bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Early Pleistocene grounded ice sheet in the Central North Sea
Authors: Buckley F. A. 
Published: March 2012

Abstract
Evidence is presented for an Early Pleistocene grounded ice sheet in the Central North Sea (CNS). Dated basal Quaternary deposits from UK well 30/13-2 Josephine coincide with the lowest iceberg ploughmarked horizon in a southern CNS depocentre. This horizon has been traced northwards into the central CNS where it is identified as the Crenulate reflection, which exhibits a series of deep, channel-like features, interpreted as subglacial meltwater channels. Further north, a seismic reflection at the same level is characterized by megascale lineations that are interpreted to be the result of erosion, deposition and deformation of sediment beneath an advancing ice sheet. An overlying seismic reflection is characterized by a well-developed channel system that is thought to have drained the retreating ice sheet prior to a post-glacial marine transgression. A southern CNS Early Pleistocene depocentre is shown to have become inactive sometime in the Early to Middle Pleistocene and was replaced by a developing depocentre in the central and northern CNS that remained active into the Late Pleistocene. Evidence for an Elsterian or older grounded ice sheet in UK Continental Shelf Quad 22 is presented in the form of glaciotectonic thrust features.
A Novel Tankyrase Inhibitor Decreases Canonical Wnt Signaling in Colon Carcinoma Cells and Reduces Tumor Growth in Conditional APC Mutant Mice
Authors: Waaler Jo , Machon Ondrej , Tumova Lucie , Dinh Huyen , Korinek Vladimir , Wilson Steven Ray , Paulsen Jan Erik , Pedersen Nina Marie , Eide Tor J. , Machonova Olga , Gradl Dietmar , Voronkov Andrey , von Kries Jens Peter , Krauss Stefan 
Published: March 2012

Abstract
Increased nuclear accumulation of β-catenin, a mediator of canonical Wnt signaling, is found in numerous tumors and is frequently associated with tumor progression and metastasis. Inhibition of Wnt/β-catenin signaling therefore is an attractive strategy for anticancer drugs. In this study, we have identified a novel small molecule inhibitor of the β-catenin signaling pathway, JW55, that functions via inhibition of the PARP domain of tankyrase 1 and tankyrase 2 (TNKS1/2), regulators of the β-catenin destruction complex. Inhibition of TNKS1/2 poly(ADP-ribosyl)ation activity by JW55 led to stabilization of AXIN2, a member of the β-catenin destruction complex, followed by increased degradation of β-catenin. In a dose-dependent manner, JW55 inhibited canonical Wnt signaling in colon carcinoma cells that contained mutations in either the APC (adenomatous polyposis coli) locus or in an allele of β-catenin. In addition, JW55 reduced XWnt8-induced axis duplication in Xenopus embryos and tamoxifen-induced polyposis formation in conditional APC mutant mice. Together, our findings provide a novel chemotype for targeting canonical Wnt/β-catenin signaling through inhibiting the PARP domain of TNKS1/2. Cancer Res; 72(11); 2822–32. ©2012 AACR.
Hypoxia-Induced Autophagy Promotes Tumor Cell Survival and Adaptation to Antiangiogenic Treatment in Glioblastoma
Authors: Hu Yu-Long , DeLay Michael , Jahangiri Arman , Molinaro Annette M. , Rose Samuel D. , Carbonell W. Shawn , Aghi Manish K. 
Published: March 2012

Abstract
Antiangiogenic therapy leads to devascularization that limits tumor growth. However, the benefits of angiogenesis inhibitors are typically transient and resistance often develops. In this study, we explored the hypothesis that hypoxia caused by antiangiogenic therapy induces tumor cell autophagy as a cytoprotective adaptive response, thereby promoting treatment resistance. Hypoxia-induced autophagy was dependent on signaling through the hypoxia-inducible factor-1α (HIF-1α)/AMPK pathway, and treatment of hypoxic cells with autophagy inhibitors caused a shift from autophagic to apoptotic cell death in vitro. In glioblastomas, clinically resistant to the VEGF-neutralizing antibody bevacizumab, increased regions of hypoxia and higher levels of autophagy-mediating BNIP3 were found when compared with pretreatment specimens from the same patients. When treated with bevacizumab alone, human glioblastoma xenografts showed increased BNIP3 expression and hypoxia-associated growth, which could be prevented by addition of the autophagy inhibitor chloroquine. In vivo targeting of the essential autophagy gene ATG7 also disrupted tumor growth when combined with bevacizumab treatment. Together, our findings elucidate a novel mechanism of resistance to antiangiogenic therapy in which hypoxia-mediated autophagy promotes tumor cell survival. One strong implication of our findings is that autophagy inhibitors may help prevent resistance to antiangiogenic therapy used in the clinic. Cancer Res; 72(7); 1773–83. ©2012 AACR.
Clinical Context and Mechanism of Functional Tricuspid Regurgitation in Patients With and Without Pulmonary Hypertension
Authors: Topilsky Yan , Khanna Amber , Le Tourneau Thierry , Park Soon , Michelena Hector , Suri Rakesh , Mahoney Douglas W. , Enriquez-Sarano Maurice 
Published: March 2012

