bluuebunny/crossref_metadata_2025 huggingface dataset:
Alzheimer's Disease Effects on Semantic Memory: Loss of Structure or Impaired Processing?
Authors: Bayles Kathryn A. , Tomoeda Cheryl K. , Kaszniak Alfred W. , Trosset Michael W.
Published: February 2008

Results of several prior studies, in which Alzheimer's disease (AD) patients missed the same concepts on multiple tasks, have been used to substantiate the theory that AD causes concept-specific loss of information from semantic memory However, sample sizes in these studies are modest, test-retest intervals small, and typically only a few tasks were used. In the present study 69 An subjects were annually administered 11 tasks, each using the same 13 concepts. Only a few instances were observed in which a concept was missed across all 11 tasks. When performances on the Oral Reading and Dictation tasks were removed from analysis, because of their questionable reliance on semantic memory, the number of missed concepts rose only modestly. A substantial rise in the number of missed concepts occurred, however, when performances on the four multiple- choice tasks were removed. Interpreting the larger number of missed concepts on the five remaining generative semantic tasks as evidence of item-specific loss is problematic, nonetheless, because the generative semantic tasks were among the hardest in the battery and the frequency with which an individual subject missed a concept across all tasks accorded with the subject's dementia severity level. Results also indicate that task difficulty, more than concept specificity, determine whether a concept is missed. Overall, results suggest that a concept will “disappear” when all of the tasks in which it is a stimulus become too difficult for the patient to perform. Study results call into question the appropriateness of using batteries of effortful, attention demanding tasks for ascertaining whether AD causes item-specific loss of conceptual knowledge.
Extrageniculate Contributions to Reflex Visual Orienting in Normal Humans: A Temporal Hemifield Advantage
Authors: Rafal Robert , Henik Avishai , Smith Jean
Published: February 2008

Evidence is presented that the phylogenetically older retin-otectal pathway contributes to reflex orienting of visual attention in normal human subjects. The study exploited a lateralized neuroanatomic arrangement of retinotectal pathways that distinguishes them from those of the geniculostriate system; namely, more direct projections to the colliculus from the temporal hemifield. Subjects were tested under monocular viewing conditions and responded to the detection of a peripheral signal by making either a saccade to it or a choice reaction time manual keypress. Attention was summoned by noninformative peripheral precues, and the benefits and costs of attention were calculated relative to a central precue condition. Both the benefits and costs of orienting attention were greater when attention was summoned by signals in the temporal hemifield. This temporal hemifield advantage was present for both saccade and manual responses. These findings converge with observations in patients with occipital and midbrain lesions to show that the phylogenetically older retinotectal pathway retains an important role in controlling visually guided behavior; and they demonstrate the usefulness of temporal-nasal hemifield asymmetries as a marker for investigating extrageniculate vision in humans.
Dissociation of Object and Spatial Vision in Human Extrastriate Cortex: Age-Related Changes in Activation of Regional Cerebral Blood Flow Measured with [15 O]Water and Positron Emission Tomography
Authors: Grady Cheryl L. , Haxby James V. , Horwitz Barry , Schapiro Mark B. , Rapoport Stanley I. , Ungerleider Leslie G. , Mishkin Mortimer , Carson Richard E. , Herscovitch Peter
Published: February 2008

We previously reported selective activation of regional cerebral blood flow (rCBF) in occipitotemporal cortex during a face matching task (object vision) and activation in superior parietal cortex during a dot-location matching task (spatial vision) in young subjects, The purpose of the present study was to determine the effects of aging on these extrastriate visual processing systems. Eleven young (mean age 27 ± 4 years) and nine old (mean age 72 ± 7 years) male subjects were studied. Positron emission tomographic scans were performed using a Scanditronix PC1024–7B tomograph and H2 15O to measure rCBF. To locate brain areas that were activated by the visual tasks, pixel-by-pixel difference images were computed between images from a control task and images from the face and dot-location matching tasks. Both young and old subjects showed rCBF activation during face matching primarily in occipitotemporal cortex, and activation of superior parietal cortex during dot-location matching. Statistical comparisons of these activations showed that the old subjects had more activation of occipitotemporal cortex during the spatial task and more activation of superior parietal cortex during the object task than did the young subjects. These results show less functional separation of the dorsal and ventral visual pathways in older subjects, and may reflect an age-related reduction in the processing efficiency of these visual cortical areas.
Declarative and Nondeclarative Memory: Multiple Brain Systems Supporting Learning and Memory
Authors: Squire Larry R.
Published: February 2008

The topic of multiple forms of memory is considered from a biological point of view. Fact-and-event (declarative, explicit) memory is contrasted with a collection of non conscious (non-declarative, implicit) memory abilities including skills and habits, priming, and simple conditioning. Recent evidence is reviewed indicating that declarative and non declarative forms of memory have different operating characteristics and depend on separate brain systems. A brain-systems framework for understanding memory phenomena is developed in light of lesion studies involving rats, monkeys, and humans, as well as recent studies with normal humans using the divided visual field technique, event-related potentials, and positron emission tomography (PET).
Priming and Multiple Memory Systems: Perceptual Mechanisms of Implicit Memory
Authors: Schacter Daniel L.
Published: February 2008

