bluuebunny/crossref_metadata_2025 huggingface dataset:
Through-Silicon Via Fill for 3D Interconnect Applications
Authors: Mathew Varughese , Chatterjee Ritwik , Jones Robert , Garcia Sam , Acosta Eddie , Huang Zhihong
Published: March 2009

Through Silicon Vias (TSV) can provide high density inter-strata connections with reduced signal delay and power consumption for stacked multi-chip interconnection and packaging. Among the various process steps to form a TSV, filling of the via with metal is the most difficult and costly for high aspect ratio features. A robust TSV filling by electroplating requires continuous seed coverage and plating conditions that result in void free filling. Discontinuous seed can result from ledges and overhangs when reentrant TSV hole profiles form. Such TSVs are filled by creating electrical continuity through one of the two methods (a) electroless seed enhancement of the discontinuous copper seed or (b) by the deposition of a thin film of TiN prior to the barrier and seed. Both plating process conditions and bath composition are optimized to achieve void free filling of TSVs of various geometries.
Electrodeposition of Tin-Rich, Tin-Gold Eutectic Solders for Optoelectronic and MEMS Applications
Authors: Watt Charles S. , Liu Qi , Ivey Douglas
Published: March 2009

Tin-rich, Sn-Au solder films were fabricated using electrodeposition, from a suspension composed of a Sn electrolyte with suspended Au particles. The Sn-rich eutectic alloy offers a potentially cheaper alternative to the Au-rich eutectic for optoelectronic and MEMS device packaging and may be applicable as a Pb-free solder for microelectronic packaging. Eutectic and near-eutectic deposits, with uniform thicknesses and compositions were fabricated. Gold content in the deposits increased with increasing Au particle loading in the electrolyte and increasing current density. Room temperature aging led to the formation of AuSn4 at the Au particle-Sn matrix interface. Reflow of deposits with near-eutectic compositions resulted in the formation of the two eutectic phases, Sn and AuSn4.
Maskless Fabrication for Micropad Interconnection using Electroless NiB Deposition and Application to "Chemical" Flip-Chip Bonding
Authors: Yokoshima Tokihiko , Yamaji Yasuhiro , Igawa Noboru , Kikuchi Katsuya , Nakagawa Hiroshi , Aoyagi Masahiro
Published: March 2009

Deposition behavior of localized electroless NiB deposition for pad-to-pad connection was investigated. Localized deposition occurred mainly on the area between facing pads, and anisotropic deposition toward each facing pad was obtained. Thus, this connection, "preferential bridge connection", is no need of photolithographic technique. These results indicated that this process is one of the maskless fabrication processes. Moreover, chemical flip-chip bonding containing preferential bridge interconnection was demonstrated. The chip-to-substrate interconnection with 30 micrometer pitch was successfully achieved.
Role of SIRT1 in regulation of LPS- or two ethanol metabolites-induced TNF-α production in cultured macrophage cell lines
Authors: Shen Zheng , Ajmo Joanne M. , Rogers Christopher Q. , Liang Xiaomei , Le Lisa , Murr Michel M. , Peng Yanhua , You Min
Published: March 2009

Dysregulation of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) has been implicated in the pathogenesis of alcoholic liver injury. Sirtuin 1 (SIRT1) is an NAD+-dependent class III protein deacetylase that is known to be involved in regulating production of proinflammatory cytokines including TNF-α. In the present study, we examined the role of SIRT1 signaling in TNF-α generation stimulated by either lipopolysaccharide (LPS), acetaldehyde (AcH), or acetate (two major metabolites of ethanol) in two cultured macrophage cell lines. In both rat Kupffer cell line 1 (RKC1) and murine RAW 264.7 macrophages, treatment with either LPS, AcH, or acetate caused significant decreases in SIRT1 transcription, translation, and activation, which essentially demonstrated an inverse relationship with TNF-α levels. LPS, AcH, and acetate each provoked the release of TNF-α from RKC1 cells, whereas coincubation with resveratrol (a potent SIRT1 agonist) inhibited this effect. Conversely, addition of sirtinol (a known SIRT1 inhibitor) or knocking down SIRT1 by the small silencing SIRT1 plasmid (SIRT1shRNA) augmented TNF-α release, suggesting that impairment of SIRT1 may contribute to TNF-α secretion. Further mechanistic studies revealed that inhibition of SIRT1 by LPS, AcH, or acetate was associated with a marked increase in the acetylation of the RelA/p65 subunit of nuclear transcription factor (NF-κB) and promotion of NF-κB transcriptional activity. Taken together, our findings suggest that SIRT1-NF-κB signaling is involved in regulating LPS- and metabolites-of-ethanol-mediated TNF-α production in rat Kupffer cells and in murine macrophages. Our study provides new insights into understanding the molecular mechanisms underlying the development of alcoholic steatohepatitis.
Endothelin antagonism in portal hypertensive mice: implications for endothelin receptor-specific signaling in liver disease
Authors: Feng Hong-Qiang , Weymouth Nate D. , Rockey Don C.
Published: March 2009

