bluuebunny/crossref_metadata_2025 huggingface dataset:
The Alzheimer's Disease Neuroimaging Initiative: Annual change in biomarkers and clinical outcomes
Authors: Beckett Laurel A. , Harvey Danielle J. , Gamst Anthony , Donohue Michael , Kornak John , Zhang Hao , Kuo Julie H. ,   Alzheimer's Disease Neuroimaging Initiative
Published: May 2010

Background

The Alzheimer's Disease Neuroimaging Initiative Phase 1 (ADNI‐1) is a multisite prospective study designed to examine potential cerebrospinal fluid and imaging markers of Alzheimer's disease (AD) and their relationship to cognitive change. The objective of this study was to provide a global summary of the overall results and patterns of change observed in candidate markers and clinical measures over the first 2 years of follow‐up.

Methods

Change was summarized for 210 normal controls, 357 mild cognitive impairment, and 162 AD subjects, with baseline and at least one cognitive follow‐up assessment. Repeated measures and survival models were used to assess baseline biomarker levels as predictors. Potential for improving clinical trials was assessed by comparison of precision of markers for capturing change in hypothetical trial designs.

Results

The first 12 months of complete data on ADNI participants demonstrated the potential for substantial advances in characterizing trajectories of change in a range of biomarkers and clinical outcomes, examining their relationship and timing, and assessing the potential for improvements in clinical trial design. Reduced metabolism and greater brain atrophy in the mild cognitive impairment at baseline are associated with more rapid cognitive decline and a higher rate of conversion to AD. Use of biomarkers as study entry criteria or as outcomes could reduce the number of participants required for clinical trials.

Conclusions

Analyses and comparisons of ADNI data strongly support the hypothesis that measurable change occurs in cerebrospinal fluid, positron emission tomography, and magnetic resonance imaging well in advance of the actual diagnosis of AD.
Update on the Magnetic Resonance Imaging core of the Alzheimer's Disease Neuroimaging Initiative
Authors: Jack Clifford R. , Bernstein Matt A. , Borowski Bret J. , Gunter Jeffrey L. , Fox Nick C. , Thompson Paul M. , Schuff Norbert , Krueger Gunnar , Killiany Ronald J. , DeCarli Charles S. , Dale Anders M. , Carmichael Owen W. , Tosun Duygu , Weiner Michael W. ,   Alzheimer's Disease Neuroimaging Initiative
Published: May 2010

Functions of the Alzheimer's Disease Neuroimaging Initiative (ADNI) magnetic resonance imaging (MRI) core fall into three categories: (1) those of the central MRI core laboratory at Mayo Clinic, Rochester, Minnesota, needed to generate high quality MRI data in all subjects at each time point; (2) those of the funded ADNI MRI core imaging analysis groups responsible for analyzing the MRI data; and (3) the joint function of the entire MRI core in designing and problem solving MR image acquisition, pre‐processing, and analyses methods. The primary objective of ADNI was and continues to be improving methods for clinical trials in Alzheimer's disease. Our approach to the present (“ADNI‐GO”) and future (“ADNI‐2,” if funded) MRI protocol will be to maintain MRI methodological consistency in the previously enrolled “ADNI‐1” subjects who are followed up longitudinally in ADNI‐GO and ADNI‐2. We will modernize and expand the MRI protocol for all newly enrolled ADNI‐GO and ADNI‐2 subjects. All newly enrolled subjects will be scanned at 3T with a core set of three sequence types: 3D T1‐weighted volume, FLAIR, and a long TE gradient echo volumetric acquisition for micro hemorrhage detection. In addition to this core ADNI‐GO and ADNI‐2 protocol, we will perform vendor‐specific pilot sub‐studies of arterial spin‐labeling perfusion, resting state functional connectivity, and diffusion tensor imaging. One of these sequences will be added to the core protocol on systems from each MRI vendor. These experimental sub‐studies are designed to demonstrate the feasibility of acquiring useful data in a multicenter (but single vendor) setting for these three emerging MRI applications.
Clinical core of the Alzheimer's disease neuroimaging initiative: Progress and plans
Authors: Aisen Paul S. , Petersen Ronald C. , Donohue Michael C. , Gamst Anthony , Raman Rema , Thomas Ronald G. , Walter Sarah , Trojanowski John Q. , Shaw Leslie M. , Beckett Laurel A. , Jack Clifford R. , Jagust William , Toga Arthur W. , Saykin Andrew J. , Morris John C. , Green Robert C. , Weiner Michael W. ,   Alzheimer's Disease Neuroimaging Initiative
Published: May 2010

The Clinical Core of the Alzheimer's Disease Neuroimaging Initiative (ADNI) has provided clinical, operational, and data management support to ADNI since its inception. This article reviews the activities and accomplishments of the core in support of ADNI aims. These include the enrollment and follow‐up of more than 800 subjects in the three original cohorts: healthy controls, amnestic mild cognitive impairment (now referred to as late MCI, or LMCI), and mild Alzheimer's disease (AD) in the first phase of ADNI (ADNI 1), with baseline longitudinal, clinical, and cognitive assessments. These data, when combined with genetic, neuroimaging, and cerebrospinal fluid measures, have provided important insights into the neurobiology of the AD spectrum. Furthermore, these data have facilitated the development of novel clinical trial designs. ADNI has recently been extended with funding from an NIH Grand Opportunities (GO) award, and the new ADNI GO phase has been launched; this includes the enrollment of a new cohort, called early MCI, with milder episodic memory impairment than the LMCI group. An application for a further 5 years of ADNI funding (ADNI 2) was recently submitted. This funding would support ongoing follow‐up of the original ADNI 1 and ADNI GO cohorts, as well as additional recruitment into all categories. The resulting data would provide valuable data on the earliest stages of AD, and support the development of interventions in these critically important populations.
Addressing population aging and Alzheimer's disease through the Australian Imaging Biomarkers and Lifestyle study: Collaboration with the Alzheimer's Disease Neuroimaging Initiative
Authors: Ellis Kathryn A. , Rowe Christopher C. , Villemagne Victor L. , Martins Ralph N. , Masters Colin L. , Salvado Olivier , Szoeke Cassandra , Ames David ,   AIBL research group
Published: May 2010

