bluuebunny/crossref_metadata_2025 huggingface dataset:
A Psychiatric Clinic within a Geriatric Medical Day Hospital: Descriptive Study
Authors: Agbayewa M. Oluwafemi
Published: December 2010

A survey of the first two years of a psychiatric clinic within a geriatric medical day hospital was undertaken to determine the role of such a clinic. Forty per cent of all day hospital attenders were referred for psychiatric evaluation: at least 80 per cent of these had major psychiatric diagnoses and 20 per cent had other conditions needing psychosocial intervention. Depression and dementia accounted for 62 per cent of all psychiatric referrals. Those who were referred to the psychiatric clinic were quite comparable to the unreferred group in age, sex, marital status, pre-retirement employment and source of referral to the day hospital. The outcomes of intervention at three, six and 12 months were similar in both groups but referred patients stayed longer in the program. It is concluded that such a clinic provides a necessary mental health service where it is needed.
Pain, Anxiety and Analgesics: A Comparative Study of Elderly and Younger Surgical Patients
Authors: Oberle Kathleen , Paul Pauline , Wry Judy , Grace Michael
Published: December 2010

Afin de déterminer si l'expérience postopératoire diffère entre les patients âgés et les patients plus jeunes, 41 patients âgés (65 ans et plus) et 249 patients plus jeunes (moins de 65 ans) participèrent à cette étude. La douleur et l'anxiété furent mesurées les deuxième et troisième jours postopératoires. L'anxiété fut aussi mesurée avant la chirurgie. Le nombre d'analgésiques presents et donnés, ainsi que le délai entre l'administration du dernier analgésique et l'evaluation de la douleur furent notés. Tandis que l'intensité de la douleur ne variait pas significativement, le nombre d'analgésiques donnés était significativement différent, les personnes âgées en recevant moins. Les patients des deux groupes reçurent moins d'analgésiques le troisième jour postopératoire, indépendamment de l'intensité de la douleur. Les sujets des deux groupes choisirent les descripteurs de douleur de façon presque identique. De fortes associations furent observées entre l'anxiété postopératoire et la douleur, alors que l'anxiété préopératoire et la douleur, ne semblèrent pas reliées. II fut conclu que les professionels de la santé traitent la douleur des personnes âgées et plus jeunes de façon similaire, et que les personnes âgées requièrent moins d'analgésiques.
Factors Predicting Medicine Use in Institutionalized and Non-institutionalized Elderly
Authors: McKim William A. , Stones Michael J. , Kozma Albert
Published: December 2010

Pour cette étude, une quantité de données démographiques sur la santé et la personnalité ont été recueillies à partir d'échantillons de persones âgées institutionnalisées et non-institutionnalisées à Terre-Neuve. Puis ces données ont été reportées au nombre de médicaments utilisés. Dans les deux échantillons, l'analyse a démontré que l'usage de médicaments peut être prédit d'abord et avant tout en tenant compte de la gravité de la maladie (Disease Severity), une combinaison du nombre de différentes maladies ou désordres et leur gravité. Ce facteur représente entre 28 et 33 pour cent de la variance. Aucun autre facteur n'a prédit l'usage de médicaments chez les personnes âgées institutionnalisées. Cependant, chez les gens âgés non-institutionnalisés, le baromètre de la santé (Health Rating), c'est-à-dire la façon dont la personne perçoit son état de santé, représente un autre 5 à 7 pour cent de la variance. Il n'y a aucun effet de réciprocité entre la gravité de la maladie (Disease Severity) et le baromètre de la santé (Health Rating), mais ces deux facteurs contribuent indépendamment et de façon complémentaire à prédire l'usage de médicaments. Ces deux facteurs servent également à prédire l'usage total de médicaments et les changements de médications durant une période de 12 à 18 mois. Le sexe et l'âge ne représentent pas des éléments qui aident à prédire l'usage de médicaments lorsqu'on tient compte de la variance causée par la gravité de la maladie (Disease Severity) et le baromètre de la santé (Health Rating).
Le loisir des aîné(e)s résidant en immeubles à logements multiples
Authors: Ouellette Pierre , Vienneau Jean-Guy , Thibault Jacques
Published: December 2010

Cette étude évalue la participation au loisir des résident(e)s de deux immeubles à logements multiples à partir des variables sexe, langue maternelle, éducation, motivation face au loisir et adhérence à un club d'âge d'or. Des analyses de la variance par voie de régression multiple font ressortir cinq catégories de participation significatives: (a) paroissiale, (b) physique, (c) populaire, (d) sociale, et (e) groupe organisé. Les diverses implications de ces résultats sont présentées en fonction de la programmation des loisirs dans les habitations à logements multiples.
ACKNOWLEDGEMENTS
Authors: Mösslang Markus
Published: December 2010

The editorial project ‘British Envoys to Germany’ was initiated with the aim of shedding new light on official British perceptions of German affairs and the states of the German Confederation, and thereby contributing to the historiography of nineteenth-century Anglo-German relations. As hoped at the outset, the diplomatic dispatches proved to be a valuable source, providing insights into many aspects of nineteenth-century history. The quantity and quality of reporting, the informative and often subtle nature of the dispatches, and the freedom of their authors to report on topics other than the political made working on the dispatches a challenging and often very enjoyable task. The selection in this series gives an idea of the richness of the thousands of letters stored at The National Archives, and a visit to Kew is recommended to anyone who wants to ‘delve’ into the nineteenth-century diplomats' world and Anglo-German relations at that time.
Das intrakranielle Meningeom – Therapeutische Möglichkeiten und Grenzen
Authors: Stienen  , Lücke  , Fournier  , Hildebrandt  , Gautschi
Published: December 2010

