bluuebunny/crossref_metadata_2025 huggingface dataset:
Leitlinien zur Diagnostik und Psychotherapie von depressiven Störungen im Kindes- und Jugendalter: Ein evidenzbasierter Diskussionsvorschlag
Authors: Ihle Wolfgang , Ahle Maria Elisabeth , Jahnke Dörte , Esser Günter
Published: May 2004

Zusammenfassung. Ein Entwurf evidenzbasierter Leitlinien zur Diagnostik und Psychotherapie von depressiven Störungen im Kindes- und Jugendalter wird vorgestellt. Für die Diagnosestellung depressiver Störungen im Kindes- und Jugendalter müssen die gleichen diagnostischen Kriterien nach ICD-10 erfüllt sein wie für Erwachsene. Allerdings kann das klinische Bild einer Depression in verschiedenen Altersgruppen deutlich variieren. Depressive Störungen sind vor allem im Jugendalter häufig, chronische Verläufe und Rückfälle treten auf und sie gehen oft mit komorbiden Störungen wie Angststörungen, Störungen des Sozialverhaltens und Störungen durch Substanzgebrauch einher. Wirksame Interventionsansätze zur Prävention depressiver Störungen und zur Akutbehandlung bei leichten und mittelschweren depressiven Störungen stehen zur Verfügung. Die psychotherapeutischen Interventionen der Wahl stellen derzeit kognitiv-verhaltenstherapeutische Ansätze (KVT) und die interpersonale Therapie (IPT) dar. Die Antidepressiva der Wahl sind derzeit selektive Serotoninwiederaufnahmehemmer (SSRI). Weitere Studien, vor allem hinsichtlich Rückfallprophylaxe und der Evaluation der Wirksamkeit einer Kombinationsbehandlung von Psychotherapie mit antidepressiver Medikation stehen noch aus.
Leitlinien zur Diagnostik und Psychotherapie von aggressiv-dissozialen Störungen im Kindes- und Jugendalter: Ein evidenzbasierter Diskussionsvorschlag
Authors: Döpfner Manfred , Petermann Franz
Published: May 2004

Zusammenfassung. Es wird ein Vorschlag zu evidenzbasierten Leitlinien zur Diagnostik und Psychotherapie aggressiv-dissozialer Störungen formuliert; die Ausführungen schließen Aussagen zur Behandlung oppositionellen Trotzverhaltens mit ein. Für eine aussagekräftige Diagnostik wird eine multimodale Strategie empfohlen. Auf der Basis eines differenzialtherapeutischen Entscheidungsbaumes werden Interventionsstrategien empfohlen und das Prozedere detailliert ausgeführt.
Effects of wave shape on sheet flow sediment transport
Authors: Hsu Tian‐Jian , Hanes Daniel M.
Published: May 2004

A two‐phase model is implemented to study the effects of wave shape on the transport of coarse‐grained sediment in the sheet flow regime. The model is based on balance equations for the average mass, momentum, and fluctuation energy for both the fluid and sediment phases. Model simulations indicate that the responses of the sheet flow, such as the velocity profiles, the instantaneous bed shear stress, the sediment flux, and the total amount of the mobilized sediment, cannot be fully parameterized by quasi‐steady free‐stream velocity and may be correlated with the magnitude of local horizontal pressure gradient (or free‐stream acceleration). A net sediment flux in the direction of wave advance is obtained for both skewed and saw‐tooth wave shapes typical of shoaled and breaking waves. The model further suggests that at critical values of the horizontal pressure gradient, there is a failure event within the bed that mobilizes more sediment into the mobile sheet and enhances the sediment flux. Preliminary attempts to parameterize the total bed shear stress and the total sediment flux appear promising.
California Undercurrent variability and eddy transport estimated from RAFOS float observations
Authors: Collins Curtis A. , Ivanov Leonid M. , Melnichenko Oleg V. , Garfield Newell
Published: May 2004

RAFOS float observations collected between 1992 and 2002 were analyzed to identify the seasonal variability of circulation in four geographical boxes which extended along the central and northern California coast and were successively located farther offshore. The mean pressure of the floats was 375 dbar. Poleward flow associated with the California Undercurrent dominated the two boxes closest to shore, extending from the 400‐m isobath to a distance of 190 km offshore. For the box closest to shore, the monthly mean alongshore velocity was maximum (minimum), 5.4 cm/s (1.7 cm/s), in May–June (February), while the eddy kinetic energy (EKE) was minimum was 33 cm2/s2 (21 cm2/s2) in September (December–February). The mean EKE in the coastal region was 28 cm2/s2, increasing to 50 cm2/s2 for the region farthest offshore, a distance of about 400 km. For that region farthest offshore, EKE had a broad maximum from June to November and a minimum in April. Lagrangian correlation and dispersion tensors were estimated for floats that left the coastal region. Three different dispersive regimes of float motion were identified as ballistic transport, normal diffusion, and anomalous sub‐diffusion. Westward sub‐diffusion was induced by Rossby wave‐like structures with a periodicity of 100–120 days.
Spectral composition and quanta‐to‐energy ratio of diffuse photosynthetically active radiation under diverse cloud conditions
Authors: Dye Dennis G.
Published: May 2004

