which is of interest to both policymakers as well as the retailing industry in general.The first paper examines the effects of IKEA on retail revenues and employment in the municipalities that IKEA chose to enter between 2000 and 2011; Gothenburg, Haparanda, Kalmar and Karlstad. By means of a matching method we first identify non-entry municipalities that have a similar probability of IKEA entry as the true entry municipalities. Then, using these non-entry municipalities as a control group, the causal effects of IKEA entry can be estimated using a treatment-control approach. We also extend the analysis to examine the spatial impact of IKEA by estimating the effects on retail in neighboring municipalities. It is found that a new IKEA store increases revenues in durable goods trade with 20% in the entry municipality and the number of employees with 17%. Only small, and in most cases statistically insignificant, negative effects were found in neighboring municipalities.It appears that there is a positive net effect on durables retail sales and employment in the entry municipality. However, the analysis is based on data on an aggregated municipality level and thereby it remains unclear if and how the effects vary within the entry municipalities. In addition, the data used in the first study includes the sales and employment of IKEA itself, which could account for the majority of the increases in employment and retail. Thereby the potential spillover effects on incumbent retailers in the entry municipalities cannot be discerned in the first study.IIITo examine effects of IKEA entry on incumbent retail firms, the second paper in this thesis analyses how IKEA entry affects the revenues and employment of local retail firms in three municipalities; Haparanda, Kalmar and Karlstad, which experienced entry by IKEA between 2000 and 2010. In this second study, we exclude Gothenburg due to the fact that big-box entry appears to have weaker effects in metropolitan areas (as indicated by Artz & Stone 2006). By excluding Gothenburg we aim to reduce the geographical heterogeneity in our study. We obtain control municipalities that are as similar as possible to the three entry municipalities using the same method as in the previous study, but including a slightly different set of variables in the selection equation. Using similar retail firms in the control municipalities as our comparison group, we estimate the impact of IKEA entry on revenues and employment for retail firms located at varying distances from the IKEA entry site.The results generated in this study imply that entry by IKEA increases revenues in incumbent retail firms by, on average, 11% in the entry municipalities. In addition, we do not find any significant impact on retail revenues in the city centers of the entry municipalities. However, we do find that retail firms within 1 km of the IKEA experience increases in revenues of about 26%, which indicates large spillover effects in the area nearby the entry site. As expected, this impact decreases as we expand the buffer zone: firms located between 0-2 km experiences a 14% increase and firms in 2-5 km experiences an increase of 10%. We do not find any significant impacts on retail employment.

Determinants and effects of central bank independence reforms

This thesis consists of four empirically oriented papers on central bank independence (CBI) reforms.    Paper [1] is an investigation of why politicians around the world have chosen to give up power to independent central banks, thereby reducing their ability to control the economy. A new data-set, including the possible occurrence of CBI-reforms in 132 countries during 1980-2005, was collected. Politicians in non-OECD countries were more likely to delegate power to independent central banks if their country had been characterized by high variability in inflation and if they faced a high probability of being replaced. No such effects were found for OECD countries.    Paper [2], using a difference-in-difference approach, studies whether CBI reform matters for inflation performance. The analysis is based on a dataset including the possible occurrence of CBI-reforms in 132 countries during the period of 1980-2005. CBI reform is found to have contributed to bringing down inflation in high-inflation countries, but it seems unrelated to inflation performance in low-inflation countries.    Paper [3] investigates whether CBI-reforms are important in reducing inflation and maintaining price stability, using a random-effects random-coefficients model to account for heterogeneity in the effects of CBI-reforms on inflation. CBI-reforms are found to have reduced inflation on average by 3.31 percent, but the effect is only present when countries with historically high inflation rates are included in the sample. Countries with more modest inflation rates have achieved low inflation without institutional reforms that grant central banks more independence, thus undermining the time-inconsistency theory case for CBI. There is furthermore no evidence that CBI-reforms have contributed to lower inflation variability    Paper [4] studies the relationship between CBI and a suggested trade-off between price variability and output variability using data on CBI-levels, and data the on implementation dates of CBI-reforms. The results question the existence of such a trade-off, but indicate that there may still be potential gains in stabilization policy from CBI-reforms.

