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Arsenic concentration in the pore water of paddy fields (C soln ) irrigated with arsenic-rich groundwater is a key parameter in arsenic uptake by rice. Pore water extracts from cores and in situ deployment of DET and DGT probes were used to measure the arsenic concentration in the pore water. Ferrihydrite (Fe) and titanium dioxide (Ti) were used as DGT binding agents. Six sampling events during different growing stages of the rice, inducing different biogeochemical conditions, were performed in one rice field. A time series of DGT experiments allow the determination of an in situ arsenic diffusion coefficient in the diffusive gel (3.34 × 10 − 6 cm 2 s − 1 ) needed to calculate the so-called C DGT (Fe) and C DGT (Ti) concentrations. Over 3 days of a given sampling event and for cores sampled at intervals smaller than 50 cm, great variability in arsenic C soln concentrations between vertical profiles was observed, with maxima of concentrations varying from 690 to 2800 μg L − 1 . Comparisons between arsenic measured C sol and C DET and calculated C DGT (Fe) and C DGT (Ti) concentrations show either, in a few cases, roughly similar vertical profiles, or in other cases, significantly different profiles. An established iron oxyhydroxide precipitation in the DET gel may explain why measured arsenic C DET concentrations occasionally exceeded C soln . The large spread in results suggests limitations to the use of DET and type of DGT probes used here for similarly representing the spatio-temporal variations of arsenic content in soil pore water in specific environmental such as paddy soils. [ABSTRACT FROM AUTHOR]

Abstract: The joint paper presents a common view of fast reactor specific missions in the development of nuclear energy and a cross-analysis of merits and demerits of several Fast Reactors concepts studied worldwide and especially in the Generation-IV International Forum (GIF) framework. The paper provides the context for fast reactors development in the United States, France and Japan and focuses on the comparison on Sodium-cooled Fast Reactor (SFR), Gas-cooled Fast Reactor (GFR), and Lead-cooled Fast Reactor (LFR), i.e. the three fast reactor concepts that have the potential to meet the nuclear fuel cycle sustainability goals. The information provided in the article permits the reader to understand each country''s objectives to see that not only the objectives searched for but also the technical orientations are converging. The authors underline that SFR technology evaluation relies significantly on the substantial base technology development programs within each country which is without comparison for the other two fast reactor technologies, e.g., SFR technology has already been developed to commercial or near commercial scale in each country whereas the performance of LFR and GFR technology is still uncertain. The main GFR merits are the potential for high temperatures and the easier possibilities for inspections and repairs. The main challenges are the fuel (fabrication, in-pile behavior), materials for high temperatures, and the implementation of mitigation means to manage severe core degradation. The main LFR merit is the lack of chemical reactivity of the lead coolant with air and water. The main challenges are the development of corrosion resistant structural and cladding materials, the implementation of mitigation means to manage severe core degradation, the density of the lead, and the comparably large core size. The selection of a reference fast reactor concept in view of possible industrialization is made on a national base, taking into account the each countries’ strategic objectives, existing technology base, the proven or expected technical performance, the R&D challenges and technical means to conduct that R&D, the possibility to share development costs and risks, etc. It is important to note that in different contexts, the U.S., French, and Japanese organizations have selected the SFR as their reference fast reactor concept. [Copyright &y& Elsevier]

LHCb aims to use its O(20000) CPU cores in the high level trigger (HLT) and its 120 TB Online storage system for data reprocessing during LHC shutdown periods. These periods can last a few days for technical maintenance or only a few hours during beam interfill gaps. These jobs run on files which are staged in from tape storage to the local storage buffer. The result are again one or more files. Efficient file writing and reading is essential for the performance of the system. Rather than using a traditional shared file-system such as NFS or CIFS we have implemented a custom, light-weight, non-Posix network file-system for the handling of these files. Streaming this file-system for the data-access allows to obtain high performance, while at the same time keep the resource consumption low and add nice features not found in NFS such as high-availability, transparent fail-over of the read and write service. The writing part of this streaming service is in successful use for the Online, real-time writing of the data during normal data acquisition operation. The network file system relies on a commercial file system which manages the data on persistent disk storage. The implementation together with performance figures are presented. [ABSTRACT FROM PUBLISHER]

The LHCb experiment uses a single, high performance storage system to serve all kinds of storage needs: home directories, shared areas, raw data storage and buffer storage for event reconstruction. All these applications are concurrent and require careful optimisation. In particular for accessing the raw data in read and write mode, a custom light weight non-POSIX compliant file system has been developed. File serving is achieved by running several redundant file servers in an active/active configuration with high availability capabilities and good performance. In this paper we describe the design and current architecture of this storage system. We discuss implementation issues and problems we had to overcome during the hitherto 18 months running period. Based on our experience we will also discuss the relative advantages and disadvantages of such a system over another composed of several smaller storage systems. We also present performance measurements. [ABSTRACT FROM AUTHOR]

An efficient one-pot procedure is described for the reduction of aryl iodides to aryl anions using a structurally simple bis-pyridinylidene electron donor, prepared in situ by treating 4-DMAP methiodide salt with base. The results show (i) that pyridinylidene carbenes can be easily used for intermolecular C-C bond formation, (ii) that bis-pyridinylidenes demonstrate superior robustness compared to electron-donor systems based on bis-imidazolylidenes, and (iii) that electron-donor strength is enhanced in the simplified DMAP-based donor. Deuterated analogues of this donor also provide mechanistic information on the source of protons when the aryl anions are quenched in situ. [ABSTRACT FROM AUTHOR]

