bluuebunny/crossref_metadata_2025_split huggingface dataset:
Site-Specific Association with Host and Viral Chromatin by Kaposi's Sarcoma-Associated Herpesvirus LANA and Its Reversal during Lytic Reactivation
Authors: Mercier Alexandre , Arias Carolina , Madrid Alexis S. , Holdorf Meghan M. , Ganem Don 
Published: April 2014

ABSTRACT
Latency-associated nuclear antigen (LANA), a multifunctional protein expressed by the Kaposi sarcoma-associated herpesvirus (KSHV) in latently infected cells, is required for stable maintenance of the viral episome. This is mediated by two interactions: LANA binds to specific sequences (LBS1 and LBS2) on viral DNA and also engages host histones, tethering the viral genome to host chromosomes in mitosis. LANA has also been suggested to affect host gene expression, but both the mechanism(s) and role of this dysregulation in KSHV biology remain unclear. Here, we have examined LANA interactions with host chromatin on a genome-wide scale using chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) and show that LANA predominantly targets human genes near their transcriptional start sites (TSSs). These host LANA-binding sites are generally found within transcriptionally active promoters and display striking overrepresentation of a consensus DNA sequence virtually identical to the LANA-binding site 1 (LBS1) motif in KSHV DNA. Comparison of the ChIP-seq profile with whole-transcriptome (high-throughput sequencing of RNA transcripts [RNA-seq]) data reveals that few of the genes that are differentially regulated in latent infection are occupied by LANA at their promoters. This suggests that direct LANA binding to promoters is not the prime determinant of altered host transcription in KSHV-infected cells. Most surprisingly, the association of LANA to both host and viral DNA is strongly disrupted during the lytic cycle of KSHV. This disruption can be prevented by the inhibition of viral DNA synthesis, suggesting the existence of novel and potent regulatory mechanisms linked to either viral DNA replication or late gene expression.

IMPORTANCE
Here, we employ complementary genome-wide analyses to evaluate the distribution of the highly abundant latency-associated nuclear antigen, LANA, on the host genome and its impact on host gene expression during KSHV latent infection. Combined, ChIP-seq and RNA-seq reveal that LANA accumulates at active gene promoters that harbor specific short DNA sequences that are highly reminiscent of its cognate binding sites in the virus genome. Unexpectedly, we found that such association does not lead to remodeling of global host transcription during latency. We also report for the first time that LANA's ability to bind host and viral chromatin is highly dynamic and is disrupted in cells undergoing an extensive lytic reactivation. This therefore suggests that the association of LANA to chromatin during a productive infection cycle is controlled by a new regulatory mechanism.
Primary Human Macrophages Serve as Vehicles for Vaccinia Virus Replication and Dissemination
Authors: Byrd Daniel , Shepherd Nicole , Lan Jie , Hu Ningjie , Amet Tohti , Yang Kai , Desai Mona , Yu Qigui 
Published: April 2014

ABSTRACTHuman monocytic and professional antigen-presenting cells have been reported only to exhibit abortive infections with vaccinia virus (VACV). We found that monocyte-derived macrophages (MDMs), including granulocyte macrophage colony-stimulating factor (GM-CSF)-polarized M1 and macrophage colony-stimulating factor (M-CSF)-polarized M2, but not human AB serum-derived cells, were permissive to VACV replication. The titers of infectious virions in both cell-free supernatants and cellular lysates of infected M1 and M2 markedly increased in a time-dependent manner. The majority of virions produced in permissive MDMs were extracellular enveloped virions (EEV), a secreted form of VACV associated with long-range virus dissemination, and were mainly found in the culture supernatant. Infected MDMs formed VACV factories, actin tails, virion-associated branching structures, and cell linkages, indicating that MDMs are able to initiatede novosynthesis of viral DNA and promote virus release. VACV replication was sensitive to inhibitors against the Akt and Erk1/2 pathways that can be activated by VACV infection and M-CSF stimulation. Classical activation of MDMs by lipopolysaccharide (LPS) plus gamma interferon (IFN-γ) stimulation caused no effect on VACV replication, while alternative activation of MDMs by interleukin-10 (IL-10) or LPS-plus-IL-1β treatment significantly decreased VACV production. The IL-10-mediated suppression of VACV replication was largely due to Stat3 activation, as a Stat3 inhibitor restored virus production to levels observed without IL-10 stimulation. In conclusion, our data demonstrate that primary human macrophages are permissive to VACV replication. After infection, these cells produce EEV for long-range dissemination and also form structures associated with virions which may contribute to cell-cell spread.IMPORTANCEOur results provide critical information to the burgeoning fields of cancer-killing (oncolytic) virus therapy with vaccinia virus (VACV). One type of macrophage (M2) is considered a common presence in tumors and is associated with poor prognosis. Our results demonstrate a preference for VACV replication in M2 macrophages and could assist in designing treatments and engineering poxviruses with special considerations for their effect on M2 macrophage-containing tumors. Additionally, this work highlights the importance of macrophages in the field of vaccine development using poxviruses as vectors. The understanding of the dynamics of poxvirus-infected foci is central in understanding the effectiveness of the immune response to poxvirus-mediated vaccine vectors. Monocytic cells have been found to be an important part of VACV skin lesions in mice in controlling the infection as well as mediating virus transport out of infected foci.
Giraffes' greater good?
Authors: Sayers Ian 
Published: April 2014