Meningeome sind häufige intrakranielle Tumoren, die durch die Entartung von Zellen der Arachnoidea mater entstehen. Klinisch manifestieren sie sich in Form von Kopfschmerzen, fokalen oder generalisierten Krampfanfällen oder kompressionsbedingten neurologischen Ausfällen. Über 90% der in der Regel langsam wachsenden Meningeome sind benigne. Bei den meisten symptomatischen Patienten wird die Tumorresektion in kurativer oder zumindest symptomlindernder Intention angestrebt. Bei subtotaler Resektion besteht die Möglichkeit einer adjuvanten Bestrahlung. Eine stereotaktische Radiotherapie kann jedoch auch als Ersttherapie bei Patienten erfolgen, die sich durch hohes Alter oder Tumoren in eloquenten oder chirurgisch schlecht erreichbaren Arealen nicht für eine neuro-chirurgische Operation qualifizieren. Bei nicht resezierbaren Tumoren oder falls alle vorherigen Therapien keinen Erfolg gebracht haben, kann eine Hormon- oder Chemotherapie in Erwägung gezogen werden.
Faiblesse et douleurs musculaires généralisées chez une patiente de 88 ans: avez-vous pensé aux médicaments?
Authors: Arnold  , Lamy  , Hagmann
Published: December 2010

Nous rapportons le cas d'une patiente de 88 ans hospitalisée pour des douleurs et une faiblesse musculaires diffuses. La patiente est traitée par simvastatine au long cours et a reçu une antibiothérapie de clarithromycine pour une bronchite. Nous retenons le diagnostic de rhabdomyolyse induite par statines sur interaction médicamenteuse. L'évolution est favorable à l'arrêt de la statine et réhydratation intraveineuse agressive. Ce cas illustre l'importance de connaître les voies de métabolisme des statines, leurs inhibiteurs et les facteurs de risque entraînants des myopathies.
Submarine landslides along the Malacca Strait‐Mergui Basin shelf margin: Insights from sequence‐stratigraphic analysis
Authors: Lin Yu‐nung Nina , Sieh Kerry , Stock Joann
Published: December 2010

The enormously destructive tsunami of December 2004, caused by sudden motion of the Sunda megathrust beneath the Indian Ocean, raised concerns about tectonically induced tsunami worldwide. Submarine landslides may also trigger dangerous tsunami. However, the potential and repeat time for such events is in most places poorly known due to inadequate exploration of the sea floor and age constraints. The high sediment flux and tectonic subsidence rate of the Malacca Strait‐Mergui Basin shelf margin NE of northernmost Sumatra provide a favorable environment to generate and preserve submarine landslides. From ten seismic reflection profiles acquired in 2006, we identify three sediment packages that exhibit sliding characteristics such as headscarps, distorted beds and debris‐toe structures. We assign lowstand marine isotope stages to the paleo‐shoreline indicators observed in the profiles. We then determine the ages of these submarine landslides as 20–30 ka, 342–364 ka and 435–480 ka by the paleo‐shoreline indicators that bound the top and bottom of the slide bodies. This sequence‐stratigraphic approach shows that these events occurred near times of sea‐level lowstands, which implies that a large amount of direct sediment influx during glacial periods is an essential precondition for basin‐margin submarine landsliding. Spatiotemporal variations of sediment input due to lobe switching or Asian monsoon intensity changes also control basin‐margin instability. Because we are currently at a highstand stage, and sediment flux to the continental margin is relatively small, so the chance of having a repeat submarine landslide and landslide tsunami along this basin‐margin is low.
Characteristics and controlling factors of dispersion in bounded heterogeneous porous media
Authors: Lu Zhiming , Wolfsberg Andrew V. , Dai Zhenxue , Zheng Chunmiao
Published: December 2010

In this study, we present first‐order (in terms of the log conductivity variance) analytical solutions to displacement covariances Xij and macrodispersion coefficients Dij for transport of conservative solutes in two‐dimensional, bounded heterogeneous porous media. These solutions are presented as infinity series and are explicit functions of the statistics of the log hydraulic conductivity. Using numerical examples, the convergence of these solutions in terms of the number of terms in truncated finite summations is first investigated, and the accuracy of these solutions is examined by comparing them with results from Monte Carlo simulations and the semianalytical solutions of Osnes (1998). Through several examples, the general features of time‐dependent Xij and Dij are discussed. Unlike in unbounded domains, the longitudinal macrodispersivity D11 for bounded domains does not approach an asymptotic value at large dimensionless time but instead increases quickly near the downstream constant head boundary. In addition, D11 for bounded domains is always larger than that in unbounded domains, and accordingly, the transverse macrodispersivity D22 in bounded domains is smaller than that in unbounded domains. These differences stem from the lateral no‐flow boundaries in our bounded domain models. We also investigated the effect of domain sizes on Xij and Dij. Our study shows that both Xij and Dij depend not only on the dimensionless size of the domain but also on its aspect ratio. The dependence of Xij and Dij on the particles' initial location has also been investigated at detail. Our results indicate that while this dependence is very small for X11 and D11, the release location has a significant impact on both X22 and D22. Our solutions to both displacement covariances and macrodispersivity are compared against those derived from tracer test data at the Borden site. The comparison shows that our solutions are quite close to observed data, indicating that they may be applicable to predict solute transport at the field scale.
Disentangling uncertainties in distributed hydrological modeling using multiplicative error models and sequential data assimilation
Authors: Salamon Peter , Feyen Luc
Published: December 2010

