bluuebunny/crossref_metadata_2025 huggingface dataset:
Accumulation and enhanced cycling of polyphosphate by Sargasso Sea plankton in response to low phosphorus
Authors: Martin Patrick , Dyhrman Sonya T. , Lomas Michael W. , Poulton Nicole J. , Van Mooy Benjamin A. S.
Published: April 2014

Significance

Phosphorus is scarce in many subtropical ocean regions, and phytoplankton in these regions adjust their biochemical composition such that they require less of it. We show here that phytoplankton in the ultra–low-phosphorus Sargasso Sea are enriched in polyphosphate (polyP), a phosphorus molecule hitherto thought of primarily as a luxury storage product in marine phytoplankton. We further show that polyP appears to be more readily recycled in the surface ocean than other phosphorus-containing biochemicals. Thus, the high relative levels, and fast cycling, of polyP in low-phosphorus environments may form a feedback loop that contributes bioavailable phosphorus for primary production, potentially reducing the likelihood of growth limitation by phosphorus.
Neural sensitivity to eudaimonic and hedonic rewards differentially predict adolescent depressive symptoms over time
Authors: Telzer Eva H. , Fuligni Andrew J. , Lieberman Matthew D. , Galván Adriana
Published: April 2014

Significance

Although optimal well-being may be achieved through eudaimonic activities (meaning and purpose), individuals tend to orient toward hedonic activities (pleasure seeking), potentially placing them at risk for ill-being. We find that reward-related neural activation during eudaimonic decisions predicts longitudinal declines in depressive symptoms, whereas reward-related neural activation to hedonic decisions predicts longitudinal increases in depressive symptoms. We identified a potential neural mechanism by which adolescents may develop or be protected from developing ill-being. These findings underscore how the motivational context underlying neural sensitivity to rewards can differentially predict changes in well-being over time. To our knowledge, this is the first study to show that reward-related neural activation within an individual can be both a source of risk and protection.
A bimodular nuclear localization signal assembled via an extended double-stranded RNA-binding domain acts as an RNA-sensing signal for transportin 1
Authors: Barraud Pierre , Banerjee Silpi , Mohamed Weaam I. , Jantsch Michael F. , Allain Frédéric H.-T.
Published: April 2014

Significance

The double-stranded RNA-binding domain (dsRBD) is an abundant, conserved RNA-binding motif. Besides RNA binding, dsRBDs can serve as protein-interaction domains. In the human RNA-editing enzyme adenosine deaminase acting on RNA (ADAR1), one of its three dsRBDs mediates nuclear import by interacting with the import receptor transportin 1 (Trn1). RNA binding interferes with Trn1 binding, thereby preventing nuclear import. Using NMR spectroscopy and cell biological analysis, we show that the regions flanking this dsRBD form a bimodular Trn1-dependent nuclear localization signal. The dsRBD itself is not involved in Trn1 interaction but properly positions the Trn1 interacting regions. Using molecular modeling, we provide a structural explanation on how dsRNA binding prevents the dsRBD from accessing the interacting cavity of Trn1, thereby preventing nuclear import of RNA-bound ADAR1.
Lead in ancient Rome’s city waters
Authors: Delile Hugo , Blichert-Toft Janne , Goiran Jean-Philippe , Keay Simon , Albarède Francis
Published: April 2014

Significance

Thirty years ago, Jerome Nriagu argued in a milestone paper that Roman civilization collapsed as a result of lead poisoning. Clair Patterson, the scientist who convinced governments to ban lead from gasoline, enthusiastically endorsed this idea, which nevertheless triggered a volley of publications aimed at refuting it. Although today lead is no longer seen as the prime culprit of Rome’s demise, its status in the system of water distribution by lead pipes (
fistulæ
) still stands as a major public health issue. By measuring Pb isotope compositions of sediments from the Tiber River and the Trajanic Harbor, the present work shows that “tap water” from ancient Rome had 100 times more lead than local spring waters.
An outer membrane channel protein of
Mycobacterium tuberculosis
with exotoxin activity
Authors: Danilchanka Olga , Sun Jim , Pavlenok Mikhail , Maueröder Christian , Speer Alexander , Siroy Axel , Marrero Joeli , Trujillo Carolina , Mayhew David L. , Doornbos Kathryn S. , Muñoz Luis E. , Herrmann Martin , Ehrt Sabine , Berens Christian , Niederweis Michael
Published: April 2014

Significance

The mechanisms that enable
Mycobacterium tuberculosis
, the causative agent of tuberculosis, to resist drug treatment and survive the immune response are poorly understood. In this study we discovered that
M. tuberculosis
produces the protein channel protein with necrosis-inducing toxin (CpnT), which forms a channel in the outer membrane and releases a toxic domain into the extracellular milieu. This toxin has no similarity to known bacterial toxins and kills eukaryotic cells by necrosis, suggesting that it is required for escape of
M. tuberculosis
from macrophages and for dissemination. The channel domain of CpnT is used for uptake of nutrients across the outer membrane. Taken together, CpnT is a protein with functions in two fundamental processes in
M. tuberculosis
physiology: nutrient acquisition and control of host cell death.
Hypermutable DNA chronicles the evolution of human colon cancer
Authors: Naxerova Kamila , Brachtel Elena , Salk Jesse J. , Seese Aaron M. , Power Karen , Abbasi Bardia , Snuderl Matija , Chiang Sarah , Kasif Simon , Jain Rakesh K.
Published: April 2014

