The role of nucleation and of overlap in electrocrystallisation reactions

A generalised method of calculating the transients due to crystal growth processes is presented which allows separated for ingestion due to the acts of nucleation and crystal growth. General equations for two- and three-dimensional nucleation and crystal growth are derived and compared to the special cases which have been obtained previously.     

A Metallic Magnetic Calorimeter for Hard X-Ray and Gamma Ray Spectrometry

The CEA/LNHB is responsible for the determination and publication of atomic and nuclear data such as X-ray and gamma ray emission probabilities. In order to reduce uncertainties on the determination of these data, a high energy resolution associated with a good intrinsic detection efficiency is required. Hence taking into account these two aspects, we are developing cryogenic detectors, especially metallic magnetic calorimeters (MMCs) for photon spectrometry from few keV up to 200 keV. A MMC using a meander pick-up coil made of niobium thin films has been optimized. The gold absorber (diameter: 1.1 mm, thickness: 335 μm) has an intrinsic detection efficiency larger than 70% for photons from few keV up to 100 keV. From an energy spectrum obtained with a ¹³³Ba multi-gamma source, we have characterized this first detector. The energy resolution is 320 eV and 560 eV respectively at 30 keV and 357 keV. Possible improvements of the performance of the detector are discussed.     

Global sequence diversity of BRCA2: analysis of 71 breast cancer families and 95 control individuals of worldwide populations

The aim of this study was to evaluate the prevalence of simple sequence variation in the BRCA2 gene. To this end, 71 breast and breast-ovarian cancer (HBC/HBOC) families along with 95 control individuals from a wide range of ethnicities were analyzed by means of denaturing high-performance liquid chromatography (DHPLC) and direct sequence analysis. In the coding (10 257 bp) and non-coding (2799 bp) sequences of BRCA2, 82 sequence variants were identified. Three different, apparently disease-associated BRCA2 mutations were found in six HBC/HBOC families (8%): two splice site mutations in introns 5 and 21, and one frameshift mutation in exon 11. In the coding region, 53 simple sequence variants were found: 35 missense mutations, one 2 bp deletion (CT) resulting in a stop at codon 3364, one nonsense mutation with a stop at codon 3326, one deletion of a complete codon (AAA) resulting in the loss of leucine, and 15 silent mutations. In the non-coding region, 26 polymorphisms were detected. Of the 79 sequence variants that were not obviously disease-associated, eight were detected only in HBC/HBOC families. The remaining 71 variants were identified in both HBC/HBOC families and control individuals. Sixty three sequence variants (80%) were specific for a continent. Forty two percent (33 out of 79) of the sequence variants were detected exclusively in Africa, though only 13% of the 332 chromosomes screened were of African origin. Our data indicate that, in BRCA2, simple sequence variation is frequent [in the coding region 1 in 194 bp (straight theta = 2.2 x 10(-4)), and in the non-coding region 1 in 108 bp (straight theta = 4.4 x 10(-4)), respectively].     

Prototyping networked embedded systems

Sophisticated consumer devices that support multimedia-personal digital assistants, network computers, and mobile communication devices-pose challenges for embedded systems designers. The low-cost, consumer-oriented, fast time-to-market mentality that dominates embedded system design today forces design teams to use hardware-software codesign to cope with growing design complexities. New codesign methodologies and tools must support a key characteristic of next-generation embedded systems: the capability to communicate over networks and adapt to different operating environments. The paper discusses two emerging classes of embedded systems: multifunction systems and multimode systems     

