julilili42/papers huggingface dataset:
Estimation of volume changes of mountain glaciers from ICESat data: an example from the Aletsch Glacier, Swiss Alps
2013-07-02

Abstract. Worldwide estimation of recent changes in glacier volume is challenging, but becomes more feasible with the help of present and future remote sensing missions. NASA's Ice Cloud and Elevation Satellite (ICESat) mission provides accurate elevation estimates derived from the two way travel time of the emitted laser pulse. In this study two different methods were employed for derivation of surface elevation changes from ICESat records on example of the Aletsch Glacier. A statistical approach relies on elevation differences of ICESat points to a reference DEM while an analytical approach compares spatially similar ICESat tracks. Using the statistical approach, in the upper and lower parts of the ablation area, the surface lowering was found to be from −2.1 ± 0.15 m yr−1 to −2.6 ± 0.10 m yr−1 and from −3.3 ± 0.36 m yr−1 to −5.3 ± 0.39 m yr−1, respectively, depending on the DEM used. Employing the analytical method, the surface lowering in the upper part of the ablation area was estimated as −2.5 ± 1.3 m yr−1 between 2006 and 2009. In the accumulation area both methods revealed no significant trend. The trend in surface lowering derived by the statistical method allows an estimation of the mean mass balance in the period 2003–2009 assuming constant ice density and a linear change of glacier surface lowering with altitude in the ablation area. The resulting mass balance was validated by a comparison to another geodetic approach based on the subtraction of two DEMs for the years 2000 and 2009. We conclude that ICESat data is a valid source of information on surface elevation changes and on mass balance of mountain glaciers.
Complex grammar in lesion-induced right-hemispheric language—A child-friendly fMRI paradigm
2013-07-02

Aims: The developing brain's right hemisphere (RH) seems to compensate for pre-/perinatally left-hemispheric (LH) lesions by taking over the language function, usually localized in the LH. Recent linguistic investigations revealed subtle but robust deficits in the processing of complex syntax in children with RH language. The neurological correlate of complex syntax processing in these children is unclear.
Contrast Dependence and Differential Contributions from Somatostatin- and Parvalbumin-Expressing Neurons to Spatial Integration in Mouse V1
2013-07-03

A characteristic feature in the primary visual cortex is that visual responses are suppressed as a stimulus extends beyond the classical receptive field. Here, we examined the role of inhibitory neurons expressing somatostatin (SOM+) or parvalbumin (PV+) on surround suppression and preferred receptive field size. We recorded multichannel extracellular activity in V1 of transgenic mice expressing channelrhodopsin in SOM+ neurons or PV+ neurons. Preferred size and surround suppression were measured using drifting square-wave gratings of varying radii and at two contrasts. Consistent with findings in primates, we found that the preferred size was larger for lower contrasts across all cortical depths, whereas the suppression index (SI) showed a trend to decrease with contrast. We then examined the effect of these metrics on units that were suppressed by photoactivation of either SOM+ or PV+ neurons. When activating SOM+ neurons, we found a significant increase in SI at cortical depths >400 μm, whereas activating PV+ neurons caused a trend toward lower SIs regardless of cortical depth. Conversely, activating PV+ neurons significantly increased preferred size across all cortical depths, similar to lowering contrast, whereas activating SOM+ neurons had no systematic effect on preferred size across all depths. These data suggest that SOM+ and PV+ neurons contribute differently to spatial integration. Our findings are compatible with the notion that SOM+ neurons mediate surround suppression, particularly in deeper cortex, whereas PV+ activation decreases the drive of the input to cortex and therefore resembles the effects on spatial integration of lowering contrast.
Age-associated alterations in γδ T-cells are present predominantly in individuals infected with Cytomegalovirus
2013-07-03

