bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose Separation Does Not Overcome the Pharmacokinetic Interaction between Fosamprenavir and Lopinavir/Ritonavir
Authors: Corbett Amanda H. , Patterson Kristine B. , Tien Hsiao-Chuan , Kalvass Leslie A. , Eron Joseph J. , Ngo Linh T. , Lim Michael L. , Kashuba Angela D. M.
Published: July 2006

Previous investigations have shown a significant negative two-way drug interaction between fosamprenavir (FPV) and lopinavir/ritonavir (LPV/RTV) in both human immunodeficiency virus (HIV)-infected patients and seronegative volunteers. This randomized, nonblinded, three-way crossover study of HIV-seronegative adult volunteers investigated dose separation and increased doses of RTV as a means to overcome the interaction between FPV and LPV/RTV. Eleven HIV-seronegative volunteers were given FPV plus LPV/RTV at 700 mg plus 400/100 mg every 12 hours (q12h) simultaneously for 10 days and then randomized to receive each of three 7-day treatments in one of six possible sequences, as follows: FPV plus LPV/RTV at 700 mg plus 400 mg/100 mg q12h simultaneously, FPV/RTV at 700 mg/100 mg q12h plus LPV/RTV at 400 mg/100 mg q12h, with doses separated by 4 h, and FPV/RTV at 1,400 mg/200 mg in the morning plus LPV/RTV at 800 mg/200 mg in the evening. Pharmacokinetic sampling was performed on day 8 of each treatment, and samples were analyzed for FPV, amprenavir (APV), LPV, and RTV concentrations by high-performance liquid chromatography-tandem mass spectrometry. Geometric mean ratios (GMR [with 95% confidence intervals]) for the 4- and 12-h dose separation strategies compared to simultaneous administration were calculated for the areas under the concentration-time curves from 0 to 24 h. Compared to simultaneous administration, RTV exposures increased with both 4-h and 12-h dose separation strategies (GMR, 5.30 [3.66 to 7.67] and 4.45 [3.09 to 6.41], respectively). LPV exposures also significantly increased with both 4-h and 12-h dose separation strategies (GMR, 1.76 [1.34 to 2.32] and 1.43 [1.02 to 2.01], respectively). However, both the 4- and 12-h strategies resulted in greater reductions in APV exposure (0.67 [0.54 to 0.83] and 0.77 [0.59 to 0.99], respectively) compared to simultaneous administration. Additional investigations are warranted to determine the optimal dosing of FPV with LPV/RTV.
Alkoxyalkyl Esters of (
S
)-9-[3-Hydroxy-2-(Phosphonomethoxy)Propyl]Adenine Are Potent Inhibitors of the Replication of Wild-Type and Drug-Resistant Human Immunodeficiency Virus Type 1 In Vitro
Authors: Hostetler Karl Y. , Aldern Kathy A. , Wan William B. , Ciesla Stephanie L. , Beadle James R.
Published: July 2006

(
S
)-9-[3-Hydroxy-2-(phosphonomethoxy)propyl]adenine [(
S
)-HPMPA], is an effective broad-spectrum antiviral against many DNA viruses but has been reported to be inactive against human immunodeficiency virus (HIV). We synthesized several alkoxyalkyl esters of (
S
)-HPMPA and now report that hexadecyloxypropyl-(
S
)-HPMPA [HDP-(
S
)-HPMPA] and octadecyloxyethyl-(
S
)-HPMPA [ODE-(
S
)-HPMPA]had 50% effective concentrations of 0.4 to 7.0 nanomolar and were nearly fully active against HIV variants having reverse transcriptase mutations M184V and K103N and against a zidovudine-resistant variant with mutations D67N, K70R, T215Y, and K219Q. Resistance to HDP-(
S
)-HPMPA and ODE-(
S
)-HPMPA was noted for a mutant with mutation K65R. HDP-(
S
)-HPMPA is also active against herpes simplex virus type 1, human cytomegalovirus, hepatitis B virus, adenoviruses, and orthopoxviruses and is worthy of further evaluation as a possibly therapy for HIV infection.
Outer Membrane Protein Changes and Efflux Pump Expression Together May Confer Resistance to Ertapenem in
Enterobacter cloacae
Authors: Szabó Dóra , Silveira Fernanda , Hujer Andrea M. , Bonomo Robert A. , Hujer Kristine M. , Marsh Jane W. , Bethel Christopher R. , Doi Yohei , Deeley Kathleen , Paterson David L.
Published: July 2006

We investigated ertapenem-susceptible and -resistant extended-spectrum β-lactamase-producing
Enterobacter cloacae
isolates obtained from the same patient. Gene transcription of OmpD and OmpF was diminished in the ertapenem-resistant isolate. An efflux pump inhibitor decreased the MICs of ertapenem in the resistant strain, suggesting a potential role of efflux pumps in ertapenem resistance.
Model for Intracellular Lamivudine Metabolism in Peripheral Blood Mononuclear Cells Ex Vivo and in Human Immunodeficiency Virus Type 1-Infected Adolescents
Authors: Zhou Zexun , Rodman John H. , Flynn Patricia M. , Robbins Brian L. , Wilcox Carrie K. , D'Argenio David Z.
Published: July 2006

