bluuebunny/crossref_metadata_2025 huggingface dataset:
What do fully visible primes and brain potentials reveal about morphological decomposition?
Authors: Lavric Aureliu , Rastle Kathleen , Clapp Amanda
Published: September 2010

To examine the role of meaning in morphological decomposition ({re‐}+{play}), researchers have employed the priming paradigm. Perceptually masked primes lead to facilitation both when decomposition is semantically appropriate (hunter‐HUNT) and when it is not (corner‐CORN), whereas with fully visible primes facilitation is observed only in the former case. We investigated the N400 brain potential time‐locked to words preceded by fully visible primes. At ∼300–380 ms, N400 was equally attenuated in the semantically “transparent” condition (hunter‐HUNT) and semantically “opaque” condition (corner‐CORN). In the transparent condition, N400 remained attenuated after 380 ms, whereas in the opaque condition it returned to the level of a nonmorphological form condition (brothel‐BROTH). This pattern of N400 priming is consistent with an orthography‐based, morphological decomposition mechanism, “licensed” at a later stage by semantic information.
Neural evidence for the threat detection advantage: Differential attention allocation to angry and happy faces
Authors: Feldmann‐Wüstefeld Tobias , Schmidt‐Daffy Martin , Schubö Anna
Published: September 2010

Threat stimuli are considered to be processed with higher priority due to an automatic threat detection system that enables rapid shifts of attention. However, direct evidence is still missing. The present study used the face‐in‐the‐crowd task and event‐related potentials to find evidence for the functionality of attention shifts in threat detection. The threat detection advantage was replicated in the behavioral results. An N2pc was observed that was more pronounced and earlier for angry compared to happy faces, suggesting differential attention allocation underlying the threat detection advantage. A larger sustained posterior contralateral negativity indicated that angry faces also gained more enhanced subsequent processing. An early posterior negativity observed 160 ms after stimulus onset revealed early emotion‐specific processing that may have caused differences in attention allocation toward threatening stimuli.
Loss of sphingosine kinase‐1 in carcinoma cells increases formation of reactive oxygen species and sensitivity to doxorubicin‐induced DNA damage
Authors: Huwiler Andrea , Kotelevets Nataliya , Xin Cuiyan , Pastukhov Oleksandr , Pfeilschifter Josef , Zangemeister‐Wittke Uwe
Published: September 2010

BACKGROUND AND PURPOSE Sphingosine kinases (SK) catalyse the formation of sphingosine 1‐phosphate, which is a key lipid mediator regulating cell responses such as proliferation, survival and migration. Here we have investigated the effect of targeted inhibition of SK‐1 on cell damage and elucidated the mechanisms involved.

EXPERIMENTAL APPROACH Three human carcinoma cell lines (colon HCT‐116, breast MDA‐MB‐231, lung NCI‐H358) were used, which were either transduced with shRNA constructs to deplete SK‐1, or treated with a SK‐1 inhibitor. Cell growth and viability were assayed by [3H]thymidine incorporation and colony formation. Reactive oxygen species (ROS) were measured by fluorescence and apoptosis by annexin V with flow cytometry. Proteins were analysed by Western blotting. DNA damage was induced by doxorubicin.

KEY RESULTS Knock‐down of SK‐1 by shRNA strongly inhibited DNA synthesis and colony formation of carcinoma cells. SK‐1 knock‐down (SK‐1kd) cells revealed dysfunctional extracellular signal‐regulated protein kinase and PKB/Akt cascades, and contained increased levels of ROS. After SK‐1kd, treatment with doxorubicin increased DNA damage, measured by histone‐2AX phosphorylation. Similar effects were found in cells with a SK‐1 inhibitor and doxorubicin. The increased damage response in SK‐1kd cells was accompanied by greater reduction of DNA synthesis and colony formation, and by more pronounced apoptosis. Addition of a NADPH oxidase inhibitor reduced the increased apoptosis in doxorubicin‐treated SK‐1kd cells.

CONCLUSIONS AND IMPLICATIONS SK‐1kd in carcinoma cells triggered oxidative stress by increasing intracellular Ros production. Targeted inhibition of SK‐1 represents a promising approach to sensitize cells to DNA damage and facilitate apoptosis upon doxorubicin treatment.
Lovastatin Promotes Redifferentiation of Human Nucleus Pulposus Cells During Expansion in Monolayer Culture
Authors: Hu Ming‐Hsiao , Hung Li‐Wei , Yang Shu‐Hua , Sun Yuan‐Hui , Shih Tiffany Ting‐Fang , Lin Feng‐Huei
Published: September 2010

To acquire the capacities for matrix production and preservation of an expanded volume within a damaged intervertebral disc (IVD), cells isolated from human nucleus pulposus (NP) tissues must undergo several passages in monolayer culture. However, chondrocytes and IVD cells in monolayer culture undergo “dedifferentiation,” characterized by decreased synthesis of type II collagen and increased synthesis of type I collagen, thereby compromising the properties of regenerative tissues. The present study was undertaken to ascertain whether lovastatin reverses “dedifferentiation” of human NP cells during monolayer expansion. Expression of genes encoding type II collagen and transcription factor SOX9 in these cells was upregulated by lovastatin, with maximal stimulations observed at 5 µM, whereas type I collagen gene expression was suppressed by the drug, with maximal inhibitions observed at 5–10 µM. At lovastatin concentrations ≥1 µM, expression of genes encoding the bone morphogenetic proteins BMP‐2 and BMP‐7 was also significantly enhanced. Furthermore, the number of NP cells exhibiting a rounded shape and positive staining for S‐100 protein and type II collagen protein increased during treatment with lovastatin. These findings strongly support the induction by lovastatin of “redifferentiation” of human NP cells during their expansion in monolayer culture.
Mild adolescent/adult onset epilepsy and paroxysmal exercise‐induced dyskinesia due to GLUT1 deficiency
Authors: Afawi Zaid , Suls Arvid , Ekstein Dana , Kivity Sara , Neufeld Miriam Y , Oliver Karen , De Jonghe Peter , Korczyn Amos D , Berkovic Samuel F.
Published: September 2010