Abstract Background Despite the common perception that latent Cytomegalovirus (CMV) infection is usually symptom-free, emerging epidemiological evidence suggests that it may in fact be associated with higher mortality over extended follow-up. Mechanisms responsible for this potentially important effect are unclear. CMV infection is known to have a large impact on the distribution of T cell phenotypes, especially the accumulation of late-stage differentiated CD8 + , as well as Vδ2 - γδ T-cells, which are the main subset of γδ T-cells involved in anti-CMV immunity. Its impact on γδ T-cells in the aging context is less well-defined. Results Here, we investigated a group of healthy individuals aged between 21 and 89 years, in order to correlate the frequency and differentiation status of γδ T-cells with age. We found that these parameters were only marginally influenced by age, but were marked in people with a latent CMV infection. Thus, we observed a significant age-associated accumulation of late-differentiated T-cells within the Vδ2 - population, but only in CMV-seropositive donors. There was also a strong trend towards reduced frequency of early-differentiated cells within the Vδ2 - phenotype. Older people had significantly higher anti-CMV IgG titers, which in turn correlated significantly with a lower Vδ2 + /Vδ2 - ratio and a shift from early- to a late-differentiated Vδ2 - T-cell phenotype. Conclusions Our findings demonstrate a strong influence of CMV on γδ T-cells during human ageing, similar to that observed for αβ T-cells. Differences between donors of different ages are more marked in CMV-infected individuals. The biological implications of this potent age-associated CMV-mediated immune-modulation require clarification.
CYP2B6*6 is associated with increased breast cancer risk
2013-07-03

The cytochrome P450 2B6 (CYP2B6) is involved in the metabolism of testosterone. Functional changes in this enzyme may influence endogenous hormone exposure, which has been associated with risk of breast cancer. To assess potential associations between two functional polymorphisms CYP2B6 _516_G&gt;T (rs3745274) and CYP2B6 _785_A&gt;G (rs2279343) and breast cancer risk, we established a specific matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry assay. The GENICA breast cancer case–control study showed associations between the variant genotypes CYP2B6 _516_TT and CYP2B6 _785_GG and breast cancer risk with odds ratios (ORs) of 1.34 ( p = 0.001) and 1.31 ( p = 0.002), respectively. A similar effect was observed for carriers of the CYP2B6 _516_T allele in a validation study including four independent studies from Germany, Sweden and USA. In a pooled analysis of all five studies involving 4,638 breast cancer cases and 3,594 controls of European ancestry, carriers of the CYP2B6 _516_G and the CYP2B6 _785_G variant had an increased breast cancer risk with ORs of 1.10 ( p = 0.027) and 1.10 ( p = 0.031), respectively. We conclude that the genetic variants CYP2B6 _516_G and CYP2B6 _785_G (designated CYP2B6 *6), which are known to decrease activity of the CYP2B6 enzyme, contribute to an increased breast cancer risk.
Accelerating type‐specific ovarian carcinoma research: Calculator for Ovarian Subtype Prediction (COSP) is a reliable high‐throughput tool for case review
2013-07-03

Aims The recent recognition that ovarian carcinoma is composed of five distinct disease entities has served to increase the value of accurate histotyping. Reliable identification of histotypes is essential for the success of studies testing novel therapies, as well as for biomarker discovery research. The aim of this study was to examine the utility of a nine‐marker immunohistochemical ( IHC ) panel, designated the Calculator for Ovarian Subtype Prediction ( COSP ), to reliably reproduce the consensus diagnosis of two expert gynaecological pathologists. Methods and results A total of 423 cases from the AGO ‐ OVAR 11 trial were evaluated using the COSP IHC panel, and compared to original diagnoses from &gt;100 local contributing pathologists and independent expert gynaecopathology review. The overall concordance between COSP and expert review was 89%; in cases where a local pathologist's diagnosis was confirmed by COSP , the expert gynaecopathologist also agreed in 97.5% of cases. Conclusions The incorporation of COSP into a high‐throughput diagnostic review algorithm will decrease the need for expert review by identifying a small number of difficult cases that truly require expert review. This modification will serve to increase the efficiency of the diagnostic review process, which will probably serve to reduce operational costs and expedite translational studies on ovarian carcinoma.
Sulphatation Does Not Appear to Be a Protective Mechanism to Prevent Oxysterol Accumulation in Humans and Mice
2013-07-03

