bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extremes of Age Are Associated with Indeterminate QuantiFERON-TB Gold Assay Results
Authors: Tebruegge Marc , de Graaf Hans , Sukhtankar Priya , Elkington Paul , Marshall Ben , Schuster Helmut , Patel Sanjay , Faust Saul N. 
Published: May 2014

ABSTRACT

Results from 3,263 QuantiFERON-TB Gold in-tube (QFT-GIT) assays were analyzed to determine the impact of age on test performance. The proportion of indeterminate results was significantly higher in pediatric and elderly (9.1% and 7.4%, respectively) than in adult (2.6%; chi-square test,
P
< 0.0001) patients. A detailed analysis of indeterminate QFT-GIT assay results is presented.
Adeno-Associated Virus Rep Represses the Human Integration Site Promoter by Two Pathways That Are Similar to Those Required for the Regulation of the Viral p5 Promoter
Authors: Dutheil Nathalie , Smith Sarah C. , Agúndez Leticia , Vincent-Mistiaen Zoé I. , Escalante Carlos R. , Linden R. Michael , Henckaerts Els 
Published: May 2014

ABSTRACT

Adeno-associated virus serotype 2 (AAV2) can efficiently replicate in cells that have been infected with helper viruses, such as adenovirus or herpesvirus. However, in the absence of helper virus infection, AAV2 establishes latency by integrating its genome site specifically into
PPP1R12C
, a gene located on chromosome 19. This integration target site falls into one of the most gene-dense regions of the human genome, thus inviting the question as to whether the virus has evolved mechanisms to control this complex transcriptional environment in order to facilitate integration, maintain an apparently innocuous latency, and/or establish conditions that are conducive to the rescue of the integrated viral genome. The viral replication (Rep) proteins control and direct every known aspect of the viral life cycle and have been shown to tightly control all AAV2 promoters. In addition, a number of heterologous promoters are repressed by the AAV2 Rep proteins. Here, we demonstrate that Rep proteins efficiently repress expression from the target site
PPP1R12C
promoter. We find evidence that this repression employs mechanisms similar to those described for Rep-mediated AAV2 p5 promoter regulation. Furthermore, we show that the repression of the cellular target site promoter is based on two distinct mechanisms, one relying on the presence of a functional Rep binding motif within the 5′ untranslated region (UTR) of
PPP1R12C
, whereas the second pathway requires only an intact nucleoside triphosphate (NTP) binding site within the Rep proteins, indicating the possible reliance of this pathway on interactions of the Rep proteins with cellular proteins that mediate or regulate cellular transcription.

IMPORTANCE
The observation that repression of transcription from the adeno-associated virus serotype 2 (AAV2) p5 and integration target site promoters is mediated by shared mechanisms highlights the possible coevolution of virus and host and could lead to the identification of host factors that the virus exploits to navigate its life cycle.
Towards global benchmarking of food environments and policies to reduce obesity and diet-related non-communicable diseases: design and methods for nation-wide surveys
Authors: Vandevijvere Stefanie , Swinburn Boyd ,   for the International Network for Food and Obesity/non-communicable diseases (NCDs) Research, Monitoring and Action Support (INFORMAS)
Published: May 2014

IntroductionUnhealthy diets are heavily driven by unhealthy food environments. The International Network for Food and Obesity/non-communicable diseases (NCDs) Research, Monitoring and Action Support (INFORMAS) has been established to reduce obesity, NCDs and their related inequalities globally. This paper describes the design and methods of the first-ever, comprehensive national survey on the healthiness of food environments and the public and private sector policies influencing them, as a first step towards global monitoring of food environments and policies.Methods and analysisA package of 11 substudies has been identified: (1) food composition, labelling and promotion on food packages; (2) food prices, shelf space and placement of foods in different outlets (mainly supermarkets); (3) food provision in schools/early childhood education (ECE) services and outdoor food promotion around schools/ECE services; (4) density of and proximity to food outlets in communities; food promotion to children via (5) television, (6) magazines, (7) sport club sponsorships, and (8) internet and social media; (9) analysis of the impact of trade and investment agreements on food environments; (10) government policies and actions; and (11) private sector actions and practices. For the substudies on food prices, provision, promotion and retail, ‘environmental equity’ indicators have been developed to check progress towards reducing diet-related health inequalities. Indicators for these modules will be assessed by tertiles of area deprivation index or school deciles. International ‘best practice benchmarks’ will be identified, against which to compare progress of countries on improving the healthiness of their food environments and policies.DisseminationThis research is highly original due to the very ‘upstream’ approach being taken and its direct policy relevance. The detailed protocols will be offered to and adapted for countries of varying size and income in order to establish INFORMAS globally as a new monitoring initiative to reduce obesity and diet-related NCDs.
Repeated injection of hydrothermal fluids into downdip carbonates: a diagenetic and stratigraphic mechanism for localization of reservoir porosity, Indian Basin Field, New Mexico, USA
Authors: Hiemstra Erik J. , Goldstein Robert H. 
Published: May 2014