Paroxysmal exercise‐induced dyskinesia (PED) and epilepsy without intellectual disability have recently been recognized as manifestations of deficiency of the glucose transporter GLUT1, due to mutations in the gene SLC2A1. We describe a family with six definitely affected members in two generations. Two had PED, three had epilepsy, and one had both. A missense mutation in SLC2A1 (c.950A>C; p.N317T) was detected in five living affected members, but absent in three nonaffected first‐degree members and in one subject believed to be a phenocopy. The clinical picture of mild epilepsy with onset in adolescence or early adulthood plus PED should raise a suspicion of GLUT1 deficiency.
STXBP1 mutations in early infantile epileptic encephalopathy with suppression‐burst pattern
Authors: Saitsu Hirotomo , Kato Mitsuhiro , Okada Ippei , Orii Kenji E. , Higuchi Tsukasa , Hoshino Hideki , Kubota Masaya , Arai Hiroshi , Tagawa Tetsuzo , Kimura Shigeru , Sudo Akira , Miyama Sahoko , Takami Yuichi , Watanabe Toshihide , Nishimura Akira , Nishiyama Kiyomi , Miyake Noriko , Wada Takahito , Osaka Hitoshi , Kondo Naomi , Hayasaka Kiyoshi , Matsumoto Naomichi
Published: September 2010

Purpose:  De novo STXBP1 mutations have been found in individuals with early infantile epileptic encephalopathy with suppression‐burst pattern (EIEE). Our aim was to delineate the clinical spectrum of subjects with STXBP1 mutations, and to examine their biologic aspects.

Methods:  STXBP1 was analyzed in 29 and 54 cases of cryptogenic EIEE and West syndrome, respectively, as a second cohort. RNA splicing was analyzed in lymphoblastoid cells from a subject harboring a c.663 + 5G>A mutation. Expression of STXBP1 protein with missense mutations was examined in neuroblastoma2A cells.

Results:  A total of seven novel STXBP1 mutations were found in nine EIEE cases, but not in West syndrome. The mutations include two frameshift mutations, three nonsense mutations, a splicing mutation, and a recurrent missense mutation in three unrelated cases. Including our previous data, 10 of 14 individuals (71%) with STXBP1 aberrations had the onset of spasms after 1 month, suggesting relatively later onset of epileptic spasms. Nonsense‐mediated mRNA decay associated with abnormal splicing was demonstrated. Transient expression revealed that STXBP1 proteins with missense mutations resulted in degradation in neuroblastoma2A cells.

Discussion:  Collectively, STXBP1 aberrations can account for about one‐third individuals with EIEE (14 of 43). These genetic and biologic data clearly showed that haploinsufficiency of STXBP1 is the important cause for cryptogenic EIEE.
Effect of levetiracetam on testosterone levels in male patients
Authors: Harden Cynthia L. , Nikolov Blagovest G. , Kandula Padmaja , Labar Douglas R. , Pannullo Susan
Published: September 2010

We sought to determine whether the testosterone increase found with levetiracetam exposure in animal studies also occurs in patients. Adult male patients were evaluated for reproductive hormone levels before and 1 month after levetiracetam therapy. Eight subjects met inclusion/exclusion criteria (mean age 46 years, range 29–75 years). Total testosterone prior to starting levetiracetam ranged from 206–787 ng/dl [mean 445, standard deviation (SD) 227]. The mean total testosterone after levetiracetam therapy increased to 592 ng/dl (range 216–981, SD 297), an increase of 16% (p = 0.036). The free testosterone increased from a mean of 64 pg/ml (range 36–115, SD 30) to a mean of 76 pg/ml (range 35–155, SD 44), an increase of 19% (p = 0.080). The magnitude of change in testosterone levels correlated with the initial testosterone level (p = 0.038, r = 0.734). These results suggest that levetiracetam increases testosterone levels and that an initial testosterone level may predict the magnitude of increase.
Predictors of Parental Risk Perceptions: The Case of Child Pedestrian Injuries in School Context
Authors: Cloutier Marie‐Soleil , Bergeron Jacques , Apparicio Philippe
Published: September 2010

The objective of this article is to explore the factors that influence parental risk perceptions of child pedestrian injuries in the elementary school context. Parents (n= 193) from six different schools responded to a questionnaire on road safety, including a measure of their risk perception. Results of bivariate analyses show that eight variables are significantly related to risk perception. Environmental variables, as we measure them, were not significant, contrary to our initial hypotheses. Only three variables, parent's gender, perceived primary source of danger, and sense of control remained significant in OLS regression analyses (adjusted R2 of 0.16, F= 9.27; p= 0.00). Since parents’ perceptions of road risks are an important factor in their road safety practices and in their choice of transportation mode used for their child's journey to school, our analysis elucidates factors underlying these choices. Our results can help decisionmakers to design traffic injury prevention measures and to promote physical activity through the use of active modes of transport.
Fast Pathway Ablation Using Cryotherapy for a Patient with a long PR interval in Sinus Rhythm and AVNRT
Authors: LINTON NICK W. F. , DAVIES D. WYN , MASON ANTONY , LEFROY DAVID
Published: September 2010

