bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population Genetics of Vibrio cholerae from Nepal in 2010: Evidence on the Origin of the Haitian Outbreak
Authors: Hendriksen Rene S. , Price Lance B. , Schupp James M. , Gillece John D. , Kaas Rolf S. , Engelthaler David M. , Bortolaia Valeria , Pearson Talima , Waters Andrew E. , Prasad Upadhyay Bishnu , Devi Shrestha Sirjana , Adhikari Shailaja , Shakya Geeta , Keim Paul S. , Aarestrup Frank M. 
Published: August 2011

ABSTRACT

Cholera continues to be an important cause of human infections, and outbreaks are often observed after natural disasters, such as the one following the 2010 earthquake in Haiti. Once the cholera outbreak was confirmed, rumors spread that the disease was brought to Haiti by a battalion of Nepalese soldiers serving as United Nations peacekeepers. This possible connection has never been confirmed. We used whole-genome sequence typing (WGST), pulsed-field gel electrophoresis (PFGE), and antimicrobial susceptibility testing to characterize 24 recent
Vibrio cholerae
isolates from Nepal and evaluate the suggested epidemiological link with the Haitian outbreak. The isolates were obtained from 30 July to 1 November 2010 from five different districts in Nepal. We compared the 24 genomes to 10 previously sequenced
V. cholerae
isolates, including 3 from the Haitian outbreak (began July 2010). Antimicrobial susceptibility and PFGE patterns were consistent with an epidemiological link between the isolates from Nepal and Haiti. WGST showed that all 24
V. cholerae
isolates from Nepal belonged to a single monophyletic group that also contained isolates from Bangladesh and Haiti. The Nepalese isolates were divided into four closely related clusters. One cluster contained three Nepalese isolates and three Haitian isolates that were almost identical, with only 1- or 2-bp differences. Results in this study are consistent with Nepal as the origin of the Haitian outbreak. This highlights how rapidly infectious diseases might be transmitted globally through international travel and how public health officials need advanced molecular tools along with standard epidemiological analyses to quickly determine the sources of outbreaks.

IMPORTANCE
Cholera is one of the ancient classical diseases and particularly prone to cause major outbreaks following major natural disasters, such as earthquakes and hurricanes, where the normal separation between sewage and drinking water is destroyed. This was the case following the 2010 earthquake in Haiti. Rumors spread that the disease was brought to Haiti by a battalion of Nepalese soldiers serving as United Nations peacekeepers. This possible connection has never been confirmed. Sequencing the genomes of bacteria can give detailed information on whether isolates from different sites share a common origin. We used this technology to sequence isolates of
Vibrio cholerae
from Nepal, identify single-nucleotide polymorphisms (SNPs), and compare these high-resolution genotypes to the complete genome sequences of isolates from the Haiti outbreak. We provide support for the hypothesis that the isolates were brought to Haiti from Nepal.
Transient middle cerebral artery occlusion and reperfusion alters inducible NOS expression within the ventrolateral medulla and modulates cardiovascular function during static exercise
Authors: Ally Ahmmed , Maher Timothy J. 
Published: August 2011

A major cause of stroke is cerebral ischemia in regions supplied by the middle cerebral artery (MCA). In this study, we hypothesized that compromised cardiovascular function during static exercise may involve altered expression of inducible NOS (iNOS) protein within the rostral ventrolateral medulla (RVLM) and caudal ventrolateral medulla (CVLM). We compared cardiovascular responses and iNOS protein expression within the left and right sides of both RVLM and CVLM in sham-operated rats and in rats with a 90 min left-sided MCA occlusion (MCAO) followed by 24 h of reperfusion. Increases in blood pressure during a static muscle contraction were attenuated in MCAO rats compared with sham-operated rats. Also, iNOS expression within the left RVLM was augmented compared with the right RVLM in MCAO rats and compared with both RVLM quadrants in sham-operated rats. In contrast, compared with sham-operated rats and the right CVLM of MCAO rats, iNOS expression was attenuated in the left CVLM in left-sided MCAO rats. These data suggest that the attenuation of pressor responses during static exercise in MCAO rats involves overexpression of iNOS within the ipsilateral RVLM and attenuation in iNOS within the ipsilateral CVLM. Differential expression of iNOS within the medulla plays a role in mediating cardiovascular responses during static exercise following stroke.
Long Noncoding RNA HOTAIR Regulates Polycomb-Dependent Chromatin Modification and Is Associated with Poor Prognosis in Colorectal Cancers
Authors: Kogo Ryunosuke , Shimamura Teppei , Mimori Koshi , Kawahara Kohichi , Imoto Seiya , Sudo Tomoya , Tanaka Fumiaki , Shibata Kohei , Suzuki Akira , Komune Shizuo , Miyano Satoru , Mori Masaki 
Published: August 2011