Significance

Genetic heterogeneity in systemic cancer is of great clinical interest because it impacts therapeutic response and reflects how tumor cells grow and spread. We present a methodology that enables efficient evaluation of intratumor heterogeneity in patients through analysis of neutral somatic variation hotspots. Using only 20 genomic markers, we demonstrate a unique pattern of clonal diversity in each patient. Some tumors are significantly more diversified than others. Our data suggest that distinct clones can give rise to lymphatic and distant metastases. Our methodology is applicable to other human cancer types and facilitates high-throughput investigation of tumor evolution.
Symbol addition by monkeys provides evidence for normalized quantity coding
Authors: Livingstone Margaret S. , Pettine Warren W. , Srihasam Krishna , Moore Brandon , Morocz Istvan A. , Lee Daeyeol
Published: April 2014

Significance

Symbol-literate monkeys can be trained to combine, or add, pairs of large numbers. They transfer to a novel symbol set, ruling out memorization of each symbol pair. Their addition behavior indicates an underlying relative scaling of magnitude.
Patterns of coding variation in the complete exomes of three Neandertals
Authors: Castellano Sergi , Parra Genís , Sánchez-Quinto Federico A. , Racimo Fernando , Kuhlwilm Martin , Kircher Martin , Sawyer Susanna , Fu Qiaomei , Heinze Anja , Nickel Birgit , Dabney Jesse , Siebauer Michael , White Louise , Burbano Hernán A. , Renaud Gabriel , Stenzel Udo , Lalueza-Fox Carles , de la Rasilla Marco , Rosas Antonio , Rudan Pavao , Brajković Dejana , Kucan Željko , Gušic Ivan , Shunkov Michael V. , Derevianko Anatoli P. , Viola Bence , Meyer Matthias , Kelso Janet , Andrés Aida M. , Pääbo Svante
Published: April 2014

Significance

We use a hybridization approach to enrich the DNA from the protein-coding fraction of the genomes of two Neandertal individuals from Spain and Croatia. By analyzing these two exomes together with the genome sequence of a Neandertal from Siberia we show that the genetic diversity of Neandertals was lower than that of present-day humans and that the pattern of coding variation suggests that Neandertal populations were small and isolated from one another. We also show that genes involved in skeletal morphology have changed more than expected on the Neandertal evolutionary lineage whereas genes involved in pigmentation and behavior have changed more on the modern human lineage.
The ‘Yidishe Paganini’: Sholem Aleichem's Stempenyu, the Music of Yiddish Theatre and the Character of the Shtetl Fiddler
Authors: Walden Joshua S.
Published: April 2014

This article explores the music of Yiddish theatre in early twentieth-century New York by considering multiple adaptations of Russian Jewish author Sholem Aleichem's 1888 novel Stempenyu, about a klezmer violinist, which was transformed into two theatrical productions in 1907 and 1929, and finally inspired a three-movement recital work for accompanied violin by Joseph Achron. The multiple versions of Stempenyu present the eponymous musician as an allegory for the ambivalent role of the shtetl – the predominantly Jewish small town of Eastern Europe – in defining diasporic Jewish life in Europe and America, and as a medium for the sonic representation of shtetl culture as it was reformulated in the memories of the first generations of Jewish immigrants. The variations in the evocations of Eastern European klezmer in these renderings of Stempenyu indicate complex changes in the ways Jewish immigrants and their children conceived of their connection to Eastern Europe over four decades. The paper concludes by viewing changes in the symbolic character type of the shtetl fiddler in its most famous and recent manifestation, in the stage and screen musical Fiddler on the Roof.
Who is speaking? The Indignados as political subjects
Authors: Eklundh Emmy
Published: April 2014

Since 2011, the Indignados have been a prominent feature of Spanish politics. Based on the emotional characteristics and framing of the movement, this article argues that our common notions of how democracy and legitimacy should work, and in particular ideas of deliberative democracy, consistently favour political behaviour of a certain kind, namely that of rational action. This article argues that ideas of radical democracy, especially those of Jacques Rancière, could help broaden the idea of politics, in arguing that only recognising rational actions is an exclusionary practice. The article thus uses the case of the Indignados in order to rethink some dimensions of democratic theory. It starts out with an outlook on the current situation in Spain and then moves on to describe the main tenets of deliberative democracy and the problem the Indignados pose to such a theory. In opposition to this it introduces Rancière's works, and argues that this has much higher bearing for our contemporary problems of democracy. The article concludes by saying that deliberative democracy lacks explanatory power when it comes to the Indignados. By requiring a unified sovereign, a distinction between voice and noise, and a consensual form of legitimate decision-making, the Indignados are not deemed political subjects in deliberative democratic theory. This can be seen as an exclusionary practice, since the Indignados still form a noticeable presence in today's political landscape. Therefore, there is a need for revising what constitutes a political subject and a political action.
ProSAP1 and membrane nanodomain-associated syndapin I promote postsynapse formation and function
Authors: Schneider Katharina , Seemann Eric , Liebmann Lutz , Ahuja Rashmi , Koch Dennis , Westermann Martin , Hübner Christian A. , Kessels Michael M. , Qualmann Britta
Published: April 2014

