Proteins Marking the Sequence of Genotoxic Signaling from Irradiated Mesenchymal Stromal Cells to CD34+ Cells

Non-targeted effects (NTE) of ionizing radiation may initiate myeloid neoplasms (MN). Here, protein mediators (I) in irradiated human mesenchymal stromal cells (MSC) as the NTE source, (II) in MSC conditioned supernatant and (III) in human bone marrow CD34+ cells undergoing genotoxic NTE were investigated. Healthy sublethal irradiated MSC showed significantly increased levels of reactive oxygen species. These cells responded by increasing intracellular abundance of proteins involved in proteasomal degradation, protein translation, cytoskeleton dynamics, nucleocytoplasmic shuttling, and those with antioxidant activity. Among the increased proteins were THY1 and GNA11/14, which are signaling proteins with hitherto unknown functions in the radiation response and NTE. In the corresponding MSC conditioned medium, the three chaperones GRP78, CALR, and PDIA3 were increased. Together with GPI, these were the only four altered proteins, which were associated with the observed genotoxic NTE. Healthy CD34+ cells cultured in MSC conditioned medium suffered from more than a six-fold increase in γH2AX focal staining, indicative for DNA double-strand breaks, as well as numerical and structural chromosomal aberrations within three days. At this stage, five proteins were altered, among them IQGAP1, HMGB1, and PA2G4, which are involved in malign development. In summary, our data provide novel insights into three sequential steps of genotoxic signaling from irradiated MSC to CD34+ cells, implicating that induced NTE might initiate the development of MN.     

Use of copper shavings to remove mercury from contaminated groundwater or wastewater by amalgamation

The efficacy of copper shavings (Cu(0)) for the removal of Hg2+ from aqueous solution by amalgamation is demonstrated. Two kinds of copper shavings were investigated: (a) chemically processed shavings (Fluka) and (b) recycled shavings from scrap metal. Batch sorption experiments yielded very high retardation coefficients of 28 850-82 830 for the concentration range studied (1-10 000 microg/L Hg2+ dissolved in distilled water or in a 0.01 M CaCl2 matrix solution). Sorption data were well-described bythe Freundlich isotherm equation. Kinetic batch sorption experiments showed that 96-98% of Hg2+ was removed within 2 h. Column experiments were performed with a mercury solution containing 1000 microg/L Hg in a 0.01 M CaCl2 matrix with a flow rate of 0.5 m/d. No mercury breakthrough (c/c(0) = 0.5) could be detected after more than 2300 percolated pore volumes, and the high retardation coefficients determined in the batch studies could be confirmed. Copper was released from the shavings due to the amalgamation process and to copper corrosion by oxygen, resulting in concentrations of mobilized copper of 0.2-0.6 mg/L. Due to their high efficiency in removing Hg2+ from aqueous solution, the use of copper shavings for the removal of mercury from contaminated water is suggested, employing a sequential system of mercury amalgamation followed by the removal of mobilized copper by an ion exchanger such as zeolites. Possible applications could be in environmental technologies such as wastewater treatment or permeable reactive barriers for in situ groundwater remediation.     

The hydrodynamics of spherical capsules

With water as the conveying liquid the pressure gradient of a train of spheres is comprised of a basic pressure gradient due to shear of the surrounding liquid, to which has to be added a very small density-dependent increment due to solid friction, and a further increment due to any irregularity of the spheres. With viscous liquids the pressure gradient generally rises rapidly with specific gravity and with increase of viscosity. Even at the low specific gravity of 1.25 the power require-nients of cast spheres conveyed by water are generally lower than those of smooth cylinders, and the advantage increases with increase of specific gravity. However, the lower power require-uient has to be weighed against the possibly greater cost of forming spheres, and the cost of larger pipe that would be neces-sary to secure a given throughput, particularly if the spheres were run at low velocities to secure very low pressure gradients.     

Use of copper shavings to remove mercury from contaminated groundwater or wastewater by amalgamation

The efficacy of copper shavings (Cu(0)) for the removal of Hg2+ from aqueous solution by amalgamation is demonstrated. Two kinds of copper shavings were investigated: (a) chemically processed shavings (Fluka) and (b) recycled shavings from scrap metal. Batch sorption experiments yielded very high retardation coefficients of 28 850-82 830 for the concentration range studied (1-10 000 microg/L Hg2+ dissolved in distilled water or in a 0.01 M CaCl2 matrix solution). Sorption data were well-described bythe Freundlich isotherm equation. Kinetic batch sorption experiments showed that 96-98% of Hg2+ was removed within 2 h. Column experiments were performed with a mercury solution containing 1000 microg/L Hg in a 0.01 M CaCl2 matrix with a flow rate of 0.5 m/d. No mercury breakthrough (c/c(0) = 0.5) could be detected after more than 2300 percolated pore volumes, and the high retardation coefficients determined in the batch studies could be confirmed. Copper was released from the shavings due to the amalgamation process and to copper corrosion by oxygen, resulting in concentrations of mobilized copper of 0.2-0.6 mg/L. Due to their high efficiency in removing Hg2+ from aqueous solution, the use of copper shavings for the removal of mercury from contaminated water is suggested, employing a sequential system of mercury amalgamation followed by the removal of mobilized copper by an ion exchanger such as zeolites. Possible applications could be in environmental technologies such as wastewater treatment or permeable reactive barriers for in situ groundwater remediation.     