24S- and 27-hydroxycholesterol (24OHC and 27OHC) are potent regulators of different biochemical systems in vitro and are the major circulating oxysterols. A small fraction of these oxysterols has been reported to be sulphated but there are no detailed studies. We considered the possibility that sulphatation is a protective mechanism preventing accumulation of free oxysterols. Using an accurate assay we found the sulphated fraction of 24OHC and 27OHC in circulation of adults to be less than 15% of total. In two patients with a mutation in CYP7B1 and markedly increased levels of 27OHC the sulphated fraction was 8% and 10% respectively. Infants with severe neonatal cholestasis had however markedly increased sulphate fraction of the above oxysterols. In untreated mice the degree of sulphatation of 24OHC and 27OHC in serum varied between 0 and 16%. Similar degree of sulphatation was found in two mouse models with markedly increased levels of 27OHC and 24OHC respectively. Bile duct ligated mice had higher levels of oxysterols than sham-operated controls but the sulphate fraction was not increased. We conclude that a primary increase in the levels of the oxysterols due to increased synthesis or reduced metabolism in adults and mice does not induce increased sulphatation.
Emergence of Agriculture in the Foothills of the Zagros Mountains of Iran
2013-07-04

Early Farmers? What was the role of the eastern Fertile Crescent (which includes southeastern Turkey, northeastern Iraq, and western Iran) in the transition from foraging to farming? Riehl et al. (p. 65 ; see the Perspective by Willcox ) investigated an archaeobotanical assemblage from Chogha Golan, in modern Iran over an apparently continuous occupation of the site over 2000 years, which captures the transition from foraging to farming. The rich archaeobotanical remains suggest the use of a wide array of plant species, including the progenitors of key crop plants (wheat, barley, and large-seeded legumes). Residents of the eastern Fertile Crescent thus appear to have been involved in plant management and possibly in the domestication of wild crop plants.
Arabidopsis HEAT SHOCK TRANSCRIPTION FACTORA1b overexpression enhances water productivity, resistance to drought, and infection
2013-07-04

Heat-stressed crops suffer dehydration, depressed growth, and a consequent decline in water productivity, which is the yield of harvestable product as a function of lifetime water consumption and is a trait associated with plant growth and development. Heat shock transcription factor (HSF) genes have been implicated not only in thermotolerance but also in plant growth and development, and therefore could influence water productivity. Here it is demonstrated that Arabidopsis thaliana plants with increased HSFA1b expression showed increased water productivity and harvest index under water-replete and water-limiting conditions. In non-stressed HSFA1b-overexpressing (HSFA1bOx) plants, 509 genes showed altered expression, and these genes were not over-represented for development-associated genes but were for response to biotic stress. This confirmed an additional role for HSFA1b in maintaining basal disease resistance, which was stress hormone independent but involved H2O2 signalling. Fifty-five of the 509 genes harbour a variant of the heat shock element (HSE) in their promoters, here named HSE1b. Chromatin immunoprecipitation-PCR confirmed binding of HSFA1b to HSE1b in vivo, including in seven transcription factor genes. One of these is MULTIPROTEIN BRIDGING FACTOR1c (MBF1c). Plants overexpressing MBF1c showed enhanced basal resistance but not water productivity, thus partially phenocopying HSFA1bOx plants. A comparison of genes responsive to HSFA1b and MBF1c overexpression revealed a common group, none of which harbours a HSE1b motif. From this example, it is suggested that HSFA1b directly regulates 55 HSE1b-containing genes, which control the remaining 454 genes, collectively accounting for the stress defence and developmental phenotypes of HSFA1bOx.
European Financial Capitalism and the Politics of (De-)financialization
2013-07-04

Over recent decades, the political economy of the European Union has been marked by the emergence of a European financial capitalism and various processes of financialization. This article aims to explore the constitutive role of political strategies, decisions and conflicts in these developments, in particular with regard to ongoing European crises tendencies. For this purpose, it draws on a neo-Gramscian and regulationist conceptual framework which differentiates between three levels of analysis: that of a ‘historic bloc’ or specific societal formation; a ‘hegemonic bloc’ or particular alliance of leading social forces; and ‘political projects’, which are problem- or crisis-induced political initiatives. The article shows that in the course of the crisis the major political projects have been initiated or controlled by a finance-dominated transnational alliance. In this sense, European financial capitalism and financialization have been politically promoted and stabilized, so far. At the same time, however, the article also identifies increasing political contradictions and conflicts which indicate the precarious nature of past stabilization attempts.
The AT2 Domain of KirCI Loads Malonyl Extender Units to the ACPs of the Kirromycin PKS
2013-07-04