Abstract
A detailed study of the Pennsylvanian Indian Basin Field of New Mexico, USA is used to develop a conceptual model that predicts reservoir porosity in clean down-depositional-dip marine carbonate, where repeated fracturing allows for hydrothermal fluid flow. Strata updip probably experienced repeated events of subaerial exposure, resulting in mineralogical stabilization and extensive calcite cementation that prevented extensive hydrothermal alteration. Clean, carbonate sediment deposited downdip was more prone to alteration by hydrothermal fluids. In the reservoir, cement stratigraphy shows regionally persistent zones closely associated with fracturing. Fluid inclusion data show high temperatures and repeated rises and falls, indicating tectonic valving in a hydrothermal system. Salinity data support this and indicate a late event of meteoric influx. Sr- and O-isotope data indicate higher temperature and less rock–water interaction in fault damage zones, evidence for intensified fluid flow in such areas. Formation of vugs and molds was associated with the hydrothermal fluid flow, which was driven by convection, probably initiated during 40–30 Ma intrusive activity and continuing after the onset of Basin and Range uplift and unroofing.
Rapid Decreases in Blood Pressure from Antihypertensive Treatment were Associated with Increased Cancer Mortality in the Systolic Hypertension in the Elderly Program
Authors: Swerdel Joel N. , Janevic Teresa M. , Cabrera Javier , Cosgrove Nora M. , Sedjro Jeanine E. , Pressel Sara L. , Davis Barry R. , Kostis John B. 
Published: May 2014

Abstract
Background: Research on the association between antihypertensive drug treatment (HTDT) and cancer is equivocal. We tested the hypothesis that large, rapid decreases in blood pressure following HTDT are associated with higher cancer mortality.
Methods: Data from the Systolic Hypertension in the Elderly Program (SHEP) with 15-year cause-specific follow-up for mortality were used. We used changes from baseline in seated and standing systolic blood pressure (SBP) measurements at 3, 6, 9, and 12 months after the initiation of HTDT. Hazard ratios adjusted for demographics, comorbidities, and competing risk of non–cancer-related deaths were estimated to determine the association between SBP change, as a continuous or time-dependent measure, and cancer-related death.
Results: SHEP participants taking antihypertensive medication who exhibited a decrease in seated SBP of 29 mm Hg or more (50th percentile and above) at 3 months were at a 58% greater risk of cancer-related death during a 15-year follow-up compared with those with no decrease in SBP (P = 0.007, 42% increased risk P = 0.02 for standing SBP). Those participants whose maximal seated SBP change occurred in the first 3 months of treatment had 2.6-times greater risk of cancer mortality compared with those whose maximal seated SBP change occurred at 12 months (P = 0.004).
Conclusions: Large SBP decreases early in HTDT were associated with an increased risk of cancer-related death during a 15-year follow-up. Further studies are needed to confirm and explore the potential mechanisms for this association.
Impact: Rapid decreases in blood pressure following HTDT may be a risk factor for cancer. Cancer Epidemiol Biomarkers Prev; 23(8); 1589–97. ©2014 AACR.
Genome-Wide Association Study: A Useful Tool to Identify Common Genetic Variants Associated with Drug Toxicity and Efficacy in Cancer Pharmacogenomics
Authors: Low Siew-Kee , Takahashi Atsushi , Mushiroda Taisei , Kubo Michiaki 
Published: May 2014