A 53‐year‐old man with previous aortic valve surgery presented with paroxysmal narrow complex tachycardia, induced by exercise. His PR interval was greater than 400 ms when in sinus rhythm and atrioventricular nodal reentry tachycardia (AVNRT) was diagnosed with invasive electrophysiological studies. Single echoes were repeatedly inducible with single‐paced extrastimuli. Cryotherapy was then used to ablate the fast pathway using single echoes to monitor anterograde slow pathway and retrograde fast pathway function during ablation. PACE 2012; 35:e47–e51)
Migration background: a risk factor for caries development during adolescence
Authors: Julihn Annika , Ekbom Anders , Modéer Thomas
Published: September 2010

Julihn A, Ekbom A, Modéer T. Migration background: a risk factor for caries development during adolescence. Eur J Oral Sci 2010; 118: 618–625. © 2010 Eur J Oral Sci

The influence of child and parental migration background on the risk of approximal caries increment in Swedish adolescents was investigated. This retrospective longitudinal register‐based cohort study included all 13‐yr‐old adolescents (n = 18,142) who were resident in the County of Stockholm, Sweden, in 2000, and followed them up to 19 yr of age. At follow‐up, 15,538 subjects were examined. Caries data [decayed, missing, and filled teeth/surfaces (DMFT/S)], were collected from a dental database. Socio‐demographic determinants were collected from Swedish National Registers. After adjustments for socio‐demographic confounders, logistic regression analysis revealed that adolescents with foreign‐born parents, irrespective of whether the child was born in Sweden or abroad, exhibited a significantly elevated risk for approximal caries increment (DMFSa > 0), and developed, on average, 0.53 and 1.14 more approximal caries lesions, respectively, compared with their counterparts with Swedish‐born parents. Furthermore, adolescents born in eastern Europe exhibited an increased risk for approximal caries increment (DMFSa > 0) and developed, on average, 1.06 more approximal caries lesions compared with Swedish‐born adolescents. In conclusion, parental migration background must be considered as a risk factor for caries development during adolescence, irrespective of whether or not the adolescent was born in Sweden.
Changes in the quality of life of Tanzanian school children after treatment interventions using the Child‐OIDP
Authors: Mashoto Kijakazi O. , Åstrøm Anne N. , Skeie Marit S. , Masalu Joyce R.
Published: September 2010

Mashoto KO, Åstrøm AN, Skeie MS, Masalu JR. Changes in the quality of life of Tanzanian school children after treatment interventions using the Child‐OIDP. Eur J Oral Sci 2010; 118: 626–634. © 2010 Eur J Oral Sci

This study aimed to examine the evaluative properties of the Child Oral Impacts on Daily Performances (Child‐OIDP) inventory and to estimate treatment‐associated changes in the OIDP and self‐reported oral health following atraumatic restorative treatment (ART) and oral health education (OHE). A total of 1,306 school attendees in Kilwa, Tanzania, completed the Child‐OIDP inventory before, and 6 months after, treatment. The post‐treatment questionnaire assessed change in perceived oral health. Complete baseline and follow‐up data were obtained for 104, 117, and 1,085 participants who received, respectively, ART fillings (Group A), ART fillings and tooth extraction (Group B), and OHE only (Group C). The longitudinal validity, responsiveness, and treatment‐associated changes were calculated using anova, effect sizes, and repeated general linear models (GLM). The follow‐up prevalence was 73.8%. The mean changes in the OIDP total‐ and subscale scores were negative within those who reported ‘worsened’ oral health, and positive in subjects reporting ‘improved’ oral health. Effect sizes for the total OIDP score ranged from −0.2 within the category ‘worsened’ to 0.4 within the category ‘improved’. Changes following treatment were more extensive in Group B compared with Groups A and C, and in Group C compared with Group A. The Child‐OIDP showed promising evaluative properties and responsiveness to change following ART fillings, ART fillings and tooth extraction, and OHE.
The four hour target to reduce emergency department ‘waiting time’: A systematic review of clinical outcomes
Authors: Jones Peter , Schimanski Karen
Published: September 2010

Governments in Australasia are introducing emergency department length of stay (EDLOS) time targets similar to the UK ‘four hour rule’. There is debate about whether this rule had beneficial effects on health‐care outcomes. We sought to determine what effects the four hour time target for EDLOS had on clinically relevant outcomes in the UK by conducting a systematic search for evidence. Articles were screened by both authors independently and assessed for quality using standard tools. Differences in outcomes measured and how they were measured precluded meta‐analysis. There were inconsistencies between target achievement reported by Trusts and that reported in the studies, and empirical evidence that the target might be unattainable. National Health Service spending on ED increased £820 000 000.00 (1998–2007) and emergency admissions rose overall by 35% (2002–2006), but not in all hospitals. Time to see a treating clinician and hospital mortality was unchanged. One hospital demonstrated a small reduction in return rate. The impact of the introduction of an ED time target and the associated massive financial investment has not resulted in a consistent improvement in care with markedly varying effects being reported between hospitals. Countries seeking to emulate the UK experience should proceed with caution.
γ-rays from molecular clouds illuminated by accumulated diffusive protons from supernova remnant W28
Authors: Li Hui , Chen Yang
Published: September 2010

