bluuebunny/crossref_metadata_2025 huggingface dataset:
Activity of the Motor Cortex During Scratching
Authors: Sirota Mikhail G. , Pavlova Galina A. , Beloozerova Irina N.
Published: October 2005

In awake cats sitting with the head restrained, scratching was evoked using stimulation of the ear. Cats scratched the shoulder area, consistently failing to reach the ear. Kinematics of the hind limb movements and the activity of ankle muscles, however, were similar to those reported earlier in unrestrained cats. The activity of single neurons in the hind limb representation of the motor cortex, including pyramidal tract neurons (PTNs), was examined. During the protraction stage of the scratch response, the activity in 35% of the neurons increased and in 50% decreased compared with rest. During the rhythmic stage, the motor cortex population activity was approximately two times higher compared with rest, because the activity of 53% of neurons increased and that of 33% decreased in this stage. The activity of 61% of neurons was modulated in the scratching rhythm. The average depth of frequency modulation was 12.1 ± 5.3%, similar to that reported earlier for locomotion. The phases of activity of different neurons were approximately evenly distributed over the scratch cycle. There was no simple correlation between resting receptive field properties and the activity of neurons during the scratch response. We conclude that the motor cortex participates in both the protraction and the rhythmic stages of the scratch response.
Power-Law Neuronal Fluctuations in a Recurrent Network Model of Parametric Working Memory
Authors: Miller Paul , Wang Xiao-Jing
Published: October 2005

In a working memory system, persistent activity maintains information in the absence of external stimulation, therefore the time scale and structure of correlated neural fluctuations reflect the intrinsic microcircuit dynamics rather than direct responses to sensory inputs. Here we show that a parametric working memory model capable of graded persistent activity is characterized by arbitrarily long correlation times, with Fano factors and power spectra of neural activity described by the power laws of a random walk. Collective drifts of the mnemonic firing pattern induce long-term noise correlations between pairs of cells, with the sign (positive or negative) and amplitude proportional to the product of the gradients of their tuning curves. None of the power-law behavior was observed in a variant of the model endowed with discrete bistable neural groups, where noise fluctuations were unable to cause long-term changes in rate. Therefore such behavior can serve as a probe for a quasi-continuous attractor. We propose that the unusual correlated fluctuations have important implications for neural coding in parametric working memory circuits.
Object-Selective Cortex Exhibits Performance-Independent Repetition Suppression
Authors: Sayres Rory , Grill-Spector Kalanit
Published: October 2005

Object-selective cortical regions exhibit a decreased response when an object stimulus is repeated [repetition suppression (RS)]. RS is often associated with priming: reduced response times and increased accuracy for repeated stimuli. It is unknown whether RS reflects stimulus-specific repetition, the associated changes in response time, or the combination of the two. To address this question, we performed a rapid event-related functional MRI (fMRI) study in which we measured BOLD signal in object-selective cortex, as well as object recognition performance, while we manipulated stimulus repetition. Our design allowed us to examine separately the roles of response time and repetition in explaining RS. We found that repetition played a robust role in explaining RS: repeated trials produced weaker BOLD responses than nonrepeated trials, even when comparing trials with matched response times. In contrast, response time played a weak role in explaining RS when repetition was controlled for: it explained BOLD responses only for one region of interest (ROI) and one experimental condition. Thus repetition suppression seems to be mostly driven by repetition rather than performance changes. We further examined whether RS reflects processes occurring at the same time as recognition or after recognition by manipulating stimulus presentation duration. In one experiment, durations were longer than required for recognition (2 s), whereas in a second experiment, durations were close to the minimum time required for recognition (85–101 ms). We found significant RS for brief presentations (albeit with a reduced magnitude), which again persisted when controlling for performance. This suggests a substantial amount of RS occurs during recognition.
Long Time-Constant Behavior of the Oculomotor Plant in Barbiturate-Anesthetized Primate
Authors: Sklavos S. , Dimitrova D. M. , Goldberg S. J. , Porrill J. , Dean P.
Published: October 2005

The mechanics of the extraocular muscles and orbital tissue (“oculomotor plant”) can be approximated by a small number of viscoelastic (Voigt) elements in series. Recent analysis of the eye's return from displacement in lightly anesthetized rhesus monkeys has suggested a four-element plant model with time constants (TCs) of ∼0.01, 0.1, 1, and 10 s. To demonstrate directly the presence of long (1,10 s) TC elements and to assess their contribution quantitatively, horizontal eye displacement was induced in Cynomolgus monkeys under deep barbiturate anesthesia that prevented interference from spontaneous eye movements. The displacement was maintained for either a prolonged (30 s) or brief (0.2 s) period before release. Return to resting position took 20–30 s after prolonged displacement but only 1–2 s after brief displacement, consistent with the presence of long TC elements that would only be substantially stretched in the former condition. Quantitative fitting of the release curves after prolonged displacement indicated that the two long TC elements contribute a substantial proportion (∼30%) of the total plant compliance. A model based on the estimated compliance values is shown to account quantitatively both for our release data and for Goldstein and Robinson's data on hysteresis of ocular motoneuron firing rates measured after centripetal saccades following prolonged eccentric fixation. Long time-constant elements in the plant thus make a substantial contribution to some types of eye movement, and their inclusion in plant models can help interpret the firing patterns of single units in the oculomotor system.
A Comparative Voltage and Current-Clamp Analysis of Feedback and Feedforward Synaptic Transmission in the Striatal Microcircuit In Vitro
Authors: Gustafson Nicholas , Gireesh-Dharmaraj Elakkat , Czubayko Uwe , Blackwell Kim T. , Plenz Dietmar
Published: October 2005