Abstract: A new preparation of 3,5,5-trialkyl-γ-butyrolactones of defined absolute configuration is reported. This method involves the diastereoselective alkylation of 3,4-ethylenic acids after incorporation of a chiral Evans auxiliary, and then after separation of the two diastereomers and hydrolysis of the auxiliary, stereospecific halo lactonizations. This method was applied to the preparation of a natural product, present in a sponge. [Copyright &y& Elsevier]

Abstract: Aim of the study: l-DOPA/tyrosine ratio (an index of tyrosinase activity), melanoma antigens S100B and MIA, lactate deshydrogenase (LDH) and their combinations were evaluated for clinical value as tumour markers in melanoma. Methods: Blood samples were obtained in 170 melanoma patients (stage I–II: n =57, III: n =54, IV: n =59) at inclusion and in a sub-group of 82 subjects during follow-up for up to 4 years. Laboratory analyses were performed by HPLC (l-DOPA, l-tyrosine), immunoassays (S100B, MIA) and colourimetry (LDH). Results: All markers, except LDH, were elevated in stage IV versus other stages. S100B and MIA highly correlated, especially in stage IV (r s : 0.849, p <0.001). The combination of l-DOPA/tyrosine ratio with S100B displayed the highest sensitivity/specificity (73/70%) to confirm stage III–IV or stage IV alone (69/75%) (ROC optimised cut-off). Only the l-DOPA/tyrosine ratio significantly increased (+36% over 5 months, p =0.001) during progression from stage I–III to higher stages. S100B, MIA and LDH, but not the l-DOPA/tyrosine ratio, responded to progression towards death in stage IV. All markers exhibited a prognostic value in deceased patients (n =44); S100B and MIA were the best predictors of survival time by Cox proportional-hazards regression. Conclusion: The combination of plasma l-DOPA/tyrosine ratio and S100B appears an attractive approach for the biological follow-up of melanoma patients. [Copyright &y& Elsevier]

Abstract: The influence of two types of colloids (natural organic matter, NOM), a colloid with high affinity for radionuclides (RN(s)), and hydrophilic synthetic latex (SHL), a colloid with low affinity for RN(s) on the transfer of 60Co and 85Sr in a silica sand column was studied under different physicochemical conditions : pH (4.9), ionic strength (10−3 M and 10−2 M), concentration of colloids (100mgl−1, 10mgl−1), flow velocity (12.4cmh−1 and 3.7cmh−1), water saturation of the column (100% and 70%). In the absence of colloids, the transfer of 60Co and 85Sr was retarded compared to the transfer of the conservative tracer. In the presence of colloids and according to the specific physicochemical conditions, an acceleration or retardation of 60Co and 85Sr transfer was observed compared to their transfer in the absence of colloids. Our results evidenced that any colloids even with low reactivity could significantly modify the RN transfer. However, the extent to which the transfer was influenced differs according to the colloid type; the NOM exhibiting higher impact than SHL. Batch experiments helped in interpreting of the interactions between the colloids, RN(s) and solid phase observed in column. [Copyright &y& Elsevier]

Abstract: The desorption kinetic of trace elements (Cd, Zn, Co, Mn, Fe, Ag, and Cs) associated with Loire river natural suspended particulate matter (SPM; 0.4–63 μm) was followed up on times varying from 0.5 h to 30 days, from SPM previously contaminated during 1 h, 24 h and 30 days. Long term sorption kinetics indicated that the difference between sorption occurring during the period 0–30 days (time investigated in this study) and the period 0–48 h (time often used for sorption experiments) ranges from few to 25% according to the element. Desorption kinetics show that, whatever the age of the complex formed during the sorption step, the release tends to equilibrium between complexed and dissolved elements equivalent to the equilibrium obtained for sorption after a given time. However, the time to get this equilibrium depends on the aging of the complex and on the element. All the above features indicate different types of complexes formation and strength of the binding according to the age of the complex and according to the element. Using a multi-compartmental model, simulating the transfer of metals between water and different types of particulate sites, the relationships between the parameters describing slow and rapid processes helped in explaining the “aging” effect observed. [Copyright &y& Elsevier]

Announces that the 5th European Biophysical Societies Association (EBSA) and the 15th International Union of Pure and Applied Biophysics International Biophysics Congress will be held in Montpellier, France on August 27-September 1, 2005. Organizing committee; Information on EBSA; Schedule of the EBSA Congress.

The behavior of dissolved cadmium (Cd) in the Danube estuary was investigated through field sampling and mixing experiments using Danube River water and Black Sea water. The experiments were performed by mixing these two end-member waters in various proportions, with the addition of stable or radioactive Cd to the freshwater Danube end-member prior to the mixing. The release of Cd that resulted in maximum concentrations under field conditions was well simulated by mixing experiments. The experimental results were modeled assuming that the release of Cd was the sum of the contribution of physical effects resulting from dilution effects and the contribution of chemical effects resulting from dissolved Cd-complex formation (and isotopic exchange when concerned). In the absence of dissolved Cd-complexing ligands, the release of Cd due to the dilution of the particulate phase during mixing could explain part of the maximum concentrations observed in field conditions. Kinetic effects were established by comparing the theoretical and measured contribution of chemical effects resulting from dissolved Cd-complex formation. The non-equilibrium state observed during the mixing experiment suggested the presence of particulate labile Cd that was not easily mobilized. All these features supported the hypothesis that Cd released in estuaries is controlled both by the dilution of the particulate phase and by kinetic competitive complexation between particulate ligands (covering a large spectrum of nature and strength) and dissolved ligands. [Copyright &y& Elsevier]

