bluuebunny/crossref_metadata_2025_split huggingface dataset:
K-shell spectroscopy of Au plasma generated with a short-pulse laser1This article is part of a Special Issue on the 10th International Colloquium on Atomic Spectra and Oscillator Strengths for Astrophysical and Laboratory Plasmas.
Authors: Zulick C. , Dollar F. , Chen H. , Falk K. , Gregori G. , Hazi A. , Murphy C.D. , Park J. , Seely J. , Szabo C.I. , Tommasini R. , Shepherd R. , Krushelnick K. 
Published: May 2011

The production of X-rays from electron transitions into K-shell vacancies (Kα,β) emission) is a well-known process in atomic physics and has been extensively studied as a plasma diagnostic in low- and mid-Z materials. However, X-ray spectra from near neutral high-Z ions are very complex, and their interpretation requires the use of state-of-the-art atomic calculations. In this experiment, the Titan laser system at Lawrence Livermore National Laboratory was used to deliver an approximately 350 J laser pulse, with a 10 ps duration and a wavelength of 1054 nm, to a gold (Au) target. A transparent bent quartz crystal spectrometer with a hard X-ray energy window, ranging from 17 to 102 keV, was used to measure the emission spectrum. Kα1,α2 and Kβ1,γ1 transitions were observed over a range of target sizes. Additionally, a series of shots were conducted with a pre-ionizing long pulse (3 ns, 1–10 J, 527 nm) on the backside of the target. FLYCHK, an atomic non-LTE code, designed to provide ionization and population distributions, was used to model the experiment. Kα/Kβ ratios were found to be in good agreement with the predicted value for room temperature Au targets.
Anaplastic Thyroid Cancers Harbor Novel Oncogenic Mutations of the ALK Gene
Authors: Murugan Avaniyapuram Kannan , Xing Mingzhao 
Published: May 2011

Abstract
Thyroid cancer is the most common endocrine cancer, and targeted approaches to treat it pose considerable interest. In this study, we report the discovery of ALK gene mutations in thyroid cancer that may rationalize clinical evaluation of anaplastic lymphoma kinase (ALK) inhibitors in this setting. In undifferentiated anaplastic thyroid cancer (ATC), we identified two novel point mutations, C3592T and G3602A, in exon 23 of the ALK gene, with a prevalence of 11.11%, but found no mutations in the matched normal tissues or in well-differentiated thyroid cancers. These two mutations, resulting in L1198F and G1201E amino acid changes, respectively, both reside within the ALK tyrosine kinase domain where they dramatically increased tyrosine kinase activities. Similarly, these mutations heightened the ability of ALK to activate the phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein (MAP) kinase pathways in established mouse cells. Further investigations showed that these two ALK mutants strongly promoted cell focus formation, anchorage-independent growth, and cell invasion. Similar oncogenic properties were observed in the neuroblastoma-associated ALK mutants K1062M and F1174L but not in wild-type ALK. Overall, our results reveal two novel gain-of-function mutations of ALK in certain ATCs, and they suggest efforts to clinically evaluate the use of ALK kinase inhibitors to treat patients who harbor ATCs with these mutations. Cancer Res; 71(13); 4403–11. ©2011 AACR.
An Increased Burden of Common and Rare Lipid-Associated Risk Alleles Contributes to the Phenotypic Spectrum of Hypertriglyceridemia
Authors: Johansen Christopher T. , Wang Jian , Lanktree Matthew B. , McIntyre Adam D. , Ban Matthew R. , Martins Rebecca A. , Kennedy Brooke A. , Hassell Reina G. , Visser Maartje E. , Schwartz Stephen M. , Voight Benjamin F. , Elosua Roberto , Salomaa Veikko , O'Donnell Christopher J. , Dallinga-Thie Geesje M. , Anand Sonia S. , Yusuf Salim , Huff Murray W. , Kathiresan Sekar , Cao Henian , Hegele Robert A. 
Published: May 2011

Objective—
Earlier studies have suggested that a common genetic architecture underlies the clinically heterogeneous polygenic Fredrickson hyperlipoproteinemia (HLP) phenotypes defined by hypertriglyceridemia (HTG). Here, we comprehensively analyzed 504 HLP-HTG patients and 1213 normotriglyceridemic controls and confirmed that a spectrum of common and rare lipid-associated variants underlies this heterogeneity.