The quantification of uncertainty in hydrologic modeling is a difficult task, as it arises from a combination of physical measurement errors, errors due to different temporal or spatial scales, and errors in the mathematical description of hydrologic processes. This paper presents an approach to infer during a calibration process the statistical properties of the principal error sources, namely, parameter, precipitation, potential evapotranspiration, and structural model uncertainty, by means of sequential data assimilation (SDA). We perform SDA using a particle filter that combines stochastic universal resampling and kernel smoothing with local shrinkage to improve its performance in comparison to traditional filters. Precipitation, potential evapotranspiration, and structural model uncertainty are incorporated into the calibration process using multiplicative error models. The particle filter is applied to a large‐scale distributed model of the Rhine River to demonstrate its usefulness when characterizing error sources. Diagnostic checks and a synthetic case study show that the posterior distributions can be considered as reliable. The posterior multiplier distributions are used to identify whether a systematic bias exists and to illustrate that uncertainty from those sources can be reduced significantly in comparison to the prior assumptions adopted. Evaluating the predictive uncertainty shows that the overall error in hydrologic models is sufficiently characterized by the different error sources used here. Results indicate, however, that the assumptions taken in the output error model and the simplifications of the multiplicative models do not always hold in practice. Therefore, more sophisticated error models and a better quantification of the discharge measurement error are required to further improve characterization of error sources.
Solar wind influence on Pc4 and Pc5 ULF wave activity in the inner magnetosphere
Authors: Liu W. , Sarris T. E. , Li X. , Ergun R. , Angelopoulos V. , Bonnell J. , Glassmeier K. H.
Published: December 2010

Abundant evidence has shown that ULF wave activity measured at geosynchronous orbit is well correlated with solar wind parameters, such as the solar wind velocity and dynamic pressure. However, many of the past studies were based on magnetic field measurements near the equatorial plane and thus could not unambiguously describe ULF waves, as magnetic field oscillations in the fundamental toroidal mode have a node at the magnetic equator. In this study, we use, for the first time, simultaneous electric and magnetic field measurements by Time History of Events and Macroscale Interactions during Substorms satellites throughout the inner magnetosphere to statistically examine the correlation between ULF wave activity in the inner magnetosphere and the solar wind parameters: velocity, dynamic pressure, and variation in dynamic pressure. On the basis of electric field observations from August 2007 to May 2009, we found that, among the three parameters, the solar wind velocity has the strongest correlation with the daily averaged Pc4 and 5 wave magnitude in 4 ∼ 9 RE. For example, the correlation coefficient of δEr (the square root of the integrated power spectral density of the radial component of the electric field) in the Pc5 frequency range with the solar wind dynamic pressure is 0.35; with the dynamic pressure variation, it is 0.42; and with the solar wind velocity, it is 0.55. However, using only magnetic field observations, the variation in dynamic pressure is best correlated, with correlation coefficients of δBr (the square root of the integrated power spectral density of the radial component of the magnetic field) with the dynamic pressure being 0.59, with the dynamic pressure variation being 0.63 and with the solar wind velocity being 0.53. We suggest that this difference arises because toroidal and poloidal mode pulsations are not detected with the same effectiveness in the electric field and the magnetic field near the magnetic equator and/or because of the presence of broadband ULF noise. We further suggest that either directly measured or flow‐derived electric field measurements are better suited in the study of the relationship between wave power of fundamental field line resonance (i.e., in Pc5 frequency range) and solar wind conditions.
Response of Mount Etna to dynamic stresses from distant earthquakes
Authors: Cannata Andrea , Di Grazia Giuseppe , Montalto Placido , Aliotta Marco , Patanè Domenico , Boschi Enzo
Published: December 2010

Influences of distant earthquakes on volcanic systems by dynamic stress transfer are well documented. We analyzed seismic signals and volcanic activity at Mount Etna during two periods, January 2006 and May 2008, that clearly showed variations coincident with distant earthquakes. In the first period, characterized by mild volcano activity, the effect of the dynamic stress transfer, caused by an earthquake in Greece (M = 6.8), was twofold: (1) banded tremor activity changed its features and almost disappeared; (2) a swarm of volcano‐tectonic (VT) earthquakes took place. The changes of the banded tremor were likely due to variations in rock permeability, caused by fluid flows driven by dynamic strain. The VT earthquake swarm probably developed as a secondary process, promoted by the dynamically triggered activation of magmatic fluids. The second period, May 2008, showed an intense explosive activity. During this interval, the dynamic stress transfer, associated with the arrival of the seismic waves of the Sichuan earthquake (M = 7.9), affected the character of the seismo‐volcanic signals and on the following day triggered an eruption. In particular, we observed changes in volcanic tremor and increases of both occurrence rate and energy of long period events. In this case, we suggest that dynamic stress transfer caused nucleation of new bubbles in volatile‐rich magma bodies with consequent buildup of pressure, highlighted by the increase of long period activity, followed by the occurrence of an eruption. We conclude that stresses from distant earthquakes are capable of modifying the state of the volcano.
Impact of future land use and land cover changes on atmospheric chemistry‐climate interactions
Authors: Ganzeveld Laurens , Bouwman Lex , Stehfest Elke , van Vuuren Detlef P. , Eickhout Bas , Lelieveld Jos
Published: December 2010