Endothelin-1 (ET-1), a potent vasoactive peptide, plays an important role in the pathogenesis of liver disease and portal hypertension. Two major endothelin receptors (ET-A and ET-B) mediate biological effects, largely on the basis of their known downstream signaling pathways. We hypothesized that the different receptors are likely to mediate divergent effects in portal hypertensive mice. Liver fibrosis and cirrhosis and portal hypertension were induced in 8-wk-old male BALB/c mice by gavage with carbon tetrachloride (CCl4). Portal pressure was recorded acutely during intravenous infusion of endothelin receptor antagonists in normal or portal hypertensive mice. In vivo microscopy was used to monitor sinusoidal dynamics. Additionally, the effect of chronic exposure to endothelin antagonists was assessed in mice during induction of fibrosis and cirrhosis with CCl4 for 8 wk. Intravenous infusion of ET-A receptor antagonists into normal and cirrhotic mice reduced portal pressure whereas ET-B receptor antagonism increased portal pressure. A mixed endothelin receptor antagonist also significantly reduced portal pressure. Additionally, the ET-A receptor antagonist caused sinusoidal dilation, whereas the ET-B receptor antagonist caused sinusoidal constriction. Chronic administration of each the endothelin receptor antagonists during the induction of fibrosis and portal hypertension led to reduced fibrosis, a significant reduction in portal pressure, and altered sinusoidal dynamics relative to controls. Acute effects of endothelin receptor antagonists are likely directly on the hepatic and sinusoidal vasculature, whereas chronic endothelin receptor antagonism appears to be more complicated, likely affecting fibrogenesis and the hepatic microcirculation. The data imply a relationship between hepatic fibrogenesis or fibrosis and vasomotor responses.
Cholinergic giant migrating contractions in conscious mouse colon assessed by using a novel noninvasive solid-state manometry method: modulation by stressors
Authors: Gourcerol G. , Wang L. , Adelson D. W. , Larauche M. , Taché Y. , Million M.
Published: March 2009

There is a glaring lack of knowledge on mouse colonic motility in vivo, primarily due to unavailability of adequate recording methods. Using a noninvasive miniature catheter pressure transducer inserted into the distal colon, we assessed changes in colonic motility in conscious mice induced by various acute or chronic stressors and determined the neurotransmitters mediating these changes. Mice exposed to restraint stress (RS) for 60 min displayed distal colonic phasic contractions including high-amplitude giant migrating contractions (GMCs), which had peak amplitudes >25 mmHg and occurred at a rate of 15–25 h−1 of which over 50% were aborally propagative. Responses during the first 20-min of RS were characterized by high-frequency and high-amplitude contractions that were correlated with defecation. RS-induced GMCs and fecal pellet output were blocked by atropine (0.5 mg/kg ip) or the corticotrophin releasing factor (CRF) receptor antagonist astressin-B (100 μg/kg ip). RS activated colonic myenteric neurons as shown by Fos immunoreactivity. In mice previously exposed to repeated RS (60 min/day, 14 days), or in transgenic mice that overexpress CRF, the duration of stimulation of phasic colonic contractions was significantly shorter (10 vs. 20 min). In contrast to RS, abdominal surgery abolished colonic contractions including GMCs. These findings provide the first evidence for the presence of frequent cholinergic-dependent GMCs in the distal colon of conscious mice and their modulation by acute and chronic stressors. Noninvasive colonic manometry opens new venues to investigate colonic motor function in genetically modified mice relevant to diseases that involve colonic motility alterations.
Continued artificial selection for running endurance in rats is associated with improved lung function
Authors: Kirkton Scott D. , Howlett Richard A. , Gonzalez Norberto C. , Giuliano Patrick G. , Britton Steven L. , Koch Lauren G. , Wagner Harrieth E. , Wagner Peter D.
Published: March 2009

Previous studies found that selection for endurance running in untrained rats produced distinct high (HCR) and low (LCR) capacity runners. Furthermore, despite weighing 14% less, 7th generation HCR rats achieved the same absolute maximal oxygen consumption (V̇o2max) as LCR due to muscle adaptations that improved oxygen extraction and use. However, there were no differences in cardiopulmonary function after seven generations of selection. If selection for increased endurance capacity continued, we hypothesized that due to the serial nature of oxygen delivery enhanced cardiopulmonary function would be required. In the present study, generation 15 rats selected for high and low endurance running capacity showed differences in pulmonary function. HCR, now 25% lighter than LCR, reached a 12% higher absolute V̇o2max than LCR, P < 0.05 (49% higher V̇o2max/kg). Despite the 25% difference in body size, both lung volume (at 20 cmH2O airway pressure) and exercise diffusing capacity were similar in HCR and LCR. Lung volume of LCR lay on published mammalian allometrical relationships while that of HCR lay above that line. Alveolar ventilation at V̇o2max was 30% higher, P < 0.05 (78% higher, per kg), arterial Pco2 was 4.5 mmHg (17%) lower, P < 0.05, while total pulmonary vascular resistance was (insignificantly) 5% lower (30% lower, per kg) in HCR. The smaller mass of HCR animals was due mostly to a smaller body frame rather than to a lower fat mass. These findings show that by generation 15, lung size in smaller HCR rats is not reduced in concert with their smaller body size, but has remained similar to that of LCR, supporting the hypothesis that continued selection for increased endurance capacity requires relatively larger lungs, supporting greater ventilation, gas exchange, and pulmonary vascular conductance.
Rab8 Regulates ABCA1 Cell Surface Expression and Facilitates Cholesterol Efflux in Primary Human Macrophages
Authors: Linder Matts D. , Mäyränpää Mikko I. , Peränen Johan , Pietilä Taija E. , Pietiäinen Vilja M. , Uronen Riikka-Liisa , Olkkonen Vesa M. , Kovanen Petri T. , Ikonen Elina
Published: March 2009