Research examining the relation between explicit and implicit forms of memory has generated a great deal of evidence concerning the issue of multiple memory systems. This article focuses on an extensively studied implicit memory phenomenon, known as direct or repetition priming, and examines the hypothesis that priming effects on various tasks reflect the operation of a perceptual representation system (PRS)—a class of cortically based subsystems that operate at a presemantic level and support non conscious expressions of memory. Three PRS subsystems are examined: visual word form, structural description, and auditory word form. Pertinent cognitive, neuropsychological, and neurobiological evidence is reviewed, alternative classificatory schemes are discussed, and important conceptual and terminological issues are considered.
Bridging the Gap: Evidence from ERPs on the Processing of Unbounded Dependencies
Authors: Kluender Robert , Kutas Marta
Published: February 2008

Since the early days of generative grammar, the study of “unbounded dependencies” such as wh-questions and relative clauses has occupied a central place in both syntactic theory and language processing research. The problem that such constructions pose is as follows. In a normal wh-question, a wh-phrase is typically displaced to the left periphery of a clause (What did you say — to John?); this displaced constituent is often referred to as a “filler.” The vacant position (indicated in the previous example by a blank line) where it would ordinarily occur in an “echo” question (You said what to John?) is correspondingly referred to as a “gap.” Filler and gap are mutually dependent on each other since they share syntactic and semantic information essential for successful sentence interpretation. However, since sentence processing is a sequential operation, a filler cannot be assigned to its gap until some time after it has occurred. In other words, the filler must be held in working memory until such time as filler-gap assignment can take place. The intent of the research reported here was to examine the processing of unbounded dependencies in English as revealed in event-related brain potentials (ERPs). To this end, subjects were shown both grammatical and ungrammatical yes/no-questions (Did you say something to John?) and wh-questions. A number of comparisons made at various points in these questions showed that both the storage of a filler in working memory and its subsequent retrieval for filler-gap assignment were associated with an enhanced negativity between 300 and 500 msec poststimulus over left anterior sites. This effect of left anterior negativity (LAN) was independent of and orthogonal to the grammaticality of the eliciting condition. We show how this interpretation coincides with recent studies that demonstrate a correlation between left anterior negativity, working memory capacity, and successful language processing.
Visual Extinction and Stimulus Repetition
Authors: Baylis Gordon C. , Driver Jon , Rafal Robert D.
Published: February 2008

Five patients with visual extinction following unilateral brain injury were briefly presented with colored letters in either or both visual fields, and required to report and locate the colors or the shapes. On double simultaneous stimulation, they tended to miss the event contralateral to their lesion. This extinction was increased when the two stimuli were the same on the reported dimension, Similarity on the irrelevant dimension had no effect. These data suggest that extinguished colors and shapes may be correctly extracted by the visual system (when task-relaant) even though they are unavailable for verbal report. An analogy is made with the phenomena of “repetition blindness” in normal observers, and it is proposed that extinction may reflect failure in a token-individuation process for correctly extracted visual types.
On Language
Authors: Pinker Steven
Published: February 2008

Steven Pinker is a professor in the Department of Brain and Cognitive Sciences at MIT, and in 1994 will become director of its McDonnell-Pew Center for Cognitive Neuroscience. He received his B.K from McGill University in 1976 and his Ph.D. from Harvard University in 1979, both in experimental psychology, and taught at Harvard and Stanford before joining the faculty of MIT in 1982. He has done research in visual cognition and the psychology of language, and is the author of Language Learnability and Language Development (1984) and Learnability and Cognition (1989) and the editor of Visual Cognition (1985), Connections and Symbol (1988, with Jacques Mehler), and Lexical and Conceptual Semantics (1992, with Beth Levin). He was the recipient of the Early Career Award in 1984 and the Boyd McCandless Award in 1986 from the American Psychological Association, a Graduate Teaching Award from MIT in 1986, and the Troland Research Award from the National Academy of Sciences in 1993. His newest book, The Language Instinct, will be published by William Morrow & Company in January 1994.
Susceptibility to Memory Interference Effects following Frontal Lobe Damage: Findings from Tests of Paired-Associate Learning
Authors: Shimamura Arthur P. , Jurica Paul J. , Mangels Jennifer A. , Gershberg Felick B. , Knight Robert T.
Published: February 2008

Patients with frontal lobe lesions were adminstered tests of paired-associate learning in which cue and response words are manipulated to increase interference across two study lists. In one test of paired-associate learning (AB-AC test), cue words used in one list are repeated in a second list but are associated with different response words (e.g., LION-HUNTER, LION-CIRCUS). In another test (AB-ABr test), words used in one list are repeated in a second list but are rearranged to form new pairs. Compared to control subjects, patients with frontal lobe lesions exhibited disproportionate impairment of second-list learning as a result of interference effects. In particular, patients exhibited the poorest performance during the initial trial of the second list, a trial in which interference effects from the first list would be most apparent. These findings suggest that the on-line control of irrelevant or competing memory associations is disrupted following frontal lobe lesions. This disruption may be indicative of an impaired gating or filtering mechanism that affects not only memory function but other cognitive function as well.
Representation of Grammatical Categories of Words in the Brain
Authors: Hillis Argye E. , Caramazza Alfonso
Published: February 2008