Insights into mechanisms coordinating membrane remodeling, local actin nucleation, and postsynaptic scaffolding during postsynapse formation are important for understanding vertebrate brain function. Gene knockout and RNAi in individual neurons reveal that the F-BAR protein syndapin I is a crucial postsynaptic coordinator in formation of excitatory synapses. Syndapin I deficiency caused significant reductions of synapse and dendritic spine densities. These syndapin I functions reflected direct, SH3 domain–mediated associations and functional interactions with ProSAP1/Shank2. They furthermore required F-BAR domain-mediated membrane binding. Ultra-high-resolution imaging of specifically membrane-associated, endogenous syndapin I at membranes of freeze-fractured neurons revealed that membrane-bound syndapin I preferentially occurred in spines and formed clusters at distinct postsynaptic membrane subareas. Postsynaptic syndapin I deficiency led to reduced frequencies of miniature excitatory postsynaptic currents, i.e., to defects in synaptic transmission phenocopying ProSAP1/Shank2 knockout, and impairments in proper synaptic ProSAP1/Shank2 distribution. Syndapin I–enriched membrane nanodomains thus seem to be important spatial cues and organizing platforms, shaping dendritic membrane areas into synaptic compartments.
Vinculin phosphorylation differentially regulates mechanotransduction at cell–cell and cell–matrix adhesions
Authors: Bays Jennifer L. , Peng Xiao , Tolbert Catlin E. , Guilluy Christophe , Angell Ashley E. , Pan Yuan , Superfine Richard , Burridge Keith , DeMali Kris A.
Published: April 2014

Cells experience mechanical forces throughout their lifetimes. Vinculin is critical for transmitting these forces, yet how it achieves its distinct functions at cell–cell and cell–matrix adhesions remains unanswered. Here, we show vinculin is phosphorylated at Y822 in cell–cell, but not cell–matrix, adhesions. Phosphorylation at Y822 was elevated when forces were applied to E-cadherin and was required for vinculin to integrate into the cadherin complex. The mutation Y822F ablated these activities and prevented cells from stiffening in response to forces on E-cadherin. In contrast, Y822 phosphorylation was not required for vinculin functions in cell–matrix adhesions, including integrin-induced cell stiffening. Finally, forces applied to E-cadherin activated Abelson (Abl) tyrosine kinase to phosphorylate vinculin; Abl inhibition mimicked the loss of vinculin phosphorylation. These data reveal an unexpected regulatory mechanism in which vinculin Y822 phosphorylation determines whether cadherins transmit force and provides a paradigm for how a shared component of adhesions can produce biologically distinct functions.
Mitochondrial fusion is frequent in skeletal muscle and supports excitation–contraction coupling
Authors: Eisner Verónica , Lenaers Guy , Hajnóczky György
Published: April 2014

Genetic targeting experiments indicate a fundamental role for mitochondrial fusion proteins in mammalian physiology. However, owing to the multiple functions of fusion proteins, their related phenotypes are not necessarily caused by altered mitochondrial fusion. Perhaps the biggest mystery is presented by skeletal muscle, where mostly globular-shaped mitochondria are densely packed into the narrow intermyofilamental space, limiting the interorganellar interactions. We show here that mitochondria form local networks and regularly undergo fusion events to share matrix content in skeletal muscle fibers. However, fusion events are less frequent and more stable in the fibers than in nondifferentiated myoblasts. Complementation among muscle mitochondria was suppressed by both in vivo genetic perturbations and chronic alcohol consumption that cause myopathy. An Mfn1-dependent pathway is revealed whereby fusion inhibition weakens the metabolic reserve of mitochondria to cause dysregulation of calcium oscillations during prolonged stimulation. Thus, fusion dynamically connects skeletal muscle mitochondria and its prolonged loss jeopardizes bioenergetics and excitation–contraction coupling, providing a potential pathomechanism contributing to myopathies.
RGMb is a novel binding partner for PD-L2 and its engagement with PD-L2 promotes respiratory tolerance
Authors: Xiao Yanping , Yu Sanhong , Zhu Baogong , Bedoret Denis , Bu Xia , Francisco Loise M. , Hua Ping , Duke-Cohan Jonathan S. , Umetsu Dale T. , Sharpe Arlene H. , DeKruyff Rosemarie H. , Freeman Gordon J.
Published: April 2014

We report that programmed death ligand 2 (PD-L2), a known ligand of PD-1, also binds to repulsive guidance molecule b (RGMb), which was originally identified in the nervous system as a co-receptor for bone morphogenetic proteins (BMPs). PD-L2 and BMP-2/4 bind to distinct sites on RGMb. Normal resting lung interstitial macrophages and alveolar epithelial cells express high levels of RGMb mRNA, whereas lung dendritic cells express PD-L2. Blockade of the RGMb–PD-L2 interaction markedly impaired the development of respiratory tolerance by interfering with the initial T cell expansion required for respiratory tolerance. Experiments with PD-L2–deficient mice showed that PD-L2 expression on non–T cells was critical for respiratory tolerance, but expression on T cells was not required. Because PD-L2 binds to both PD-1, which inhibits antitumor immunity, and to RGMb, which regulates respiratory immunity, targeting the PD-L2 pathway has therapeutic potential for asthma, cancer, and other immune-mediated disorders. Understanding this pathway may provide insights into how to optimally modulate the PD-1 pathway in cancer immunotherapy while minimizing adverse events.
MyD88-dependent interplay between myeloid and endothelial cells in the initiation and progression of obesity-associated inflammatory diseases
Authors: Yu Minjia , Zhou Hao , Zhao Junjie , Xiao Nengming , Roychowdhury Sanjoy , Schmitt David , Hu Bingqing , Ransohoff Richard M. , Harding Clifford V. , Hise Amy G. , Hazen Stanley L. , DeFranco Anthony L. , Fox Paul L. , Morton Richard E. , Dicorleto Paul E. , Febbraio Maria , Nagy Laura E. , Smith Jonathan D. , Wang Jian-an , Li Xiaoxia
Published: April 2014