The pharmacologic variability of nucleoside reverse transcriptase inhibitors such as lamivudine (3TC) includes not only systemic pharmacokinetic variability but also interindividual differences in cellular transport and metabolism. A modeling strategy linking laboratory studies of intracellular 3TC disposition with clinical studies in adolescent patients is described. Data from ex vivo laboratory experiments using peripheral blood mononuclear cells (PBMCs) from uninfected human subjects were first used to determine a model and population parameter estimates for 3TC cellular metabolism. Clinical study data from human immunodeficiency virus type 1-infected adolescents were then used in a Bayesian population analysis, together with the prior information from the ex vivo analysis, to develop a population model for 3TC systemic kinetics and cellular kinetics in PBMCs from patients during chronic therapy. The laboratory results demonstrate that the phosphorylation of 3TC is saturable under clinically relevant concentrations, that there is a rapid equilibrium between 3TC monophosphate and diphosphate and between 3TC diphosphate and triphosphate, and that 3TC triphosphate is recycled to 3TC monophosphate through a 3TC metabolite that remains to be definitively characterized. The resulting population model shows substantial interindividual variability in the cellular kinetics of 3TC with population coefficients of variation for model parameters ranging from 47 to 87%. This two-step ex vivo/clinical modeling approach using Bayesian population modeling of 3TC that links laboratory and clinical data has potential application for other drugs whose intracellular pharmacology is a major determinant of activity and/or toxicity.
qnr
Prevalence in Ceftazidime-Resistant
Enterobacteriaceae
Isolates from the United States
Authors: Robicsek A. , Strahilevitz J. , Sahm D. F. , Jacoby G. A. , Hooper D. C.
Published: July 2006

We screened 313 ceftazidime-resistant
Enterobacteriaceae
isolates obtained in the United States from 1999 to 2004 for all three known
qnr
genes. A
qnr
gene was present in 20% of
Klebsiella pneumoniae
isolates, 31% of
Enterobacter
sp. isolates, and 4% of
Escherichia coli
isolates.
qnrA
and
qnrB
occurred with equivalent frequencies and, except for
qnrB
in enterobacters, were stable over time.
qnrS
was absent.
LAGRANGE FORMULATION OF THE SYMMETRIC TELEPARALLEL GRAVITY
Authors: ADAK M. , KALAY M. , SERT Ö.
Published: July 2006

We develop a symmetric teleparallel gravity model in a space–time with only the nonmetricity as nonzero, in terms of a Lagrangian quadratic in the nonmetricity tensor. We present a detailed discussion of the variations that may be used for any gravitational formulation. We seek Schwarzschild-type solutions because of its observational significance and obtain a class of solutions that includes Schwarzschild-type, Schwarzschild–de Sitter-type, and Reissner–Nordström-type solutions for certain values of the parameters. We also discuss the physical relevance of these solutions.
CROSSING OF THE w = -1 BARRIER IN VISCOUS MODIFIED GRAVITY
Authors: BREVIK IVER
Published: July 2006

We consider a modified form of gravity in which the action contains a power α of the scalar curvature. It is shown how the presence of a bulk viscosity in a spatially flat universe may drive the cosmic fluid into the phantom region (w < -1) and thus into a Big Rip singularity, even if it lies in the quintessence region (w > -1) in the nonviscous case. The condition for this to occur is that the bulk viscosity contains the power (2α-1) of the scalar expansion. Two specific examples are discussed in detail. The present paper is a generalization of the recent investigation dealing with barrier crossing in Einstein's gravity: I. Brevik and O. Gorbunova, Gen. Relativ. Gravit.37, 2039 (2005).
Optimizing bitmap indices with efficient compression
Authors: Wu Kesheng , Otoo Ekow J. , Shoshani Arie
Published: July 2006

Bitmap indices are efficient for answering queries on low-cardinality attributes. In this article, we present a new compression scheme called
Word-Aligned Hybrid
(WAH) code that makes compressed bitmap indices efficient even for high-cardinality attributes. We further prove that the new compressed bitmap index, like the best variants of the B-tree index, is optimal for one-dimensional range queries. More specifically, the time required to answer a one-dimensional range query is a linear function of the number of hits. This strongly supports the well-known observation that compressed bitmap indices are efficient for multidimensional range queries because results of one-dimensional range queries computed with bitmap indices can be easily combined to answer multidimensional range queries. Our timing measurements on range queries not only confirm the linear relationship between the query response time and the number of hits, but also demonstrate that WAH compressed indices answer queries faster than the commonly used indices including projection indices, B-tree indices, and other compressed bitmap indices.
Real-time BRDF editing in complex lighting
Authors: Ben-Artzi Aner , Overbeck Ryan , Ramamoorthi Ravi
Published: July 2006

