Molecular analysis of a mutant Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV) shows an interruption of an inhibitor of apoptosis gene (iap-3) by a new class-II piggyBac-related insect transposon

A new piggyBac-related transposable element (TE) was found in the genome of a mutant Anticarsia gemmatalis multiple nucleopolyhedrovirus interrupting an inhibitor of apoptosis gene. This mutant virus induces apoptosis upon infection of an Anticarsia gemmatalis cell line, but not in a Trichoplusia ni cell line. The sequence of the new TE (which was named IDT for iap disruptor transposon) has 2531 bp with two DNA sequences flanking a putative Transposase (Tpase) ORF of 1719 bp coding for a protein with 572 amino acids. These structural features are similar to the piggyBac TE, also reported for the first time in the genome of a baculovirus. We have also isolated variants of this new TE from different lepidopteran insect cells and compared their Tpase sequences.

Using on-line delivery to support students during practicum placements.

Finding ways to effectively support students while on placement remains a continuing endeavour for those who teach in professional education programmes. In The present paper, the multiple challenges and learning opportunities that social work students encounter during practicum learning will be discussed. Next, drawing from constructivist pedagogy and using authentic examples from an online discussion board, ways to supplement the support and educational input provided to students on placement will be demonstrated. Finally, some of the risks and limitations in engaging with on-line delivery are examined with the view to understanding how e-learning can be facilitated most effectively for students during the practicum.

On-line tool condition monitoring and control system in forging processes

Cold bulk metal forming has made large-scale production of small complex solid parts economically feasible. Tooling used in metal forming poses many uncertainties in the preliminary cost estimation and production process and continual tool replacement and maintenance dramatically reduces productivity and raises manufacturing cost. In order to tackle this, an on-line tool condition monitoring system using artificial neural network (ANN) to integrate information from multiple sensors for forging process has been developed. Together with the force, acoustic emission signals and process conditions, information developed from theoretical models is integrated into the ANN tool monitoring system to predict tool life and provide the maintenance schedule.

Evaluation of the fuzzy ARTMAP neural network using off-line and on-line learning strategies

This paper describes an experimental study of the Fuzzy ARTMAP (FAM) neural network as an autonomous learning system for pattern classification tasks. A benchmark database of radar signals from ionosphere has been employed for the system to classify arbitrary sequences of pattern into distinct categories. A number of simulations have been conducted systematically to evaluate the applicability and usefulness of FAM in this context. First, we identify the 'optimum' parameter settings of FAM for the problem at hand, and investigate the effects of different training schemes and learning rules on classification results, using an off-line learning methodology. We then examine a voting strategy to improve classification accuracy by combining results from multiple FAM classifiers. In addition to off-line learning, we evaluate the prospect of using FAM as an autonomously learning pattern classification system for on-line, non-stationary environments. The performance of FAM is comparable with other reported results, but with the added advantage of on-line and incremental learning.

Dichloroacetate inhibits aerobic glycolysis in multiple myeloma cells and increases sensitivity to bortezomib

Background:
Dichloroacetate (DCA), through the inhibition of aerobic glycolysis (the ‘Warburg effect’) and promotion of pyruvate oxidation, induces growth reduction in many tumours and is now undergoing several clinical trials. If aerobic glycolysis is active in multiple myeloma (MM) cells, it can be potentially targeted by DCA to induce myeloma growth inhibition.

Methods:
Representative multiple myeloma cell lines and a myeloma-bearing mice were treated with DCA, alone and in combination with bortezomib.

Results:
We found that aerobic glycolysis occurs in approximately half of MM cell lines examined, producing on average 1.86-fold more lactate than phorbol myristate acetate stimulated-peripheral blood mononuclear cells and is associated with low-oxidative capacity. Lower doses of DCA (5–10 mM) suppressed aerobic glycolysis and improved cellular respiration that was associated with activation of the pyruvate dehydrogenase complex. Higher doses of DCA (10–25 mM) induced superoxide production, apoptosis, suppressed proliferation with a G0/1 and G2M phase arrest in MM cell lines. In addition, DCA increased MM cell line sensitivity to bortezomib, and combinatorial treatment of both agents improved the survival of myeloma-bearing mice.

Conclusion:
Myeloma cells display aerobic glycolysis and DCA may complement clinically used MM therapies to inhibit disease progression.