Low-grade systemic inflammation is often associated with metabolic syndrome, which plays a critical role in the development of the obesity-associated inflammatory diseases, including insulin resistance and atherosclerosis. Here, we investigate how Toll-like receptor–MyD88 signaling in myeloid and endothelial cells coordinately participates in the initiation and progression of high fat diet–induced systemic inflammation and metabolic inflammatory diseases. MyD88 deficiency in myeloid cells inhibits macrophage recruitment to adipose tissue and their switch to an M1-like phenotype. This is accompanied by substantially reduced diet-induced systemic inflammation, insulin resistance, and atherosclerosis. MyD88 deficiency in endothelial cells results in a moderate reduction in diet-induced adipose macrophage infiltration and M1 polarization, selective insulin sensitivity in adipose tissue, and amelioration of spontaneous atherosclerosis. Both in vivo and ex vivo studies suggest that MyD88-dependent GM-CSF production from the endothelial cells might play a critical role in the initiation of obesity-associated inflammation and development of atherosclerosis by priming the monocytes in the adipose and arterial tissues to differentiate into M1-like inflammatory macrophages. Collectively, these results implicate a critical MyD88-dependent interplay between myeloid and endothelial cells in the initiation and progression of obesity-associated inflammatory diseases.
Pentraxin‐3 and the Right Ventricle: The Multi‐Ethnic Study of Atherosclerosis–Right Ventricle Study
Authors: Leary Peter J. , Jenny Nancy S. , Barr R. Graham , Bluemke David A. , Harhay Michael O. , Heckbert Susan R. , Kronmal Richard A. , Lima João A. , Mikacenic Carmen , Tracy Russell P. , Kawut Steven M.
Published: April 2014

Pentraxin‐3 (PTX3) is a protein mediator of innate immunity that is elevated in the setting of left heart disease and pulmonary arterial hypertension. The relationship between PTX3 and right ventricular (RV) structure and function is not known. We included men and women with magnetic resonance imaging assessment of RV structure and function and measurement of PTX3 from the Multi‐Ethnic Study of Atherosclerosis, a study of individuals free of clinical cardiovascular disease. Multivariable linear regression estimated associations between PTX3 protein levels and RV measures after adjusting for demographic characteristics, anthropometrics, smoking status, diabetes mellitus, hypertension, and corresponding left ventricular (LV) parameters. Instrumental variable analysis exploiting Mendelian randomization was attempted using two‐stage least squares regression. The study sample included 1,779 participants with available PTX3 levels, RV measures, and all covariables. Mean PTX3 level was 2.1 ng/mL. Higher PTX3 was independently associated with greater RV mass and larger RV end‐diastolic volume with and without adjustment for the corresponding LV parameters or C‐reactive protein (all P <. 05). There was no association between PTX3 and RV ejection fraction or stroke volume. Single‐nucleotide polymorphisms were not associated with PTX3 protein levels or RV measures after accounting for race. Instrumental variable analysis could not be reliably performed. Higher PTX3 protein levels were associated with greater RV mass and larger RV end‐diastolic volume. These associations were independent of common cardiovascular risk factors and LV morphologic changes. Inflammation is associated with differences in the pulmonary circulation‐RV axis in adults without clinical cardiovascular disease.
On left Köthe rings and a generalization of a Köthe-Cohen-Kaplansky theorem
Authors: Behboodi M. , Ghorbani A. , Moradzadeh-Dehkordi A. , Shojaee S.
Published: April 2014

In this paper, we obtain a partial solution to the following question of Köthe: For which rings

R
R

is it true that every left (or both left and right)

R
R

-module is a direct sum of cyclic modules? Let

R
R

be a ring in which all idempotents are central. We prove that if

R
R

is a left Köthe ring (i.e., every left

R
R

-module is a direct sum of cyclic modules), then

R
R

is an Artinian principal right ideal ring. Consequently,

R
R

is a Köthe ring (i.e., each left and each right

R
R

-module is a direct sum of cyclic modules) if and only if

R
R

is an Artinian principal ideal ring. This is a generalization of a Köthe-Cohen-Kaplansky theorem.
Density problems on vector bundles and manifolds
Authors: Bandara Lashi
Published: April 2014

We study some canonical differential operators on vector bundles over smooth, complete Riemannian manifolds. Under very general assumptions, we show that smooth, compactly supported sections are dense in the domains of these operators. Furthermore, we show that smooth, compactly supported functions are dense in second order Sobolev spaces on such manifolds under the sole additional assumption that the Ricci curvature is uniformly bounded from below.
A Khovanov stable homotopy type
Authors: Lipshitz Robert , Sarkar Sucharit
Published: April 2014

Given a link diagram

L
L

we construct spectra

X

K
h

j

(
L
)

\mathcal {X}_{Kh}^j(L)

so that the Khovanov homology

K

i
,
j

(
L
)

K^{i,j}(L)

is isomorphic to the (reduced) singular cohomology

H
~

i

(

X

K
h

j

(
L
)
)

\widetilde {H}^{i}(\mathcal {X}_{Kh}^j(L))

. The construction of

X

K
h

j

(
L
)

\mathcal {X}_{Kh}^j(L)

is combinatorial and explicit. We prove that the stable homotopy type of

X

K
h

j

(
L
)

\mathcal {X}_{Kh}^j(L)

depends only on the isotopy class of the corresponding link.
Improving B-cell epitope prediction and its application to global antibody-antigen docking
Authors: Krawczyk Konrad , Liu Xiaofeng , Baker Terry , Shi Jiye , Deane Charlotte M.
Published: April 2014

Motivation: Antibodies are currently the most important class of biopharmaceuticals. Development of such antibody-based drugs depends on costly and time-consuming screening campaigns. Computational techniques such as antibody–antigen docking hold the potential to facilitate the screening process by rapidly providing a list of initial poses that approximate the native complex.