The Australian Imaging Biomarkers and Lifestyle (AIBL) study is a longitudinal study of 1112 volunteers from healthy, mild cognitive impairment, and Alzheimer's disease (AD) populations who can be assessed and followed up for prospective research into aging and AD. AIBL aims to improve understanding of the pathogenesis, early clinical manifestation, and diagnosis of AD, and identify diet and lifestyle factors that influence the development of AD. For AIBL, the magnetic resonance imaging parameters of Alzheimer's Disease Neuroimaging Initiative (ADNI) were adopted and the Pittsuburgh compound B (11C‐PiB) positron emission tomography (PET) acquisition and neuropsychological tests were designed to permit comparison and pooling with ADNI data. Differences to ADNI include assessment every 18‐months, imaging in 25% (magnetic resonance imaging, 11C‐PiB PET but no fluorodeoxyglucose PET), more comprehensive neuropsychological testing, and detailed collection of diet and lifestyle data. AIBL has completed the first 18‐month follow‐up and is making imaging and clinical data available through the ADNI website. Cross‐sectional analysis of baseline data is revealing links between cognition, brain amyloid burden, structural brain changes, biomarkers, and lifestyle.
The Alzheimer's Disease Neuroimaging Initiative: Perspectives of the Industry Scientific Advisory Board
Authors: Schmidt Mark E. , Siemers Eric , Snyder Peter J. , Potter William Z. , Cole Patricia , Soares Holly
Published: May 2010

The Industry Scientific Advisory Board (ISAB) consists of representatives from the private companies and nonprofit foundations participating as sponsors of Alzheimer's Disease Neuroimaging Initiative (ADNI). Currently 21 companies are represented including pharmaceutical, imaging, and biotech concerns, and two foundations including the Alzheimer's Association. ISAB members meet regularly by teleconference or face‐to‐face at ADNI meetings and participate in the ADNI Core groups, all administered and organized by the Foundation for the National Institutes of Health. ISAB ‘deliverables' include dissemination of information to sponsors, assisting in scientific review of protocols and results, initiation and consideration of “add‐on” studies and analyses, and generation of consensus positions on industry priorities and concerns. Although positioned as an advisory body, ISAB also actively contributes to the ADNI mission of identifying biomarkers of disease progression.
Alzheimer's Disease Neuroimaging Initiative biomarkers as quantitative phenotypes: Genetics core aims, progress, and plans
Authors: Saykin Andrew J. , Shen Li , Foroud Tatiana M. , Potkin Steven G. , Swaminathan Shanker , Kim Sungeun , Risacher Shannon L. , Nho Kwangsik , Huentelman Matthew J. , Craig David W. , Thompson Paul M. , Stein Jason L. , Moore Jason H. , Farrer Lindsay A. , Green Robert C. , Bertram Lars , Jack Clifford R. , Weiner Michael W. ,   Alzheimer's Disease Neuroimaging Initiative
Published: May 2010

The role of the Alzheimer's Disease Neuroimaging Initiative Genetics Core is to facilitate the investigation of genetic influences on disease onset and trajectory as reflected in structural, functional, and molecular imaging changes; fluid biomarkers; and cognitive status. Major goals include (1) blood sample processing, genotyping, and dissemination, (2) genome‐wide association studies (GWAS) of longitudinal phenotypic data, and (3) providing a central resource, point of contact and planning group for genetics within the Alzheimer's Disease Neuroimaging Initiative. Genome‐wide array data have been publicly released and updated, and several neuroimaging GWAS have recently been reported examining baseline magnetic resonance imaging measures as quantitative phenotypes. Other preliminary investigations include copy number variation in mild cognitive impairment and Alzheimer's disease and GWAS of baseline cerebrospinal fluid biomarkers and longitudinal changes on magnetic resonance imaging. Blood collection for RNA studies is a new direction. Genetic studies of longitudinal phenotypes hold promise for elucidating disease mechanisms and risk, development of therapeutic strategies, and refining selection criteria for clinical trials.
Feline orofacial pain syndrome (FOPS): A retrospective study of 113 cases
Authors: Rusbridge Clare , Heath Sarah , Gunn-Moore Danièlle A. , Knowler Susan Penelope , Johnston Norman , McFadyen Angus Kennedy
Published: May 2010