DNA-PKcs: a T-cell tumour suppressor encoded at the mouse scid locus

Severe combined immunodeficiency (SCID) mice are defective in their ability to rearrange their variable (V), diversity (D) and joining (J) genetic elements to generate functional immunoglobulin (Ig) and T-cell receptor (TCR) molecules; as a result, they lack mature B and T cells. These mice are highly sensitive to ionizing radiation, suggesting that the product of the scid gene plays a critical role in both V(D)J recombination and DNA double-strand break repair. Recent studies suggest that the SCID defect lies in the gene encoding the catalytic subunit of DNA-dependent protein kinase (DNA-PK; refs 6-8), a nuclear protein made up of the Ku 70 and Ku 86 subunits as well as the large catalytic subunit, DNA-PKcs. Other reports have implied that the SCID phenotype correlates with nonsense mutations at the extreme 3' end of Prkdc, the DNA-PKcs gene. The identity of the gene remains in doubt, however, because the consequences of genetic inactivation of Prkdc have not been determined. This study shows that complete inactivation of Prkdc in a novel insertional mouse mutant recapitulates the SCID phenotype and that Prkdc and scid are alleic. Significantly, DNA-PKcs null mice demonstrate complete penetrance of thymic lymphoblastic lymphomas, strongly suggesting that Prkdc functions in mice as a T-cell tumour suppressor and, by virtue of its association with DNA repair and recombination, belongs to the 'caretaker' class of tumour-suppressor genes that includes ATM, BRCA1 and BRCA2 (ref. 15).     

Functional characteristics of ES cell-derived cardiac precursor cells identified by tissue-specific expression of the green fluorescent protein

In contrast to terminally differentiated cardiomyocytes, relatively little is known about the characteristics of mammalian cardiac cells before the initiation of spontaneous contractions (precursor cells). Functional studies on these cells have so far been impossible because murine embryos of the corresponding stage are very small, and cardiac precursor cells cannot be identified because of the lack of cross striation and spontaneous contractions. In the present study, we have used the murine embryonic stem (ES, D3 cell line) cell system for the in vitro differentiation of cardiomyocytes. To identify the cardiac precursor cells, we have generated stably transfected ES cells with a vector containing the gene of the green fluorescent protein (GFP) under control of the cardiac alpha-actin promoter. First, fluorescent areas in ES cell-derived cell aggregates (embryoid bodies [EBs]) were detected 2 d before the initiation of contractions. Since Ca2+ homeostasis plays a key role in cardiac function, we investigated how Ca2+ channels and Ca2+ release sites were built up in these GFP-labeled cardiac precursor cells and early stage cardiomyocytes. Patch clamp and Ca2+ imaging experiments proved the functional expression of the L-type Ca2+ current (ICa) starting from day 7 of EB development. On day 7, using 10 mM Ca2+ as charge carrier, ICa was expressed at very low densities 4 pA/pF. The biophysical and pharmacological properties of ICa proved similar to terminally differentiated cardiomyocytes. In cardiac precursor cells, ICa was found to be already under control of cAMP-dependent phosphorylation since intracellular infusion of the catalytic subunit of protein kinase A resulted in a 1.7-fold stimulation. The adenylyl cyclase activator forskolin was without effect. IP3-sensitive intracellular Ca2+ stores and Ca2+-ATPases are present during all stages of differentiation in both GFP-positive and GFP-negative cells. Functional ryanodine-sensitive Ca2+ stores, detected by caffeine-induced Ca2+ release, appeared in most GFP-positive cells 1-2 d after ICa. Coexpression of both ICa and ryanodine-sensitive Ca2+ stores at day 10 of development coincided with the beginning of spontaneous contractions in most EBs. Thus, the functional expression of voltage-dependent L-type Ca2+ channel (VDCC) is a hallmark of early cardiomyogenesis, whereas IP3 receptors and sarcoplasmic Ca2+-ATPases are expressed before the initiation of cardiomyogenesis. Interestingly, the functional expression of ryanodine receptors/sensitive stores is delayed as compared with VDCC.     

Severity assessment of acute pulmonary embolism with spiral CT: evaluation of two modified angiographic scores and comparison with clinical data

Adolescent patients qualifying for a DSM-II-R diagnosis of alcohol use disorder were studied to determine whether a multidimensional schema could classify subjects into subgroups. The Drug Use Screening Inventory was administered to 151 subjects. To test the concurrent validity of the subtypes, subjects also received a structured diagnostic psychiatric evaluation along with measures of personality, academic achievement, and drinking behavior. Two clusters were identified for each gender. Differences between clusters were reflected primarily on indicators of severity of disorder. Young women were more inclined toward affective disturbances, whereas conduct disorder was the most frequent disorder in young men. This study underscores the heterogeneity of the adolescent population qualifying for a diagnosis of alcohol use disorder. The differential pattern of alcohol involvement and comorbid psychopathology within clusters and between genders demonstrates the need for interventions tailored to specific clinical presentation.