Abstract The antibiotic kirromycin is assembled by a hybrid modular polyketide synthases (PKSs)/nonribosomal peptide synthetases (NRPSs). Five of six PKSs of this complex assembly line do not have acyltransferase (AT) and have to recruit this activity from discrete AT enzymes. Here, we show that KirCI is a discrete AT which is involved in kirromycin production and displays a rarely found three‐domain architecture (AT 1 ‐AT 2 ‐ER). We demonstrate that the second AT domain, KirCI‐AT 2 , but not KirCI‐AT 1 , is the malonyl‐CoA‐specific AT which utilizes this precursor for loading the acyl carrier proteins (ACPs) of the trans ‐AT PKS in vitro. In the kirromycin biosynthetic pathway, ACP5 is exclusively loaded with ethylmalonate by the enzyme KirCII and is not recognized as a substrate by KirCI. Interestingly, the excised KirCI‐AT 2 can also transfer malonate to ACP5 and thus has a relaxed ACP‐specificity compared to the entire KirCI protein. The ability of KirCI‐AT 2 to load different ACPs provides opportunities for AT engineering as a potential strategy for polyketide diversification.
Diabetes Subphenotypes and Metabolomics: The Key to Discovering Laboratory Markers for Personalized Medicine?
2013-07-04

For decades, glucose, hemoglobin A1c, insulin, and C peptide have been the laboratory tests of choice to detect and monitor diabetes (1). However, these tests do not identify individuals at risk for developing type 2 diabetes (T2Dm)4 (so-called prediabetic individuals and the subphenotypes therein), which would be a prerequisite for individualized prevention. Nor are these parameters suitable to identify T2Dm subphenotypes, a prerequisite for individualized therapeutic interventions. The oral glucose tolerance test (oGTT) is still the only means for the early and reliable identification of people in the prediabetic phase with impaired glucose tolerance (IGT). This procedure, however, is very time-consuming and expensive and is unsuitable as a screening method in a doctor&amp;prime;s office. Hence, there is an urgent need for innovative laboratory tests to simplify the early detection of alterations in glucose metabolism.
Development and application of an automated extraction algorithm for fetal magnetocardiography – normal data and arrhythmia detection
2013-07-04

Abstract Introduction: Current standard methods of monitoring fetal heart function are mainly based on echocardiography, which provides indirect information (through mechanical assessment) of the fetal heart rhythm. Fetal magnetocardiography (fMCG) allows a reliable quantification of the temporal structure of fetal heart signals. However, its application in clinical studies is difficult because extracting the fetal heart signal for most current applications requires user intervention. To overcome this limitation, we developed a completely automated extraction algorithm. Patients and methods: The fMCG recordings were acquired using a 156-channel biomagnetic system. To perform an automated analysis, a combination of orthogonal projection and independent component analysis was used. fMCG recordings from 69 healthy uncomplicated singleton pregnancies with normally developing fetuses were included in the study. Results: The normal values achieved by the automated algorithm were comparable to previously published data. The majority of the cardiac time intervals were positively correlated with gestational age (GA). The ST segment, T wave and QT interval did not show any correlation. Conclusions: The automated detection of fetal heart signals was possible beginning at a GA of 19 weeks. This automated analysis of fMCG recordings might be an objective and easily applicable approach for clinicians to analyze fetal heart signals.
Measurement of tumour size with mammography, sonography and magnetic resonance imaging as compared to histological tumour size in primary breast cancer
2013-07-05

