bluuebunny/crossref_metadata_2025 huggingface dataset:
Accurate prediction of autologous stem cell apheresis yields using a double variable‐dependent method assures systematic efficiency control of continuous flow collection procedures
Authors: Pierelli L. , Maresca M. , Piccirillo N. , Pupella S. , Gozzer M. , Foddai M. L. , Vacca M. , Adorno G. , Coppetelli U. , Paladini U.
Published: May 2006

Background and Objectives  Stem cell collection is a standard procedure for the procurement of autologous grafts to rescue myelosuppression induced by high‐dose treatments. Accurate prediction of collection yields may contribute to optimize planning and quality control of collection.

Materials and Methods  Data of 313 autologous haematopoietic stem cell (AHSC) evaluable collections performed in 208 patients with haematologic and non‐haematologic neoplasms from seven centres were prospectively analysed to test the accuracy of yield predictions generated by a formula that required the input of peripheral blood (PB) CD34+ cell precount and desired PB volume to be processed. Data were matched in a standard linear regression, in a zero‐point regression analysis and tested for prediction accuracy. Further 165 AHSC collections were analysed on a single‐centre basis, using yield predictions as reference standards.

Results  Analysis showed high levels of correlation between measured collection yields (my) and predictions (py) (R = 0·85; P = 0·000000) as well as high degree of prediction accuracy (my vs. py at paired t‐test: P = 0·114781; median my/py ratio = 1·23). Analysis of additional 165 AHSC collections on a single‐centre basis showed that the analysed centres had 70% or more measured yields comprising the 0·6–1·8 interval of the my/py ratio. The observance of the ‘efficiency’ my/py interval assured collection quality control in these centres confirming the reliability of the method.

Conclusions  This prediction method generates accurate and immediate yield predictions allowing collection planning and rapid efficiency control. As a consequence of our study, four centres out of seven use the described method to plan both leukapheresis number and single‐procedure blood processing volume while the remaining three centres plan leukapheresis number on the basis of our predictions, maintaining a fixed single‐procedure 200 ml/kg blood volume processing, according to their centre AHSC collection policy.
Grain‐scale permeabilities of faceted polycrystalline aggregates
Authors: PRICE J. D. , WARK D. A. , WATSON E. B. , SMITH A. M.
Published: May 2006

Porous synthetic quartzites and amphibolites, each with faceted pore walls, were synthesized and evaluated to examine the permeability of pore networks similar to those of the lower crust and mantle. Quartzite with a fluid in equilibrium with an Mg–clinopyroxene contained connected networks of pores with a dihedral angle of 30° bounded by walls that were 10–50% faceted. The relationship of their permeability (k) to porosity (φ) is approximated by the previously determined relationship for relatively nonfaceted synthetic quartzite
image

Amphibolite with an HF fluid contained fluorotremolite and a connected network of pores bounded by walls exhibiting 78–90% faceting. These materials showed much lower k for a given φ, with an apparent permeability threshold at φc = 0.04. A curve fit to these data yields
image

The results suggest that moderate faceting has little effect on the transmission of fluids through rocks, but extensive faceting significantly alters permeability. This difference is most likely produced through isolation of the fluid to the grain corners at low φ with extensive faceting. Rocks with pores that tend toward faceting may impede the flow of fluids and melt.
Habitat requirements of the long‐tailed ground squirrel (Spermophilus undulatus) in the southern Altai
Authors: Ricankova V. , Fric Z. , Chlachula J. , Stastna P. , Faltynkova A. , Zemek F.
Published: May 2006

The long‐tailed ground squirrels Spermophilus undulatus represent the most abundant burrowing herbivorous species in the southern Altai grasslands and are suggested to play an important role in the maintenance of this mountain ecosystem. The aim of this study was to identify the key features that influence their habitat use in the southern part of the Altai Republic (south‐west Siberia, Russia). The research area represents a complete sequence of altitudinal vegetation zones from steppe, forest‐steppe, forest, sub‐alpine and alpine tundra. Our results suggest that S. undulatus prefers short‐grass steppes, near the water source and with a thin layer of a chernozem soil containing a large amount of coarse clastics. The species strictly avoids forests and tolerates only a low density of bush cover. Altitude and exposure to sun do not represent significant factors in the habitat choice of S. undulatus. Neither the presence of pikas nor the presence of marmots influences habitat selection of the ground squirrels. Strong preferences for habitats near a water source may limit the distribution of the species to mountain areas. Degree of human disturbance was not a significant factor affecting distribution and the species even displays slight preferences for heavily grazed habitat near human settlements and roads. Intensive grazing prevents shrubs and forest invasion, keeps vegetation low and thus provides appropriate conditions for the ground squirrels, favouring an open habitat where predators can be easily detected by sight. Our results suggest that the habitat selection of ground squirrels may be determined rather by a protection from predators and burrowing conditions than by food availability.
Cytokines and the Molecular Mechanisms of Alcoholic Liver Disease
Authors: Diehl Anna Mae
Published: May 2006