To demonstrate potential future consequences of land cover and land use changes beyond those for physical climate and the carbon cycle, we present an analysis of large‐scale impacts of land cover and land use changes on atmospheric chemistry using the chemistry‐climate model EMAC (ECHAM5/MESSy Atmospheric Chemistry) constrained with present‐day and 2050 land cover, land use, and anthropogenic emissions scenarios. Future land use and land cover changes are expected to result in an increase in global annual soil NO emissions by ∼1.2 TgN yr−1 (9%), whereas isoprene emissions decrease by ∼50 TgC yr−1 (−12%). The analysis shows increases in simulated boundary layer ozone mixing ratios up to ∼9 ppbv and more than a doubling in hydroxyl radical concentrations over deforested areas in Africa. Small changes in global atmosphere‐biosphere fluxes of NOx and ozone point to compensating effects. Decreases in soil NO emissions in deforested regions are counteracted by a larger canopy release of NOx caused by reduced foliage uptake. Despite this decrease in foliage uptake, the ozone deposition flux does not decrease since surface layer mixing ratios increase because of a reduced oxidation of isoprene by ozone. Our study indicates that the simulated impact of land cover and land use changes on atmospheric chemistry depends on a consistent representation of emissions, deposition, and canopy interactions and their dependence on meteorological, hydrological, and biological drivers to account for these compensating effects. It results in negligible changes in the atmospheric oxidizing capacity and, consequently, in the lifetime of methane. Conversely, we expect a pronounced increase in oxidizing capacity as a consequence of anthropogenic emission increases.
Gravity wave activity in the Arctic stratosphere and mesosphere during the 2007–2008 and 2008–2009 stratospheric sudden warming events
Authors: Thurairajah Brentha , Collins Richard L. , Harvey V. Lynn , Lieberman Ruth S. , Gerding Michael , Mizutani Kohei , Livingston John M.
Published: December 2010

We report Rayleigh lidar measurements of nightly temperature profiles in the 40–80 km altitude region and 30 min relative density profiles in the 40–50 km altitude region at Chatanika, Alaska (65°N, 147°W) in December, January, February, and March over two winters (2007–2008, 2008–2009). We characterize the gravity wave activity in terms of the measurements of buoyancy period and relative density fluctuations and estimate the gravity wave potential energy density. We compare these measurements with measurements at Kangerlussuaq, Greenland (67°N, 51°W) and Kühlungsborn, Germany (54°N, 12°E). We use satellite and global meteorological data to analyze the synoptic structure of the stratospheric vortex and the Aleutian anticyclone, the planetary wave activity, and the mean winds. Major stratospheric warmings with displacement of the vortex and splitting of the vortex occurred in 2007–2008 and 2008–2009, respectively. We find a positive correlation between the gravity wave activity in the upper stratosphere and the winds in the stratosphere at all three sites. During January and February 2008, we attribute the lower average potential energy density (1.6 J/kg) at Chatanika (relative to 4.7 J/kg at Kangerlussuaq and 2.6 J/kg at Kühlungsborn) to the blocking of gravity waves by the lower winds in the Aleutian anticyclone, while the higher value at Kangerlussuaq (where the winds are similar in strength to those at Kühlungsborn) may reflect stronger sources of gravity waves. During February and March 2009, we attribute the lower average potential energy density (1.1 J/kg) at both Chatanika and Kühlungsborn to the seasonal decrease of the middle atmosphere winds. In general the gravity wave activity is lowest when the wind is weak at the lowest altitudes. We compare the gravity wave activity and winds in these winters at Chatanika with the winter of 2003–2004, when an extreme warming event occurred resulting in an elevated stratopause and major reduction of gravity wave activity. We find that the 2004 warming had a stronger influence on the gravity wave activity.
Characteristics of channel base currents and close magnetic fields in triggered flashes in SHATLE
Authors: Yang Jing , Qie Xiushu , Zhang Guangshu , Zhang Qilin , Feng Guili , Zhao Yang , Jiang Rubin
Published: December 2010

