Water Policies: Regions with Open-Pit Lignite Mining (Introduction to the IIASA Study)

There is an apparent need for the analysis of long-term regional water policies to reconcile conflicting interests in regions with open-pit lignite mining. The most important. interest groups in such regions are mining, municipal and industrial water supply, agriculture as well as the "environment". A scientifically sound and practically simple policy-oriented system of methods and computerized procedures has to be developed. To develop such a system is part of the research work in the Regional Water Policies project carried out at the International Institute for Applied Systems Analysis (IIASA) in collaboration with research institutes in the German Democratic Republic, Poland, and in other countries as well. A test area that includes typical water-related elements of mining regions and significant conflicts and interest groups has been chosen. The first stage in the analysis is oriented towards developing a scenario generating system as a tool to choose "good" policies from the regional point of view. Therefore a policy-oriented interactive decision support model system is under development, considering the dynamic, nonlinear and uncertain systems behaviour. It combines a model for multi-criteria analysis in planning periods with a simulation model for monthly systems behaviour. The paper outlines the methodological approach. describes the test region in the GDR, and the submodels for the test region

A superconducting levitation transport model system for dynamical and didactical studies

Superconducting levitation transport systems might become very attractive in the near future due to various reasons. The realisation of contactless systems allows e.g. extended maintenance-free operation with high efficiency since such a system only needs energy for cooling and propulsion. We established a small superconducting levitation transport model system called "SupraTrans Mini" consisting of permanent magnetic rails and a levitated vehicle including four YBCO-bulk samples in a cryostat. The rail system consists of an oval shaped loop (2.90 m x 1.44 m), which was build up from individual linear and curved track modules. Inside the vehicle position variations of the superconductors are possible. By means of velocity, acceleration and temperature measurements different dynamical aspects of our complex levitation system can be investigated. We also show the broad applicability of the experimental setup for didactical studies in physics

A superconducting levitation transport model system for dynamical and didactical studies

Superconducting levitation transport systems might become very attractive in the near future due to various reasons. The realisation of contactless systems allows e.g. extended maintenance-free operation with high efficiency since such a system only needs energy for cooling and propulsion. We established a small superconducting levitation transport model system called "SupraTrans Mini" consisting of permanent magnetic rails and a levitated vehicle including four YBCO-bulk samples in a cryostat. The rail system consists of an oval shaped loop (2.90 m x 1.44 m), which was build up from individual linear and curved track modules. Inside the vehicle position variations of the superconductors are possible. By means of velocity, acceleration and temperature measurements different dynamical aspects of our complex levitation system can be investigated. We also show the broad applicability of the experimental setup for didactical studies in physics