Accurate and detailed modeling of vegetation photosynthesis and ecosystem‐atmosphere CO2 exchange, particularly for forests, requires data on the diffuse and global fluxes of photosynthetically active radiation (PAR) (400–700 nm). Such ecosystem process models typically employ PAR data in quantum units (photosynthetic photon flux density, Qp, μmol m−2 s−1), although PAR is often reported in energy units (irradiance, Rp, W m−2). Reliable conversion of diffuse PAR data from energy units (Rp,d, W m−2) to quantum units (Qp,d, μmol m−2 s−1) requires knowledge of how the conversion factor β*p,d (quanta‐to‐energy ratio for diffuse PAR at an arbitrary timescale, μmol J−1) varies across a broad range of sky conditions that includes variations in cloudiness, including broken clouds. This study employs spectral measurements of the diffuse irradiance of PAR to examine the influence of a diverse range of observed sky conditions on the spectral composition of Rp,d and the value of β*p,d at 1‐minute and daily timescales. The results indicate that the enhanced contribution of green‐to‐red (550–700 nm) radiation to the spectral composition of Rp,d, induced by atmospheric scattering and diffuse reflectance by clouds, causes β*p,d at the daily timescale (β′p,d) to increase nonlinearly by up to 7% relative to clean, cloudless sky conditions. The relation is explained well (R = 0.98) by the equation β′p,d = (4.5886 × f′p,d)/(0.010773 + f′p,d), where f′p,d is equal to the diffuse fraction of the daily total irradiation of global PAR. These results may be useful for conversion of diffuse PAR data between energy and quantum units for environments where clouds are the dominant agent of atmospheric scattering. The observed quanta‐to‐energy ratio for global PAR at the daily timescale (β′p,g), while not strictly constant, is relatively insensitive to atmospheric scattering, and a representative value of 4.56 μmol J−1 may be employed for a wide range of cloud conditions with little or no error.
Maximum likelihood Bayesian averaging of spatial variability models in unsaturated fractured tuff
Authors: Ye Ming , Neuman Shlomo P. , Meyer Philip D.
Published: May 2004

Hydrologic analyses typically rely on a single conceptual‐mathematical model. Yet hydrologic environments are open and complex, rendering them prone to multiple interpretations and mathematical descriptions. Adopting only one of these may lead to statistical bias and underestimation of uncertainty. Bayesian model averaging (BMA) [Hoeting et al., 1999] provides an optimal way to combine the predictions of several competing models and to assess their joint predictive uncertainty. However, it tends to be computationally demanding and relies heavily on prior information about model parameters.Neuman[2002,2003]proposed a maximum likelihood version (MLBMA) of BMA to render it computationally feasible and to allow dealing with cases where reliable prior information is lacking. We apply MLBMA to seven alternative variogram models of log air permeability data from single‐hole pneumatic injection tests in six boreholes at the Apache Leap Research Site (ALRS) in central Arizona. Unbiased ML estimates of variogram and drift parameters are obtained using adjoint state maximum likelihood cross validation [Samper and Neuman, 1989a] in conjunction with universal kriging and generalized least squares. Standard information criteria provide an ambiguous ranking of the models, which does not justify selecting one of them and discarding all others as is commonly done in practice. Instead, we eliminate some of the models based on their negligibly small posterior probabilities and use the rest to project the measured log permeabilities by kriging onto a rock volume containing the six boreholes. We then average these four projections and associated kriging variances, using the posterior probability of each model as weight. Finally, we cross validate the results by eliminating from consideration all data from one borehole at a time, repeating the above process and comparing the predictive capability of MLBMA with that of each individual model. We find that MLBMA is superior to any individual geostatistical model of log permeability among those we consider at the ALRS.
Forest harvesting impacts on the peak flow regime in the Columbia Mountains of southeastern British Columbia: An investigation using long‐term numerical modeling
Authors: Schnorbus Markus , Alila Younes
Published: May 2004

Numerical hydrologic simulation, in combination with synthetic weather generation, was used to assess the sensitivity of the peak flow regime for hourly, daily, and 7‐day discharge to hypothetical harvesting scenarios in Redfish Creek in southern British Columbia. Simulation was based on stationary vegetation cover, thus representing potential peak flow regime adjustments during the first few critical years following harvesting. The relative difference between preharvest and postharvest peak discharge quantiles (ΔQT), estimated by comparing GEV distributions fit to the simulated preharvest and postharvest annual maximum series, tended to increase with increasing harvest area; however, the relationship was strongly influenced by the elevation distribution of harvest blocks. Although rainfall was determined to be a factor in roughly three quarters of all peak discharge events, the flood frequency of Redfish Creek is fundamentally a function of the frequency structure of snowmelt runoff. Consequently, changes in runoff synchronization between various elevation bands largely drove the magnitude of ΔQT, and the degree of increased synchronization was found to be greatest following harvesting above H60 (elevation above which lies 60% of basin area) and least following harvesting below H60. As a result, only harvesting schemes that incorporated cut blocks above H60 tended to generate significant (α = 0.05) ΔQTfor a wide range of return periods (T), regardless of discharge timescale. Significant ΔQTranged from 6 to 14% for hourly, 5 to 14% for daily, and 5 to 20% for 7‐day discharge in the range of 1.25 ≤T≤ 100 years. For a given scenario, hourly and daily ΔQTshowed little variation withT, suggesting that small and large discharge events responded similarly to forest harvesting. However, this apparent trend substantially overstates ΔQTfor the largest hourly and daily peak discharge events such that the relationship of ΔQTtoTis inconclusive forT> 30 years. For 7‐day discharge, ΔQTincreases with increasingTfor 1.25 ≤T≤ 100 years.
Rapid ice discharge from southeast Greenland glaciers
Authors: Rignot E. , Braaten D. , Gogineni S. P. , Krabill W. B. , McConnell J. R.
Published: May 2004