We report the performance of a patient who, as a consequence of left frontal and temporoparietal strokes, makes far more errors on nouns than on verbs in spoken output tasks, but makes far more errors on verbs than on nouns in written input tasks. This double dissociation within a single patient with respect to grammatical category provides evidence for the hypothesis that phonological and orthographic representations of nouns and verbs are processed by independent neural mechanisms. Furthermore, the opposite dissociation in the verbal output modality, an advantage for nouns over verbs in spoken tasks, by a different patient using the same stimuli has also been reported (Caramazza & Hillis, 1991). This double dissociation across patients on the same task indicates that results cannot be ascribed to "greater difficulty" with one type of stimulus, and provides further evidence for the view that grammatical category information is an important organizational principle of lexical knowledge in the brain.
Modulation of Event-Related Potentials by Semantic Priming: Effects of Color-Cued Selective Attention
Authors: Kellenbach Marion L. , Michie Patricia T.
Published: February 2008

The processing nature of N400, an event-related brain potential (ERP) component associated with semantic processing, was investigated in a paradigm combining a semantic priming lexical decision task and color-cued selective attention. Semantic priming effects on ERPs and reaction time (RT) were examined when targets and preceding semantically related primes were either both attended or both unattended, and when only either the prime or target was the focus of attention. Priming effects were determined by comparing semantically primed target ERPs (and RTs when appropriate) to their prime (in those conditions where the prime and target had the same attentional status) and/or to an unprimed control target matched to the attentional status of the primed target. Control stimuli were examined for ERP effects of color-cued selective attention unconfounded by priming factors. Experiment 1 required overt responses to words and nonwords in a binary choice task, while Experiment 2 required response only to nonwords. RTs in Experiment 1 indicated facilitatory priming effects to all semantically primed attended targets. In Experiments 1 and 2 ERPs to primes and controls were consistently more negative than the primed target trace in the N400 latency range in conditions with attended primes, suggesting priming effects on N400 are contingent on attentional processing of the prime. Removal of the attention manipulation (Experiment 3) resulted in an N400 component with a well-defined peak not evident in the first two experiments, indicating modulation of N400 by overlapping effects of attention.
A Locus in Human Extrastriate Cortex for Visual Shape Analysis
Authors: Kanwisher Nancy , Woods Roger P. , Iacoboni Marco , Mazziotta John C.
Published: February 2008

Positron emission tomography (PET) was used to locate an area in human extrastriate cortex that subserves a specific component process of visual object recognition. Regional blood flow increased in a bilateral extrastriate area on the inferolateral surface of the brain near the border between the occipital and temporal lobes (and a smaller area in the right fusiform gyms) when subjects viewed line drawings of 3-dimensional objects compared to viewing scrambled drawings with no clear shape interpretation. Responses were Seen for both novel and familiar objects, implicating this area in the bottom-up (i.e., memory-independent) analysis of visual shape.
Spoken Sentence Comprehension in Aphasia: Event-related Potential Evidence for a Lexical Integration Deficit
Authors: Swaab Tamara , Brown Colin , Hagoort Peter
Published: February 2008

In this study the N400 component of the event-related potential was used to investigate spoken sentence understanding in Broca's and Wernicke's aphasics. The aim of the study was to determine whether spoken sentence comprehension problems in these patients might result from a deficit in the on-line integration of lexical information. Subjects listened to sentences spoken at a normal rate. In half of these sentences, the meaning of the final word of the sentence matched the semantic specifications of the preceding sentence context. In the other half of the sentences, the sentence-final word was anomalous with respect to the preceding sentence context. The N400 was measured to the sentence-final words in both conditions. The results for the aphasic patients (n = 14) were analyzed according to the severity of their comprehension deficit and compared to a group of 12 neurologically unimpaired age-matched controls, as well as a group of 6 nonaphasic patients with a lesion in the right hemisphere. The nonaphasic brain damaged patients and the aphasic patients with a light comprehension deficit (high comprehenders, n = 7) showed an N400 effect that was comparable to that of the neurologically unimpaired subjects. In the aphasic patients with a moderate to severe comprehension deficit (low comprehenders, n = 7), a reduction and delay of the N400 effect was obtained. In addition, the P300 component was measured in a classical oddball paradigm, in which subjects were asked to count infrequent low tones in a random series of high and low tones. No correlation was found between the occurrence of N400 and P300 effects, indicating that changes in the N400 results were related to the patients' language deficit. Overall, the pattern of results was compatible with the idea that aphasic patients with moderate to severe comprehension problems are impaired in the integration of lexical information into a higher order representation of the preceding sentence context.
Higher-Order Associative Learning in Amnesia: Evidence from the Serial Reaction Time Task
Authors: Curran Tim
Published: February 2008