Three-dimensional extension of non-linear shell formulation based on the enhanced assumed strain concept

Conventional shell formulations, such as 3- or 5-parameter theories or even 6-parameter theories including the thickness change as extra parameter, require a condensation of the constitutive law in order to avoid a significant error due to the assumption of a linear displacement field across the thickness. This means that the normal stress in thickness direction has to either vanish or be constant. In general, these extra constraints cannot be satisfied explicitly or they Sead to elaborate strain expressions. The main objective of the present study is to introduce directly a complete 3-D constitutive law without modification. Therefore, a 7-parameter theory is utilized which includes a linear varying thickness stretch as extra variable allowing also large strain effects. In order to preserve the basic features of a displacement formulation the extra strain term is incorporated via the enhanced assumed strain concept recently proposed by Simo and Rifai to improve the performance of finite elements. Since the extra strain parameter can be eliminated on the element level after discretization, the formulation preserves the formal structure of a 6-parameter shell theory. The resulting hybrid-mixed shell formulation is applied to large deformation problems with hyperelasticity, small and large strain plasticity.     

A full genome scan for late onset Alzheimer's disease

We have genotyped 292 affected sibling pairs (ASPs) with Alzheimer's disease (AD) according to NINCDS-ADRDA diagnostic criteria and with onset ages of >/=65 years using 237 microsatellite markers separated by an average distance of 16.3 cM. Data were analysed by SPLINK and MAPMAKER/SIBS on the whole sample of 292 ASPs and subsets of 162 ASPs where both members possessed an apolipoprotein E (APOE)straightepsilon4 allele and 63 pairs where neither possessed anstraightepsilon4 allele. Sixteen peaks with a multipoint lod score (MLS) >1 either in the whole sample, the straightepsilon4-positive or -negative subgroups were observed on chromosomes 1 (two peaks), 2, 5, 6, 9 (two peaks), 10 (two peaks), 12, 13, 14, 19, 21 and X (two peaks). Simulation studies revealed that these findings exceeded those expected by chance, although many are likely to be false positives. The highest lod scores on chromosomes 1 (MLS 2.67), 9 (MLS 2.38), 10 (MLS 2.27) and 19 (MLS 1.79) fulfilLander and Kruglyak's definition of 'suggestive' in that they would be expected to occur by chance once or less per genome scan. Several other peaks were only marginally less significant than this, in particular those on chromosomes 14 (MLS 2.16), 5 (MLS 2.00), 12, close to alpha2-macroglobulin (MLS 1.91), and 21, close to amyloid precursor protein (MLS 1.77). This is the largest genome scan to date in AD and shows for the first time that this is a genetically complex disorder involving several, perhaps many, genes in addition to APOE. Moreover, our data will be of interest to those hoping to identify positional candidate genes using information emerging from neurobiological studies of AD.     

A compartmental model of zinc metabolism in healthy women using oral and intravenous stable isotope tracers

A mathematical model of zinc metabolism in six healthy women (average age: 30 +/- 11 y) was developed by using stable isotopes of zinc. After equilibration on a constant diet containing 7.0 mg Zn/d, an oral tracer highly enriched in 67Zn and an intravenous tracer highly enriched in 70Zn were administered simultaneously. Multiple plasma and 24-h urine samples were collected for the next 7 d with complete fecal collections for 11 d. Tracer-trace ratios in plasma, urine, and feces were calculated from isotope ratios of 67Zn to 66Zn and 70Zn to 66Zn measured by using inductively coupled plasma-mass spectrometry. An a priori identifiable model composed of seven compartments was developed to describe the kinetics of both tracers as well as that of naturally occurring zinc. The parameters of the model were fitted to the data by using the SAAM-CONSAM modeling software and were estimated with good precision. Several important, not directly measurable zinc variables were estimated (mean +/- SEM) from the model including the fractional absorption from the gastrointestinal tract (0.279 +/- 0.043), the rates of endogenous secretion (2.79 +/- 0.49 mg/d) and excretion (2.01 +/- 0.35 mg/d), the fractional turnover rate of the plasma pool (131 +/- 20/d), and the sizes (7.2 +/- 1.2 and 77.1 +/- 6.4 mg) and fractional turnover rates (22.3 +/- 7.1 and 1.49 +/- 0.18/d) of the fast and slow tissue pools equilibrating with the plasma, respectively.     

A Microprocessor-Controlled Chemical Detection and Alarm System Based on Ion Mobility Spectrometry

This paper describes a chemical alarm system based on ion mobility spectrometry. The system consists of an ion mobility cell, a microprocessor, and an operator interface. The unit is designed to alarm on specific chemical vapors based on a signal acquired from the ion mobility cell by the microprocessor. The microprocessor triggers the cell, collects the data, filters the data, and implements a decision process based on linear discriminant functions. The paper describes the overall system and looks at the filtering and decision processes in detail.     

“Bottom, thou art translated”: the making of VRML Dream

Bringing virtual theater to the Web requires 3D graphics, efficient networking, and strong content. We discuss the VRML Dream Project, a real time Internet performance. In the late summer of 1997, the authors sat in a pub in Toronto, Canada, and began planning an ambitious project: to create a new entertainment medium. The idea was to mount a live performance of Shakespeare's A Midsummer Night's Dream and “broadcast” it over the Internet. The sets, props, and all the characters were to be modeled using the Virtual Reality Modeling Language (VRML) 2.0. A group of actors would provide the voices, and puppeteers would control the characters. Both the voices and the motion data would be digitized, compressed, and sent out over the Internet in real time. Moreover, people would be able to access this broadcast with a 28.8-Kbps modem connection and a 150-MHz Pentium computer. Less than six months later, VRML Dream made Internet history (D. Coco, 1998). VRML Dream was the first live, streaming, VRML entertainment project with a running time of more than two or three minutes, and it proved that streaming both motion and voice data over standard Internet connections was possible. The article looks at the development of the project, its models and technology, and the main issues that influenced the final design. It also examines the technology needed to create live, streaming, real time 3D animation for the Internet as well as some of the challenges that lie ahead