Persistence on therapy and propensity matched outcome comparison of two subcutaneous interferon beta 1a dosages for multiple sclerosis

To compare treatment persistence between two dosages of interferon β-1a in a large observational multiple sclerosis registry and assess disease outcomes of first line MS treatment at these dosages using propensity scoring to adjust for baseline imbalance in disease characteristics. Treatment discontinuations were evaluated in all patients within the MSBase registry who commenced interferon β-1a SC thrice weekly (n = 4678). Furthermore, we assessed 2-year clinical outcomes in 1220 patients treated with interferon β-1a in either dosage (22 µg or 44 µg) as their first disease modifying agent, matched on propensity score calculated from pre-treatment demographic and clinical variables. A subgroup analysis was performed on 456 matched patients who also had baseline MRI variables recorded. Overall, 4054 treatment discontinuations were recorded in 3059 patients. The patients receiving the lower interferon dosage were more likely to discontinue treatment than those with the higher dosage (25% vs. 20% annual probability of discontinuation, respectively). This was seen in discontinuations with reasons recorded as “lack of efficacy” (3.3% vs. 1.7%), “scheduled stop” (2.2% vs. 1.3%) or without the reason recorded (16.7% vs. 13.3% annual discontinuation rate, 22 µg vs. 44 µg dosage, respectively). Propensity score was determined by treating centre and disability (score without MRI parameters) or centre, sex and number of contrast-enhancing lesions (score including MRI parameters). No differences in clinical outcomes at two years (relapse rate, time relapse-free and disability) were observed between the matched patients treated with either of the interferon dosages. Treatment discontinuations were more common in interferon β-1a 22 µg SC thrice weekly. However, 2-year clinical outcomes did not differ between patients receiving the different dosages, thus replicating in a registry dataset derived from “real-world” database the results of the pivotal randomised trial. Propensity score matching effectively minimised baseline covariate imbalance between two directly compared sub-populations from a large observational registry.

Leakage Detection And Localization Method Based On A Hybrid Inverse/Direct Modelling Approach Suitable For Handling Multiple-Leak Scenarios

When an accurate hydraulic network model is available, direct modeling techniques are very straightforward and reliable for on-line leakage detection and localization applied to large class of water distribution networks. In general, this type of techniques based on analytical models can be seen as an application of the well-known fault detection and isolation theory for complex industrial systems. Nonetheless, the assumption of single leak scenarios is usually made considering a certain leak size pattern which may not hold in real applications. Upgrading a leak detection and localization method based on a direct modeling approach to handle multiple-leak scenarios can be, on one hand, quite straightforward but, on the other hand, highly computational demanding for large class of water distribution networks given the huge number of potential water loss hotspots. This paper presents a leakage detection and localization method suitable for multiple-leak scenarios and large class of water distribution networks. This method can be seen as an upgrade of the above mentioned method based on a direct modeling approach in which a global search method based on genetic algorithms has been integrated in order to estimate those network water loss hotspots and the size of the leaks. This is an inverse / direct modeling method which tries to take benefit from both approaches: on one hand, the exploration capability of genetic algorithms to estimate network water loss hotspots and the size of the leaks and on the other hand, the straightforwardness and reliability offered by the availability of an accurate hydraulic model to assess those close network areas around the estimated hotspots. The application of the resulting method in a DMA of the Barcelona water distribution network is provided and discussed. The obtained results show that leakage detection and localization under multiple-leak scenarios may be performed efficiently following an easy procedure.

A robust poverty profile for Brazil using multiple data sources

This paper presents a poverty profile for Brazil, based on three different sources of household data for 1996. We use PPV consumption data to estimate poverty and indigence lines. “Contagem” data is used to allow for an unprecedented refinement of the country’s poverty map. Poverty measures and shares are also presented for a wide range of population subgroups, based on the PNAD 1996, with new adjustments for imputed rents and spatial differences in cost of living. Robustness of the profile is verified with respect to different poverty lines, spatial price deflators, and equivalence scales. Overall poverty incidence ranges from 23% with respect to an indigence line to 45% with respect to a more generous poverty line. More importantly, however, poverty is found to vary significantly across regions and city sizes, with rural areas, small and medium towns and the metropolitan peripheries of the North and Northeast regions being poorest.

Unemployment insurance an analysis of optimal mechanisms under aggregate shocks

The purpose of this work is to provide a brief overview of the literature on the optimal design of unemployment insurance systems by analyzing some of the most influential articles published over the last three decades on the subject and extend the main results to a multiple aggregate shocks environment. The properties of optimal contracts are discussed in light of the key assumptions commonly made in theoretical publications on the area. Moreover, the implications of relaxing each of these hypothesis is reckoned as well. The analysis of models of only one unemployment spell starts from the seminal work of Shavell and Weiss (1979). In a simple and common setting, unemployment benefits policies, wage taxes and search effort assignments are covered. Further, the idea that the UI distortion of the relative price of leisure and consumption is the only explanation for the marginal incentives to search for a job is discussed, putting into question the reduction in labor supply caused by social insurance, usually interpreted as solely an evidence of a dynamic moral hazard caused by a substitution effect. In addition, the paper presents one characterization of optimal unemployment insurance contracts in environments in which workers experience multiple unemployment spells. Finally, an extension to multiple aggregate shocks environment is considered. The paper ends with a numerical analysis of the implications of i.i.d. shocks to the optimal unemployment insurance mechanism.