Representations of culture in EIL : Cultural representation in Swedish EFL textbooks

The English language has become an international language and is globally used as a lingua franca. Therefore, there has been a shift in English-language education toward teaching English as an interna-tional language (EIL). Teaching from the EIL paradigm means that English is seen as an international language used in communication by people from different linguistic and cultural backgrounds. As the approach to English-language education changes from the traditional native-speaker, target country context, so does the role of culture within English-language teaching. The aim of this thesis is to in-vestigate and analyse cultural representations in two Swedish EFL textbooks used in upper-secondary school to see how they correspond with the EIL paradigm. This is done by focusing on the geograph-ical origin of the cultural content as well as looking at what kinds of culture are represented in the textbooks. A content analysis of the textbooks is conducted, using Kachru’s Concentric Circles of English as the model for the analysis of the geographical origin. Horibe’s model of the three different kinds of culture in EIL is the model used for coding the second part of the analysis. The results of the analysis show that culture of target countries and "Culture as social custom" dominate the cultural content of the textbook. Thus, although there are some indications that the EIL paradigm has influ-enced the textbooks, the traditional approach to culture in language teaching still prevails in the ana-lysed textbooks. Because of the relatively small sample included in the thesis, further studies need to be conducted in order to make conclusions regarding the Swedish context as a whole.

Effects of fragmented habitat and fire on the distribution and ecology of the swamp antechinus (Antechinus minimus maritimus) in the Eastern Otways, Victoria

This study investigated the distribution, habitat and population dynamics of the swamp antechinus (Antechinus minimus maritimus) in the eastern Otway Ranges. The species has a restricted, disjunct distribution and has been recorded at 25 sites between 1969 and 1999. All sites were located within 7 km of the coast, occurred at altitudes up to 80 m above sea level and within 10 m of a gully. Analysis of landscape site variables identified sun index as being significant in determination of the probability of occurrence of A. minimus. The presence of A. minimus is negatively associated with sun index, occuring at sites that have a southerly aspect and gentle slope. A. minimus was located in a range of structural vegetation including Open Forest, Low Woodland, Shrubland and Hummock Grassland and a number of floristic groups, some characterised by high frequencies of sclerophyll shrubs, others by high frequencies of Pteridium esculentum, hummock grasses and herbaceous species. A. minimus occurs in fragmented, small populations with maximum population densities of 1.1–18 ha^–1. Populations at inland sites became extinct after the 1983 wildfire which burnt 41 000 ha. These sites have not been recolonised since, while on the coast the species did not re-establish until 1993–97. One population that is restricted to a narrow coastal strip of habitat is characterised by high levels of transient animals. The species is subject to extinction in the region due to habitat fragmentation, coastal developments and fire. Management actions to secure the present populations and ensure long-term survival of the species in the area are required and include implementation of appropriate fire regimes, prevention of habitat fragmentation, revegetation of habitat, and establishment of corridor habitat.

Visual perception of movement kinematics and the acquisition of "action prototypes"

Recognizing a class of movements as belonging to a "nominal" action category, such as walking, running, or throwing, is a fundamental human ability. Three experiments were undertaken to test the hypothesis that common ("prototypical") features of moving displays could be learned by observation. Participants viewed moving stick-figure displays resembling forearm flexion movements in the saggital plane. Four displays (presentation displays) were first presented in which one or more movement dimensions were combined with 2 respective cues: direction (up, down), speed (fast, slow), and extent (long, short). Eight test displays were then shown, and the observer indicated whether each test display was like or unlike those previously seen. The results showed that without corrective feedback, a single cue (e.g., up or down) could be correctly recognized, on average, with the proportion correct between .66 and .87. When two cues were manipulated (e.g., up and slow), recognition accuracy remained high, ranging between .72 and .89. Three-cue displays were also easily identified. These results provide the first empirical demonstration of action-prototype learning for categories of human action and show how apparently complex kinematic patterns can be categorized in terms of common features or cues. It was also shown that probability of correct recognition of kinematic properties was reduced when the set of 4 presentation displays were more variable with respect to their shared kinematic property, such as speed or amplitude. Finally, while not conclusive, the results (from 2 of the 3 experiments) did suggest that similarity (or "likeness") with respect to a common kinematic property (or properties) is more easily recognized than dissimilarity.