Feline orofacial pain syndrome (FOPS) is a pain disorder of cats with behavioural signs of oral discomfort and tongue mutilation. This report describes the findings from a case series of 113 cats including 100 Burmese. FOPS is suspected to be a neuropathic pain disorder and the predominance within the Burmese cat breed suggests an inherited disorder, possibly involving central and/or ganglion processing of sensory trigeminal information. The disease is characterised by an episodic, typically unilateral, discomfort with pain-free intervals. The discomfort is triggered, in many cases, by mouth movements. The disease is often recurrent and with time may become unremitting — 12% of cases in this series were euthanased as a consequence of the condition. Sensitisation of trigeminal nerve endings as a consequence of oral disease or tooth eruption appears to be an important factor in the aetiology — 63% of cases had a history of oral lesions and at least 16% experienced their first sign of discomfort during eruption of permanent teeth. External factors can also influence the disease as FOPS events could be directly linked to a situation causing anxiety in 20% of cats. FOPS can be resistant to traditional analgesics and in some cases successful management required anti-convulsants with an analgesic effect.
The Three-Factor Eating Questionnaire and BMI in adolescents: results from the Québec Family Study
Authors: Gallant A. R. , Tremblay A. , Pérusse L. , Bouchard C. , Després J.-P. , Drapeau V.
Published: May 2010

Eating behaviour traits are associated with body weight variations in adults. The Three-Factor Eating Questionnaire (TFEQ) measures cognitive restraint, disinhibition and hunger, as well as their corresponding subscales, e.g. rigid and flexible control. The TFEQ has not been widely used in adolescents to investigate eating behaviour traits associated with body weight. The aim of the present study was to assess whether eating behaviour traits were associated with BMI in male and female adolescents. Sixty adolescents (thirty females and thirty males; mean age 15·0 (sd 2·4) years) from the Québec Family Study completed the TFEQ and 3 d dietary records. There were no sex differences in the TFEQ scores. Rigid control, disinhibition and emotional susceptibility (to overeat) were positively related to BMI z-scores for the entire sample (r 0·3, P < 0·05). There was a positive relationship between BMI z-scores and rigid control (r 0·39, P < 0·05) in females, while BMI z-scores were positively related to emotional susceptibility (r 0·42, P < 0·02) and disinhibition (r 0·41, P < 0·03) in males. Adolescents characterised by both high disinhibition and high rigid control had significantly higher BMI z-scores than those by both low disinhibition and low rigid control. There were no significant differences in BMI z-scores between the flexible control categories. Dietary macronutrient content was not consistently related to eating behaviour traits. These results show that the eating behaviour traits of disinhibition and rigid control are independently related to BMI z-scores in this group of adolescents.
Spatio-temporal evolution of thin Alfven resonance layer
Authors: DMITRIENKO I. S.
Published: May 2010

We describe the spatio-temporal evolution of one-dimensional Alfven resonance disturbance in the presence of various factors of resonance detuning: dispersion and absorption of Alfven disturbance, nonstationarity of large-scale wave generating resonant disturbance. Using analytical solutions to the resonance equation, we determine conditions for forming qualitatively different spatial and temporal structures of resonant Alfven disturbances. We also present analytical descriptions of quasi-stationary and non-stationary spatial structures formed in the resonant layer, and their evolution over time for cases of drivers of different types corresponding to large-scale waves localized in the direction of inhomogeneity and to nonlocalized large-scale waves.
A Preliminary Account of the Production of Annual Rings in the Scales of Plaice and Flounders
Authors: Cutler D. Ward
Published: May 2010

It is only within comparatively recent times that it has been proved that the otoliths and scales of certain Teleostean fish can be used for the determination of their age.

Rings of growth, as they are called, are produced on these structures, and it is by counting the number that the age is ascertained, in much the same way as the approximate age of a tree may be determined by counting the annual rings.
A List of the Maritime, Sub-Maritime and Coast-frequenting Coleoptera of South Devon and South Cornwall, with especial reference to the Plymouth District
Authors: Keys James H.
Published: May 2010

It may perhaps be well to say that by maritime species are meant those Beetles whose habitats are covered by the sea for a considerable time during the flow and ebb of the tide. By sub-maritime species are meant the dwellers at high-tide mark or thereabouts, subjected to occasional wettings by the sea, and the species inhabiting brackish pools and wet places in salt-marshes. The coast species comprise individuals living under stones and rejectamenta, as a rule safe from the reach of high tide, and those peculiar to the roots, leaves and flowers of plants attached to the coast, as well as inhabitants of wooden piles on the shore and the denizens of the ooze of fresh-water trickles on the cliffs—excepting species equally obtainable inland.
The older, the lonelier? Risk factors for social loneliness in old age
Authors: HEYLEN LEEN
Published: May 2010

Loneliness is often associated with old age, but many studies have shown that the relationship is not straightforward. This paper seeks a better understanding of the impact of social isolation on feelings of loneliness among older people, by building on the theoretical and actual distinction between social and emotional loneliness. Social loneliness refers to a lack of feelings of social integration; emotional loneliness emerges in the absence of an attachment figure. This paper focuses on social loneliness and has two aims, first to disentangle the direct and intermediate effects of both the number and the quality of social relationships on social loneliness in old age, and second to detect the groups at risk of social loneliness by identifying which personal features correspond with which relational deficits and therefore indirectly increase the risk on social loneliness. Data are analysed for a sample of 1,414 respondents aged 55 or more years drawn from the Panel Study of Belgian Households conducted in 2000. The results confirm that improved understanding is gained by decomposing the interrelation between age and other background features, on the one hand, and the social relational features, on the other, as indirect and direct predictors of social loneliness. Generally, this approach promotes a correct identification of the groups at risk of social loneliness in old age.
Origin, evolution and paleoepidemiology of brucellosis
Authors: D'ANASTASIO R. , STANISCIA T. , MILIA M. L. , MANZOLI L. , CAPASSO L.
Published: May 2010

