Autophagy in dental tissues: a double-edged sword

Biotechnology and Biological Sciences Research Council [BB/L02392X/1]SCI(E)PubMedEDITORIAL [email protected]

Optimisation and assessment of theoretical impurity line power coefficients relevant to ITER and DEMO

Total radiated line power coefficients for ions of medium to heavy weight elements, called PLT coefficients in the Atomic Data and analysis Structure (ADAS), have been improved by algorithmically optimising the selection of configuration sets that underpin the calculation to include the most important radiating transitions driven by both the ground and metastable configurations and to establish and limit the error of truncation. The optimised calculations typically differ from Pütterich by 20 − 30% with truncation error ≲5%. Further appraisal of error due to atomic level bundling, atomic structure and collision strength calculation methods has been carried out. It is shown that bundling to configurations is accurate to ≲10% for all ions except those with closed-shell ground configurations which give errors up to a factor 2−3. For near neutral, closed-shell ions, plane-wave Born collision strength calculations, which omit spin-change, give substantial error in comparison with distorted-wave calculations of PLT. For highly charged ions, spin-system breakdown reduces the error in the PLT markedly, typically ≲10%. The error introduced by the atomic structure codes used here, autostructure and the cowan code, is probably limited to ≲30%

Do borrão às aguadas: os engenheiros militares e a representação da Capitania de São Paulo

A análise do papel dos engenheiros militares perpassa as discussões sobre regiões específicas, mesmo quando eles, aparentemente, estão ausentes delas. Sua presença ou ausência sempre foi sinônimo de interesse e de projeto colonizador mais ou menos dirigido. Este ensaio tem como objeto de estudo a cartografia dos engenheiros militares atuantes na Capitania de São Paulo, território comumente visto como economicamente periférico e mais autônomo face aos desígnios da Coroa portuguesa. Com foco no corpus cartográfico de alguns profissionais que aqui atuaram, trata indiretamente da multifacetada atuação desses engenheiros, bem como do processo de feitura das cartas geográficas, corográficas e topográficas, do borrão às aguadas. Investigar a cartografia de alguns desses profissionais permite não apenas explorar a riqueza de suas biografias, como, também, acompanhar o processo de produção técnica dos mapas e os desígnios políticos envolvidos no devassamento e representação das terras descobertas no Novo Mundo.Analyzing the role of military engineers means venturing into discussions about specific regions, even those from which they are apparently absent. Their presence or absence has always been synonymous with interest and a more or less directed colonization project. This essay examines the maps produced by the military engineers working in the Captaincy of São Paulo, a territory often looked upon as one of little economic import and a rather autonomous area in light of the plans of the Portuguese Crown. By focusing on the cartographic corpus bequeathed by certain professionals serving in this region, we deal indirectly with the multifaceted role of these engineers as well as with the process of making geographic, chorographic and topographic charts - all the way from the sketch to watercolored maps. Perusing the charts constructed by some of these professionals enabled us not only to delve into the rich details of their biographies but also to observe the technical mapmaking process and to unravel the political designs behind the exploration and representation of the lands discovered in the New World

Overview of progress in European medium sized tokamaks towards an integrated plasma-edge/wall solution

Integrating the plasma core performance with an edge and scrape-off layer (SOL) that leads to tolerable heat and particle loads on the wall is a major challenge. The new European medium size tokamak task force (EU-MST) coordinates research on ASDEX Upgrade (AUG), MAST and TCV. This multi-machine approach within EU-MST, covering a wide parameter range, is instrumental to progress in the field, as ITER and DEMO core/pedestal and SOL parameters are not achievable simultaneously in present day devices. A two prong approach is adopted. On the one hand, scenarios with tolerable transient heat and particle loads, including active edge localised mode (ELM) control are developed. On the other hand, divertor solutions including advanced magnetic configurations are studied. Considerable progress has been made on both approaches, in particular in the fields of: ELM control with resonant magnetic perturbations (RMP), small ELM regimes, detachment onset and control, as well as filamentary scrape-off-layer transport. For example full ELM suppression has now been achieved on AUG at low collisionality with n  =  2 RMP maintaining good confinement HH(98,y2)≈0.95. Advances have been made with respect to detachment onset and control. Studies in advanced divertor configurations (Snowflake, Super-X and X-point target divertor) shed new light on SOL physics. Cross field filamentary transport has been characterised in a wide parameter regime on AUG, MAST and TCV progressing the theoretical and experimental understanding crucial for predicting first wall loads in ITER and DEMO. Conditions in the SOL also play a crucial role for ELM stability and access to small ELM regimes.Integrating the plasma core performance with an edge and scrape-off layer (SOL) that leads to tolerable heat and particle loads on the wall is a major challenge. The new European medium size tokamak task force (EU-MST) coordinates research on ASDEX Upgrade (AUG), MAST and TCV. This multi-machine approach within EU-MST, covering a wide parameter range, is instrumental to progress in the field, as ITER and DEMO core/pedestal and SOL parameters are not achievable simultaneously in present day devices. A two prong approach is adopted. On the one hand, scenarios with tolerable transient heat and particle loads, including active edge localised mode (ELM) control are developed. On the other hand, divertor solutions including advanced magnetic configurations are studied. Considerable progress has been made on both approaches, in particular in the fields of: ELM control with resonant magnetic perturbations (RMP), small ELM regimes, detachment onset and control, as well as filamentary scrape-off-layer transport. For example full ELM suppression has now been achieved on AUG at low collisionality with n = 2 RMP maintaining good confinement H-H(98,H-y2) approximate to 0.95. Advances have been made with respect to detachment onset and control. Studies in advanced divertor configurations (Snowflake, Super-X and X-point target divertor) shed new light on SOL physics. Cross field filamentary transport has been characterised in a wide parameter regime on AUG, MAST and TCV progressing the theoretical and experimental understanding crucial for predicting first wall loads in ITER and DEMO. Conditions in the SOL also play a crucial role for ELM stability and access to small ELM regimes.Peer reviewe