Current systems for editing BRDFs typically allow users to adjust analytic parameters while visualizing the results in a simplified setting (e.g. unshadowed point light). This paper describes a real-time rendering system that enables interactive edits of BRDFs, as rendered in their final placement on objects in a static scene, lit by direct, complex illumination. All-frequency effects (ranging from near-mirror reflections and hard shadows to diffuse shading and soft shadows) are rendered using a precomputation-based approach. Inspired by real-time relighting methods, we create a linear system that fixes lighting and view to allow real-time BRDF manipulation. In order to linearize the image's response to BRDF parameters, we develop an intermediate curve-based representation, which also reduces the rendering and precomputation operations to 1D while maintaining accuracy for a very general class of BRDFs. Our system can be used to edit complex analytic BRDFs (including anisotropic models), as well as measured reflectance data. We improve on the standard precomputed radiance transfer (PRT) rendering computation by introducing an incremental rendering algorithm that takes advantage of frame-to-frame coherence. We show that it is possible to render reference-quality images while only updating 10% of the data at each frame, sustaining frame-rates of 25-30fps.
Image enhancement by unsharp masking the depth buffer
Authors: Luft Thomas , Colditz Carsten , Deussen Oliver
Published: July 2006

We present a simple and efficient method to enhance the perceptual quality of images that contain depth information. Similar to an unsharp mask, the difference between the original depth buffer content and a low-pass filtered copy is utilized to determine information about spatially important areas in a scene. Based on this information we locally enhance the contrast, color, and other parameters of the image. Our technique aims at improving the perception of complex scenes by introducing additional depth cues. The idea is motivated by artwork and findings in the field of neurology, and can be applied to images of any kind, ranging from complex landscape data and technical artifacts, to volume rendering, photograph, and video with depth information.
The Shazam music recognition service
Authors: Wang Avery
Published: July 2006

Guided by a user's query-by-example music sample, it delivers the matching song, as well as related music information, of immediate interest to the user.
Desensitization of the pancreatic β-cell: effects of sustained physiological hyperglycemia and potassium
Authors: Yamazaki Hanae , Zawalich Kathleen C. , Zawalich Walter S.
Published: July 2006

The impact of modest but prolonged (3 h) exposure to high physiological glucose concentrations and hyperkalemia on the insulin secretory and phospholipase C (PLC) responses of rat pancreatic islets was determined. In acute studies, glucose (5–20 mM) caused a dose-dependent increase in secretion with maximal release rates 25-fold above basal secretion. When measured after 3 h of exposure to 5–10 mM glucose, subsequent stimulation of islets with 10–20 mM glucose during a dynamic perifusion resulted in dose-dependent decrements in secretion and PLC activation. Acute hyperkalemia (15–30 mM) stimulated calcium-dependent increases in both insulin secretion and PLC activation; however, prolonged hyperkalemia resulted in a biochemical and secretory lesion similar to that induced by sustained modest hyperglycemia. Glucose- (8 mM) desensitized islets retained significant sensitivity to stimulation by either carbachol or glucagon-like peptide-1. These findings emphasize the vulnerability of the β-cell to even moderate sustained hyperglycemia and provide a biochemical rationale for achieving tight glucose control in diabetic patients. They also suggest that PLC activation plays a critically important role in the physiological regulation of glucose-induced secretion and in the desensitization of release that follows chronic hyperglycemia or hyperkalemia.
Angiotensin II, interstitial inflammation, and the pathogenesis of salt-sensitive hypertension
Authors: Franco Martha , Martínez Flavio , Rodríguez-Iturbe Bernardo , Johnson Richard J. , Santamaría José , Montoya Angélica , Nepomuceno Tomas , Bautista Rocío , Tapia Edilia , Herrera-Acosta Jaime
Published: July 2006

Transient administration of ANG II causes persistent salt-sensitive hypertension associated with arteriolopathy, interstitial inflammation, and cortical vasoconstriction; blocking the vascular and inflammatory changes with mycophenolate mofetil (MMF) prevents vasoconstriction. While infiltrating leukocytes during the salt-sensitive hypertension phase express ANG II, the functional role of ANG II during this phase is not known. We examined the acute effect of candesartan on renal hemodynamics during the established salt-sensitive hypertensive phase and related these findings to direct measurement of intrarenal ANG II and inflammatory cells in rats previously exposed to ANG II with or without MMF treatment. Sham controls were also examined. The administration of ANG II, followed by exposure to high-salt diet, resulted in hypertension, cortical vasoconstriction, an increase in interstitial inflammatory cells (44.8 ± 1.3 lymphocytes/mm2, and 30.8 ± 1.2 macrophages/mm2ANG II vs. 19.6 ± 2 lymphocytes/mm2, and 22 ± 0.7 macrophages/mm2Sham), and increase in renal ANG II levels (1,358 ± 74.6 pg/ml ANG II vs. 194 ± 9.28 pg/ml Sham). Treatment with MMF during the administration of exogenous ANG II resulted in reduction in renal interstitial inflammation (19.7 ± 0.9 lymphocytes/mm2and 15.9 ± 0.8 machophages/mm2), ANG II levels (436.9 ± 52.29 pg/ml), cortical vasoconstriction, and stable blood pressure levels during the subsequent challenge with a high-salt diet. Acute administration of candesartan similarly reduced renal vasoconstriction and blood pressure. We conclude that the cortical vasoconstriction occurring with salt-sensitive hypertension following exposure to ANG II is mediated by intrarenal ANG II, related, at least in part, to the interstitial inflammation.
High Stiffness of Human Digital Flexor Tendons Is Suited for Precise Finger Positional Control
Authors: Ward Samuel R. , Loren Gregory J. , Lundberg Scott , Lieber Richard L.
Published: July 2006

