bluuebunny/crossref_metadata_2025_split huggingface dataset:
T2 Hyperintensity of Medial Lemniscus: Higher Threshold Application to ROI Measurements is More Accurate in Predicting Small Vessel Disease
Authors: Hakky Michael M. , Erbay Kaan D. , Brewer Edward , Midle Jennifer B. , French Robert , Erbay Sami H. 
Published: January 2013

ABSTRACTBACKGROUNDMedial lemniscus T2 hyperintensity (MLH) has been recently demonstrated as potential imaging marker for small vessel disease (SVD). Our purpose in this study is to improve accuracy of regions of interest (ROI) analysis for this imaging finding.METHODS AND METHODSTwo neuroradiologists retrospectively reviewed 103 consecutive outpatient brain MRI. Medial lemniscus signal in dorsal pons was evaluated; visually on FLAIR and with ROI on T2. Original MRI interpretations were divided into three categories; SVD, multiple sclerosis (MS), and nonspecific WM changes (non).RESULTSThirty‐seven patients had SVD, 14 patients had MS, 52 had Non. Visual MLH was seen exclusively with SVD and was generally bilateral. Patients with visual MLH belonged to advanced SVD by imaging and clinical parameters. Compared to visual data, ROI analyses of MLH has been known to be compounded by false positives and negatives at low threshold (20% of adjacent to normal brainstem signal). With application of higher ROI threshold (25%), false positives were eliminated but false negatives increased. ROI analyses of MLH by experienced neuroradiologist were more reliable.CONCLUSIONMLH seen on high threshold ROI analysis is a reliable radiologic marker in predicting SVD. ROI analysis of MLH should be performed by an experienced neuroradiologist.
Current Account Imbalances in the Euro Area: Does Catching up Explain the Development?
Authors: Belke Ansgar , Dreger Christian 
Published: January 2013

AbstractIn the debate on global imbalances, the euro area countries received inreasing attention since the outbreak of the financial crisis. While the current account is on balance for the entire area, divergences between individual member states have increased since the introduction of the common currency and are part of the excessive imbalances procedure. This paper explores the determinants of the imbalances by using paneleconometric techniques. The analysis shows that a lack in competitiveness is the main explanation for the external deficits of the countries that are at the heart of the euro area debt crisis. As a deterioration of competitiveness is not feasible for the surplus countries, an asymmetric response is required to reduce the imbalances.
Short‐ and Long‐term Growth Effects of Exchange Rate Adjustment
Authors: Kočenda Evžen , Maurel Mathilde , Schnabl Gunther 
Published: January 2013

AbstractThe European sovereign debt crisis revived the discussion concerning pros and cons of exchange rate adjustment in the face of asymmetric shocks. In the spirit of Keynes, exit from the euro area is to regain rapidly international competitiveness. In the spirit of Schumpeter, exchange rate stability with structural reforms would be beneficial towards the long‐run growth performance. Previous literature has estimated the average growth of countries with different degrees of exchange rate flexibility. This literature is augmented by analyzing short‐ and long‐term growth effects of exchange rate flexibility in a panel‐cointegration framework for a sample of 60 countries clustered in five country groups. The estimations show that countries with a high degree of exchange rate stability exhibit a higher long‐term growth performance. It is shown that the degree of business cycle synchronization with the anchor country matters for the impact of exchange rate flexibility on growth.
Dual Liquidity Crises—A Financial Accounts Framework
Authors: Bindseil Ulrich , Winkler Adalbert 
Published: January 2013

AbstractThis paper analyzes dual liquidity crises, i.e. funding crises which encompass the private and the public sector, and the shock absorbing capacity of central banks within a closed system of financial accounts. We find that a central bank that operates under a flexible exchange rate is most effective in containing a dual liquidity crisis. A central bank of a euro area type monetary union has a similar capacity as long as the integrity of the union is beyond doubt. By contrast, within any fixed exchange rate system the availability of inter‐central bank credit determines the elasticity of a central bank in providing liquidity. Finally, domestic constraints, i.e. collateral rules, risk taking ability or legal prohibitions, can limit the elasticity of the central bank's response to liquidity shocks.
The Alpine Tethys rifted margins: Reconciling old and new ideas to understand the stratigraphic architecture of magma‐poor rifted margins
Authors: Masini Emmanuel , Manatschal Gianreto , Mohn Geoffroy 
Published: January 2013

