Clinically applicable optical imaging technology for body size and shape analysis: comparison of systems differing in design.

BACKGROUND/OBJECTIVES: Recent advances have extended anthropometry beyond flexible tape measurements to automated three-dimensional optical devices that rapidly acquire hundreds of body surface dimensions. Three new devices were recently introduced that share in common inexpensive optical cameras. The design, and thus potential clinical applicability, of these systems differ substantially leading us to critically evaluate their accuracy and precision. SUBJECTS/METHODS: 113 adult subjects completed evaluations by the three optical devices (KX-16 (16 stationary cameras), Proscanner (1 vertically oscillating camera), and Styku scanner (1 stationary camera)), air displacement plethysmography (ADP), dual-energy X-ray absorptiometry (DXA) and a flexible tape measure. Optical measurements were compared to reference method estimates that included results acquired by flexible tape, DXA and ADP. RESULTS: Optical devices provided respective circumference and regional volume estimates that overall were well-correlated with those obtained from flexible tape measurements (for example, hip circumference: R2, 0.91, 0.90, 0.96 for the KX-16, Proscanner, and Styku scanner, respectively) and DXA (for example, trunk volume: R2, 0.97, 0.97, and 0.98). Total body volumes measured by the optical devices were highly correlated with those from the ADP system (all R2s, 0.99). Coefficient of variations obtained from duplicate measurements (n, 55) were larger in optical than in reference measurements and significant (P<0.05) bias was present for some optical measurements relative to reference method estimates. CONCLUSIONS: Overall, the evaluated optical imaging systems differing in design provided body surface measurements that compared favorably with corresponding reference methods. However, our evaluations uncovered system measurement limitations, such as discrepancies in landmarking, that with correction have the potential to improve future developed devices.

Atmospheric, long baseline, and reactor neutrino data constraints on theta_{13}.

An atmospheric neutrino oscillation tool that uses full three-neutrino oscillation probabilities and a full three-neutrino treatment of the Mikheyev-Smirnov-Wolfenstein effect, together with an analysis of the K2K, MINOS, and CHOOZ data, is used to examine the bounds on theta_{13}. The recent, more finely binned, Super-K atmospheric data are employed. For L/E_{nu} greater, similar 10;{4} km/GeV, we previously found significant linear in theta_{13} terms. This analysis finds theta_{13} bounded from above by the atmospheric data while bounded from below by CHOOZ. The origin of this result arises from data in the previously mentioned very long baseline region; here, matter effects conspire with terms linear in theta_{13} to produce asymmetric bounds on theta_{13}. Assuming CP conservation, we find theta_{13} = -0.07_{-0.11};{+0.18} (90% C.L.).

A transmission imaging spectrograph and microfabricated channel system for DNA analysis.

In this paper we present the development of a DNA analysis system using a microfabricated channel device and a novel transmission imaging spectrograph which can be efficiently incorporated into a high throughput genomics facility for both sizing and sequencing of DNA fragments. The device contains 48 channels etched on a glass substrate. The channels are sealed with a flat glass plate which also provides a series of apertures for sample loading and contact with buffer reservoirs. Samples can be easily loaded in volumes up to 640 nL without band broadening because of an efficient electrokinetic stacking at the electrophoresis channel entrance. The system uses a dual laser excitation source and a highly sensitive charge-coupled device (CCD) detector allowing for simultaneous detection of many fluorescent dyes. The sieving matrices for the separation of single-stranded DNA fragments are polymerized in situ in denaturing buffer systems. Examples of separation of single-stranded DNA fragments up to 500 bases in length are shown, including accurate sizing of GeneCalling fragments, and sequencing samples prepared with a reduced amount of dye terminators. An increase in sample throughput has been achieved by color multiplexing.

Effect of a bath on the epicardial transmembrane potential during internal defibrillation shocks.

Using a three-dimensional model of cardiac tissue, we consider a rectangular slab of tissue. We examine the effect of a defibrillating shock from an intracavitary electrode upon the epicardial transmembrane potential (Vm) for two cases: one in which the epicardium is bounded by air and another in which it is bounded by a conductive bath. We find that the inclusion of the bath changes the polarity of the steady-state Vm in the epicardial region that is closest to the shock electrode. In addition, the magnitude of Vm is increased dramatically if the bath is present; the degree of hyperpolarization increases twenty-fivefold, while the degree of depolarization increases elevenfold. The remaining bulk of the cardiac tissue is relatively unaffected by the inclusion of the bath.

Electrical stimulation of cardiac tissue by a bipolar electrode in a conductive bath.

A three-dimensional (3-D) computer simulation of the electrical stimulation of passive cardiac tissue from a bipolar electrode placed within a conductive bath is presented. Through the bidomain model, the syncytial and anisotropic properties of cardiac tissue are taken into account; tissues with equal anisotropy and no transverse coupling are also considered. The membrane is represented by a capacitor and passive resistor in parallel. Located within an isotropic bath, the bipolar electrode is oriented either perpendicular or parallel to the tissue surface. For anisotropic tissue with a small cathode-tissue separation, the tissue surface is highly depolarized under the cathode with the depolarization persisting a considerable distance from the electrode in the transverse fiber direction. Adjacent to this region in the longitudinal direction, areas of hyperpolarization exist. At large distances from the cathode, the tissue surface is hyperpolarized in all directions when the electrode axis is perpendicular to the tissue. In the parallel case, surface depolarization creates buried regions of hyperpolarization. For the perpendicular configuration, the ratio of the steady-state maximum depolarization to steady-state maximum hyperpolarization, an estimate of the ratio of anodal to cathodal threshold, decreases rapidly with increasing cathode-tissue separation. In the parallel case, the depth of the conductive bath significantly affected the transmembrane potential distribution in the tissue. The use of a 3-D model more realistically simulates real-life electrical stimulation (such as stimulation with an implantable pacemaker) and provides insight into the effect of the volume conductor adjacent to the tissue.