Abstract
In recent years, the utilization of genome-wide association study (GWAS) has proved to be a beneficial method to identify novel common genetic variations not only for disease susceptibility but also for drug efficacy and drug-induced toxicity, creating a field of pharmacogenomics studies. In addition, the findings from GWAS also generate new biologic hypotheses that could improve the understanding of pathophysiology for disease or the mechanism of drug-induced toxicity. This review highlights the implications of GWAS that have been published to date and discusses the successes as well as challenges of using GWAS in cancer pharmacogenomics. The aim of pharmacogenomics is to realize the vision of personalized medicine; it is hoped that through GWAS, novel common genetic variations could be identified to predict clinical outcome and/or toxicity in cancer therapies that subsequently could be implemented to improve the quality of lives of patients with cancer. Nevertheless, given the complexity of cancer therapies, underpowered studies, and large heterogeneity of study designs, collaborative efforts are needed to validate these findings and overcome the limitations of GWA studies before clinical implementation.
See all articles in this CCR Focus section, “Progress in Pharmacodynamic Endpoints.”
Clin Cancer Res; 20(10); 2541–52. ©2014 AACR.
Titration of the gap junction protein Connexin43 reduces atherogenesis
Authors: Morel Sandrine , Chanson Marc , Nguyen Thien D. , Glass Aaron M. , Sarieddine Maya Z. Richani , Meens Merlijn J. , Burnier Laurent , Taffet Steven M. , Kwak Brenda R. 
Published: May 2014

SummaryUbiquitous reduction of the gap junction protein Connexin43 (Cx43) in mice provides beneficial effects on progression and composition of atherosclerotic lesions. Cx43 is expressed in multiple atheroma-associated cells but its function in each cell type is not known. To examine specifically the role of Cx43 in immune cells, we have lethally irradiated low-density lipoprotein receptor-deficient mice and reconstituted with Cx43+/+, Cx43+/− or Cx43−/− haematopoietic fetal liver cells. Progression of atherosclerosis was significantly lower in aortic roots of Cx43+/− chimeras compared with Cx43+/+ and Cx43−/− chimeras, and their plaques contained significantly less neutrophils. The relative proportion of circulating leukocytes was similar between the three groups. Interestingly, the chemoattraction of neutrophils, which did not express Cx43, was reduced in response to supernatant secreted by Cx43+/− macrophages in comparison with the ones of Cx43+/+ and Cx43−/− macrophages. Cx43+/− macrophages did not differ from Cx43+/+ and Cx43−/− macrophages in terms of M1/M2 polarisation but show modified gene expression for a variety chemokines and complement components. In conclusion, titration of Cx43 expression in bone marrow-derived macrophages reduces atherosclerotic plaque formation and chemoattraction of neutrophils to the lesions.
Inhibition of the Plasma SCUBE1, a Novel Platelet Adhesive Protein, Protects Mice Against Thrombosis
Authors: Wu Meng-Ying , Lin Yuh-Charn , Liao Wei-Ju , Tu Cheng-Fen , Chen Ming-Huei , Roffler Steve R. , Yang Ruey-Bing 
Published: May 2014

Objective—
Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1), a secreted and surface-exposed glycoprotein on activated platelets, promotes platelet–platelet interaction and supports platelet–matrix adhesion. Its plasma level is a biomarker of platelet activation in acute thrombotic diseases. However, the exact roles of plasma SCUBE1 in vivo remain undefined.

Approach and Results—
We generated new mutant (Δ) mice lacking the soluble but retaining the membrane-bound form of SCUBE1. Plasma SCUBE1-depleted Δ/Δ mice showed normal hematologic and coagulant features and expression of major platelet receptors, but Δ/Δ platelet-rich plasma showed impaired platelet aggregation in response to ADP and collagen treatment. The addition of purified recombinant SCUBE1 protein restored the aggregation of platelets in Δ/Δ platelet-rich plasma and further enhanced platelet aggregation in +/+ platelet-rich plasma. Plasma deficiency of SCUBE1 diminished arterial thrombosis in mice and protected against lethal thromboembolism induced by collagen-epinephrine treatment. Last, antibodies directed against the epidermal growth factor–like repeats of SCUBE1, which are involved in trans-homophilic protein–protein interactions, protected mice against fatal thromboembolism without causing bleeding in vivo.