W28 is one of the archetypal supernova remnants (SNRs) interacting with molecular clouds (MCs). HESS observation found four TeV sources which are coincident with the MCs around W28, but Fermi LAT detected no prominent GeV counterparts for two of them. An accumulative diffusion model is established in this Letter, and the energetic protons colliding with the nearby MCs are considered to be an accumulation of the diffusive protons escaping from the shock front throughout the history of the SNR expansion. We have fitted the γ-ray spectra of the four sources and naturally explained the GeV spectral break of the north-eastern source (source N) and the non-significant GeV emission of southern sources A and C. The distances of sources A and C from the SNR centre are found to be much larger than those of sources N and B, which may be the basic reason for the faint GeV γ-rays of the two former sources.
Otolith size and location in digestive tracts of northern fur seals (Callorhinus ursinus): Implications for dietary interpretations
Authors: Sinclair E. H. , York A. E. , Antonelis G. A.
Published: September 2010

Abstract

Walleye pollock (Theragra chalcogramma) otoliths (n= 2,706) recovered from stomachs, small intestines, and colons of 43 northern fur seals (Callorhinus ursinus) were evaluated for size and wear by location in the digestive tract. Pollock fork length was regressed on otolith length after correction for erosion, and age was estimated from the calculated body size. Age‐1+ pollock otoliths (≥6.3‐mm length) were concentrated in stomachs while age‐0 otoliths (≤6.2‐mm length) were concentrated in colons. Less than 10% of otoliths were found in the small intestines. Pollock age decreased with progression along seal gastrointestinal tracts. Otolith quality increased along gastrointestinal tracts in numbers ≥20, which was typical of age‐0 otoliths recovered from colons. Otolith distribution by age and quality along gastrointestinal tracts suggests that small (≤12 cm) schooling prey are consumed in large volume and passed as a bolus rapidly through the digestive tract before significant erosion of bony remains occurs; while larger prey are eaten in smaller volume and subjected to otolith erosion due to longer retention in the stomach. Our results illustrate the importance of multiple sampling strategies to comprehensively represent prey size in pinniped diet.
Selective Inhibition of Early—but Not Late—Expressed HIF‐1α Is Neuroprotective in Rats after Focal Ischemic Brain Damage
Authors: Yeh Shiu‐Hwa , Ou Li‐Chin , Gean Po‐Wu , Hung Jan‐Jong , Chang Wen‐Chang
Published: September 2010

The expression of hypoxia‐inducible factor‐1‐alpha (HIF‐1α) is upregulated in ischemic stroke, but its function is still unclear. In the present study, biphasic expression of HIF‐1α was observed during 1–12 h and after 48 h in neurons exposed to ischemic stress in vitro and in vivo. Treating neurons with 2‐methoxyestradiol (2ME2) 0.5 h after ischemic stress or pre‐silencing HIF‐1α with small interfering RNA (siRNA) decreased brain injury, brain edema and number of apoptotic cell, and downregulates Nip‐like protein X (Nix) expression. Conversely, applying 2ME2 to neurons 8 h after ischemic stress or silencing the HIF‐1α with siRNA 12 h after oxygen–glucose deprivation (OGD) increased neuron damage and decreased vascular endothelial growth factor (VEGF) expression. Taken together, these results demonstrate that HIF‐1α induced by ischemia in early and late times leads cellular apoptosis and survival, respectively, and provides a new insight into the divergent roles of HIF‐1α expression in neurons after ischemic stroke.
Correlation of Polydispersed Prion Protein and Characteristic Pathology in the Thalamus in Variant Creutzfeldt‐Jakob Disease: Implication of Small Oligomeric Species
Authors: Choi Young Pyo , Gröner Albrecht , Ironside James W. , Head Mark W.
Published: September 2010

The vacuolation, neuronal loss and gliosis that characterize human prion disease pathology are accompanied by the accumulation of an aggregated, insoluble and protease‐resistant form (termed PrPSc) of the host‐encoded normal cellular prion protein (PrPC). In variant Creutzfeldt‐Jakob disease the frontal cortex and cerebellum exhibit intense vacuolation and the accumulation of PrPSc in the form of amyloid plaques and plaque‐like structures. In contrast the posterior thalamus is characterized by intense gliosis and neuronal loss, but PrPSc plaques are rare and vacuolation is patchy. We have used sucrose density gradient centrifugation coupled with conformation dependent immunoassay to examine the biochemical properties of the PrPSc that accumulates in these different brain regions. The results show a greater degree of PrPSc polydisperal in thalamus compared with frontal cortex or cerebellum, including a subpopulation PrPSc molecules in the thalamus that have sedimentation properties resembling those of PrPC. Much effort has focused on identifying aspects of PrPSc biochemistry that distinguish between different forms of human prion disease and contribute to differential diagnosis. Here we show that PrPSc sedimentation properties, which can depend on aggregation state, correlate with, and may underlie the distinct neurodegenerative processes occurring in different regions of the variant Creutzfeldt‐Jakob disease brain.
Association between painful physical symptoms and clinical outcomes in Taiwanese patients with major depressive disorder: A three‐month observational study
Authors: Chen Kuang‐Peng , Chiu Nan‐Ying , Shen Yu‐Chih , Hou Yuh‐Ming , Yeh Chin‐Bin , Ouyang Wen‐Chen , Singh Pritibha , Granger Renee E. , Raskin Joel , Lin Chaucer C.H.
Published: September 2010

Introduction: Reports from non‐Asian populations indicate that painful physical symptoms are associated with poorer clinical and functional outcomes in patients with Major Depressive Disorder (MDD). This paper shows the changes in disease characteristics and quality of life in Taiwanese MDD patients, with or without painful physical symptoms, over 3 months' observation.

Methods: Taiwanese patients from an observational study of six East Asian countries/regions were classified as painful physical symptom positive (PPS+) or negative (PPS−) based on a mean score of ≥2 or <2, respectively, on the modified Somatic Symptom Inventory. Changes from baseline in outcomes were compared between the groups.