Progress in animal nutrition, reproduction, quantitative genetics, and the development of molecular genetics, proteomics, and functional genomics open new perspectives for the meat sector. The most promising developments include a wider utilisation of molecular markers, the possibilities of semen sexing and the targeted use of nutrition to modify the composition of meat. The increased use of biotechnology will have a considerable impact on the economics of production of meat and further processed products. New technologies will increase the possibilities for product differentiation and improve homogeneity of live animals. The consumer and society in general will influence the direction of these developments. This review will focus on the long-term impact of new technologies for the meat production chain. [Copyright &y& Elsevier]

Investigates the sorption of four trace metals (Cd, Zn, Co, and Mn) onto alumina, silica, and kaolinite in the presence or absence of salicylic acid. Different pH edge behaviors of four metals' sorption in the absence or absence of salicylic acid; Simulation of the diffuse layer model; Discrepancies of the experimental data.

Reports the results from an investigation into the distribution of CdII, ZnII, CoII, MnII, feII, AgII, and CsI in the colloidal fractions of water from the Vienne river. How the distribution of these elements were investigated; Methodology used in the study; Results of the study.

Investigates the kinetic binding of trace elements in tagged river suspended matter as well as the kinetics of the speciation within the filterable phase. Determination of partitioning of trace elements between the dissolved and the particulate phase; Details on the features of the speciation of trace elements in the filterable phase.

The article describes two cases related to false results of glucose and ketone fingerprick testing in users of skin lightening cosmetics that could have been prevented by careful hand washing. The two patients were a sub-Saharan African woman and an African woman that both have history of insulin treated diabetes and are using the skin lightening cream, Skin Light. The chemical compound that interferes with the results was identified as the hydroquinone.

The objective of this paper is to present a model simulating and predicting the exchange kinetics of lead (Pb) between contaminated sediments and water during resuspension events potentially occurring in reservoirs. We developed an innovative model that combines thermodynamic speciation of particulate surfaces (oxides and Particulate Organic Carbon (POC)), thermodynamic Pb speciation in water, and kinetic modelling of exchanges between free Pb and particulate sites (i.e., dissolution of a carbonate carrier phase, adsorption/coprecipitation and desorption/dissolution to/from oxides, and adsorption and desorption/degradation to/from particulate organic particles). We used results from laboratory resuspension experiments performed on sediments from three contaminated dam reservoirs to calibrate a new chemical speciation model. Uptake and release processes to/from sediments were found to be controlled by at least two successive reactions that are associated with two particulate pools (here oxides and POC). Kinetic adsorption and desorption rates were calibrated for seven experimental conditions. Variability in kinetic rates allowed evaluation of the effect of the solid-to-liquid ratio and sediment origin on exchange kinetics at the water-particle interface. The kinetic release of dissolved Pb by desorption or dissolution from the oxides was reproduced almost identically between the experiments, regardless of the solid-to-liquid ratio or sediment origin. Long-term readsorption on POC sites is more variable, even if ranges of variation in the adsorption and desorption kinetic rates related to POC remain limited, considering that tested sediments vary significantly. A kinetic model simulating the dynamics of lead (Pb) during sediment resuspension was developed and calibrated to laboratory experiments performed on three contaminated sediments. Unlabelled Image • A kinetic model simulating the dynamics of trace metals during sediment resuspension was developed • Laboratory resuspension experiments on sediments of three reservoirs were used to calibrate the new chemical speciation model • Uptake and release processes to/from sediments are controlled by two successive reactions associated to oxides and POC pools. • Variability in kinetic rates allowed to evaluate the effect of solid-to-liquid ratio and sediment origin on exchange kinetics [ABSTRACT FROM AUTHOR]

Simple cyclopropanols are obtained on addition of ethylmagnesium halides to esters in the presence of titanium isoprop�oxide. Alternatively, we have found that they may also be prepared in moderate to good yields through unexpected vinyl transfer from vinyl ethers via a titanium-promoted inter- or intramolecular reaction. On the basis of deuterium labeling experiments, a mechanism has been proposed. [ABSTRACT FROM AUTHOR]

Reports on a resurgence in the use of spinal anesthesia for pediatric surgery in preterm infants. Safety issues and concerns; Potential complications; Theoretical significance to pediatric anesthesia.

System reconfiguration is essential in complex systems management, as it is an enabler of system flexibility and adaptability. It ensures system operation and increases reliability, availability, maintainability, testability, safety, and reuse of system entities and technologies. For the reconfiguration of a system in use, it is necessary to assess, in continuity, the system's state with regard to its context. Identifying data supporting system reconfiguration represents a major industrial challenge and is linked directly to the development of industrial reconfiguration tools. Reconfiguration tools are based on a data model, also called ontology, which represents key concepts of system reconfiguration and their relationships. A particular difficulty of developing the data model is the multi‐domain nature of reconfiguration. Furthermore, it needs to address a considerable diversity of system types. Few publications propose an ontology supporting data identification and tool development for the entire process. Hence, in this paper we propose to formalize the system reconfiguration process and propose an overarching ontology, which we call OSysRec. This ontology considers data at the management, dynamics, and structure level. The proposed ontology has been developed based upon expert knowledge and several industrial uses cases. The OSysRec ontology allowed a better understanding of the reconfiguration process, and hence it can be deployed for developing efficient and effective reconfiguration tools at the industrial scale. The ontology has been tested on an industrial case study to validate the proposed approach. [ABSTRACT FROM AUTHOR]

Reports on concerns of international unions about the guaranteed and sustained public availability of scientific data. Importance of open access to taxonomic data; Need for the safe deposition of the data in public archival databases; Suggestions given by the Inter-Union Bioinformatics Group for the safe deposition of the data.