Interferometric synthetic‐aperture radar (InSAR) observations of southeast Greenland glaciers acquired by the Earth Remote Sensing Satellites (ERS‐1/2) in 1996 were combined with ice sounding radar data collected in the late 1990s to estimate a total discharge of 46 ± 3 km3 ice per year between 62°N and 66°N, which is significantly lower than a mass input of 29 ± 3 km3 ice per year calculated from a recent compilation of snow accumulation data. Further north, Helheim Glacier discharges 23 ± 1 km3/yr vs 30 ± 3 km3/yr accumulation; Kangerdlugssuaq Glacier discharges 29 ± 2 km3/yr vs 23 ± 2 km3/yr; and Daugaard‐Jensen Glacier discharges 10.5 ± 0.6 km3/yr vs 10.5 ± 1 km3/yr. The mass balance of east Greenland glaciers is therefore dominated by the negative mass balance of southeast Greenland glaciers (−17 ± 4 km3/yr), equivalent to a sea level rise of 0.04 ± 0.01 mm/yr. Warmer and drier conditions cannot explain the imbalance which we attribute to long‐term changes in ice dynamics.
Optical cavity resonances in water micro‐droplets: Implications for shortwave cloud forcing
Authors: Cappa C. D. , Wilson K. R. , Messer B. M. , Saykally R. J. , Cohen R. C.
Published: May 2004

The influence of narrow optical resonances, which result from trapping of light rays via total internal reflection in water droplets, on the absorption of shortwave (SW) solar radiation has been estimated through high resolution Mie scattering calculations. Our results indicate that these resonances engender an increase in absorption of solar radiation by cloud droplets that is several W/m2above the linear direct absorption process. Mie scattering calculations performed at the Δx = 0.1 (x = 2πr/λ) resolution typically implemented in cloudy sky radiative transfer models are shown to be insufficient for accurate determination of the attenuation of SW radiation when considered over relatively narrow wavelength ranges, consistent with the recent finding ofNussenzveig[2003]. However, for broadband calculations we find positive and negative errors in Mie calculations at Δx = 0.1 nearly cancel resulting in reasonable estimates of SW attenuation.
Viscoelastic deformation for a clustered earthquake cycle
Authors: Meade Brendan J. , Hager Bradford H.
Published: May 2004

The clustering of earthquakes in time on the same fault affects the rate and pattern of interseismic deformation. We develop a simple analytic viscoelastic model of the surface velocity field through a clustered earthquake cycle by superposing the velocities of individual earthquake cycles of constant period but varying phase. Velocity profiles prior to and after an earthquake show a wider range of behavior than they do for earthquake cycles with constant repeat times. These new types of behavior provide possible explanations for discrepancies between geologic estimates of long‐term fault slip rates and slip rate estimates from geodetic data.
Akimotoite to perovskite phase transition in MgSiO3
Authors: Wentzcovitch R. M. , Stixrude L. , Karki B. B. , Kiefer B.
Published: May 2004

The akimotoite to perovskite phase transition of MgSiO3 is shown by first principles calculations to have a negative Clapeyron slope, consistent with experimental observations. The origin of the negative slope, i.e., the increase of entropy across the transformation, can be attributed to the larger density of states of low frequency vibrations in the perovskite phase. Such vibrations consist of 1) magnesium displacements and 2) octahedral rotations, with the larger magnesium coordination and larger Mg‐O bond lengths, as well as a lower degree of polyhedral connectivity accounting for the existence of low frequency modes. The larger density of states in perovskite in this regime accounts also for the increase in other thermodynamic properties across the phase transition. This ab initio calculation of a solid‐solid phase boundary provides new insights into our ability to predict high pressure‐temperature transformations by first principles.
Egg viability and worker policing in honey bees
Authors: Pirk Christian W. W. , Neumann Peter , Hepburn Randall , Moritz Robin F. A. , Tautz Jürgen
Published: May 2004

In many species of social Hymenoptera, unmated workers can lay eggs that will produce males by parthenogenesis. Nevertheless, in queenright honey bee colonies (
Apis mellifera
), worker reproduction is low. One possible mechanism for this difference is worker policing, the removal of worker-laid eggs by other workers. This behavior can evolve in species in which queens are multiply mated, where workers are more closely related to the sons of their mother than those of their sisters. Another possible mechanism of the low level of worker reproduction is worker-laid eggs being less viable than queen-laid eggs. We show that this difference in quality is the case for honey bees.
Long-term combined beneficial effects of physical training and metabolic treatment on atherosclerosis in hypercholesterolemic mice
Authors: Napoli Claudio , Williams-Ignarro Sharon , de Nigris Filomena , Lerman Lilach O. , Rossi Loredana , Guarino Carmen , Mansueto Gelsomina , Di Tuoro Francesco , Pignalosa Orlando , De Rosa Gaetano , Sica Vincenzo , Ignarro Louis J.
Published: May 2004