The objective of this study was to define the biomechanical properties of the human digital flexor tendons and to compare these biomechanical properties to other muscle-tendon units in the forearm. Mechanical measurements were performed on fresh-frozen tendons under physiological load and temperature conditions. Loads were determined by first measuring the physiological cross-sectional area of each digital belly of the flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) and estimating maximum tension ( Po) of that specific muscle head. Loading each tendon to the appropriate Po resulted in no significant difference in tendon strain among any of the tendons within each muscle ( P > 0.05; digits 2–5) or between muscle types (FDP vs. FDS). The one exception to this finding was that a significantly higher strain at Po was observed in the FDP tendon to the small finger ( P < 0.05). Average absolute strains observed for the FDP and FDS tendons (1.20 ± 0.38%, mean ± SD; n = 39) were significantly lower than those observed previously in a study of the prime movers of the wrist. The measured strain of ∼1.5% was less than half of that predicted to occur in muscles of this architectural design. Modeling sarcomere shortening magnitudes during FDP or FDS contraction yielded a value of only 0.10 μm, which would have a negligible effect on the force generating capacity of these muscles. Thus the high stiffness of the digital flexor tendons suits them well for fine positional control and would render their muscle spindles quite sensitive to length perturbations at the fingertips.
Kidney collecting duct acid-base “regulon”
Authors: Cheval Lydie , Morla Luciana , Elalouf Jean-Marc , Doucet Alain
Published: July 2006

Kidneys are essential for acid-base homeostasis, especially when organisms cope with changes in acid or base dietary intake. Because collecting ducts constitute the final site for regulating urine acid-base balance, we undertook to identify the gene network involved in acid-base transport and regulation in the mouse outer medullary collecting duct (OMCD). For this purpose, we combined kidney functional studies and quantitative analysis of gene expression in OMCDs, by transcriptome and candidate gene approaches, during metabolic acidosis. Furthermore, to better delineate the set of genes concerned with acid-base disturbance, the OMCD transcriptome of acidotic mice was compared with that of both normal mice and mice undergoing an adaptative response through potassium depletion. Metabolic acidosis, achieved through an NH4Cl-supplemented diet for 3 days, not only induced acid secretion but also stimulated the aldosterone and vasopressin systems and triggered cell proliferation. Accordingly, metabolic acidosis increased the expression of genes involved in acid-base transport, sodium transport, water transport, and cell proliferation. In particular, >25 transcripts encoding proteins involved in urine acidification (subunits of H-ATPase, kidney anion exchanger, chloride channel Clcka, carbonic anhydrase-2, aldolase) were co-regulated during acidosis. These transcripts, which cooperate to achieve a similar function and are co-regulated during acidosis, constitute a functional unit that we propose to call a “regulon”.
An Alternative Foundation for the Planning and Evaluation of Linkage Analysis
Authors: Strug Lisa J. , Hodge Susan E.
Published: July 2006

The lod score, which is based on the likelihood ratio (LR), is central to linkage analysis. Users interpret lods by translating them into standard statistical concepts such as p values, α levels and power. An alternative statistical paradigm, the Evidential Framework, in contrast, works directly with the LR. A key feature of this paradigm is that it decouples error probabilities from measures of evidence. We describe the philosophy behind and the operating characteristics of this paradigm – based on new, alternatively-defined error probabilities. We then apply this approach to linkage studies of a genetic trait for: I. fully informative gametes, II. double backcross sibling pairs, and III. nuclear families. We consider complete and incomplete penetrance for the disease model, as well as using an incorrect penetrance. We calculate the error probabilities (exactly for situations I and II, via simulation for III), over a range of recombination fractions, sample sizes, and linkage criteria. We show how to choose linkage criteria and plan linkage studies, such that the probabilities of being misled by the data (i.e. concluding either that there is strong evidence favouring linkage when there is no linkage, or that there is strong evidence against linkage when there is linkage) are low, and the probability of observing strong evidence in favour of the truth is high. We lay the groundwork for applying this paradigm in genetic studies and for understanding its implications for multiple tests.
Sensitivity of Radiative–Convective Equilibrium Simulations to Horizontal Resolution
Authors: Pauluis Olivier , Garner Stephen
Published: July 2006

This paper investigates the impacts of horizontal resolution on the statistical behavior of convection. An idealized radiative–convective equilibrium is simulated for model resolutions ranging between 2 and 50 km. The simulations are compared based upon the analysis of the mean state, the energy and water vapor transport, and the probability distribution functions for various quantities. It is shown that, at a coarse resolution, the model is unable to capture the mixing associated with shallow clouds. This results in a dry bias in the lower troposphere, and in an excessive amount of water clouds. Despite this deficiency, the coarse resolution simulations are able to reproduce reasonably well the statistical properties of deep convective towers. This is particularly apparent in the cloud ice and vertical velocity distributions that exhibit a very robust behavior.