Objective: To define for women at low obstetric risk methods of management that respect the rhythm and the spontaneous course of giving birth as well as each woman’s preferences. Methods: These clinical practice guidelines were developed through professional consensus based on an analysis of the literature and of the French and international guidelines available on this topic. Results: Labor should be monitored with a partograph (professional consensus). Digital cervical examination should be offered every 4 h during the first stage of labor, hourly during the second. The choice between continuous (cardiotocography) or discontinuous (by cardiotocography or intermittent auscultation) monitoring should be left to the woman (professional consensus). In the active phase of the first stage of labor, dilation speed is considered abnormal if it is less than 1 cm/4 h between 5 and 7 cm or less than 1 cm/2 h after 7 cm. In those cases, an amniotomy is recommended if the membranes are intact, and the administration of oxytocin if the membranes are already broken and uterine contractions are judged insufficient (professional consensus). It is recommended that pushing not begin when full dilation has been reached; rather, the fetus should be allowed to descend (grade A). Umbilical cord clamping should be delayed beyond the first 30 s in newborns who do not require resuscitation (grade C). Conclusion: The establishment of these clinical practice guidelines should enable women at low obstetric risk to receive better care in conditions of optimal safety while supporting physiologic birth. [ABSTRACT FROM AUTHOR]

The LHCb event-builder is implemented using a large Gigabit Ethernet network using a push-protocol for a single stage read-out at a 1 MHz event injection rate. The destination assignment and dynamic load-balancing are facilitated by LHCb's Timing and Fast Control system. The assembly of event fragments is done on each event-filter farm node instead of having dedicated builder units. The design of the event-builder will be shortly described, followed by a description of the implementation, the protocol used and the performance during first data taking. The emphasis will be on the experience we gained during the running of such a large event-building network. We will discuss the problems we encountered and how we overcame them. [ABSTRACT FROM PUBLISHER]

The High Level Trigger (HLT) and Data Acquisition System select about 2 kHz of events out of the 40 MHz of beam crossings. The selected events are consolidated into files in onsite storage and then sent to permanent storage for subsequent analysis on the Grid. For local and full-chain tests a method to exercise the data-flow through the High Level Trigger is needed in the absence of real data. In order to test the system as much as possible under identical conditions as for data-taking, the solution would be to inject data at the input of the HLT at a minimum rate of 2 kHz. This is done via a software implementation of the trigger system which sends data to the HLT. The application has to simulate that the data it sends come from real LHCb readout-boards. Data can come from several input streams, which are selected according to probabilities or frequencies. Therefore the emulator offers runs which are not only identical data-flows coming from a sequence on tape, but physics-like pseudo-indeterministic data-flow, including lumi events and candidate b-quark events. Both simulation data and previously recorded real data can be re-played through the system in this manner. As the data rate is high (100 MB/s), care has been taken to optimize the emulator for throughput from the Storage Area Network. The emulator can be run in stand-alone mode, but even more interesting is that it can emulate any partition of LHCb in parallel with the real hardware partition. In this mode it is fully integrated into the standard run-control. The architecture, implementation, and performance results of the emulator and full tests will be presented. This emulator is a crucial part of the ongoing data-challenges in LHCb. Results from these Full System Integration Tests (FEST) will be presented, which helped to verify and benchmark the entire LHCb data-flow. [ABSTRACT FROM AUTHOR]

Abstract: The novel cobalt(II) crown carbene complex 12(II) has been prepared and characterised by X-ray crystallography. This complex is reduced in a one-electron process to a cobalt(I) complex that acts as a powerful single electron donor, reducing aryl halides, including aryl chlorides and demonstrating the strong electron-enriching effect on cobalt of the crown carbene ligand. The metal ion is tightly held in a tetrahedral conformation by its enveloping crown ligand—this prevents what would otherwise be expected to be an easy oxidation to cobalt(III) under standard electrochemical conditions. Complex 12 is shown to be an effective catalyst in mediated electrochemical reductions of aryl iodides at room temperature and aryl bromides at 90°C. The electrochemically produced catalyst [from 10mol% of added Co(II) complex] also triggers reduction of aryl chlorides, although this seems at the limit of its reactivity. However, when the cobalt(II) complex is reduced by sodium amalgam, this affords stoichiometric quantities of the active cobalt reducing agent, which affords reduction of aryl iodides and bromides as above, but also reduces aryl chlorides at elevated temperatures. [Copyright &y& Elsevier]