THIS series gives readers the opportunity to consider and contribute to discussion of some of the ethical dilemmas that can arise in veterinary practice. Each month, a case scenario is presented, followed by discussion of some of the issues involved.In addition, a possible way forward is suggested; however, there is rarely a cut‐and‐dried answer in such cases, and readers may wish to suggest an alternative approach. This month's dilemma, ‘Giraffes’ greater good?', was submitted and is discussed by Ian Sayers. Readers with comments to contribute are invited to send them as soon as possible, so that they can be considered for publication in the next issue. Discussion of the dilemma ‘Looking a store horse in the mouth’, which was published in the March issue of In Practice, appears on page 215.The series is being coordinated by Siobhan Mullan, of the University of Bristol. It is hoped it will provide a framework that will help practices find solutions when facing similar dilemmas.
Multigene profiling to identify alternative treatment options for glioblastoma: a pilot study
Authors: Tabone Tania , Abuhusain Hazem J , Nowak Anna K ,   Australian Genomics and Clinical Outcome of Glioma (AGOG) Network, Erber Wendy N , McDonald Kerrie L 
Published: April 2014

Glioblastoma (GBM) is a highly aggressive malignancy and the most effective treatment regime has a high relapse rate. Increasingly, the development of therapies involves defining drug–diagnostic combinations where the presence of a molecular target or marker identifies patients who are most likely to respond to a specific therapy. Trials in other solid cancers have demonstrated clear utility in the incorporation of biomarkers to stratify patients to targeted treatment, however, there are no mutations that are currently used to inform treatment options for GBM.AimsWe piloted the use of high-throughput next-generation sequencing technology to identify genetic mutations in 44 GBM specimens that may be amenable to current or future targeted therapeutic strategies.MethodSomatic mutation profiling was performed using the AmpliSeq Cancer Hotspot Panel v2 and semiconductor sequencing technology.ResultsA total of 66 mutations were detected in 35/44 (80%) patients. The number of mutations per tumour ranged from 0 to 4 (average per tumour=1.5). The most frequent mutations were inTP53(n=12),PTEN(n=9),EGFR(n=8) andPIK3CA(n=5). Clinically actionable somatic mutations were detected in 24/35 (69%) patients.ConclusionsThis study demonstrates that the use of an ‘off-the-shelf’ oncogene primer panel and benchtop next-generation sequencer can identify mutations and potentially actionable targets in the majority of GBM patients. Data from this pilot highlights the potential for targeted genetic resequencing to identify mutations that may inform treatment options and predict outcomes.
An Alternate Proof of the De Branges Theorem on Canonical Systems
Authors: Acharya Keshav Raj 
Published: April 2014

The aim of this paper is to show that, in the limit circle case, the defect index of a symmetric relation induced by canonical systems, is constant on ℂ. This provides an alternative proof of the De Branges theorem that the canonical systems with tr H1 imply the limit point case. To this end, we discuss the spectral theory of a linear relation induced by a canonical system.
A Soluble Form of CD80 Enhances Antitumor Immunity by Neutralizing Programmed Death Ligand-1 and Simultaneously Providing Costimulation
Authors: Haile Samuel T. , Horn Lucas A. , Ostrand-Rosenberg Suzanne 
Published: April 2014