Patients with anterograde amnesia are commonly believed to exhibit normal implicit learning. Research with the serial reaction time (SRT) task suggests that normal subjects can implicitly learn visuospatial sequences through a process that is sensitive to higher-order information that is more complex than pairwise associations between adjacent stimuli. The present research reexamined SRT learning in a group of amnesic patients with a design intended to specifically address the learning of higher-order information. Despite seemingly normal learning effects on average, the results suggest that amnesic patients do not learn higher-order information as well as control subjects. These results suggest that amnesic patients have an associative learning impairment, even when learning is implicit, and that the medial temporal lobe and/or diencephalic brain areas typically damaged in cases of amnesia normally contribute to implicit sequence learning.
Common Blood Flow Changes across Visual Tasks: I. Increases in Subcortical Structures and Cerebellum but Not in Nonvisual Cortex
Authors: Shulman Gordon L. , Corbetta Maurizio , Buckner Randy L. , Fiez Julie A. , Miezin Francis M. , Raichle Marcus E. , Petersen Steven E.
Published: February 2008

Nine positron emission tomography (PET) studies of human visual information processing were reanalyzed to determine the consistency across experiments of blood flow increases during active tasks relative to passive viewing of the same stimulus array. No consistent blood flow increases were found in cerebral cortex outside of the visual system, but increases were seen in the thalamus and cerebellum. Although most tasks involve increases in arousal, establishing an intention or behavioral goal, setting up control structures for sequencing task operations, detecting targets, etc., these operations do not produce blood flow increases, detectable with the present methods, in localized cortical regions that are common across tasks. Common subcortical regions, however, may be involved.

A left cerebellar and a medial cerebellar focus reflected motor-related processes. Blood flow increases in these regions only occurred in experiments in which the subject made an overt response and were largest when the response was made in the active but not passive condition. These motor-related processes were more complex than simple motor execution, however, since increases were still present when the response was made in both the active and passive conditions. These cerebellar increases may reflect processes related to response selection.Blood flow increases in a right cerebellar region were not motor-related. Increases were not modulated by the presence or absence of motor responses during either the active or passive conditions, and increases were sensitive to within-experiment variables that held the motor response constant. Increases occurred in both language and nonlanguage tasks and appeared to involve a general nonmotor process, but the nature of that process was difficult to specify.

A right thalamic focus was sensitive to variables related to focal attention, suggesting that this region was involved in attentional engagement. Right thalamic increases were also correlated over conditions with increases in the left and medial cerebellum, perhaps reflecting additional contributions from motor-related nuclei receiving cerebellar projections.

Blood flow increases in a left thalamic focus were completely uncorrelated over conditions with increases in the right thalamus, indicating that it was involved in different functions. Both the left thalamus and right cerebellum yielded larger blood flow increases when subjects performed a complex rather than simple language task, possibly reflecting a language-related pathway. Blood flow increases in the left thalamus were also observed, however, during nonlanguage tasks.
Sentence Reading: A Functional MRI Study at 4 Tesla
Authors: Bavelier D. , Corina D. , Jezzard P. , Padmanabhan S. , Clark V. P. , Karni A. , Prinster A. , Braun A. , Lalwani A. , Rauschecker J. P. , Turner R. , Neville H.
Published: February 2008

In this study, changes in blood oxygenation and volume were monitored while monolingual right-handed subjects read English sentences. Our results confirm the role of the left peri-sylvian cortex in language processing. Interestingly, individual subject analyses reveal a pattern of activation characterized by several small, limited patches rather than a few large, anatomically well-circumscribed centers. Between-subject analyses confirm a lateralized pattern of activation and reveal active classical language areas including Broca's area, Wernicke's area, and the angular gyms. In addition they point to areas only more recently considered as language-relevant including the anterior portion of the superior temporal sulcus. This area has not been reliably observed in imaging studies of isolated word processing. This raises the hypothesis that activation in this area is dependent on processes specific to sentence reading.
Deviance-elicited Changes in Event-related Potentials are Attenuated by Ketamine in Mice
Authors: Ehrlichman Richard S. , Maxwell Christina R. , Majumdar Sonalee , Siegel Steven J.
Published: February 2008

Background: People with schizophrenia exhibit reduced ability to detect change in the auditory environment, which has been linked to abnormalities in N-methyl-D-aspartate (NMDA) receptor-mediated glutamate neurotransmission. This ability to detect changes in stimulus qualities can be measured with electroencephalography using auditory event-related potentials (ERPs). For example, reductions in the N100 and mismatch negativity (MMN), in response to pitch deviance, have been proposed as endophenotypes of schizophrenia. This study examines a novel rodent model of impaired pitch deviance detection in mice using the NMDA receptor antagonist ketamine. Methods: ERPs were recorded from unanesthetized mice during a pitch deviance paradigm prior to and following ketamine administration. First, N40 amplitude was evaluated using stimuli between 4 and 10 kHz to assess the amplitude of responses across the frequency range used. The amplitude and latency of the N40 were analyzed following standard (7 kHz) and deviant (5–9 kHz) stimuli. Additionally, we examined which portions of the ERP are selectively altered by pitch deviance to define possible regions for the mouse MMN. Results: Mice displayed increased N40 amplitude that was followed by a later negative component between 50 and 75 msec in response to deviant stimuli. Both the increased N40 and the late N40 negativity were attenuated by ketamine. Ketamine increased N40 latency for both standard and deviant stimuli alike. Conclusions: The mouse N40 and a subsequent temporal region have deviance response properties similar to the human N100 and, possibly, MMN. Deviance responses were abolished by ketamine, suggesting that ketamine-induced changes in mice mimic deviance detection deficits in schizophrenia.
Social Identity and Patterns of Interaction in the Sharia Court of Kastamonu (1740-44)
Authors: Ergene Bogaç
Published: February 2008