A theoretical scaling for the vertical velocity as function of the grid resolution is derived based upon the behavior of an idealized air bubble. It is shown that the vertical velocity of an ascending air parcel is determined by its aspect ratio, with a wide, flat parcel rising at a much slower pace than a narrow one. This theoretical scaling law exhibits a similar sensitivity to that of the numerical simulations. It is used to renormalize the probability distribution functions for vertical velocity, which show a very good agreement for resolutions up to 16 km. This new scaling law offers a way to improve direct simulations of deep convection in coarse resolution models.
Solar Tides as Revealed by Measurements of Mesosphere Temperature by the MLS Experiment on UARS
Authors: Forbes Jeffrey M. , Wu Dong
Published: July 2006

Temperatures between 25 and 86 km measured by the Microwave Limb Sounder (MLS) experiment on the Upper Atmosphere Research Satellite (UARS) are analyzed to delineate diurnal, semidiurnal, and terdiurnal tidal structures and stationary planetary waves. These Fourier components are determined from temperatures averaged in bins covering 5° latitude, 30° longitude and 1 h in local time. This study confirms the presence of diurnal nonmigrating tides with zonal wavenumbers s = 0, 2, −3 [s > 0 (s < 0) implying westward (eastward) propagation] and semidiurnal tides with s = 1 and 3, and some components of lesser importance that were previously determined from UARS wind measurements near 95 km. The seasonal–latitudinal and height structures of these components are now revealed, and utilized to aid in interpreting their behaviors and ascertaining their origins. New discoveries include the terdiurnal s = 2 and s = 4 components, and trapped nonmigrating diurnal tides with s = 0 and s = 2. The former are likely to arise from nonlinear interaction between the migrating (s = 3) terdiurnal tide and the stationary planetary wave with s = 1. The latter may reflect the presence of a longitude-dependent in situ heat source, or in situ nonlinear interaction between the migrating diurnal tide and a stationary planetary wave with s = 1. The present results provide a rich mixture of observational results to challenge both mechanistic and general circulation models of the middle atmosphere. In addition, internal consistency is established between the MLS tidal temperatures at 86 km and previously derived tidal winds at 95 km within the context of tidal theory. This result represents one step in the validation of measurements required for successful application of data-model assimilation techniques to the mesosphere and lower thermosphere.
Circulation Sensitivity to Tropopause Height
Authors: Williams G. P.
Published: July 2006

The possibility that the tropopause could be lower during an ice-age cooling leads to an examination of the general sensitivity of global circulations to the tropopause height by altering a constant stratospheric temperature Ts in calculations with a dry, global, multilevel, spectral, primitive equation model subject to a simple Newtonian heating function. In general, lowering the tropopause by increasing the stratospheric temperature causes the jet stream to move to lower latitudes and the eddies to become smaller. Near the standard state with Ts = 200 K, the jets relocate themselves equatorward by 2° in latitude for every 5 K increase in the stratospheric temperature. A double-jet system, with centers at 30° and 60° latitude, occurs when the equatorial tropopause drops to 500 mb (for Ts = 250 K), with the high-latitude component extending throughout the stratosphere.

The eddy momentum flux mainly traverses poleward across the standard jet at 40°, in keeping with the predominantly equatorward propagation of the planetary waves. But when the jet lies at 30° (for Ts = 225 K) the flux converges on the jet in keeping with planetary waves that propagate both equatorward and poleward. Two sets of such wave propagation occur in the double-jet system. As the troposphere becomes even shallower, the flux reverts to being primarily poleward across the jet (for Ts = 260 K) but then becomes uniquely primarily equatorward across the jet (for Ts = 275 K) before the circulation approaches extinction. Thus the existence of a predominantly poleward flux in the standard state appears to be parametrically fortuitous.
Numerical and Analytical Estimates of M2 Tidal Conversion at Steep Oceanic Ridges
Authors: Di Lorenzo Emanuele , Young William R. , Smith Stefan Llewellyn
Published: July 2006

Numerical calculations of the rate at which energy is converted from the external to internal tides at steep oceanic ridges are compared with estimates from analytic theories. The numerical calculations are performed using a hydrostatic primitive equation ocean model that uses a generalized s-coordinate system as the vertical coordinate. The model [Regional Ocean Modeling System (ROMS)] estimates of conversion compare well with inviscid and nondiffusive theory in the sub- and supercritical regimes and are insensitive to the strength of viscosity and diffusivity. In the supercritical regime, the nondissipative analytic solution is singular all along the internal tide beams. Because of dissipation the ROMS solutions are nonsingular, although the density gradients are strongly enhanced along the beams. The agreement between model and theory indicates that the prominent singularities in the inviscid solution do not compromise the estimates of tidal conversion and that the linearization used in deriving the analytical estimates is valid. As the model beams radiate from the generation site the density gradients are further reduced and up to 20% of the energy is lost by model dissipation (vertical viscosity and diffusion) within 200 km of the ridge. As a result of the analysis of the numerical calculations the authors also report on the sensitivity of tidal conversion to topographic misrepresentation errors. These errors are associated with inadequate resolution of the topographic features and with the smoothing required to run the ocean model. In regions of steep topographic slope (i.e., the Hawaiian Ridge) these errors, if not properly accounted for, may lead to an underestimate of the true conversion rate up to 50%.
Structure of the Baroclinic Tide Generated at Kaena Ridge, Hawaii
Authors: Nash Jonathan D. , Kunze Eric , Lee Craig M. , Sanford Thomas B.
Published: July 2006