Abstract
The functional impact of recently discovered long noncoding RNAs (ncRNAs) in human cancer remains to be clarified. One long ncRNA which has attracted attention is the Hox transcript antisense intergenic RNA termed HOTAIR, a long ncRNA expressed from the developmental HOXC locus located on chromosome 12q13.13. In cooperation with Polycomb complex PRC2, the HOTAIR long ncRNA is reported to reprogram chromatin organization and promote breast cancer metastasis. In this study, we examined the status and function of HOTAIR in patients with stage IV colorectal cancer (CRC) who have liver metastases and a poor prognosis. HOTAIR expression levels were higher in cancerous tissues than in corresponding noncancerous tissues and high HOTAIR expression correlated tightly with the presence of liver metastasis. Moreover, patients with high HOTAIR expression had a relatively poorer prognosis. In a subset of 32 CRC specimens, gene set enrichment analysis using cDNA array data revealed a close correlation between expression of HOTAIR and members of the PRC2 complex (SUZ12, EZH2, and H3K27me3). Our findings suggest that HOTAIR expression is associated with a genome-wide reprogramming of PRC2 function not only in breast cancer but also in CRC, where upregulation of this long ncRNA may be a critical element in metastatic progression. Cancer Res; 71(20); 6320–6. ©2011 AACR.
Therapeutic Oligonucleotides: The Road Not Taken
Authors: Stein Cy A. , Goel Sanjay 
Published: August 2011

Abstract
Antisense oligonucleotide therapeutics have been in development for almost 25 years without a single U.S. Food and Drug Administration–approved product in cancer. The reasons for this absence stem, in part, from a deep lack of understanding about how to deliver these molecules to cancer cells in vivo. Clin Cancer Res; 17(20); 6369–72. ©2011 AACR.
Impact of KRAS Mutations on Clinical Outcomes in Pancreatic Cancer Patients Treated with First-line Gemcitabine-Based Chemotherapy
Authors: Kim Seung Tae , Lim Do Hyoung , Jang Kee-Taek , Lim Taekyu , Lee Jeeyun , Choi Yoon-La , Jang Hye-Lim , Yi Jun Ho , Baek Kyung Kee , Park Se Hoon , Park Young Suk , Lim Ho Yeong , Kang Won Ki , Park Joon Oh 
Published: August 2011

Abstract
Although erlotinib has become an important therapeutic option in addition to gemcitabine, the high frequency of KRAS mutations in pancreatic cancer probably limits the benefits. We retrospectively studied 136 pancreatic cancer patients with available formalin-fixed paraffin-embedded tumor blocks from 2003 to 2009 to understand the clinical significance of KRAS mutations in pancreatic cancer patients treated with gemcitabine-based chemotherapy. KRAS mutations were analyzed by sequencing codons 12, 13, and 61. In this study, 71 (52.2%) of the 136 pancreatic adenocarcinomas examined harbored a point mutation in codons 12 (n = 70) and 61 (n = 1) of KRAS. KRAS mutation was not associated with clinicopathologic parameters. Patients with KRAS mutations showed a worse response (11.3%) than those with wild-type KRAS (26.2%) and poor survival (mutant KRAS, 5.8 months vs. wild-type KRAS, 8.0 months; P = 0.001). Multivariate analysis revealed good prognostic factors for overall survival as well to moderately differentiated histology (P &lt; 0.001; HR = 0.437, 95% CI: 0.301–0.634), locally advanced disease (P &lt; 0.001; HR = 0.417, 95% CI: 0.255–0.681), response to first-line chemotherapy (P = 0.003; HR = 0.482, 95% CI: 0.297–0.780), and wild-type KRAS (P = 0.001; HR = 0.523, 95% CI: 0.355–0.770). However, the observed survival advantage is derived from the subgroup of patients treated with gemcitabine/erlotinib (9.7 vs. 5.2 months; P = 0.002), whereas no survival difference based on KRAS mutation status is obvious in the other subgroup of patients treated without erlotinib (7.0 vs. 7.0 months; P = 0.121). These results need to be further explored in upcoming prospective studies to provide a rationale for personalized medicine in pancreatic cancer. Mol Cancer Ther; 10(10); 1993–9. ©2011 AACR.
Targeting the Intracellular MUC1 C-terminal Domain Inhibits Proliferation and Estrogen Receptor Transcriptional Activity in Lung Adenocarcinoma Cells
Authors: Klinge Carolyn M. , Radde Brandie N. , Imbert-Fernandez Yoannis , Teng Yun , Ivanova Margarita M. , Abner Sabra M. , Martin Alexandra L. 
Published: August 2011