Striatal spiny projection (SP) neurons control movement initiation by integrating cortical inputs and inhibiting basal ganglia outputs. Central to this control lies a “microcircuit” that consists of a feedback pathway formed by axon collaterals between GABAergic SP neurons and a feedforward pathway from fast spiking (FS) GABAergic interneurons to SP neurons. Here, somatically evoked postsynaptic potentials (PSPs) and currents (PSCs) were compared for both pathways with dual whole cell patch recording in voltage- and current-clamp mode using cortex-striatum-substantia nigra organotypic cultures. On average, feedforward inputs were 1 ms earlier, more reliable, and about twice as large in amplitude compared with most feedback inputs. On the other hand, both pathways exhibited widely varying, partially overlapping amplitude distributions. This variability was already established for single FS neurons targeting many SP neurons. In response to precisely timed action potential bursts, feedforward and feedback inputs consistently showed short-term depression ≤50–70% in voltage-clamp, although feedback inputs also displayed strong augmentation in current-clamp in line with previous reports. The augmentation of feedback inputs was absent in gramicidin D perforated-patch recording, which also showed the natural reversal potential for both inputs to be near firing threshold. Preceding depolarizing feedback inputs during the down state did not consistently change subsequent postsynaptic action potentials. We conclude that feedback and feedforward inputs have their dominant effect during the up-state. The reversal potential close to the up-state potential, which supports shunting operation with millisecond precision and the strong synaptic depression, should enable both pathways to carry time-critical information.
A Method for Generating Precise Temporal Patterns of Retinal Spiking Using Prosthetic Stimulation
Authors: Fried S. I. , Hsueh H. A. , Werblin F. S.
Published: October 2005

The goal of retinal prosthetic devices is to generate meaningful visual information in patients that have lost outer retinal function. To accomplish this, these devices should generate patterns of ganglion cell activity that closely resemble the spatial and temporal components of those patterns that are normally elicited by light. Here, we developed a stimulus paradigm that generates precise temporal patterns of activity in retinal ganglion cells, including those patterns normally generated by light. Electrical stimulus pulses (≥1-ms duration) elicited activity in neurons distal to the ganglion cells; this resulted in ganglion cell spiking that could last as long as 100 ms. However, short pulses, <0.15 ms, elicited only a single spike within 0.7 ms of the leading edge of the pulse. Trains of these short pulses elicited one spike per pulse at frequencies ≤250 Hz. Patterns of short electrical pulses (derived from normal light elicited spike patterns) were delivered to ganglion cells and generated spike patterns that replicated the normal light patterns. Finally, we found that one spike per pulse was elicited over almost a 2.5:1 range of stimulus amplitudes. Thus a common stimulus amplitude could accommodate a 2.5:1 range of activation thresholds, e.g., caused by differences arising from cell biophysical properties or from variations in electrode-to-cell distance arising when a multielectrode array is placed on the retina. This stimulus paradigm can generate the temporal resolution required for a prosthetic device.
SA1 and RA Afferent Responses to Static and Vibrating Gratings
Authors: Bensmaïa S. J. , Craig J. C. , Yoshioka T. , Johnson K. O.
Published: October 2005

SA1 and RA afferent fibers differ both in their ability to convey information about the fine spatial structure of tactile stimuli and in their frequency sensitivity profiles. In the present study, we investigated the extent to which the spatial resolution of the signal conveyed by SA1 and RA fibers depends on the temporal properties of the stimulus. To that end, we recorded the responses evoked in SA1 and RA fibers of macaques by static and vibrating gratings that varied in spatial period, vibratory frequency, and amplitude. Gratings were oriented either parallel to the long axis of the finger (vertical) or perpendicular to it (horizontal). We examined the degree to which afferent responses were dependent on the spatial period, vibratory frequency, amplitude, and orientation of the gratings. We found that the spatial modulation of the afferent responses increased as the spatial period of the gratings increased; the spatial modulation was the same for static and vibrating gratings, despite large differences in evoked spike rates; the spatial modulation in SA1 responses was independent of stimulus amplitude over the range of amplitudes tested, whereas RA modulation decreased slightly as the stimulus amplitude increased; vertical gratings evoked stronger and more highly modulated responses than horizontal gratings; the modulation in SA1 responses was higher than that in RA responses at all frequencies and amplitudes. The behavioral consequences of these neurophysiological findings are examined in a companion paper.
Temporal Factors in Tactile Spatial Acuity: Evidence for RA Interference in Fine Spatial Processing
Authors: Bensmaïa S. J. , Craig J. C. , Johnson K. O.
Published: October 2005