Methods and Results—

First, we demonstrated that genetic determinants of plasma lipids and lipoproteins, including common variants associated with plasma triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) from the Global Lipids Genetics Consortium were associated with multiple HLP-HTG phenotypes. Second, we demonstrated that weighted risk scores composed of common TG-associated variants were distinctly increased across all HLP-HTG phenotypes compared with controls; weighted HDL-C and LDL-C risk scores were also increased, although to a less pronounced degree with some HLP-HTG phenotypes. Interestingly, decomposition of HDL-C and LDL-C risk scores revealed that pleiotropic variants (those jointly associated with TG) accounted for the greatest difference in HDL-C and LDL-C risk scores. The
APOE
E2/E2 genotype was significantly overrepresented in HLP type 3 versus other phenotypes. Finally, rare variants in 4 genes accumulated equally across HLP-HTG phenotypes.

Conclusion—
HTG susceptibility and phenotypic heterogeneity are both influenced by accumulation of common and rare TG-associated variants.
Microbleeds Are Associated With Subsequent Hemorrhagic and Ischemic Stroke in Healthy Elderly Individuals
Authors: Bokura Hirokazu , Saika Reiko , Yamaguchi Takuya , Nagai Atsushi , Oguro Hiroaki , Kobayashi Shotai , Yamaguchi Shuhei 
Published: May 2011

Background and Purpose—
Cerebral microbleeds (MBs) are frequently detected in patients with stroke, especially those who experience intracerebral hemorrhage. However, the clinical significance of MBs in subjects without cerebrovascular disease is still unclear. We performed a prospective study to determine whether the presence of MBs provides useful prognostic information in healthy elderly individuals.

Methods—
We tracked 2102 subjects (mean age, 62.1 years) over a mean interval of 3.6 years after they voluntarily participated in the brain checkup system at the Shimane Institute of Health Science. An initial assessment was performed to document the presence of MBs and silent ischemic brain lesions and to map the location of the MBs. During the follow-up period, we obtained information about stroke events that occurred in each subject.

Results—
MBs were detected in 93 of the 2102 subjects (4.4%). Strokes occurred in 44 subjects (2.1%) during the follow-up period. They were significantly more common among subjects with MBs. Age and hypertension were independent risk factors for MBs. The presence of MBs was more strongly associated with a deep brain hemorrhage (hazard ratio, 50.2; 95% CI, 16.7 to 150.9) than ischemic stroke (hazard ratio, 4.48; 95% CI, 2.20 to 12.2). All hemorrhagic strokes occurred in deep brain regions, and they were associated with MBs located in the deep brain region.

Conclusions—
This longitudinal study demonstrated that the presence of MBs can be used to predict hemorrhagic and ischemic stroke, even in healthy elderly individuals.
Characteristics and Changes of Extreme Precipitation in the Yellow–Huaihe and Yangtze–Huaihe Rivers Basins, China
Authors: Dong Quan , Chen Xing , Chen Tiexi 
Published: May 2011

Abstract
Many works suggest that the intensity of extreme precipitation might be changing under the background of global warming. Because of the importance of extreme precipitation in the Yellow–Huaihe and Yangtze–Huaihe River basins of China and to compare the spatial difference, the generalized Pareto distribution (GPD) function is used to fit the daily precipitation series in these basins and an estimate of the extreme precipitation spatial distribution is presented. At the same time, its long-term trends are estimated for the period between 1951 and 2004 by using a generalized linear model (GLM), which is based on GPD. High quality daily precipitation data from 215 observation stations over the area are used in this study. The statistical significance of the trend fields is tested with a Monte Carlo experiment based on a two-dimensional Hurst coefficient, H2.
The spatial distribution of the shape parameter of GPD indicates that the upper reaches of the Huaihe River (HuR) basin have the largest probability of extreme rainfall events, which is consistent with most historical flood records in this region. Spatial variations in extreme precipitation trends are found and show significant positive trends in the upper reaches of Poyang Lake in the Yangtze River (YaR) basin and a significant negative trend in the mid- to lower reaches of the Yellow River (YeR) and Haihe River (HaR) basins. The trends in the HuR basin and the lower reaches of Poyang Lake in the YaR basin are nearly neutral. All trend fields are significant at the 5% level of significance from the Monte Carlo experiments.
Altimetry Combined with Hydrography for Ocean Transport Estimation
Authors: Gourcuff Claire , Lherminier Pascale , Mercier Herlé , Le Traon Pierre Yves 
Published: May 2011