AbstractTumor cells use various methods of immunosuppression to overcome antitumor immunity. One such method is that of programmed death ligand-1 (PD-L1 or B7-H1), which upon binding its receptor PD-1 on T cells triggers apoptotic death of the activated T cells. Overexpression of the costimulatory molecule CD80 on PD-L1+ tumor cells, or inclusion of a soluble form of CD80 (CD80-Fc), maintains the activation of PD-1+–activated T cells. Using T cells from CD28-deficient mice and antibodies to block CD28 on human T cells, we now report that a soluble form of CD80 mediates this effect by simultaneously neutralizing PD-1–PD-L1-mediated immunosuppression and by providing CD80–CD28 costimulation, and is more effective than antibodies to PD-L1 or PD-1 in maintaining IFNγ production by PD-1+ activated T cells. Therefore, soluble CD80 may be a more effective therapeutic than these checkpoint antibodies for facilitating the development and maintenance of antitumor immunity because it has the dual functions of preventing PD-L1–mediated immunosuppression and simultaneously delivering the second signal for T-cell activation. Cancer Immunol Res; 2(7); 610–5. ©2014 AACR.
Modeling and Interpretation of S-Band Ice Crystal Depolarization Signatures from Data Obtained by Simultaneously Transmitting Horizontally and Vertically Polarized Fields
Authors: Hubbert J. C. , Ellis S. M. , Chang W.-Y. , Rutledge S. , Dixon M. 
Published: April 2014

AbstractData collected by the National Center for Atmospheric Research S-band polarimetric radar (S-Pol) during the Terrain-Influenced Monsoon Rainfall Experiment (TiMREX) in Taiwan are analyzed and used to infer storm microphysics in the ice phase of convective storms. Both simultaneous horizontal (H) and vertical (V) (SHV) transmit polarization data and fast-alternating H and V (FHV) transmit polarization data are used in the analysis. The SHV Zdr (differential reflectivity) data show radial stripes of biased data in the ice phase that are likely caused by aligned and canted ice crystals. Similar radial streaks in the linear depolarization ratio (LDR) are presented that are also biased by the same mechanism. Dual-Doppler synthesis and sounding data characterize the storm environment and support the inferences concerning the ice particle types. Small convective cells were observed to have both large positive and large negative Kdp (specific differential phase) values. Negative Kdp regions suggest that ice crystals are vertically aligned by electric fields. Since high |Kdp| values of 0.8° km−1 in both negative and positive Kdp regions in the ice phase are accompanied by Zdr values close to 0 dB, it is inferred that there are two types of ice crystals present: 1) smaller aligned ice crystals that cause the Kdp signatures and 2) larger aggregates or graupel that cause the Zdr signatures. The inferences are supported with simulated ice particle scattering calculations. A radar scattering model is used to explain the anomalous radial streaks in SHV and LDR.
Eddy-Induced Growth Rate of Low-Frequency Variability and Its Mid- to Late Winter Suppression in the Northern Hemisphere
Authors: Ren Hong-Li , Jin Fei-Fei , Kug Jong-Seong 
Published: April 2014

Abstract
Synoptic eddy and low-frequency flow (SELF) feedback plays an important role in reinforcing low-frequency variability (LFV). Recent studies showed that an eddy-induced growth (EIG) or instability makes a fundamental contribution to the maintenance of LFV. To quantify the efficiency of the SELF feedback, this study examines the spatiotemporal features of the empirical diagnostics of EIG and its associations with LFV. The results show that, in terms of eddy vorticity forcing, the EIG rate of LFV is generally larger (smaller) in the upper (lower) troposphere, whereas, in terms of eddy potential vorticity forcing, it is larger in the lower troposphere to partly balance the damping effect of surface friction. The local EIG rate shows a horizontal spatial distribution that corresponds to storm-track activity, which tends to be responsible for maintaining LFV amplitudes and patterns as well as sustaining eddy-driven jets. In fact, the EIG rate has a well-defined seasonality, being generally larger in cold seasons and smaller in the warmest season, and this seasonality is stronger in the Northern Hemisphere than in the Southern Hemisphere. This study also reveals a mid- to late winter (January–March) suppression of the EIG rate in the Northern Hemisphere, which indicates a reduced eddy feedback efficiency and may be largely attributed to the eddy kinetic energy suppression and the midlatitude zonal wind maximum in the midwinter of the Northern Hemisphere.
Wind-Driven Coastal Sea Level Variability in the Northeast Pacific
Authors: Thompson Philip R. , Merrifield Mark A. , Wells Judith R. , Chang Chantel M. 
Published: April 2014