AbstractThis study focuses on the assessment of the stratigraphic architecture of the proximal and distal Jurassic Alpine Tethys rifted margins. The aim of the study was to reconcile the major observations performed in the Alps through time with what is observed in present‐day magma‐poor rifted margins. The proximal and distal rifted margins reflect two evolutionary phases of rifting involving different structures and isostatic evolutions leading to different stratigraphic records. The proximal rifted margins formed from Upper Triassic to Pliensbachian times and resulted in the formation of classical half graben basins. Rift evolution changed drastically during Pliensbachian to Toarcian times when extension started to localize in the future distal rifted margins. Low‐angle detachment faults become the new elementary structure controlling final crustal tapering and eventually mantle exhumation to the sea floor. New structural elements controlling the stratigraphic architecture of the distal rifted margins include extensional allochthons and breakaway blocks, both resulting from the delamination of a keystone block, also referred to as hangingwall block, during hyper‐extension processes. To define the stratigraphic architecture of the proximal and distal rifted margins, three stratigraphic marker horizons are used, namely the top of the pre‐rift sequences, the top of the proximal margin syn‐tectonic sequence and the base of post‐rift sequences. Based on the distribution of these stratigraphic marker horizons across the Alpine units and a structural re‐evaluation of the rift structures, a synthetic tectono‐stratigraphic evolution of the Alpine Tethys domain is proposed that reconciles old and new ideas about how rift systems may evolve in space and time.
Mesozoic radiolarites – accumulation as a function of sea surface fertility on Tethyan margins and in ocean basins
Authors: Baumgartner Peter O. 
Published: January 2013

AbstractRadiolarites, commonly comprising chert‐shale couplets, feature prominently in the Mesozoic stratigraphy of the Neotethyan realm. The origin and significance of these deposits, especially with regard to understanding palaeoproductivity in that region, remains controversial. This study examines transport processes and accumulation rates of radiolarians/radiolarites, as well as the chronology of radiolarite sedimentation based on revised data from the Southern Alps and new data from the Balagne Nappes, Alpine Corsica. Results suggest that the spatio‐temporal distribution of carbonate and silica on Tethyan margins was governed by extensive lateral transport of radiolarian tests from topographic highs to basins. Palaeoclimatic, rather than palaeotectonic, changes seem to have triggered changes in surface fertility which, in turn, brought about major facies changes observed in Tethyan marginal basins: Regional platform demise – possibly due to eutrophication and onset of radiolarite deposition in the Early Bajocian – can be correlated with a positive shift in the carbon isotope curve, whereas platform recovery and the end of radiolarite accumulation correlates with a gradual decline in δ13C‐values. The existence of a vigorous trans‐Pangaean, equatorial current system that could have produced regional upwelling is questioned because of evidence for Middle Jurassic to Early Cretaceous oligotrophic conditions in the Proto‐Caribbean and the Central Atlantic. The ‘Caribbean River Plume Model’ is proposed as a possible alternative to upwelling in the Jurassic Western Tethys. Dissolved nutrients may have been dispersed in low salinity lids that originated from river plumes of rivers from tropical Africa and warm‐temperate Eurasia. Vast areas of the pre‐Late Cretaceous world ocean must have accumulated radiolarites at low rates (<4 g cm−2 10−3years) represented by the condensed, long‐lived (>50 Myr) radiolarite sections observed in many Circumpacific terranes. Radiolarian chert and claystone could be the normal pelagic sediment during Ordovician to Early Cretaceous time in far‐offshore, open oceanic settings, where dilution by terrigenous material and periplatform shallow‐water carbonates was absent.
Myeloid Dendritic Cells (DCs) of Mice Susceptible to Paracoccidioidomycosis Suppress T Cell Responses whereas Myeloid and Plasmacytoid DCs from Resistant Mice Induce Effector and Regulatory T Cells
Authors: Pina Adriana , Frank de Araujo Eliseu , Felonato Maíra , Loures Flávio V. , Feriotti Claudia , Bernardino Simone , Barbuto José Alexandre M. , Calich Vera L. G. 
Published: January 2013