Hepatocellular adenoma: what is new in 2008

Patients (85%) with hepatocellular adenoma (HCA) are women taking oral contraceptives. They can be divided into four subgroups according to their genotype/phenotype features. (1) Hepatocyte nuclear factor 1α (HNF1α) biallelic somatic mutations are observed in 35% of the HCA cases. It occurs in almost all cases in women. HNF1α-mutated HCA are most of the time, highly steatotic, with a lack of expression of liver fatty acid binding protein (LFABP) in immunohistochemistry analyses. Adenomatosis is frequently detected in this context. An HNF1α germline mutation is observed in less than 5% of HCA cases and can be associated with MODY 3 diabetes. (2) An activating β-catenin mutation was found in 10% of HCA. These β-catenin activated HCAs are observed in men and women, and specific risk factors, such as male hormone administration or glycogenosis, are associated with their development. Immunohistochemistry studies show that these HCAs overexpress β-catenin (nuclear and cytoplasmic) and glutamine synthetase. This group of tumours has a higher risk of malignant transformation into hepatocellular carcinoma. (3) Inflammatory HCAs are observed in 40% of the cases, and they are most frequent in women but are also found in men. Lesions are characterised by inflammatory infiltrates, dystrophic arteries, sinusoidal dilatation and ductular reaction. They express serum amyloid A and C-reactive protein. In this group, GGT is frequently elevated, with a biological inflammatory syndrome present. Also, there are more overweight patients in this group. An additional 10% of inflammatory HCAs express β-catenin, and are also at risk of malignant transformation. (4) Currently, less than 10% of HCAs are unclassified. It is hoped that in the near future it will be possible with clinical, biological and imaging data to predict in which of the 2 major groups (HNF1α-mutated HCA and inflammatory HCA) the patient belongs and to propose better guidelines in terms of surveillance and treatment

Decifrando mapas:sobre o conceito de "território" e suas vinculações com a cartografia

This essay studies the cartographic documentation left by military engineers in Portugal, during the 18th Century. The technical dimension of map making is analysed, focusing on the instruments and the methods employed both in field surveys and in subsequent graphic representations. From the point of view of Material Culture, maps are understood as cultural artefacts, therefore historical artefacts; in this sense, the particularities of cartographic language reveal the world conceptions particular to each period. This article proposes a methodology of morphological analysis of the cartographic language, deconstructing the several strata in the organisation of this kind of visual representation. In order to do so, a vast array of heterogeneous correlate documents is mobilised, such as practical geometry, drawing and architecture treatises, contemporary to the period studied.O ensaio versa sobre a documentação cartográfica legada pelos engenheiros militares, em Portugal, no século XVIII. Analisa a dimensão técnica da produção de mapas, focalizando os instrumentos e os métodos empregados nos levantamentos de campo e no desenho de gabinete. Do ponto de vista da cultura material, os mapas são interpretados como artefatos culturais e, portanto, históricos; dessa forma, as particularidades da linguagem cartográfica revelam as concepções de mundo, o estado do conhecimento científico, as convenções e os códigos de representação próprios de cada período. Propõe uma metodologia de análise morfológica da linguagem cartográfica, desconstruindo os diversos estratos da tessitura desse tipo de representação visual. Para tanto, mobiliza um vasto campo de documentos correlatos, heterogêneos, tais como tratados de geometria prática, desenho e arquitetura, contemporâneos ao objeto de estudo

Overview of progress in European medium sized tokamaks towards an integrated plasma-edge/wall solution