Results: Of 194 patients with MDD, 69% were PPS+ at baseline. These PPS+ patients were more depressed (17‐item Hamilton Depression Rating Scale total; mean [SD] 27.1 [6.26] versus 21.8 [5.94] PPS−, P<0.001), in more pain (Visual Analog Scale overall; median [range] 73.5 [9–100] versus 40 [0 to 80] PPS−, P<0.001) and had poorer quality of life at baseline (EuroQoL; mean [SD] 42.9 [18.26] versus 59.8 [18.21] PPS−,P<0.001). At endpoint (n=118), PPS− patients showed greater improvement on depression outcomes (Clinical Global Impression of Severity; P=0.011) and had a higher remission rate (52.8 % versus 14.6% PPS+, P=0.007).

Discussion: Painful physical symptoms were frequently observed in Taiwanese patients with MDD. As PPS are associated with more severe depression, poorer quality of life, and poorer remission outcomes, clinical management should address both the mental and physical symptoms associated with this disorder.
Impaired working memory in children with attention deficit hyperactivity disorder and their siblings
Authors: Wee Kok Wei , Yaacob Mohd Jamil , Wan Abdullah Wan Norhaida , Nakaria Norzila , Pridmore Saxby
Published: September 2010

Introduction: Impairment of working memory in children with attention deficit hyperactivity disorder (ADHD) has been well described. If similar impairment in working memory can be demonstrated among their siblings, this could suggest impaired working memory is a genetic component of ADHD.

Methods: Fifty‐seven subjects were recruited: (1) ADHD group (n=21); (2) siblings of ADHD children group (n=15); and (3) non‐ADHD children with chronic medical condition as the control group (n=21). All subjects were aged between 6 and 15 years, and ADHD was diagnosed according to DSM‐IV‐TR. Those with other comorbidity or IQ<70 were excluded. Digit Recall was used for assessment of the phonological loop component, Maze Memory test for the visuospatial sketch pad component and Backward Digit Recall for the central executive component of working memory.

Results: ADHD children and their siblings showed similar impairment and both differed from the control group on the Maze Memory test. ADHD children also showed impairment in the Digit Recall test; however, the sibling group did not differ from the control group on this test. The Backward Digit Recall score did not show any significant difference between the three groups.

Discussion: Impairment of the visuospatial sketch pad component of working memory seems to cluster in ADHD children and their siblings. Thus, impairment of the visuospatial sketch pad component of working memory may point towards a genetic predisposition of ADHD.
CFD-Assisted Optimization of Chimneylike Flows to Cool an Electronic Device
Authors: Panthalookaran Varghese
Published: September 2010

Natural convection cooling provides a reliable, cost-effective, energy-efficient and noise-free method to cool electronic equipment. However, the heat transfer coefficient associated with natural convection mode is usually insufficient for electronic cooling and it requires enhancement. Chimneylike flows developed within the cabinets of electronic devices can provide better mass flow and heat transfer rates and can lead to greater cooling efficiency. Constraints in the design of natural convection cooling systems include efficiency of packing, aesthetics, and concerns of material reduction. In this paper, methods based on computational fluid dynamics are used to study the effects of parameters such as (1) vertical alignment of the slots, (2) horizontal alignment of slots, (3) area of slots, (4) differential slot opening, and (5) zonal variation in heat generation on natural convection cooling within such design constraints. Insights thus derived are found useful for designing an energy-efficient and ecofriendly cooling system for electronic devices.
Principles of Tissue Engineering With Nonthermal Irreversible Electroporation
Authors: Phillips Mary , Maor Elad , Rubinsky Boris
Published: September 2010

Nonthermal irreversible electroporation (NTIRE) is an emerging tissue ablation modality that may be ideally suited in developing a decellularized tissue graft. NTIRE utilizes short electric pulses that produce nanoscale defects in the cell membrane lipid bilayer. The electric parameters can be chosen in such a way that Joule heating to the tissue is minimized and cell death occurs solely due to loss in cell homeostasis. By coupling NTIRE with the body’s response, the cells can be selectively ablated and removed, leaving behind a tissue scaffold. Here, we introduce two different methods for developing a decellularized arterial scaffold. The first uses an electrode clamp that is applied to the outside of a rodent carotid artery and the second applies an endovascular minimally invasive approach to apply electric fields from the inner surface of the blood vessels. Both methods are first modeled using a transient finite element analysis of electric and thermal fields to ensure that the electric parameters used in this study will result in minimal thermal damage. Experimental work demonstrates that both techniques result in not only a decellularized arterial construct but an endothelial regrowth is evident along the lumen 7 days after treatment, indicating that the extracellular matrix was not damaged by electric and thermal fields and is still able to support cell growth.
Comment on “The Human K-Complex Represents an Isolated Cortical Down-State”
Authors: Amzica Florin
Published: September 2010

Cash
et al
. (Reports, 22 May 2009, p. 1084) argue that the human K-complex, a defining characteristic of slow-wave sleep, is a unipolar electroencephalogram (EEG) wave reflecting a simple neuronal hyperpolarizing event. We disagree with this conclusion and point to several confounding aspects of the study.
Pathogenomics of
Culex quinquefasciatus
and Meta-Analysis of Infection Responses to Diverse Pathogens
Authors: Bartholomay Lyric C. , Waterhouse Robert M. , Mayhew George F. , Campbell Corey L. , Michel Kristin , Zou Zhen , Ramirez Jose L. , Das Suchismita , Alvarez Kanwal , Arensburger Peter , Bryant Bart , Chapman Sinead B. , Dong Yuemei , Erickson Sara M. , Karunaratne S. H. P. Parakrama , Kokoza Vladimir , Kodira Chinnappa D. , Pignatelli Patricia , Shin Sang Woon , Vanlandingham Dana L. , Atkinson Peter W. , Birren Bruce , Christophides George K. , Clem Rollie J. , Hemingway Janet , Higgs Stephen , Megy Karine , Ranson Hilary , Zdobnov Evgeny M. , Raikhel Alexander S. , Christensen Bruce M. , Dimopoulos George , Muskavitch Marc A. T.
Published: September 2010