ABSTRACTThe protective adaptive immune response in paracoccidioidomycosis, a mycosis endemic among humans, is mediated by T cell immunity, whereas impaired T cell responses are associated with severe, progressive disease. The early host response toParacoccidioides brasiliensisinfection is not known since the disease is diagnosed at later phases of infection. Our laboratory established a murine model of infection where susceptible mice reproduce the severe disease, while resistant mice develop a mild infection. This work aimed to characterize the influence of dendritic cells in the innate and adaptive immunity of susceptible and resistant mice. We verified thatP. brasiliensisinfection induced in bone marrow-derived dendritic cells (DCs) of susceptible mice a prevalent proinflammatory myeloid phenotype that secreted high levels of interleukin-12 (IL-12), tumor necrosis factor alpha, and IL-β, whereas in resistant mice, a mixed population of myeloid and plasmacytoid DCs secreting proinflammatory cytokines and expressing elevated levels of secreted and membrane-bound transforming growth factor β was observed. In proliferation assays, the proinflammatory DCs from B10.A mice induced anergy of naïve T cells, whereas the mixed DC subsets from resistant mice induced the concomitant proliferation of effector and regulatory T cells (Tregs). Equivalent results were observed during pulmonary infection. The susceptible mice displayed preferential expansion of proinflammatory myeloid DCs, resulting in impaired proliferation of effector T cells. Conversely, the resistant mice developed myeloid and plasmacytoid DCs that efficiently expanded gamma interferon-, IL-4-, and IL-17-positive effector T cells associated with increased development of Tregs. Our work highlights the deleterious effect of excessive innate proinflammatory reactions and provides new evidence for the importance of immunomodulation during pulmonary paracoccidioidomycosis.
Role of Host Xanthine Oxidase in Infection Due to Enteropathogenic and Shiga-Toxigenic Escherichia coli
Authors: Crane John K. , Naeher Tonniele M. , Broome Jacqueline E. , Boedeker Edgar C. 
Published: January 2013

ABSTRACT

Xanthine oxidase (XO), also known as xanthine oxidoreductase, has long been considered an important host defense molecule in the intestine and in breastfed infants. Here, we present evidence that XO is released from and active in intestinal tissues and fluids in response to infection with enteropathogenic
Escherichia coli
(EPEC) and Shiga-toxigenic
E. coli
(STEC), also known as enterohemorrhagic
E. coli
(EHEC). XO is released into intestinal fluids in EPEC and STEC infection in a rabbit animal model. XO activity results in the generation of surprisingly high concentrations of uric acid in both cultured cell and animal models of infection. Hydrogen peroxide (H
2
O
2
) generated by XO activity triggered a chloride secretory response in intestinal cell monolayers within minutes but decreased transepithelial electrical resistance at 6 to 22 h. H
2
O
2
generated by XO activity was effective at killing laboratory strains of
E. coli
, commensal microbiotas, and anaerobes, but wild-type EPEC and STEC strains were 100 to 1,000 times more resistant to killing or growth inhibition by this pathway. Instead of killing pathogenic bacteria, physiologic concentrations of XO increased virulence by inducing the production of Shiga toxins from STEC strains.
In vivo
, exogenous XO plus the substrate hypoxanthine did not protect and instead worsened the outcome of STEC infection in the rabbit ligated intestinal loop model of infection. XO released during EPEC and STEC infection may serve as a virulence-inducing signal to the pathogen and not solely as a protective host defense.
Comparative Genomics of Recent Shiga Toxin-Producing Escherichia coli O104:H4: Short-Term Evolution of an Emerging Pathogen
Authors: Grad Yonatan H. , Godfrey Paul , Cerquiera Gustavo C. , Mariani-Kurkdjian Patricia , Gouali Malika , Bingen Edouard , Shea Terrence P. , Haas Brian J. , Griggs Allison , Young Sarah , Zeng Qiandong , Lipsitch Marc , Waldor Matthew K. , Weill François-Xavier , Wortman Jennifer R. , Hanage William P. 
Published: January 2013

