bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic Effects of Psychological Autopsies
Authors: Henry Melissa , Greenfield Brian J.
Published: January 2009

Background. Several authors have observed a therapeutic impact of the psychological autopsy on the interviewee, although they do not explicitly define what aspects of the process were helpful. Aims. This article aims to identify these therapeutic effects and to discuss their potential impact on participants narratives. Methods. This article derives from 35 psychological autopsy interviews that were conducted to better understand adolescent and young adult suicide. Interviews lasted approximately 6 to 8 h each and consisted of both a battery of questionnaires and open-ended questions. They were mostly conducted with the families of the deceased, including parents and siblings, and on occasion were done with a single family member or friend. The time elapsed since the suicide ranged from 6 to 18 months. Results. Psychological autopsies were helpful to interviewees in allowing them to find meaning in the suicide, to find purpose through their altruistic participation, to obtain psychological support, to experience connectedness with others, to accept the loss as real, and to gain insight into their functioning. Negative reactions to the interviews, albeit uncommon, are also briefly described. Conclusions. We recommend that interviewers receive preparatory training and ongoing supervision while conducting interviews, to assure a reflective and professional stance.
Can Postvention Be Prevention?
Authors: Andriessen Karl
Published: January 2009

Background. There has been recent interest in postvention activities which involve provision of support to family members and others affected by a suicide death. Aims. To review the current status of postvention support, including definitions used and the objectives and effectiveness of support activities for people bereaved by suicide. Methods. Selected controlled studies of support activities and programs are reviewed with narrative comment. Results. Not applicable. Conclusions. Effective postvention support can be viewed as contributing toward suicide prevention among those people who are bereaved by suicide. Further development of support programs is needed.
Optimistic Explanatory Style as a Moderator of the Association Between Negative Life Events and Suicide Ideation
Authors: Hirsch Jameson K. , Wolford Karen , LaLonde Steven M. , Brunk Lisa , Parker-Morris Amanda
Published: January 2009

Background: Individuals experiencing negative and potentially traumatic life events are at increased risk for suicidal thoughts and behaviors; however, suicidal outcomes are not inevitable. Individuals who attribute negative life events to external, transient, and specific factors, rather than internal, stable, and global self-characteristics, may experience fewer deleterious outcomes, including suicidal behavior. Aims: This study examines the moderating effect of explanatory style on the relationship between negative life experiences and suicide ideation in a college student sample. Methods: A total of 138 participants (73% female) were recruited from a rural, Eastern college and completed a self-report psychosocial assessment. Results: Optimistic explanatory style mitigates the influence of negative and potentially traumatic life events on thoughts of suicide, above and beyond the effects of hopelessness and depression. Conclusions: Beliefs about the origin, pervasiveness, and potential recurrence of a negative life event may affect psychological outcomes. Optimistic explanatory style was associated with reduced suicide ideation, whereas pessimistic explanatory style was associated with increased thoughts of suicide. Optimistic reframing of negative life events for clients may have treatment implications for the prevention of suicidal activity.
Managing Multiple Roles
Authors: Wierda-Boer Hilde H. , Gerris Jan R.M. , Vermulst Ad A.
Published: January 2009

Today many parents have multiple roles. This study examined how personality, domain-specific stress, and work-family interference are interrelated. Questionnaire data of 276 Dutch dual-earner couples with young children were analyzed using structural equation modeling. Findings demonstrated that job stress and parenting stress were positively related to work-to-family conflict and family-to-work conflict, respectively. For women, additionally, family-to-work conflict was strongly associated with increased levels of job stress. Finally, emotional stability functioned as an indirect predictor of work-family interference by decreasing the levels of job stress and parenting stress for both genders, but in distinctive ways. The use of couple data and inclusion of personality showed a valuable extension of existing models linking work and family.
Validation of TRMM precipitation radar monthly rainfall estimates over Brazil
Authors: Franchito Sergio H. , Rao V. Brahmananda , Vasques Ana C. , Santo Clovis M. E. , Conforte Jorge C.
Published: January 2009

In an attempt to validate the Tropical Rainfall Measuring Mission (TRMM) precipitation radar (PR) over Brazil, TRMM PR estimates are compared with rain gauge station data from Agência Nacional de Energia Elétrica (ANEEL). The analysis is conducted on a seasonal basis and considers five geographic regions with different precipitation regimes. The results showed that TRMM PR seasonal rainfall is well correlated with ANEEL rainfall (correlation coefficients are significant at the 99% confidence level) over most of Brazil. The random and systematic errors of TRMM PR are sensitive to seasonal and regional differences. During December to February and March to May, TRMM PR rainfall is reliable over Brazil. In June to August (September to November) TRMM PR estimates are only reliable in the Amazonian and southern (Amazonian and southeastern) regions. In the other regions the relative RMS errors are larger than 50%, indicating that the random errors are high.
A synoptic view of solar transient evolution in the inner heliosphere using the Heliospheric Imagers on STEREO
Authors: Davies J. A. , Harrison R. A. , Rouillard A. P. , Sheeley N. R. , Perry C. H. , Bewsher D. , Davis C. J. , Eyles C. J. , Crothers S. R. , Brown D. S.
Published: January 2009