This manuscript was given as a plenary lecture at the annual meeting of the Research Society on Alcoholism in July of 1999. It describes the general mechanisms by which tumor necrosis factor (TNF) alpha, an injury‐related cytokine, promotes liver regeneration and then details how TNF‐initiated hepa‐totrophic signals are inhibited by chronic ethanol consumption. There is evidence that chronic ethanol exposure impairs the TNF‐dependent activation of stress‐activated protein kinases and some of their targets, including the growth‐stimulatory DNA binding protein, c‐Jun. Ethanol exposure also prevents TNF from activating the redox‐sensitive transcription factor, NF kappa B, in regenerating hepatocytes. These effects are followed by decreased hepatocyte proliferation, as well as by impaired induction of TNF‐regulated survival factors, such as Bcl‐xL, in the liver. Thus, chronic ethanol consumption may damage the liver by inhibiting the hepatotrophic and hepatoprotective actions of TNFa and other growth‐regulatory cytokines.
Monitoring Ethanol Exposure in a Clinical Setting by Analysis of Blood, Breath, Saliva, and Urine
Authors: Bendtsen P. , Hultberg J. , Carlsson M. , Jones A. W.
Published: May 2006

Background: Several new technologies have been developed for estimating blood alcohol concentration (BAC), among others, by the analysis of alcohol in saliva specimens. The Q.E.D.™ is a new quantitative test designed for measuring ethanol in saliva and promising results have been obtained in various experimental settings.

Methods: In the present study, venous BAC was determined in 28 patients on arrival and when they were discharged from a detoxification unit. The results were compared with breath, saliva, and urine alcohol concentrations. Headspace gas chromatography was used for analysis of ethanol in blood and urine, and breath alcohol was determined with an Alcolmeter S‐D2 instrument.

Results: The concentration of alcohol in urine was always higher than the BAC (mean difference, 0.62 mg/ml) and individual values were highly correlated (n= 42; r= 0.92). The handheld breath‐alcohol instrument (Alcolmeter S‐D2) showed good agreement with venous BAC (n= 52; r= 0.97; mean difference, 0.04 mg/ml). The saliva‐alcohol test failed to perform well in our tests (n= 36; r= 0.75; mean difference, 0.55 mg/ml) mainly because of problems encountered in obtaining a sufficient sample for analysis in highly intoxicated patients.

Conclusions: Because of the relatively low cost of the Q.E.D. TMsaliva test, in comparison with a breath alcohol analyzer, the saliva test could be a cost‐effective alternative in public health settings where mildly to moderately intoxicated persons are encountered.
Factor Structure and Predictive Validity of the Obsessive Compulsive Drinking Scale
Authors: Roberts James S. , Anton Raymond F. , Latham Patricia K. , Moak Darlene H.
Published: May 2006

Background: The Obsessive Compulsive Drinking Scale (OCDS) is a 14‐item, self‐report instrument developed to measure obsessive thoughts about alcohol use and compulsive behaviors toward drinking. The objective of this study was to ascertain the factor structure underlying responses to the OCDS, and to further assess whether subscale scores derived from this structure were distinctive, internally consistent, predictive of future drinking, and able to differentiate between patients receiving naltrexone versus placebo in a controlled alcoholism treatment trial.

Methods: OCDS data were collected from a total of 132 alcohol‐dependent subjects at up to 15 assessment points during the study. Interitem correlations were pooled across assessment periods, and an iterated principal axis factor analysis with oblique promax rotation was performed. The factor analysis suggested that three primary factors could parsimoniously account for the common variance in item responses. Subscale scores were formed by summing responses to the most salient items on each factor.

Results: The three common factors were interpreted as “resistance/control impairment,”“obsession,” and “interference.” The subscale scores corresponding to these three factors were internally consistent, and their correlation with other baseline measures of alcohol use and severity suggested that they were distinct. Scores on each subscale reliably distinguished between subjects who remained abstinent, exhibited “slip” drinking, or relapsed to heavy drinking during the 12 weeks of active treatment. Additionally, scores on the resistance/control impairment subscale distinguished between those patients receiving treatment with naltrexone or placebo. Scores from each subscale also were able to predict the hazard for heavy drinking in the following week of treatment.

Conclusions: The three OCDS factors are easily estimated with the summated scoring approach, and the resulting subscales appear to be internally consistent and distinctive. Moreover, the group differentiation capability and predictive utility of the subscale scores suggest that they might be useful as either predictor or outcome variables in alcoholism treatment trials. The duration of time for which a given OCDS assessment maintains its predictive utility awaits further confirmation.
Alcohol‐Related Problems and Intimate Partner Violence Among White, Black, and Hispanic Couples in the U.S.
Authors: Cunradi Carol B. , Caetano Raul , Clark Catherine L. , Schafer John
Published: May 2006

Objectives: This study analyzes gender and ethnic/racial differences in the prevalence of alcohol‐related problems among white, black and Hispanic couples in the United States, and assesses their contribution to the risk of intimate partner violence (IPV).

Methods: Our study population consisted of 1440 white, black, and Hispanic couples obtained through a multistage area household probability sample from the 1995 National Alcohol Survey. Alcohol‐related problems (i.e., drinking consequences and alcohol dependence symptoms in the last 12 months) were assessed among respondents and their partners. Male‐to‐female and female‐to‐male partner violence (MFPV, FMPV) were measured separately using the Conflict Tactics Scale.

