Simulation of a fully coupled 3D glacial isostatic adjustment – ice sheet model for the Antarctic ice sheet over a glacial cycle

Glacial isostatic adjustment (GIA) has a stabilizing effect on the evolution of the Antarctic ice sheet by reducing the grounding line migration following ice melt. The timescale and strength of this feedback depends on the spatially varying viscosity of the Earth's mantle. Most studies assume a relatively long and laterally homogenous response time of the bedrock. However, the mantle viscosity is spatially variable, with a high mantle viscosity beneath East Antarctica and a low mantle viscosity beneath West Antarctica. For this study, we have developed a new method to couple a 3D GIA model and an ice sheet model to study the interaction between the solid Earth and the Antarctic ice sheet during the last glacial cycle. With this method, the ice sheet model and GIA model exchange ice thickness and bedrock elevation during a fully coupled transient experiment. The feedback effect is taken into account with a high temporal resolution, where the coupling time steps between the ice sheet and GIA model are 5000 years over the glaciation phase and vary between 500 and 1000 years over the deglaciation phase of the last glacial cycle. During each coupling time step, the bedrock elevation is adjusted at every ice sheet model time step, and the deformation is computed for a linearly changing ice load. We applied the method using the ice sheet model ANICE and a 3D GIA finite element model. We used results from a regional seismic model for Antarctica embedded in the global seismic model SMEAN2 to determine the patterns in the mantle viscosity. The results of simulations over the last glacial cycle show that differences in mantle viscosity of an order of magnitude can lead to differences in the grounding line position up to 700 km and to differences in ice thickness of the order of 2 km for the present day near the Ross Embayment. These results underline and quantify the importance of including local GIA feedback effects in ice sheet models when simulating the Antarctic ice sheet evolution over the last glacial cycle.</p

A global transcriptional regulatory role for c-Myc in Burkitt's lymphoma cells

Overexpression of c-Myc is one of the most common alterations in human cancers, yet it is not clear how this transcription factor acts to promote malignant transformation. To understand the molecular targets of c-Myc function, we have used an unbiased genome-wide location-analysis approach to examine the genomic binding sites of c-Myc in Burkitt's lymphoma cells. We find that c-Myc together with its heterodimeric partner, Max, occupy >15% of gene promoters tested in these cancer cells. The DNA binding of c-Myc and Max correlates extensively with gene expression throughout the genome, a hallmark attribute of general transcription factors. The c-Myc/Max heterodimer complexes also colocalize with transcription factor IID in these cells, further supporting a general role for overexpressed c-Myc in global gene regulation. In addition, transcription of a majority of c-Myc target genes exhibits changes correlated with levels of c-myc mRNA in a diverse set of tissues and cell lines, supporting the conclusion that c-Myc regulates them. Taken together, these results suggest a general role for overexpressed c-Myc in global transcriptional regulation in some cancer cells and point toward molecular mechanisms for c-Myc function in malignant transformation

Sea-level rise: from global perspectives to local services

Coastal areas are highly diverse, ecologically rich, regions of key socio-economic activity, and are particularly sensitive to sea-level change. Over most of the 20th century, global mean sea level has risen mainly due to warming and subsequent expansion of the upper ocean layers as well as the melting of glaciers and ice caps. Over the last three decades, increased mass loss of the Greenland and Antarctic ice sheets has also started to contribute significantly to contemporary sea-level rise. The future mass loss of the two ice sheets, which combined represent a sea-level rise potential of ∼65 m, constitutes the main source of uncertainty in long-term (centennial to millennial) sea-level rise projections. Improved knowledge of the magnitude and rate of future sea-level change is therefore of utmost importance. Moreover, sea level does not change uniformly across the globe and can differ greatly at both regional and local scales. The most appropriate and feasible sea level mitigation and adaptation measures in coastal regions strongly depend on local land use and associated risk aversion. Here, we advocate that addressing the problem of future sea-level rise and its impacts requires (i) bringing together a transdisciplinary scientific community, from climate and cryospheric scientists to coastal impact specialists, and (ii) interacting closely and iteratively with users and local stakeholders to co-design and co-build coastal climate services, including addressing the high-end risks

Recommendations for the nutrition management of phenylalanine hydroxylase deficiency

The effectiveness of a phenylalanine-restricted diet to improve the outcome of individuals with phenylalanine hydroxylase deficiency (OMIM no. 261600) has been recognized since the first patients were treated 60 years ago. However, the treatment regime is complex, costly, and often difficult to maintain for the long term. Improvements and refinements in the diet for phenylalanine hydroxylase deficiency have been made over the years, and adjunctive therapies have proven to be successful for certain patients. Yet evidence-based guidelines for managing phenylalanine hydroxylase deficiency, optimizing outcomes, and addressing all available therapies are lacking. Thus, recommendations for nutrition management were developed using evidence from peer-reviewed publications, gray literature, and consensus surveys. The areas investigated included choice of appropriate medical foods, integration of adjunctive therapies, treatment during pregnancy, monitoring of nutritional and clinical markers, prevention of nutrient deficiencies, providing of access to care, and compliance strategies. This process has not only provided assessment and refinement of current nutrition management and monitoring recommendations but also charted a direction for future studies. This document serves as a companion to the concurrently published American College of Medical Genetics and Genomics guideline for the medical treatment of phenylalanine hydroxylase deficiency