Results: We have developed a new method to identify the epitope region on the antigen, given the structures of the antibody and the antigen—EpiPred. The method combines conformational matching of the antibody–antigen structures and a specific antibody–antigen score. We have tested the method on both a large non-redundant set of antibody–antigen complexes and on homology models of the antibodies and/or the unbound antigen structure. On a non-redundant test set, our epitope prediction method achieves 44% recall at 14% precision against 23% recall at 14% precision for a background random distribution. We use our epitope predictions to rescore the global docking results of two rigid-body docking algorithms: ZDOCK and ClusPro. In both cases including our epitope, prediction increases the number of near-native poses found among the top decoys.

Availability and implementation: Our software is available from http://www.stats.ox.ac.uk/research/proteins/resources.

Contact:  deane@stats.ox.ac.uk

Supplementary information:  Supplementary Data are available at Bioinformatics online.
‘An Experiment in Constructive Unionism’: Isaac Butt, Home Rule and Federalist Political Thought during the 1870s
Authors: Reid Colin W.
Published: April 2014

Federalism has a rich, if chequered, history within the political discourse of the British and Irish Isles. This article examines the political thought of one much misunderstood advocate of federalism, Isaac Butt, and the debate that his proposal to transform the British constitution prompted. It seeks to recast Butt, the founding father of Irish Home Rule, as a champion of the Union. Historians of Ireland, Britain and federalism, like many of Butt’s contemporaries, struggle to position him within the spectrum of nineteenth-century political thought. The most important work on Isaac Butt and the early Home Rule movement in Ireland remains David Thornley’s study from 1964, which skews its subject matter by framing Butt as representative of ‘a curious imperial nationalism’. This article argues that there was nothing ‘curious’ about Butt’s political thought, and that his conception of a distinct Irish identity within the broader rubric of the Union has been under-appreciated.

For Butt, Home Rule was the mechanism to bind Ireland to Britain and its Empire, thus resolving the ambiguities of the Act of Union of 1800. Butt’s formulation of Home Rule in 1870 envisaged a federalised United Kingdom, which would have weakened Irish exceptionalism within a broader British context. The article positions Butt as representative of a constructive national unionism, and explores the implications of this for Ireland’s relationship with British identity and the Union during the nineteenth century.
Hospital Case Volume Is Associated With Improved Survival for Patients With Metastatic Melanoma
Authors: Huo Jinhai , Lairson David R. , Du Xianglin L. , Chan Wenyaw , Jiang Jing , Buchholz Thomas A. , Guadagnolo B. Ashleigh
Published: April 2014

Objectives:

Hospital case volume has been shown to be a predictor of patient mortality for treatment for various cancers. The influence of hospital case volume on malignant melanoma survival and treatment utilization is unknown.

Methods:

We used the Surveillance, Epidemiology, and End Results-Medicare linked databases to identify patients aged 65 years or older diagnosed with metastatic melanoma between 2000 and 2009. We analyzed claims data to ascertain cancer treatment variation by hospital case volume. Overall survival was evaluated using propensity score methods.

Results:

Among 1438 patients, 612 (42.6%) were treated in low-volume hospitals (≤5 patients) after receiving their diagnosis, 479 (33.3%) were treated in intermediate-volume hospitals (6 to 10 patients), and 347 (24.1%) were treated in high-volume hospitals (>10 patients). In Cox proportional hazards models, treatment in a high-volume hospital after propensity score adjustment was associated with a significant improvement in survival when adjusting for other characteristics (intermediate volume: hazard ratio [HR]=0.70, P=0.0007; high volume: HR=0.63, P<0.0001). Patients treated in high-volume hospitals were less likely to receive chemotherapy, surgery, and/or radiation therapy after a metastatic melanoma diagnosis.

Conclusions:

For patients diagnosed with metastatic melanoma, being treated in a high-volume hospital was associated with an improvement in survival and lower utilization of chemotherapy, immunotherapy, surgery, and radiation therapy.
Outcomes Following Hypofractionated Stereotactic Radiotherapy in the Management of Brain Metastases
Authors: Ahmed Kamran A. , Sarangkasiri Siriporn , Chinnaiyan Prakash , Sahebjam Solmaz , Yu Hsiang-Hsuan Michael , Etame Arnold B. , Rao Nikhil G.
Published: April 2014

Objective:

To evaluate the outcomes of patients treated with hypofractionated stereotactic radiotherapy (HSRT) for radiosensitive and radioresistant brain metastases.

Methods:

Between August 2006 and July 2013, a total of 56 lesions in 44 patients with brain metastases were treated with HSRT. Twenty-three (41.1%) lesions were radioresistant. Patients were treated to a total dose of 24 to 30 Gy in 3 to 5 fractions. Median planning target volume was 6.18 cm3. The primary endpoint for this study was local control with secondary endpoints of overall survival, distant failure, performance status, and treatment toxicity.