Results and Conclusions: Alcohol‐related problems were more prevalent among men than women. Our bivariate analysis demonstrated a significant positive association between male alcohol‐related problems and IPV across racial/ethnic groups, and a similar association between female alcohol‐related problems and IPV for white and black couples. In the multivariate logistic regression analyses, however, many of these associations were attenuated. After controlling for sociodemographic and psychosocial covariates, male alcohol‐related problems were no longer significantly associated with an increased risk of MFPV among white or Hispanic couples. Female alcohol‐related problems predicted FMPV, but not MFPV, among white couples. Among black couples, however, male and female alcohol‐related problems remained strong predictors of intimate partner violence.

Significance: Alcohol‐related problems are important predictors of intimate partner violence, and the exact association between problems and violence seems to be ethnic‐specific. Alcohol‐related problems, rather than level of alcohol consumption, may be the more relevant factor to consider in the alcohol‐partner violence association. Future research is needed to explore the temporal relationships between the development of alcohol‐related problems and the occurrence of partner violence.
ACOUSTIC EMISSION, FRACTURE BEHAVIOR AND MORPHOLOGY OF DRY CRISPY FOODS: A DISCUSSION ARTICLE
Authors: LUYTEN HANNEMIEKE , VLIET TON VAN
Published: May 2006

This article describes sound properties that are special for crispy foods and relates them to general knowledge on the acoustic emission and mechanical properties of fracturing materials. From properties like the occurrence of sound, the sound energy, the duration of single sound waves, the time interval between the sound pulses and from the force drops involved, it was possible to calculate the morphological constraints for dry, crispy cellular foods. We present data for the minimum and maximum sizes of the pores and of the sizes of the solid material element surrounding them. The loss of crispness in foods caused by aging under deteriorating circumstances was found not to be caused by changes in the type of elements that fracture.
EFFECT OF ADDITIVES ON RHEOLOGICAL CHARACTERISTICS AND QUALITY OF WHEAT FLOUR PAROTTA
Authors: INDRANI D. , VENKATESWARA RAO G.
Published: May 2006

Effects of oxidizing agents (potassium bromate [20 and 40 ppm], ascorbic acid [100 and 200 ppm] and potassium iodate [20 and 40 ppm]), reducing agents (potassium metabisulphite [100 and 200 ppm] and cysteine hydrochloride [50 and 100 ppm]), enzymes (fungalα‐amylase [10 and 20 ppm] and protease [10 and 20 ppm]) and dry gluten powder (1, 2 and 3%) on rheological characteristics of dough and quality of parotta were studied. Addition of oxidizing agents and dry glutenincreased values for farinograph stability, extensograph and mixograph areas, apparent biaxial extensional viscosity, compressive stress, hardness and cohesiveness, while reducing agents and enzymes decreased the aforementioned characteristics and increased force decay parameter and adhesiveness of the dough. Among the different additives studied, incorporation of 100‐ppm potassium metabisulphite, 50‐ppm cysteine hydrochloride and 10‐ppm protease increased the overall quality score of parotta.
Simulation of Film Cooling Enhancement With Mist Injection
Authors: Li Xianchang , Wang Ting
Published: May 2006

Cooling of gas turbine hot-section components, such as combustor liners, combustor transition pieces, and turbine vanes (nozzles) and blades (buckets), is a critical task for improving the life and reliability of them. Conventional cooling techniques using air-film cooling, impingement jet cooling, and turbulators have significantly contributed to cooling enhancements in the past. However, the increased net benefits that can be continuously harnessed by using these conventional cooling techniques seem to be incremental and are about to approach their limit. Therefore, new cooling techniques are essential for surpassing these current limits. This paper investigates the potential of film-cooling enhancement by injecting mist into the coolant. The computational results show that a small amount of injection (2% of the coolant flow rate) can enhance the adiabatic cooling effectiveness about 30–50%. The cooling enhancement takes place more strongly in the downstream region, where the single-phase film cooling becomes less powerful. Three different holes are used in this study including a two-dimensional (2D) slot, a round hole, and a fan-shaped diffusion hole. A comprehensive study is performed on the effect of flue gas temperature, blowing angle, blowing ratio, mist injection rate, and droplet size on the cooling effectiveness with 2D cases. Analysis on droplet history (trajectory and size) is undertaken to interpret the mechanism of droplet dynamics.
Natural
Convection Measurements for a Concentric Spherical
Enclosure
Authors: Teertstra Peter
M. , Yovanovich M.
Michael , Culham J. Richard
Published: May 2006

An experimental test program is described for the measurement of natural convection for an isothermal, heated sphere centrally located in an isothermal, cooled spherical enclosure. A transient test method is used in a reduced pressure environment to provide data for a wide range of Rayleigh number, from the limiting case of laminar boundary layer convection to the diffusive limit. Tests are performed using a fixed outer diameter for four different inner sphere diameters, resulting in diameter ratios in the range 1.5⩽do∕di⩽4.8. The data are in excellent agreement with the exact solution for the conductive limit and are shown to be bounded by a model for the isolated, isothermal sphere.
Analytical Solution of Forced Convection in a Duct of Rectangular Cross Section Saturated by a Porous Medium
Authors: Hooman Kamel , Merrikh Ali A.
Published: May 2006