Conclusions—
We conclude that plasma SCUBE1 participates in platelet aggregation by bridging adjacent activated platelets in thrombosis. Blockade of soluble SCUBE1 might represent a novel antithrombotic strategy.
Caucasian, Iranian and Urartian Bronze Bells
Authors: Castelluccia Manuel , Dan Roberto 
Published: May 2014

AbstractThis paper presents a review of metal “bells”, a category of metal object often found in Iron Age archaeological contexts of Caucasian, north Iranian and Urartian cultures. Each cultural sphere is considered separately, focusing on material brought to light during archaeological excavations. An analysis of these three different traditions allows comparison of these artifacts in order to detect evidence of contacts and reciprocal influences between these cultural regions, which strongly interacted during the first half of the Iron Age.
Effective Isentropic Diffusivity of Tropospheric Transport
Authors: Chen Gang , Plumb Alan 
Published: May 2014

Abstract
Tropospheric transport can be described qualitatively by the slow mean diabatic circulation and rapid isentropic mixing, yet a quantitative understanding of the transport circulation is complicated, as nearly half of the isentropic surfaces in the troposphere frequently intersect the ground. A theoretical framework for the effective isentropic diffusivity of tropospheric transport is presented. Compared with previous isentropic analysis of effective diffusivity, a new diagnostic is introduced to quantify the eddy diffusivity of the near-surface isentropic flow. This diagnostic also links the effective eddy diffusivity directly to a diffusive closure of eddy fluxes through a finite-amplitude wave activity equation.
The theory is examined in a dry primitive equation model on the sphere. It is found that the upper troposphere is characterized by a diffusivity minimum at the jet’s center with enhanced mixing at the jet’s flanks and that the lower troposphere is dominated by stronger mixing throughout the baroclinic zone. This structure of isentropic diffusivity is generally consistent with the diffusivity obtained from the geostrophic component of the flow. Furthermore, the isentropic diffusivity agrees broadly with the tracer equivalent length obtained from either a spectral diffusion scheme or a semi-Lagrangian advection scheme, indicating that the effective diffusivity of tropospheric transport is largely dictated by large-scale stirring rather than details of the small-scale diffusion acting on the tracers.
A Formal Analysis of the Feedback Concept in Climate Models. Part II: Tangent Linear Systems in GCMs
Authors: Lahellec Alain , Dufresne Jean-Louis 
Published: May 2014

Abstract
Climate analysis is greatly simplified in perturbation analysis when filtered anomalies show linear behavior. In the first part (part I) of this two-part analysis, the formal tangent linear system (TLS) that handles linear behavior was used to demonstrate the strict equivalence between feedback and sensitivity analysis but at the cost of reducing the generality of its application to GCMs. In this second part, the full feedback analysis is introduced from the application of the so-called regression method of Gregory et al. The authors give a complete example of its use in the global analysis of the phase 5 of the Coupled Model Intercomparison Project (CMIP5) abrupt 4×CO2 and ramp experiments. A simple 1D model with only two ocean layers is shown to be able to explain the slow climate warming of the next century. An extension of the formal results in part I allows a new perturbation method to be designed in GCMs to determine the TLS in models. A series of illustrations demonstrates the advantages of implementing such a method in GCMs.
KLF1 mutations are relatively more common in a thalassemia endemic region and ameliorate the severity of β-thalassemia
Authors: Liu Dun , Zhang Xinhua , Yu Lihua , Cai Ren , Ma Xiaoxia , Zheng Chengguang , Zhou Yuqiu , Liu Qiji , Wei Xiaofeng , Lin Li , Yan Tizhen , Huang Jiwei , Mohandas Narla , An Xiuli , Xu Xiangmin 
Published: May 2014

Key Points
The prevalence of KLF1 mutations is significantly higher in a thalassemia endemic region of China than in a nonendemic region. KLF1 mutations ameliorate the clinical and hematologic features of β-thalassemia.
A novel mouse model for inhibition of DOHH mediated hypusine modification reveals crucial function for embryonic development, proliferation and oncogenic transformation
Authors: Sievert Henning , Pällmann Nora , Miller Katharine K. , Hermans-Borgmeyer Irm , Venz Simone , Sendoel Ataman , Preukschas Michael , Schweizer Michaela , Böttcher Steffen , Janiesch P. Christoph , Streichert Thomas , Walther Reinhard , Hengartner Michael O. , Manz Markus G. , Brümmendorf Tim H , Bokemeyer Carsten , Braig Melanie , Hauber Joachim , Duncan Kent E. , Balabanov Stefan 
Published: May 2014