Results:

The median follow-up for all patients was 5 months (range, 0.4 to 58.3 mo). Six- and 12-month Kaplan-Meier estimates of local control for all lesions were 85.6% and 79.4%, respectively. Radioresistant tumors had a 6- and 12-month local control rate of 87.0%, whereas radiosensitive tumors had a 6- and 12-month local control rate of 82.5% and 72.2%, respectively (P=0.41). Six- and 12-month distant brain control rates were 56.8% and 46.9%, respectively. Overall survival was significantly associated with recursive partitioning analysis classes I, II, and III (P=0.0003) and graded prognostic assessment classes 2 to 3 and 1 to 1.5 (P=0.041).

Conclusions:

HSRT is a safe and feasible alternative to single-session stereotactic radiosurgery for brain metastases. No difference was observed in local control rates between radioresistant and radiosensitive tumors.
Long-term Outcomes After Gamma Knife Radiosurgery for Meningiomas
Authors: Kondziolka Douglas , Patel Agam D. , Kano Hideyuki , Flickinger John C. , Lunsford L. Dade
Published: April 2014

Background:

Gamma knife stereotactic radiosurgery (SRS) has become an important management strategy for patients with meningiomas. Although prior reports have studied early tumor control, neurological response, and associated morbidity, our purpose was to use clinical and imaging studies to determine whether long-term outcomes remain stable over time.

Materials and Methods:

We studied 290 consecutive patients (92 men and 198 women) who underwent gamma knife SRS for a meningioma between 1987 and 1997. The median tumor margin dose was 15 Gy and the median tumor volume was 5.5 mL. Target definition was performed using contrast enhanced computed tomography in 72 patients and magnetic resonance imaging in 218 patients. The median patient age at radiosurgery was 61 years. Twenty patients had a history of fractionated radiation therapy, 136 patients had undergone a subtotal resection, and 22 patients had recurrences after initial gross total resection.

Results:

The overall tumor control rate was 91%. Twenty-six patients (9%) had evidence of delayed local tumor growth and 44 (15%) had regional tumor progression, which occurred at a median of 38 months. The 10- and 20-year actuarial rates of freedom from tumor progression of the targeted tumor were 87.7%±2.5% and 87.2%±4.2%. Of 234 patients who had symptoms before SRS (n=62, 26%) improved, 126 (54%) had no change in symptoms and 46 (20%) gradually worsened. Thirty-two of 34 (94%) asymptomatic patients remained asymptomatic. We found no difference in long-term tumor control rates between patients who had undergone craniotomy before radiosurgery (89%) and patients who underwent primary radiosurgery (93.1%). Adverse radiation effects were detected in 3.1% of patients. Factors associated with worse progression-free survival included prior radiation therapy (P<0.0001) and higher grade meningioma (P<0.0001). At a median of 8.7 years after SRS, 137 patients were dead at a median age of 77 years.

Conclusions:

We found that gamma knife SRS provided durable tumor control with low morbidity in meningioma patients.
On the relationship between histogram indexing and block-mass indexing
Authors: Amir Amihood , Butman Ayelet , Porat Ely
Published: April 2014

Histogram indexing
, also known as
jumbled pattern indexing
and
permutation indexing
is one of the important current open problems in pattern matching. It was introduced about 6 years ago and has seen active research since. Yet, to date there is no algorithm that can preprocess a text
T
in time
o
(|
T
|
2
/polylog|
T
|) and achieve histogram indexing, even over a binary alphabet, in time independent of the text length. The pattern matching version of this problem has a simple linear-time solution.
Block-mass pattern matching
problem is a recently introduced problem, motivated by issues in mass-spectrometry. It is also an example of a pattern matching problem that has an efficient, almost linear-time solution but whose indexing version is daunting. However, for fixed finite alphabets, there has been progress made. In this paper, a strong connection between the histogram indexing problem and the block-mass pattern indexing problem is shown. The reduction we show between the two problems is amazingly simple. Its value lies in recognizing the connection between these two apparently disparate problems, rather than the complexity of the reduction. In addition, we show that for both these problems, even over unbounded alphabets, there are algorithms that preprocess a text
T
in time
o
(|
T
|
2
/polylog|
T
|) and enable answering indexing queries in time polynomial in the query length. The contributions of this paper are twofold: (i) we introduce the idea of allowing a trade-off between the preprocessing time and query time of various indexing problems that have been stumbling blocks in the literature. (ii) We take the first step in introducing a class of indexing problems that, we believe, cannot be pre-processed in time
o
(|
T
|
2
/polylog|
T
|) and enable linear-time query processing.
Fast computation of a string duplication history under no-breakpoint-reuse
Authors: Brejová Broňa , Kravec Martin , Landau Gad M. , Vinař Tomáš
Published: April 2014

In this paper, we provide an
O
(
n
log
2
n
log log
n
log*
n
) algorithm to compute a duplication history of a string under no-breakpoint-reuse condition. The motivation of this problem stems from computational biology, in particular, from analysis of complex gene clusters. The problem is also related to computing edit distance with block operations, but, in our scenario, the start of the history is not fixed, but chosen to minimize the distance measure.
String search experimentation using massive data
Authors: Moffat Alistair , Gog Simon
Published: April 2014

Descriptions of new string search or indexing algorithms are often accompanied by an experimental evaluation. In this article, we provide guidance as to how such investigations can be carried out, drawing on our experience of measurement in this field. In particular, we describe methodologies for stratifying patterns according to their length and frequency, so that precise response-time measurements can be made; and we describe a metric for categorizing the extent of ‘repetitiveness’ in a text, so that dataset type can also be factored into evaluations. We show that separating these concepts allows a greater understanding of the behaviour of string search algorithms.
Hepatitis B and hepatitis C virus infections among antiretroviral-naive and -experienced HIV co-infected adults
Authors: Manyazewal Tsegahun , Sisay Zufan , Biadgilign Sibhatu , Abegaz Woldaregay Erku
Published: April 2014

