The renal factor in the post-traumatic "fluid overload" syndrome

Hypervolemia with hypertension often occurs 36-72 hours following massive blood and fluid replacement for hypovolemic shock. This syndrome of "fluid overload" has been attributed to the rapid intravascular flux of previously sequestered fluid in patients with impaired diuresis. This hypothesis was tested in 35 injured patients who received a mean of 9.3 L of blood and 17.4 L of salt during resucitation. The renal parameters measured soon after resuscitation included: 1) renal clearance of inulin (GFR), para-amino hippurate (ERPF), milliosmoles, sodium, and free water; 2) inulin space, renal vascular resistance (RVR), O2 consumption, renin, renal blood flow (RBF), and response to furosemide. Eighteen patients developed hypertension, hypervolemia, and respiratory insufficiency. When compared to the 17 normovolemic, non-hypertensive patients, the 18 hypervolemic patients had significantly increased RVR, with a significant decrease in RBF despite an increase in plasma volume and cardiac output. Furosemide produced less diuresis and natriuresis in the hypertensive patients. The balance between hypovolemia and "fluid overload" seemed percarious in the hypertensive patients. Peripheral renin and catecholamine levels were normal in both groups. Patients with post-traumatic "fluid overload" appear to have a combination of hypervolemia, respiratory insufficiency, hypertension, increased cardiac output, decreased extracellular fluid space, and decreased renal perfusion. These findings suggest that decreased interstitial fluid space compliance rather than "fluid overload" is the underlying factor leading to respiratory insufficiency. The therapeutic aspects of these findings are discussed.     

Psychosomatic disease and the problem of causation

Despite its impressive rate of growth in the past decades, an increasing amount if dissatisfaction with the area of psychosomatic medicine is reflected in recent literature. The discipline's failures relate to concepts of pathogenesis and therapeutic application of research findings. These failures are explained as a necessary consequence of the philosophical tenet of mind-body dualism which underlies medical theory. It is urged that advocates of psychosomatic medicine give the concept of "holism" meaning at the most fundamental level by establishing a rational basis for theory, or else forsake this line of research for others which yield causal relationships conductive to effective therapy.     

Learning from designing the RoboFesta—Blue Peter robots

Can children and adults learn anything from building robots? In 2001 we ran a robot design competition with the BBC TelevisionBlue Peter, program. Some 32 000 children, aged between 5 and 16 years, submitted paper designs. We built prototypes of the four winners' robots for a Robot Design MasterClass at the London Science Museum. It is widely believed that across the curriculum, robotics is a powerful force in motivating education. We ask what the children learned from the robot design process. Our answer is that they learned many things, both inside and outside the science and technology curriculum.     

A Conditionally Fluorescent Peptide Reporter of Secondary Structure Modulation

Proteins containing intrinsic disorder often form secondary structure upon interaction with a binding partner. Modulating such structures presents an approach for manipulating the resultant functional outcomes. Translational repressor protein 4E-BP1 is an example of an intrinsically disordered protein that forms an α-helix upon binding to its protein ligand, eIF4E. Current biophysical methods for analyzing binding-induced structural changes are low-throughput, require large amounts of sample, or are extremely sensitive to signal interference by the ligand itself. Herein, we describe the discovery and development of a conditionally fluorescent 4E-BP1 peptide that reports structural changes of its helix in high-throughput format. This reporter peptide is based on conditional quenching of fluorescein by thioamides. In this case, fluorescence signal increases as the peptide becomes more ordered. Conversely, destabilization of the α-helix results in decreased fluorescence signal. The low concentration and low volume of peptide required make this approach amenable for high-throughput screening to discover ligands that alter peptide secondary structure.     

Swelling and microstructure of austenitic stainless steel ChS-68 CW after high dose neutron irradiation

Austenitic stainless steel ChS-68 serving as fuel pin cladding was irradiated in the 20% cold-worked condition in the BN-600 fast reactor in the range 56-84 dpa. This steel was developed to replace EI-847 which was limited by its insufficient resistance to void swelling. Comparison of swelling between EI-847 and ChS-68 under similar irradiation conditions showed improvement of the latter steel by an extended transient regime of an additional ∼10 dpa. Concurrent with swelling was the development of a variety of phases. In the temperature range 430-460 °С where the temperature peak of swelling was located, the principal type of phase generated during irradiation was G-phase, with volume fraction increasing linearly with dose to ∼0.5% at 84 dpa. While the onset of swelling is concurrent with formation of G-phase, the action of G-phase cannot be confidently ascribed to significant removal from solution of swelling-suppressive elements such as silicon. A plausible mechanism for the higher resistance to void swelling of ChS-68 as compared with EI-847 may be related to an observed higher stability of faulted dislocation loops in ChS-68 that impedes the formation of a glissile dislocation network. The higher level of boron in ChS-68 is thought to be one contributor that might play this role.     