By exploiting data from the STEREO/heliospheric imagers (HI) we extend a well‐established technique developed for coronal analysis by producing time‐elongation plots that reveal the nature of solar transient activity over a far more extensive region of the heliosphere than previously possible from coronagraph images. Despite the simplicity of these plots, their power in demonstrating how the plethora of ascending coronal features observed near the Sun evolve as they move antisunward is obvious. The time‐elongation profile of a transient tracked by HI can, moreover, be used to establish its angle out of the plane‐of‐the‐sky; an illustration of such analysis reveals coronal mass ejection material that can be clearly observed propagating out to distances beyond 1AU. This work confirms the value of the time‐elongation format in identifying/characterising transient activity in the inner heliosphere, whilst also validating the ability of HI to continuously monitor solar ejecta out to and beyond 1AU.
Evidence for coseismic and aseismic uplift in the last 1000 years in the focal area of a shallow thrust earthquake on the Noto Peninsula, west‐central Japan
Authors: Shishikura Masanobu , Echigo Tomoo , Namegaya Yuichi
Published: January 2009

Raised shorelines on the Noto Peninsula on the western coast of central Japan suggest a millennial history of recurrent uplift. Emergence of the coastline by up to 50 cm was recently recorded in association with a moderate earthquake (Mw 6.7) on 25 March 2007. The shoreline uplift is indicated by the displacement of sessile organisms such as calcareous tubeworms, which can also be examined as indicators of past shifts in shoreline level. Three levels of pre‐2007 paleo‐shorelines are thus identified on this stretch of the Japan Sea coast. The lowest of these, dated at AD 1720–1950, tilts northward away from the likely source of a pair of ca. M 6.4 earthquakes in 1892, which occurred in a different area to the 2007 earthquake. The middle paleo‐shoreline, dated at AD 1430–1655, records a 30–40 cm emergence that may be aseismic. The high paleo‐shoreline, dated at AD 1025–1235, records a coseismic uplift of 50 cm and is limited to the area raised coseismically in 2007. The most recent event preceding the 2007 earthquake thus appears to have occurred approximately 1000 years ago.
Theoretical model of rainfall in tropical cyclones for the assessment of long‐term risk
Authors: Langousis Andreas , Veneziano Daniele
Published: January 2009

We propose a theoretical model to evaluate the rainfall intensity field due to large‐scale horizontal wind convergence in tropical cyclones (TCs). The model is intended as one component of a methodology to assess the risk of extreme rainfall intensities from TCs. The other components are a recurrence relation for the model parameters and track and a statistical representation of the deviations of rainfall intensity from model predictions. The latter are primarily caused by rainbands and local convective activity and are the focus of an upcoming communication. The vertical flux of moisture and the associated surface rain rate are calculated using basic thermodynamics and a simple numerical model for the vertical winds inside the TC boundary layer. The tropical cyclone is characterized by the radial profile of the tangential wind speed at gradient level, the storm translation velocity, the surface drag coefficient, and the average temperature and saturation ratio inside the TC boundary layer. A parametric analysis shows the sensitivity of the symmetric and asymmetric components of the rainfall field to various storm characteristics.
Numerical and analytical models of cosmogenic radionuclide dynamics in landslide‐dominated drainage basins
Authors: Yanites Brian J. , Tucker Gregory E. , Anderson Robert S.
Published: January 2009

In many tectonically active regions on Earth, landslides dominate sediment delivery to channels. While cosmogenic radionuclides (CRN) represent a valuable tool to document basin‐averaged erosion rates, a better understanding of CRN dynamics in these systems is required before erosion rates can be reliably inferred from CRN concentrations. The stochastic nature of landslides results in variability of CRN concentrations in both alluvial and hillslope samples that is both difficult to document and poorly understood. To guide sampling strategies, we developed a 2‐D plan view model to simulate the influence of landslides on CRN dynamics. We employ a sediment mixing model, in which concentrations of CRNs from material eroded by both landslides and steady processes are combined to evaluate how best to infer erosion rates from CRN concentrations. This model is further used to test a new analytical solution for the distribution of CRN concentrations on hillslopes in a landslide‐prone system. Results suggest that for landscapes dominated by deep (>5 m) landslides, only large drainage basins (≥100 km2) provide consistently reliable estimates of erosion rates from CRN concentrations. For landscapes dominated by shallow landslides (0.7–2 m), smaller basins can produce reliable estimates. Results further suggest that the distribution of concentrations from hillslope samples could be used to deduce the relative contribution of material derived from landslide and steady processes. These findings underscore the need to consider carefully the sources of natural variability in sampling and analyzing CRNs; if properly done, the variability can reveal useful information about geomorphic processes in landslide‐prone areas.
A similarity framework to assess controls on shallow subsurface flow dynamics in hillslopes
Authors: Harman Ciaran , Sivapalan Murugesu
Published: January 2009