Statistical distributions of channel base currents and close magnetic fields have been investigated by using data measured during Shandong Artificially Triggering Lightning Experiment (SHATLE) from 2005 to 2009. Effects of different factors on close magnetic fields have been examined by using numerical method. Statistical results showed that return stroke peak currents varied from 5.8 kA to 45.7 kA with a geometric mean (GM) of 14.1 kA. The GM of 10–90% risetime, 30–90% risetime, and half‐peak width in current waveforms were consistent with most of the results found in the literature. The magnetic fields at 60 m, based on 32 return strokes, varied from 18 μT to 148 μT with a GM of 52 μT. The peak value of the 10–90% risetime in magnetic field waveform was between 1 and 2 μs with a minimum of 0.4 μs and a maximum of 8.4 μs, covering a relatively wide range compared with other studies. The numerical modeling results showed that for larger return stroke speeds, the magnetic field peaks are larger, half‐peak widths and risetimes are smaller. Effects of distance on time‐variation contribution of induction and radiation components are quite different from that of return stroke speed and current risetime. With increasing the distance or current risetime, the magnetic field peak decreases, but the risetime and half‐peak width increase.
Basalt and olivine dissolution under cold, salty, and acidic conditions: What can we learn about recent aqueous weathering on Mars?
Authors: Hausrath E. M. , Brantley S. L.
Published: December 2010

To test which variables may be important for weathering on Mars, the effects of temperature (22°C, 6°C, and −19°C), high ionic strength, and oxygen concentrations were investigated in batch dissolution experiments containing forsterite, fayalite, and basalt glass. CaCl2‐NaCl‐H2O brine can remain liquid to temperatures of −55°C and thus may be liquid in the cold, dry climate that currently characterizes Mars. To understand weathering under such conditions, dissolution rates were measured in experiments in distilled water with and without CaCl2 and NaCl. As observed by others, dissolution rates increased with temperature, and only fayalite dissolution was significantly affected by the presence or absence of oxygen. Enhanced fayalite dissolution under anoxic conditions suggests that Fe‐rich olivine would dissolve more rapidly than Mg‐rich olivine on Mars. Dissolution in the two most dilute experimental solutions (deionized water and CaCl2‐NaCl‐H2O solution of ionic strength = 0.7 m) were the same within uncertainty, but apparent dissolution rate constants in CaCl2‐NaCl‐H2O brines were significantly slower. Steady silica concentrations are decreased in the brines, consistent with other work, and precipitation rates of silica decrease with decreasing temperatures. These results suggest that enhanced silica precipitation could be an indicator of high ionic strength solutions on Mars. Consistent with these observations, weathering of basalt has been observed to sometimes be accompanied by precipitated layers of silica in cold, dry environments on Earth. If dissolution on Mars occurs or occurred under conditions similar to our experiments, cation leaching would be expected to be accompanied by silica precipitates on weathering surfaces.
Physical controls of near‐surface soil moisture across varying spatial scales in an agricultural landscape during SMEX02
Authors: Joshi Champa , Mohanty Binayak P.
Published: December 2010

Understanding of near‐surface soil moisture variability at different spatial scales and associated dominant physical controls is limited. In the past, soil moisture dynamics studies have been conducted extensively at different spatial scales using both in situ and remote sensing (RS) data in the subhumid Southern Great Plains region, which has mostly pasture and range land cover with rolling topography. Compared to the past efforts, we investigated the space‐time characterization of near‐surface soil moisture and associated physical controls at multiple scales (field, watershed, and region) in a humid hydroclimatic region with different topography and agricultural land cover. Soil moisture data from two different measurement support scales (theta probe based (point scale) and airborne RS derived; footprint scale, 800 m × 800 m), obtained during the Soil Moisture Experiment 2002 (SMEX02) in Iowa were used. Geostatistical analysis showed the spatial soil moisture correlation lengths varied between 78 m and 307 m (at the field scale), 2044 m and 11,882 m (at the watershed scale), and 19,500 m and 118,500 m (at the regional scale). The correlation length values were usually smaller on wet days than the relatively dry days at the field and watershed scales. The trend was opposite at the regional scale with correlation lengths being larger on wet days. Furthermore, the soil moisture data sets were decomposed into spatial Empirical Orthogonal Function (EOF) patterns, and their relationship with various geophysical parameters (rainfall, topography, soil texture, and vegetation) was examined to determine the dominant control on the near‐surface soil moisture variability. At the field scale, the first four EOFs together explained about 81% of the total variability. At the watershed scale, the first two EOFs were dominant explaining about 93% of the total variance, whereas at the regional scale, the primary EOF itself explained more than 70% of the variance. In other words, the complicated dynamics of near‐surface soil moisture fields can be described by a few underlying orthogonal spatial structures related to the geophysical attributes of the region. Correlation analysis of the RS soil moisture data showed that rainfall, topography, and soil texture have mixed effects on the variability explained by the dominant EOFs, at both watershed and regional scales, with limited influence of vegetation parameters. The effect of rainfall on the soil moisture variability is higher at the watershed scale compared to the regional scale in Iowa.
Interpretation of column experiments of transport of solutes undergoing an irreversible bimolecular reaction using a continuum approximation
Authors: Sanchez‐Vila Xavier , Fernàndez‐Garcia Daniel , Guadagnini Alberto
Published: December 2010