Abstract
The rate of coastal sea level change in the northeast Pacific (NEP) has decreased in recent decades. The relative contributions to the decreased rate from remote equatorial wind stress, local longshore wind stress, and local windstress curl are examined. Regressions of sea level onto wind stress time series and comparisons between NEP and Fremantle sea levels suggest that the decreased rate in the NEP is primarily due to oceanic adjustment to strengthened trade winds along the equatorial and coastal waveguides. When taking care to account for correlations between the various wind stress time series, the roles of longshore wind stress and local windstress curl are found to be of minor importance in comparison to equatorial forcing. The predictability of decadal sea level change rates along the NEP coastline is therefore largely determined by tropical variability. In addition, the importance of accounting for regional, wind-driven sea level variations when attempting to calculate accelerations in the long-term rate of sea level rise is demonstrated.
Identification of intermediate-risk patients with acute symptomatic pulmonary embolism
Authors: Bova Carlo , Sanchez Olivier , Prandoni Paolo , Lankeit Mareike , Konstantinides Stavros , Vanni Simone , Jiménez David 
Published: April 2014

The identification of normotensive patients with acute pulmonary embolism (PE) at high risk of adverse PE-related clinical events (i.e.intermediate-risk group) is a major challenge.We combined individual patient data from six studies involving 2874 normotensive patients with PE. We developed a prognostic model for intermediate-risk PE based on the clinical presentation and the assessment of right ventricular dysfunction and myocardial injury. We used a composite of PE-related death, haemodynamic collapse or recurrent PE within 30 days of follow-up as the main outcome measure.The primary outcome occurred in 198 (6.9%) patients. Predictors of complications included systolic blood pressure 90–100 mmHg (adjusted odds ratio (aOR) 2.45, 95% CI 1.50–3.99), heart rate ≥110 beats per min (aOR 1.87, 95% CI 1.31–2.69), elevated cardiac troponin (aOR 2.49, 95% CI 1.71–3.69) and right ventricular dysfunction (aOR 2.28, 95% CI 1.58–3.29). We used these variables to construct a multidimensional seven-point risk index; the odds ratio for complications per one-point increase in the score was 1.55 (95% CI 1.43–1.68; p<0.001). The model identified three stages (I, II and III) with 30-day PE-related complication rates of 4.2%, 10.8% and 29.2%, respectively.In conclusion, a simple grading system may assist clinicians in identifying intermediate-risk PE.
Syntheses, Crystal Structures, and Reversible Structural Transformation of Two Zinc Coordination Polymers
Authors: Zhang Lina , Chen Jinxi , Ling Yun , Chen Zhenxia 
Published: April 2014

Abstract
Two zinc coordination polymers, [Zn(H2dhtp)(2,2′-bpy)(H2O)] (1) and [Zn(H2dhtp)(2,2′-bpy)] (2) (H4dhtp: 2,5-dihydroxyterephthalic acid), have been simultaneously synthesized from a one-pot reaction system. Pure phase of 1 could be obtained by varying the ratio of Zn(II) salt/H4dhtp, while that of 2 could not. A reversible structural transformation between 1 and 2 was observed by heating and immersing in mother liquid, and their photoluminescent properties were also studied.
Reviews
Authors: Stanhope Zara , Allen Felicity , Connolly Maeve , Pedersen Courtney 
Published: April 2014

Abstract
‘Iteration: Again’, Contemporary Art Spaces Tasmania, Hobart, Australia, 18 September–15 October 2011
Smadar Dreyfus’ School, Folkestone Triennial 2011, Folkestone, UK, 25 June–25 September 2011
Chance, flow and measurement: Reviewing the Conference ‘TIMING – on the Temporal Dimension of Exhibiting’, Cultures of the Curatorial and Studio International, Academy of Visual Arts, Leipzig, 19–21 JANUARY 2012
The Culture of Curating and the Curating of Culture(s), Paul O’Neill (2012) Cambridge, MA and London, England: The MIT Press, 192 pp. ISBN: 9780262017725, h/bk, £19.95 (black and white illustrations)
The algebra of essential relations on a finite set
Authors: Bouc Serge , Thévenaz Jacques 
Published: April 2014