In this article I introduce quantitative techniques and procedures to analyze how various social groups in mid-18th-century Ottoman Kastamonu experienced the court process. By processing the information found in three Kastamonu court registers, I attempt to determine the group identities of court clients and to compare the choices made by different groups in various legal circumstances. I will identify the kinds of issues brought to court by different segments of the social hierarchy, and the legal adversaries and/or contracting parties brought to court by these court clients; and I will assess how these groups fared in their disputes. My analysis confirms the existence of diverse patterns of court use by various groups in 18th-century Kastamonu and the differential use of the court's services by clients with different social and economic backgrounds.
Gendering Border Spaces: Impact of Open Border Policy Between Cambodia-Thailand on Small-scale Women Fish Traders
Authors: Kusakabe Kyoko , Sereyvath Prak , Suntornratana Ubolratana , Sriputinibondh Napaporn
Published: February 2008

The study examined how the commodity chain of freshwater fresh fish trade between Thailand and Cambodia developed and became sex segregated, and how women small-scale traders are positioned in the chain. The open border policy increased trade and demand for fish, and made it more difficult for small-scale traders to secure fish. Lack of state control led to rent-seeking, which further closed opportunities for resourceless small-scale traders. Women small-scale border traders tried to counter the marginalization through establishing social networks, but with limited success. Field interviews with 86 traders at the border areas of Thailand and Cambodia were conducted to explore these points.
Between Local and Colonial Perceptions: The History of Slum Clearances in Lagos (Nigeria), 1924-1960
Authors: Bigon Liora
Published: February 2008

Following the establishment of the British rule in Lagos in the mid-19th century, the pre-colonial settlement became most central in West Africa, economically and administratively. Yet, scarce resources at the disposal of the colonial government and its exploitive nature prevented any serious remedy for the increasingly pressing residential needs. This article examines slum clearances in Lagos from the early 20th century until the de-colonization era in Nigeria (the 1950s), from a perspective of cultural history. This perspective reveals the width of the conceptual gaps between the colonizers and the colonized, and the chronic mutual misunderstanding regarding the nature of slums and the appropriate ways to eliminate them. Tracing the indigenous perceptions and reactions concerning slum clearance shows that the colonial situation was far from being an overwhelmingly hegemonic one.
Advection, Phase Distortion, and the Frequency Spectrum of Finescale Fields in the Sea
Authors: Pinkel Robert
Published: February 2008

Continuous depth–time measurements of upper-ocean velocity are used to estimate the wavenumber–frequency spectrum of shear. A fundamental characteristic of these spectra is that the frequency bandwidth increases linearly with increasing wavenumber magnitude. This can be interpreted as the signature of Doppler shifting of the observations by time-changing “background” currents as well as by instrument motion. Here, the hypothesis is posed that the apparently continuous wavenumber–frequency spectrum of oceanic shear results from the advective “smearing” of discrete spectral lines. In the Arctic Ocean, lines at the inertial (ω = −f ) and vortical (ω = 0) frequencies (where f is the Coriolis frequency) account for most of the variance in the shear spectrum. In the tropical ocean, two classes of inertial waves are considered, accounting for 70% of the observed shear variance. A simple model is introduced to quantify the effects of lateral advection, random vertical advection (“fine-structure contamination”), and deterministic (tidal) vertical advection on these “otherwise monochromatic” records. Model frequency spectra are developed in terms of the probability density and/or spectrum of the advecting fields for general but idealized situations. The model successfully mimics the increasing frequency bandwidth of the shear spectrum with increasing vertical wavenumber. Excellent fits to the observed frequency spectrum of shear are obtained for the Arctic (weak advection and short-spatial-scale inertial waves) and low-latitude (strong advection and long and short inertial waves) observations. While successfully replicating the wavenumber–frequency spectrum of shear, the model does not even consider motion at scales greater than ∼250 m, the “energy containing” scales of the internal wave field. To a first approximation, the waves with the majority of the kinetic and potential energy constitute a population apart from those with the momentum, shear, and strain.
Subsurface Salinity Balance in the South China Sea*
Authors: Yu Zuojun , McCreary Julian P. , Yaremchuk Max , Furue Ryo
Published: February 2008

The South China Sea (SCS) is often treated as a semienclosed water body, with the Luzon Strait as its only connection to the Pacific Ocean. A branch of the Kuroshio flows northwestward across the Luzon Strait to enter the SCS, carrying North Pacific Tropical Water (NPTW) into the basin. Using the subsurface salinity maximum as a tracer for NPTW, the authors show how important three secondary straits—the Taiwan Strait to the north and the Karimata and Mindoro Straits to the south—are to the NPTW intrusion at the Luzon Strait. The authors demonstrate that the SCS cannot reach an equilibrium state that is consistent with the observed subsurface salinity distribution unless all of the following components are in place: the Kuroshio, transports through the three secondary straits, downward mixing of freshwater, horizontal mixing induced by mesoscale eddies, and forcing by the local monsoonal winds.
Buffering Effect and Its Related Ocean Dynamics in the Indonesian Throughflow Region*
Authors: Qu Tangdong , Du Yan , McCreary Julian P. , Meyers Gary , Yamagata Toshio
Published: February 2008