An understanding of the dominant controls on water fluxes through landscapes at scales smaller than the resolution of a hydrologic model is useful for choosing appropriate parameterizations, and for developing a classification system for landscape hydrology. The links between these controls and the parameters in hillslope‐scale models of subsurface lateral saturated flow have been treated implicitly in both physical (e.g., Characteristic Response Function) and empirical formulations, such as power law storage‐discharge relations. In particular, the controls exerted by the boundary condition at the toe of the hilslope and the temporal variability of the recharge have not been integrated with the understanding of the controls of topography and soil properties. In this work, we develop a dimensionless similarity framework for assessing these controls on the subsurface flow dynamics, based on the Boussinesq equation in an idealized hillslope system. Using this framework we demonstrate the relationship between (1) the exponents of the storage‐discharge relations, (2) the boundary conditions and (3) the characteristic storage thickness used in the Characteristic Response Function parameterization. We use the concept of hydrologic regimes to incorporate information about the population of recharge events that drive the system and set up the initial condition of saturated storage for each storm event. The analysis demonstrates that for planar hillslopes with uniform soil properties, exponents range between 0 (when the flow through the hillslope is dominated by the topographic gradients, and is in the early stages of draining) and 2 (when the flow is driven by water table gradients, and the thickness of the aquifer at the seepage face is small compared to the average thickness). The similarity framework can be used to make first‐order predictions of these exponents, and classify hillslopes using a simple typology of subsurface flows based on two components of the behavior: the relative dominance of the topographic and water‐table gradients, and the responsiveness of the hillslope discharge to temporal variability of the recharge inputs.
Development of Overweight in Children in Relation to Parental Weight and Socioeconomic Status
Authors: Semmler Claudia , Ashcroft Jo , van Jaarsveld Cornelia H.M. , Carnell Susan , Wardle Jane
Published: January 2009

The purpose of the study was to test the hypothesis that socioeconomic status (SES) moderates the association between parental weight and changes in BMI from childhood to early adolescence. Participants included 428 twin children from 100 families with obese parents (“obese families”) and 114 sociodemographically matched families with normal‐weight parents (“lean families”) who were assessed in their homes (age = 4.4). Follow‐up study was conducted 7 years later (age = 11.2) on 346 children (81%). Complete data were available for 333 children. Family SES was indexed with maternal education. Children's weights and heights were measured to calculate BMI s.d. scores based on 1990 British norms. Overweight was defined as >91st BMI centile. In children with obese parents, BMI s.d. scores increased from 0.51 at age 4 to 1.06 at age 11. In children with lean parents, BMI s.d. scores decreased from 0.11 to 0.05. Prevalence of overweight remained stable from age 4 to 11 in children with lean parents (8% to 9%), but it more than doubled in children with obese parents (17% to 45%). There was a significant interaction between parental weight and family SES (P < 0.01), so that in children with lean parents there was no SES difference in the BMI status from age 4 to 11; however, in children with obese parents, the increase in adiposity was significantly greater in lower SES families. These results suggest that parental leanness confers significant protection against development of overweight in children regardless of family SES, while parental obesity is an adverse prognostic sign, especially in lower SES families.
Inflammation and Race and Gender Differences in Computerized Tomography‐measured Adipose Depots
Authors: Beasley Lydia E. , Koster Annemarie , Newman Anne B. , Javaid M. Kassim , Ferrucci Luigi , Kritchevsky Stephen B. , Kuller Lewis H. , Pahor Marco , Schaap Laura A. , Visser Marjolein , Rubin Susan M. , Goodpaster Bret H. , Harris Tamara B. ,   The Health ABC study
Published: January 2009

A growing body of evidence has consistently shown a correlation between obesity and chronic subclinical inflammation. It is unclear whether the size of specific adipose depots is more closely associated with concentrations of inflammatory markers than overall adiposity. This study investigated the relationship between inflammatory markers and computerized tomography‐derived abdominal visceral and subcutaneous fat and thigh intermuscular and subcutaneous fat in older white and black adults. Data were from 2,651 black and white men and women aged 70–79 years participating in the Health, Aging, and Body Composition (Health ABC) study. Inflammatory markers, interleukin‐6 (IL‐6), C‐reactive protein (CRP), and tumor necrosis factor‐α (TNF‐α) were obtained from serum samples. Abdominal visceral and subcutaneous fat and thigh intermuscular and subcutaneous fat were quantified on computerized tomography images. Linear regression analysis was used to evaluate the cross‐sectional relationship between specific adipose depots and inflammatory markers in four race/gender groups. As expected, blacks have less visceral fat than whites and women less visceral fat than men. However, abdominal visceral adiposity was most consistently associated with significantly higher IL‐6 and CRP concentrations in all race/gender groups (P < 0.05), even after controlling for general adiposity. Thigh intermuscular fat had an inconsistent but significant association with inflammation, and there was a trend toward lower inflammatory marker concentration with increasing thigh subcutaneous fat in white and black women. Despite the previously established differences in abdominal fat distribution across gender and race, visceral fat remained a significant predictor of inflammatory marker concentration across all four subgroups examined.
Role of aryl hydrocarbon receptor in modulation of the expression of the hypoxia marker carbonic anhydrase IX
Authors: Takacova Martina , Holotnakova Tereza , Vondracek Jan , Machala Miroslav , Pencikova Katerina , Gradin Katarina , Poellinger Lorenz , Pastorek Jaromir , Pastorekova Silvia , Kopacek Juraj
Published: January 2009