We provide a quantitative interpretation of the column experiment reported by Gramling et al. (2002). The experiment involves advection‐dominated transport in porous media of three dissolved species, i.e., two reactants undergoing a fast irreversible reaction and the resulting product. The authors found that their observations could not be properly fitted with a model based on an advection‐dispersion‐reaction equation (ADRE) assuming the reaction was instantaneous, the actual measured total reaction product being lower than predictions for all times. The data have been recently well reproduced by Edery et al. (2009, 2010) by means of a particle tracking approach in a continuous time random walk framework. These and other authors have questioned the use of partial differential equation (PDE)–based approaches to quantify reactive transport because of the difficulty in capturing local‐scale mixing and reaction. We take precisely this approach and interpret the experiments mentioned by means of a continuum‐scale model based on the ADRE. Our approach differs from previous modeling attempts in that we imbue effects of incomplete mixing at the pore scale in a time‐dependent kinetic reaction term and show that this model allows quantitative interpretation of the experiments in terms of both reaction product profiles and time‐dependent global production rate. The time dependence of the kinetic term presented accounts for the progressive effects of incomplete mixing due to pore‐scale rate‐limited mass transfer, and follows a power law, which is consistent with the compilation of existing experiments reported by Haggerty et al. (2004). Our interpretation can form the basis for further research to assess the potential use of PDE approaches for the interpretation of reactive transport problems in moderately heterogeneous media.
The ESCRT machinery: a cellular apparatus for sorting and scission
Authors: Carlton Jeremy
Published: December 2010

The ESCRT (endosomal sorting complex required for transport) machinery is a group of multisubunit protein complexes conserved across phyla that are involved in a range of diverse cellular processes. ESCRT proteins regulate the biogenesis of MVBs (multivesicular bodies) and the sorting of ubiquitinated cargos on to ILVs (intraluminal vesicles) within these MVBs. These proteins are also recruited to sites of retroviral particle assembly, where they provide an activity that allows release of these retroviruses. More recently, these proteins have been shown to be recruited to the intracellular bridge linking daughter cells at the end of mitosis, where they act to ensure the separation of these cells through the process of cytokinesis. Although these cellular processes are diverse, they share a requirement for a topologically unique membrane-fission step for their completion. Current models suggest that the ESCRT machinery catalyses this membrane fission.
Manipulation of the host by pathogens to survive the lysosome
Authors: Pryor Paul R. , Raines Sally A.
Published: December 2010

Lysosomes form part of our innate immunity and are an important line of defence against microbes, viruses and parasites. Although it is more than 50 years since de Duve discovered lysosomes, it is only in more recent years that we are slowly unravelling the molecular mechanisms involved in the delivery of material to the lysosome. However, successful intracellular pathogens often have a better grip on the mechanisms involved in delivery to the lysosome and can manipulate membrane trafficking pathways to create an intracellular environment that is favourable for replication. By studying pathogen effector proteins that are secreted into the host's cytosol, we can learn about both pathogen-survival mechanisms and further regulatory elements involved in trafficking to the lysosome.
Endolysosomal calcium regulation and disease
Authors: Lloyd-Evans Emyr , Waller-Evans Helen , Peterneva Ksenia , Platt Frances M.
Published: December 2010

Until recently, the mechanisms that regulate endolysosomal calcium homoeostasis were poorly understood. The discovery of the molecular target of NAADP (nicotinic acid–adenine dinucleotide phosphate) as the two-pore channels resident in the endolysosomal system has highlighted this compartment as an important calcium store. The recent findings that dysfunctional NAADP release leads to defective endocytic function which in turn results in secondary lipid accumulation in the lysosomal storage disease Niemann–Pick type C, is the first evidence of a direct connection between a human disease and defective lysosomal calcium release. In the present review, we provide a summary of the current knowledge on mechanisms of calcium homoeostasis within the endolysosomal system and how these mechanisms may be affected in human metabolic disorders.
HSP70 and lysosomal storage disorders: novel therapeutic opportunities
Authors: Petersen Nikolaj H.T. , Kirkegaard Thomas
Published: December 2010

Lysosomes, with their arsenal of catabolic enzymes and crucial metabolic housekeeping functions are experiencing a revived research interest after having lived a rather quiet life for the last few decades. With the discovery of the interaction of the lysosomes with another ancient component of cellular homoeostasis, the molecular chaperone HSP70 (heat-shock protein 70), the stage seems set for further discoveries of the mechanisms regulating cellular and physiological stress responses to otherwise detrimental challenges.
Current therapies for the soluble lysosomal forms of neuronal ceroid lipofuscinosis
Authors: Wong Andrew M.S. , Rahim Ahad A. , Waddington Simon N. , Cooper Jonathan D.
Published: December 2010

The NCLs (neuronal ceroid lipofuscinoses) are the most common inherited paediatric neurodegenerative disorder. Although genetically distinct, NCLs can be broadly divided into two categories: one in which the mutation results in a defect in a transmembrane protein, and the other where the defect lies in a soluble lysosomal enzyme. A number of therapeutic approaches are applicable to the soluble lysosomal forms of NCL based on the phenomenon of cross-correction, whereby the ubiquitously expressed mannose 6-phosphate/IGF (insulin-like growth factor) II receptor provides an avenue for endocytosis, trafficking and lysosomal processing of extracellularly delivered enzyme. The present review discusses therapeutic utilization of cross-correction by enzyme-replacement therapy, gene therapy and stem cell therapy for the NCLs, along with an overview of the recent progress in translating these treatments into the clinic.
In utero gene transfer to the mouse nervous system
Authors: Rahim Ahad A. , Wong Andrew M.S. , Buckley Suzanne M.K. , Chan Jerry K.Y. , David Anna L. , Cooper Jonathan D. , Coutelle Charles , Peebles Donald M. , Waddington Simon N.
Published: December 2010