The pathogenic mechanisms by which physical exercise influences atherosclerotic lesion formation remain poorly understood. Because vigorous physical training increases oxidative stress, this study tested the hypothesis that graduated and moderate physical exercise together with metabolic intervention (
l
-arginine and antioxidants) may contribute to increased vascular protection. Exercise training in mice was induced by graduated swimming. In hypercholesterolemic male mice on an atherogenic high-cholesterol diet, graduated and moderate exercise lowered plasma cholesterol and decreased atherosclerotic lesions compared with sedentary control mice. Antioxidants (1.0% vitamin E added to the chow and 0.05% vitamin C added to the drinking water) and
l
-arginine (6% in drinking water) supplementation to exercising hypercholesterolemic mice further and synergistically reduced atherosclerosis compared with untreated exercised mice. Arterial oxidation-specific epitopes and systemic oxidative stress were reduced by metabolic intervention. Graduated chronic exercise elicited an increase in production of nitric oxide through increased endothelial nitric oxide synthase expression and ameliorated scavenger activities. Thus, metabolic intervention with
l
-arginine and antioxidants together with graduated and moderate exercise training reduce atherosclerotic lesion formation.
The 5′-HS4 chicken β-globin insulator is a CTCF-dependent nuclear matrix-associated element
Authors: Yusufzai Timur M. , Felsenfeld Gary
Published: May 2004

The protein CTCF plays an essential role in the action of a widely distributed class of vertebrate enhancer-blocking insulators, of which the first example was found in a DNA sequence element, HS4, at the 5′ end of the chicken β-globin locus. HS4 contains a binding site for CTCF that is necessary and sufficient for insulator action. Purification of CTCF has revealed that it interacts with proteins involved in subnuclear architecture, notably nucleophosmin, a 38-kDa nucleolar phosphoprotein that is concentrated in nuclear matrix preparations. In this report we show that both CTCF and the HS4 insulator element are incorporated in the matrix; HS4 incorporation depends on the presence of an intact CTCF-binding site. However the DNA sequence in the neighborhood of HS4 is not like that of canonical matrix attachment regions, and its incorporation into the matrix fraction is not sensitive to ribonuclease, suggesting that the insulator is a distinct matrix-associated element.
53BP1 is required for class switch recombination
Authors: Ward Irene M. , Reina-San-Martin Bernardo , Olaru Alexandru , Minn Kay , Tamada Koji , Lau Julie S. , Cascalho Marilia , Chen Lieping , Nussenzweig Andre , Livak Ferenc , Nussenzweig Michel C. , Chen Junjie
Published: May 2004

53BP1 participates early in the DNA damage response and is involved in cell cycle checkpoint control. Moreover, the phenotype of mice and cells deficient in 53BP1 suggests a defect in DNA repair (Ward et al., 2003b). Therefore, we asked whether or not 53BP1 would be required for the efficient repair of DNA double strand breaks. Our data indicate that homologous recombination by gene conversion does not depend on 53BP1. Moreover, 53BP1-deficient mice support normal V(D)J recombination, indicating that 53BP1 is not required for “classic” nonhomologous end joining. However, class switch recombination is severely impaired in the absence of 53BP1, suggesting that 53BP1 facilitates DNA end joining in a way that is not required or redundant for the efficient closing of RAG-induced strand breaks. These findings are similar to those observed in mice or cells deficient in the tumor suppressors ATM and H2AX, further suggesting that the functions of ATM, H2AX, and 53BP1 are closely linked.
The Cell Fate Determinant Numb Interacts with EHD/Rme-1 Family Proteins and Has a Role in Endocytic Recycling
Authors: Smith Christian A. , Dho Sascha E. , Donaldson Julie , Tepass Ulrich , McGlade C. Jane
Published: May 2004

The adaptor protein Numb is necessary for the cell fate specification of progenitor cells in the Drosophila nervous system. Numb is evolutionarily conserved and previous studies have provided evidence for a similar functional role during mammalian development. The Numb protein has multiple protein-protein interaction regions including a phosphotyrosine binding (PTB) domain and a carboxy-terminal domain that contains conserved interaction motifs including an EH (Eps15 Homology) domain binding motif and α-adaptin binding site. In this study we identify the EHD/Rme-1/Pincher family of endocytic proteins as Numb interacting partners in mammals and Drosophila. The EHD/Rme-1 proteins function in recycling of plasma membrane receptors internalized by both clathrin-mediated endocytosis and a clathrin-independent pathway regulated by ADP ribosylation factor 6 (Arf6). Here we report that Numb colocalizes with endogenous EHD4/Pincher and Arf6 and that Arf6 mutants alter Numb subcellular localization. In addition, we present evidence that Numb has a novel function in endosomal recycling and intracellular trafficking of receptors.
Temporal Characteristics of the Predictive Synchronous Firing Modeled by Spike-Timing-Dependent Plasticity
Authors: Kitano Katsunori , Fukai Tomoki
Published: May 2004

When a sensory cue was repeatedly followed by a behavioral event with fixed
delays, pairs of premotor and primary motor neurons showed significant
increases of coincident spikes at times a monkey was expecting the event.
These results provided evidence that neuronal firing synchrony has predictive
power. To elucidate the underlying mechanism, here we argue some nontrivial
characteristics of the predictive synchronous firing developed by
spike-timing-dependent plasticity in a paradigm similar to classical
conditioning. We find that the computationally developed synchrony shows the
modulations of temporal precision, which are quite similar to those observed
experimentally. Thus, our model suggests that the important characteristics of
predictive synchronous firing, which were previously attributed to an animal's
higher cognitive function, can emerge from a synaptic-level mechanism.
Sex-Related Hemispheric Lateralization of Amygdala Function in Emotionally Influenced Memory: An fMRI Investigation
Authors: Cahill Larry , Uncapher Melina , Kilpatrick Lisa , Alkire Mike T. , Turner Jessica
Published: May 2004