Background: Formal classification of a large collection of protein structures aids the understanding of evolutionary relationships among them. Classifications involving manual steps, such as SCOP and CATH, face the challenge of increasing volume of available structures. Automatic methods such as FSSP or Dali Domain Dictionary, yield divergent classifications, for reasons not yet fully investigated. One possible reason is that the pairwise similarity scores used in automatic classification do not adequately reflect the judgments made in manual classification. Another possibility is the difference between manual and automatic classification procedures. We explore the degree to which these two factors might affect the final classification. Results: We use DALI, SHEBA and VAST pairwise scores on the SCOP C class domains, to investigate a variety of hierarchical clustering procedures. The constructed dendrogram is cut in a variety of ways to produce a partition, which is compared to the SCOP fold classification. Ward's method dendrograms led to partitions closest to the SCOP fold classification. Dendrogram- or tree-cutting strategies fell into four categories according to the similarity of resulting partitions to the SCOP fold partition. Two strategies which optimize similarity to SCOP, gave an average of 72% true positives rate (TPR), at a 1% false positive rate. Cutting the largest size cluster at each step gave an average of 61% TPR which was one of the best strategies not making use of prior knowledge of SCOP. Cutting the longest branch at each step produced one of the worst strategies. We also developed a method to detect irreducible differences between the best possible automatic partitions and SCOP, regardless of the cutting strategy. These differences are substantial. Visual examination of hard-to-classify proteins confirms our previous finding, that global structural similarity of domains is not the only criterion used in the SCOP classification. Conclusion: Different clustering procedures give rise to different levels of agreement between automatic and manual protein classifications. None of the tested procedures completely eliminates the divergence between automatic and manual protein classifications. Achieving full agreement between these two approaches would apparently require additional information. [ABSTRACT FROM AUTHOR]

Polarized intracellular trafficking in epithelia is critical in development, immunity, and physiology to deliver morphogens, defensins, or ion pumps to the appropriate membrane domain. The mechanisms that control apical trafficking remain poorly defined. Using Caenorhabditis elegans, we characterize a novel apical secretion pathway involving multivesicularbodies and the release of exosomes at the apical plasma membrane. By means of two different genetic approaches, we show that the membrane-bound V0 sector of the vacuolar H[sup +]-ATPase (V-ATPase) acts in this pathway, independent of its contribution to the V-ATPase proton pump activity. Specifically, we identified mutations in the V0 "a" subunit VHA-5 that affect either the V0-specific function or the V0+V1 function of the V-ATPase. These mutations allowed us to establish that the V0 sector mediates secretion of Hedgehog-related proteins. Our data raise the possibility that the V0 sector mediates exosome and morphogen release in mammals. [ABSTRACT FROM AUTHOR]

Focuses on a study that explored retinoic acid (RA) action during eye morphogenesis in a mouse. Mediators of the effects of paracrine RA signal on the periocular mesenchyme (POM); Functions of heterodimers in POM; Enzymes that are required for RA synthesis in the eye region.

Retinoic acid (RA) activity plays sequential roles during the development of the ventral spinal cord. Here, we have investigated the functions of local RA synthesis in the process of motoneuron specification and early differentiation using a conditional knockout strategy that ablates the function of the retinaldehyde dehydrogenase 2 (Raldh2) synthesizing enzyme essentially in brachial motoneurons, and later in mesenchymal cells at the base of the forelimb. Mutant (Raldh2L-/-) embryos display an early embryonic loss of a subset of Lim1+ brachial motoneurons, a mispositioning of Islet1+ neurons and inappropriate axonal projections of one of the nerves innervating extensor limb muscles, which lead to an adult forepaw neuromuscular defect. The molecular basis of the Raldh2L-/- phenotype relies in part on the deregulation of Hoxc8, which in turn regulates the RA receptor RARβ. We further show that Hoxc8 mutant mice, which exhibit a similar congenital forepaw defect, display at embryonic stages molecular defects that phenocopy the Raldh2L-/-motoneuron abnormalities. Thus, interdependent RA signaling and Hox gene functions are required for the specification of brachial motoneurons in the mouse. [ABSTRACT FROM AUTHOR]

System reconfiguration is essential in complex systems management, as it is an enabler of system adaptability with regard to system evolutions. System evolutions have to be managed to ensure system effectiveness and efficiency through its whole life cycle, particularly when it comes to complex systems that take years of development and dozens of years of usage. In this context, system reconfiguration ensures system operation and maintains system "ilities" (e.g., reliability, availability, maintainability, testability, and safety). This research has been conducted in the context of a large international aerospace, space, ground transportation, defense, and security company. This research aims at supporting system reconfiguration during operations. Within current industrial practices, the development of reconfiguration support is challenging as it requires integrating data related to observations (from operations) and system design (from engineering). More specifically, there is a need to integrate and link relevant reconfiguration data concerning the system objectives, operational context, and level of functioning. This paper proposes integrating and linking this fundamental data within a reconfiguration method. MBSysRec is a multidisciplinary method that involves configuration generation and a multicriteria decision-making method for configuration evaluation and selection to support system reconfiguration during operations. The method has been implemented on two projects based on historical data. Resulting configurations have been discussed and assessed by system reconfiguration experts. A Search and Rescue (SAR) case study is used to demonstrate the method. The method is proven effective for finding relevant system configurations for reconfiguring the already deployed system to achieve search and rescue missions. [ABSTRACT FROM AUTHOR]