We investigated the extent to which subjects’ ability to perceive the fine spatial structure of a stimulus depends on its temporal properties (namely the frequency at which it vibrates). Subjects were presented with static or vibrating gratings that varied in spatial period (1–8 mm) and vibratory frequency (5–80 Hz) and judged the orientation of the gratings, presented either parallel or perpendicular to the long axis of the finger. We found that the grating orientation threshold (GOT)—the spatial period at which subjects can reliably discriminate the orientation of the grating—increased as the vibratory frequency of the gratings increased. As the spatial modulation of SA1 and RA afferent fibers has been found to be independent of vibratory frequency, the frequency dependence of spatial acuity cannot be attributed to changes in the quality of the peripheral signal. Furthermore, we found GOTs to be relatively independent of stimulus amplitude, so the low spatial acuity at high flutter frequencies does not appear to be due to an inadequacy in the strength of the afferent response at those frequencies. We hypothesized that the RA signal, the strength of which increases with vibratory frequency, interfered with the spatially modulated signal conveyed by SA1 fibers. Consistent with this hypothesis, we found that adapting RA afferent fibers improved spatial acuity, as gauged by GOTs, at the high flutter frequencies.
Persistent Synchronized Bursting Activity in Cortical Tissues With Low Magnesium Concentration: A Modeling Study
Authors: Golomb David , Shedmi Anat , Curtu Rodica , Ermentrout G. Bard
Published: October 2005

We explore the mechanism of synchronized bursting activity with frequency of ∼10 Hz that appears in cortical tissues at low extracellular magnesium concentration [Mg2+]o. We hypothesize that this activity is persistent, namely coexists with the quiescent state and depends on slow N-methyl-d-aspartate (NMDA) conductances. To explore this hypothesis, we construct and investigate a conductance-based model of excitatory cortical networks. Population bursting activity can persist for physiological values of the NMDA decay time constant (∼100 ms). Neurons are synchronized at the time scale of bursts but not of single spikes. A reduced model of a cell coupled to itself can encompass most of this highly synchronized network behavior and is analyzed using the fast-slow method. Synchronized bursts appear for intermediate values of the NMDA conductance gNMDAif NMDA conductances are not too fast. Regular spiking activity appears for larger gNMDA. If the single cell is a conditional burster, persistent synchronized bursts become more robust. Weakly synchronized states appear for zero AMPA conductance gAMPA. Enhancing gAMPAincreases both synchrony and the number of spikes within bursts and decreases the bursting frequency. Too strong gAMPA, however, prevents the activity because it enhances neuronal intrinsic adaptation. When [Mg2+]ois increased, higher gNMDAvalues are needed to maintain bursting activity. Bursting frequency decreases with [Mg2+]o, and the network is silent with physiological [Mg2+]o. Inhibition weakly decreases the bursting frequency if inhibitory cells receive enough NMDA-mediated excitation. This study explains the importance of conditional bursters in layer V in supporting epileptiform activity at low [Mg2+]o.
Bursts of Information: Coordinating Interneurons Encode Multiple Parameters of a Periodic Motor Pattern
Authors: Mulloney Brian , Harness Patricia I. , Hall Wendy M.
Published: October 2005

The limbs on different segments of the crayfish abdomen that drive forward swimming are directly controlled by modular pattern-generating circuits. These circuits are linked together by axons of identified coordinating interneurons. We described the distributions of these neurons in each abdominal ganglion and monitored their firing during expression of the swimming motor pattern. We analyzed the timing, the numbers of spikes, and the duration of each burst of spikes in these coordinating neurons. To see what information these neurons encoded, we correlated these parameters with the timing, durations, and strengths of bursts of spikes in motor axons from the same modules. During the power-stroke phase of each output cycle, the anterior-projecting neurons fired bursts of spikes that encoded information about the start-time, duration, and strength of each burst of spikes in power-stroke motor neurons from the same module. When the period and intensity of the motor output fluctuated, the bursts of spikes in these neurons tracked these fluctuations accurately. Each additional spike in these neurons signified an increase in the strength of the power-stroke burst. The posterior-projecting neurons that fired during the return-stroke phase encoded similar information about the return-stroke motor neurons. Although homologous neurons from different ganglia were qualitatively similar, neurons from posterior ganglia fired significantly more spikes per burst than those from more anterior ganglia, a segmental gradient that correlates with the normal posterior-to-anterior phase progression of limb movements. We propose that this gradient and a similar gradient in the durations of bursts in power-stroke motor neurons might reflect a hitherto-undetected difference in the excitation or intrinsic excitability of swimmeret modules in different segments.
nfi-1 affects behavior and life-span in C. elegansbut is not essential for DNA replication or survival
Authors: Lazakovitch Elena , Kalb John M , Matsumoto Reiko , Hirono Keiko , Kohara Yuji , Gronostajski Richard M
Published: October 2005

Background

The Nuclear Factor I (one) (NFI) family of transcription/replication factors plays essential roles in mammalian gene expression and development and in adenovirus DNA replication. Because of its role in viral DNA replication NFI has long been suspected to function in host DNA synthesis. Determining the requirement for NFI proteins in mammalian DNA replication is complicated by the presence of 4 NFI genes in mice and humans. Loss of individual NFI genes in mice cause defects in brain, lung and tooth development, but the presence of 4 homologous NFI genes raises the issue of redundant roles for NFI genes in DNA replication. No NFI genes are present in bacteria, fungi or plants. However single NFI genes are present in several simple animals including Drosophila and C. elegans, making it possible to test for a requirement for NFI in multicellular eukaryotic DNA replication and development. Here we assess the functions of the single nfi-1 gene in C. elegans.