Abstract
A method to estimate mass and heat transports across hydrographic sections using hydrography together with altimetry data in a geostrophic inverse box model is presented. Absolute surface velocities computed from Archiving, Validation, and Interpretation of Satellite Oceanographic data (AVISO) altimetry products made up of a combination of sea surface height measurements and geoid estimate are first compared to ship acoustic Doppler current profiler (S-ADCP) measurements of the Observatoire de la Variabilité Interannuelle et Décennale (OVIDE) project along hydrographic sections repeated every 2 yr in summer from Portugal to Greenland. The RMS difference between S-ADCP and altimetry velocities averaged on distances of about 100 km accounts for 3.3 cm s−1. Considering that the uncertainty of S-ADCP velocities is found at 1.5 cm s−1, altimetry errors are estimated at 3 cm s−1. Transports across OVIDE sections previously obtained using S-ADCP data to constrain the geostrophic inverse box model are used as a reference. The new method is found useful to estimate absolute transports across the sections, as well as part of their variability. Despite associated uncertainties that are about 50% larger than when S-ADCP is used, the results for the North Atlantic Current and heat transports, with uncertainties of 10%–15%, reproduce the already observed variability. The largest uncertainties are found in the estimates of the East Greenland Irminger Current (EGIC) transport (30%), induced by larger uncertainties associated with altimetry data at the western boundary.
The Meteorological Global Model GLOBO at the ISAC-CNR of Italy Assessment of 1.5 Yr of Experimental Use for Medium-Range Weather Forecasts
Authors: Malguzzi Piero , Buzzi Andrea , Drofa Oxana 
Published: May 2011

Abstract
Since August 2009, the GLOBO atmospheric general circulation model has been running experimentally at the Institute of Atmospheric Sciences and Climate (ISAC) of the National Council of Research of Italy. GLOBO is derived from the Bologna Limited Area Model (BOLAM), a gridpoint limited-area meteorological model that was developed at the same institute and that has been extended to the entire earth atmosphere. The main dynamical features and physical parameterizations of GLOBO are presented. Starting from initial conditions obtained from the analysis of the NCEP Global Forecast System (GFS) model valid at 0000 UTC, 6-day forecasts with average horizontal resolution of 32 km were performed on a daily basis and in real time. The assessment of the forecast skill during the 1.5-yr period included the calculation of the monthly averaged root-mean-square errors (model prediction versus gridded analyses) of geopotential height at 500 hPa and mean sea level pressure for the northern and southern extratropics, performed accordingly to WMO Commission for Basic Systems (CBS) standards. The verification results are compared with models from other global data processing and forecasting system centers, as are available in the literature. The GLOBO skill for medium-range forecasts turns out to be comparable to that of the above models. The lack of analyses based on model forecasts and data assimilation is likely to penalize the scores for shorter-term forecasts.
Second-Generation Autologous Chondrocyte Implantation
Authors: Kon Elizaveta , Filardo Giuseppe , Condello Vincenzo , Collarile Marco , Di Martino Alessandro , Zorzi Claudio , Marcacci Maurilio 
Published: May 2011

Background Aging is responsible for degenerative changes in all cartilage elements, thus impairing its properties and healing potential. Most studies on surgical procedures for cartilage focus on young patients because these procedures are generally not considered suitable for older patients. Purpose To analyze the clinical outcome of cartilage lesion treatment using second-generation autologous chondrocyte implantation (ACI) techniques in patients more than 40 years old with no clear signs of osteoarthritis, to understand their real potential in relation to aging, the failure rate, and complications in older patients. Study Design Case series; Level of evidence, 4. Methods Sixty-one patients with grade III to IV cartilaginous lesions of the condyles with no clear signs of osteoarthritis and a minimum age of 40 years were treated with second-generation ACI and prospectively evaluated at 5 years’ follow-up. Twenty-two patients were treated with arthroscopic Hyalograft C implantation, and 39 underwent the open Chondro-Gide MACI procedure. Results A significant improvement in both subjective and objective evaluations was observed. The International Knee Documentation Committee (IKDC) subjective score improved from 36.8 ± 8.4 to 68.1 ± 21.8 at the final evaluation. The failure rate was 20%. A faster improvement was observed in the group treated with the arthroscopic Hyalograft C technique, whereas similar scores were found at the 24-month follow-up and final evaluation. Conclusion A clinical improvement was found in patients more than 40 years old, who in most cases benefited from second-generation ACI with good results lasting at medium-term follow-up. However, the results were inferior with respect to those previously found for younger populations, and the failure rate at medium-term follow-up was also higher. These findings were consistent in the 2 treatment groups. The only difference was the faster recovery when the arthroscopic approach was used.
A tumor suppressor function of the Msr1 gene in leukemia stem cells of chronic myeloid leukemia
Authors: Chen Yaoyu , Sullivan Con , Peng Cong , Shan Yi , Hu Yiguo , Li Dongguang , Li Shaoguang 
Published: May 2011