The amygdala appears necessary for enhanced long-term memory associated with emotionally arousing events. Recent brain imaging investigations support this view and indicate a sex-related hemispheric lateralization exists in the amygdala relationship to memory for emotional material. This study confirms and further explores this finding. Healthy men and women underwent functional Magnetic Resonance Imaging (fMRI) while viewing a series of standardized slides that were rated by the subjects as ranging from emotionally neutral to highly arousing. Two weeks later, memory for the slides was assessed in an incidental recognition test. The results demonstrate a significantly stronger relationship in men than in women between activity of the right hemisphere amygdala and memory for those slides judged as arousing, and a significantly stronger relationship in women than in men between activity of the left hemisphere amygdala and memory for arousing slides. An ANOVA confirmed a significant interaction between sex and hemisphere regarding amygdala function in memory. These results provide the strongest evidence to date of a sex-related hemispheric lateralization of amygdala function in memory for emotional material. Furthermore, they underscore the view that investigations of neural mechanisms underlying emotionally influenced memory must anticipate, and begin to account for, the apparently substantial influence of sex.
Learning and Memory Deficits Upon TAU Accumulation in Drosophila
Mushroom Body Neurons
Authors: Mershin Andreas , Pavlopoulos Elias , Fitch Olivia , Braden Brittany C. , Nanopoulos Dimitri V. , Skoulakis Efthimios M.C.
Published: May 2004

Mutations in the neuronal-specific microtubule-binding protein TAU are
associated with several dementias and neurodegenerative diseases. However, the
effects of elevated TAU accumulation on behavioral plasticity are unknown. We
report that directed expression of wild-type vertebrate and
Drosophila TAU in adult mushroom body neurons, centers for olfactory
learning and memory in Drosophila, strongly compromised associative
olfactory learning and memory, but olfactory conditioning-relevant osmotactic
and mechanosensory responses remained intact. In addition, TAU accumulation in
mushroom body neurons did not result in detectable neurodegeneration or
premature death. Therefore, TAU-mediated structural or functional perturbation
of the microtubular cytoskeleton in mushroom body neurons is likely causal of
the behavioral deficit. These results indicate that behavioral plasticity
decrements may be the earliest detectable manifestations of tauopathies.
Activity of cGMP-Dependent Protein Kinase (PKG) Affects Sucrose Responsiveness and Habituation inDrosophila melanogaster
Authors: Scheiner Ricarda , Sokolowski Marla B. , Erber Joachim
Published: May 2004

The cGMP-dependent protein kinase (PKG) has many cellular functions in vertebrates and insects that affect complex behaviors such as locomotion and foraging. Theforaging(for) gene encodes a PKG inDrosophila melanogaster. Here, we demonstrate a function for theforgene in sensory responsiveness and nonassociative learning. Larvae of the natural variant sitter (fors) show less locomotor activity during feeding and have a lower PKG activity than rover (forR) larvae. We used rover and sitter adult flies to test whether PKG activity affects (1) responsiveness to sucrose stimuli applied to the front tarsi, and (2) habituation of proboscis extension after repeated sucrose stimulation. To determine whether the differences observed resulted from variation in theforgene, we also testedfors2, a sitter mutant produced on a rover genetic background. We found that rovers (forR) were more responsive to sucrose than sitters (forsandfors2) at 1-, 2-, and 3-wk old. This was true for both sexes. Differences in sucrose responsiveness between rovers and sitters were greater after 2 h of food deprivation than after 24 h. Of flies with similar sucrose responsiveness,forRrovers showed less habituation and generalization of habituation thanforsandfors2sitters. These results show that the PKG encoded byforindependently affects sensory responsiveness and habituation inDrosophila melanogaster.
Task Requirements Influence Sensory Integration During Grasping in Humans
Authors: Säfström Daniel , Edin Benoni B.
Published: May 2004

The sensorimotor transformations necessary for generating appropriate motor
commands depend on both current and previously acquired sensory information.
To investigate the relative impact (or weighting) of visual and haptic
information about object size during grasping movements, we let normal
subjects perform a task in which, unbeknownst to the subjects, the object seen
(visual object) and the object grasped (haptic object) were never the same
physically. When the haptic object abruptly became larger or smaller than the
visual object, subjects in the following trials automatically adapted their
maximum grip aperture when reaching for the object. This adaptation was not
dependent on conscious processes. We analyzed how visual and haptic
information were weighted during the course of sensorimotor adaptation. The
adaptation process was quicker and relied more on haptic information when the
haptic objects increased in size than when they decreased in size. As such,
sensory weighting seemed to be molded to avoid prehension error. We conclude
from these results that the impact of a specific source of sensory information
on the sensorimotor transformation is regulated to satisfy task
requirements.
Context-Dependent Olfactory Learning in an Insect
Authors: Matsumoto Yukihisa , Mizunami Makoto
Published: May 2004