Brucellosis is a worldwide disease. Although it has been eradicated in some countries, it continues to be an important disease in many farming areas. Previous works have described the evolution and diffusion of brucellosis in antiquity through direct analysis of ancient human remains collected by the University Museum of Chieti, Italy, and by using paleopathological and historical data. The earliest published case was reported in a skeletal individual dated to the Middle Bronze Age. However, our research group has diagnosed vertebral brucellosis in the partial skeleton of the late PlioceneAustralopithecus africanus, demonstrating that this infectious disease occasionally affected our direct ancestors 2·3–2·5 million years ago. The frequency of brucellosis increased during the Roman period, when the disease would almost certainly have been endemic in Roman society, and during the Middle Ages. Most paleopathological cases involve adult male skeletal individuals, and lumbar vertebrae and sacroiliac joints are most commonly involved.
The emblem that cried wolf: ICRC study on the use of the emblems
Authors: Rolle Baptiste , Lafontaine Edith
Published: May 2010

The ICRC Study on Operational and Commercial and Other Non-operational Issues Involving the Use of the Emblems (‘the Emblem Study’) is an efficient and user-friendly tool to tackle issues regarding the use of the emblems of the red cross, red crescent, and red crystal. This article presents the Emblem Study's origin and objectives, and explains the structure and the methodology followed in its preparation. Recurrent questions regarding joint use of emblems and other signs are also examined, in order to demonstrate the Emblem Study's potential as an analytical and practical tool. Particular emphasis is placed on the need to avoid diluting the protective value of the emblems by maintaining a distinction between those entitled to use the emblems, their partners, and other players in the humanitarian field.
Climate‐dependent CO2 emissions from lakes
Authors: Kosten Sarian , Roland Fábio , Da Motta Marques David M. L. , Van Nes Egbert H. , Mazzeo Néstor , Sternberg Leonel da S. L. , Scheffer Marten , Cole Jon J.
Published: May 2010

Inland waters, just as the world's oceans, play an important role in the global carbon cycle. While lakes and reservoirs typically emit CO2, they also bury carbon in their sediment. The net CO2 emission is largely the result of the decomposition or preservation of terrestrially supplied carbon. What regulates the balance between CO2 emission and carbon burial is not known, but climate change and temperature have been hypothesized to influence both processes. We analyzed patterns in carbon dioxide partial pressure (pCO2) in 83 shallow lakes over a large climatic gradient in South America and found a strong, positive correlation with temperature. The higher pCO2 in warmer lakes may be caused by a higher, temperature‐dependent mineralization of organic carbon. This pattern suggests that cool lakes may start to emit more CO2 when they warm up because of climate change.
Analysis of UV flashes of millisecond scale detected by a low‐orbit satellite
Authors: Shneider Mikhail N. , Milikh Gennady M.
Published: May 2010

The microsatellite Tatiana recently detected two scales of the UV flash duration: 1–4 ms and 10–64 ms. This paper studies the atmospheric electricity phenomena that can serve as a source for short‐millisecond‐range flashes. It is shown that UV flashes in the millisecond scale detected by Tatiana may be explained as generated by gigantic blue jets (GBJ). The influence of an assumed self‐consistent governing electric field in the GBJ streamer zone on the UV pulse shape and duration is revealed. It is also shown that red sprites can be a source for UV flashes with similar temporal profiles but at much lower intensity. The model results are also compared with the observations made by the Imager of Sprites and Upper Atmospheric Lightnings imager on board the FORMOSAT‐2 satellite.
Program of transient UV event research at Tatiana‐2 satellite
Authors: Garipov G. K. , Khrenov B. A. , Klimov P. A. , Morozenko V. S. , Panasyuk M. I. , Petrova S. N. , Tulupov V. I. , Shahparonov V. M. , Svertilov S. I. , Vedenkin N. N. , Yashin I. V. , Jeon J. A. , Jeong S. M. , Jung A. R. , Kim J. E. , Lee J. , Lee H. Y. , Na G. W. , Nam J. W. , Nam S. , Park I. H. , Suh J. E. , Jin J. Y. , Kim M. , Kim Y. K. , Yoo B. W. , Park Y.‐S. , Yu H. J. , Lee C.‐H. , Park J. H. , Salazar H. I. , Martinez O. B. , Ponce E. L. , Cotsomi J. P.
Published: May 2010

In a new Tatiana‐2 mission the measurement of transient luminous events (TLE) in the Earth atmosphere in nadir direction are planned. Near UV temporal images of TLE in millisecond scale will be measured together with temporal profiles in 8 channels of wide spectrum of TLE emission. Simultaneously temporal variation of electron flux at the satellite orbit will be measured. Aims of these measurements are to continue research of bright UV flashes, started in the Tatiana‐1 mission (Universitetsky–Tatiana satellite), their global distribution, their rate over oceans and continents, and their possible correlation with lunar phase. Special attention will be paid to search for correlation between UV flashes from the atmosphere and variations of electron flux in the atmosphere‐magnetosphere system.
Geochronological evidence for continuous exhumation through the ductile‐brittle transition along a crustal‐scale low‐angle normal fault: Simplon Fault Zone, central Alps
Authors: Campani M. , Mancktelow N. , Seward D. , Rolland Y. , Müller W. , Guerra I.
Published: May 2010