The retinoic acid (RA) signal, produced locally from vitarnin A by retinaldehyde dehydrogenase (Raldh) and transduced by the nuclear receptors for retinoids (RA receptor and 9-cis-RA receptor), is indispensable for ontogenesis and horneostasis of nurnerous tissues. We demonstrate that Raldh3 knockout in mouse suppresses RA synthesis and causes malformations restricted to ocular and nasal regions, which are similar to those observed in vitamin A-deficient fetuses and/or in retinoid receptor mutants. Raldh3 knockout notably causes choanal atresia (CA), which is responsible for respiratory distress and death of Raldh3-null mutants at birth. CA is due to persistence of nasal fins, whose rupture normally allows the communication between nasal and oral cavities. This malformation, which is similar to isolated congenital CA in humans and may result from impaired RA-controlled down-regulation of Fgf8 expression in nasal fins, can be prevented by a simple maternal treatment with RA. [ABSTRACT FROM AUTHOR]

Retinoic acid (RA), the active derivative of vitamin A, is involved in various developmental and homeostatic processes. To define whether certain developmental events are particularly sensitive to a decrease in embryonic RA levels, we generated mice bearing a hypomorphic allele of the RA-synthesizing enzyme Raldh2. The resulting mutant mice, which die perinatally, exhibit the features of the human DiGeorge syndrome (DGS) with heart outflow tract septation defects and anomalies of the aortic arch-derived head and neck arteries, laryngeal-tracheal cartilage defects, and thymus/parathyroid aplasia or hypoplasia. Analysis of Raldh2 hypomorph embryos reveal selective defects of the posterior (third to sixth) branchial arches, including absence or hypoplasia of the corresponding aortic arches and pharyngeal pouches, and local down-regulation of RA-target genes. Thus, a decreased level of embryonic RA (through genetic and/or nutritional causes) could represent a major modifier of the expressivity of human 22q11delassociated DiGeorge/velocardiofacial syndromes and, if severe enough, could on its own lead to the clinical features of the DiGeorge syndrome. [ABSTRACT FROM AUTHOR]

The human general transcription factor TFIID is composed of the TATA-binding protein (TBP) and 13 TBP-associated factors (TAFs). In eukaryotic cells, TFIID is thought to nucleate RNA polymerase II (Pol II) preinitiation complex formation on all protein coding gene promoters and thus, be crucial for Pol II transcription. TFIID is composed of three lobes, named A, B, and C. A 5TAF core complex can be assembled in vitro constituting a building block for the further assembly of either lobe A or B in TFIID. Structural studies showed that TAF8 forms a histone fold pair with TAF10 in lobe B and participates in connecting lobe B to lobe C. To better understand the role of TAF8 in TFIID, we have investigated the requirement of the different regions of TAF8 for the in vitro assembly of lobe B and C and the importance of certain TAF8 regions for mouse embryonic stem cell (ESC) viability. We have identified a region of TAF8 distinct from the histone fold domain important for assembling with the 5TAF core complex in lobe B. We also delineated four more regions of TAF8 each individually required for interacting with TAF2 in lobe C. Moreover, CRISPR/Cas9-mediated gene editing indicated that the 5TAF core-interacting TAF8 domain and the proline-rich domain of TAF8 that interacts with TAF2 are both required for mouse embryonic stem cell survival. Thus, our study defines distinct TAF8 regions involved in connecting TFIID lobe B to lobe C that appear crucial for TFIID function and consequent ESC survival. [ABSTRACT FROM AUTHOR]

NSD1, a novel 2588 amino acid mouse nuclear protein that interacts directly with the ligand-binding domain (LBD) of several nuclear receptors (NRs), has been identified and characterized. NSD1 contains a SET domain and multiple PHD fingers. In addition to these conserved domains found in both positive and negative Drosophila chromosomal regulators, NSD1 contains two distinct NR interaction domains, NID-L and NID+L, that exhibit binding properties of NIDs found in NR corepressors and coactivators, respectively. NID-L, but not NID+L, interacts with the unliganded LBDs of retinoic acid receptors (RAR) and thyroid hormone receptors (TR), and this interaction is severely impaired by mutations in the LBD α-helix 1 that prevent binding of corepressors and transcriptional silencing by apo- NRs. NID+L, but not NID-L, interacts with the liganded LBDs of RAR, TR, retinoid X receptor (RXR), and estrogen receptor (ER), and this interaction is abrogated by mutations in the LBD α-helix 12 that prevent binding of coactivators of the ligand-induced transcriptional activation function AF-2. A novel variant (FxxLL) of the NR box motif (LxxLL) is present in NID1L and is required for the binding of NSD1 to holo- LBDs. Interestingly, NSD1 contains separate repression and activation domains. Thus, NSD1 may define a novel class of bifunctional transcriptional intermediary factors playing distinct roles in both the presence and absence of ligand. [ABSTRACT FROM AUTHOR]

The "specific reactivity" of β-galactosidase from Eacherichia coli for different substrates has been studied at the optimal pH value The pH dependence of the enzyme activity has been reinvestigated in highly controlled conditions with respect to Mg2+ and Na+ concentrations and ionic strength. The different kinetic parameters kcat, Km and the kcat/Km ratio have been determined with o-nitrophenyl-β-D-galactoside and o-mtrophenyl-β-D-fucoside, at different pH values between 5.16 and 10, for both Mg2+ enzyme and Mg2+-free enzyme, since a residual activity has been found in the absence of Mg2+. The activity of both types of enzyme is controlled by a protonated group which ionizes in the alkaline range and by at least one unprotonated group which ionizes in the acidic range. This latter group has a pK smaller than 6 in both types of enzyme; it is plausible to assume that this group is a carboxylate. In the alkaline range, the pK of the involved group shifts from about 6.5 in Mg2+-free enzyme to 8.4 in the Mg2+ enzyme. Either the substrate or the Mg binding induces this shaft in the ionization of the group. The β galactosidase catalyzed reactions proceed via two intermediary complexes. For o-nitrophenyl-β-D-galactoside substrate the limiting process is not the same for the Mg2+ enzyme and for the Mg2+free enzyme. [ABSTRACT FROM AUTHOR]