Repeat transects of full-depth density and velocity are used to quantify generation and radiation of the semidiurnal internal tide from Kaena Ridge, Hawaii. A 20-km-long transect was sampled every 3 h using expendable current profilers and the absolute velocity profiler. Phase and amplitude of the baroclinic velocity, pressure, and vertical displacement were computed, as was the energy flux. Large barotropically induced isopycnal heaving and strong baroclinic energy-flux divergence are observed on the steep flanks of the ridge where upward and downward beams radiate off ridge. Directly above Kaena Ridge, strong kinetic energy density and weak net energy flux are argued to be a horizontally standing wave. The phasing of velocity and vertical displacements is consistent with this interpretation. Results compare favorably with the Merrifield and Holloway model.
Internal Tides and Turbulence along the 3000-m Isobath of the Hawaiian Ridge
Authors: Lee Craig M. , Sanford Thomas B. , Kunze Eric , Nash Jonathan D. , Merrifield Mark A. , Holloway Peter E.
Published: July 2006

Full-depth velocity and density profiles taken along the 3000-m isobath characterize the semidiurnal internal tide and bottom-intensified turbulence along the Hawaiian Ridge. Observations reveal baroclinic energy fluxes of 21 ± 5 kW m−1 radiating from French Frigate Shoals, 17 ± 2.5 kW m−1 from Kauai Channel west of Oahu, and 13 ± 3.5 kW m−1 from west of Nihoa Island. Weaker fluxes of 1–4 ± 2 kW m−1 radiate from the region near Necker Island and east of Nihoa Island. Observed off-ridge energy fluxes generally agree to within a factor of 2 with those produced by a tidally forced numerical model. Average turbulent diapycnal diffusivity K is (0.5–1) × 10−4 m2 s–1 above 2000 m, increasing exponentially to 20 × 10−4 m2 s–1 near the bottom. Microstructure values agree well with those inferred from a finescale internal wave-based parameterization. A linear relationship between the vertically integrated energy flux and vertically integrated turbulent dissipation rate implies that dissipative length scales for the radiating internal tide exceed 1000 km.
Tidal Mixing Events on the Deep Flanks of Kaena Ridge, Hawaii
Authors: Aucan Jerome , Merrifield Mark A. , Luther Douglas S. , Flament Pierre
Published: July 2006

A 3-month mooring deployment (August–November 2002) was made in 2425-m depth, on the south flank of Kaena Ridge, Hawaii, to examine tidal variations within 200 m of the steeply sloping bottom. Horizontal currents and vertical displacements, inferred from temperature fluctuations, are dominated by the semidiurnal internal tide with amplitudes of ≥ 0.1 m s−1 and ∼100 m, respectively. A series of temperature sensors detected tidally driven overturns with vertical scales of ∼100 m. A Thorpe scale analysis of the overturns yields a time-averaged dissipation near the bottom of 1.2 × 10−8 W kg−1, 10–100 times that at similar depths in the ocean interior 50 km from the ridge. Dissipation events much larger than the overall mean (up to 10−6 W kg−1) occur predominantly during two phases of the semidiurnal tide: 1) at peak downslope flows when the tidal stratification is minimum (N = 5 × 10−4 s−1) and 2) at the flow reversal from downslope to upslope flow when the tidal stratification is ordinarily increasing (N = 10−3 s−1). Dissipation associated with flow reversal mixing is 2 times that of downslope flow mixing. Although the overturn events occur at these tidal phases and they exhibit a general spring–neap modulation, they are not as regular as the tidal currents. Shear instabilities, particularly due to tidal strain enhancements, appear to trigger downslope flow mixing. Convective instabilities are proposed as the cause for flow reversal mixing, owing to the oblique propagation of the internal tide down the slope. The generation of similar tidally driven mixing features on continental slopes has been attributed to oblique wave propagation in previous studies. Because the mechanical energy source for mixing is primarily due to the internal tide rather than the surface tide, the observed intermittency of overturn events is attributed to the broadbanded nature of the internal tide.
Designing and Implementing E-Government Systems
Authors: Brewer Gene A. , Neubauer Bruce J. , Geiselhart Karin
Published: July 2006

This article explores the emerging challenges and opportunities of information technology in government and argues that designing and implementing e-government systems involves more than merely improving the instrumental processes of government. Democratic values can serve as design elements and anchors for these systems. Thus, the authors argue that public administrators should take an active role in designing and implementing e-government systems to instill democratic values and ensure that democratic processes and outcomes are realized. The resulting communications infrastructures can help government agencies respond quickly and effectively to chaotic events while still retaining their essential democratic nature.
Structural Features of Sibling Dyads and Attitudes Toward Sibling Relationships in Young Adulthood
Authors: Riggio Heidi R.
Published: July 2006

This study examined sibling-dyad structural variables (sex composition, age difference, current coresidence, position adjacency, family size, respondent and/or sibling ordinal position) and attitudes toward adult sibling relationships. A sample of 1,053 young adults ( M age = 22.1 years) described one sibling using the Lifespan Sibling Relationship Scale. Position adjacency and family size were related to attitudes toward sibling relationships, including more positive recalled childhood sibling relationships in adjacent dyads and larger families and less positive sibling relationships recalled from childhood and in adulthood experienced by individuals with only one sibling. Results for respondent and sibling ordinal position were consistent, with individuals in the youngest-of-two ordinal position and those describing eldest siblings reporting less positive attitudes toward adult siblings. Implications for future research on the quality of adult sibling relationships throughout the life span are discussed.
Stepfather Involvement and Adolescent Well-Being
Authors: Yuan Anastasia S. Vogt , Hamilton Hayley A.
Published: July 2006