Results

C. elegans NFI protein (CeNFI) binds specifically to the same NFI-binding site recognized by vertebrate NFIs. nfi-1 encodes alternatively-spliced, maternally-inherited transcripts that are expressed at the single cell stage, during embryogenesis, and in adult muscles, neurons and gut cells. Worms lacking nfi-1 survive but have defects in movement, pharyngeal pumping and egg-laying and have a reduced life-span. Expression of the muscle gene Ce titin is decreased in nfi-1 mutant worms.

Conclusion

NFI gene function is not needed for survival in C. elegans and thus NFI is likely not essential for DNA replication in multi-cellular eukaryotes. The multiple defects in motility, egg-laying, pharyngeal pumping, and reduced lifespan indicate that NFI is important for these processes. Reduction in Ce titin expression could affect muscle function in multiple tissues. The phenotype of nfi-1 null worms indicates that NFI functions in multiple developmental and behavioral systems in C. elegans, likely regulating genes that function in motility, egg-laying, pharyngeal pumping and lifespan maintenance.
Comparative genomics of Thermus thermophilus and Deinococcus radiodurans: divergent routes of adaptation to thermophily and radiation resistance
Authors: Omelchenko Marina V , Wolf Yuri I , Gaidamakova Elena K , Matrosova Vera Y , Vasilenko Alexander , Zhai Min , Daly Michael J , Koonin Eugene V , Makarova Kira S
Published: October 2005

Background

Thermus thermophilusandDeinococcus radioduransbelong to a distinct bacterial clade but have remarkably different phenotypes.T. thermophilusis a thermophile, which is relatively sensitive to ionizing radiation and desiccation, whereasD. radioduransis a mesophile, which is highly radiation- and desiccation-resistant. Here we present an in-depth comparison of the genomes of these two related but differently adapted bacteria.

Results

By reconstructing the evolution ofThermusandDeinococcusafter the divergence from their common ancestor, we demonstrate a high level of post-divergence gene flux in both lineages. Various aspects of the adaptation to high temperature inThermuscan be attributed to horizontal gene transfer from archaea and thermophilic bacteria; many of the horizontally transferred genes are located on the single megaplasmid ofThermus. In addition, theThermuslineage has lost a set of genes that are still present inDeinococcusand many other mesophilic bacteria but are not common among thermophiles. By contrast,Deinococcusseems to have acquired numerous genes related to stress response systems from various bacteria. A comparison of the distribution of orthologous genes among the four partitions of theDeinococcusgenome and the two partitions of theThermusgenome reveals homology between theThermusmegaplasmid (pTT27) andDeinococcusmegaplasmid (DR177).

Conclusion

After the radiation from their common ancestor, theThermusandDeinococcuslineages have taken divergent paths toward their distinct lifestyles. In addition to extensive gene loss,Thermusseems to have acquired numerous genes from thermophiles, which likely was the decisive contribution to its thermophilic adaptation. By contrast,Deinococcuslost few genes but seems to have acquired many bacterial genes that apparently enhanced its ability to survive different kinds of environmental stresses. Notwithstanding the accumulation of horizontally transferred genes, we also show that the single megaplasmid ofThermusand the DR177 megaplasmid ofDeinococcusare homologous and probably were inherited from the common ancestor of these bacteria.
Assessing the power of tag SNPs in the mapping of quantitative trait loci (QTL) with extremal and random samples
Authors: Zhang Kui , Sun Fengzhu
Published: October 2005

Background

Recent studies have indicated that the human genome could be divided into regions with low haplotype diversity interspersed with regions of high haplotype diversity. In regions of low haplotype diversity, a small fraction of SNPs (tag SNPs) are sufficient to account for most of the haplotype diversity of the human genome. These tag SNPs can be extremely useful for testing the association of a marker locus with a qualitative or quantitative trait locus in that it may not be necessary to genotype all the SNPs. When tag SNPs are used to reduce the genotyping effort in association studies, it is important to know how much power is lost. It is also important to know how much power is gained when tag SNPs instead of the same number of randomly chosen SNPs are used.

Results

We design a simulation study to tackle these problems for a variety of quantitative association tests using either case-parent samples or unrelated population samples. First, the samples are generated based on the quantitative trait model with the assumption of either an extremal sampling scheme or a random sampling scheme. Second, a small number of samples are selected to determine the haplotype blocks and the tag SNPs. Third, the statistical power of the tests is evaluated using four kinds of data: (1) all the SNPs and the corresponding haplotypes, (2) the tag SNPs and the corresponding haplotypes, (3) the same number of evenly spaced SNPs with minor allele frequency greater than a threshold and the corresponding haplotypes, (4) the same number of randomly chosen SNPs and their corresponding haplotypes.