Abstract
We have shown that Alox5 is a critical regulator of leukemia stem cells (LSCs) in a BCR-ABL–induced chronic myeloid leukemia (CML) mouse model, and we hypothesize that the Alox5 pathway represents a major molecular network that regulates LSC function. Therefore, we sought to dissect this pathway by comparing the gene expression profiles of wild type and Alox5−/− LSCs. DNA microarray analysis revealed a small group of candidate genes that exhibited changes in the levels of transcription in the absence of Alox5 expression. In particular, we noted that the expression of the Msr1 gene was upregulated in Alox5−/− LSCs, suggesting that Msr1 suppresses the proliferation of LSCs. Using CML mouse model, we show that Msr1 is downregulated by BCR-ABL and this down-regulation is partially restored by Alox5 deletion, and that Msr1 deletion causes acceleration of CML development. Moreover, Msr1 deletion markedly increases LSC function through its effects on cell cycle progression and apoptosis. We also show that Msr1 affects CML development by regulating the PI3K-AKT pathway and β-Catenin. Together, these results demonstrate that Msr1 suppresses LSCs and CML development. The enhancement of the tumor suppressor function of Msr1 may be of significance in the development of novel therapeutic strategies for CML.
Tissue inflammation modulates gene expression of lymphatic endothelial cells and dendritic cell migration in a stimulus-dependent manner
Authors: Vigl Benjamin , Aebischer David , Nitschké Maximilian , Iolyeva Maria , Röthlin Tamara , Antsiferova Olga , Halin Cornelia 
Published: May 2011

AbstractChemokines and adhesion molecules up-regulated in lymphatic endothelial cells (LECs) during tissue inflammation are thought to enhance dendritic cell (DC) migration to draining lymph nodes, but the in vivo control of this process is not well understood. We performed a transcriptional profiling analysis of LECs isolated from murine skin and found that inflammation induced by a contact hypersensitivity (CHS) response up-regulated the adhesion molecules ICAM-1 and VCAM-1 and inflammatory chemokines. Importantly, the lymphatic markers Prox-1, VEGFR3, and LYVE-1 were significantly down-regulated during CHS. By contrast, skin inflammation induced by complete Freund adjuvant induced a different pattern of chemokine and lymphatic marker gene expression and almost no ICAM-1 up-regulation in LECs. Fluorescein isothiocyanate painting experiments revealed that DC migration to draining lymph nodes was more strongly increased in complete Freund adjuvant-induced than in CHS-induced inflammation. Surprisingly, DC migration did not correlate with the induction of CCL21 and ICAM-1 protein in LECs. Although the requirement for CCR7 signaling became further pronounced during inflammation, CCR7-independent signals had an additional, albeit moderate, impact on enhancing DC migration. Collectively, these findings indicate that DC migration in response to inflammation is stimulus-specific, mainly CCR7-dependent, and overall only moderately enhanced by LEC-induced genes other than CCL21.
Small vessels, big trouble in the kidneys and beyond: hematopoietic stem cell transplantation–associated thrombotic microangiopathy
Authors: Laskin Benjamin L. , Goebel Jens , Davies Stella M. , Jodele Sonata 
Published: May 2011