Major low‐angle normal faults juxtapose different structural levels of the crust that record both brittle and ductile deformation. Field relationships alone cannot establish whether these different responses to deformation represent (1) parts of a single process of exhumation along the detachment or (2) two separate events, with the later, more discrete brittle detachment exhuming a fossil ductile shear zone from depth. These two general models are critically assessed for the low‐angle normal Simplon Fault Zone (SFZ) in the central Alps. The SFZ shows a spatial transition from a broad ductile mylonitic shear zone to a discrete brittle detachment with identical kinematics. The age of the ductile shear zone and ductile‐brittle transition is controversial. We present a detailed geochronological study based on fission track, 40Ar/39Ar, and Rb/Sr microsampling dating, coupled with structural, petrological, and chemical analyses that provides tight constraints on SFZ timing. Discontinuous mineral cooling ages over a broad range of temperatures across the fault zone argue for fault activity between 20 and 3 Ma. On the basis of synkinematic white mica in low‐temperature shear zones and necks of foliation boudinage, the brittle‐ductile transition in the footwall could be dated at ∼14.5–10 Ma. Overall, the data presented here are consistent with a continuous transition from ductile shearing to a more localized zone of brittle deformation within the same geological framework, over a period of ∼15 Ma. The SFZ is therefore an example of a telescoped crustal section within a single major low‐angle fault, involving a continuous period of exhumation rather than a two‐stage structure.
Biological Response to Recent Pacific Arctic Sea Ice Retreats
Authors: Grebmeier Jacqueline M. , Moore Sue E. , Overland James E. , Frey Karen E. , Gradinger Rolf
Published: May 2010

Although recent major changes in the physical domain of the Arctic region, such as extreme retreats of summer sea ice since 2007, are well documented, large uncertainties remain regarding responses in the biological domain. In the Pacific Arctic north of Bering Strait, reduction in sea ice extent has been seasonally asymmetric, with minimal changes until the end of June and delayed sea ice formation in late autumn. The effect of extreme ice retreats and seasonal asymmetry in sea ice loss on primary production is uncertain, with no clear shift over time (2003–2008) in satellite‐derived chlorophyll concentrations. However, clear changes have occurred during summer in species ranges for zooplankton, bottom‐dwelling organisms (benthos), and fish, as well as through the loss of sea ice as habitat and platform for marine mammals.
Reply to Comment on “The Prediction of Two Large Earthquakes in Greece”
Authors: Uyeda Seiya , Kamogawa Masashi
Published: May 2010

We welcome the critical comments of Papadopoulos [2010]. We must point out, however, that most of them are incorrect.

First, on 1 February 2008, P. A. Varotsos et al. (Seismic electric signals and 1/f “noise” in natural time, version 3, 2008; available at http://arxiv.org/abs/0711.3766v3) did document the seismic electric signal (SES) activity for the M 6—class earthquake, recorded at station PIR (one of the SES measuring stations located close to Pirgos city in western Greece) on 14 January 2008, and assigned the epicentral area (approximately 250 × 250 kilometers). Two weeks after the documentation, the Mw 6.9 Greek earthquake in question occurred, on 14 February 2008. As to the occurrence time of this earthquake, the newspaper Ethnos on 10 February 2008 (http://www.ethnos.gr/article.asp?catid=11424&subid2&tag=8777&pubid=444473) reported it as “imminent.” Second, we did not mention two relatively small Patras shocks on 4 February 2008 simply because VAN also documented them (P. A. Varotsos et al., 2008, version 3) based on separate SES activity recorded on 10 January 2008 at Patras.
Improving Understanding of the Agulhas Current and Its Global Climate Impacts: Working Group on the Climatic Importance of the Greater Agulhas System; Portland, Oregon, 20–21 February 2010
Authors: Beal Lisa , Biastoch Arne
Published: May 2010

The first meeting of the new Scientific Committee on Oceanic Research (SCOR) Working Group 136 was held to discuss recent developments in understanding the greater Agulhas Current system and future research directions. The overarching goal of the working group is to improve understanding and awareness of the regional and global climate impacts of the Agulhas Current, a major western boundary current that flows along the east coast of Africa, and its interocean leakage.

In addition to studying modern circulation, the working group is motivated by recent paleodata that suggest that through the currents' southern influence on the Atlantic meridional overturning circulation (AMOC), changes in the leakage of warm and salty Agulhas waters into the Atlantic may have triggered the end of ice ages. In terms of global climate, this arguably puts the importance of the greater Agulhas system on a par with Heinrich (land‐ice release) events and high‐latitude deepwater formation.
Congratulations to AGU's 50‐ and 25‐Year Members in 2010
Authors: Anonymous
Published: May 2010

Please join us in congratulating 889 AGU members who achieved milestones of 50 and 25 consecutive years of membership in 2010. As a token of our appreciation and to honor their dedication and support of our organization, gold (50‐year) or silver (25‐year) lapel pins with AGU's logo recently were sent from AGU president Tim Grove to the members listed below. Grove stated, “Through the commitment of members like you, AGU has become one of the leading scientific societies in the world.” —April Orr, Director, Marketing and Membership, AGU
SOX5 controls cell cycle progression in neural progenitors by interfering with the WNT–β‐catenin pathway
Authors: Martinez‐Morales Patricia L , Quiroga Alejandra C , Barbas Julio A , Morales Aixa V
Published: May 2010