Using the National Longitudinal Study of Adolescent Health, the authors explore how aspects of stepfather involvement are related to adolescent well-being and whether these relationships depend on maternal involvement, non-residential father involvement, or amount of time in the household. Results indicate that a close, nonconflictual stepfather-stepchild relationship improves adolescent well-being, but it is most beneficial when the adolescent also has a close, nonconflictual mother-child relationship. Engaging in shared activities with the stepfather decreases depression when the stepfather has been in the household for a longer period of time. The relationships between stepfather involvement and adolescent well-being are separate from nonresidential father involvement.
Litigating Equality
Authors: Zeigler Sara L.
Published: July 2006

This article assesses the effectiveness of legal remedies available under the Equal Pay Act (EPA) in closing the gender gap in pay. Although employers frequently attribute women’s lesser pay to lags in seniority and the life choices made by women, the evidence suggests that the narrow language of the EPA, its omission of the more subtle forms of sex discrimination, and the powerful disincentives for most women to pursue claims under the act have rendered it largely ineffective in curtailing sex discrimination in compensation. Through an examination of recent developments in the area of pay equality, the article demonstrates that the act, as enforced, has produced neither equality nor equity. Arguing that the reality of sex discrimination in pay shapes life choices (rather than the reverse), the article identifies the obstacles to closing the pay gap and strategies for more effective enforcement.
A Mixed Bag
Authors: Wilkins Vicky M.
Published: July 2006

In Smith v. City of Jackson, Mississippi (2005), the U.S. Supreme Court held that employees may bring disparate impact claims under the Age Discrimination inEmploymentAct(ADEA). Asaresult, olderworkerscannowpursuean ADEA claim if they are disproportionately harmed by a policy that their employer applies to its entire workforce, even if the resulting adverse impact on workers older than 40 is unintentional. This article reviews the ruling and discusses the implications of the revisions on the work of public personnel managers.
Polyvinyl Alcohol—Gelatin Patches of Salicylic Acid: Preparation, Characterization and Drug Release Studies
Authors: Pal Kunal , Banthia A. K. , Majumdar D. K.
Published: July 2006

Polyvinyl alcohol—gelatin patches were developed and salicylic acid was incorporated at different stages of preparation of the patches. The patches were characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), differential scanning calorimetry, tensile strength test, and scanning electron microscopy. The release patterns of the drug from the patches were also studied. The FTIR spectra of the blank patch indicated complete esterification of the free carboxylic groups of gelatin. The XRD studies indicated a crystalline form of the drug entrapped in the patches. Release of the drug from the patches followed Higuchian/Fickian kinetics indicating a diffusion-controlled release process.
Roles and Influence in Marriages: Both Spouses' Perceptions Contribute to Marital Commitment
Authors: Weigel Daniel J. , Bennett Kymberley K. , Ballard‐Reisch Deborah S.
Published: July 2006

This study used responses from both spouses to examine the multiple ways in which perceptions of roles and influence were related to marital commitment. Using a dyadic approach, the authors investigated four types of associations—self, cross‐spouse, gender, and additive—among perceptions of role and influence quality with reports of marital commitment. Data gathered from 107 married couples revealed that when spouses saw their roles and levels of influence in the relationship as equal, fair, and satisfying, they were more likely to experience positive levels of commitment. In addition, the findings indicated that people's perceptions of commitment were associated not only by their own perceptions of roles and influence but also with the perceptions of their partners. Findings are discussed in relation to the need to take account of both spouses' perceptions when examining marital commitment.
Legal Standards for Establishing Concealment: A Theoretical Framework for Statistical Analysis
Authors: Mason Marianne , Mason Robert
Published: July 2006

This article demonstrates a technique linguists can use to objectively determine a speaker’s intent to conceal. The article reviews the theoretical foundation for classifying reference forms in wiretapped data. After classifying data obtained from a criminal trial that involves speakers from a drug cartel, the article presents simple statistics to support the argument that a speaker’s intent to conceal can be objectively determined, provided a larger study is undertaken to set statistical standards as reference points. The article contains an outline on how to conduct this study.
The Training of Law Enforcement Officers in Detecting Deception: A Survey of Current Practices and Suggestions for Improving Accuracy
Authors: Colwell Lori H. , Miller Holly A. , Lyons Phillip M. , Miller Rowland S.
Published: July 2006

The current study surveyed a random sample of Texas law enforcement officers (N = 109) about their training in detecting deception. Texas officers reported that their training entailed the equivalent of a 2-day, lecture-style workshop in the kinesic interview technique or Reid technique, two popular police training modules, with subsequent training more often the exception than the rule. The authors examine these results in light of previous social science research regarding officers’ accuracy in detecting deception and make suggestions for future training programs for police officers in this area.
Deadly Force Programs Among Larger U.S. Police Departments
Authors: Morrison Gregory B.
Published: July 2006