Conclusion

Our results suggest that in most situations genotyping efforts can be significantly reduced by using tag SNPs for mapping the QTL in association studies without much loss of power, which is consistent with previous studies on association mapping of qualitative traits. For all situations considered, two-locus haplotype analysis using tag SNPs are more powerful than those using the same number of randomly selected SNPs, but the degree of such power differences depends upon the sampling scheme and the population history.
i-Tracker: For quantitative proteomics using iTRAQ™
Authors: Shadforth Ian P , Dunkley Tom PJ , Lilley Kathryn S , Bessant Conrad
Published: October 2005

Background

iTRAQ™ technology for protein quantitation using mass spectrometry is a recent, powerful means of determining relative protein levels in up to four samples simultaneously. Although protein identification of samples generated using iTRAQ may be carried out using any current identification software, the quantitation calculations have been restricted to the ProQuant software supplied by Applied Biosciences. i-Tracker software has been developed to extract reporter ion peak ratios from non-centroided tandem MS peak lists in a format easily linked to the results of protein identification tools such as Mascot and Sequest. Such functionality is currently not provided by ProQuant, which is restricted to matching quantitative information to the peptide identifications from Applied Biosciences' Interrogator™ software.

Results

i-Tracker is shown to generate results that are consistent with those produced by ProQuant, thus validating both systems.

Conclusion

i-Tracker allows quantitative information gained using the iTRAQ protocol to be linked with peptide identifications from popular tandem MS identification tools and hence is both a timely and useful tool for the proteomics community.
Long-term all-sites cancer mortality time trends in Ohio, USA, 1970–2001: differences by race, gender and age
Authors: Tyczynski Jerzy E , Berkel Hans J
Published: October 2005

Background

There were significant changes in cancer mortality in the USA over the last several decades, in the whole country and in particular states. However, no in depth analysis has been published so far, dealing with changes in mortality time trends in the state of Ohio. Since the state of Ohio belongs to the states of relatively high level of all-sites mortality in both males and females, it is of interest to analyze recent changes in mortality rates, as well as to compare them with the situation in the rest of the USA. The main aim of this study was to analyze, describe and interpret all-sites cancer mortality time trends in the population of the State of Ohio.

Methods

Cancer mortality data by age, sex, race and year for the period 1970–2001 were obtained from the Surveillance Research Program of the National Cancer Institute SEER*Stat software. A joinpoint regression methodology was used to provide estimated annual percentage changes (EAPCs) and to detect points in time where significant changes in the trends occurred.

Results

In both, males and females mortality rates were higher in blacks compared with whites. The difference was bigger in males (39.9%) than in women (23.3%). Mortality rates in Ohio are generally higher than average USA rates – an overall difference was 7.5% in men in 1997–2001, and 6.1% in women. All-sites mortality trends in Ohio and in the whole USA are similar. However, in general, mortality rates in Ohio remained elevated compared with the USA rates throughout the entire analyzed period. The exceptions are the rates in young and middle-aged African Americans.

Conclusion

Although direction of time trends in Ohio are similar in Ohio and the whole US, Ohio still have cancer mortality rates higher than the US average. In addition, there is a significant discrepancy between white and black population of Ohio in all-sites mortality level, with disadvantage for Blacks. To diminish disparities in cancer mortality between African Americans and white inhabitants of Ohio efforts should be focused on increasing knowledge of black people regarding healthy lifestyle and behavioral risk factors, but also on diminishing socioeconomic differences, and last but not least, on better access to medical care.
Missing effects of zinc in a porcine model of recurrent endotoxemia
Authors: Krones Carsten J , Klosterhalfen Bernd , Anurov Michael , Stumpf Michael , Klinge Uwe , Oettinger Alexander P , Schumpelick Volker
Published: October 2005

Background

Chronic human sepsis often is characterised by the compensatory anti-inflammatory response syndrome (CARS). During CARS, anti-inflammatory cytokines depress the inflammatory response leading to secondary and opportunistic infections. Provedin vitroas well asin vivo, zinc's pro-inflammatory effect might overcome this depression.

Methods

We used the model of porcine LPS-induced endotoxemia established by Klosterhalfen et al. 10 pigs were divided into two groups (n = 5). Endotoxemia was induced by recurrent intravenous LPS-application (1.0 μg/kg E. coli WO 111:B4) at hours 0, 5, and 12. At hour 10, each group received an intravenous treatment (group I = saline, group II = 5.0 mg/kg elementary zinc). Monitoring included hemodynamics, blood gas analysis, and the thermal dilution technique for the measurement of extravascular lung water and intrapulmonary shunt. Plasma concentrations of IL-6 and TNF-alpha were measured by ELISA. Morphology included weight of the lungs, width of the alveolar septae, and rate of paracentral liver necrosis.