Objective—

ATP-binding cassette transporter A1 (ABCA1) is thought to lipidate apolipoprotein A-I (apoA-I) at the plasma membrane, with endosomal cholesterol contributing as substrate. The mechanisms of ABCA1 surface delivery are not well understood. We have shown that Rab8 regulates endosomal cholesterol removal to apoA-I in human fibroblasts. Here, we investigated whether Rab8 plays a role in ABCA1 plasma membrane expression and cholesterol removal in primary human macrophages.

Methods and Results—

We found that Rab8 was abundantly expressed in human atherosclerotic lesional macrophages and upregulated on lipid loading of macrophages in vitro. Adenoviral overexpression of Rab8 increased ABCA1 protein levels and reduced cholesterol deposition in macrophage foam cells incubated with apoA-I. Depletion of Rab8 decreased the fraction of ABCA1 at the plasma membrane and inhibited the efflux of lipoprotein-derived endosomal cholesterol to apoA-I. In Rab8-depleted cells, ABCA1-GFP localized in β1 integrin and transferrin receptor containing recycling organelles.

Conclusion—

Rab8 reduces foam cell formation by facilitating ABCA1 surface expression and stimulating endosomal cholesterol efflux to apoA-I in primary human macrophages.
Calcification by Valve Interstitial Cells Is Regulated by the Stiffness of the Extracellular Matrix
Authors: Yip Cindy Ying Yin , Chen Jan-Hung , Zhao Ruogang , Simmons Craig A.
Published: March 2009

Objective—

Extensive remodeling of the valve ECM in calcific aortic valve sclerosis alters its mechanical properties, but little is known about the impact of matrix mechanics on the cells within the valve interstitium. In this study, the influence of matrix stiffness in modulating calcification by valve interstitial cells (VICs), and their differentiation to pathological phenotypes was assessed.

Methods and Results—

Primary porcine aortic VICs were cultured in standard media or calcifying media on constrained type I fibrillar collagen gels. Matrix stiffness was altered by changing only the thickness of the gels. Calcification did not occur in standard media, regardless of matrix stiffness. However, when VICs were grown in calcifying media on relatively compliant matrices with stiffness similar to that of normal tissue, they readily formed calcified aggregates of viable cells that expressed osteoblast-related transcripts and proteins. In contrast, VICs cultured in calcifying media on stiffer matrices (similar to stenotic tissue) differentiated to myofibroblasts and formed calcified aggregates that contained apoptotic cells. Actin depolymerization reduced aggregation on stiff, but not compliant, matrices. TGF-β1 potentiated aggregate formation on stiff matrices by enhancing α-smooth muscle actin expression and cellular contractility, but not on compliant matrices attributable to downregulation of TGF-β receptor I. Cell contraction by VICs inhibited Akt activation and enhanced apoptosis-dependent calcification on stiff matrices.

Conclusions—

Differentiation of VICs to pathological phenotypes in response to biochemical cues is modulated by matrix stiffness. Although osteogenic or myofibrogenic differentiation of VICs can result in calcification, the processes are distinct.
In Vivo Quantification of Carotid Artery Wall Dimensions
Authors: Duivenvoorden R. , de Groot E. , Elsen B.M. , Laméris J.S. , van der Geest R.J. , Stroes E.S. , Kastelein J.J.P. , Nederveen A.J.
Published: March 2009

Background—

Our aim was to compare common carotid mean wall thickness (MWT) measurements by 3.0-T MRI with B-mode ultrasound common carotid intima-media thickness (CCIMT) measurements, a validated surrogate marker for cardiovascular disease.

Methods and Results—

B-mode ultrasound and 3.0-T MRI scans of the left and right common carotid arteries were repeated 3 times in 15 healthy younger volunteers (age, 26�2.6 years), 15 healthy older volunteers (age, 57�3.2 years), and 15 subjects with cardiovascular disease and carotid atherosclerosis (age, 63�9.8 years). MWT was 0.711 (SD, 0.229) mm and mean CCIMT was 0.800 (SD, 0.206) mm. MWT and CCIMT were highly correlated (
r
=0.89,
P
<0.001). The intraclass correlation coefficients for interscan and interobserver and intraobserver agreements of MRI MWT measurements were larger than 0.95 with small confidence intervals, indicating excellent reproducibility. Power calculations indicate that 89 subjects are required to detect a 4% difference in MRI MWT compared with 469 subjects to detect similar differences with ultrasound IMT in follow-up studies.

