Operant serial feature-positive conditional discrimination with composite features and different topography responses

In a serial feature-positive conditional discrimination procedure the properties of a target stimulus A are defined by the presence or not of a feature stimulus X preceding it. In the present experiment, composite features preceded targets associated with two different topography operant responses (right and left bar pressing); matching and non-matching-to-sample arrangements were also used. Five water-deprived Wistar rats were trained in 6 different trials: X-R®Ar and X-L®Al, in which X and A were same modality visual stimuli and the reinforcement was contingent to pressing either the right (r) or left (l) bar that had the light on during the feature (matching-to-sample); Y-R®Bl and Y-L®Br, in which Y and B were same modality auditory stimuli and the reinforcement was contingent to pressing the bar that had the light off during the feature (non-matching-to-sample); A- and B- alone. After 100 training sessions, the animals were submitted to transfer tests with the targets used plus a new one (auditory click). Average percentages of stimuli with a response were measured. Acquisition occurred completely only for Y-L®Br+; however, complex associations were established along training. Transfer was not complete during the tests since concurrent effects of extinction and response generalization also occurred. Results suggest the use of both simple conditioning and configurational strategies, favoring the most recent theories of conditional discrimination learning. The implications of the use of complex arrangements for discussing these theories are considered.

Training conditional and cumulative risk judgements: the role of frequencies, problem-structure and Einstellung

Two experiments implement and evaluate a training scheme for learning to apply frequency formats to probability judgements couched in terms of percentages. Results indicate that both conditional and cumulative probability judgements can be improved in this manner, however the scheme is insufficient to promote any deeper understanding of the problem structure. In both experiments, training on one problem type only (either conditional or cumulative risk judgements) resulted in an inappropriate transfer of a learned method at test. The obstacles facing a frequency-based training programme for teaching appropriate use of probability data are discussed. Copyright (c) 2006 John Wiley & Sons, Ltd.

Conditional transgenic expression of fibroblast growth factor 9 in the adult mouse heart reduces heart failure mortality after myocardial infarction

BACKGROUND: Fibroblast growth factor 9 (FGF9) is secreted from bone marrow cells, which have been shown to improve systolic function after myocardial infarction (MI) in a clinical trial. FGF9 promotes cardiac vascularization during embryonic development but is only weakly expressed in the adult heart. METHODS AND RESULTS: We used a tetracycline-responsive binary transgene system based on the α-myosin heavy chain promoter to test whether conditional expression of FGF9 in the adult myocardium supports adaptation after MI. In sham-operated mice, transgenic FGF9 stimulated left ventricular hypertrophy with microvessel expansion and preserved systolic and diastolic function. After coronary artery ligation, transgenic FGF9 enhanced hypertrophy of the noninfarcted left ventricular myocardium with increased microvessel density, reduced interstitial fibrosis, attenuated fetal gene expression, and improved systolic function. Heart failure mortality after MI was markedly reduced by transgenic FGF9, whereas rupture rates were not affected. Adenoviral FGF9 gene transfer after MI similarly promoted left ventricular hypertrophy with improved systolic function and reduced heart failure mortality. Mechanistically, FGF9 stimulated proliferation and network formation of endothelial cells but induced no direct hypertrophic effects in neonatal or adult rat cardiomyocytes in vitro. FGF9-stimulated endothelial cell supernatants, however, induced cardiomyocyte hypertrophy via paracrine release of bone morphogenetic protein 6. In accord with this observation, expression of bone morphogenetic protein 6 and phosphorylation of its downstream targets SMAD1/5 were increased in the myocardium of FGF9 transgenic mice. CONCLUSIONS: Conditional expression of FGF9 promotes myocardial vascularization and hypertrophy with enhanced systolic function and reduced heart failure mortality after MI. These observations suggest a previously unrecognized therapeutic potential for FGF9 after MI.

Informal sanctions and conditional cooperation: : A natural experiment on voluntary contributions to a public good.

In a natural experiment, this paper studies the impact of an informal sanctioning mechanism on individuals’ voluntary contribution to a public good. Cross-country skiers’ actual cash contributions in two ski resorts, one with and one without an informal sanctioning system, are used. I find the contributing share to be higher in the informal sanctioning system (79 percent) than in the non-sanctioning system (36 percent). Previous studies in one-shot public good situations have found an increasing conditional contribution (CC) function, i.e. the relationship between expected average contributions of other group members and the individual’s own contribution. In contrast, the present results suggest that the CC-function in the non-sanctioning system is non-increasing at high perceived levels of others’ contribution. This relationship deserves further testing in lab.