Results

Zinc's application only trended to partly improve the pulmonary function. Compared to saline, significant differences were very rare. IL-6 and TNF-alpha were predominately measured higher in the zinc group. Again, significance was only reached sporadically. Hemodynamics and morphology revealed no significant differences at all.

Conclusion

The application of zinc in this model of recurrent endotoxemia is feasible and without harmful effects. However, a protection or restoration of clinical relevance is not evident in our setting. The pulmonary function just trends to improve, cytokine liberation is only partly activated, hemodynamics and morphology were not influenced. Further pre-clinical studies have to define zinc's role as a therapeutic tool during CARS.
Status of national research bioethics committees in the WHO African region
Authors: Kirigia Joses M , Wambebe Charles , Baba-Moussa Amido
Published: October 2005

Background

The Regional Committee for Africa of the World Health Organization (WHO) in 2001 expressed concern that some health-related studies undertaken in the Region were not subjected to any form of ethics review. In 2003, the study reported in this paper was conducted to determine which Member country did not have a national research ethics committee (REC) with a view to guiding the WHO Regional Office in developing practical strategies for supporting those countries.

Methods

This is a descriptive study. The questionnaire was prepared and sent by diplomatic pouch to all the 46 Member States in the WHO African Region, through the WHO country representatives, for facilitation and follow up. The data were entered in Excel spreadsheet and subsequently exported to STATA for analysis. A Chi-Squared test (χ
2) for independence was undertaken to test the relationship between presence/absence of Research Ethics Committee (REC) and selected individual socioeconomic and health variables.

Results

The main findings were as follows: the response rate was 61% (28/46); 64% (18/28) confirmed the existence of RECs; 36% (10/28) of the respondent countries did not have a REC (although 80% of them reported that they had in place an ad hoc ethical review mechanism); 85% (22/26) of the countries that responded to this question indicated that ethical approval of research proposals was, in principle, required; and although 59% of the countries that had a REC expected it to meet every month, only 44% of them reported that the REC actually met on a monthly basis. In the Chi-Squared test, only the average population in the group of countries with a REC was statistically different (at 5% level of significance) from that of the group of countries without a REC.

Conclusion

In the current era of globalized biomedical research, good ethics stewardship demands that every country, irrespective of its level of economic development, should have in place a functional research ethics review system in order to protect the dignity, integrity and safety of its citizens who participate in research.
The importance of immune gene variability (MHC) in evolutionary ecology and conservation
Authors: Sommer Simone
Published: October 2005

Genetic studies have typically inferred the effects of human impact by documenting patterns of genetic differentiation and levels of genetic diversity among potentially isolated populations using selective neutral markers such as mitochondrial control region sequences, microsatellites or single nucleotide polymorphism (SNPs). However, evolutionary relevant and adaptive processes within and between populations can only be reflected by coding genes. In vertebrates, growing evidence suggests that genetic diversity is particularly important at the level of the major histocompatibility complex (MHC). MHC variants influence many important biological traits, including immune recognition, susceptibility to infectious and autoimmune diseases, individual odours, mating preferences, kin recognition, cooperation and pregnancy outcome. These diverse functions and characteristics place genes of the MHC among the best candidates for studies of mechanisms and significance of molecular adaptation in vertebrates. MHC variability is believed to be maintained by pathogen-driven selection, mediated either through heterozygote advantage or frequency-dependent selection. Up to now, most of our knowledge has derived from studies in humans or from model organisms under experimental, laboratory conditions. Empirical support for selective mechanisms in free-ranging animal populations in their natural environment is rare. In this review, I first introduce general information about the structure and function of MHC genes, as well as current hypotheses and concepts concerning the role of selection in the maintenance of MHC polymorphism. The evolutionary forces acting on the genetic diversity in coding and non-coding markers are compared. Then, I summarise empirical support for the functional importance of MHC variability in parasite resistance with emphasis on the evidence derived from free-ranging animal populations investigated in their natural habitat. Finally, I discuss the importance of adaptive genetic variability with respect to human impact and conservation, and implications for future studies.
Review: intravenous immunoglobulin therapy and thromboembolic complications
Authors: Katz U , Shoenfeld Y
Published: October 2005

Intravenous immunglobulin (IVIg) is used to treat a number of immune-deficiences and autoimmune diseases. Safety concerns related to a number of reported thromboembolic complications prompted us to review the literature. These complications happened mainly in individuals that had risk factors for thromboembolism, like advanced age, previous thromboembolic diseases, bed-ridden, and in individuals in which high doses or high infusion rates of IVIg were administered. The mechanism responsible for these events seems to be a rise in plasma viscosity that can trigger a thromboembolic event, especially in cases in which there is an underlying circulation impairment. Complications can be minimized by using IVIg only in clear-cut indications, weighting risk versus benefit in patients who are at high risk for thromboembolism and by sticking to carefully monitored slow infusion rates. IVIg for the treatment of autoimmune disorders should be administered as a five-day course of 2 g/kg of body weight. Each daily dose of 400 mg/kg should be given in not less than eight hours.
Can systemic lupus erythematosus be the cause of collapsing glomerulopathy?
Authors: Marques L PJ , Pacheco G GLC , Rioja L S , Nunes S N , Velone S T , Santos O R
Published: October 2005