Conclusions—

The study data for carotid MRI and ultrasound IMT showed strong agreement, indicating that both modalities measure the thickness of the intima and media. The advantage of MRI over ultrasound is that the measurement variability is smaller, enabling smaller sample sizes and potentially shorter study duration in cardiovascular prevention trials.
Differential Infraslow (<0.1 Hz) Cortical Activations in the Affected and Unaffected Hemispheres From Patients With Subacute Stroke Demonstrated by Noninvasive DC-Magnetoencephalography
Authors: Leistner Stefanie , Sander Tilmann , Wachs Michaela , Burghoff Martin , Curio Gabriel , Trahms Lutz , Mackert Bruno-Marcel
Published: March 2009

Background and Purpose—

Sustained mass depolarization of neurons, termed cortical spreading depolarization, is one electrophysiological correlate of the ischemic injury of neurons. Cortical spreading depolarizations spread in the gray matter at a rate of approximately 3 mm/min and are associated with large infraslow extracellular potential changes (<0.05 Hz). Moreover, smaller infraslow potential changes accompany functional activation and might help to assess neuronal repair after stroke. The objective of the present pilot study was to investigate whether it is feasible to apply noninvasive near-DC-magnetoencephalography to detect and monitor infraslow field changes in patients with acute stroke.

Methods—

A simple motor condition was used to induce physiological cortical infraslow field changes. Five patients in a subacute state after ischemic stroke performed self-paced simple finger movements (30-second periods of finger movements, always separated by 30-second periods of rest, for a total of 15 minutes). Near-DC-magnetoencephalography signals were recorded over the contralateral primary motor cortex for the affected and unaffected hemisphere, respectively.

Results—

In all patients, the time courses of the contralateral cortical field amplitudes in the infraslow frequency range followed closely the motor task cycles revealing statistically significant differences between finger movement and rest periods. In 4 of 5 patients, infraslow field amplitudes were significantly stronger over the unaffected hemisphere compared with the affected hemisphere.

Conclusions—

This study demonstrates that cortical infraslow activity can be recorded noninvasively in patients in the subacute state after ischemic stroke. It is suggested that near-DC-magnetoencephalography is a promising tool to also detect cortical spreading depolarization noninvasively.
Relationships Between Cerebral Perfusion and Reversibility of Acute Diffusion Lesions in DEFUSE
Authors: Olivot Jean-Marc , Mlynash Michael , Thijs Vincent N. , Purushotham Archana , Kemp Stephanie , Lansberg Maarten G. , Wechsler Lawrence , Bammer Roland , Marks Michael P. , Albers Gregory W.
Published: March 2009

Background and Purpose—

Acute ischemic lesions with restricted diffusion can resolve after early recanalization. The impact of superimposed perfusion abnormalities on the fate of acute diffusion lesions is unclear.

Methods—

Data were obtained from DEFUSE, a prospective multicenter study of patients treated with IV tPA 3 to 6 hours after stroke onset. Thirty-two patients with baseline diffusion and perfusion lesions and 30 day FLAIR scans were coregistered. The acute diffusion lesion was divided into 3 regions according to the Tmax delay of the superimposed perfusion lesion: normal baseline perfusion; mild-moderately hypoperfused (2 s8 s). The reversal rate was calculated as the percentage of the acute diffusion lesion that did not overlap with the final infarct on 30-day FLAIR. Diffusion reversal rates were compared based on whether a favorable clinical response occurred and whether early recanalization was achieved.

Results—

On average, 54% of the acute diffusion lesion volume had normal perfusion. Diffusion reversal rates were significantly increased among cases with favorable clinical response and in patients with early recanalization, especially in regions with normal baseline perfusion. The portion of the diffusion lesion with normal perfusion had significantly higher mean apparent diffusion coefficient values and reversal rates.

Conclusion—

Acute ischemic lesions with restricted diffusion are most likely to recover if reperfusion occurs within 6 hours of symptom onset, and reversibility is associated with early recanalization and favorable clinical outcome. We propose the term RADAR (Reversible Acute Diffusion lesion Already Reperfused) to describe regions of acute restricted diffusion with normal perfusion.
Relation Between Cerebral Perfusion Territories and Location of Cerebral Infarcts
Authors: Hendrikse Jeroen , Petersen Esben Thade , Chèze Amandine , Chng Soke Miang , Venketasubramanian Narayanaswamy , Golay Xavier
Published: March 2009

Background and Purpose—The perfusion territories of the brain-feeding arteries are difficult to assess in vivo and therefore standard cerebral perfusion territory templates are often used to determine the relation between cerebral infarcts and the feeding vasculature. In the present study, we compared this infarct classification, using standard templates, with the individualized depiction of cerebral perfusion territories on MRI.

Methods—The ethics committee of our institution approved the study protocol. A total of 159 patients (92 male, 67 female; mean age, 58.9 years) with first-time clinical symptoms of cerebral ischemia were included in the study. Diffusion-weighted imaging was used for depiction of the area of ischemia and the perfusion territories of the left internal carotid artery, right internal carotid artery, and vertebrobasilar arteries were visualized with territorial arterial spin labeling MRI. Infarct locations with respect to cerebral perfusion territories were evaluated with and without territorial arterial spin labeling MRI images.

Results—In 92% of the patients, the territorial arterial spin labeling images were of diagnostic quality. One hundred thirty-six patients showed areas of ischemia on diffusion-weighted images. The additional information from the territorial arterial spin labeling images changed the classification in 11% of the cortical or border zone infarcts (6 of 56), whereas no territorial changes were observed in lacunar, periventricular, cerebellar, and brainstem infarcts.