Role of headmasters, teachers and supervisors in knowledge transfer about occupational health and safety to pupils in vocational education

Background Young people are at an increased risk for illness in working life. The authorities stipulate certain goals for training in occupational health and safety (OHS) in vocational schools. A previous study concluded that pupils in vocational education had limited knowledge in the prevention of health risks at work. The aim of the current study, therefore, was to study how OHS training is organized in school and in workplace-based learning (WPL).   Method The study design featured a qualitative approach, which included interviews with 12 headmasters, 20 teachers, and 20 supervisors at companies in which the pupils had their WPL. The study was conducted at 10 upper secondary schools, located in Central Sweden, that were graduating pupils in four vocational programs.   Result The interviews with headmasters, teachers, and supervisors indicate a staggered picture of how pupils are prepared for safe work. The headmasters generally give teachers the responsibility for how goals should be reached. Teaching is very much based on risk factors that are present in the workshops and on teachers’ own experiences and knowledge. The teaching during WPL also lacks the systematic training in OHS as well as in the traditional classroom environment.   Conclusion Teachers and supervisors did not plan the training in OHS in accordance with the provisions of systematic work environment management. Instead, the teachers based the training on their own experiences. Most of the supervisors did not get information from the schools as to what should be included when introducing OHS issues in WPL.

Managing Dual Enrollment Programs: Review of Program Models, Operations, and Outcomes

Universities that offer dual enrollment programs for high school students must manage increasing student demand in the face of changing state legislation. This brief examines how institutions finance their dual enrollment programs, and how they ensure academic rigor as their programs continue to grow. The report also considers how dual enrollment programs ensure that students can transfer credits, and what strategies they use to encourage DE students to matriculate as undergraduates.

Podem os programas sociais e de transferência de renda influenciar a oferta de trabalho em atividades não agrícolas? uma análise para as famílias em condição de pobreza no meio rural do nordeste

This study aims to analyze the main effect of social programs and cash transfers on the labor supply of non-farm family members in poverty in rural areas of the Northeast. Among the specific objectives, we sought to investigate the effects of these programs and individual characteristics on the decision of participation and allocation of working hours of parents and children in non-agricultural activities. It was assumed, as a theoretical basis, the model of neoclassical labor supply as well as the principle that the decision of allocation of working hours, non-agricultural, is subject to the initial choice of the worker devote or not the non-agricultural employment . The hypothesis assumes that access to social programs and income transfer contributes to the dismay of rural workers, in poverty, in its decision to participate and offer hours of work in non-agricultural activities. To achieve this objective, we applied the models of Heckman (1979) and Double Hurdle, of Cragg (1971), consisting of associating the decision to participate in the labor market with the decision on the amount of hours allocated. The database used was the National Survey by Household Sampling (PNAD) of 2006. The results of the heads of households showed that transfers of income, although they may have some effect on labor supply rural nonfarm, the magnitude has to say that there may be some dependence on benefits. The estimates for the joint children of 10 to 15 years showed that the programs have negatively influenced participation in suggesting an increase in school participation, although for the allocation of working hours the results were not significant on the incidence of child labor

Effects of broiler breeder genetic, diet type, and feeding program on maternal antibody transfer and development of lymphoid tissues in chicken progeny

Maternal antibody (MatAb) transfer is important for early chicken survivability. Diet composition and the amount of feed given to breeder pullets during rearing may affect the development of immunity and the transfer of MatAb to progeny, and could affect progeny performance and resistance to disease. The effects of broiler breeder nutrition and feeding management practices were evaluated for the transfer of MatAb to progeny and for spleen and bursa development at hatching in 2 genetic strains (A and B). In this experiment, the levels of MatAb against Newcastle disease virus were assessed by enzyme-linked immunosorbent assays in serum samples taken of pedigreed chicken progeny from hatching to 13 d of age. Chickens were fed corn-and wheat-based diets, as were their parents. The breeder feeding program and diet type altered the Newcastle disease virus MatAb found in progeny at hatching and affected how long these antibodies were maintained in circulation. Bursal follicle size at hatching was influenced by an interaction among all factors evaluated. Percentage of white pulp in the spleen was affected mainly by genetic strain and diet type, but responses varied according to the breeder feeding program. It was concluded that breeder feeding programs influence MatAb transfer and half-life, and may also affect the early development of lymphoid tissues.