Most HIV positive people have not been tested for viral hepatitis and their treatments have not been optimized for possible co-infections. The aim of this study was to investigate the serological pattern of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among antiretroviral (ARV)-naive and -experienced HIV co-infected adults in Addis Ababa, Ethiopia. A total of 500 frozen HIV positive serum and plasma samples collected from ARV-naive (n = 250) and -experienced (n = 250) adults were randomly selected and screened for HBsAg, anti-HBs, HBeAg and anti-HCV using rapid two-site sandwich immunochromatographic assay. The test was performed at Aklilu Lemma Institute of Pathobiology, Addis Ababa University. Positive specimens for HBsAg and anti-HCV markers were further confirmed using third generation ELISA. Of the 500 specimens tested, 15 (3 %), 58 (11.6 %), 3 (0.6 %), 18 (3.6 %), 3 (0.6 %) and 1 (0.2 %) were positive for HBsAg, anti-HBs, HBeAg, anti-HCV, HBsAg and HBeAg, and HBsAg and anti-HBs markers, respectively. No specimen tested positive for both HBeAg and anti-HBs, and 442 (88.4 %) individuals were non-immune to HBV. Of the 250 ARV-naive individuals, 8 (3.2 %), 33 (13.2 %), 2 (0.8 %), 10 (4 %), 2 (0.8 %), and 1 (0.4 %) were positive for HBsAg, anti-HBs, HBeAg, anti-HCV, HBsAg and HBeAg, and HBsAg and anti-HBs markers, respectively. Of the 250 ARV-experienced individuals, 7 (2.8 %), 25 (10 %), 1 (0.4 %), 8 (3.2 %), 1 (0.4 %), and 0 (0 %) were positive for HBsAg, Anti-HBs, HBeAg, anti-HCV, HBsAg and HBeAg, and HBsAg and anti-HBs markers, respectively. In summary, seroprevalence of HIV/HBV and HIV/HCV co-infections was lower in Addis Ababa, Ethiopia, than in Sub-Saharan Africa and globally. HBV and HCV infections were not significantly different between HIV positive subjects who were or who were not on ARV. This suggests that the two groups have equal chance of being infected with these two viruses; despite this, disease progression could be different.
Tissue-specific SMARCA4 binding at active and repressed regulatory elements during embryogenesis
Authors: Attanasio Catia , Nord Alex S. , Zhu Yiwen , Blow Matthew J. , Biddie Simon C. , Mendenhall Eric M. , Dixon Jesse , Wright Crystal , Hosseini Roya , Akiyama Jennifer A. , Holt Amy , Plajzer-Frick Ingrid , Shoukry Malak , Afzal Veena , Ren Bing , Bernstein Bradley E. , Rubin Edward M. , Visel Axel , Pennacchio Len A.
Published: April 2014

The SMARCA4 (also known as BRG1 in humans) chromatin remodeling factor is critical for establishing lineage-specific chromatin states during early mammalian development. However, the role of SMARCA4 in tissue-specific gene regulation during embryogenesis remains poorly defined. To investigate the genome-wide binding landscape of SMARCA4 in differentiating tissues, we engineered a Smarca4FLAG knock-in mouse line. Using ChIP-seq, we identified ∼51,000 SMARCA4-associated regions across six embryonic mouse tissues (forebrain, hindbrain, neural tube, heart, limb, and face) at mid-gestation (E11.5). The majority of these regions was distal from promoters and showed dynamic occupancy, with most distal SMARCA4 sites (73%) confined to a single or limited subset of tissues. To further characterize these regions, we profiled active and repressive histone marks in the same tissues and examined the intersection of informative chromatin states and SMARCA4 binding. This revealed distinct classes of distal SMARCA4-associated elements characterized by activating and repressive chromatin signatures that were associated with tissue-specific up- or down-regulation of gene expression and relevant active/repressed biological pathways. We further demonstrate the predicted active regulatory properties of SMARCA4-associated elements by retrospective analysis of tissue-specific enhancers and direct testing of SMARCA4-bound regions in transgenic mouse assays. Our results indicate a dual active/repressive function of SMARCA4 at distal regulatory sequences in vivo and support its role in tissue-specific gene regulation during embryonic development.
A Shoot-Specific Hypoxic Response of Arabidopsis Sheds Light on the Role of the Phosphate-Responsive Transcription Factor PHOSPHATE STARVATION RESPONSE1
Authors: Klecker Maria , Gasch Philipp , Peisker Helga , Dörmann Peter , Schlicke Hagen , Grimm Bernhard , Mustroph Angelika
Published: April 2014