Background—
Functional tricuspid regurgitation (FTR) with structurally normal valve is of poorly defined mechanisms. Prevalence and clinical context of idiopathic FTR (Id-FTR) (without overt TR cause) are unknown.

Methods and Results—

To investigate prevalence, clinical context, and mechanisms specific to FTR types, Id-FTR versus pulmonary hypertension-related (PHTN-FTR, systolic pulmonary pressure ≥50 mm Hg), we analyzed 1161 patients with prospectively quantified TR. Id-FTR (prevalence 12%) was associated with aging and atrial fibrillation. For mechanistic purposes, we measured valvular and right ventricular (RV) remodeling in 141 Id-FTR matched to 140 PHTN-FTR and to 99 controls with trivial TR for age, sex, atrial fibrillation, and ejection fraction. PHTN-FTR and Id-FTR were also matched for TR effective-regurgitant-orifice (ERO). Id-FTR valvular alterations (versus controls) were largest annular area (3.53±0.6 versus 2.74±0.4 cm
2
,
P
<0.0001) and lowest valvular/annular coverage ratio (1.06±0.1 versus 1.45±0.2,
P
<0.0001) but normal valve tenting height. PHTN-FTR had mild annular enlargement but excessive valve tenting height (0.8±0.3 versus 0.35±0.1 cm,
P
<0.0001). Valvular changes were linked to specific RV changes, largest basal dilatation, and normal length (RV conical deformation) in Id-FTR versus longest RV with elliptical/spherical deformation in PHTN-FTR. With increasing FTR severity (ERO ≥40 mm
2
), changes specific to each FTR type were accentuated, and RV function (index of myocardial performance) was consistently reduced.

Conclusions—
Id-FTR is frequent, linked to aging and atrial fibrillation, can be severe, and is of unique mechanism. In Id-FTR, excess annular and RV-basal enlargement exhausts valvular/annular coverage reserve, and RV conical deformation does not cause notable valvular tenting. Conversely, PHTN-FTR is determined by valvular tethering with tenting linked to RV elongation and elliptical/spherical deformation. These specific FTR-mechanisms may be important in considering surgical correction in FTR.
Endoscopic Surgery for Fronto‐Ethmoidal Mucoceles
Authors: Dhepnorrarat Rataphol Chris , Subramaniam Somasundaram , Sethi Dharmbir Singh 
Published: March 2012

ObjectiveTo add to the existing knowledge of endoscopic surgery for fronto‐ethmoidal mucoceles and to determine factors that influence the outcomes of endoscopic surgery.Study DesignCase series with chart review.SettingUniversity adult tertiary care institution.Subjects and MethodsA database of patients treated surgically for mucoceles of the paranasal sinus has been kept by the senior author since 1995. It was used to identify those who have had endoscopic surgery for fronto‐ethmoidal mucoceles from 1995 to 2010. All adult patients with 6 months or more of follow‐up were included. The database was reviewed and assessed for variables that may affect outcome after surgery.ResultsForty patients underwent 44 endoscopic procedures for treatment of fronto‐ethmoidal mucoceles and the complications of surgery. The mean age was 46.3 years, and mean follow‐up time was 74.9 months. Two patients had a history of head trauma. A total of 28 Draf IIa procedures, 13 Draf IIb, and 3 Draf III procedures were performed. Three patients had combined open approaches. Two patients had bilateral surgery, and 2 patients required revision surgery: 1 for restenosis after a Draf IIa procedure (1/28) and 1 for disease recurrence. Stenosis was found in a further 3 patients who had Draf IIb surgery (3/13).ConclusionThe current series represents one of the largest for the endoscopic management of fronto‐ethmoidal mucoceles. Endoscopic approaches are suitable for most mucoceles. The most common complication, restenosis of the frontal recess, was more likely following Draf IIb procedures (23%) than Draf IIa (3.6%) procedures.
Twin Deficits or Distant Cousins? Evidence from India1
Authors: Ratha Artatrana 
Published: March 2012