Targeting neuronal populations by AAV-mediated gene transfer for studying the endocannabinoid system

The cannabinoid type 1 (CB1) receptor is involved in a plethora of physiological functions and heterogeneously expressed on different neuronal populations. Several conditional loss-of-function studies revealed distinct effects of CB1 receptor signaling on glutamatergic and GABAergic neurons, respectively. To gain a comprehensive picture of CB1 receptor-mediated effects, the present study aimed at developing a gain-of-function approach, which complements conditional loss-of-function studies. Therefore, adeno-associated virus (AAV)-mediated gene delivery and Cre-mediated recombination were combined to recreate an innovative method, which ensures region- and cell type-specific transgene expression in the brain. This method was used to overexpress the CB1 receptor in glutamatergic pyramidal neurons of the mouse hippocampus. Enhanced CB1 receptor activity at glutamatergic terminals caused impairment in hippocampus-dependent memory performance. On the other hand, elevated CB1 receptor levels provoked an increased protection against kainic acid-induced seizures and against excitotoxic neuronal cell death. This finding indicates the protective role of CB1 receptor on hippocampal glutamatergic terminals as a molecular stout guard in controlling excessive neuronal network activity. Hence, CB1 receptor on glutamatergic hippocampal neurons may represent a target for novel agents to restrain excitotoxic events and to treat neurodegenerative diseases. Endocannabinoid synthesizing and degrading enzymes tightly regulate endocannabinoid signaling, and thus, represent a promising therapeutic target. To further elucidate the precise function of the 2-AG degrading enzyme monoacylglycerol lipase (MAGL), MAGL was overexpressed specifically in hippocampal pyramidal neurons. This genetic modification resulted in highly increased MAGL activity accompanied by a 50 % decrease in 2-AG levels without affecting the content of arachidonic acid and anandamide. Elevated MAGL protein levels at glutamatergic terminals eliminated depolarization-induced suppression of excitation (DSE), while depolarization-induced suppression of inhibition (DSI) was unchanged. This result indicates that the on-demand availability of the endocannabinoid 2-AG is crucial for short-term plasticity at glutamatergic synapses in the hippocampus. Mice overexpressing MAGL exhibited elevated corticosterone levels under basal conditions and an increase in anxiety-like behavior, but surprisingly, showed no changes in aversive memory formation and in seizure susceptibility. This finding suggests that 2 AG-mediated hippocampal DSE is essential for adapting to aversive situations, but is not required to form aversive memory and to protect against kainic acid-induced seizures. Thus, specific inhibition of MAGL expressed in hippocampal pyramidal neurons may represent a potential treatment strategy for anxiety and stress disorders. Finally, the method of AAV-mediated cell type-specific transgene expression was advanced to allow drug-inducible and reversible transgene expression. Therefore, elements of the tetracycline-controlled gene expression system were incorporated in our “conditional” AAV vector. This approach showed that transgene expression is switched on after drug application and that background activity in the uninduced state was only detectable in scattered cells of the hippocampus. Thus, this AAV vector will proof useful for future research applications and gene therapy approaches.

Studies on the {\it in vivo} function of a phosphatidylinositol transfer protein from {\it Saccharomyces cerevisiae}

Phosphatidylinositol transfer proteins (PI-TP's) catalyze the transfer of phosphatidylinositol and phosphatidylcholine between membranes in vitro. However the in vivo function of these proteins is unknown. In this thesis we have used a combined biochemical and genetic approach to determine the importance of PI-TP in vivo. An oligonucleotide based on the amino terminal sequence of the PI-TP from Saccharomyces cerevisiae, was used to screen a yeast genomic library for the gene encoding PI-TP (PIT1 gene). Yeast strains transformed with the positive clones showed overproduction of transfer activities and transfer protein in the 100,000 x g supernatants. The 5$\sp\prime$ terminus of the PIT1 gene correlates with the predicted codons for residues 3-30 of the determined protein sequence. Tetrad analysis of a heterozygous diploid (PIT1/pit1::LEU2) revealed that the PIT1 gene is essential for cell growth. Non-viable spores could be rescued by transformation of the above diploid prior to sporulation, with a plasmid borne copy of the wild type gene. Sequencing of the entire PIT1 gene has revealed that the PIT1 gene is identical to the SEC14 gene. The sec14 ts mutant which exhibits conditional defects at the Golgi stage of protein secretion, is also temperature sensitive for PI-TP activity in vitro. These findings represent the first instance in which a physiological function has been assigned to any phospholipid transfer protein. ^

Automatic compile-time parallelization of logic programs for restricted, goal-level, independent and-parallelism.