Conclusion—The diagnostic information provided by perfusion territory imaging in patients with stroke is valuable for the classification of cortical and border zone infarcts, whereas no change of the textbook-based classification was observed for other infarct types.
Perception of Face Parts and Face Configurations: An fMRI Study
Authors: Liu Jia , Harris Alison , Kanwisher Nancy
Published: March 2009

fMRI studies have reported three regions in human ventral visual cortex that respond selectively to faces: the occipital face area (OFA), the fusiform face area (FFA), and a face-selective region in the superior temporal sulcus (fSTS). Here, we asked whether these areas respond to two first-order aspects of the face argued to be important for face perception, face parts (eyes, nose, and mouth), and the T-shaped spatial configuration of these parts. Specifically, we measured the magnitude of response in these areas to stimuli that (i) either contained real face parts, or did not, and (ii) either had veridical face configurations, or did not. The OFA and the fSTS were sensitive only to the presence of real face parts, not to the correct configuration of those parts, whereas the FFA was sensitive to both face parts and face configuration. Further, only in the FFA was the response to configuration and part information correlated across voxels, suggesting that the FFA contains a unified representation that includes both kinds of information. In combination with prior results from fMRI, TMS, MEG, and patient studies, our data illuminate the functional division of labor in the OFA, FFA, and fSTS.
Auditory Working Memory Load Impairs Visual Ventral Stream Processing: Toward a Unified Model of Attentional Load
Authors: Klemen Jane , Büchel Christian , Bühler Mira , Menz Mareike M. , Rose Michael
Published: March 2009

Attentional interference between tasks performed in parallel is known to have strong and often undesired effects. As yet, however, the mechanisms by which interference operates remain elusive. A better knowledge of these processes may facilitate our understanding of the effects of attention on human performance and the debilitating consequences that disruptions to attention can have. According to the load theory of cognitive control, processing of task-irrelevant stimuli is increased by attending in parallel to a relevant task with high cognitive demands. This is due to the relevant task engaging cognitive control resources that are, hence, unavailable to inhibit the processing of task-irrelevant stimuli. However, it has also been demonstrated that a variety of types of load (perceptual and emotional) can result in a reduction of the processing of task-irrelevant stimuli, suggesting a uniform effect of increased load irrespective of the type of load. In the present study, we concurrently presented a relevant auditory matching task [n-back working memory (WM)] of low or high cognitive load (1-back or 2-back WM) and task-irrelevant images at one of three object visibility levels (0%, 50%, or 100%). fMRI activation during the processing of the task-irrelevant visual stimuli was measured in the lateral occipital cortex and found to be reduced under high, compared to low, WM load. In combination with previous findings, this result is suggestive of a more generalized load theory, whereby cognitive load, as well as other types of load (e.g., perceptual), can result in a reduction of the processing of task-irrelevant stimuli, in line with a uniform effect of increased load irrespective of the type of load.
Lesions to the Motor System Affect Action Perception
Authors: Serino Andrea , De Filippo Laura , Casavecchia Chiara , Coccia Michela , Shiffrar Maggie , Làdavas Elisabetta
Published: March 2009

Several studies have shown that the motor system is involved in action perception, suggesting that action concepts are represented through sensory–motor processes. Such conclusions imply that motor system impairments should diminish action perception. To test this hypothesis, a group of 10 brain-damaged patients with hemiplegia (specifically, a lesion at the motor system that affected the contralesional arm) viewed point-light displays of arm gestures and attempted to name each gesture. To create the dynamic stimuli, patients individually performed simple gestures with their unaffected arm while being videotaped. The videotapes were converted into point-light animations. Each action was presented as it had been performed, that is, as having been produced by the observer's unaffected arm, and in its mirror reversed orientation, that is, as having been produced by the observer's hemiplegic arm. Action recognition accuracy by patients with hemiplegia was compared with that by 8 brain-damaged patients without any motor deficit and by 10 healthy controls. Overall, performance was better in control observers than in patients. Most importantly, performance by hemiplegic patients, but not by nonhemiplegic patients and controls, varied systematically as a function of the observed limb. Action recognition was best when hemiplegic patients viewed actions that appeared to have been performed by their unaffected arm. Action recognition performance dropped significantly when hemiplegic patients viewed actions that appeared to have been produced with their hemiplegic arm or the corresponding arm of another person. The results of a control study involving the recognition of point-light defined animals in motion indicate that a generic deficit to visual and cognitive functions cannot account for this laterality-specific deficit in action recognition. Taken together, these results suggest that motor cortex impairment decreases visual sensitivity to human action. Specifically, when a cortical lesion renders an observer incapable of performing an observed action, action perception is compromised, possibly by a failure to map the observed action onto the observer's contralesional hemisoma.
Investigating Occipito-temporal Contributions to Reading with TMS
Authors: Duncan Keith J. , Pattamadilok Chotiga , Devlin Joseph T.
Published: March 2009