We studied the capability of the cricket Gryllus bimaculatus to
select one of a pair of odors and to avoid the other in one context and to do
the opposite in another context. One group of crickets was trained to
associate one of a pair of odors (conditioned stimulus, CS1) with water reward
(appetitive unconditioned stimulus, US+) and another odor (CS2) with saline
solution (aversive US, US-) under illumination and to associate CS1 with US-
and CS2 with US+ in the dark. Another group of crickets received training of
the opposite stimulus arrangement. At 1 d after the training for 3 d, the
former group significantly preferred CS1 over CS2 under illumination but
preferred CS2 over CS1 in the dark, and the latter group exhibited the
opposite odor preference. The results of control experiments showed that the
background light condition had no significant effects on memory formation or
retrieval unless it was explicitly associated with US during training. Thus,
the visual context affected learning performance only when crickets were
requested to use it to disambiguate the meaning of CSs and to predict USs.
Selective Modulation of Some Forms of Schaffer Collateral-CA1 Synaptic
Plasticity in Mice With a Disruption of the CPEB-1 Gene
Authors: Alarcon Juan M. , Hodgman Rebecca , Theis Martin , Huang Yi-Shuian , Kandel Eric R. , Richter Joel D.
Published: May 2004

CPEB-1 is a sequence-specific RNA binding protein that stimulates the
polyadenylation-induced translation of mRNAs containing the cytoplasmic
polyadenylation element (CPE). Although CPEB-1 was identified originally in
Xenopus oocytes, it has also been found at postsynaptic sites of hippocampal
neurons where, in response to N-methyl-D-aspartate receptor
activation, it is thought to induce the polyadenylation and translation of
αCaMKII and perhaps other CPE-containing mRNAs. Because some forms of
synaptic modification appear to be influenced by local (synaptic) protein
synthesis, we examined long-term potentiation (LTP) in CPEB-1 knockout mice.
Although the basal synaptic transmission of Schaffer collateral-CA1 neurons
was not affected in the knockout mice, we found that there was a modest
deficit in LTP evoked by a single train of 100 Hz stimulation, but a greater
deficit in LTP evoked by one train of theta-burst stimulation. In contrast,
LTP evoked by either four trains of 100 Hz stimulation or five trains of
theta-burst stimulation were not or were only modestly affected, respectively.
The deficit in LTP evoked by single stimulation in knockout mice appeared
several minutes after tetanic stimulation. Long-term depression (LTD) evoked
by 1 Hz stimulation was moderately facilitated; however, a stronger and more
enduring form of LTD induced by paired-pulse 1 Hz stimulation was unaffected.
These data suggest that CPEB-1 contributes in the translational control of
mRNAs that is critical only for some selected forms of LTP and LTD.
Enhancement of Inhibitory Avoidance and Conditioned Taste Aversion Memory With Insular Cortex Infusions of 8-Br-cAMP: Involvement of the Basolateral Amygdala
Authors: Miranda María I. , McGaugh James L.
Published: May 2004

There is considerable evidence that in rats, the insular cortex (IC) and
amygdala are involved in the learning and memory of aversively motivated
tasks. The present experiments examined the effects of 8-Br-cAMP, an analog of
cAMP, and oxotremorine, a muscarinic agonist, infused into the IC after
inhibitory avoidance (IA) training and during the acquisition/consolidation of
conditioned taste aversion (CTA). Posttraining infusion into the IC of 0.3
μg oxotremorine and 1.25 μg 8-Br-cAMP enhanced IA retention. Infusions
of 8-Br-cAMP, but not oxotremorine, into the IC enhanced taste aversion. The
experiments also examined whether noradrenergic activity in the basolateral
amygdala (BLA) is critical in enabling the enhancement of CTA and IA memory
induced by drug infusions administered into the IC. For both CTA and IA,
ipsilateral infusions of β-adrenergic antagonist propranolol administered
into the BLA blocked the retention-enhancing effect of 8-Br-cAMP or
oxotremorine infused into the IC. These results indicate that the IC is
involved in the consolidation of memory for both IA and CTA, and this effect
requires intact noradrenergic activity into the BLA. These findings provide
additional evidence that the BLA interacts with other brain regions, including
sensory cortex, in modulating memory consolidation.
Neurobiological and Endocrine Correlates of Individual Differences in Spatial Learning Ability
Authors: Sandi Carmen , Cordero M. Isabel , Merino José J. , Kruyt Nyika D. , Regan Ciaran M. , Murphy Keith J.
Published: May 2004

The polysialylated neural cell adhesion molecule (PSA-NCAM) has been implicated in activity-dependent synaptic remodeling and memory formation. Here, we questioned whether training-induced modulation of PSA-NCAM expression might be related to individual differences in spatial learning abilities. At 12 h posttraining, immunohistochemical analyses revealed a learning-induced up-regulation of PSA-NCAM in the hippocampal dentate gyrus that was related to the spatial learning abilities displayed by rats during training. Specifically, a positive correlation was found between latency to find the platform and subsequent activated PSA levels, indicating that greater induction of polysialylation was observed in rats with the slower acquisition curve. At posttraining times when no learning-associated activation of PSA was observed, no such correlation was found. Further experiments revealed that performance in the massed water maze training is related to a pattern of spatial learning and memory abilities, and to learning-related glucocorticoid responsiveness. Taken together, our findings suggest that the learning-related neural circuits of fast learners are better suited to solving the water maze task than those of slow learners, the latter relying more on structural reorganization to form memory, rather than the relatively economic mechanism of altering synaptic efficacy that is likely used by the former.
A Cell-Permeable Phospholipase Cγ1-Binding Peptide Transduces Neurons and Impairs Long-Term Spatial Memory
Authors: Blum Sonja , Dash Pramod K.
Published: May 2004