Abstract: Modified vaccinia virus Ankara (MVA) is a safe vector for high-level expression of proteins in mammalian cells. To simplify the molecular cloning procedures for shuttling genes into the MVA genome, we constructed generic destination plasmids that allow in vitro recombinational cloning (Gateway) and quick isolation of expression plasmids for any gene to be incorporated into the virus. Downstream purification steps were simplified by including N-terminal peptide tags (His, Strep, and Flag) in the generic plasmids. We demonstrate the ability to produce 10mg of β-glucuronidase from 108 hamster cells and to purify tagged proteins with affinity gels. [Copyright &y& Elsevier]

Satellite cells (SC) are muscle stem cells that can regenerate adult muscles upon injury. Most SC originate from PAX7+ myogenic precursors set aside during development. Although myogenesis has been studied in mouse and chicken embryos, little is known about human muscle development. Here, we report the generation of human induced pluripotent stem cell (iPSC) reporter lines in which fluorescent proteins have been introduced into the PAX7 and MYOG loci. We use single cell RNA sequencing to analyze the developmental trajectory of the iPSC-derived PAX7+ myogenic precursors. We show that the PAX7+ cells generated in culture can produce myofibers and selfrenew in vitro and in vivo. Together, we demonstrate that cells exhibiting characteristics of human fetal satellite cells can be produced in vitro from iPSC, opening interesting avenues for muscular dystrophy cell therapy. This work provides significant insights into the development of the human myogenic lineage. [ABSTRACT FROM AUTHOR]

Introduction: To determine a minimum threshold of medical staffing needs (obstetricians-gynecologists, anesthesiologists-resuscitation specialists, nurse-anesthetists, pediatricians, and midwives) to ensure the safety and quality of care for unscheduled obstetrics-gynecology activity.Materials and Methods: Face to face meetings of French healthcare professionals involved in perinatal care in different types of practices (academic hospital, community hospital or private practice) who belong to French perinatal societies: French National College of Gynecologists-Obstetricians (CNGOF), the French Society of Anesthesia and Resuscitation Specialists (SFAR), the French Society of Neonatology (SFN), the French Society of Perinatal Medicine (SFMP), the National College of French Midwives (CNSF), and the French Federation of Perinatal Care Networks (FFRSP).Results: Different minimum thresholds for each category of care provider were proposed according to the number of births/year in the facility. These minimum thresholds can be modulated upwards as a function of the level of care (Level 1, 2 or 3 for perinatal centers), existence of an emergency department, and responsibilities as a referral center for maternal-fetal and/or surgical care. For example, an obstetrics-gynecology department handling 3000-4500 births per year without serving as a referral center must have an obstetrician-gynecologist, an anesthesiologist-resuscitation specialist, a nurse-anesthetist, and a pediatrician onsite specifically to provide care for unscheduled obstetrics-gynecology needs and a second obstetrician-gynecologist available within a time compatible with security requirements 24/7; the number of midwives always present (24/7) onsite and dedicated to unscheduled care is 5.1 for 3000 births and 7.2 for 4500 births. A maternity unit's occupancy rate must not exceed 85 %.Conclusion: The minimum thresholds proposed here are intended to improve the safety and quality of care of women who require unscheduled care in obstetrics-gynecology or during the perinatal period. [ABSTRACT FROM AUTHOR]

Background: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation.Methods and Findings: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44-1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40-1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44-1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30-2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11-1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84-1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.Conclusions: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk. [ABSTRACT FROM AUTHOR]