The twin-deficits theory has intrigued economists and policy-makers alike for the past few decades. In a Keynesian economy, budget deficit increases the absorption of the economy, causes import expansions, and thereby, worsens the trade deficit. It also causes domestic interest rates to rise, domestic currency to appreciate, and thereby, contributes to trade deficits. However, according to the Ricardian Equivalence Hypothesis (REH), rising budget deficits imply higher future tax liabilities so people would save more and consume less. As a result, an inter-temporal shift between taxes and budget deficits would have no impact on the real interest, or the trade deficit. Thus, the issue of whether the twin-deficits phenomenon holds becomes more of an empirical question, and the recent fiscal expansions to curb recession makes it timely to revisit the phenomenon, especially for the developing countries confronting both the deficits on a chronic basis. To this end, we make a case study of India, using the bounds- testing approach to cointegration and error-correction modelling on monthly and quarterly data over 1998–2009. Our results suggest that the twin-deficits theory holds for India in the short-run (validating the Keynesian channel) but not in the long-run (validating the REH). JEL: F32, H62
Financial Liberalization, Savings and the Banking Sector in Bangladesh
Authors: Murshed Syed Mansoob , Robin Iftekhar Ahmed 
Published: March 2012

This article explores the consequences of financial liberalization policy on the banking sector in Bangladesh. Following a motivating portfolio selection theor-etical model on the impact of liberalization, it applies time series techniques with annual banking sector data for the period 1981–2008. The study suggests that the main objective of financial liberalization to promote domestic private savings by raising real interest rates has not worked. No significant positive correlation is observed between domestic private savings and the real deposit interest rate. JEL: E21, E44, E42, C22
Proteomic analysis of effluents from perfused human heart for transplantation: identification of potential biomarkers for ischemic heart damage
Authors: Li Hong , Li Jiyuan , Wang Ying , Yang Tiande 
Published: March 2012

Abstract

Background
Biomarkers released from the heart at early stage of ischemia are very important to diagnosis of ischemic heart disease and salvage myocytes from death. Known specific markers for blood tests including CK-MB, cardiac troponin T (cTnT) and cardiac troponin I (cTnI) are released after the onset of significant necrosis instead of early ischemia. Thus, they are not good biomarkers to diagnose myocardial injury before necrosis happens. Therefore, in this study, we performed proteomic analysis on effluents from perfused human hearts of donors at different ischemic time.

Results
After global ischemia for 0 min, 30 min and 60 min at 4°C, effluents from five perfused hearts were analyzed respectively, by High performance liquid chromatography-Chip-Mass spectrometry (HPLC-Chip-MS) system. Total 196 highly reliable proteins were identified. 107 proteins were identified at the beginning of ischemia, 174 and 175 proteins at ischemic 30 min and ischemic 60 min, respectively. With the exception of cardiac troponin I and T, all known biomarkers for myocardial ischemia were detected in our study. However, there were four glycolytic enzymes and two targets of matrix metalloproteinase released significantly from the heart when ischemic time was increasing. These proteins were L-lactate dehydrogenase B(LDHB), glyceraldehyde-3-phosphate dehydrogenase, glucose-6-phosphate isomerase (GPI), phosphoglycerate mutase 2 (PGAM2), gelsolin and isoform 8 of titin. PGAM2, LDHB and titin were measured with enzyme-linked immunosorbent assays kits. The mean concentrations of LDHB and PGAM2 in samples showed an increasing trend when ischemic time was extending. In addition, 33% identified proteins are involved in metabolism. Protein to protein interaction network analysis showed glycolytic enzymes, such as isoform alpha-enolase of alpha-enolase, isoform 1 of triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase, had more connections than other proteins in myocardial metabolism during ischemia.