Collapsing glomerulopathy is a severe form of glomerular injury, closely associated with HIV infection, characterized by the collapsing feature of glomerular damage with frequent tubulointerstitial involvement and rapid progression to terminal renal failure. The etiopathogenesis in non-HIV infected patients remains obscure. We reported a patient whose diagnosis of collapsing glomerulopathy (CG) and systemic lupus erythematosus (SLE) was done simultaneously and described the diseases characteristics suggesting that SLE could be an etiologic factor for the induction of this glomerulopathy, clinical evolution and treatment.
Lymphocyte subpopulations and intima media thickness in primary antiphospholipd syndrome
Authors: Ames P RJ , Tommasino C , Fossati G , Matsuura E , Margarita A , Saulino A , Lopez L , Scenna G , Brancaccio V
Published: October 2005

The aim of this study was to evaluate a possible association between lymphocyte subsets and intima media thickness (IMT) of carotid arteries in primary antiphospholipid syndrome (PAPS). We used a cross-sectional study on PAPS patients ( n = 18) and healthy controls ( n = 16). IgG anti-cardiolipin antibody (aCL), IgG anti-β2glycoprotein-I (anti-β2GPI), IgG anti-β2glycoprotein-I complexed to oxidized low-density lipoprotein (oxLDL) and to a specific oxidized moiety of LDL (oxLig1), and β2GPI-oxLDL were measured by ELISA. Lymphocyte immunophenotyping was performed using pairs of monoclonal antibodies directly labelled with fluorescein isothiocyanate, or phycoerythrin or phycoerythrin-Texas-red-X. Intima media thickness (IMT) of carotid arteries was determined by high-resolution sonography. Total peripheral blood lymphocytes did not differ between PAPS and controls. Memory CD4+/CD45RO + T cells were lower in PAPS than controls ( P = 0.0007) as well as CD16+56+ natural killer cells ( P = 0.02). In PAPS memory T CD45RO + cells positively correlated with IgG anti-β2GPI-oxLig1 ( P = 0.002) and to IMT of carotid arteries (common carotid P = 0.02, bifurcation P = 0.007). Naïve CD4+/CD45RA+ T cells inversely correlated with β2GPI-oxLDL ( P = 0.009). The relation between IgG anti-β2GPI-oxLig1 and IMT of carotid arteries with memory CD45RO + T lymphocytes suggests a role for the latter in PAPS related atherogenesis.
Mast cells, TGF-β1 and myofibroblasts expression in lupus nephritis outcome
Authors: Ravinal R Cuan , Costa R S , Coimbra T M , Dantas M , dos Reis M A
Published: October 2005

Renal biopsies of 69 patients with lupus nephritis were studied according to the WHO classification. The aim of the present study was to correlate the interstitial tryptase-positive mast cells with the interstitial TGF-β1 and α-SM actin expression and clinical outcome of lupus nephritis, and identify the pathological role of the interstitial tryptase-positive mast cells in lupus nephritis. The mean follow-up time was 70.7 ± 54.4 months. Eight patients were grouped as WHO class II lupus nephritis, 15 patients as class III, 28 patients as class IV and 18 patients as class V. Interstitial tryptase-positive mast cells were not correlated with clinical outcome and interstitial TGF-β1 expression in lupus nephritis. Interstitial tryptase-positive mast cells were correlated with tubulo-interstitial α-SM actin expression for WHO class V lupus nephritis, but not to the other classes. In conclusion, in spite of interstitial tryptase-positive mast cells being related to renal interstitial fibrosis process, their expression according to the clinical outcome of lupus nephritis was not significant.
The functional p53 codon 72 polymorphism is associated with systemic lupus erythematosus
Authors: Lee Y H , Rho Y H , Choi S J , Ji J D , Song G G
Published: October 2005

The aim of the study is to investigate whether the functional p53 codon 72 polymorphism is associated with susceptibility to SLE and its clinical features. A polymerase chain reaction of genomic DNA-restriction fragment length polymorphism was used to determine genotypes of the p53 codon 72 in 90 SLE patients and 114 healthy controls. Clinical/serological manifestations were analysed in each patient and correlated with the genotypes. The OR of the association of the Pro allele with SLE was 1.70 (95% CI, 1.15-2.53, P = 0.0079) and the OR of the Pro/Pro (a recessive model) was significantly increased (OR = 2.58, 95% CI = 1.24-5.39, P = 0.0093). The Armitage’s trend test indicated a significant dosage effect of the Pro allele for SLE (OR = 1.73, chi-square = 7.08, P = 0.0078). However, there was no significant association of the polymorphism with clinical/serological manifestations studied here. In conclusion, our finding suggests the functional p53 codon 72 polymorphism may be associated with SLE susceptibility, suggesting individuals who carry the Pro allele may have a higher risk to SLE susceptibility than those with the Arg allele. Further studies for replications are needed to confirm that the p53 polymorphism contributes to SLE.
Acute lupus myocarditis: clinical features and outcome of an oriental case series
Authors: Law W G , Thong B Y , Lian T Y , Kong K O , Chng H H
Published: October 2005