Actinobacillus actinomycetemcomitans lipopolysaccharide induces interleukin-6 expression through multiple mitogen-activated protein kinase pathways in periodontal ligament fibroblasts

Actinobacillus actinomycetemcomitans plays a major role in the pathogenesis of aggressive periodontitis. Lipopolysaccharide (LPS) derived from A. actinomycetemcomitans is a key factor in inflammatory cytokine generation within periodontal tissues. In this study, we identify major mitogen-activated protein kinase (MAPK) signaling pathways induced by A. actinomycetemcomitans LPS, Escherichia coli LPS and interleukin-1 beta (IL-1 beta) in a murine periodontal ligament (mPDL) fibroblast cell line. Immunoblot analysis was used to assess the phosphorylated forms of p38, extracellular-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) MAPK following stimulation with A. actinomycetemcomitans LPS, E. coli LPS and IL-1 beta. IL-6 mRNA induction was detected via reverse transcription-polymerase chain reaction, while protein levels were quantified via enzyme-linked immunosorbent assays (ELISA). We utilized biochemical inhibitors of p38, ERK and JNK MAPK to identify the MAPK signaling pathways needed for IL-6 expression. Additional use of stable mPDL cell lines containing dominant negative mutant constructs of MAPK kinase-3 and -6 (MKK-3/6) and p38 null mutant mouse embryonic fibroblast (MEF) cells were used to substantiate the biochemical inhibitor data. Blocking p38 MAPK with SB203580 reduced the induction of IL-6 mRNA by A. actinomycetemcomitans LPS, E. coli LPS and IL-1 beta by > 70%, > 95% and similar to 60%, respectively. IL-6 ELISA indicated that blocking p38 MAPK reduced the IL-6 protein levels induced by A. actinomycetemcomitans LPS, E. coli LPS and IL-1 beta by similar to 60%, similar to 50% and similar to 70%, respectively. All MAPK inhibitors significantly reduced the IL-6 protein levels induced by A. actinomycetemcomitans LPS, E. coli LPS and IL-1 beta whereas only p38 inhibitors consistently reduced the A. actinomycetemcomitans LPS, E. coli LPS and IL-1 beta induction of IL-6 mRNA steady-state levels. The contribution of p38 MAPK LPS-induced IL-6 expression was confirmed using MKK-3/6 dominant negative stable mPDL cell lines. Wild-type and p38 alpha(-/-) MEF cells provided additional evidence to support the role of p38 alpha MAPK in A. actinomycetemcomitans LPS-stimulated IL-6. Our results indicate that induction of IL-6 by E. coli LPS, IL-1 beta and A. actinomycetemcomitans LPS requires signaling through MKK-3-p38 alpha ERK, JNK and p38 MAPK in mPDL cells.

Effects of light-curing time on the cytotoxicity of a restorative resin composite applied to an immortalized odontoblast-cell line

This in vitro study evaluated the cytotoxic effects of a restorative resin composite applied to an immortalized odontoblast-cell line (MDPC-23). Seventy-two round resin discs (2-mm thick and 4 mm in diameter) were light-cured for 20 or 40 seconds and rinsed, or not, with PBS and culture medium. The resin discs were divided into four experimental groups: Group 1: Z-100/20 seconds; Group 2: Z-100/20 seconds/rinsed; Group 3: Z100/40 seconds; Group 4: Z-100/40 seconds/rinsed. Circular filter paper was used as a control material (Group 5). The round resin discs and filter papers were placed in the bottom of wells of four 24-well dishes (18 wells for each experimental and control group). MDPC-23 cells (30,000 cells/cm(2)) were plated in the wells and allowed to incubate for 72 hours. The zone of inhibition around the resin discs was measured under inverted light microscopy; the MTT assay was carried out for mitochondrial respiration and cell morphology was measured under SEM. The scores obtained from inhibition zone and MTT assay were analyzed with the Kruskal-Wallis followed by Dunnett tests. In Groups 1, 2, 3 and 4, the thickness of the inhibition zone was 1,593 +/- 12.82 mum, 403 +/- 15.49 mum, 1,516 +/- 9.81 mum and 313 +/- 13.56 mum, respectively. There was statistically significant difference among the experimental and control groups at the 0.05 level of significance. The MTT assay demonstrated that the resin discs of the experimental groups 1, 2, 3 and 4 reduced the cell metabolism by 83%, 40.1%, 75.5% and 24.5%. Only between the Groups 2 and 4 was there no statistically significant difference for mitochondrial respiration. Close to the resin discs, the MDPC-23 cells exhibited rounded shapes, with only a few cellular processes keeping the cells attached to the substrate or, even disruption of plasma membrane. Adjacent to the inhibition zone, the cultured cells exhibited multiple fine cellular processes on the cytoplasmic membrane organized in epithelioid nodules, similar to the morphology observed to the control group. Based on the results, the authors may conclude that the Z-100 resin composite light cured for 20 seconds was more cytopathic to MDPC-23 cells than Z-100 light cured for 40 seconds. The cytotoxic effects of the resin discs decreased after rinsing them with PBS and culture medium. This was confirmed by MTT assay and upon evaluation of the inhibition zone, which was narrower following rinsing of the resin discs.