The debate regarding the role of ventral occipito-temporal cortex (vOTC) in visual word recognition arises, in part, from difficulty delineating the functional contributions of vOTC as separate from other areas of the reading network. Here, we investigated the feasibility of using TMS to interfere with vOTC processing in order to explore its specific contributions to visual word recognition. Three visual lexical decision experiments were conducted using neuronavigated TMS. The first demonstrated that repetitive stimulation of vOTC successfully slowed word, but not nonword, responses. The second confirmed and extended these findings by demonstrating the effect was specific to vOTC and not present in the adjacent lateral occipital complex. The final experiment used paired-pulse TMS to investigate the time course of vOTC processing for words and revealed activation starting as early as 80–120 msec poststimulus onset—significantly earlier than that expected based on electrophysiological and magnetoencephalography studies. Taken together, these results clearly indicate that TMS can be successfully used to stimulate parts of vOTC previously believed to be inaccessible and provide a new tool for systematically investigating the information processing characteristics of vOTC. In addition, the findings provide strong evidence that lexical status and frequency significantly affect vOTC processing, findings difficult to reconcile with prelexical accounts of vOTC function.
Visual Short-term Memory Capacity for Simple and Complex Objects
Authors: Luria Roy , Sessa Paola , Gotler Alex , Jolicœur Pierre , Dell'Acqua Roberto
Published: March 2009

Does the capacity of visual short-term memory (VSTM) depend on the complexity of the objects represented in memory? Although some previous findings indicated lower capacity for more complex stimuli, other results suggest that complexity effects arise during retrieval (due to errors in the comparison process with what is in memory) that is not related to storage limitations of VSTM, per se. We used ERPs to track neuronal activity specifically related to retention in VSTM by measuring the sustained posterior contralateral negativity during a change detection task (which required detecting if an item was changed between a memory and a test array). The sustained posterior contralateral negativity, during the retention interval, was larger for complex objects than for simple objects, suggesting that neurons mediating VSTM needed to work harder to maintain more complex objects. This, in turn, is consistent with the view that VSTM capacity depends on complexity.
Target Detection by Opponent Coding in Monkey Prefrontal Cortex
Authors: Kusunoki Makoto , Sigala Natasha , Nili Hamed , Gaffan David , Duncan John
Published: March 2009

The pFC plays a key role in flexible, context-specific decision making. One proposal [Machens, C. K., Romo, R., & Brody, C. D. Flexible control of mutual inhibition: A neural model of two-interval discrimination. Science, 307, 1121–1124, 2005] is that prefrontal cells may be dynamically organized into opponent coding circuits, with competitive groups of cells coding opposite behavioral decisions. Here, we show evidence for extensive, temporally evolving opponent organization in the monkey pFC during a cued target detection task. More than a half of all randomly selected cells discriminated stimulus category in this task. The largest set showed target-positive activity, with the strongest responses to the current target, intermediate activity for a nontarget that was a target on other trials, and lowest activity for nontargets never associated with the target category. Second most frequent was a reverse, antitarget pattern. In the ventrolateral frontal cortex, opponent organization was strongly established in phasic responses at stimulus onset; later, such activity was widely spread across dorsolateral and ventrolateral sites. Task-specific organization into opponent cell groups may be a general feature of prefrontal decision making.
Bayesian k-Means as a “Maximization-Expectation” Algorithm
Authors: Kurihara Kenichi , Welling Max
Published: March 2009

We introduce a new class of “maximization-expectation” (ME) algorithms where we maximize over hidden variables but marginalize over random parameters. This reverses the roles of expectation and maximization in the classical expectation-maximization algorithm. In the context of clustering, we argue that these hard assignments open the door to very fast implementations based on data structures such as kd-trees and conga lines. The marginalization over parameters ensures that we retain the ability to infer model structure (i.e., number of clusters). As an important example, we discuss a top-down Bayesian k-means algorithm and a bottom-up agglomerative clustering algorithm. In experiments, we compare these algorithms against a number of alternative algorithms that have recently appeared in the literature.
Spatial Patterns of Glaciers in Response to Spatial Patterns in Regional Climate
Authors: Huybers Kathleen , Roe Gerard H.
Published: March 2009

Glaciers are direct recorders of climate history and have come to be regarded as emblematic of climate change. They respond to variations in both accumulation and ablation, which can have separate atmospheric controls, leading to some ambiguity in interpreting the causes of glacier changes. Both climate change and climate variability have characteristic spatial patterns and time scales. The focus of this study is the regional-scale response of glaciers to natural patterns of climate variability. Using the Pacific Northwest of North America as the setting, the authors employ a simple linear glacier model to study how the combination of patterns of melt-season temperature and patterns of annual accumulation produce patterns of glacier length variations. Regional-scale spatial correlations in glacier length variations reflect three factors: the spatial correlations in precipitation and melt-season temperature, the geometry of a glacier and how it determines the relative importance of temperature and precipitation, and the climatic setting of the glaciers (i.e., maritime or continental). With the self-consistent framework developed here, the authors are able to evaluate the relative importance of these three factors. The results also highlight that, in order to understand the natural variability of glaciers, it is critically important to know the small-scale patterns of climate in mountainous terrain. The method can be applied to any area containing mountain glaciers and provides a baseline expectation for natural glacier variation against which the effects of climate changes can be evaluated.
Five-Year Growth Trajectories of Kindergarten Children With Learning Difficulties in Mathematics
Authors: Morgan Paul L. , Farkas George , Qiong Wu
Published: March 2009