Pancreatite aguda grave em centro de terapia intensiva: análise de 10 anos

OBJECTIVE: To evaluate etiology, complications, treatment, hospital and intensive care unit stay and mortality in all patients hospitalized in the intensive care unit of Hospital de Clínicas de Porto Alegre with acute pancreatitis, from January 1st, 1990 to December 31st, 1999. MATERIALS AND METHODS: We performed a historical cohort study with 57 patients, 37% female and 63% male, with an age average of 48±17 years. Patients were classified in two groups – survivors (n=26, 45.6%) and non-survivors (n=31, 54.4%) – and compared considering hospital and intensive care unit stay, Ranson’s and modified Glasgow’s signs, APACHE II (acute physiology and chronic health evaluation), organ failure, surgery, parenteral nutrition and antibiotics.RESULTS: The most common causes of severe acute pancreatitis were alcohol (37%) and gallstones (31%). Mortality was 54.4 %. Hospital stays were longer for survivors than for non-survivors. Non-survivors presented more organ failures (respiratory, renaland cardiovascular failures) and more Ranson’s and modified Glasgow’s signs than survivors. Other parameters were similar in both groups.CONCLUSIONS: In order to better evaluate the reasons for the high rate of mortality identified in the present group in the studied period it would be necessary to perform a prospective study with stronger control of the interfering factors, including an evaluation of the cases of severe acute pancreatitis that are not admitted in the intensive care unit.OBJETIVO: Avaliar etiologia, complicações, tratamento, tempo de internação – hospitalar e em centro de terapia intensiva – e mortalidade de todos os pacientes internados por pancreatite aguda no centro de tratamento intensivo do Hospital de Clínicas de Porto Alegre, no período de janeiro de 1990 a dezembro de 1999.MATERIAIS E MÉTODOS: Realizamos um estudo de coorte histórico, no qual foram avaliados 57 pacientes, 37% do sexo feminino e 63% do sexo masculino, com média de idade de 48 ± 17 anos. Os pacientes foram divididos em dois grupos – sobreviventes (n=26;45,6%) e não-sobreviventes (n=31;54,4%) –, e foram comparados quanto a tempo de internação, critérios de Ranson e de Glasgow modificados, APACHE II (acute physiology and chronic health evaluation), falências orgânicas, procedimentos cirúrgicos, nutrição parenteral e antibióticos recebidos.RESULTADOS: As etiologias mais freqüentes foram alcoólica (37%) e biliar (31%). A mortalidade foi de 54,4%. Os sobreviventes apresentaram maior tempo de internação que os não-sobreviventes (47 ± 36 dias contra 21 ± 20 dias). Os não-sobreviventes apresentaram maiores taxas de falências orgânicas (respiratória, renal e cardiovascular) e maior número de critérios de Ranson e de Glasgow modificados, quando comparados aos sobreviventes. Os parâmetros restantes foram semelhantes entre os dois grupos.CONCLUSÕES: Para melhor avaliar os motivos da alta taxa de mortalidade identificada neste grupo, neste período, seria necessário um trabalho prospectivo com melhor controle dos fatores interferentes e que incluísse ainda a avaliação dos casos de pancreatite aguda com critérios de gravidade que não são admitidos no centro de tratamento intensivo

The Max b-HLH-LZ Can Transduce into Cells and Inhibit c-Myc Transcriptional Activities

The inhibition of the functions of c-Myc (endogenous and oncogenic) was recently shown to provide a spectacular therapeutic index in cancer mouse models, with complete tumor regression and minimal side-effects in normal tissues. This was achieved by the systemic and conditional expression of omomyc, the cDNA of a designed mutant of the b-HLH-LZ of c-Myc named Omomyc. The overall mode of action of Omomyc consists in the sequestration of Max and the concomitant competition of the Omomyc/Max complex with the endogenous c-Myc/Max heterodimer. This leads to the inhibition of the transactivation of Myc target genes involved in proliferation and metabolism. While this body of work has provided extraordinary insights to guide the future development of new cancer therapies that target c-Myc, Omomyc itself is not a therapeutic agent. In this context, we sought to exploit the use of a b-HLH-LZ to inhibit c-Myc in a cancer cell line in a more direct fashion. We demonstrate that the b-HLH-LZ domain of Max (Max*) behaves as a bona fide protein transduction domain (PTD) that can efficiently transduce across cellular membrane via through endocytosis and translocate to the nucleus. In addition, we show that the treatment of HeLa cells with Max* leads to a reduction of metabolism and proliferation rate. Accordingly, we observe a decrease of the population of HeLa cells in S phase, an accumulation in G1/G0 and the induction of apoptosis. In agreement with these phenotypic changes, we show by q-RT-PCR that the treatment of HeLa cells with Max* leads to the activation of the transcription c-Myc repressed genes as well as the repression of the expression of c-Myc activated genes. In addition to the novel discovery that the Max b-HLH-LZ is a PTD, our findings open up new avenues and strategies for the direct inhibition of c-Myc with b-HLH-LZ analogs