ABSTRACT

The large outbreak of diarrhea and hemolytic uremic syndrome (HUS) caused by Shiga toxin-producing
Escherichia coli
O104:H4 in Europe from May to July 2011 highlighted the potential of a rarely identified
E. coli
serogroup to cause severe disease. Prior to the outbreak, there were very few reports of disease caused by this pathogen and thus little known of its diversity and evolution. The identification of cases of HUS caused by
E. coli
O104:H4 in France and Turkey after the outbreak and with no clear epidemiological links raises questions about whether these sporadic cases are derived from the outbreak. Here, we report genome sequences of five independent isolates from these cases and results of a comparative analysis with historical and 2011 outbreak isolates. These analyses revealed that the five isolates are not derived from the outbreak strain; however, they are more closely related to the outbreak strain and each other than to isolates identified prior to the 2011 outbreak. Over the short time scale represented by these closely related organisms, the majority of genome variation is found within their mobile genetic elements: none of the nine O104:H4 isolates compared here contain the same set of plasmids, and their prophages and genomic islands also differ. Moreover, the presence of closely related HUS-associated
E. coli
O104:H4 isolates supports the contention that fully virulent O104:H4 isolates are widespread and emphasizes the possibility of future food-borne
E. coli
O104:H4 outbreaks.

IMPORTANCE
In the summer of 2011, a large outbreak of bloody diarrhea with a high rate of severe complications took place in Europe, caused by a previously rarely seen
Escherichia coli
strain of serogroup O104:H4. Identification of subsequent infections caused by
E. coli
O104:H4 raised questions about whether these new cases represented ongoing transmission of the outbreak strain. In this study, we sequenced the genomes of isolates from five recent cases and compared them with historical isolates. The analyses reveal that, in the very short term, evolution of the bacterial genome takes place in parts of the genome that are exchanged among bacteria, and these regions contain genes involved in adaptation to local environments. We show that these recent isolates are not derived from the outbreak strain but are very closely related and share many of the same disease-causing genes, emphasizing the concern that these bacteria may cause future severe outbreaks.
Five New Genes Are Important for Common Polysaccharide Antigen Biosynthesis in Pseudomonas aeruginosa
Authors: Hao Youai , King Jerry D. , Huszczynski Steven , Kocíncová Dana , Lam Joseph S. 
Published: January 2013

ABSTRACT

Common polysaccharide antigen (CPA) is a conserved cell surface polysaccharide produced by
Pseudomonas aeruginosa
. It contains a rhamnan homopolymer and is one of the two forms of O polysaccharide attached to
P. aeruginosa
lipopolysaccharide (LPS). Our laboratory has previously characterized an eight-gene cluster (
pa5447-pa5454
in
P. aeruginosa
PAO1) required for biosynthesis of CPA. Here we demonstrate that an adjacent five-gene cluster
pa5455-pa5459
is also involved. Using reverse transcriptase PCR (RT-PCR), we showed that the original eight-gene cluster and the new five-gene cluster are both organized as operons. We have analyzed the LPS phenotypes of in-frame deletion mutants made in each of the five genes, and the results verified that these five genes are indeed required for CPA biosynthesis, extending the CPA biosynthesis locus to contain 13 contiguous genes. By performing overexpression experiments of different sets of these biosynthesis genes, we were able to obtain information about their possible functions in CPA biosynthesis.

IMPORTANCE
Lipopolysaccharide (LPS) is an important cell surface structure of Gram-negative bacteria. The human opportunistic pathogen
Pseudomonas aeruginosa
simultaneously produces an O-antigen-specific (OSA) form and a common polysaccharide antigen (CPA) form of LPS. CPA, the focus of this study, is composed of α-1-2, α1-3-linked
d
-rhamnose sugars and has been shown to be important for attachment of the bacteria to human airway epithelial cells. Genome sequencing of this species revealed a new five-gene cluster that we predicted to be involved in CPA biosynthesis and modification. In this study, we have generated chromosomal knockouts by performing in-frame deletions and allelic replacements. Characterizing the function of each of the five genes is important for us to better understand CPA biosynthesis and the mechanisms of chain length termination and regulation of this unique D-rhamnan polysaccharide.
Contribution of OATP1B1 and OATP1B3 to the Disposition of Sorafenib and Sorafenib-Glucuronide
Authors: Zimmerman Eric I. , Hu Shuiying , Roberts Justin L. , Gibson Alice A. , Orwick Shelley J. , Li Lie , Sparreboom Alex , Baker Sharyn D. 
Published: January 2013