Genes of the SOX family of high‐mobility group transcription factors are essential during nervous system development. In this study, we show that SOX5 is expressed by neural progenitors in the chick spinal cord and is turned off as differentiation proceeds. The overexpression of SOX5 in neural progenitors causes premature cell cycle exit and prevents terminal differentiation. Conversely, knocking down SOX5 protein extends the proliferative period of neural progenitors and causes marked cell death in a dorsal interneuron (dI3) population. Furthermore, SOX5 reduces WNT–β‐catenin signalling, thereby triggering the expression of the negative regulator of the pathway axin2. We propose that SOX5 regulates the timing of cell cycle exit by opposing WNT–β‐catenin activity on cell cycle progression.
PELP1 is a reader of histone H3 methylation that facilitates oestrogen receptor‐α target gene activation by regulating lysine demethylase 1 specificity
Authors: Nair Sujit S , Nair Binoj C , Cortez Valerie , Chakravarty Dimple , Metzger Eric , Schüle Roland , Brann Darrell W , Tekmal Rajeshwar R , Vadlamudi Ratna K
Published: May 2010

Histone methylation has a key role in oestrogen receptor (ERα)‐mediated transactivation of genes. Proline glutamic acid and leucine‐rich protein 1 (PELP1) is a new proto‐oncogene that functions as an ERα co‐regulator. In this study, we identified histone lysine demethylase, KDM1, as a new PELP1‐interacting protein. These proteins, PELP1 and KDM1, were both recruited to ERα target genes, and PELP1 depletion affected the dimethyl histone modifications at ERα target genes. Dimethyl‐modified histones H3K4 and H3K9 are recognized by PELP1, and PELP1 alters the substrate specificity of KDM1 from H3K4 to H3K9. Effective demethylation of dimethyl H3K9 by KDM1 requires a KDM1–ERα–PELP1 functional complex. These results suggest that PELP1 is a reader of H3 methylation marks and has a crucial role in modulating the histone code at the ERα target genes.
Consent to ‘personal’ genomics and privacy
Authors: Knoppers Bartha Maria
Published: May 2010

Direct‐to‐consumer genetic testing and population genome research projects challenge traditional notions of privacy and consent that were originally developed for clinical research. Bartha Maria Knoppers analyses the implications and proposes new approaches to govern both population‐based genome research and commercial direct‐to‐consumer genetic tests.
Sterol-regulatory-element-binding protein 2 and nuclear factor Y control human farnesyl diphosphate synthase expression and affect cell proliferation in hepatoblastoma cells
Authors: Ishimoto Kenji , Tachibana Keisuke , Hanano Ikuko , Yamasaki Daisuke , Nakamura Hiroki , Kawai Megumi , Urano Yasuomi , Tanaka Toshiya , Hamakubo Takao , Sakai Juro , Kodama Tatsuhiko , Doi Takefumi
Published: May 2010

FDPS (farnesyl diphosphate synthase) catalyses the formation of farnesyl diphosphate, a key intermediate in the synthesis of cholesterol and isoprenylated cellular metabolites. FDPS is also the molecular target of nitrogen-containing bisphosphonates, which are used as bone-antiresorptive drugs in various disorders. In the present study, we characterized the sterol-response element and NF-Y (nuclear factor Y)-binding site in the human FDPS promoter. Using a luciferase assay, electrophoretic mobility-shift assay and chromatin immunoprecipitation assay, we demonstrated that these elements are responsible for the transcription of the FDPS gene, and that its transcriptional activation is mediated by SREBP-2 (sterol-regulatory-element-binding protein 2) and NF-Y. We also investigated whether sterol-mediated FDPS expression is involved in the cell proliferation induced by zoledronic acid, an FDPS inhibitor. We show that the SREBP-2- and NF-Y-mediated regulation of FDPS gene transcription modulates cell proliferation. These results suggest that SREBP-2 and NF-Y are required to trigger cell proliferation through the induction of FDPS expression and that the pharmacological action of zoledronic acid is involved in this pathway.
Pleiotropic mechanisms facilitated by resveratrol and its metabolites
Authors: Calamini Barbara , Ratia Kiira , Malkowski Michael G. , Cuendet Muriel , Pezzuto John M. , Santarsiero Bernard D. , Mesecar Andrew D.
Published: May 2010

Resveratrol has demonstrated cancer chemopreventive activity in animal models and some clinical trials are underway. In addition, resveratrol was shown to promote cell survival, increase lifespan and mimic caloric restriction, thereby improving health and survival of mice on high-calorie diet. All of these effects are potentially mediated by the pleiotropic interactions of resveratrol with different enzyme targets including COX-1 (cyclo-oxygenase-1) and COX-2, NAD+-dependent histone deacetylase SIRT1 (sirtuin 1) and QR2 (quinone reductase 2). Nonetheless, the health benefits elicited by resveratrol as a direct result of these interactions with molecular targets have been questioned, since it is rapidly and extensively metabolized to sulfate and glucuronide conjugates, resulting in low plasma concentrations. To help resolve these issues, we tested the ability of resveratrol and its metabolites to modulate the function of some known targets in vitro. In the present study, we have shown that COX-1, COX-2 and QR2 are potently inhibited by resveratrol, and that COX-1 and COX-2 are also inhibited by the resveratrol 4′-O-sulfate metabolite. We determined the X-ray structure of resveratrol bound to COX-1 and demonstrate that it occupies the COX active site similar to other NSAIDs (non-steroidal anti-inflammatory drugs). Finally, we have observed that resveratrol 3- and 4′-O-sulfate metabolites activate SIRT1 equipotently to resveratrol, but that activation is probably a substrate-dependent phenomenon with little in vivo relevance. Overall, the results of this study suggest that in vivo an interplay between resveratrol and its metabolites with different molecular targets may be responsible for the overall beneficial health effects previously attributed only to resveratrol itself.
Conformational flexibility and allosteric regulation of cathepsin K
Authors: Novinec Marko , Kovačič Lidija , Lenarčič Brigita , Baici Antonio
Published: May 2010