Tumour-associated expression of CA IX (carbonic anhydrase IX) is to a major extent regulated by HIF-1 (hypoxia-inducible factor-1) which is important for transcriptional activation and consists of the oxygen-regulated subunit HIF-1α and the partner factor ARNT [AhR (aryl hydrocarbon receptor) nuclear translocator]. We have previously observed that HIF-1α competes with the AhR for interaction with ARNT under conditions when both conditionally regulated factors are activated. We have therefore investigated whether TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin)-induced activation of the AhR pathway might interfere with CA IX expression. The results from the present study suggest that TCDD treatment reduces hypoxic induction of both CA IX mRNA and protein expression. Moreover, the transcriptional activity of the CA9 promoter was significantly reduced by expression of CAAhR (constitutively active AhR), which activates transcription in a ligand-independent manner. Finally, we found that ARNT is critical for both hypoxic induction and the TCDD-mediated inhibition of CA9 expression.
Distribution of CRISPR spacer matches in viruses and plasmids of crenarchaeal acidothermophiles and implications for their inhibitory mechanism
Authors: Shah Shiraz Ali , Hansen Niels R. , Garrett Roger A.
Published: January 2009

Transcripts from spacer sequences within chromosomal repeat clusters [CRISPRs (clusters of regularly interspaced palindromic repeats)] from archaea have been implicated in inhibiting or regulating the propagation of archaeal viruses and plasmids. For the crenarchaeal thermoacidophiles, the chromosomal spacers show a high level of matches (∼30%) with viral or plasmid genomes. Moreover, their distribution along the virus/plasmid genomes, as well as their DNA strand specificity, appear to be random. This is consistent with the hypothesis that chromosomal spacers are taken up directly and randomly from virus and plasmid DNA and that the spacer transcripts target the genomic DNA of the extrachromosomal elements and not their transcripts.
Molecular biology of Hel308 helicase in archaea
Authors: Woodman Isabel L. , Bolt Edward L.
Published: January 2009

Hel308 is an SF2 (superfamily 2) helicase with clear homologues in metazoans and archaea, but not in fungi or bacteria. Evidence from biochemistry and genetics implicates Hel308 in remodelling compromised replication forks. In the last 4 years, significant advances have been made in understanding the biochemistry of archaeal Hel308, most recently through atomic structures from cren- and eury-archaea. These are good templates for SF2 helicase function more generally, highlighting co-ordinated actions of accessory domains around RecA folds. We review the emerging molecular biology of Hel308, drawing together ideas of how it may contribute to genome stability through the control of recombination, with reference to paradigms developed in bacteria.
Lessons from structural and biochemical studies on the archaeal exosome
Authors: Hartung Sophia , Hopfner Karl-Peter
Published: January 2009

The RNA exosome is a multisubunit exonuclease involved in numerous RNA maturation and degradation processes. Exosomes are found in eukaryotes and archaea and are related to bacterial polynucleotide phosphorylates. Over the past years structural and biochemical analysis revealed that archaeal exosomes have a large processing chamber with three phosphorolytic active sites that degrade RNA in the 3′→5′ direction in a highly processive manner. A narrow entry pore, framed by putative RNA-binding domains, could account for the high processivity and also prevent degradation of structured RNA. The phosphorolytic nuclease activity is reversible, leading to formation of heteropolymeric tails from nucleoside diphosphates as substrate. This reversibility is difficult to regulate, suggesting why, during evolution and emergence of stable poly(A) tails in eukaryotes, polyadenylation and nuclease activities in the human exosome and associated factors have been separated.
The interaction of Nanoarchaeum equitans with Ignicoccus hospitalis: proteins in the contact site between two cells
Authors: Burghardt Tillmann , Junglas Benjamin , Siedler Frank , Wirth Reinhard , Huber Harald , Rachel Reinhard
Published: January 2009

The two archaea Ignicoccus hospitalis and Nanoarchaeum equitans form a unique intimate association, the character of which is not yet fully understood. Electron microscopic investigations show that at least two modes of cell–cell interactions exist: (i) the two cells are interconnected via thin fibres; and (ii) the two cell surfaces are in direct contact with each other. In order to shed further light on the molecules involved, we isolated a protein complex, by using detergent-induced solubilization of cell envelopes, followed by a combination of chromatography steps. Analysis by MS and comparison with databases revealed that this fraction contained two dominant proteins, representing the respective major envelope proteins of the two archaea. In addition, a considerable set of membrane proteins is specifically associated with these proteins. They are now the focus of further biochemical and ultrastructural investigations.
Small RNAs of the halophilic archaeon Haloferax volcanii
Authors: Soppa Jörg , Straub Julia , Brenneis Mariam , Jellen-Ritter Angelika , Heyer Ruth , Fischer Susan , Granzow Michaela , Voss Björn , Hess Wolfgang R. , Tjaden Brian , Marchfelder Anita
Published: January 2009

In recent years, sRNAs (small non-coding RNAs) have been found to be abundant in eukaryotes and bacteria and have been recognized as a novel class of gene expression regulators. In contrast, much less is known about sRNAs in archaea, except for snoRNAs (small nucleolar RNAs) that are involved in the modification of bases in stable RNAs. Therefore bioinformatic and experimental RNomics approaches were undertaken to search for the presence of sRNAs in the model archaeon Haloferax volcanii, resulting in more than 150 putative sRNA genes being identified. Northern blot analyses were used to study (differential) expression of sRNA genes. Several chromosomal deletion mutants of sRNA genes were generated and compared with the wild-type. It turned out that two sRNAs are essential for growth at low salt concentrations and high temperatures respectively, and one is involved in the regulation of carbon metabolism. Taken together, it could be shown that sRNAs are as abundant in H. volcanii as they are in well-studied bacterial species and that they fulfil important biological roles under specific conditions.
Evolution and assembly of ESCRTs
Authors: Ghazi-Tabatabai Sara , Obita Takayuki , Pobbati Ajaybabu V. , Perisic Olga , Samson Rachel Y. , Bell Stephen D. , Williams Roger L.
Published: January 2009