Growth factor-mediated signaling has emerged as an essential component of
memory formation. In this study, we used a phospholipase C gamma 1
(PLCγ1) binding, cell-penetrating peptide to sequester PLCγ1 away
from its target, the phosphotyrosine residues within the activated growth
factor receptor. Peptides appear to transduce neurons but not astrocytes or
oligodendrocytes. The presence of the peptides in the hippocampus during
training in the Morris water maze significantly impaired long-term memory, but
not memory acquisition. These results, along with previous studies on
extracellular signal-regulated kinase (ERK) and phosphoinositide-3 kinase
(PI3K), implicate all three key growth factor receptor-activated intracellular
signaling pathways in memory storage.
Time‐Dependent ROC Curves for Censored Survival Data and a Diagnostic Marker
Authors: Heagerty Patrick J. , Lumley Thomas , Pepe Margaret S.
Published: May 2004

Summary. ROC curves are a popular method for displaying sensitivity and specificity of a continuous marker, X, for a binary disease variable, D. However, many disease outcomes are time dependent, D(t, and ROC curves that vary as a function of time may be mire appropriate. A common examples of a time‐dependent variable is vital status, where D(t) = 1 if a patient has died prior to time t and zero otherwise. We propose summarizing the discrimination potential of a marker X, measured at baseline (t= 0), by calculating ROC Curves for cumulative disease or death incidence by time t, which we denote as ROC(t). A typical complexity with survival data is that observations may be censored. Two ROC curve estimators are proposed that can accommodate censored data. A simple estimator is based on using the Kaplan‐Meier estimated for each possible subset X > c. However, this estimator does not guarantee the necessary condition that sensitivity and specificity are monotone in X. An alternative estimator that does guarantee monotonicity is based on a nearest neighbor estimator for the bivariate distribution function of (X, T), where T represents survival time (Akritas, M. J., 1994, Annals of Statistics22, 1299–1327). We present an example where ROC(t) is used to compare a standard and a modified flow cytometry measurement for predicting survival after detection of breast cancer and an example where the ROC(t) curve displays the impact of modifying eligibility criteria for sample size and power in HIV prevention trials.
Random Effects in Censored Ordinal Regression: Latent Structure and Bayesian Approach
Authors: Xie Minge , Simpson Douglas G. , Carroll Raymond J.
Published: May 2004

Summary. This paper discusses random effects in censored ordinal regression and presents a Gibbs sampling approach to fit the regression model. A latent structure and its corresponding Bayesian formulation are introduced to effectively deal with heterogeneous and censored ordinal observations. This work is motivated by the need to analyze interval‐censored ordinal data from multiple studies in toxicological risk assessment. Application of our methodology to the data offers further support to the conclusions developed earlier using GEE methods yet provides additional insight into the uncertainty levels of the risk estimates.
Evaluating Decision Rules for Nitrogen Fertilization
Authors: Antoniadou T. , Wallach D.
Published: May 2004

Summary. It is important, both for farmer profit and for the environment, to correctly dose nitrogen fertilizer for crop growth. Fertilizer recommendations are embodied in decision rules, which give a recommended dose of nitrogen (N) as a function of information available at the time the decision is made. In this paper, we first propose a criterion for evaluating decision rules. The proposed criterion is the expectation of the objective function when the decision rule is implemented. The major problem here is the estimation of this criterion. Two estimators are considered, a model‐based and a nonparametric estimator. A simulation study shows that, in essentially all cases, the nonparametric estimator is better or no worse than the model‐based estimator. The bias in the nonparametric estimator is always very small.
Mixture Models, Robustness, and the Weighted Likelihood Methodology
Authors: Markatou Marianthi
Published: May 2004

Summary. Problems associated with the analysis of data from a mixture of distributions include the presence of outliers in the sample, the fact that a component may not be well represented in the data, and the problem of biases that occur when the model is slightly misspecified. We study the performance of weighted likelihood in this context. The method produces estimates with low bias and mean squared error, and it is useful in that it unearths data substructures in the form of multiple roots. This in turn indicates multiple potential mixture model fits due to the presence of more components than originally specified in the model. To compute the weighted likelihood estimates, we use as starting values the method of moment estimates computed on bootstrap subsamples drawn from the data. We address a number of important practical issues involving bootstrap sample size selection, the role of starting values, and the behavior of the roots. The algorithm used to compute the weighted likelihood estimates is competitive with EM, and it is similar to EM when the components are not well separated. Moreover, we propose a new statistical stopping rule for the termination of the algorithm. An example and a small simulation study illustrate the above points.
Regression Analysis When Covariates Are Regression Parameters of a Random Effects Model for Observed Longitudinal Measurements
Authors: Wang C. Y. , Wang Naisyin , Wang Suojin
Published: May 2004