Closing the Vector Circle

The genome sequence of
Culex quinquefasciatus
offers a representative of the third major genus of mosquito disease vectors for comparative analysis. In a major international effort,

Arensburger
et al.

(p.
86
) uncovered divergences in the
C. quinquefasciatus
genome compared with the representatives of the other two genera
Aedes aegypti
and
Anopheles gambiae
. The main difference noted is the expansion of numbers of genes, particularly for immunity, oxidoreductive functions, and digestive enzymes, which may reflect specific aspects of the
Culex
life cycle.

Bartholomay
et al.

(p.
88
) explored infection-response genes in
Culex
in more depth and uncovered 500 immune response-related genes, similar to the numbers seen in
Aedes
, but fewer than seen in
Anopheles
or the fruit fly
Drosophila melanogaster
. The higher numbers of genes were attributed partly to expansions in those encoding serpins, C-type lectins, and fibrinogen-related proteins, consistent with greater immune surveillance and associated signaling needed to monitor the dangers of breeding in polluted, urbanized environments. Transcriptome analysis confirmed that inoculation with unfamiliar bacteria prompted strong immune responses in
Culex
. The worm and virus pathogens that the mosquitoes transmit naturally provoked little immune activation, however, suggesting that tolerance has evolved to any damage caused by replication of the pathogens in the insects.
When Humans Arrived in the New Guinea Highlands
Authors: Gosden Chris
Published: September 2010

In a high valley, humans were using plants and felling trees nearly 50,000 years ago.
Neutrophils Find Smoke Attractive
Authors: Barnes Peter J.
Published: September 2010

The altered activity of a neutrophil enzyme promotes the type of persistent lung inflammation seen in chronic pulmonary disease and cystic fibrosis.
Caught in the Net
Access Controlled
The Shaping of Power, Rights, and Rule in Cyberspace

Ronald Deibert, John Palfrey, Rafal Rohozinski, and Jonathan Zittrain, Eds.

MIT Press, Cambridge, MA, 2010. 633 pp. $50, £37.95. ISBN 9780262014342. Paper, $25, £18.95. ISBN 9780262514354. Information Revolution and Global Politics.
Authors: Tambini Damian
Published: September 2010

The contributors, participants in an OpenNet Initiative project, discuss tools for Internet controls that go beyond simple denial of access—such as targeted viruses, denial of service attacks, surveillance, take-down notices, and stringent usage policies.
A Dance of Extrasolar Planets
Authors: Laughlin Gregory
Published: September 2010

The Kepler space telescope has found a system of planets whose orbital timing varies due to gravitational coupling.
Rival Teams Identify a Virus Behind Deaths in Central China
Authors: Stone Richard
Published: September 2010

New findings unmask a dangerous new emerging virus—not a bacterial outbreak as previously believed—behind a deadly disease outbreak in central China and explain why antibiotics failed to stop it. Behind the scenes, however, a fierce argument has broken out over who discovered the virus.
Social Savvy Boosts the Collective Intelligence of Groups
Authors: Miller Greg
Published: September 2010

A
study
published online this week in
Science
argues that groups have a "collective intelligence" that predicts their performance on a range of collaborative tasks.
Counting the Ocean's Creatures, Great and Small
Authors: Normile Dennis
Published: September 2010

Next week, participants will gather in London to celebrate the first ever Census of Marine Life (CoML).
Science
interviews tropical marine ecologist Ian Poiner, chair of the scientific steering committee for CoML since 2008.
Growing Prospects For Life on Mars Divide Astrobiologists
Authors: Kerr Richard A.
Published: September 2010

As discoveries on Mars, including warm spells and salty soil, raise the chances of finding life there, scientists are considering how best to look for it within their budget.
Game-Miners Grapple With Massive Data
Authors: Bohannon John
Published: September 2010

Researchers have been using massively multiplayer online games as natural laboratories, but the data are a challenge to interpret. At the meeting, a computer scientist presented results obtained using a mathematical tool called archetype analysis that works by identifying the most extreme data points and describes the rest as combinations of these archetypes.
Rifampin-Isoniazid Oligonucleotide Typing: an Alternative Format for Rapid Detection of Multidrug-Resistant
Mycobacterium tuberculosis
Authors: Hernández-Neuta Iván , Varela Andrés , Martin Anandi , von Groll Andrea , Jureen Pontus , López Beatriz , Imperiale Belén , Šķenders Ģirts , Ritacco Viviana , Hoffner Sven , Morcillo Nora , Palomino Juan Carlos , Del Portillo Patricia
Published: September 2010