Conclusion
It is the first time to use effluents of human perfused heart to study the proteins released during myocardial ischemia by HPLC-Chip-MS system. There might be many potential biomarkers for mild ischemic injury in myocardium, especially isoform 8 of titin and M-type of PGAM2 that are more specific in the cardiac tissue than in the others. Furthermore, glycolysis is one of the important conversions during early ischemia in myocardium. This finding may provide new insight into pathology and biology of myocardial ischemia, and potential diagnostic and therapeutic biomarkers.
Remotely sensed image retrieval based on region-level semantic mining
Authors: Liu Tingting , Zhang Liangpei , Li Pingxiang , Lin Hui 
Published: March 2012

AbstractAs satellite images are widely used in a large number of applications in recent years, content-based image retrieval technique has become important tools for image exploration and information mining; however, their performances are limited by the semantic gap between low-level features and high-level concepts. To narrow this semantic gap, a region-level semantic mining approach is proposed in this article. Because it is easier for users to understand image content by region, images are segmented into several parts using an improved segmentation algorithm, each with homogeneous spectral and textural characteristics, and then a uniform region-based representation for each image is built. Once the probabilistic relationship among image, region, and hidden semantic is constructed, the Expectation Maximization method can be applied to mine the hidden semantic. We implement this approach on a dataset consisting of thousands of satellite images and obtain a high retrieval precision, as demonstrated through experiments.
Evaluation of limited blood sampling population input approaches for kinetic quantification of [18F]fluorothymidine PET data
Authors: Contractor Kaiyumars B , Kenny Laura M , Coombes Charles R , Turkheimer Federico E , Aboagye Eric O , Rosso Lula 
Published: March 2012

Abstract

Background
Quantification of kinetic parameters of positron emission tomography (PET) imaging agents normally requires collecting arterial blood samples which is inconvenient for patients and difficult to implement in routine clinical practice. The aim of this study was to investigate whether a population-based input function (POP-IF) reliant on only a few individual discrete samples allows accurate estimates of tumour proliferation using [18F]fluorothymidine (FLT).

Methods
Thirty-six historical FLT-PET data with concurrent arterial sampling were available for this study. A population average of baseline scans blood data was constructed using leave-one-out cross-validation for each scan and used in conjunction with individual blood samples. Three limited sampling protocols were investigated including, respectively, only seven (POP-IF7), five (POP-IF5) and three (POP-IF3) discrete samples of the historical dataset. Additionally, using the three-point protocol, we derived a POP-IF3M, the only input function which was not corrected for the fraction of radiolabelled metabolites present in blood. The kinetic parameter for net FLT retention at steady state, Ki, was derived using the modified Patlak plot and compared with the original full arterial set for validation.

Results
Small percentage differences in the area under the curve between all the POP-IFs and full arterial sampling IF was found over 60 min (4.2%-5.7%), while there were, as expected, larger differences in the peak position and peak height.
A high correlation between Ki values calculated using the original arterial input function and all the population-derived IFs was observed (R2 = 0.85-0.98). The population-based input showed good intra-subject reproducibility of Ki values (R2 = 0.81-0.94) and good correlation (R2 = 0.60-0.85) with Ki-67.

Conclusions
Input functions generated using these simplified protocols over scan duration of 60 min estimate net PET-FLT retention with reasonable accuracy.
Multiple Pathways Suppress Telomere Addition to DNA Breaks in the Drosophila Germline
Authors: Beaucher Michelle , Zheng Xiao-Feng , Amariei Flavia , Rong Yikang S 
Published: March 2012

Abstract
Telomeres protect chromosome ends from being repaired as double-strand breaks (DSBs). Just as DSB repair is suppressed at telomeres, de novo telomere addition is suppressed at the site of DSBs. To identify factors responsible for this suppression, we developed an assay to monitor de novo telomere formation in Drosophila, an organism in which telomeres can be established on chromosome ends with essentially any sequence. Germline expression of the I-SceI endonuclease resulted in precise telomere formation at its cut site with high efficiency. Using this assay, we quantified the frequency of telomere formation in different genetic backgrounds with known or possible defects in DNA damage repair. We showed that disruption of DSB repair factors (Rad51 or DNA ligase IV) or DSB sensing factors (ATRIP or MDC1) resulted in more efficient telomere formation. Interestingly, partial disruption of factors that normally regulate telomere protection (ATM or NBS) also led to higher frequencies of telomere formation, suggesting that these proteins have opposing roles in telomere maintenance vs. establishment. In the ku70 mutant background, telomere establishment was preceded by excessive degradation of DSB ends, which were stabilized upon telomere formation. Most strikingly, the removal of ATRIP caused a dramatic increase in telomeric retrotransposon attachment to broken ends. Our study identifies several pathways thatsuppress telomere addition at DSBs, paving the way for future mechanistic studies.
Developmental Genetics of Secretory Vesicle Acidification DuringCaenorhabditis elegansSpermatogenesis
Authors: Gleason Elizabeth J , Hartley Paul D , Henderson Melissa , Hill-Harfe Katherine L , Price Paul W , Weimer Robby M , Kroft Tim L , Zhu Guang-dan , Cordovado Suzanne , L’Hernault Steven W 
Published: March 2012