Abstract Background Tumour size in breast cancer influences therapeutic decisions. The purpose of this study was to evaluate sizing of primary breast cancer using mammography, sonography and magnetic resonance imaging (MRI) and thereby establish which imaging method most accurately corresponds with the size of the histological result. Methods Data from 121 patients with primary breast cancer were analysed in a retrospective study. The results were divided into the groups “ductal carcinoma in situ (DCIS)”, invasive ductal carcinoma (IDC) + ductal carcinoma in situ (DCIS)”, “invasive ductal carcinoma (IDC)”, “invasive lobular carcinoma (ILC)” and “other tumours” (tubular, medullary, mucinous and papillary breast cancer). The largest tumour diameter was chosen as the sizing reference in each case. Bland-Altman analysis was used to determine to what extent the imaging tumour size correlated with the histopathological tumour sizes. Results Tumour size was found to be significantly underestimated with sonography, especially for the tumour groups IDC + DCIS, IDC and ILC. The greatest difference between sonographic sizing and actual histological tumour size was found with invasive lobular breast cancer. There was no significant difference between mammographic and histological sizing. MRI overestimated non-significantly the tumour size and is superior to the other imaging techniques in sizing of IDC + DCIS and ILC. Conclusions The histological subtype should be included in imaging interpretation for planning surgery in order to estimate the histological tumour size as accurately as possible.
Characterization of incidental cardiac masses in oncological patients using a new CT-based tumor volume perfusion technique
2013-07-05

Cardiac masses are challenging for non-invasive diagnostic procedures and therapy, respectively. In tumor patients differentiation between primary or secondary cardiac neoplasm and thrombus is a frequent and knowingly difficult task to manage. To avoid complex and unnecessary surgical diagnostic procedures non-invasive methods are in favor. For initiation of adequate therapy and evaluation of prognosis, however, early and reliable diagnosis is mandatory. So far, echocardiography and magnetic resonance imaging represent the mainstay for cardiac imaging diagnosis. Recently, the new technique of CT-based tumor volume perfusion (VPCT) measurement has advanced to a potent, reliable, and easy to perform alternative for cardiac imaging. The purpose of this study was to review the existing spectrum of diagnostic modalities for characterization of cardiac masses in an oncologic patient cohort with emphasis on their strengths and limitations and to present the benefit from using the novel technique called VPCT for this purpose.
Anti‐leukaemic activity of a novel haploidentical‐transplantation approach employing unmanipulated bone marrow followed by CD6‐depleted peripheral blood stem cells in children with refractory/relapsed acute leukaemia
2013-07-06

Summary The treatment outcome of children with refractory acute leukaemia or relapse post‐stem cell transplantation is dismal. We report 10 children (non‐remission n = 7) who underwent a new haploidentical transplant approach utilizing unmanipulated bone marrow followed by CD 6‐depleted peripheral blood stem cells. Nine patients had successful engraftment and no evidence of leukaemia. Acute and chronic graft‐versus‐host‐disease was observed in five and three patients, respectively; two patients died of treatment‐related toxicity. Seven patients relapsed after 7 (range 3–34) months, however two patients are alive at 6·5 and 7·0 years. This approach provides anti‐leukaemic activity even in heavily pre‐treated children but long‐term disease control requires further intervention.
Two paralogous yefM-yoeB loci from Staphylococcus equorum encode functional toxin–antitoxin systems
2013-07-07

Toxin-antitoxin (TA) systems are small genetic elements of prokaryotes associated with persister cell formation, phage defence, stress regulation and programmed cell arrest. In this study, we characterized two paralogues of the ribosome-dependent RNase YefM-YoeB TA system from the Gram-positive organism Staphylococcus equorum SE3. 5' Rapid amplification of cDNA ends confirmed transcriptional activity in the exponential growth phase and revealed an extended 5' untranslated region upstream of the yefM-seq1 gene. Inducible expression of the putative yoeB-seq1/2 toxins led to growth defects of Escherichia coli, which were counteracted by simultaneous induction of the cognate yefM-seq1/2 antitoxin candidates in a strictly pairwise manner. Bacterial two-hybrid assays revealed interaction between YoeB-seq1 and YefM-seq1 but not YoeB-seq1 and YefM-seq2, also indicating two independent systems. In vivo primer extensions demonstrated specific RNA cleavage adjacent to the start codons by YoeB-seq proteins, and YoeB-seq2 activity could be neutralized by the corresponding antitoxin YefM-seq2. Together, these results indicate that the two yefM-yoeB-seq1/2 paralogues from S. equorum encode functional TA systems.