The human cysteine peptidase cathepsin K is a key enzyme in bone homoeostasis and other physiological functions. In the present study we investigate the mechanism of cathepsin K action at physiological plasma pH and its regulation by modifiers that bind outside of the active site. We show that at physiological plasma pH the enzyme fluctuates between multiple conformations that are differently susceptible to macromolecular inhibitors and can be manipulated by varying the ionic strength of the medium. The behaviour of the enzyme in vitro can be described by the presence of two discrete conformations with distinctive kinetic properties and different susceptibility to inhibition by the substrate benzyloxycarbonyl-Phe-Arg-7-amino-4-methylcoumarin. We identify and characterize sulfated glycosaminoglycans as natural allosteric modifiers of cathepsin K that exploit the conformational flexibility of the enzyme to regulate its activity and stability against autoproteolysis. All sulfated glycosaminoglycans act as non-essential activators in assays using low-molecular-mass substrates. Chondroitin sulfate and dermatan sulfate bind at one site on the enzyme, whereas heparin binds at an additional site and has a strongly stabilizing effect that is unique among human glycosaminoglycans. All glycosaminoglycans stimulate the elastinolytic activity of cathepsin K at physiological plasma pH, but only heparin also increases the collagenolytic activity of the enzyme under these conditions. Altogether these results provide novel insight into the mechanism of cathepsin K function at the molecular level and its regulation in the extracellular space.
HSG cells, a model in the submandibular clock
Authors: Onishi Yoshiaki
Published: May 2010

Circadian rhythm of vital processes is essential to health, and various tissues show unique peripheral rhythms. HSG is the human submandibular gland cell line that has been used for analysing the effects of steroids and growth factors. In the present study, we analysed the transcriptional regulation of the BMAL1 gene, a critical component of the mammalian clock system to investigate the possibility of using HSG cells as a model system of the submandibular clock. The BMAL1 gene was expressed with circadian oscillation after stimulation with dexamethasone, and its regulatory region contained two recognition motifs for ROR (retinoic acid-receptor-related orphan receptor) and ROREs [RORα (ROR α-subunit)-binding elements] in hypomethylated CpG islands with an open chromatin structure. REV-ERBα was expressed with circadian oscillation, and knockdown experiments suggested that REV-ERBα is involved in circadian transcription of the BMAL1 gene in HSG cells. These results are similar to those in NIH 3T3 cells, a standard model for the circadian system, whereas RORα required for REV-ERBα antagonism was expressed very little in HSG cells. These findings show that in the salivary gland cell line HSG there is a rhythm in the core oscillator components BMAL1 and REV-ERBα, indicating that circadian-based transcriptional regulation can be modelled in this peripheral cell type.
ChIP (chromatin immunoprecipitation) analysis demonstrates co‐ordinated binding of two transcription factors to the promoter of the p53 tumour‐suppressor gene
Authors: Polson Amanda , Takahashi Paula , Reisman David
Published: May 2010

p53 is a tumour‐suppressor protein that plays a role in many cellular processes, including regulation of the cell cycle, DNA repair, transcriptional regulation of genes, chromosomal segregation, cell senescence and apoptosis. The protein's role as a transcription factor has shown that deregulated transcription, whether increased or decreased, has the potential to contribute to the formation of human cancers. It was previously reported that binding of two transcription factors, C/EBPβ and RBP‐Jκ, to a regulatory site on the p53 promoter regulates its activity, in vitro, in a cell cycle‐dependent manner. C/EBPβ is a CCAAT enhancer‐binding protein that is a member of the basic leucine zipper transcription factor (bZIP) family that plays an important role in mediating cell proliferation, differentiation and can also be involved in inflammatory responses, metabolism, cellular transformation, oncogene‐induced senescence and tumorigenesis. RBP‐Jκ participates in the transcriptional regulation of target genes by interacting with the cytoplasmic domain of the Notch receptors. When RBP‐Jκ is released, transcriptional repression of its target genes occurs through the recruitment of co‐repressor complexes and prevents transcription from occurring. Our reports, here and previously published, show that repression of p53 by RBP‐Jκ and activation of p53 by C/EBPβ through differential binding of these two factors indicates a type of co‐operative regulation in p53 expression. Here, we demonstrate through the use of chromatin immunoprecipitation (ChIP) assays that the co‐ordinated binding of these two factors to the p53 promoter occurs in vivo and serves to regulate p53's activity during the cell cycle.
Angiotensin II and the ERK pathway mediate the induction of myocardin by hypoxia in cultured rat neonatal cardiomyocytes
Authors: Chiu Chiung-Zuan , Wang Bao-Wei , Chung Tun-Hui , Shyu Kou-Gi
Published: May 2010