A police firearms training survey collected data on U.S. state and larger municipal and county police departments (N = 51) regarding in-service deadly force program staffing models and instructor development, training frameworks, requalification, and access to information from officer-involved shootings. Findings reveal a wide range of policies and practices among departments, although there were no statistically significant correlations between particular program variables or factors and violent crime levels or numbers of self-reported officer-involved shootings. There are important implications for deadly force training among the many findings, and this article concludes with recommendations designed to improve the empirical foundation of contemporary police deadly force programs.
Cluster analysis for DNA methylation profiles having a detection threshold
Authors: Marjoram Paul , Chang Jing , Laird Peter W , Siegmund Kimberly D
Published: July 2006

Background

DNA methylation, a molecular feature used to investigate tumor heterogeneity, can be measured on many genomic regions using the MethyLight technology. Due to the combination of the underlying biology of DNA methylation and the MethyLight technology, the measurements, while being generated on a continuous scale, have a large number of 0 values. This suggests that conventional clustering methodology may not perform well on this data.

Results

We compare performance of existing methodology (such as k-means) with two novel methods that explicitly allow for the preponderance of values at 0. We also consider how the ability to successfully cluster such data depends upon the number of informative genes for which methylation is measured and the correlation structure of the methylation values for those genes. We show that when data is collected for a sufficient number of genes, our models do improve clustering performance compared to methods, such as k-means, that do not explicitly respect the supposed biological realities of the situation.

Conclusion

The performance of analysis methods depends upon how well the assumptions of those methods reflect the properties of the data being analyzed. Differing technologies will lead to data with differing properties, and should therefore be analyzed differently. Consequently, it is prudent to give thought to what the properties of the data are likely to be, and which analysis method might therefore be likely to best capture those properties.
Molecular characterization of retinal stem cells and their niches in adult zebrafish
Authors: Raymond Pamela A , Barthel Linda K , Bernardos Rebecca L , Perkowski John J
Published: July 2006

Background

The persistence in adult teleost fish of retinal stem cells that exhibit all of the features of true 'adult stem cells' – self-renewal, multipotency, and the capacity to respond to injury by mitotic activation with the ability to regenerate differentiated tissues – has been known for several decades. However, the specialized cellular and molecular characteristics of these adult retinal stem cells and the microenvironmental niches that support their maintenance in the differentiated retina and regulate their activity during growth and regeneration have not yet been elucidated.

Results

Our data show that the zebrafish retina has two kinds of specialized niches that sustain retinal stem cells: 1) a neuroepithelial germinal zone at the interface between neural retina and ciliary epithelium, called the ciliary marginal zone (CMZ), a continuous annulus around the retinal circumference, and 2) the microenvironment around some Müller glia in the differentiated retina. In the uninjured retina, scattered Müller glia (more frequently those in peripheral retina) are associated with clusters of proliferating retinal progenitors that are restricted to the rod photoreceptor lineage, but following injury, the Müller-associated retinal progenitors can function as multipotent retinal stem cells to regenerate other types of retinal neurons. The CMZ has several features in common with the neurogenic niches in the adult mammalian brain, including access to the apical epithelial surface and a close association with blood vessels. Müller glia in the teleost retina have a complex response to local injury that includes some features of reactive gliosis (up-regulation of glial fibrillary acidic protein, GFAP, and re-entry into the cell cycle) together with dedifferentiation and re-acquisition of phenotypic and molecular characteristics of multipotent retinal progenitors in the CMZ (diffuse distribution of N-cadherin, activation of Notch-Delta signaling, and expression of rx1, vsx2/Chx10, and pax6a) along with characteristics associated with radial glia (expression of brain lipid binding protein, BLBP). We also describe a novel specific marker for Müller glia, apoE.

Conclusion

The stem cell niches that support multi-lineage retinal progenitors in the intact, growing and regenerating teleost retina have properties characteristic of neuroepithelia and neurogenic radial glia. The regenerative capacity of the adult zebrafish retina with its ability to replace lost retinal neurons provides an opportunity to discover the molecular regulators that lead to functional repair of damaged neural tissue.
Differential activation of nerve fibers with magnetic stimulation in humans
Authors: Tuday Eric C , Olree Kenneth S , Horch Kenneth W
Published: July 2006

Background

Earlier observations in our lab had indicated that large, time-varying magnetic fields could elicit action potentials that travel in only one direction in at least some of the myelinated axons in peripheral nerves. The objective of this study was to collect quantitative evidence for magnetically induced unidirectional action potentials in peripheral nerves of human subjects. A magnetic coil was maneuvered to a location on the upper arm where physical effects consistent with the creation of unidirectional action potentials were observed.

Electromyographic (EMG) and somatosensory evoked potential (SEP) recordings were then made from a total of 20 subjects during stimulation with the magnetic coil.

Results

The relative amplitudes of the EMG and SEP signals changed oppositely when the current direction in the magnetic coil was reversed. This effect was consistent with current direction in the coil relative to the arm for all subjects.

Conclusion

A differential evocation of motor and sensory fibers was demonstrated and indicates that it may be possible to induce unidirectional action potentials in myelinated peripheral nerve fibers with magnetic stimulation.