Analysis of results from a high-resolution general circulation model confirms the existence of a “buffering” effect in the Indo-Australian Basin in which the upper ocean receives an excess of water from February to June and releases it during the rest of the year. A similar, but significantly weaker, phenomenon exists in the Indonesian seas. The buffering mostly results from geostrophic convergence, with the directly wind-driven Ekman divergence playing a role only within the Indonesian seas. Upward phase propagation, or equivalently, downward energy propagation, is revealed, indicating the prominent influence of remotely forced Kelvin waves originating in the equatorial Indian Ocean. The model demonstrates that these Kelvin waves penetrate as far eastward as the Ombai Strait along the southern Indonesian coastal waveguide, and that they have a notable influence on the upper-ocean convergence/divergence in the Indo-Australian Basin. Some of the semiannual signal turns northward through the Lombok and Ombai Straits to impact the circulation and thermal structure within the Indonesian seas.
Asymmetry of Free Circulations in Closed Ocean Gyres
Authors: LaCasce J. H. , Nøst O. A. , Isachsen P. E.
Published: February 2008

Steady flows in regions of closed geostrophic contours, such as in ocean basins or over seamounts, are examined by calculating solutions to the nonlinear quasigeostrophic and shallow-water equations with topography. For oceanically realistic choices of parameters, the solutions are asymmetric in that those with cyclonic circulation resemble the topography while those with anticyclonic circulation exhibit small-scale structure and cross-isobath flow. These small-scale structures reflect topographic wave modes, which are stationary with the anticyclonic circulation. The implication of the asymmetry is that random wind forcing is much more likely to excite persistent cyclonic than anticyclonic flow. This may explain why the circulation in the Norwegian and Greenland Gyres is most often cyclonic.
A Simple Linear Model of the Depth Dependence of the Wind-Driven Variability of the Meridional Overturning Circulation
Authors: Killworth Peter D.
Published: February 2008

The part of the meridional overturning circulation driven by time-varying winds is usually assumed to be an Ekman flux within a mixed layer, and a depth- and laterally independent return flow beneath. For a simple linear frictional ocean model, the return flow is studied for a range of frequencies from several days to decades. It is shown that while the east–west integral of the return flow is usually, but not always, almost independent of depth, the spatial distribution of the return flow varies strongly with both horizontal and vertical position. This can have important consequences for calculations of the northward heat flux, which traditionally assumes a spatially uniform return flow.
Social Control, Serious Delinquency, and Risky Behavior
Authors: Booth Jeb A. , Farrell Amy , Varano Sean P.
Published: February 2008

Social control theory asserts that strong social bonds inhibit delinquency, whereas weak bonds offer little resistance to offending. In the development of this theoretical perspective, new research suggests that the type and magnitude of social bonds have differing effects on male and female delinquency. This study adds to our understanding of how social control factors of parental attachment, involvement in diverse prosocial activities, belief in traditional norms, and school climate affect both young men's and young women's reports of serious delinquency and risky behavior in a sample of high school youth. Whereas previous research has generally either controlled for the effect of gender statistically or studied all-male samples, this article uses separate models to examine the independent effects of social bonds on male and female delinquency. The findings support the development of gender-specific analyses to understand how social control affects male and female pathways into delinquency.
A Review of the Empirical Literature on the Relationships Between Indoor Environment and Stress in Health Care and Office Settings
Authors: Rashid Mahbub , Zimring Craig
Published: February 2008

A conceptual framework linking indoor environment and stress is provided. The framework suggests that, in many cases, indoor environments may set forth a process leading to stress by affecting individual and/or workplace needs. The framework also suggests that because any direct causal relation between indoor environment and stress may be difficult to establish, researchers should focus more on the evidence that links indoor environment to individual and/or workplace needs. This review focuses primarily on the evidence that relates indoor environment to individual and/or workplace needs in health care and office settings. It shows a growing body of literature addressing these relationships in both settings. However, because the available evidence is uneven, there is a great need for the sharing of knowledge among researchers of these settings. In this regard, differences in organizational factors, user and workplace needs, and physical settings are some issues that need to be carefully considered.
Pharmacokinetics of Intravenous Levosimendan and Its Metabolites in Subjects With Hepatic Impairment
Authors: Puttonen Jaakko , Kantele Sampo , Ruck Angela , Ramela Meri , Häkkinen Sari , Kivikko Matti , Pentikäinen Pertti J.
Published: February 2008