Fructan and hormone connections

Plants rely on “reserve” (stored) carbon (C) for growth and survival when newly synthesized C becomes limited. Besides a classic yet recalcitrant C reserve starch, fructans, a class of sucrose-derived soluble fructosyl-oligosaccharides, represent a major store of C in many temperate plant species including the economically important Asteraceae and Poaceae families (Hendry, 1993). Dicots typically accumulate inulin-type fructans as long-term storage (underground organs) whilst grasses and cereals accumulate fructans as short-term reserves in above-ground parts (Pollock and Cairns, 1991; Van Laere and Van den Ende, 2002). Unlike chloroplast-based water-insoluble starch, fructans are semi-soluble, possess flexible structures (Phelps, 1965; Valluru and Van den Ende, 2008), can be synthesized at low temperatures (Pollock and Cairns, 1991), and are degraded by a single type of fructan hydrolases, fructan exohydrolases (FEHs). Unlike starch that store in plastids, fructans store in vacuoles, which is physically less stressful to the active constituents of, and allows more C synthesis by, the photosynthetic cell, which may be different in dicots where fructans do not typically accumulate in green parts

The Action Mechanism of the Myc Inhibitor Termed Omomyc May Give Clues on How to Target Myc for Cancer Therapy

Recent evidence points to Myc – a multifaceted bHLHZip transcription factor deregulated in the majority of human cancers – as a priority target for therapy. How to target Myc is less clear, given its involvement in a variety of key functions in healthy cells. Here we report on the action mechanism of the Myc interfering molecule termed Omomyc, which demonstrated astounding therapeutic efficacy in transgenic mouse cancer models in vivo. Omomyc action is different from the one that can be obtained by gene knockout or RNA interference, approaches designed to block all functions of a gene product. This molecule – instead – appears to cause an edge-specific perturbation that destroys some protein interactions of the Myc node and keeps others intact, with the result of reshaping the Myc transcriptome. Omomyc selectively targets Myc protein interactions: it binds c- and N-Myc, Max and Miz-1, but does not bind Mad or select HLH proteins. Specifically, it prevents Myc binding to promoter E-boxes and transactivation of target genes while retaining Miz-1 dependent binding to promoters and transrepression. This is accompanied by broad epigenetic changes such as decreased acetylation and increased methylation at H3 lysine 9. In the presence of Omomyc, the Myc interactome is channeled to repression and its activity appears to switch from a pro-oncogenic to a tumor suppressive one. Given the extraordinary therapeutic impact of Omomyc in animal models, these data suggest that successfully targeting Myc for cancer therapy might require a similar twofold action, in order to prevent Myc/Max binding to E-boxes and, at the same time, keep repressing genes that would be repressed by Myc

Co-Localization of the Oncogenic Transcription Factor MYCN and the DNA Methyl Binding Protein MeCP2 at Genomic Sites in Neuroblastoma

MYCN is a transcription factor that is expressed during the development of the neural crest and its dysregulation plays a major role in the pathogenesis of pediatric cancers such as neuroblastoma, medulloblastoma and rhabdomyosarcoma. MeCP2 is a CpG methyl binding protein which has been associated with a number of cancers and developmental disorders, particularly Rett syndrome.Using an integrative global genomics approach involving chromatin immunoprecipitation applied to microarrays, we have determined that MYCN and MeCP2 co-localize to gene promoter regions, as well as inter/intragenic sites, within the neuroblastoma genome (MYCN amplified Kelly cells) at high frequency (70.2% of MYCN sites were also positive for MeCP2). Intriguingly, the frequency of co-localization was significantly less at promoter regions exhibiting substantial hypermethylation (8.7%), as determined by methylated DNA immunoprecipitation (MeDIP) applied to the same microarrays. Co-immunoprecipitation of MYCN using an anti-MeCP2 antibody indicated that a MYCN/MeCP2 interaction occurs at protein level. mRNA expression profiling revealed that the median expression of genes with promoters bound by MYCN was significantly higher than for genes bound by MeCP2, and that genes bound by both proteins had intermediate expression. Pathway analysis was carried out for genes bound by MYCN, MeCP2 or MYCN/MeCP2, revealing higher order functions.Our results indicate that MYCN and MeCP2 protein interact and co-localize to similar genomic sites at very high frequency, and that the patterns of binding of these proteins can be associated with significant differences in transcriptional activity. Although it is not yet known if this interaction contributes to neuroblastoma disease pathogenesis, it is intriguing that the interaction occurs at the promoter regions of several genes important for the development of neuroblastoma, including ALK, AURKA and BDNF