The AAA (ATPase associated with various cellular activities) proteins participate in membrane trafficking, organelle biogenesis, DNA replication, intracellular locomotion, cytoskeletal remodelling, protein folding and proteolysis. The AAA Vps (vacuolar protein sorting) 4 is central to traffic to lysosomes, retroviral budding and mammalian cell division. It dissociates ESCRTs (endosomal sorting complexes required for transport) from endosomal membranes, enabling their recycling to the cytosol, and plays a role in fission of intraluminal vesicles within MVBs (multivesicular bodies). The mechanism of Vps4-catalysed disassembly of ESCRT networks is unknown; however, it requires interaction between Vps4 and ESCRT-III subunits. The 30 C-terminal residues of Vps2 and Vps46 (Did2) subunits are both necessary and sufficient for interaction with the Vps4 N-terminal MIT (microtubule-interacting and transport) domain, and the crystal structure of the Vps2 C-terminus in a complex with the Vps4 MIT domain shows that MIT helices α2 and α3 recognize a (D/E)XXLXXRLXXL(K/R) MIM (MIT-interacting motif). These Vps2–MIT interactions are essential for vacuolar sorting and for Vps4-catalysed disassembly of ESCRT-III networks in vitro. Electron microscopy of ESCRT-III filaments assembled in vitro has enabled us to identify surfaces of the Vps24 subunit that are critical for protein sorting in vivo. The ESCRT-III–Vps4 interaction predates the divergence of Archaea and Eukarya. The Crenarchaea have three classes of ESCRT-III-like subunits, and one of these subunits interacts with an archaeal Vps4-like protein in a manner closely related to the human Vps4–human ESCRT-III subunit Vps20 interaction. This archaeal Vps4–ESCRT-III interaction appears to have a fundamental role in cell division in the Crenarchaea.
ESCRT proteins and the regulation of endocytic delivery to lysosomes
Authors: Luzio J. Paul , Piper Siân C. , Bowers Katherine , Parkinson Michael D.J. , Lehner Paul J. , Bright Nicholas A.
Published: January 2009

In mammalian cells, there is evidence of cargo specificity in the requirement for particular ESCRT (endosomal sorting complex required for transport) proteins to sort cargo into the luminal vesicles of MVBs (multivesicular bodies). We have focussed on studying the ESCRT requirements for delivery of MHC class I to lysosomes following polyubiquitination by the Kaposi's sarcoma-associated herpesvirus protein K3. Down-regulation of polyubiquitinated cell-surface MHC class I in HeLa cells stably expressing K3 is achieved via clathrin-mediated endocytosis, followed by sorting into the luminal vesicles of MVBs and eventual delivery to lysosomes. Depletion of ESCRT-I and some ESCRT-III components interferes with this sorting and allows recycling of MHC class I to the cell surface. Depletion of ESCRT-II components has no effect on K3-mediated down-regulation of MHC class I and no gross morphological effect on endocytic compartments. Thus virally polyubiquitinated MHC class I does not require all of the ESCRT proteins in order to be sorted into the luminal vesicles of MVBs. However, there may be a further requirement for ESCRT-III proteins to ensure the efficient fusion of MVBs with lysosomes.
The mechanism of Ca2+-dependent recognition of Alix by ALG-2: insights from X-ray crystal structures
Authors: Suzuki Hironori , Kawasaki Masato , Inuzuka Tatsutoshi , Okumura Mayumi , Kakiuchi Takeshi , Shibata Hideki , Wakatsuki Soichi , Maki Masatoshi
Published: January 2009

Alix [ALG-2 (apoptosis-linked gene 2)-interacting protein X] was originally identified as a protein that interacts with ALG-2, a member of the penta-EF-hand Ca2+-binding protein family. ALG-2 binds to its C-terminal proline-rich region that contains four tandem repeats of PXY (where X represents an uncharged amino acid). Recent X-ray crystal structural analyses of the Ca2+-free and Ca2+-bound forms of ALG-2, as well as the complex with an Alix oligopeptide, have revealed a mechanism of Ca2+-dependent binding of ALG-2 to its target protein. Binding of Ca2+ to EF3 (third EF-hand) enables the side chain of Arg125, present in the loop connecting EF3 and EF4 (fourth EF-hand), to move sufficiently to make a primary hydrophobic pocket accessible to the critical PPYP (Pro-Pro-Tyr-Pro) motif in Alix, which partially overlaps with the GPP (Gly-Pro-Pro) motif for binding to Cep55 (centrosome protein of 55 kDa). The fact that ALG-2 forms a homodimer and each monomer has one peptide-binding site indicates the possibility that ALG-2 bridges two interacting proteins, including Alix and Tsg101 (tumour susceptibility gene 101), and functions as a Ca2+-dependent adaptor protein.
mTOR: dissecting regulation and mechanism of action to understand human disease
Authors: Goberdhan Deborah C.I. , Boyd C.A. Richard
Published: January 2009