Levosimendan is a vasodilator used in the treatment of acute heart failure. In the present study, the effect of hepatic impairment on the pharmacokinetics of levosimendan and its 2 metabolites, OR‐1855 and OR‐1896 (pharmacologically active), was investigated in 12 healthy subjects and 12 subjects with moderate hepatic impairment due to alcoholic cirrhosis of the liver but with no heart failure. In addition, the effect of acetylator status on the pharmacokinetics of levosimendan, OR‐1855, and OR‐1896 was evaluated. Safety and tolerability of levosimendan were also assessed. Levosimendan was given as an intravenous infusion of 0.1 μg/kg/min for 24 hours. Levosimendan showed similar Cmax, AUC, and elimination half‐life (t1/2), with a mean (±SEM) t1/2 of 0.9 ± 0.0 hours in healthy subjects and 0.8 ± 0.1 hours in hepatically impaired subjects, respectively (not significant). The t1/2 of OR‐1855 was 61 ± 5 hours in healthy subjects and 82 ± 3 hours (P < .01) in subjects with hepatic impairment. The t1/2 of OR‐1896 was 62 ± 5 hours and 91 ± 5 hours (P <.01), respectively. However, the AUCs of OR‐1855 and OR‐1896 were similar in healthy volunteers and hepatically impaired subjects. The effect of acetylator status was seen as higher Cmax and AUC of OR‐1855 in slow acetylators. Correspondingly, higher Cmax and AUC of OR‐1896 were observed in rapid acetylators. Levosimendan was well tolerated in both study groups. In conclusion, the pharmacokinetics of the parent drug levosimendan was unaltered in subjects with moderate hepatic impairment, whereas the elimination of the metabolites was prolonged. However, because the maximum duration of levosimendan infusion is 24 hours, dosing adjustments of levosimendan may not be required in subjects with impaired hepatic function.
Pharmacokinetics and Biological Activity of Atacicept in Patients With Rheumatoid Arthritis
Authors: Nestorov Ivan , Munafo Alain , Papasouliotis Orestis , Visich Jennifer
Published: February 2008

Atacicept is a recombinant fusion protein containing the extracellular ligand‐binding portion of the transmembrane activator and CAML interactor (TACI, CD267) receptor and inhibits B lymphocyte stimulator (BLyS, CD257) and a proliferation‐inducing ligand (APRIL, CD256), both potent stimulators of B cell maturation, proliferation, and survival. Atacicept pharmacokinetics and pharmacodynamics were assessed in a double‐blind, placebo‐controlled, phase I study in patients with active, moderate to severe rheumatoid arthritis receiving atacicept either as a single subcutaneous or repeated, every other week dose. Pharmacokinetic profiles were determined by measuring serum concentrations of free atacicept and its complex with BLyS. Nonspecific immunoglobulin (Ig)M, IgG, and IgA; IgM‐RF (rheumatoid factor), IgG‐RF, and IgA‐RF antibody levels; and B cell profiles provided markers of biological activity. Pharmacokinetic, biological activity, and relationships between atacicept dose and Ig antibody response were evaluated. Pharmacokinetic profiles of atacicept were nonlinear, influenced by saturable binding with its ligands, but were consistent and predictable. Atacicept treatment reduced Ig and RF serum concentration. IgM antibody levels were most sensitive to atacicept, followed by IgA and IgG, underlining the biological activity of atacicept in patients with rheumatoid arthritis. These findings can be used to explore dosing regimen design scenarios in future studies.
Chlorpromazine attenuates pancreatic β-cell function and mass through IRS2 degradation, while exercise partially reverses the attenuation
Authors: Park S. , Hong SM , Lee JE , Sung SR , Kim SH
Published: February 2008

We investigated the effect and mechanism of exercise and chlorpromazine (CPZ), a conventional anti-psychotic drug, on β-cell function and mass in 90% pancreatectomized (Px) male rats. The diabetic Px rats were divided into two groups, one of which was provided with exercise whereas the other was not. Both groups were subdivided into the three groups and administered with 0, 5 or 50 mg CPZ per kg body weight (control, low dosage of chlorpromazine (LCPZ), high dosage chlorpromazine (HCPZ)) for 8 weeks. LCPZ did not modulate glucose homeostasis. HCPZ impaired acute phase and second phase insulin secretion during hyperglycemic clamp. Apoptosis of pancreatic β-cells increased in the HCPZ group, and proliferation decreased, contributing to reduced β-cell mass. Exercise partially improved glucose-stimulated insulin secretion and β-cell mass in HCPZ-treated rats. Interestingly, insulin receptor substrate-2 (IRS2) protein levels in islets decreased by increased degradation in the HCPZ group, whereas exercise partially reversed this trend by induction of IRS2 expression. In isolated islets, 50 μM CPZ decreased IRS2 expression by promoting ubiquitin-proteasome degradation, which had been prevented by proteasome inhibitors. Furthermore, similar to the effect of HCPZ treatment, a high dosage of rottlerin, a protein kinase C-δ inhibitor, reduced IRS2 levels in the islets. In conclusion, exercise partially recovered the diabetic symptoms exacerbated by HCPZ through enhancement of β-cell function and mass in diabetic rats. This modulation by HCPZ and exercise was associated with increasing intracellular IRS2 protein levels in independent pathways.
The effects of experimentally lowered serotonin function on emotional information processing and memory in remitted depressed patients
Authors: Merens W. , Booij L. , Haffmans PM Judith , van der Does AJW
Published: February 2008

It has been well documented that acute tryptophan depletion (ATD) induces symptoms in remitted depressed patients treated with an SSRI. ATD also has effects on cognition, both in patients and in healthy samples. The exact nature of ATD-induced cognitive changes in depression remains unclear. It is also unclear whether cognitive effects can be induced through partial ('low-dose') depletion. The aim of this study is to investigate the differential effects of low-dose and high-dose ATD on emotional information processing and mood in remitted depressed patients.