Symptomatic myocarditis in systemic lupus erythematosus (SLE) is uncommon. We describe the clinical characteristics, management and outcomes of 11 SLE patients without any atherosclerotic risk factors, who presented with acute lupus myocarditis (ALM). All patients were female, 46% Chinese with mean age of 27 < 10 years at diagnosis of SLE. ALM was one of the initial manifestations of SLE in eight (73%) patients. The median duration from onset ALM to initiation of treatment was two weeks (range: 0.3-8). All had clinical feature of left ventricle dysfunction. The most common electrocardiographic feature was nonspecific ST/T wave changes (91%). Common echocardiographic findings included segmental wall motion abnormalities (81%) and decreased left ventricular ejection fraction (81%). Median SLE disease activity index at presentation was 16 (range: 4-30). All patients received high dose corticosteroids and 64% received intravenous pulse cyclophosphamide. There were two deaths (18%) from infections. The remaining nine survivors had no recurrence of ALM nor suffer any SLE-related damage (median SLICC damage score of 0), up to a median follow-up of four years (range: 2.5-10.1). Repeat echocardiography after six months or later showed normal LVEF in eight patients (89%). Early immunosuppressive therapy in ALM, with high dose corticosteroids and pulse intravenous cyclophosphamide, results in good cardiac outcome.
An Overview of KRL, a Knowledge Representation Language
Authors: Bobrow Daniel G. , Winograd Terry
Published: October 2005

This paper describes KRL, a Knowledge Representation Language designed for use in understander systems. It outlines both the general concepts which underlie our research and the details of KRL‐0, an experimental implementation of some of these concepts. KRL is an attempt to integrate procedural knowledge with a broad base of declarative forms. These forms provide a variety of ways to express the logical structure of the knowledge, in order to give flexibility in associating procedures (for memory and reasoning) with specific pieces of knowledge, and to control the relative accessibility of different facts and descriptions. The formalism for declarative knowledge is based on structured conceptual objects with associated descriptions. These objects form a network of memory units with several different sorts of linkages, each having well‐specified implications for the retrieval process. Procedures can be associated directly with the internal structure of a conceptual object. This procedurul attachment allows the steps for a particular operation to be determined by characteristics of the specific entities involved.

The control structure of KRL is based on the belief that the next generation of intelligent programs will integrate data‐directed and goal‐directed processing by using multiprocessing. It provides for a priority‐ordered multiprocess agenda with explicit (user‐provided) strategies for scheduling and resource allocation. It provides procedure directories which operate along with process frameworks to allow procedural parameterization of the fundamental system processes for building, comparing, and retrieving memory structures. Future development of KRL will include integrating procedure definition with the descriptive formalism.
Human and Computational Question Answering*
Authors: Lehnert Wendy
Published: October 2005

The ability to answer questions about a text is the strongest possible demonstration of text comprehension. The question‐answering problems that arise in a story‐understanding system are discussed. Some solutions are described and illustrated by a computer program, which reads stories, and answers questions.
Definite Descriptions and Semantic Memory*
Authors: Ortony Andrew , Anderson Richard C.
Published: October 2005

Subjects were exposed to sentences containing “direct” and “indirect” uses of names and definite descriptions. On a subsequent recognition test incorrect rejections tended to be of sentences involving indirect uses, and false alarms to sentences involving direct uses. This finding is contrary to the predictions of models that suggest indiscriminate substitution of names for descriptions, as do those of Anderson and Bower, and Rumelhart and Norman. The implication is that models of semantic memory must incorporate distinct intensional and extensional representations to avoid semantic distortion.
Artificial Intelligence, Language, and the Study of Knowledge*,†
Authors: Goldstein Ira , Papert Seymour
Published: October 2005

This paper studies the relationship of Artificial Intelligence to the study of language and the representation of the underlying knowledge which supports the comprehension process. It develops the view that intelligence is based on the ability to use large amounts of diverse kinds of knowledge in procedural ways, rather than on the possession of a few general and uniform principles. The paper also provides a unifying thread to a variety of recent approaches to natural language comprehension. We conclude with a brief discussion of how Artificial Intelligence may have a radical impact on education if the principles which it utilizes to explore the representation and use of knowledge are made available to the student to use in his own learning experiences.
Induction of Augmented Transition Networks*
Authors: Anderson John R.
Published: October 2005

LAS is a program that acquires augmented transition network (ATN) grammars. It requires as data sentences of the language and semantic network representatives of their meaning. In acquiring the ATN grammars, it induces the word classes of the language, the rules of formation for sentences, and the rules mapping sentences onto meaning. The induced ATN grammar can be used both for sentence generation and sentence comprehension. Critical to the performance of the program are assumptions that it makes about the relation between sentence structure and surface structure (the graph deformation condition), about when word classes may be formed and when ATN networks may be merged, and about the structure of noun phrases. These assumptions seem to be good heuristics which are largely true for natural languages although they would not be true for many nonnatural languages. Provided these assumptions are satisfied LAS seems capable of learning any context‐free language.