mTOR (mammalian target of rapamycin) is a highly conserved serine/threonine protein kinase that has roles in cell metabolism, cell growth and cell survival. Although it has been known for some years that mTOR acts as a hub for inputs from growth factors (in particular insulin and insulin-like growth factors), nutrients and cellular stresses, some of the mechanisms involved are still poorly understood. Recent work has implicated mTOR in a variety of important human pathologies, including cancer, Type 2 diabetes and neurodegenerative disorders, heightening interest and accelerating progress in dissecting out the control and functions of mTOR.
Amino acid transporters: éminences grises of nutrient signalling mechanisms?
Authors: Taylor Peter M.
Published: January 2009

Nutrient signalling by the mTOR (mammalian target of rapamycin) pathway involves upstream sensing of free AA (amino acid) concentrations. Several AA-regulated kinases have recently been identified as putative intracellular AA sensors. Their activity will reflect the balance between AA flows through underlying mechanisms which together determine the size of the intracellular free AA pool. For indispensable AAs, these mechanisms are primarily (i) AA transport across the cell membrane, and (ii) protein synthesis/breakdown. The System L AA transporter is the primary conduit for cellular entry of indispensable neutral AAs (including leucine and phenylalanine) and potentially a key modulator of AA-sensitive mTOR signalling. Coupling of substrate flows through System L and other AA transporters (e.g. System A) may extend the scope for sensing nutrient abundance. Factors influencing AA transporter activity (e.g. hormones) may affect intracellular AA concentrations and hence indirectly mTOR pathway activity. Several AA transporters are themselves regulated by AA availability through ‘adaptive regulation’, which may help to adjust the gain of AA sensing. The substrate-binding sites of AA transporters are potentially direct sensors of AA availability at both faces of the cell surface, and there is growing evidence that AA transporters of the SNAT (sodium-coupled neutral AA transporter) and PAT (proton-assisted AA transporter) families may operate, at least under some circumstances, as transporter-like sensors (or ‘transceptors’) upstream of mTOR.
Amino acid sensing and mTOR regulation: inside or out?
Authors: Goberdhan Deborah C.I. , Ögmundsdóttir Margret H. , Kazi Shubana , Reynolds Bruno , Visvalingam Shivanthy M. , Wilson Clive , Boyd C.A. Richard
Published: January 2009

mTOR (mammalian target of rapamycin) plays a key role in determining how growth factor, nutrient and oxygen levels modulate intracellular events critical for the viability and growth of the cell. This is reflected in the impact of aberrant mTOR signalling on a number of major human diseases and has helped to drive research to understand how TOR (target of rapamycin) is itself regulated. While it is clear that amino acids can affect TOR signalling, how these molecules are sensed by TOR remains controversial, perhaps because cells use different mechanisms as environmental conditions change. Even the question of whether they have an effect inside the cell or at its surface remains unresolved. The present review summarizes current ideas and suggests ways in which some of the models proposed might be unified to produce an amino acid detection system that can adapt to environmental change.
Therapeutic targeting of mTOR in tuberous sclerosis
Authors: Sampson Julian R.
Published: January 2009

Failure in the regulation of mTOR (mammalian target of rapamycin) appears to be critical to the pathogenesis of the inherited disorder tuberous sclerosis and the related lung disease LAM (lymphangioleiomyomatosis). Both diseases are caused by mutations of TSC1 or TSC2 (TSC is tuberous sclerosis complex) that impair GAP (GTPase-activating protein) activity of the TSC1–TSC2 complex for Rheb, leading to inappropriate activity of signalling downstream of mTORC1 (mTOR complex 1). mTOR inhibitors are already used in a variety of clinical settings including as immunosuppressants, anticancer agents and antiproliferative agents in drug-eluting coronary artery stents. They also represent candidate therapies directed to the underlying molecular pathology in tuberous sclerosis and LAM. Phase I/II clinical trials of the mTORC1 inhibitor rapamycin have demonstrated reduction in size of tuberous-sclerosis- and LAM-associated renal tumours (angiomyolipomas) and some evidence for reversible improvement in lung function in patients with LAM. A case series of tuberous-sclerosis-associated brain tumours were also reported to shrink during rapamycin therapy. An important, although variable, feature of the tuberous sclerosis phenotype is learning difficulty. Recent studies in mouse models carrying heterozygous Tsc2 mutations demonstrated improvement in memory and learning deficits following treatment with rapamycin. These promising pre-clinical and early human trials are being followed by larger-scale randomized control trials of mTOR inhibitors for treatment of renal, lung and brain manifestations of TSC1- and TSC2-associated disease.
Is depression associated with dysfunction of the central reward system?
Authors: Martin-Soelch Chantal
Published: January 2009