A theoretical analysis is presented to investigate thermally and hydrodynamically fully developed forced convection in a duct of rectangular cross section filled with a hyper-porous medium. The Darcy-Brinkman model was adopted in the present analysis. A Fourier series type solution is applied to obtain the exact velocity and temperature distribution within the duct. The case of uniform heat flux on the walls, i.e., the H boundary condition in the terminology of Kays and Crawford (1993, Convective Heat and Mass Transfer, 3rd ed., McGraw-Hill, NY), is treated. Values of the Nusselt number and the friction factor as a function of the aspect ratio, the Darcy number, and the viscosity ratio are reported.
Inhibition of Mitochondrial Ca2+Uptake Affects Phasic Release From Motor Terminals Differently Depending on External [Ca2+]
Authors: Talbot Janet D. , David Gavriel , Barrett Ellen F.
Published: May 2006

We investigated how inhibition of mitochondrial Ca2+uptake affects stimulation-induced increases in cytosolic [Ca2+] and phasic and asynchronous transmitter release in lizard motor terminals in 2 and 0.5 mM bath [Ca2+]. Lowering bath [Ca2+] reduced the rate of rise, but not the final amplitude, of the increase in mitochondrial [Ca2+] during 50-Hz stimulation. The amplitude of the stimulation-induced increase in cytosolic [Ca2+] was reduced in low-bath [Ca2+] and increased when mitochondrial Ca2+uptake was inhibited by depolarizing mitochondria. In 2 mM Ca2+, end-plate potentials (epps) depressed by 53% after 10 s of 50-Hz stimulation, and this depression increased to 80% after mitochondrial depolarization. In contrast, in 0.5 mM Ca2+the same stimulation pattern increased epps by ∼3.4-fold, and this increase was even greater (transiently) after mitochondrial depolarization. In both 2 and 0.5 mM [Ca2+], mitochondrial depolarization increased asynchronous release during the 50-Hz train and increased the total vesicular release (phasic and asynchronous) measured by destaining of the styryl dye FM2-10. These results suggest that by limiting the stimulation-induced increase in cytosolic [Ca2+], mitochondrial Ca2+uptake maintains a high ratio of phasic to asynchronous release, thus helping to sustain neuromuscular transmission during repetitive stimulation. Interestingly, the quantal content of the epp reached during 50-Hz stimulation stabilized at a similar level (∼20 quanta) in both 2 and 0.5 mM Ca2+. A similar convergence was measured in oligomycin, which inhibits mitochondrial ATP synthesis without depolarizing mitochondria, but quantal contents fell to <20 when mitochondria were depolarized in 2 mM Ca2+.
Functional Roles of an ERG Current Isolated in Cerebellar Purkinje Neurons
Authors: Sacco Tiziana , Bruno Alessandro , Wanke Enzo , Tempia Filippo
Published: May 2006

Transcripts encoding ERG potassium channels are expressed by most neurons of the CNS. By patch-clamp whole cell recording from Purkinje neurons in slices of young (5–9 days old) mouse cerebellum we have been able to isolate a tail current [ IK(ERG)] with the same characteristics as previously described for ERG channels. In zero external Ca2+ and high K+ (40 mM) the V1/2 of activation was –50.7 mV, the V1/2 of inactivation was –70.6 mV, and the deactivation rate was double exponential and voltage dependent. IK(ERG) was 93.0% blocked by WAY-123,398 (1 μM) and 78.2% by haloperidol (2 μM). The role of IK(ERG) on evoked firing was studied in adult mice, where WAY-123,398 application decreased the first spike latency, increased the firing frequency, and suppressed the frequency adaptation. However, the shape of individual action potentials was not affected. Stimulation of presynaptic climbing fibers evoked the Purkinje neuron “complex spike,” composed of an initial spike and several spikelets. IK(ERG) block caused an increase of the number of spikelets of the “complex spike.” These data show, for the first time, an IK(ERG) in a neuron of the CNS, the cerebellar Purkinje neuron, and indicate that such a current is involved in the control of membrane excitability, firing frequency adaptation, and in determining the effects of the climbing fiber synapse.
Salt-Evoked Lingual Surface Potential in Humans
Authors: Feldman George M. , Mogyorósi András , Heck Gerard L. , DeSimone John A. , Santos Cecily R. , Clary Rebecca A. , Lyall Vijay
Published: May 2006

Salt sensing in animals involves the epithelial sodium channel (ENaC). If ENaC were involved in human salt sensing, then the lingual surface potential (LSP) would hyperpolarize when exposed to sodium. We developed a chamber to measure the LSP while different solutions superfused the surface of the tongue and a technique to adjust for the junction potentials induced by varying salt concentrations. Changing the superfusion solution from rinse solution (30 mM KCl) to 300 mM NaCl (+30 mM KCl) caused the LSP to hyperpolarize by 10.1 ± 0.7 mV ( n = 13, P < 0.001). With repeated challenge the LSP response was reproducible. Increasing the Na concentration from 100 to 600 mM increased hyperpolarization by 35 ± 4.8% ( n = 9, P < 0.001). To examine whether amiloride affects the LSP, 0.1 mM amiloride was added to 300 mM NaCl; it reduced the hyperpolarization by 18.5 ± 4.3% ( P < 0.005, n = 11). However, the amiloride effect was not uniform: in six volunteers, amiloride inhibited the LSP by as much as 42%, while in five subjects, amiloride inhibited <5% of the LSP. In an amiloride sensitive volunteer, amiloride exerted 50% of its effect at 1 μM. In conclusion, we have demonstrated that the LSP can be measured in humans, that Na hyperpolarizes the LSP, that increasing the Na concentration increases LSP hyperpolarization, and that amiloride inhibits the Na evoked LSP in some humans. While ENaC is involved in sensing salt, its role appears to vary among individuals.
Gravity Modulates Listing's Plane Orientation During Both Pursuit and Saccades
Authors: Hess Bernhard J.M. , Angelaki Dora E.
Published: May 2006