A reverse line blot DNA hybridization format for rapid detection of multidrug-resistant tuberculosis was developed. Simultaneous detection of rifampin and isoniazid resistance in clinical isolates of
Mycobacterium tuberculosis
was based on the same amplification/reverse hybridization principle of the widely used spoligotyping. The test involved probing nine DNA regions that are targets of common drug resistance-associated mutations in the genes
rpoB
,
katG
, and
inhA
. Addition of quaternary amine tetramethyl ammonium chloride to the hybridization buffer promoted multiple hybrid formations at a single annealing temperature irrespective of the different GC contents of probes. The assay was standardized using 20 well-documented strains from the Institute of Tropical Medicine (Belgium) and evaluated blindly in a central laboratory with 100 DNA samples that were obtained from cultured clinical isolates and shipped dried from three other countries. Compared with drug susceptibility testing, both sensitivity and specificity for rifampin resistance detection were 93.0% while for isoniazid the values were 87.7% and 97.7%, respectively. Compared with sequencing and GenoType MTBDRplus methods, sensitivity and specificity reached 96.4% and 95.5% for rifampin and 92.7% and 100% for isoniazid. Altogether, 40/45 (89%) multidrug-resistant isolates were correctly identified. Advantages of this in-house development include versatility, capacity to run up to 41 samples by triplicate in a single run, and reuse of the membrane at least 10 times. These features substantially reduce cost per reaction and make the assay an attractive tool for use in reference laboratories of countries that have a high burden of multidrug-resistant tuberculosis but that cannot afford expensive commercial tests because of limited resources.
Novel Point-of-Care Test for Simultaneous Detection of Nontreponemal and Treponemal Antibodies in Patients with Syphilis
Authors: Castro Arnold R. , Esfandiari Javan , Kumar Shailendra , Ashton Matthew , Kikkert Susan E. , Park Mahin M. , Ballard Ronald C.
Published: September 2010

We describe a point-of-care immunochromatographic test for the simultaneous detection of both nontreponemal and treponemal antibodies in the sera of patients with syphilis that acts as both a screening and a confirmatory test. A total of 1,601 banked serum samples were examined by the dual test, and the results were compared to those obtained using a quantitative rapid plasma reagin (RPR) test and the
Treponema pallidum
passive particle agglutination (TP-PA) assay. Compared to the RPR test, the reactive concordance of the dual test nontreponemal line was 98.4% when the RPR titers of sera were ≥1:2 and the nonreactive concordance was 98.6%. Compared to the TP-PA assay, the reactive and nonreactive concordances of the treponemal line were 96.5% and 95.5%, respectively. These results indicate that the dual test could be used for the serological diagnosis of syphilis in primary health care clinics or resource-poor settings and therefore improve rates of treatment where patients may fail to return for their laboratory results.
Mycobacterium neoaurum
and
Mycobacterium bacteremicum
sp. nov. as Causes of Mycobacteremia
Authors: Brown-Elliott Barbara A. , Wallace Richard J. , Petti Cathy A. , Mann Linda Bridge , McGlasson Maria , Chihara Shingo , Smith Geremy L. , Painter Patrick , Hail Daymon , Wilson Rebecca , Simmon Keith E.
Published: September 2010

Reference isolates of
Mycobacterium neoaurum
,
Mycobacterium aurum
, and the nonvalidated species “
Mycobacterium lacticola
” were the focus of two recent molecular taxonomic studies. On the basis of this grouping, we identified 46 clinical pigmented, rapidly growing mycobacterial isolates. By 16S rRNA gene sequencing, only two major taxa were identified:
M. neoaurum
and a previously uncharacterized “
M. neoaurum
-like” group. The
M. neoaurum
-like group exhibited only 99.7% identity to
M. neoaurum
by 16S rRNA gene sequencing and 96.5% identity to
M. neoaurum
by
rpoB
sequencing and was named
M. bacteremicum
. No clinical isolates of
M. aurum
or
M. lacticola
were identified. Of isolates with known sources, 4/8 (50%) of
M. bacteremicum
isolates and 22/34 (65%) of
M. neoaurum
isolates were recovered from blood, and 35% of these were known to be from patients with catheter-related sepsis. MIC and clinical data on these 46 isolates of
M. neoaurum
and
M. bacteremicum
along with a review of 16 previously reported cases of infection with the
M. neoaurum-M. lacticola
group demonstrated that the isolates were highly susceptible to all drugs tested except clarithromycin, and most clinical cases were successfully treated. The clarithromycin resistance suggested the presence of an inducible
erm
gene reported in other species of rapidly growing mycobacteria. Sequencing studies are currently required to identify these two species. Strain ATCC 25791 (originally submitted as an example of
Mycobacterium aurum
) is proposed to be the type strain of
M. bacteremicum
.
Genotyping of
Toxoplasma gondii
Isolates with 15 Microsatellite Markers in a Single Multiplex PCR Assay
Authors: Ajzenberg Daniel , Collinet Frédéric , Mercier Aurélien , Vignoles Philippe , Dardé Marie-Laure
Published: September 2010

We developed an easy-to-use method for genotyping
Toxoplasma gondii
isolates in a single multiplex PCR assay with 15 microsatellite markers. This method was validated by testing 26 reference isolates that had been characterized with other sets of markers.
Mouse Mammary Tumor Virus-Like Nucleotide Sequences in Canine and Feline Mammary Tumors
Authors: Hsu Wei-Li , Lin Hsing-Yi , Chiou Shyan-Song , Chang Chao-Chin , Wang Szu-Pong , Lin Kuan-Hsun , Chulakasian Songkhla , Wong Min-Liang , Chang Shih-Chieh
Published: September 2010