AbstractSecretory vesicles are used during spermatogenesis to deliver proteins to the cell surface. In Caenorhabditis elegans, secretory membranous organelles (MO) fuse with the plasma membrane to transform spermatids into fertilization-competent spermatozoa. We show that, like the acrosomal vesicle of mammalian sperm, MOs undergo acidification during development. Treatment of spermatids with the V-ATPase inhibitor bafilomycin blocks both MO acidification and formation of functional spermatozoa. There are several spermatogenesis-defective mutants that cause defects in MO morphogenesis, including spe-5. We determined that spe-5, which is on chromosome I, encodes one of two V-ATPase B paralogous subunits. The spe-5 null mutant is viable but sterile because it forms arrested, multi-nucleate spermatocytes. Immunofluorescence with a SPE-5-specific monoclonal antibody shows that SPE-5 expression begins in spermatocytes and is found in all subsequent stages of spermatogenesis. Most SPE-5 is discarded into the residual body during spermatid budding, but a small amount remains in budded spermatids where it localizes to MOs as a discrete dot. The other V-ATPase B subunit is encoded by vha-12, which is located on the X chromosome. Usually, spe-5 mutants are self-sterile in a wild-type vha-12 background. However, an extrachromosomal transgene containing wild-type vha-12 driven by its own promoter allows spe-5 mutant hermaphrodites to produce progeny, indicating that VHA-12 can at least partially substitute for SPE-5. Others have shown that the X chromosome is transcriptionally silent in the male germline, so expression of the autosomally located spe-5 gene ensures that a V-ATPase B subunit is present during spermatogenesis.
Endoscopically guided removal of cloacal calculi in three African spurred tortoises (Geochelone sulcata)
Authors: Mans Christoph , Sladky Kurt K. 
Published: March 2012

Abstract
Case Description—3 female African spurred tortoises (Geochelone sulcata) of various body weights (0.22, 0.77, and 2.86 kg [0.48, 1.69, and 6.29 lb]) were examined because of reduced food intake and lack of fecal output. Owners reported intermittent tenesmus in 2 of the tortoises.
Clinical Findings—Physical examinations revealed no clinically important abnormalities in the tortoises. Cloacal calculi were diagnosed on the basis of radiography and cloacoscopy in all 3 tortoises. One tortoise had another calculus in the urinary bladder.
Treatment and Outcome—Tortoises were anesthetized, and cloacal calculi were removed by use of a cutting burr (plain-fissure cutting burr and a soft tissue protector mounted to a dental handpiece that had a low-speed motor and a straight nose cone) and warm water irrigation with endoscopic guidance. Complete removal of calculus fragments was achieved by use of forceps and irrigation. In 1 tortoise, removal of the cloacal calculus was staged (2 separate procedures). In another tortoise, a second cloacal calculus (which had been located in the urinary bladder during the first examination) was successfully removed 25 days after removal of the first calculus. All 3 tortoises recovered uneventfully, and serious complications secondary to removal of the cloacal calculi were not detected.
Clinical Relevance—Cloacoscopy combined with the use of a low-speed dental drill and warm water irrigation should be considered a simple, safe, and nontraumatic treatment option for removal of obstructive cloacal calculi in tortoises.
“The Man Without a Country” and America's Post-war Crisis of National Belonging
Authors: Gibian Peter 
Published: March 2012

Abstract:Hale's “The Man Without a Country” turns on itself: The Man without a Country emerges not as the story's one-dimensional villain but as its complex hero—a new sort of cosmopolitan patriot. With its powerful evocation of sentimental attachment to the figure of the American expatriate voyager, Hale's tale reflects the author's struggle to re-assert the sentimental power of an imagined community in the new context of a wide-ranging global existence. Hale may have begun writing in response to the crisis of national belonging triggered by the Civil War, hoping that this piece of invented folklore would reinforce or restore an older mode of bounded American national self-definition, but “The Man without a Country” in fact anticipates the outline of an alternative vision and stance reflecting the new international situation emerging over the course of the 19th-century—giving us a prescient portrait of an American identity that finds itself most fully in trans-national situations.