A framework for the automatic parallelization of (constraint) logic programs is proposed and proved correct. Intuitively, the parallelization process replaces conjunctions of literals with parallel expressions. Such expressions trigger at run-time the exploitation of restricted, goal-level, independent and-parallelism. The parallelization process performs two steps. The first one builds a conditional dependency graph (which can be implified using compile-time analysis information), while the second transforms the resulting graph into linear conditional expressions, the parallel expressions of the &-Prolog language. Several heuristic algorithms for the latter ("annotation") process are proposed and proved correct. Algorithms are also given which determine if there is any loss of parallelism in the linearization process with respect to a proposed notion of maximal parallelism. Finally, a system is presented which implements the proposed approach. The performance of the different annotation algorithms is compared experimentally in this system by studying the time spent in parallelization and the effectiveness of the results in terms of speedups.

Conditional parallelization of nonStrict independence. Procedures and assessmen

This paper presents a conditional parallelization process for and-parallelism based on the notion of non-strict independence, a more relaxed notion than the traditional of strict independence. By using this notion, a parallelism annotator can extract more parallelism from programs. On the other hand, the intrinsic complexity of non-strict independence poses new challenges to this task. We report here on the implementation we have accomplished of an annotator for non-strict independence, capable of producing both static and dynamic execution graphs. This implementation, along with the also implemented independence checker and their integration in our system, have resulted what is, to the best of our knowledge, the first parallelizing compiler based on nonstrict independence which produces dynamic execution graphs. The paper also presents a preliminary assessment of the implemented tools, comparing them with the existing ones for strict independence, which shows encouraging results.

Nutrition and physical activity programs for obesity treatment (PRONAF study). methodological approach of the project

Este trabajo aborda la metodología seguida para llevar a cabo el proyecto de investigación PRONAF (Clinical Trials Gov.: number NCT01116856.) Background: At present, scientific consensus exists on the multifactorial etiopatogenia of obesity. Both professionals and researchers agree that treatment must also have a multifactorial approach, including diet, physical activity, pharmacology and/or surgical treatment. These two last ones should be reserved for those cases of morbid obesities or in case of failure of the previous ones. The aim of the PRONAF study is to determine what type of exercise combined with caloric restriction is the most appropriate to be included in overweigth and obesity intervention programs, and the aim of this paper is to describe the design and the evaluation methods used to carry out the PRONAF study. Methods/design: One-hundred nineteen overweight (46 males) and 120 obese (61 males) subjects aged 18–50 years were randomly assigned to a strength training group, an endurance training group, a combined strength + endurance training group or a diet and physical activity recommendations group. The intervention period was 22 weeks (in all cases 3 times/wk of training for 22 weeks and 2 weeks for pre and post evaluation). All subjects followed a hypocaloric diet (25-30% less energy intake than the daily energy expenditure estimated by accelerometry). 29–34% of the total energy intake came from fat, 14–20% from protein, and 50–55% from carbohydrates. The mayor outcome variables assesed were, biochemical and inflamatory markers, body composition, energy balance, physical fitness, nutritional habits, genetic profile and quality of life. 180 (75.3%) subjects finished the study, with a dropout rate of 24.7%. Dropout reasons included: personal reasons 17 (28.8%), low adherence to exercise 3 (5.1%), low adherence to diet 6 (10.2%), job change 6 (10.2%), and lost interest 27 (45.8%). Discussion: Feasibility of the study has been proven, with a low dropout rate which corresponds to the estimated sample size. Transfer of knowledge is foreseen as a spin-off, in order that overweight and obese subjects can benefit from the results. The aim is to transfer it to sports centres. Effectiveness on individual health-related parameter in order to determine the most effective training programme will be analysed in forthcoming publications.

Transgene organization in rice engineered through direct DNA transfer supports a two-phase integration mechanism mediated by the establishment of integration hot spots

Organization of transgenes in rice transformed through direct DNA transfer strongly suggests a two-phase integration mechanism. In the “preintegration” phase, transforming plasmid molecules (either intact or partial) are spliced together. This gives rise to rearranged transgenic sequences, which upon integration do not contain any interspersed plant genomic sequences. Subsequently, integration of transgenic DNA into the host genome is initiated. Our experiments suggest that the original site of integration acts as a hot spot, facilitating subsequent integration of successive transgenic molecules at the same locus. The resulting transgenic locus may have plant DNA separating the transgenic sequences. Our data indicate that transformation through direct DNA transfer, specifically particle bombardment, generally results in a single transgenic locus as a result of this two-phase integration mechanism. Transgenic plants generated through such processes may, therefore, be more amenable to breeding programs as the single transgenic locus will be easier to characterize genetically. Results from direct DNA transfer experiments suggest that in the absence of protein factors involved in exogenous DNA transfer through Agrobacterium, the qualitative and/or quantitative efficiency of transformation events is not compromised. Our results cast doubt on the role of Agrobacterium vir genes in the integration process.

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