Abstract
Purpose: Many tyrosine kinase inhibitors (TKI) undergo extensive hepatic metabolism, but mechanisms of their hepatocellular uptake remain poorly understood. We hypothesized that liver uptake of TKIs is mediated by the solute carriers OATP1B1 and OATP1B3.
Experimental Design: Transport of crizotinib, dasatinib, gefitinib, imatinib, nilotinib, pazopanib, sorafenib, sunitinib, vandetanib, and vemurafenib was studied in vitro using artificial membranes (PAMPA) and HEK293 cell lines stably transfected with OATP1B1, OATP1B3, or the ortholog mouse transporter, Oatp1b2. Pharmacokinetic studies were conducted with Oatp1b2-knockout mice and humanized OATP1B1- or OATP1B3-transgenic mice.
Results: All 10 TKIs were identified as substrates of OATP1B1, OATP1B3, or both. Transport of sorafenib was investigated further, as its diffusion was particularly low in the PAMPA assay (&lt;4%) than other TKIs that were transported by both OATP1B1 and OATP1B3. Whereas Oatp1b2 deficiency in vivo had minimal influence on parent and active metabolite N-oxide drug exposure, plasma levels of the glucuronic acid metabolite of sorafenib (sorafenib-glucuronide) were increased more than 8-fold in Oatp1b2-knockout mice. This finding was unrelated to possible changes in intrinsic metabolic capacity for sorafenib-glucuronide formation in hepatic or intestinal microsomes ex vivo. Ensuing experiments revealed that sorafenib-glucuronide was itself a transported substrate of Oatp1b2 (17.5-fold vs. control), OATP1B1 (10.6-fold), and OATP1B3 (6.4-fold), and introduction of the human transporters in Oatp1b2-knockout mice provided partial restoration of function.
Conclusions: These findings signify a unique role for OATP1B1 and OATP1B3 in the elimination of sorafenib-glucuronide and suggest a role for these transporters in the in vivo handling of glucuronic acid conjugates of drugs. Clin Cancer Res; 19(6); 1458–66. ©2013 AACR.
Induction of Cooling With a Passive Head and Neck Cooling Device
Authors: Poli Sven , Purrucker Jan , Priglinger Miriam , Diedler Jennifer , Sykora Marek , Popp Erik , Steiner Thorsten , Veltkamp Roland , Bösel Julian , Rupp André , Hacke Werner , Hametner Christian 
Published: January 2013

Background and Purpose—
Therapeutic hypothermia improves clinical outcome after cardiac arrest and appears beneficial in other cerebrovascular diseases. We conducted this study to investigate the relationship between surface head/neck cooling and brain temperature.

Methods—
Prospective observational study enrolling consecutive patients with severe ischemic or hemorrhagic stroke undergoing intracranial pressure (ICP) and brain temperature monitoring. Arterial pressure, ICP, cerebral perfusion pressure, heart rate, brain, tympanic, and bladder temperature were continuously registered. Fifty-one applications of the Sovika cooling device were analyzed in 11 individual patients.

Results—
Sovika application led to a significant decrease of brain temperature compared with baseline with a maximum of −0.36°C (SD, 0.22) after 49 minutes (SD, 17). During cooling, dynamics of brain temperature differed significantly from bladder (−0.25°C [SD, 0.15] after 48 minutes [SD, 19]) and tympanic temperature (−1.79°C [SD, 1.19] after 37 minutes [SD, 16]). Treatment led to an increase in systolic arterial pressure by >20 mm Hg in 14 applications (n=7 patients) resulting in severe hypertension (>180 mm Hg) in 4 applications (n=3). ICP increased by >10 mm Hg in 7 applications (n=3), led to ICP crisis >20 mm Hg in 6 applications (n=3), and a drop of cerebral perfusion pressure <50 mm Hg in 1 application.

Conclusions—
Although the decrease of brain temperature after Sovika cooling device application was statistically significant, we doubt clinical relevance of this rather limited effect (−0.36°C). Moreover, the transient increases of blood pressure and ICP warrant caution.