The investigators used data from the Early Childhood Longitudinal Study— Kindergarten Cohort (ECLS-K) to estimate whether and to what extent the timing and persistence of mathematics difficulties (MD) in kindergarten predicted children's first through fifth grade math growth trajectories. Results indicated that children persistently displaying MD (i.e., those experiencing MD in both fall and spring of kindergarten) had the lowest subsequent growth rates, children with MD in spring only had the second-lowest growth rates, and children with MD in the fall only (and who had thus recovered from their MD by the spring of kindergarten) had the next-lowest growth rates. The children who did not have MD in either fall or spring of kindergarten had the highest growth rates. These results were observed prior to and after statistical control for additional variables. They indicate that measuring the timing and persistence of kindergarten children's mathematics learning difficulties may help identify those most at risk for failing to become mathematically proficient during elementary school.
Clinically Important Interaction Between Tedisamil and Verapamil
Authors: van Haarst Aernout D. , Dijkmans Anneke C. , Weimann Hans‐Josef , Kemme Michiel J. B. , Bosch Jacobus J. , Schoemaker Rik C. , Cohen Adam F. , Burggraaf Jacobus
Published: March 2009

Tedisamil, a class III antiarrhythmic drug, is a P‐glycoprotein substrate. Tedisamil treatment may implicate coadministration with class IV antiarrhythmics such as verapamil, a P‐glycoprotein inhibitor. Pharmacokinetic and pharmacodynamic interactions between tedisamil and verapamil were evaluated in a double‐blind, crossover study. Twelve healthy volunteers received a 3‐day treatment of tedisamil (100 mg bid), verapamil (180 mg bid), a combination of these drugs, or placebo. Blood pressure and electrocardiograms were assessed daily and cardiac output and pharmacokinetics on day 3. Combination of tedisamil and verapamil increased tedisamil plasma concentrations (AUC0−12 h: +77%, CI90%: +51% to +108%; Cmax: +78%, CI90%: +57% to +102%) compared to tedisamil monotreatment but decreased plasma concentrations of verapamil (AUC0−12 h: −21%, CI90%: −32% to −8%; Cmax: −28%, CI90%: −39% to −14%) and norverapamil (AUC0−12 h: −17%, CI90%: −28% to −6%; Cmax: −20%, CI90%: −29% to −10%) compared to verapamil monotreatment. Compared to placebo, verapamil and the combination treatment increased PR by 23.5 (CI95%: 17.9 to 29.2) ms and 12.2 (5.7 to 17.0) ms, respectively. Compared to placebo, tedisamil and the combination treatment increased QTc by 27.8 (15.8 to 39.8) ms and 45.7 (33.7 to 57.7) ms, respectively. Thus, concomitant use of tedisamil with P‐glycoprotein inhibitors likely results in clinically significant drug interactions.
Prediction of Human Pharmacokinetics From Preclinical Information: Comparative Accuracy of Quantitative Prediction Approaches
Authors: Hosea Natilie A. , Collard Wendy T. , Cole Susan , Maurer Tristan S. , Fang Rick X. , Jones Hannah , Kakar Shefali M. , Nakai Yasuhiro , Smith Bill J. , Webster Rob , Beaumont Kevin
Published: March 2009

Quantitative prediction of human pharmacokinetics is critical in assessing the viability of drug candidates and in determining first‐in‐human dosing. Numerous prediction methodologies, incorporating both in vitro and preclinical in vivo data, have been developed in recent years, each with advantages and disadvantages. However, the lack of a comprehensive data set, both preclinical and clinical, has limited efforts to evaluate the optimal strategy (or strategies) that results in quantitative predictions of human pharmacokinetics. To address this issue, the authors conducted a retrospective analysis using 50 proprietary compounds for which in vitro, preclinical pharmacokinetic data and oral single‐dose human pharmacokinetic data were available. Five predictive strategies, involving either allometry or use of unbound intrinsic clearance from microsomes or hepatocytes, were then compared for their ability to predict human oral clearance, half‐life through predictions of systemic clearance, volume of distribution, and bioavailability. Use of a single‐species scaling approach with rat, dog, or monkey was as accurate as or more accurate than using multiple‐species allometry. For those compounds cleared almost exclusively by P450‐mediated pathways, scaling from human liver microsomes was as predictive as single‐species scaling of clearance based on data from rat, dog, or monkey. These data suggest that use of predictive methods involving either single‐species in vivo data or in vitro human liver microsomes can quantitatively predict human in vivo pharmacokinetics and suggest the possibility of streamlining the predictive methodology through use of a single species or use only of human in vitro microsomal preparations.
Maneuvering the Role as a Community College Artist-Educator
Authors: Gibson John R. , Murray John P.
Published: March 2009

This study examined how Texas community college artist-educators balance artistic productivity with their teaching responsibilities. The 98 survey respondents represented 76.6% of a stratified random sample of the full-time instructors in visual arts departments within the 50 Texas public community college districts. Access to studio space and equipment, peer support, and new avenues for artistic expression and creative stimulation were seen as promoting or enhancing artistic production. Lack of studio time for producing one's artwork was cited a barrier to artistic production, as were the demands of teaching and related responsibilities. In addition, those who saw themselves more as artists than as educators or who saw themselves equally as artists and educators were more likely to balance art with teaching and service than were those who saw themselves more as educators than as artists.
Traumatic and Overuse Injuries Among International Elite Junior Rowers
Authors: Smoljanovic Tomislav , Bojanic Ivan , Hannafin Jo A. , Hren Darko , Delimar Domagoj , Pecina Marko
Published: March 2009

Background

Junior rowers have competed internationally for over 4 decades, and there are no epidemiological data available on traumatic and overuse injury in this population.