AbstractTransplantation-associated thrombotic microangiopathy (TA-TMA) is a challenging diagnosis after hematopoietic stem cell transplantation. Although endothelial injury represents the final common pathway of disease, the exact pathophysiology of TA-TMA remains unclear. Potential causes include infections, chemotherapy, radiation, and calcineurin inhibitors. Recent literature addresses the roles of cytokines, graft-versus-host disease, the coagulation cascade, and complement in the pathogenesis of TA-TMA. Current diagnostic criteria are unsatisfactory, because patients who have received a transplant can have multiple other reasons for the laboratory abnormalities currently used to diagnose TA-TMA. Moreover, our lack of understanding of the exact mechanism of disease limits the development and evaluation of potential treatments. Short- and long-term renal complications contribute to TA-TMA's overall poor prognosis. In light of these challenges, future research must validate novel markers of disease to aid in early diagnosis, guide current and future treatments, prevent long-term morbidity, and improve outcomes. We focus on TA-TMA as a distinct complication of hematopoietic stem cell transplantation, emphasizing the central role of the kidney in this disease.
Risk stratification of intermediate-risk acute myeloid leukemia: integrative analysis of a multitude of gene mutation and gene expression markers
Authors: Rockova Veronika , Abbas Saman , Wouters Bas J. , Erpelinck Claudia A. J. , Beverloo H. Berna , Delwel Ruud , van Putten Wim L. J. , Löwenberg Bob , Valk Peter J. M. 
Published: May 2011

AbstractNumerous molecular markers have been recently discovered as potential prognostic factors in acute myeloid leukemia (AML). It has become of critical importance to thoroughly evaluate their interrelationships and relative prognostic importance. Gene expression profiling was conducted in a well-characterized cohort of 439 AML patients (age < 60 years) to determine expression levels of EVI1, WT1, BCL2, ABCB1, BAALC, FLT3, CD34, INDO, ERG and MN1. A variety of AML-specific mutations were evaluated, that is, FLT3, NPM1, N-RAS, K-RAS, IDH1, IDH2, and CEBPADM/SM (double/single). Univariable survival analysis shows that (1) patients with FLT3ITD mutations have inferior overall survival (OS) and event-free survival (EFS), whereas CEBPADM and NPM1 mutations indicate favorable OS and EFS in intermediate-risk AML, and (2) high transcript levels of BAALC, CD34, MN1, EVl1, and ERG predict inferior OS and EFS. In multivariable survival analysis, CD34, ERG, and CEBPADM remain significant. Using survival tree and regression methodologies, we show that CEBPADM, CD34, and IDH2 mutations are capable of separating the intermediate group into 2 AML subgroups with highly distinctive survival characteristics (OS at 60 months: 51.9% vs 14.9%). The integrated statistical approach demonstrates that from the multitude of biomarkers a greatly condensed subset can be selected for improved stratification of intermediate-risk AML.
Lenalidomide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone in newly diagnosed multiple myeloma: a phase 1/2 Multiple Myeloma Research Consortium trial
Authors: Jakubowiak Andrzej J. , Griffith Kent A. , Reece Donna E. , Hofmeister Craig C. , Lonial Sagar , Zimmerman Todd M. , Campagnaro Erica L. , Schlossman Robert L. , Laubach Jacob P. , Raje Noopur S. , Anderson Tara , Mietzel Melissa A. , Harvey Colleen K. , Wear Sandra M. , Barrickman Jennifer C. , Tendler Craig L. , Esseltine Dixie-Lee , Kelley Susan L. , Kaminski Mark S. , Anderson Kenneth C. , Richardson Paul G. 
Published: May 2011

AbstractThis phase 1/2 trial evaluated combination lenalidomide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone (RVDD) in newly diagnosed multiple myeloma (MM) patients. Patients received RVDD at 4 dose levels, including the maximum tolerated dose (MTD). Patients with a very good partial response or better (≥ VGPR) after cycle 4 proceeded to autologous stem cell transplantation or continued treatment. The primary objectives were MTD evaluation and response to RVDD after 4 and 8 cycles. Seventy-two patients received a median of 4.5 cycles. The MTDs were lenalidomide 25 mg, bortezomib 1.3 mg/m2, pegylated liposomal doxorubicin 30 mg/m2, and dexamethasone 20/10 mg, as established with 3-week cycles. The most common adverse events were fatigue, constipation, sensory neuropathy, and infection; there was no treatment-related mortality. Response rates after 4 and 8 cycles were 96% and 95% partial response or better, 57% and 65% ≥ VGPR, and 29% and 35% complete or near-complete response, respectively. After a median follow-up of 15.5 months, median progression-free survival (PFS) and overall survival (OS) were not reached. The estimated 18-month PFS and OS were 80.8% and 98.6%, respectively. RVDD was generally well tolerated and highly active, warranting further study in newly diagnosed MM patients. This trial was registered at www.clinicaltrials.gov as NCT00724568.