The neural substrates of MDD (major depressive disorder) are complex and not yet fully understood. In the present review, I provide a short overview of the findings supporting the hypothesis of a dysfunctional dopamine system in the pathophysiology of depression. Because the mesocorticolimbic dopamine system is involved in reward processing, it has been hypothesized that a reduced function of this system could underlie the anhedonia and amotivation associated with depression. This hypothesis is supported by several observations providing indirect evidence for reduced central dopaminergic transmission in depression. However, some of the differences observed between controls and depressed patients in dopamine function seem to be specific to a subsample of patients, and influenced by the methods chosen. Studies that investigated the neural bases of some MDD behavioural symptoms showed that anhedonia, loss of motivation and the diminished ability to concentrate or make decisions could be associated with a blunted reaction to positive reinforcers and rewards on one side, and with a bias towards negative feedback on the other side. Only a few studies have investigated the neural basis of anhedonia and the responses to rewards in MDD subjects, mostly evidencing a blunted response to reward signals that was associated with reduced brain activation in regions associated with the brain reward system. In conclusion, there is evidence for a dysfunction of the dopamine system in depression and for blunted response to reward signals. However, the exact nature of this dysfunction is not yet clear and needs to be investigated in further studies.
Titin isoform expression in aortic stenosis
Authors: WILLIAMS Lynne , Howell Neil , Pagano Domenico , Andreka Peter , Vertesaljai Marton , Pecor Tiffany , Frenneaux Michael , Granzier Henk
Published: January 2009

Titin is a giant sarcomeric protein that plays a major role in determining passive myocardial stiffness. The shorter N2B isoform results in a higher passive myocardial stiffness than the longer N2BA isoform. We hypothesised that the expression of the short N2B isoform would be increased in patients with aortic stenosis compared with healthy controls in response to pressure overload, in order to act as a modulator for the increased demand placed on the left ventricle during the early stages of the hypertrophic response. Myocardial biopsies were obtained from the left ventricle of 19 patients undergoing aortic valve replacement for aortic stenosis who had no significant co-existing coronary artery disease. Left ventricular biopsies were also obtained from 13 donor hearts for comparison. SDS-agarose gels revealed small N2B and large N2BA cardiac titin isoforms, with a mean N2BA/N2B ratio that was significantly decreased in the 19 aortic stenotic patients compared with the 13 controls (0.66±0.04 in the normal donor hearts compared with 0.48±0.03 in patients with aortic stenosis; P=0.02). However, total titin remained unchanged (0.28±0.02 compared with 0.24±0.02 respectively; P=0.29). In conclusion, the expression of less N2BA and more N2B titin in response to pressure overload may result in the generation of higher passive tension upon stretch to a given sarcomere length and this might affect cardiac performance.
Physics in France
Authors: Combrisson Jean
Published: January 2009

THE STUDY OF PHYSICAL PHENOMENA and the search for their explanation by mathematical models are intellectual activities whereby France has provided a major contribution to our knowledge of the material world surrounding us. We can cite the names of discoverers at random: Blaise Pascal, René Descartes, André Ampére, Charles Coulomb, Augustin Fresnel, Sadi Carnot; and, nearer our time: Pierre Curie, Paul Langevin, Louis de Broglie, Jean Perrin, Frédéric Joliot. Many modern inventions originated in France (for example, the metric system was introduced by the National Convention of 1972) and several international organizations (such as the International Bureau of Weights and Measures) have chosen headquarters in Paris.
Effects of the absorption coefficient on resonant infrared laser ablation of poly(ethylene glycol)
Authors: Johnson S. L. , Schriver K. E. , Haglund R. F. , Bubb D. M.
Published: January 2009

We describe experiments on resonant infrared laser ablation of poly(ethylene glycol) (PEG) at two different resonant excitation wavelengths and for different molecular weights of PEG. The two resonant wavelengths correspond to different stretching vibrations of the polymer and have absorption coefficients that differ by roughly an order of magnitude. Ablation via excitation of the O–H terminal group stretching mode at 2.94 μm, the weaker of the two absorptions, is delayed in time by several microseconds with respect to ablation at 3.47 μm, the more strongly absorbing C–H stretching mode of the polymer. Time-resolved plume shadowgraphs along with ablation rate measurements for the two modes reveal that the absorption coefficient strongly affects the physical characteristics of the ejecta and plume, as well as the time scale for material removal. Temperature-rise calculations demonstrate that phase explosion is likely the operative mechanism in ablation at the C–H mode, while normal boiling may play a role in material removal at the O–H mode.
Classical interatomic potential model for Si/H/Br systems and its application to atomistic Si etching simulation by HBr+
Authors: Nagaoka T. , Eriguchi K. , Ono K. , Ohta H.
Published: January 2009

An interatomic potential model for Si/H/Br systems has been developed for performing classical molecular dynamics simulations of Si etching processes by HBr plasmas. The potential form used here is the improved Stillinger–Weber potential function involving a correction term in order to predict the reaction dynamics more accurately. Parameters were determined based on ab initio data obtained from previous works on Si/Br systems by [Ohta et al. J. Appl. Phys. 104, 073302 (2008)]. By using this model, we performed Si etching simulations by monoenergetic HBr+ and Br+ beams. H atom has about 1% of the translational energy of cluster ions due to the small H/Br mass ratio (=1.0/79.9); therefore, H atoms in HBr+ behave like H radicals. This results in higher etch yields by HBr+ than those by Br+ in the low-energy region (less than 100 eV). This can be attributed to the chemical enhancement induced by the formation of Si–H bonds. On the other hand, yields by HBr+ and Br+ were almost the same in the high-energy region (more than 100 eV), where physical sputtering was relatively dominant and the contribution of H was small.
Polarization fatigue in ferroelectric thin films and related materials
Authors: Lou X. J.
Published: January 2009