AbstractThe central importance of translational control by posttranslational modification has spurred major interest in regulatory pathways that control translation. One such pathway uniquely adds hypusine to eukaryotic initiation factor 5A (eIF5A), and thereby affects protein synthesis and subsequently cellular proliferation through an unknown mechanism. Using a novel conditional knockout mouse model and a Caenorhabditis elegans knockout model, we found an evolutionarily conserved role for the DOHH-mediated second step of hypusine synthesis in early embryonic development. At the cellular level we observed reduced proliferation and induction of senescence in 3T3 Dohh-/- cells as well as reduced capability for malignant transformation. Furthermore, by mass spectrometry we observed that deletion of DOHH results in an unexpected complete loss of hypusine modification. Our results provide new biological insight into the physiological roles of the second step of the hypusination of eIF5A. Moreover, the conditional mouse model presented here provides a powerful tool to manipulate hypusine modification in a temporal and spatial manner, both to analyze how this unique modification normally functions in vivo, as well as how it contributes to different pathological conditions.
Encapsulation by Cyclic Porphyrin Dimers Using Various Interaction Modes
Authors: Terao Jun , Chiba Yusuke , Fujihara Tetsuaki , Tsuji Yasushi 
Published: May 2014

Abstract
We synthesized cyclic host molecules, A, B, and C, based on a rigid π-conjugated system composed of porphyrin and fluorene units. After the transformation of the ester units of cyclic host B to carboxylates, host C became soluble in water. These host molecules could encapsulate different molecules, based on various interactions: coordination bonds between porphyrin-bound metals (Zn) and N atoms, π–π interactions, or hydrophobic interactions.
First In Situ NMR Observation of Hydrogen Adsorbed inside [Cu3(btc)2] at Ambient Temperature and Pressure
Authors: Dekura Shun , Kobayashi Hirokazu , Li Guangqin , Ikeda Ryuichi , Kubota Yoshiki , Takata Masaki , Kitagawa Hiroshi 
Published: May 2014

Abstract
We report the first in situ NMR observation of 2H2 adsorbed inside [Cu3(btc)2] (HKUST-1; btc: benzenetricarboxylate) at ambient temperature and pressure. Hydrogen adsorption behavior was investigated by hydrogen sorption analysis and in situ solid-state 2H NMR under controlled 2H2 gas pressure. Although HKUST-1 adsorbed very little amount of H2 at 303 K, we could successfully observe the 2H2 signal inside HKUST-1 in the NMR spectra. Furthermore, the NMR signal demonstrated that HKUST-1 interacts with H2 molecules even at ambient temperature and hydrogen pressure.
Effects of Buffer on the Structure and Catalytic Activity of Palladium Nanomaterials Formed by Biomineralization
Authors: Janairo Jose Isagani B , Sakaguchi Kazuyasu 
Published: May 2014

Abstract
Effects of a buffer on the structure and catalytic activity of Pd nanostructures obtained from biomineralization were evaluated. Significant structural differences attributed to the buffer were observed. In addition, the Pd nanostructures prepared in buffered solutions had enhanced catalytic activity in the reduction of aminonitrophenol isomers. Our findings emphasize that the buffer selection is critical for biomineralization. Moreover, these findings indicate that the buffer can be possibly used to control the structure and activity of Pd nanomaterials, which is a very simple and cost-effective way compared with other methods.
Simple Gravity-assisted Evaluation for Self-directed Movement of a Droplet Driven by Heterogeneous Surface Energies
Authors: Kusaka Yasuyuki , Ushijima Hirobumi 
Published: May 2014

Abstract
We report a simple method that allows facile evaluation of the driving force required to move a droplet settled on a boundary of two surfaces with different surface energies. In the method, a vertically placed sample substrate holding a droplet is gradually recovered to the horizontal state, so that the driving force of the self-directed movement can be obtained from the counterbalancing gravitational force exerted on the droplet at the critical tilt angle at which the droplet starts to move.