Plant responses to biotic and abiotic stresses are often very specific, but signal transduction pathways can partially or completely overlap. Here, we demonstrate that in Arabidopsis (Arabidopsis thaliana), the transcriptional responses to phosphate starvation and oxygen deficiency stress comprise a set of commonly induced genes. While the phosphate deficiency response is systemic, under oxygen deficiency, most of the commonly induced genes are found only in illuminated shoots. This jointly induced response to the two stresses is under control of the transcription factor PHOSPHATE STARVATION RESPONSE1 (PHR1), but not of the oxygen-sensing N-end rule pathway, and includes genes encoding proteins for the synthesis of galactolipids, which replace phospholipids in plant membranes under phosphate starvation. Despite the induction of galactolipid synthesis genes, total galactolipid content and plant survival are not severely affected by the up-regulation of galactolipid gene expression in illuminated leaves during hypoxia. However, changes in galactolipid molecular species composition point to an adaptation of lipid fluxes through the endoplasmic reticulum and chloroplast pathways during hypoxia. PHR1-mediated signaling of phosphate deprivation was also light dependent. Because a photoreceptor-mediated PHR1 activation was not detectable under hypoxia, our data suggest that a chloroplast-derived retrograde signal, potentially arising from metabolic changes, regulates PHR1 activity under both oxygen and phosphate deficiency.
Construction efficiency: a tale of two developed countries
Authors: Langston Craig
Published: April 2014

Purpose

– The measurement of construction performance is a vexed problem. Despite much research effort, there remains little agreement over what to measure and how to measure it. The problem is made even more complicated by the desire to benchmark national industry performance against that of other countries. As clearly construction cost forms part of the analysis, the mere adjustment of cost data to an “international currency” has undermined past attempts to draw any meaningful conclusions. The paper aims to discuss these issues.

Design/methodology/approach

– This paper introduces a new method for comparing international construction efficiency, tested on a data set of 337 modern high-rise buildings in both Australia and the USA, and in so doing demonstrates that the ratio of cost over time is capable of ranking the efficiency of projects, building contractors, cities and even entire industries – not only today, but retrospectively over time.

Findings

– It is concluded that, based on data from the largest five cities in each country, efficiency on site is improving in both countries. The growth in baseline cost/m2 suggests a possible rise in project complexity over time. While the trend in efficiency improvement is similar, there is evidence that base costs in Australia have outstripped the USA, meaning that “real” construction efficiency in Australia is relatively less. If Australia held an advantage in the past, then it seems that advantage might be disappearing. The USA is outperforming Australia in terms of construction efficiency by 1.10 per cent per annum.

Originality/value

– Cost is measured as the number of standard “citiBLOC” baskets necessary to construct a project, where a standard basket comprises common and globally applicable construction items priced in each city in local currency, removing the need to apply currency exchange rates that otherwise introduce volatility and erroneous outcomes. Time is measured as the number of months between commencement on site and handover, inclusive of delays related to the construction process on site. Construction efficiency is defined as the ratio of construction cost per month, and is used to comment on the relative performance of the procurement process in different locations.
Improving construction productivity: a subcontractor's perspective
Authors: Loosemore Martin
Published: April 2014

Purpose

– Surprisingly, given the prominence and front-line role of subcontractors in the construction industry, their perspective is almost completely absent from construction productivity literature. Existing research in this area presents a highly one-sided principal contractor perspective and there are very few insights into what subcontractors think. The purpose of this paper is to address the imbalance by investigating the determinants of construction productivity from a subcontractor's perspective.

Design/methodology/approach

– Focus groups with 71 of Australia's leading tier-one subcontractors were conducted with the aim of exploring their insights into the productivity challenge.

Findings

– The findings indicate that the main determinants of productivity for subcontractors are: the quality of relationships with principal contractors; opportunity for early involvement in design; transparent tender practices; growing administration and document control; design management; project management and supervisory skills, particularly in planning, scheduling and coordination; risk management and; industrial relations (IR).

Research limitations/implications

– This research was conducted in Australia and similar research needs to be conducted in other countries to cross-reference and validate the results more widely.

Practical implications

– In practical terms, a “culture” of productivity improvement will need to be “nurtured” across the business and supply chain if productivity is to be improved. In particular contractors should avoid bid shopping, respect subcontractor IP and talk to subcontractors earlier in a project.

Social implications

– By respecting the opinions of subcontractors who employ the vast majority of workers in the construction industry, productivity and employment can be increased.

Originality/value

– The focus group results add significantly to a more balanced understanding of what has hitherto been a one-sided principal contractor focused debate.
Addressing effective construction logistics through the lens of vehicle movements
Authors: Ying Fei , Tookey John , Roberti Johannes
Published: April 2014

Purpose

– Construction logistics is an essential part of construction supply chain management (CSCM). However, limited attention has been paid to this issue in the New Zealand construction industry. The purpose of this paper is to contribute to the knowledge about what hampers efficiency in transporting construction materials and plants to a construction site. The intention is to gain detailed understanding of the practice and obstacles in efficient construction logistics and thus identify interventions to improve logistics efficiency, especially using the numbers of vehicle movements to the construction site as an indicator.

Design/methodology/approach

– A case study approach was adopted with on-site observations and interviews. Observations were performed during constructions on-site from the start of construction to “hand-over” to the building owner. A selection of construction suppliers and subcontractors involved in the studied project were interviewed.

Findings

– Data analysis suggested that cost-related factors affecting the construction logistics, both monetary and non-monetary factors were not measured and largely ignored, especially the possible environmental and/or social impact occurred by the truck movement. Factors in the service-related sector were insufficiently managed in the observed site. The main contribution to inefficient construction logistics are related to understanding and implementing CSCM. It is noticed that there is inadequate awareness of CSCM and logistics efficiency largely due to lack of commitment from the management level and skills at the operational level.

Originality/value

– Significant intrinsic and extrinsic interventions necessary to enhance construction logistics were acknowledged from the data analysis. These include both qualitative and quantitative data. These intrinsic and extrinsic interventions, such as implementing appropriate logistics tools that suits individual site and introducing traffic management costs, offer plausible explanations regarding how to improve the efficiency in construction logistics through optimising transportation movements to the construction site.