Mouse mammary tumor virus (MMTV) has been speculated to be involved in human breast cancer. Companion animals, dogs, and cats with intimate human contacts may contribute to the transmission of MMTV between mouse and human. The aim of this study was to detect MMTV-like nucleotide sequences in canine and feline mammary tumors by nested PCR. Results showed that the presence of MMTV-like env and LTR sequences in canine malignant mammary tumors was 3.49% (3/86) and 18.60% (16/86), respectively. For feline malignant mammary tumors, the presence of both env and LTR sequences was found to be 22.22% (2/9). Nevertheless, the MMTV-like LTR and env sequences also were detected in normal mammary glands of dogs and cats. In comparisons of the MMTV-like DNA sequences of our findings to those of NIH 3T3 (MMTV-positive murine cell line) and human breast cancer cells, the sequence similarities ranged from 94 to 98%. Phylogenetic analysis revealed that intermixing among sequences identified from tissues of different hosts, i.e., mouse, dog, cat, and human, indicated the MMTV-like DNA existing in these hosts. Moreover, the env transcript was detected in 1 of the 19 MMTV-positive samples by reverse transcription-PCR. Taken together, our study provides evidence for the existence and expression of MMTV-like sequences in neoplastic and normal mammary glands of dogs and cats.
Concurrent Isolation of Chikungunya Virus and Dengue Virus from a Patient with Coinfection Resulting from a Trip to Singapore
Authors: Chang Shu-Fen , Su Chien-Ling , Shu Pei-Yun , Yang Cheng-Fen , Liao Tsai-Ling , Cheng Chia-Hsin , Hu Huai-Chin , Huang Jyh-Hsiung
Published: September 2010

We report two cases of imported infection in patients who had returned to Taiwan from Singapore: one was coinfected with chikungunya virus and dengue virus type 2, and the other was infected with the same dengue virus. Both viruses were successfully isolated from the coinfected case by using antibody neutralization and a plaque purification technique.
Constraints on HIV-1 Diversity from Protein Structure
Authors: Woo Jeongmin , Robertson David L. , Lovell Simon C.
Published: September 2010

The high rate of HIV-1 evolution contributes to immune escape, enables the virus to escape drug therapy, and may underlie the difficulty of producing an effective vaccine. Identifying constraints on HIV evolution is therefore of prime importance. To investigate this problem, we examined the relationships between sequence diversity, selection, and protein structure. We found that while there was an increase in sequence diversity over time, this variation had a tendency to be limited to specific structural regions. When individual sites were analyzed, there was, in contrast, substantial and widespread evolutionary constraint over
gag
and
env
. This constraint was present even in the highly variable envelope proteins. The evolutionary significance of an individual site is indicated by the change in selection pressure along the time course: increasing entropy indicates that the site is evolving predominantly in a more “clock”-like manner, low entropy values with no increase indicate a high degree of constraint, and high entropy values indicate a lack of constraint. Few sites display high degrees of turnover. Mapping these sites onto the three-dimensional protein structure, we found a significant difference between evolutionary rates for regions buried in the core of the protein and those on the surface. This constraint did not change over the time period analyzed and was not subtype dependent, as similar results were found for subtypes B and C. This link between sequence and structure not only demonstrates the limits of recent HIV-1 evolution but also highlights the origins of evolutionary constraint on viral change.
Comparison of E1A CR3-Dependent Transcriptional Activation across Six Different Human Adenovirus Subgroups
Authors: Ablack Jailal N. G. , Pelka Peter , Yousef Ahmed F. , Turnell Andrew S. , Grand Roger J. A. , Mymryk Joe S.
Published: September 2010

The largest E1A isoform of human adenovirus (Ad) includes a C-4 zinc finger domain within conserved region 3 (CR3) that is largely responsible for activating transcription of the early viral genes. CR3 interacts with multiple cellular factors, but its mechanism of action is modeled primarily on the basis of the mechanism for the prototype E1A protein of human Ad type 5. We expanded this model to include a representative member from each of the six human Ad subgroups. All CR3 domains tested were capable of transactivation. However, there were dramatic differences in their levels of transcriptional activation. Despite these functional variations, the interactions of these representative CR3s with known cellular transcriptional regulators revealed only modest differences. Four common cellular targets of all representative CR3s were identified: the proteasome component human Sug1 (hSug1)/S8, the acetyltransferases p300/CREB binding protein (CBP), the mediator component mediator complex subunit 23 (MED23) protein, and TATA binding protein (TBP). The first three factors appear to be critical for CR3 function. RNA interference against human TBP showed no significant reduction in transactivation by any CR3 tested. These results indicate that the cellular factors previously shown to be important for transactivation by Ad5 CR3 are similarly bound by the E1A proteins of other types. This was confirmed experimentally using a transcriptional squelching assay, which demonstrated that the CR3 regions of each Ad type could compete with Ad5 CR3 for limiting factors. Interestingly, a mutant of Ad5 CR3 (V147L) was capable of squelching wild-type Ad5 CR3, despite its failure to bind TBP, MED23, p300/CBP-associated factor (pCAF), or p300/CBP, suggestive of the possibility that an additional as yet unidentified cellular factor is required for transactivation by E1A CR3.
Developing registries of volunteers: key principles to manage issues regarding personal information protection: Figure 1
Authors: Lévesque Emmanuelle , Leclerc Dominic , Puymirat Jack , Knoppers Bartha Maria
Published: September 2010

Much biomedical research cannot be performed without recruiting human subjects. Increasingly, volunteer registries are being developed to assist researchers with this challenging task. Yet, volunteer registries raise confidentiality issues. Having recently developed a registry of volunteers, the authors searched for normative guidance on how to implement the principle of confidentiality. The authors found that the protection of confidentiality in registries are based on the 10 key elements which are elaborated in detail in the Canadian Standards AssociationModel Code. This paper describes how these 10 detailed key principles can be used during the developmental stages of volunteer registries.