Objective

To define the types of musculoskeletal problems present in international elite-level junior rowers and to determine whether gender, physical stature, rowing discipline, and training programs affect the incidence of reported injuries.

Study Design

Descriptive epidemiology study.

Methods

Injury data were obtained from a total of 398 rowers (42% female, 58% male) who completed a 4-page questionnaire on injury incidence while participating at the Junior World Rowing Championships in Beijing, People’s Republic of China, in August 2007.

Results

Overall, 290 (73.8%) reported injuries involved overuse, and 103 (26.2%) were related to a single traumatic event. Female rowers were injured more frequently than male rowers (110.2 vs 90.5 injuries per 100 rowers). In both genders, the most common injury site was the low back followed by the knee and the forearm/wrist. The severity of reported injuries was incidental in 65.1%, minor in 21.4%, moderate in 10.4%, and major in 3.1% of cases. The rowers with traumatic injuries had less rowing experience than the uninjured rowers (median [C] ± interquartile range [Q] = 3 ± 3 years vs 4 ± 3 years; P = .043, Mann-Whitney test). Sweep rowers who changed rowing side during the current season had significantly more acute-onset low back injuries ( P = .012, χ2 test) than those who did not change rowing side during the same period. The incidence of traumatic injuries was significantly lower in rowers who regularly performed more than 10 minutes of posttraining stretching ( P = .030, χ2 test). Athletes who ran more than once a week had more overuse knee injuries than those who ran once or less per week ( P = .033, χ2 test).

Conclusion

Elite junior rowers attending the World Rowing Championships reported predominantly overuse injuries of low severity during the current rowing season. Low back injuries were the most frequent complaint of elite-level junior rowers.
Knowledge Transfer Within Multinationals and Their Foreign Subsidiaries
Authors: Zaidman Nurit , Brock David M.
Published: March 2009

The authors' research introduces a culture-sensitive approach to the analysis of knowledge transfer in multinational organizations. This article investigates the knowledge itself, how knowledge is represented, and its flow within social structures. The analysis considers forms of knowledge transfer as cultural products, and their interaction with the populations involved. Sociocultural structures as well as specific cultural characteristics of the populations are analyzed in reference to knowledge transfer as well as the interaction between the relevant contexts. Data were collected in two multinational Israeli software development companies and their affiliates in India. The analyses included various qualitative analyses of 96 interviews, informal discussions, documents, including instant messaging chats and observations. The authors show, for example, how the influences of contemporary professional work norms as well as customary behavior from the national context combine to influence who talks to whom, what kind of information is transferred, and the extent to which people of disparate status and background are willing to share.
Thirty Years of Scholarship and Science on Environment— Society Relationships
Authors: Freudenburg William R.
Published: March 2009

By 2008, “environmental sociology” had become a well-established and well-recognized field of sociology, but exactly 30 years earlier, in 1978, it was essentially nonexistent. That was the year that saw the publication of the first two articles that, along with later work by Riley Dunlap and William Catton, began to make possible the subsequent development of the field. At the time, many of the leading figures in sociology—specifically including those who called themselves “human ecologists”—were actively hostile to the idea that sociological work would include attention to environmental variables. The hostility was particularly acute for work that focused on what an important book of the time called Limits to Growth. Fortunately, these pioneers moved forward, and in doing so, they helped to change the entire field of sociology. If the earlier degree of hostility toward work on environmental problems and variables is difficult to imagine today, a significant fraction of the credit needs to go to Drs. Catton and Dunlap.
Promoting a Paradigm Change
Authors: Dunlap Riley E.
Published: March 2009

The author discusses his collaboration with William Catton that led to several early articles aimed at providing an intellectual foundation for a field of environmental sociology. The differing backgrounds and interests they each brought to their collaboration and the context in which it developed are outlined, along with the author's assessment of the major goals of their key publications. The growth of environmental sociology and increased disciplinary attention to ecological problems, spurred by the growing societal salience of such problems, suggests that sociology has begun to shed the human exemptionalist paradigm that dominated the discipline when the field of environmental sociology was launched.
Improving Child Outcomes With Data-Based Decision Making: Collecting Data
Authors: Hojnoski Robin L. , Gischlar Karen L. , Missall Kristen N.
Published: March 2009

Ms. Carol is concerned about Dominique, one of the children in her preschool class, who has difficulty interacting appropriately with peers and often engages in aggressive behaviors. Ms. Carol wants to intervene with Dominique and collect data to see how she responds. Similarly, Ms. Kathy is concerned about the early literacy development of one of the children in her class. Jaylen does not seem to be acquiring phonological awareness skills at the same rate as his peers. Ms. Kathy wants to work with him individually and track his progress, but she is not sure how to go about doing this. Another teacher, Mr. Nick, has been working on increasing Trevor's participation in activities in his inclusive preschool classroom. However, after 3 months, Mr. Nick is not seeing much improvement in this area, according to his daily class notes. These teachers have similar needs and interests_they wish to intervene with children individually and intentionally and to systematically assess the effects of their efforts to determine whether the children are making adequate progress. Where do they start?