Stimulation of MAP kinase by v-raf transformation of fibroblasts fails to induce hyperphosphorylation of transfected tau.

A proportion of the microtubule-associated protein, tau, is in an elevated state of phosphorylation in foetal and adult brain whereas all of the tau in paired helical filaments, which are characteristic of Alzheimer's disease is hyperphosphorylated; it is important therefore to elucidate the mechanisms that regulate tau phosphorylation. Here we describe results that show that although MAP kinase can hyperphosphorylate tau in vitro, activation of MAP kinase in transformed fibroblasts does not result in hyperphosphorylation of transfected tau, whereas glycogen synthase kinase-3 beta (GSK-3 beta) when co-transfected with tau does result in tau hyperphosphorylation. The findings imply that GSK-3 beta may be a stronger candidate than MAP kinase for inducing tau hyperphosphorylation in vivo.

Modulation of PHF-like tau phosphorylation in cultured neurones and transfected cells.

Two cellular systems have been used to investigate the modulation of tau hyperphosphorylation. In the first system, the effects of the excitatory amino acid glutamate, the microtubule destabilising agent colchicine, and beta 25-35-amyloid peptide on tau phosphorylation were studied in rat cortical neurones in primary culture. Using immunocytochemistry and western blot analysis, we demonstrated that tau in these cultures is normally highly phosphorylated, but a proportion becomes rapidly dephosphorylated following treatment of the cultures with glutamate or colchicine. These changes in tau phosphorylation occurred prior to cell death. In the second system, the ability of p42 MAP and p44 MAP kinases, glycogen synthase kinases 3 alpha and 3 beta (GSK-3 alpha and GSK-3 beta) to phosphorylate tau in transfected COS cells was investigated. Both GSK-3 alpha and GSK-3 beta phosphorylated tau to produce a PHF-like state of phosphorylation but the MAP kinases failed to induce such a transformation in tau. These results suggest that aberrant regulation of GSK-3 alpha/beta may be a pathogenic mechanism in Alzheimer's disease.

A scale for identifying "Stockholm syndrome" reactions in young dating women: factor structure, reliability, and validity.

The factor structure, reliability, and validity of a 49-item scale designed to measure Stockholm Syndrome (also referred to as "traumatic bonding" and "terror bonding"), that is, bonding with an abusive partner, were assessed for college women in heterosexual dating relationships. Factor analysis identified three major factors: Core Stockholm Syndrome, characterized by cognitive distortions and other strategies for coping with abuse; Psychological Damage, marked by depression, low self-esteem, and loss of sense of self; and Love-Dependence, typified by the feeling that one cannot survive without one's partner's love. The scale and factors had excellent internal consistency and good test-retest reliabilities. They correlated negatively with the Marlowe-Crowne Social Desirability scale and positively with Horowitz, Wilner, & Alvarez' (1979) Impact of Event Scale, Hyler and Rieder's (1987) Borderline Personality Disorder Scale, Hatfield and Sprecher's (1986) Passionate Love Scale, and Straus' (1979) Verbal Aggression and Violence scales of the Conflict Tactics Scales.

Alzheimer's disease-like phosphorylation of the microtubule-associated protein tau by glycogen synthase kinase-3 in transfected mammalian cells.

BACKGROUND: Paired helical filaments (PHFs) are a characteristic pathological feature of Alzheimer's disease; their principal component is the microtubule-associated protein tau. The tau in PHFs (PHF-tau) is hyperphosphorylated, but the cellular mechanisms responsible for this hyperphosphorylation have yet to be elucidated. A number of kinases, including mitogen-activated protein (MAP) kinase, glycogen synthase kinase (GSK)-3 alpha, GSK-3 beta and cyclin-dependent kinase-5, phosphorylate recombinant tau in vitro so that it resembles PHF-tau as judged by its reactivity with a panel of antibodies capable of discriminating between normal tau and PHF-tau, and by a reduced electrophoretic mobility that is characteristic of PHF-tau. To determine whether MAP kinase, GSK-3 alpha and GSK-3 beta can also induce Alzheimer's disease-like phosphorylation of tau in mammalian cells, we studied the phosphorylation status of tau in primary neuronal cultures and transfected COS cells following changes in the activities of MAP kinase and GSK-3. RESULTS: Activating MAP kinase in cultures of primary neurons or transfected COS cells expressing tau isoforms did not increase the level of phosphorylation for any PHF-tau epitope investigated. But elevating GSK-3 activity in the COS cells by co-transfection with GSK-3 alpha or GSK-3 beta decreased the electrophoretic mobility of tau so that it resembled that of PHF-tau, and induced reactivity with eight PHF-tau-selective monoclonal antibodies. CONCLUSIONS: Our data indicate that GSK-3 alpha and/or GSK-3 beta, but not MAP kinase, are good candidates for generating PHF-type phosphorylation of tau in Alzheimer's disease. The involvement of other kinases in the generation of PHFs cannot, however, be eliminated. Our results suggest that aberrant regulation of GSK-3 may be a pathogenic mechanism in Alzheimer's disease.