The cellular and molecular environment present in the fetus and early newborn provides an excellent opportunity for effective gene transfer. Innate and pre-existing anti-vector immunity may be attenuated or absent and the adaptive immune system predisposed to tolerance towards xenoproteins. Stem cell and progenitor cell populations are abundant, active and accessible. In addition, for treatment of early lethal genetic diseases of the nervous system, the overarching advantage may be that early gene supplementation prevents the onset of irreversible pathological changes. Gene transfer to the fetal mouse nervous system was achieved, albeit inefficiently, as far back as the mid-1980s. Recently, improvements in vector design and production have culminated in near-complete correction of a mouse model of spinal muscular atrophy. In the present article, we review perinatal gene transfer from both a therapeutic and technological perspective.
Translation termination in human mitochondrial ribosomes
Authors: Richter Ricarda , Pajak Aleksandra , Dennerlein Sven , Rozanska Agata , Lightowlers Robert N. , Chrzanowska-Lightowlers Zofia M.A.
Published: December 2010

Mitochondria are ubiquitous and essential organelles for all nucleated cells of higher eukaryotes. They contain their own genome [mtDNA (mitochondrial DNA)], and this autosomally replicating extranuclear DNA encodes a complement of genes whose products are required to couple oxidative phosphorylation. Sequencing of this human mtDNA more than 20 years ago revealed unusual features that included a modified codon usage. Specific deviations from the standard genetic code include recoding of the conventional UGA stop to tryptophan, and, strikingly, the apparent recoding of two arginine triplets (AGA and AGG) to termination signals. This latter reassignment was made because of the absence of cognate mtDNA-encoded tRNAs, and a lack of tRNAs imported from the cytosol. Each of these codons only occurs once and, in both cases, at the very end of an open reading frame. The presence of both AGA and AGG is rarely found in other mammals, and the molecular mechanism that has driven the change from encoding arginine to dictating a translational stop has posed a challenging conundrum. Mitochondria from the majority of other organisms studied use only UAA and UAG, leaving the intriguing question of why human organelles appear to have added the complication of a further two stop codons, AGA and AGG, or have they? In the present review, we report recent data to show that mammalian mitochondria can utilize a −1 frameshift such that only the standard UAA and UAG stop codons are required to terminate the synthesis of all 13 polypeptides.
Escape from stress granule sequestration: another way to drug resistance?
Authors: Yagüe Ernesto , Raguz Selina
Published: December 2010

Overexpression of P-glycoprotein, encoded by the MDR1 (multidrug resistance 1) gene, is often responsible for multidrug resistance and chemotherapy failure in cancer. We have demonstrated that, in leukaemic cells, P-glycoprotein expression is regulated at the translational level. More recently, we have shown that in cells overexpressing P-glycoprotein, MDR1 mRNA does not aggregate into translationally silent stress granules. Importantly, this is not unique for MDR1, since other transcripts encoding transmembrane proteins, and which are thus translated at the endoplasmic reticulum, follow the same pattern. By using a series of chimaeric transcripts, we have demonstrated that transcript localization at the endoplasmic reticulum bypasses the signals dictating stress granule sequestration. Polysome profile analyses and protein synthesis experiments indicate that, upon stress withdrawal, endoplasmic-reticulum-bound transcripts resume translation faster than those at the cytosol, which have been sequestered into stress granules. This may represent a novel mechanism by which drug-resistant cells respond quickly to stress, helping them to survive the cytotoxic effect of chemotherapeutic drugs.
Are ribosomal proteins present at transcription sites on or off ribosomal subunits?
Authors: De Sandip , Brogna Saverio
Published: December 2010

RPs (ribosomal proteins) are main components of the ribosome having essential functions in its biogenesis, function and structural integrity. Although most of the RP molecules are in the cytoplasm, being incorporated into translating ribosomes, some RPs have non-ribosomal functions when they are off ribosomal subunits. Notably, in eukaryotes, RPs are also present at transcription sites and some of these proteins have a function in transcription and pre-mRNA processing of specific genes. Although the consensus is that the proteins found at these sites are isolated RPs not assembled into ribosomal subunits, it has been proposed that ribosomal subunits might also be present. In the present paper, we review the available evidence for RPs at transcription sites and conclude that ribosomal subunits might be present, but additional studies will be required to solve this important issue.
Orchestrating ribosomal activity from inside: effects of the nascent chain on the peptidyltransferase centre
Authors: Yan Fu , Doronina Victoria A. , Sharma Pamila , Brown Jeremy D.
Published: December 2010

Ribosomal progression through the open reading frames within mRNAs is frequently considered as uneventful when compared with the highly regulated initiation step. However, both RNA and nascent peptide can interact with the ribosome to influence how translation proceeds and can modify gene expression in several ways. 2A peptides are a class of sequences that, as nascent chains, pause ribosomes and drive a translation-termination reaction on a sense (proline) codon, followed by continued downstream translation. In the present paper, what is known about the 2A reaction is discussed, and 2A is compared with other sequences that, as nascent peptides, pause or stall translation.
The role of IRES trans-acting factors in regulating translation initiation
Authors: King Helen A. , Cobbold Laura C. , Willis Anne E.
Published: December 2010