Summary.We consider regression analysis when covariate variables are the underlying regression coefficients of another linear mixed model. A naive approach is t o use each subject's repeated measurements, which are assumed to follow a linear mixed model, and obtain subject‐specific estimated coefficients to replace the covariate variables. However, directly replacing the unobserved covariates in the primary regression by these estimated coefficients may result in a significantly biased estimator. The aforementioned problem can be evaluated as a generalization of the classical additive error model where repeated measures are considered as replicates. To correct for these biases, we investigate a pseudo‐expected estimating equation (EEE) estimator, a regression calibration (RC) estimator, and a refined version of the RC estimator. For linear regression, the first two estimators are identical under certain conditions. However, when the primary regression model is a nonlinear model, the RC estimator is usually biased. We thus consider a refined regression calibration estimator whose performance is close to that of the pseudo‐EEE estimator but does not require numerical integration. The RC estimator is also extended to the proportional hazards regression model. In addition to the distribution theory, we evaluate the methods through simulation studies. The methods are applied to analyze a real dataset from a child growth study.
Risk Assessment for Quantitative Responses Using a Mixture Model
Authors: Razzaghi Mehdi , Kodell Ralph L.
Published: May 2004

Summary.A problem that frequently occurs in biological experiments with laboratory animals is that some subjects are less susceptible to the treatment than others. A mixture model has traditionally been proposed to describe the distribution of responses in treatment groups for such experiments. Using a mixture dose‐response model, we derive an upper confidence limit on additional risk, defined as the excess risk over the background risk due to an added dose. Our focus will be on experiments with continuous responses for which risk is the probability of an adverse effect defined as an event that is extremely rare in controls. The asymptotic distribution of the likelihood ratio statistic is used to obtain the upper confidence limit on additional risk. The method can also be used to derive a benchmark dose corresponding to a specified level of increased risk. The EM algorithm is utilized to find the maximum likelihood estimates of model parameters and an extension of the algorithm is proposed to derive the estimates when the model is subject to a specified level of added risk. An example is used to demonstrate the results, and it is shown that by using the mixture model a more accurate measure of added risk is obtained.
Local Estimation of Age‐Dependent Variance Components from Longitudinal Twin Data
Authors: Huggins Richard
Published: May 2004

Summary. In the study of longitudinal twin and family data, interest is often in the covariance structure of the data and the decomposition of this covariance structure into genetic and environmental components rather than in estimating the mean function. Various parametric models for covariance structures have been proposed but, e.g., in studies of children where growth spurts occur at various ages, it is difficult to a prioridetermine an appropriate parametric model for the covariance structure. In particular, there is a general lack of the visualization procedures, such as lowess, that are invaluable in the initial stages of constructing a parametric model for a mean function. Here we use kernel smoothing to modify a cross‐sectional approach based on the sample covariance matrices to obtain smoothed estimates of the genetic and environmental variances and correlations for longitudinal twin data. The methods are proposed t o be exploratory as an aid to parametric modeling rather than inferential, although approximate asymptotic standard errors are derived in the Appendix.
Weighted p‐Value Adjustments for Animal Carcinogenicity Trend Test
Authors: Chen James J. , Lin Karl K. , Huque Mohammad , Arani Ramin B.
Published: May 2004

Summary. A typical animal carcinogenicity experiment routinely analyzes approximately 10–30 tumor sites. Comparisons of tumor responses between dosed and control groups and dose‐related trend tests are often evaluated for each individual tumor site/type separately. p‐Value adjustment approaches have been proposed for controlling the overall Type I error rate or familywise error rate (FWE). However, these adjustments often result in reducing the power to detect a dose effect. This paper proposes using weighted adjustments by assuming that each tumor can be classified as either class A or class B based on prior considerations. The tumors in class A, which are considered as more critical endpoints, are given less adjustment. Two weighted methods of adjustments are presented, the weighted p adjustment and weighted α adjustment. A Monte Carlo simulation shows that both weighted adjustments control the FWE well. Furthermore, the power increases if a treatment‐dependent tumor is analyzed as in class A tumors and the power decreases if it is analyzed as in class B tumors. A data set from a National Toxicology Program (NTP) 2‐year animal carcinogenicity experiment with 13 tumor types/sites observed in male mice was analyzed using the proposed methods. The modified poly‐3 test was used to test for increased carcinogenicity since it has been adopted by the NTP as a standard test for a dose‐related trend. The unweighted adjustment analysis concluded that there was no statistically significant dose‐related trend. Using the Food and Drug Administration classification scheme for the weighted adjustment analyses, two rare tumors (with background rates of 1% or less) were analyzed as class A tumors and 11 common tumors (with background rates higher than 1%) as class B. Both weighted analyses showed a significant dose‐related trend for one rare tumor.
A Scaled Linear Mixed Model for Multiple Outcomes
Authors: Lin Xihong , Ryan Louise , Sammel Mary , Zhang Daowen , Padungtod Chantana , Xu Xiping
Published: May 2004

Summary. We propose a scaled linear mixed model to assess the effects of exposure and other covariates on multiple continuous outcomes. The most general form of the model allows a different exposure effect for each outcome. An important special case is a model that represents the exposure effects using a common global measure that can be characterized in terms of effect sizes. Correlations among different outcomes within the same subject are accommodated using random effects. We develop two approaches to model fitting, including the maximum likelihood method and the working parameter method. A key feature of both methods is that they can be easily implemented by repeatedly calling software for fitting standard linear mixed models, e.g., SAS PROC MIXED. Compared to the maximum likelihood method, the working parameter method is easier to implement and yields fully efficient estimators of the parameters of interest. We illustrate the proposed methods by analyzing data from a study of the effects of occupational pesticide exposure on semen quality in a cohort of Chinese men.