Eighteen remitted depressed patients received high-dose and low-dose ATD in a randomized, double-blind, within-subjects crossover design. Mood was assessed before and after administration of the depletion drink. Five hours after administration, patients conducted tests measuring neutral and emotional information processing.

High-dose ATD increased depressive symptoms and induced a temporary depressive 'relapse' in half of the patients. High-dose ATD also decreased the recognition of fear and impaired learning and memory retrieval. The impaired learning occurred only in mood-responders. Low-dose ATD had no effects on mood but speeded the recognition of facial expressions of disgust. Accurate recognition of sad faces at baseline was associated with mood response to ATD.

High-dose ATD leads to changes in memory and in the recognition of negative facial expressions in SSRI-treated remitted depressed patients. The effect of low-dose ATD on mood and cognition seems to be quite limited. Emotional information processing at baseline predicts mood-response to ATD.
Pharmacology of rising oral doses of 5-hydroxytryptophan with carbidopa
Authors: Smarius LJCA , Jacobs GE , Hoeberechts-Lefrandt DHM , de Kam ML , van der Post JP , de Rijk R , van Pelt J , Schoemaker RC , Zitman FG , van Gerven JMA , Gijsman HJ
Published: February 2008

5-hydroxytryptophan (5-HTP) is a direct 5-hydroxytryptamine (5-HT) precursor used to assess central serotonergic function. Its use has been limited by a narrow window between neuroendocrine changes and side effects, and variable kinetics related to inconsistent administration modes. By combining 5-HTP with carbidopa (CBD), increased bioavailability for brain penetration and decreased peripheral side effects would be expected, due to reduced peripheral decarboxylation of 5-HTP to 5-HT. A doubleblind, placebo-controlled, single rising dose, four-way crossover trial with placebo randomisation was performed in 15 healthy male volunteers to investigate the neuroendocrine dose–response relationship at various 5-HTP levels; the tolerability and subjective effects of oral 5-HTP at 100, 200 and 300mg combined with CBD and the pharmacokinetic properties of the 5-HTP/CBD-challenge. Dose-dependent increases in average cortisol concentrations were observed. Mean response (area-under-the-curve) over the first 4 hours (SD): 172.0 nmol/L (22.3) for placebo, 258.3nmol/L (72.6) for 100mg, 328.47nmol/L (84.6) for 200mg and 387.3nmol/L (82.4) for 300mg 5-HTP. Similar dose-dependent increases for prolactin were seen while adreno-corticotrophic hormone response was more variable. 5-HTP kinetics were adequately described using a one-compartment model with first-order absorption and a lag time (mean oral clearance 28 L/h interindividual coefficient of variation 31%). Nausea and vomiting occurred dose-dependently as most frequent side effects, resulting in dose-related dropout of 6.6% at 100mg and 45.5% at 300mg 5-HTP. Orally administered 5-HTP combined with CBD is an effective serotonergic challenge test, exhibiting dose-related plasma concentrations and neuroendocrine responsiveness. Frequent occurrence of nausea and vomiting limits the applicability of this challenge at 5-HTP doses above 100mg
Disruption of GABAergic tone in the dorsomedial hypothalamus attenuates responses in a subset of serotonergic neurons in the dorsal raphe nucleus following lactate-induced panic
Authors: Johnson PL , Lowry CA , Truitt W. , Shekhar A.
Published: February 2008

Panic patients are vulnerable to induction of panic attacks by sub—threshold interoceptive stimuli such as intravenous (i.v.) sodium lactate infusions. Facilitation of serotonergic signaling with selective serotonin reuptake inhibitors can suppress anxiety and panic-like responses, but the mechanisms involved are not clearly defined. We investigated the effects of i.v. 0.5 M sodium lactate or saline, in control and panic-prone rats on c-Fos expression in serotonergic neurons within subdivisions of the midbrain/pontine raphe nuclei. Rats were chronically infused with either the GABA synthesis inhibitor l-allylglycine into the dorsomedial hypo thalamus to make them panic-prone, or the enantiomer d-allylglycine (d-AG) in controls. Lactate increased c-Fos expression in serotonergic neurons located in the ventrolateral part of the dorsal raphe nucleus (DRVL) and ventrolateral periaqueductal gray (VLPAG) of control, but not panic-prone, rats. The distribution of lactate-sensitive serotonergic neurons in d-AG-treated rats is virtually identical to previously defined pre-sympathomotor serotonergic neurons with multisynaptic projections to peripheral organs mediating 'fight-or-flight'-related autonomic and motor responses. We hypothesized that serotonergic neurons within the DRVL/VLPAG region represent a 'sympathomotor control system' that normally limits autonomic/behavioral responses to innocuous interoceptive and exteroceptive stimuli, and that dysfunction of this serotonergic system contributes to an anxiety-like state and increases vulnerability to panic in animals and humans.