Abstract

Let X be a finite set and let k be a commutative ring.
We consider the k-algebra of the monoid of all relations on X,
modulo the ideal generated by the relations factorizing through a set of cardinality strictly smaller than Card(X),
called inessential relations. This quotient is called the essential algebra associated to X.
We then define a suitable nilpotent ideal of the essential algebra
and describe completely the structure of the corresponding quotient,
a product of matrix algebras over suitable group algebras.
In particular, we obtain a description of all the simple modules for the essential algebra.
Laughter on the 2008 campaign trail: How presidential candidates used humor during primary debates
Authors: Stewart Patrick 
Published: April 2014

AbstractHumor has long been an important tool for presidential candidates on the campaign trail by humanizing them while endearing them to their constituents. While this humor may reduce the chasm between candidate and voter while establishing the candidates' personal qualities and enhancing prestige, it can also be used as a tool to attack and denigrate opponents both within and outside the candidate's political party. The laughter that occurs can also serve to signal support for the candidate and increase group cohesion. This paper analyzes the use of humor by Republican and Democratic Presidential candidates during primary debates of the 2008 electoral season. Data from each political party's first three debates (Democrats: April 26, June 3, June 28; Republicans: May 3, May 15, June 5) as well as data from two additional debates which focused on both parties' front-running candidates (New Hampshire [January 5] and Super Tuesday [January 30, 31]) were collected using audience laughter as indicator of a “successful” humorous comment. Hypotheses concerning differences between the two parties and the status of the candidates as front-runners or second-tier are tested by considering the target of the humorous comment and the nature of the laughter elicited in terms of the source, as well as the length and strength of the audience response.
Deaf jokes and sign language humor
Authors: Sutton-Spence Rachel , Napoli Donna Jo 
Published: April 2014

AbstractThis paper describes the humor of Deaf communities, arguing that the humor is related primarily to the dominant visual experience of Deaf people, but also influenced by their knowledge of humor traditions in the hearing society at large. Sign language humor in America and Britain may be seen in the creation of new visual signs, the witty reanalysis of existing signs and in bilingual games in which English is manipulated within sign languages. The content of Deaf humor supports the in-group of community members who embrace their signing collective Deaf identity and denigrates out-group people, including deaf people who do not belong to the community and hearing people who are often seen as a threat to the community. Many of these jokes also make reference to sign language. We conclude that the visual nature of Deaf humor is one of its key characteristics and ask what else this can tell us about the Deaf cultural way of interacting with and presenting the world.
Are pun mechanisms universal? A comparative analysis across language families
Authors: Guidi Annarita 
Published: April 2014

AbstractThe purpose of this paper is to provide a new definition of pun, in order to describe it in a cross-linguistic perspective and to point out that puns, as verbal humorous phenomena which exploit ordinary phonetic processes, are universal. The definition is tested through a comparison among puns in 15 languages belonging to different families. I show that puns always imply the manipulation of a string through mechanisms involving all the elements of the phonetic chain. Such manipulation is realized in all possible string and syllable domains, tendentially within the threshold of five elements. Taking into account the progressive improvements in linguistic models of puns, the present study also provides a synthetic overview of the literature on puns and related phenomena. Results include some phonetic elements not considered in previous studies; a cross-linguistic formulation of phonetic distance between target and pun is also proposed.
Modelling of the Membrane Permeability Effect on the H2 Production Using CFD Method
Authors: Benguerba Yacine , Dumas Christine , Ernst Barbara 
Published: April 2014

Abstract
Autothermal reforming of CH4 in a membrane catalytic microreactor for the production of hydrogen at different temperatures over supported Ni catalysts has been studied. A three-dimensional mathematical model was developed using a computational fluid dynamics (CFD) technique. The effect of using different membranes on the performance of the micro-reactor was analysed. The amounts of hydrogen produced and separated in each case, under the same operating conditions, were compared. It was proven that using the porous membrane (Ni–Al2O3) could be an economic solution for the production and separation of hydrogen in membrane reactors.