The majority of mRNAs in eukaryotic cells are translated via a method that is dependent upon the recognition of, and binding to, the methylguanosine cap at the 5' end of the mRNA, by a set of protein factors termed eIFs (eukaryotic initiation factors). However, many of the eIFs involved in this process are modified and become less active under a number of pathophysiological stress conditions, including amino acid starvation, heat shock, hypoxia and apoptosis. During these conditions, the continued synthesis of proteins essential to recovery from stress or maintenance of a cellular programme is mediated via an alternative form of translation initiation termed IRES (internal ribosome entry site)-mediated translation. This relies on the mRNA containing a complex cis-acting structural element in its 5'-UTR (untranslated region) that is able to recruit the ribosome independently of the cap, and is often dependent upon additional factors termed ITAFs (IRES trans-acting factors). A limited number of ITAFs have been identified to date, particularly for cellular IRESs, and it is not yet fully understood how they exert their control and which cellular pathways are involved in their regulation.
Myc up-regulates formation of the mRNA methyl cap
Authors: Cowling Victoria H.
Published: December 2010

The Myc proteins c-Myc and N-Myc are essential for development and tissue homoeostasis. They are up-regulated by growth factors and transmit the signal for cell growth and proliferation. Myc proteins are also prominent oncogenes in many human tumour types. Myc proteins regulate the transcription of protein-encoding mRNAs and the tRNAs and rRNA which mediate mRNA translation into protein. Myc proteins also up-regulate translation by increasing addition of the 7-methylguanosine cap (methyl cap) to the 5′ end of pre-mRNA. Addition of the methyl cap increases the rate at which transcripts are translated by directing RNA modifications and translation initiation. Myc induces methyl cap formation by promoting RNA polymerase II phosphorylation which recruits the capping enzymes to RNA, and by up-regulating the enzyme SAHH (S-adenosylhomocysteine hydrolase), which neutralizes the inhibitory by-product of methylation reactions. Myc-induced cap methylation is a major effect of Myc function, being necessary for activated protein synthesis, cell proliferation and cell transformation. Inhibition of cap methylation is synthetic lethal with elevated Myc protein expression, which indicates the potential for cap methylation to be a therapeutic target.
Post-transcriptional gene regulation in chondrocytes
Authors: Tew Simon R. , Clegg Peter D.
Published: December 2010

The control of gene expression in articular chondrocytes is an essential factor in maintaining the homoeostasis of extracellular matrix synthesis and turnover necessary in healthy articular cartilage. Although much is known of how steady-state levels of gene expression and rates of transcription are altered, there has been a poorer understanding of gene control at the post-transcriptional level and its relevance to cartilage health and disease. Now, an emerging picture is developing of the importance of this tier of gene regulation, driven by in vitro studies and mouse genetic models. This level of cellular regulation represents an as yet unexplored area of potential intervention for the treatment of degenerative cartilage disorders such as osteoarthritis.
Molecular mechanisms of phosphorylation-regulated TTP (tristetraprolin) action and screening for further TTP-interacting proteins
Authors: Tiedje Christopher , Kotlyarov Alexey , Gaestel Matthias
Published: December 2010

TTP (tristetraprolin) is an RNA-binding protein which regulates mRNA stability or translation or both. The molecular mechanisms which are responsible and which discriminate between regulation of mRNA stability and translation are not completely understood so far, but are clearly dependent on p38 MAPK (mitogen-activated protein kinase)/MK (MAPK-activated protein kinase) 2/3-mediated phosphorylation of TTP. To learn more about these mechanisms, phosphorylation-dependent TTP-interacting proteins could be of great interest. Many interacting partners, which belong to the mRNA-processing and -regulating machinery, have been identified by hypothesis-driven co-immunoprecipitation and in the classical Y2H (yeast two-hybrid) approach, where TTP was identified as prey, and are summarized in the present paper. However, because of transactivating properties of TTP, an unbiased Y2H approach using TTP as bait was hindered. Since novel methods for the identification of phosphorylation-dependent interaction partners and of interactors of full-length auto-activating proteins in eukaryotic systems have evolved in the last few years, these methods should be applied to screen for additional phosphorylation-dependent interaction partners of TTP and could lead towards a complete understanding of TTP function at the molecular level.
Adapt or die: how eukaryotic cells respond to prolonged activation of the spindle assembly checkpoint
Authors: Rossio Valentina , Galati Elena , Piatti Simonetta
Published: December 2010

Many cancer-treating compounds used in chemotherapies, the so-called antimitotics, target the mitotic spindle. Spindle defects in turn trigger activation of the SAC (spindle assembly checkpoint), a surveillance mechanism that transiently arrests cells in mitosis to provide the time for error correction. When the SAC is satisfied, it is silenced. However, after a variable amount of time, cells escape from the mitotic arrest, even if the SAC is not satisfied, through a process called adaptation or mitotic slippage. Adaptation weakens the killing properties of antimitotics, ultimately giving rise to resistant cancer cells. We summarize here the mechanisms underlying this process and propose a strategy to identify the factors involved using budding yeast as a model system. Inhibition of factors involved in SAC adaptation could have important therapeutic applications by potentiating the ability of antimitotics to cause cell death.