Previous studies have shown that the spatial organization of all eye orientations during visually guided saccadic eye movements (Listing's plane) varies systematically as a function of static and dynamic head orientation in space. Here we tested if a similar organization also applies to the spatial orientation of eye positions during smooth pursuit eye movements. Specifically, we characterized the three-dimensional distribution of eye positions during horizontal and vertical pursuit (0.1 Hz, ±15° and 0.5 Hz, ±8°) at different eccentricities and elevations while rhesus monkeys were sitting upright or being statically tilted in different roll and pitch positions. We found that the spatial organization of eye positions during smooth pursuit depends on static orientation in space, similarly as during visually guided saccades and fixations. In support of recent modeling studies, these results are consistent with a role of gravity on defining the parameters of Listing's law.
Nature of Inhibitory Postsynaptic Activity in Developing Relay Cells of the Lateral Geniculate Nucleus
Authors: Ziburkus Jokūbas , Lo Fu-Sun , Guido William
Published: May 2006

Using intracellular recordings in an isolated (in vitro) brain stem preparation, we examined the inhibitory postsynaptic responses of developing neurons in the dorsal lateral geniculate nucleus (LGN) of the rat. As early as postnatal day (P) 1–2, 31% of all excitatory postsynaptic (EPSP) activity evoked by electrical stimulation of the optic tract was followed by inhibitory postsynaptic potentials (IPSPs). By P5, 98% of all retinally evoked EPSPs were followed by IPSP activity. During the first postnatal week, IPSPs were mediated largely by GABAA receptors. Additional GABAB-mediated IPSPs emerged at P3–4 but were not prevalent until after the first postnatal week. Experiments involving the separate stimulation of each optic nerve indicated that developing LGN cells were binocularly innervated. At P11–14, it was common to evoke EPSP/IPSP pairs by stimulating either the contralateral or ipsilateral optic nerve. During the third postnatal week, binocular excitatory responses were encountered far less frequently. However, a number of cells still maintained a binocular inhibitory response. These results provide insight about the ontogeny and nature of postsynaptic inhibitory activity in the LGN during the period of retinogeniculate axon segregation.
The Role of the Corpus Callosum in the Coupling of Bimanual Isometric Force Pulses
Authors: Diedrichsen Jörn , Hazeltine Eliot , Nurss Wesley K. , Ivry Richard B.
Published: May 2006

Two split-brain patients, a patient with callosal agenesis, and 6 age-matched control participants were tested on a bimanual force production task. The participants produced isometric responses with their index fingers, attempting to match the target force specified by a visual stimulus. On unimanual trials, the stimuli were presented in either the left or right visual field and the response was made with the ipsilateral hand. On bimanual trials, two stimuli were presented, one on each side, and the target forces could be either identical or different. Bimanual responses of the control subjects showed strong evidence of coupling. Forces produced by one hand were influenced by the forces produced by the other hand with positive correlations observed for all target force combinations. These assimilation effects and correlations were greatly attenuated in the acallosal group, with similar results observed for the split-brain patients and participant with callosal agenesis. Furthermore, the processes involved in selecting and planning the two responses occurred independently in the acallosal group; in contrast to the controls, the three acallosal participants exhibited no differences in reaction times or accuracy between bimanual trials in which the two target forces were the same or different. We also found a striking temporal desynchronization of the responses in the split-brain patients, indicating that in this context, temporal coupling is impaired after callosotomy. These results are congruent with the hypothesis that interference related to response selection and planning of bimanual force pulses arises from callosal interactions.
Branching Thalamic Afferents Link Action and Perception
Authors: Guillery R. W.
Published: May 2006

Recent observations of single axons and review of older literature show that axons afferent to the thalamus commonly branch, sending one branch to the thalamus and another to a motor or premotor center of the brain stem. That is, the messages that the thalamus relays to the cerebral cortex can be regarded as copies of motor instructions. This pattern of axonal branching is reviewed, particularly for the somatosensory and the visual pathways. The extent to which this anatomical evidence relates to views that link action to perception is explored. Most pathways going through the thalamus to the cortex are already involved in motor mechanisms. These motor links occur before and during activity in the parallel and hierarchical corticocortical circuitry that currently forms the focus of many studies of perceptual processing.
Synchrony Levels During Evoked Seizure-Like Bursts in Mouse Neocortical Slices
Authors: van Drongelen Wim , Koch Henner , Marcuccilli Charles , Penã Fernando , Ramirez Jan-Marino
Published: May 2006