Three-dimensional integrated optics using polymers

Some of the key components are demonstrated to make three-dimensional (3-D) optical integrated circuits possible using polymers. Fabrication techniques of shadow reactive ion etching, shadow photolithography, and gray-level photolithography to produce complex 3-D integrated optic structures are demonstrated. Vertical waveguide bends exhibit excess losses of <0.3 dB, and vertical power splitters possess predictable output splitting ratios between multiple core levels with excess losses of <0.5 dB. Vertical polarization splitters exhibit power extinction ratios of 15 dB between the output core layers. A 1×4 vertical-horizontal power splitter is also demonstrated. Additionally, these techniques are used to integrate different polymer materials into the same optical circuit while easily solving the mode mismatch problem. To show the technique, a polymer electrooptic modulator is vertically integrated with a low-loss waveguide     

An eigenvector method for estimating item parameters of the dichotomous and polytomous Rasch models

The purpose of this paper is to describe a technique for obtaining item parameters of the Rasch model, a technique in which the item parameters are extracted from the eigenvector of a matrix derived from comparisons between pairs of items. The technique can be applied to both dichotomous and polytomous data. In application to a previously published data set, it is shown that the technique provides item parameter estimates comparable to those produced by joint maximum likelihood estimation, and for the most difficult items, the technique appears to produce superior estimates. This method has several advantages. It easily accommodates missing data, and makes transparent the basis for item parameter estimation in the presence of missing data. Furthermore, the method provides a link to other methods in the social sciences and, in particular, provides the framework for application of graph theory to the analysis of assessment networks. Finally, it exploits several characteristics that are unique to the Rasch model.     

Fabrication and characterization of high-speedpolyurethane-disperse red 19 integrated electrooptic modulators foranalog system applications

The fabrication and characterization of polymeric electrooptic modulators, made of a thermally crosslinkable polyurethane with Disperse Red 19 side chains, are summarized in this paper. Straight channel and Mach-Zehnder modulators have been fabricated, packaged and tested for the fiber-optic analog transmission system applications. Device performances including halfwave voltage, insertion loss, on-off ratio, and modulation frequency responses were measured. Long-term halfwave voltage stability, dc-bias voltage stability, and optical power handling capability at 1.3-μm wavelength were investigated. A carrier-to-noise ratio of 53 dB and 80-channel television transmission have been demonstrated using the packaged polymer modulators     

Cloning, expression, and characterization of a DNA binding domain of gpNu1, a phage lambda DNA packaging protein

Terminase is an enzyme from bacteriophage lambda that is required for insertion of the viral genome into an empty pro-capsid. This enzyme is composed of the viral proteins gpNu1 (20.4 kDa) and gpA (73.3 kDa) in a holoenzyme complex. Current models for terminase assembly onto DNA suggest that gpNu1 binds to three repeating elements within a region of the lambda genome known as cosB which, in turn, stimulates the assembly of a gpA dimer at the cosN subsite. This prenicking complex is the first of several stable nucleoprotein intermediates required for DNA packaging. We have noted a hydrophobic region within the primary amino acid sequence of the terminase gpNu1 subunit and hypothesized that this region constitutes a protein-protein interaction domain required for cooperative assembly at cosB and that is also responsible for the observed aggregation behavior of the isolated protein. We therefore constructed a mutant of gpNu1 in which this hydrophobic "domain" has been deleted in order to test these hypotheses. The deletion mutant protein, gpNu1DeltaK, is fully soluble and, unlike full-length protein, shows no tendency toward aggregation; However, the protein is a dimer under all experimental conditions examined as determined by gel permeation and sedimentation equilibrium analysis. The truncated protein is folded with evidence of secondary and tertiary structural elements by circular dichroism and NMR spectroscopy. While physical and biological assays demonstrate that gpNu1DeltaK does not interact with the terminase gpA subunit, the deletion mutant binds with specificity to cos-containing DNA. We have thus constructed a deletion mutant of the phage lambda terminase gpNu1 subunit which constitutes a highly soluble DNA binding domain of the protein. We further propose that the hydrophobic amino acids found between Lys100 and Pro141 define a self-association domain that is required for the assembly of stable nucleoprotein packaging complexes and that the C-terminal tail of the protein defines a distinct gpA-binding site that is responsible for terminase holoenzyme formation.