Treatment of cyclic vomiting syndrome with co-enzyme Q10 and amitriptyline, a retrospective study

<p>Abstract</p> <p>Background</p> <p>Cyclic vomiting syndrome (CVS), which is defined by recurrent stereotypical episodes of nausea and vomiting, is a relatively-common disabling condition that is associated with migraine headache and mitochondrial dysfunction. Co-enzyme Q10 (Co-Q) is a nutritional supplement that has demonstrated efficacy in pediatric and adult migraine. It is increasingly used in CVS despite the complete lack of studies to demonstrate its value in treatment</p> <p>Methods</p> <p>Using an Internet-based survey filled out by subjects with CVS or their parents, the efficacy, tolerability and subject satisfaction in CVS prophylaxis were queried. Subjects taking Co-Q (22 subjects) were compared against those taking amitriptyline (162 subjects), which is the general standard-of-care.</p> <p>Results</p> <p>Subjects/parents reported similar levels of efficacy for a variety of episode parameters (frequency, duration, number of emesis, nausea severity). There was a 50% reduction in at least one of those four parameters in 72% of subjects treated with amitriptyline and 68% of subjects treated Co-Q. However, while no side effects were reported on Co-Q, 50% of subjects on amitriptyline reported side effects (P = 5 × 10^-7), resulting in 21% discontinuing treatment (P = 0.007). Subjects/parents considered the benefits to outweigh the risks of treatment in 47% of cases on amitriptyline and 77% of cases on Co-Q (P = 0.008).</p> <p>Conclusion</p> <p>Our data suggest that the natural food supplement Co-Q is potentially efficacious and tolerable in the treatment of CVS, and should be considered as an option in CVS prophylaxis. Our data would likely be helpful in the design of a double-blind clinical trial.</p

Sea-level rise: From global perspectives to local services

Coastal areas are highly diverse, ecologically rich, regions of key socio-economic activity, and are particularly sensitive to sea-level change. Over most of the 20th century, global mean sea level has risen mainly due to warming and subsequent expansion of the upper ocean layers as well as the melting of glaciers and ice caps. Over the last three decades, increased mass loss of the Greenland and Antarctic ice sheets has also started to contribute significantly to contemporary sea-level rise. The future mass loss of the two ice sheets, which combined represent a sea-level rise potential of ∼65 m, constitutes the main source of uncertainty in long-term (centennial to millennial) sea-level rise projections. Improved knowledge of the magnitude and rate of future sea-level change is therefore of utmost importance. Moreover, sea level does not change uniformly across the globe and can differ greatly at both regional and local scales. The most appropriate and feasible sea level mitigation and adaptation measures in coastal regions strongly depend on local land use and associated risk aversion. Here, we advocate that addressing the problem of future sea-level rise and its impacts requires (i) bringing together a transdisciplinary scientific community, from climate and cryospheric scientists to coastal impact specialists, and (ii) interacting closely and iteratively with users and local stakeholders to co-design and co-build coastal climate services, including addressing the high-end risks

Revista de educación

Se desarrolla el Proyecto de Innovación de Ámsterdam (IPA), llevado a cabo en 1971 con el objeto de disminuir los problemas que los hijos de los trabajadores experimentan en la enseñanza, y aumentar sus posibilidades de desarrollo. Su duración fue de siete años y en él participaron: juntas escolares, personal docente, alumnos y padres de escuelas de primaria y párvulos de barrios de trabajadores, el Centro de Asesoramiento para la Enseñanza en Ámsterdam y el Instituto de Investigación para la Psicología Aplicada. El IPA ofrece soluciones orientadas a cambios sociales y escolares. Especialmente se tratan los aspectos pedagógicos, dejando al margen las políticas a nivel urbano y nacional. Se desarrollan los medios, procedimientos y estructuras, utilizando las normas de investigación activa, con el fin de disminuir los problemas educativos de los hijos de los trabajadores.Ministerio Educación CIDEBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín, 5 - 3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]

Educational innovation project Amsterdam 1971-1978

The Innovation Project Amsterdam ( IPA ) was a large scale educational project. The longitudinal project, which lasted from 1971 until 1978, was realised as a cooperation between Amsterdam primary schools, the Advice and Guidance Centre for Education in Amsterdam ( ABC ) and the Research Institute for Applied Psychology of the University of Amsterdam. It's aim was to improve the educational facilities for working-class children in the old districts of Amsterdam, by establishing - among other things - close relationships between school, family and neighbourhood. Based on then popular principles of action-research, the research staff of the project was strongly involved with the actual changes in the field. The project started with some 15 schools and covered some 40 during it's existence. The project yielded many hundreds of raw data-files, some on punched cards and some on magnetic tape. Most of these files contained the results of educational tests and were poorly documented when transferred to the Steinmetz archive. The amount of material and the state it was in, left the archive no other choice than to "keep as is", which in turn has led to serious losses over time, due to deterioration of tapes and cards