Magneto-optical studies of the correlation between interface microroughness parameters and the photoluminescence line shape in GaAs/Ga0.7Al0.3As quantum wells

In this work we analyze the relation between the interface microroughness and the full width at half maximum (FWHM) of the photoluminescence (PL) spectra for a GaAs/Ga0.7Al0.3As multiple quantum well (QW) system. We show that, in spite of the complex correlation between the microscopic interface-defects parameters and the QW optical properties, the Singh and Bajaj model [Appl. Phys. Lett. 44, 805 (1984)] provides a good quantitative description of the excitonic PL-FWHM. ©1999 The American Physical Society.

Model to increase the lateral line length of drip irrigation systems

Non-pressure compensating drip hose is widely used for irrigation of vegetables and orchards. One limitation is that the lateral line length must be short to maintain uniformity due to head loss and slope. Any procedure to increase the length is appropriate because it represents low initial cost of the irrigation system. The hypothesis of this research is that it is possible to increase the lateral line length combining two points: using a larger spacing between emitters at the beginning of the lateral line and a smaller one after a certain distance; and allowing a higher pressure variation along the lateral line under an acceptable value of distribution uniformity. To evaluate this hypothesis, a nonlinear programming model (NLP) was developed. The input data are: diameter, roughness coefficient, pressure variation, emitter operational pressure, relationship between emitter discharge and pressure. The output data are: line length, discharge and length of the each section with different spacing between drippers, total discharge in the lateral line, multiple outlet adjustment coefficient, head losses, localized head loss, pressure variation, number of emitters, spacing between emitters, discharge in each emitter, and discharge per linear meter. The mathematical model developed was compared with the lateral line length obtained with the algebraic solution generated by the Darcy-Weisbach equation. The NLP model showed the best results since it generated the greater gain in the lateral line length, maintaining the uniformity and the flow variation under acceptable standards. It had also the lower flow variation, so its adoption is feasible and recommended.

Conventional cytogenetic characterization of a new cell line, ACP01, established from a primary human gastric tumor

Gastric cancer is the second most frequent type of neoplasia and also the second most important cause of death in the world. Virtually all the established cell lines of gastric neoplasia were developed in Asian countries, and western countries have contributed very little to this area. In the present study we describe the establishment of the cell line ACP01 and characterize it cytogenetically by means of in vitro immortalization. Cells were transformed from an intestinal-type gastric adenocarcinoma (T4N2M0) originating from a 48-year-old male patient.This is the first gastric denocarcinoma cell line established in Brazil. The most powerful application of the cell line ACP01 is in the assessment of cytotoxicity. Solid tumor cell lines from different origins have been treated with several conventional and investigational anticancer drugs. The ACP01 cell line is triploid, grows as a single, non-organized layer, similar to fibroblasts, with focus formation,heterogeneous division, and a cell cycle of approximately 40 h. Chromosome 8 trisomy, present in 60% of the cells, was the most frequent cytogenetic alteration. These data lead us to propose a multifactorial triggering of gastric cancer which evolves over multiple stages involving progressive genetic changes and clonal expansion.

Levante popular da juventude brasileira: saímos do Facebook (on line)

The paper studies the mobilization occurred in June 2013 in Brazil, initially under the banner of the Movement Free Pass, but without the existence of a lead, but multiple voices that alternate in search of social and economic change. The object of study is the communication made through social networks and their realization, or realization, the streets of major cities. The rallies demonstrate the power of communications media and a new phenomenon of talk, the use of social networks, now as uniting factor and not just a showcase of everyday life. The internet has become a new means of communication easy and free access, in addition to its fast dissipation data. Thus, the youth was used such technology to an uprising in the pursuit of social improvement of the cities where marches happened. Such a move still without an academic and social needs to be discussed so that, in addition to understood, can expand contributions to society, helping it in its claims. Was chosen as the site for the #causabrasil study and understanding of issues in which the public expresses dissatisfaction. The site performs an analysis with the combination of hastags a list of pre-registered and a list of terms used by different users of Facebook, Twitter, Instagram, Youtube and Google, through monitoring tool Seekr, and an infographic presents the main political demands of the population.