Integrating the plasma core performance with an edge and scrape-off layer (SOL) that leads to tolerable heat and particle loads on the wall is a major challenge. The new European medium size tokamak task force (EU-MST) coordinates research on ASDEX Upgrade (AUG), MAST and TCV. This multi-machine approach within EU-MST, covering a wide parameter range, is instrumental to progress in the field, as ITER and DEMO core/pedestal and SOL parameters are not achievable simultaneously in present day devices. A two prong approach is adopted. On the one hand, scenarios with tolerable transient heat and particle loads, including active edge localised mode (ELM) control are developed. On the other hand, divertor solutions including advanced magnetic configurations are studied. Considerable progress has been made on both approaches, in particular in the fields of: ELM control with resonant magnetic perturbations (RMP), small ELM regimes, detachment onset and control, as well as filamentary scrape-off-layer transport. For example full ELM suppression has now been achieved on AUG at low collisionality with n  =  2 RMP maintaining good confinement ${{H}_{\text{H}\left(98,\text{y}2\right)}}\approx 0.95$ . Advances have been made with respect to detachment onset and control. Studies in advanced divertor configurations (Snowflake, Super-X and X-point target divertor) shed new light on SOL physics. Cross field filamentary transport has been characterised in a wide parameter regime on AUG, MAST and TCV progressing the theoretical and experimental understanding crucial for predicting first wall loads in ITER and DEMO. Conditions in the SOL also play a crucial role for ELM stability and access to small ELM regimes

Real-time plasma state monitoring and supervisory control on TCV

In ITER and DEMO, various control objectives related to plasma control must be simultaneously achieved by the plasma control system (PCS), in both normal operation as well as off-normal conditions. The PCS must act on off-normal events and deviations from the target scenario, since certain sequences (chains) of events can precede disruptions. It is important that these decisions are made while maintaining a coherent prioritization between the real-time control tasks to ensure high-performance operation. In this paper, a generic architecture for task-based integrated plasma control is proposed. The architecture is characterized by the separation of state estimation, event detection, decisions and task execution among different algorithms, with standardized signal interfaces. Central to the architecture are a plasma state monitor and supervisory controller. In the plasma state monitor, discrete events in the continuous-valued plasma state are modeled using finite state machines. This provides a high-level representation of the plasma state. The supervisory controller coordinates the execution of multiple plasma control tasks by assigning task priorities, based on the finite states of the plasma and the pulse schedule. These algorithms were implemented on the TCV digital control system and integrated with actuator resource management and existing state estimation algorithms and controllers. The plasma state monitor on TCV can track a multitude of plasma events, related to plasma current, rotating and locked neoclassical tearing modes, and position displacements. In TCV experiments on simultaneous control of plasma pressure, safety factor profile and NTMs using electron cyclotron heating (ECH) and current drive (ECCD), the supervisory controller assigns priorities to the relevant control tasks. The tasks are then executed by feedback controllers and actuator allocation management. This work forms a significant step forward in the ongoing integration of control capabilities in experiments on TCV, in support of tokamak reactor operation

HNF1α inhibition triggers epithelial-mesenchymal transition in human liver cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Hepatocyte Nuclear Factor 1α (HNF1α) is an atypical homeodomain-containing transcription factor that transactivates liver-specific genes including albumin, α-1-antitrypsin and α- and β-fibrinogen. Biallelic inactivating mutations of <it>HNF1A </it>have been frequently identified in hepatocellular adenomas (HCA), rare benign liver tumors usually developed in women under oral contraceptives, and in rare cases of hepatocellular carcinomas developed in non-cirrhotic liver. HNF1α-mutated HCA (H-HCA) are characterized by a marked steatosis and show activation of glycolysis, lipogenesis, translational machinery and mTOR pathway. We studied the consequences of HNF1α silencing in hepatic cell lines, HepG2 and Hep3B and we reproduced most of the deregulations identified in H-HCA.</p> <p>Methods</p> <p>We transfected hepatoma cell lines HepG2 and Hep3B with siRNA targeting HNF1α and obtained a strong inhibition of HNF1α expression. We then looked at the phenotypic changes by microscopy and studied changes in gene expression using qRT-PCR and Western Blot.</p> <p>Results</p> <p>Hepatocytes transfected with HNF1α siRNA underwent severe phenotypic changes with loss of cell-cell contacts and development of migration structures. In HNF1α-inhibited cells, hepatocyte and epithelial markers were diminished and mesenchymal markers were over-expressed. This epithelial-mesenchymal transition (EMT) was related to the up regulation of several EMT transcription factors, in particular <it>SNAIL </it>and <it>SLUG</it>. We also found an overexpression of TGFβ1, an EMT initiator, in both cells transfected with HNF1α siRNA and H-HCA. Moreover, TGFβ1 expression is strongly correlated to HNF1α expression in cell models, suggesting regulation of TGFβ1 expression by HNF1α.</p> <p>Conclusion</p> <p>Our results suggest that HNF1α is not only important for hepatocyte differentiation, but has also a role in the maintenance of epithelial phenotype in hepatocytes.</p