Slices ( n = 45) from the somatosensory cortex of mouse (P8-13) generated spontaneous bursts of activity (0.10 ± 0.05 Hz) that were recorded extracellularly. Multiunit action potential (AP) activity was integrated and used as an index of population activity. In this experimental model, seizure-like activity (SLA) was evoked with bicuculline (5–10 μM) or N-methyl-d-aspartate (NMDA, 5 μM). SLA was an episode with repetitive bursting at a frequency of 0.50 ± 0.06 Hz. To evaluate whether SLA was associated with a change in synchrony, we obtained simultaneous intracellular and extracellular recordings ( n = 40) and quantified the relationship between individual cells and the surrounding population of neurons. During the SLA there was an increase in population activity and bursting activity was observed in neurons and areas that were previously silent. We defined synchrony as cellular activity that is consistently locked with the population bursts. Signal-averaging techniques were used to determine this component. To quantitatively assess change in synchronous activity at SLA onset, we estimated the entropy of the single cell's spike trains and subdivided this measure into network burst-related information and noise-related entropy. The burst-related information was not significantly altered at the onset of NMDA-evoked SLA and slightly increased when evoked with bicuculline. The signal-to-noise ratio determined from the entropy estimates showed a significant decrease (instead of an expected increase) during SLA. We conclude that the increased population activity during the SLA is attributed to recruitment of neurons rather than to increased synchrony of each of the individual elements.
Evidence of a Specific Spinal Pathway for the Sense of Warmth in Humans
Authors: Iannetti G.D. , Truini A. , Romaniello A. , Galeotti F. , Rizzo C. , Manfredi M. , Cruccu G.
Published: May 2006

While research on human sensory processing shows that warm input is conveyed from the periphery by specific, unmyelinated primary sensory neurons, its pathways in the central nervous system (CNS) remain unclear. To gain physiological information on the spinal pathways that convey warmth or nociceptive sensations, in 15 healthy subjects, we studied the cerebral evoked responses and reaction times in response to laser stimuli selectively exciting Aδ nociceptors or C warmth receptors at different levels along the spine. To minimize the conduction distance along the primary sensory neuron, we directed CO2-laser pulses to the skin overlying the vertebral spinous processes. Using brain source analysis of the evoked responses with high-resolution electroencephalography and a realistic model of the head based on individual magnetic resonance imaging scans, we also studied the cortical areas involved in the cerebral processing of warm and nociceptive inputs. The activation of C warmth receptors evoked cerebral potentials with a main positive component peaking at 470–540 ms, i.e., a latency clearly longer than that of the corresponding wave yielded by Aδ nociceptive input (290–320 ms). Spinal neurons activated by the warm input had a slower conduction velocity (2.5 m/s) than the nociceptive spinal neurons (11.9 m/s). Brain source analysis of the cerebral responses evoked by the Aδ input yielded a very strong fit for one single generator in the mid portion of the cingulate gyrus; the warmth-related responses were best explained by three generators, one within the cingulate and two in the right and left opercular-insular cortices. Our results support the existence of slow-conducting second-order neurons specific for the sense of warmth.
ShakerK+Channels Contribute Early Nonlinear Amplification to the Light Response inDrosophilaPhotoreceptors
Authors: Juusola Mikko , Niven Jeremy E. , French Andrew S.
Published: May 2006

We describe the contribution of rapidly inactivating Shaker K+channels to the dynamic membrane properties of Drosophila photoreceptors. Phototransduction was measured in wild-type and Shaker mutant ( Sh14) Drosophila photoreceptors by stimulating with white noise–modulated light contrast and recording the resulting intracellular membrane potential fluctuations. A second-order Volterra kernel series was used to characterize the nonlinear dynamic properties of transduction in the two situations. First-order kernels were indistinguishable in wild-type and Sh14photoreceptors, indicating that the basic light transduction machinery was always intact. However, second-order kernels of Shaker mutants lacked a large, early amplification, indicating a novel role for Shaker K+channels in amplifying and accelerating the voltage response of wild-type photoreceptors. A cascade model of two nonlinear static components surrounding one linear dynamic component was able to partially reproduce the experimental responses. Parameters obtained by fitting the model to the experimental data supported the hypothesis that normal Shaker K+channels contribute an early, positive nonlinearity that partially offsets a later attenuating nonlinearity caused by membrane shunting.
Differential and History-Dependent Modulation of a Stretch Receptor in the Stomatogastric System of the Crab,Cancer borealis
Authors: Birmingham John T. , Billimoria Cyrus P. , DeKlotz Timothy R. , Stewart Raj A. , Marder Eve
Published: May 2006

Neuromodulators can modify the magnitude and kinetics of the response of a sensory neuron to a stimulus. Six neuroactive substances modified the activity of the gastropyloric receptor 2 (GPR2) neuron of the stomatogastric nervous system (STNS) of the crab Cancer borealis during muscle stretch. Stretches were applied to the gastric mill 9 (gm9) and the cardio-pyloric valve 3a (cpv3a) muscles. SDRNFLRFamide and dopamine had excitatory effects on GPR2. Serotonin, GABA, and the peptide allatostatin-3 (AST) decreased GPR2 firing during stretch. Moreover, SDRNFLRFamide and TNRNFLRFamide increased the unstimulated spontaneous firing rate, whereas AST and GABA decreased it. The actions of AST and GABA were amplitude- and history-dependent. In fully recovered preparations, AST and GABA decreased the response to small-amplitude stretches proportionally more than to those evoked by large-amplitude stretches. For large-amplitude stretches, the effects of AST and GABA were more pronounced as the number of recent stretches increased. The modulators that affected the stretch-induced GPR2 firing rate were also tested when the neuron was operating in a bursting mode of activity. Application of SDRNFLRFamide increased the bursting frequency transiently, whereas high concentrations of serotonin, AST, and GABA abolished bursting altogether. Together these data demonstrate that the effects of neuromodulators depend on the previous activity and current state of the sensory neuron.
Saccades Exhibit Abrupt Transition Between Reactive and Predictive, Predictive Saccade Sequences Have Long-Term Correlations
Authors: Shelhamer Mark , Joiner Wilsaan M.
Published: May 2006