Hypoxic injury to cardiomyocytes is a stress that causes cardiac pathology through cardiac-restricted gene expression. SRF (serum-response factor) and myocardin are important for cardiomyocyte growth and differentiation in response to myocardial injuries. Previous studies have indicated that AngII (angiotensin II) stimulates both myocardin expression and cardiomyocyte hypertrophy. In the present study, we evaluated the expression of myocardin and AngII after hypoxia in regulating gene transcription in neonatal cardiomyocytes. Cultured rat neonatal cardiomyocytes were subjected to hypoxia, and the expression of myocardin and AngII were evaluated. Different signal transduction pathway inhibitors were used to identify the pathway(s) responsible for myocardin expression. An EMSA (electrophoretic mobility-shift assay) was used to identify myocardin/SRF binding, and a luciferase assay was used to identify transcriptional activity of myocardin/SRF in neonatal cardiomyocytes. Both myocardin and AngII expression increased after hypoxia, with AngII appearing at an earlier time point than myocardin. Myocardin expression was stimulated by AngII and ERK (extracellular-signal-regulated kinase) phosphorylation, but was suppressed by an ARB (AngII type 1 receptor blocker), an ERK pathway inhibitor and myocardin siRNA (small interfering RNA). AngII increased both myocardin expression and transcription in neonatal cardiomyocytes. Binding of myocardin/SRF was identified using an EMSA, and a luciferase assay indicated the transcription of myocardin/SRF in neonatal cardiomyocytes. Increased BNP (B-type natriuretic peptide), MHC (myosin heavy chain) and [3H]proline incorporation into cardiomyocytes was identified after hypoxia with the presence of myocardin in hypertrophic cardiomyocytes. In conclusion, hypoxia in cardiomyocytes increased myocardin expression, which is mediated by the induction of AngII and the ERK pathway, to cause cardiomyocyte hypertrophy. Myocardial hypertrophy was identified as an increase in transcriptional activities, elevated hypertrophic and cardiomyocyte phenotype markers, and morphological hypertrophic changes in cardiomyocytes.
Rigid body dynamics approach to Stokesian dynamics simulations of nonspherical particles
Authors: Kutteh Ramzi
Published: May 2010

We describe an algorithm for performing Stokesian dynamics (SD) simulations of suspensions of arbitrary shape rigid particles with hydrodynamic interactions, modeled as rigid groups of spheres, the hydrodynamic mobility matrix of which is accurately computable by several established schemes for spheres. The algorithm is based on Stokesian rigid body equations of translational and rotational motion, which we have derived by an approach formally analogous to that of Newtonian rigid body dynamics. Particle orientation is represented in terms of Euler parameters (quaternion of rotation). This rigid body SD algorithm (RBSDA) complements recently described constraint SD algorithms [R. Kutteh, J. Chem. Phys. 119, 9280 (2003); R. Kutteh, Phys. Rev. E 69, 011406 (2004)], over which it offers the same computational advantages in imposing total rigidity that the basic rigid body molecular dynamics (MD) algorithm offers over constraint MD algorithms. We show that SD simulation results generated with the RBSDA, in bounded and unbounded geometries, agree very well with those from experiment and other SD and non-SD methods, and are numerically identical to those from a constraint SD algorithm, HSHAKE. Finally, for completeness we also describe a third (additional to the constraint SD and rigid body SD approaches) more traditional approach for SD simulations of arbitrary shape rigid particles modeled as rigid groups of spheres.
Structure and activity relationship for CO and O2 adsorption over gold nanoparticles using density functional theory and artificial neural networks
Authors: Davran-Candan Tuğba , Günay M. Erdem , Yıldırım Ramazan
Published: May 2010

In this work, the structure and activity relationship for CO and O2 adsorption over Au2 to Au10 clusters was investigated using density functional theory (DFT) and artificial neural networks as a part of ongoing studies in the literature to understand CO oxidation over gold nanoparticles. The optimum structures for the anionic, neutral, and cationic clusters were determined first using DFT. The structural properties such as binding energy, highest occupied molecular orbital-lowest unoccupied molecular orbital gap, ionization potential, and electron affinity as well as the adsorption energies of CO and O2 were calculated using the same method at various values of user defined descriptors such as the size and charge of the cluster, the presence or absence of unpaired electron, and the coordination number of the adsorption site. Then, artificial neural network models were constructed to establish the relationship between these descriptors and the structural properties, as well as between the structural properties and the adsorption energies. It was concluded that the neural network models can successfully predict the adsorption energies calculated using DFT. The statistically determined relative significances of user defined descriptors and the structural properties on the adsorption energies were also found to be in good agreement with the literature indicating that this approach may be used for the other catalytic systems as well.
Significant static pressure increase in a precompression cell target for laser-driven advanced dynamic compression experiments
Authors: Kimura T. , Ozaki N. , Okuchi T. , Terai T. , Sano T. , Shimizu K. , Sano T. , Koenig M. , Hirose A. , Kakeshita T. , Sakawa Y. , Kodama R.
Published: May 2010

Laser shock compression experiments on precompressed samples offer the possibility to explore extreme material states unreachable by static or single-shock compression techniques alone. We have found significant increases in static compression pressure in a wide-opening and thin diamond precompression cell. This suggests that the precompression target is adaptable to advanced coupling techniques with laser-driven dynamic compression methods. The novel coupling techniques proposed give the potential to access outstanding material states required in planetary and condensed-matter physics.
Single and repetitive short-pulse high-power microwave window breakdown
Authors: Chang C. , Shao H. , Chen C. H. , Tang C. X. , Huang W. H.
Published: May 2010

The mechanisms of high-power microwave breakdown for single and repetitive short pulses are analyzed. By calculation, multipactor saturation with electron density much higher than the critical plasma density is found not to result in microwave cutoff. It is local high pressure about Torr class that rapid plasma avalanche and final breakdown are realized in a 10–20 ns short pulse. It is found by calculation that the power deposited by saturated multipactor and the rf loss of protrusions are sufficient to induce vaporizing surface material and enhancing the ambient pressure in a single short pulse. For repetitive pulses, the accumulation of heat and plasma may respectively carbonize the surface material and lower the repetitive breakdown threshold.