The experimental characteristics of polarization fatigue in thin-film, bulk ceramic, and single-crystalline ferroelectrics have been reviewed in detail. Various scenarios and models proposed for fatigue in ferroelectric materials during the past few decades have been discussed, together with our own model developed very recently [Phys. Rev. Lett. 97, 177601 (2006); Phys. Rev. B 75, 244104 (2007)]. Interpretations for the experimental data reviewed in this paper but untreated in our previous work [Phys. Rev. B 75, 244104 (2007)] as well as the methods of improving the fatigue endurance in ferroelectrics are given based on this model. Finally, the results on polarization fatigue in some special classes of ferroelectrics such as multiferroics (e.g., BiFeO3-based materials), ferroelectric polymers, and antiferroelectric thin films and ceramics are discussed and accounted for in light of our model.
Modifications of turbulence and turbulent transport associated with a bias-induced confinement transition in the Large Plasma Device
Authors: Carter T. A. , Maggs J. E.
Published: January 2009

Azimuthal flow is driven in the edge of the Large Plasma Device (LAPD) [W. Gekelman et al., Rev. Sci. Instrum. 62, 2875 (1991)] through biasing a section of the vacuum vessel relative to the plasma source cathode. As the applied bias exceeds a threshold, a transition in radial particle confinement is observed, evidenced by a dramatic steepening in the density profile, similar to the L- to H-mode transition in toroidal confinement devices. The threshold behavior and dynamic behavior of radial transport is related to flow penetration and the degree of spatial overlap between the flow shear and density gradient profiles. An investigation of the changes in turbulence and turbulent particle transport associated with the confinement transition is presented. Two-dimensional cross-correlation measurements show that the spatial coherence of edge turbulence in LAPD changes significantly with biasing. The azimuthal correlation in the turbulence increases dramatically, while the radial correlation length is little altered. Turbulent amplitude is reduced at the transition, particularly in electric field fluctuations, but the dominant change observed is in the cross-phase between density and electric field fluctuations. The changes in cross-phase lead to a suppression and then apparent reversal of turbulent particle flux as the threshold is exceeded.
Whispering gallery mode biosensor operated in the stimulated emission regime
Authors: Francois Alexandre , Himmelhaus Michael
Published: January 2009

Whispering gallery modes (WGMs) are generated in fluorescent polymer microparticles in phosphate buffered saline (PBS) above the threshold for stimulated emission and compared to their characteristics below threshold. The WGM microresonators show an eightfold improvement of their signal-to-noise ratio and a threefold increase in their quality factor when operated above threshold. In an investigation on the benefits for biochemical sensing, a real-time adsorption kinetics of bovine serum albumin in PBS is monitored and compared with those kinetics acquired by means of a WGM microresonator operated below threshold as well as by surface plasmon resonance (SPR).
Turbulent pair separation due to multiscale stagnation point structure and its time asymmetry in two-dimensional turbulence
Authors: Faber T. , Vassilicos J. C.
Published: January 2009

The pair separation model of Goto and Vassilicos [New J. Phys. 6, 65 (2004)] is revisited and placed on a sound mathematical foundation. A direct numerical simulation of two-dimensional homogeneous isotropic turbulence with an inverse energy cascade and a k−5/3 power law is used to investigate properties of pair separation in two-dimensional turbulence. A special focus lies on the time asymmetry observed between forward and backward separations. Application of the present model to these data suffers from finite inertial range effects and thus, conditional averaging on scales rather than on time has been employed to obtain values for the Richardson constants and their ratio. The Richardson constants for the forward and backward case are found to be (1.066±0.020) and (0.999±0.007), respectively. The ratio of Richardson constants for the backward and forward cases is therefore gb/gf=(0.92±0.03), and hence exhibits a qualitatively different behavior from pair separation in three-dimensional turbulence, where gb>gf [J. Berg et al., Phys. Rev. E 74, 016304 (2006)]. This indicates that previously proposed explanations for this time asymmetry based on the strain tensor eigenvalues are not sufficient to describe this phenomenon in two-dimensional turbulence. We suggest an alternative qualitative explanation based on the time asymmetry related to the inverse versus forward energy cascade. In two-dimensional turbulence, this asymmetry manifests itself in merging eddies due to the inverse cascade, leading to the observed ratio of Richardson constants.
Looking ahead…
Authors: Seitz Frederick
Published: January 2009

We celebrate the 25th Anniversary of the American Institute of Physics. The occasion is a notable one not only to those of us who have been active professionally during most or all of the past 25 years but also to those who begin their professional careers with the knowledge that physics is well established in our country. The Institute itself is not remarkable in the material sense. Its capital is small; its holdings in real estate are not impressive. Many of its most significant activities are routine. It is important because it symbolizes the collective unity of a group of individuals who occupy an exceptional position in the nation.
The story of the American Institute of Physics
Authors: Barton H. A.
Published: January 2009

Since its founding in 1931, the American Institute of Physics has devoted its attention to the development of physics as a field of human activity and to the economy of publishing the physics journals. In both respects there was a crisis in 1929. The Institute was founded to meet the crisis and has played a leading role in solving the problems confronting the physics field to the present time.