To compensate for neural delays, organisms require predictive motor control. We investigated the transition between reaction and prediction in saccades (rapid eye movements) to periodically paced targets. Tracking at low frequencies (0.2–0.3 Hz) is reactive (eyes lag target) and at high frequencies (0.9–1.0 Hz) is predictive (eyes anticipate target); there is an abrupt rather than smooth transition between the two modes (a “phase transition,” as found in bistable physical systems). These behaviors represent stable modes of the oculomotor control system, with attendant rapid switching between the neural pathways underlying the different modes. Furthermore, predictive saccades exhibit long-term correlations (slow decay of the autocorrelation function, manifest as a 1/ fαspectrum). This indicates that predictive trials are not independent. The findings have implications for the understanding of predictive motor control: predictive performance during a given trial is influenced by a feedback process that takes into account the latency of previous trials.
Postlesional Vestibular Reorganization Improves the Gain But Impairs the Spatial Tuning of the Maculo-Ocular Reflex in Frogs
Authors: Rohregger Martin , Dieringer Norbert
Published: May 2006

The ramus anterior (RA) of N.VIII was sectioned unilaterally. Two months later we analyzed in vivo responses of the ipsi- and of the contralesional abducens nerve during horizontal and vertical linear acceleration in darkness. The contralesional abducens nerve had become responsive again to linear acceleration either because of a synaptic reorganization in the vestibular nuclei on the operated side and/or because of a reinnervation of the utricular macula by regenerating afferent nerve fibers. Significant differences in the onset latencies and in the acceleration sensitivities allowed a separation of RA frogs in a group without and in a group with functional utricular reinnervation. Most important, the vector orientation for maximal abducens nerve responses was clearly altered: postlesional synaptic reorganization resulted in the emergence of abducens nerve responses to vertical linear acceleration, a response component that was barely detectable in RA frogs with utricular reinnervation and that was absent in controls. The ipsilesional abducens nerve, however, exhibited unaltered responses in either group of RA frogs. The altered spatial tuning properties of contralesional abducens nerve responses are a direct consequence of the postlesional expansion of signals from intact afferent nerve and excitatory commissural fibers onto disfacilitated 2nd-order vestibular neurons on the operated side. These results corroborate the notion that postlesional vestibular reorganization activates a basic neural reaction pattern with more beneficial results at the cellular than at the network level. However, given that the underlying mechanism is activityrelated, rehabilitative training after vestibular nerve lesion can be expected to shape the ongoing reorganization.
Preparatory Set Associated With Pro-Saccades and Anti-Saccades in Humans Investigated With Event-Related fMRI
Authors: DeSouza Joseph F. X. , Menon Ravi S. , Everling Stefan
Published: May 2006

Previous studies have shown that the BOLD functional MRI (fMRI) signal is increased in several cortical areas when subjects perform anti-saccades compared with pro-saccades. It remains unknown, however, whether this increase is due to an increased cortical motor signal for anti-saccades or due to differences in preparatory set between pro- and anti-saccade trials. To address this question, we measured event-related fMRI in a paradigm that allowed us to separate instruction-related brain activity from saccade-related brain activity. In this paradigm, the instruction to either generate a pro-saccade or an anti-saccade was conveyed by a switch in the color of the central fixation stimulus and preceded the presentation of a peripheral stimulus by either 6, 10, or 14 s. Cortical areas were functionally mapped using the general linear model comparing standard pro- and anti-saccade blocks with fixation blocks. When the trials were aligned on the onset of the instruction stimulus, bilateral frontal eye fields and right hemisphere dorsolateral prefrontal cortex showed an increased signal during the instruction period on anti-saccade trials as compared with pro-saccade trials. When the trials were aligned on the movement stimulus and the instruction period activity was subtracted, there were no differences between pro- and anti-saccades. This finding suggests that the increased cortical activation found in previous blocked designs originates predominately from differences in preparatory set and not from differences in the motor signal between pro- and anti-saccades.
Temporal Frequency and Velocity-Like Tuning in the Pigeon Accessory Optic System
Authors: Crowder Nathan A. , Dawson Michael R.W. , Wylie Douglas R.W.
Published: May 2006