Objective: We aimed at assessing the predictive value of plasmatic Neutrophil Gelatinase Associated Lipocalin (pNGAL) at admission and severity scores to predict major adverse kidney events (MAKE, defined as death and/or need for renal replacement therapy (RRT) and/or non-renal recovery at day 90) in critically ill burn patients.Material and Methods: Single-center cohort study in a burn critical care unit in a tertiary center, including all consecutive severely burn patients (total burned body surface >20%) from January 2012 until January 2015 with a pNGAL dosage at admission. Reclassification of patients was assessed by Integrated Discrimination Improvement (IDI).Measurements and Results: 87 patients were included. Mean age was 47.7 (IQ 25-75: 33.4-65.2) years; total burn body surface area was 40 (IQ 25-75: 30-55) % and ICU mortality 36%. 39 (44.8%) patients presented a MAKE, 32 (88.9%) patients died at day 90. pNGAL was higher in the MAKE group (423 [IQ 25-75: 327-518]pg/mL vs 184 [IQ 25-75: 147-220]pg/mL, p<0.001). In multivariate analysis, pNGAL and abbreviated burn severity index (ABSI) remained associated with MAKE (OR 1.005 [CI 95% 1.0005-1.009], p=0.03 and OR 1.682 [CI95%1.038-2.726], p=0.035 respectively). Adding pNGAL to abbreviated burn severity index, simplified organ failure assessment and the simplified acute physiology score 2 did outperform clinical scores for the prediction of MAKE and AKI and for most severe forms of AKI and allowed a statistically significant reclassification of patients compared to ABSI for MAKE, RRT, AKI at Day 7 and AKI during hospitalization with a number of patients needed to screen to detect one extra episode of MAKE was 44, 13 for severe AKI and 15 for AKI.Conclusions: pNGAL at admission is associated with the risk of MAKE in this population, and outperform severity scores when associated. Interventional studies are now needed to assess if impact of biomarkers-guided strategies would improve outcome. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to identify mutations that cause non-syndromic male infertility using whole exome sequencing of family cases. Methods: We recruited a consanguineous Turkish family comprising nine siblings with male triplets; two of the triplets were infertile as well as one younger infertile brother. Whole exome sequencing (WES) performed on two azoospermic brothers identified a mutation in the melanoma antigen family B4 ( MAGEB4) gene which was confirmed via Sanger sequencing and then screened for on control groups and unrelated infertile subjects. The effect of the mutation on messenger RNA (mRNA) and protein levels was tested after in vitro cell transfection. Structural features of MAGEB4 were predicted throughout the conserved MAGE domain. Results: The novel single-base substitution (c.1041A>T) in the X-linked MAGEB4 gene was identified as a no-stop mutation. The mutation is predicted to add 24 amino acids to the C-terminus of MAGEB4. Our functional studies were unable to detect any effect either on mRNA stability, intracellular localization of the protein, or the ability to homodimerize/heterodimerize with other MAGE proteins. We thus hypothesize that these additional amino acids may affect the proper protein interactions with MAGEB4 partners. Conclusion: The whole exome analysis of a consanguineous Turkish family revealed MAGEB4 as a possible new X-linked cause of inherited male infertility. This study provides the first clue to the physiological function of a MAGE protein. [ABSTRACT FROM AUTHOR]

Many cancers overexpress one or more of the six human pro-survival BCL2 family proteins to evade apoptosis. To determine which BCL2 protein or proteins block apoptosis in different cancers, we computationally designed three-helix bundle protein inhibitors specific for each BCL2 pro-survival protein. Following in vitro optimization, each inhibitor binds its target with high picomolar to low nanomolar affinity and at least 300-fold specificity. Expression of the designed inhibitors in human cancer cell lines revealed unique dependencies on BCL2 proteins for survival which could not be inferred from other BCL2 profiling methods. Our results show that designed inhibitors can be generated for each member of a closely-knit protein family to probe the importance of specific protein-protein interactions in complex biological processes. [ABSTRACT FROM AUTHOR]

New therapeutic targets are needed to address the poor prognosis of patients with highrisk multiple myeloma. Myeloma cells usually express a range of the prosurvival BCL2 proteins. To define the hierarchy of their relative importance for maintaining the survival of myeloma cells, we targeted each of them in a large panel of cell lines, using pharmacological inhibitors or gene editing or by peptide-based approaches, alone or in combination. The majority of well-established immortalized cell lines (17/25) or lowpassage myeloma cell lines (5/7) are readily killed when MCL1 is targeted, even including those cell lines sensitive to BCL2 inhibition. Targeting MCL1 also constrained the growth of myeloma in vivo. We also identified a previously unrecognized subset of myeloma that is highly BCLXL-dependent, and has the potential for cotargeting MCL1 and BCLXL. As MCL1 is pivotal for maintaining survival of most myelomas, it should be prioritized for targeting in the clinic once high-quality, validated inhibitors become available. [ABSTRACT FROM AUTHOR]

The low density lipoprotein receptor-related protein 1 (LRP1) is a ubiquitously expressed cell surface receptor that protects from intracellular cholesterol accumulation. However, the underlying mechanisms are unknown. Here we show that the extracellular (α) chain of LRP1 mediates TGFβ-induced enhancement of Wnt5a, which limits intracellular cholesterol accumulation by inhibiting cholesterol biosynthesis and by promoting cholesterol export. Moreover, we demonstrate that the cytoplasmic (β) chain of LRP1 suffices to limit cholesterol accumulation in LRP1-/- cells. Through binding of Erk2 to the second of its carboxyl-terminal NPXY motifs, LRP1 β-chain positively regulates the expression of ATP binding cassette transporter A1 (ABCA1) and of neutral cholesterol ester hydrolase (NCEH1). These results highlight the unexpected functions of LRP1 and the canonical Wnt5a pathway and new therapeutic potential in cholesterol-associated disorders including cardiovascular diseases. [ABSTRACT FROM AUTHOR]

During embryonic development, skeletal muscles arise from somites, which derive from the presomitic mesoderm (PSM). Using PSM development as a guide, we establish conditions for the differentiation of monolayer cultures of mouse embryonic stem (ES) cells into PSM-like cells without the introduction of transgenes or cell sorting. We show that primary and secondary skeletal myogenesis can be recapitulated in vitro from the PSM-like cells, providing an efficient, serum-free protocol for the generation of striated, contractile fibers from mouse and human pluripotent cells. The mouse ES cells also differentiate into Pax7+ cells with satellite cell characteristics, including the ability to form dystrophin+ fibers when grafted into muscles of dystrophin-deficient mdx mice, a model of Duchenne muscular dystrophy (DMD). Fibers derived from ES cells of mdx mice exhibit an abnormal branched phenotype resembling that described in vivo, thus providing an attractive model to study the origin of the pathological defects associated with DMD. [ABSTRACT FROM AUTHOR]