Neurons in the accessory optic system (AOS) and pretectum are involved in the analysis of optic flow and the generation of the optokinetic response. Previous studies found that neurons in the pretectum and AOS exhibit direction selectivity in response to large-field motion and are tuned in the spatiotemporal domain. Furthermore, it has been emphasized that pretectal and AOS neurons are tuned to a particular temporal frequency, consistent with the “correlation” model of motion detection. We examined the responses of neurons in the nucleus of the basal optic root (nBOR) of the AOS in pigeons to large-field drifting sine wave gratings of varying spatial (SF) and temporal frequencies (TF). nBOR neurons clustered into two categories: “Fast” neurons preferred low SFs and high TFs, and “Slow” neurons preferred high SFs and low TFs. The fast neurons were tuned for TF, but the slow nBOR neurons had spatiotemporally oriented peaks that suggested velocity tuning (TF/SF). However, the peak response was not independent of SF; thus we refer to the tuning as “apparent velocity tuning” or “velocity-like tuning.” Some neurons showed peaks in both the fast and slow regions. These neurons were TF-tuned at low SFs, and showed velocity-like tuning at high SFs. We used computer simulations of the response of an elaborated Reichardt detector to show that both the TF-tuning and velocity-like tuning shown by the fast and slow neurons, respectively, may be explained by modified versions of the correlation model of motion detection.
Actions of U-92032, a T-Type Ca2+ Channel Antagonist, Support a Functional Linkage Between I T and Slow Intrathalamic Rhythms
Authors: Porcello Darrell M. , Smith Stephen D. , Huguenard John R.
Published: May 2006

Thalamic relay neurons express high levels of T-type Ca2+ channels, which support the generation of robust burst discharges. This intrinsically mediated form of phasic spike firing is thought to be critical in the generation of slow (3–4 Hz) synchronous oscillatory activity of absence epilepsy. Recordings made from brain slices or whole animals have shown that slow synchronous absence-like activity can be abolished when Ca2+-dependent burst firing in relay neurons is interrupted by the pharmacological or genetic inactivation of T-channels. Because succinimide drugs act as incomplete and nonspecific antagonists, we tested whether the novel T-channel antagonist U-92032 could provide stronger support for a role of T-channels in slow oscillatory activity. Ca2+-dependent rebound (LTS) bursts were recorded using whole cell current clamp in relay cells of the ventral basal complex (VB) from thalamic slices of adult rats. We used LTS kinetics to measure the availability of T-channels in VB cells after TTX. U-92032 (1 and 10 μM) reduced the maximum rate of depolarization of the isolated LTS by 51% and 90%, respectively, compared with the 35% reduction due to 2 mM methylphenylsuccinimide (MPS), the active metabolite of the antiabsence drug methsuximide. U-92032 (1 and 10 μM) also suppressed evoked, slow oscillations in thalamic slices with a time course similar for observed intracellular effects. Unlike MPS, we observed no substantial effects of short-term U-92032 applications (≤2 h) on the generation of action potentials in VB cells. Our findings show U-92032 is a more potent, effective, and specific T-channel antagonist than previously studied succinimide antiabsence drugs and that it dramatically reduces epileptiform synchronous activity. This suggests that U-92032 or other specific T-channel antagonists may provide effective drug treatments for absence epilepsy.
Neuroimaging of Direction-Selective Mechanisms for Second-Order Motion
Authors: Nishida Shin'ya , Sasaki Yuka , Murakami Ikuya , Watanabe Takeo , Tootell Roger B. H.
Published: May 2006

Psychophysical findings have revealed a functional segregation of processing for 1st-order motion (movement of luminance modulation) and 2nd-order motion (e.g., movement of contrast modulation). However neural correlates of this psychophysical distinction remain controversial. To test for a corresponding anatomical segregation, we conducted a new functional magnetic resonance imaging (fMRI) study to localize direction-selective cortical mechanisms for 1st- and 2nd-order motion stimuli, by measuring direction-contingent response changes induced by motion adaptation, with deliberate control of attention. The 2nd-order motion stimulus generated direction-selective adaptation in a wide range of visual cortical areas, including areas V1, V2, V3, VP, V3A, V4v, and MT+. Moreover, the pattern of activity was similar to that obtained with 1st-order motion stimuli. Contrary to expectations from psychophysics, these results suggest that in the human visual cortex, the direction of 2nd-order motion is represented as early as V1. In addition, we found no obvious anatomical segregation in the neural substrates for 1st- and 2nd-order motion processing that can be resolved using standard fMRI.
Kinematics and Kinetics of Multijoint Reaching in Nonhuman Primates
Authors: Graham Kirsten M. , Moore Kimberly D. , Cabel D. William , Gribble Paul L. , Cisek Paul , Scott Stephen H.
Published: May 2006

The present study identifies the mechanics of planar reaching movements performed by monkeys ( Macaca mulatta) wearing a robotic exoskeleton. This device maintained the limb in the horizontal plane such that hand motion was generated only by flexor and extensor motions at the shoulder and elbow. The study describes the kinematic and kinetic features of the shoulder, elbow, and hand during reaching movements from a central target to peripheral targets located on the circumference of a circle: the center-out task. While subjects made reaching movements with relatively straight smooth hand paths and little variation in peak hand velocity, there were large variations in joint motion, torque, and power for movements in different spatial directions. Unlike single-joint movements, joint kinematics and kinetics were not tightly coupled for these multijoint movements. For most movements, power generation was predominantly generated at only one of the two joints. The present analysis illustrates the complexities inherent in multijoint movements and forms the basis for understanding strategies used by the motor system to control reaching movements and for interpreting the response of neurons in different brain regions during this task.