Abstract
Mucin 1 (MUC1) is a diagnostic factor and therapy target in lung adenocarcinoma. MUC1 C-terminal intracellular domain (CD) interacts with estrogen receptor (ER) α and increases gene transcription in breast cancer cells. Because lung adenocarcinoma cells express functional ERα and ERβ, we examined MUC1 expression and MUC1–ER interaction. Because blocking MUC1 CD with an inhibitory peptide (PMIP) inhibited breast tumor growth, we tested whether PMIP would inhibit lung adenocarcinoma cell proliferation. We report that MUC1 interacts with ERα and ERβ within the nucleus of H1793 lung adenocarcinoma cells in accordance with MUC1 expression. PMIP was taken up by H23 and H1793 cells and inhibited the proliferation of H1793, but not H23 cells, concordant with higher MUC1 protein expression in H1793 cells. Lower MUC1 protein expression in H23 does not correspond to microRNAs miR-125b and miR-145 that have been reported to reduce MUC1 expression. PMIP had no effect on the viability of normal human bronchial epithelial cells, which lack MUC1 expression. PMIP inhibited estradiol-activated reporter gene transcription and endogenous cyclin D1 and nuclear respiratory factor-1 gene transcription in H1793 cells. These results indicate MUC1–ER functional interaction in lung adenocarcinoma cells and that inhibiting MUC1 inhibits lung adenocarcinoma cell viability. Mol Cancer Ther; 10(11); 2062–71. ©2011 AACR.
Adenosine Stress High-Pitch 128-Slice Dual-Source Myocardial Computed Tomography Perfusion for Imaging of Reversible Myocardial Ischemia
Authors: Feuchtner Gudrun , Goetti Robert , Plass André , Wieser Monika , Scheffel Hans , Wyss Christophe , Stolzmann Paul , Donati Olivio , Schnabl Johannes , Falk Volkmar , Alkadhi Hatem , Leschka Sebastian , Cury Ricardo C. 
Published: August 2011

Background—
Coronary computed tomography angiography (CTA) enables accurate anatomic evaluation of coronary artery stenosis but lacks information about hemodynamic significance. The aim of this study was to evaluate 128-slice myocardial CT perfusion (CTP) imaging with adenosine stress using a high-pitch mode, in comparison with cardiac MRI (CMR).

Methods and Results—
Thirty-nine patients with intermediate to high coronary risk profile underwent adenosine stress 128-slice dual source CTP (128×0.6 mm, 0.28 seconds). Among those, 30 patients (64±10 years, 6% women) also underwent adenosine stress CMR (1.5T). The 2-step CTP protocol consisted of (1) adenosine stress-CTP using a high-pitch factor (3.4) ECG-synchronized spiral mode and (2) rest-CTP/coronary-CTA using either high-pitch (heart rate <63 bpm) or prospective ECG-triggering (heart rate >63 bpm). Results were compared with CMR and with invasive angiography in 25 patients. The performance of stress-CTP for detection of myocardial perfusion defects compared with CMR was sensitivity, 96%; specificity, 88%; positive predictive value (PPV), 93%; negative predictive value (NPV), 94% (per vessel); and sensitivity, 78%; specificity, 87%; PPV, 83%; NPV, 84% (per segment). The accuracy of stress-CTP for imaging of reversible ischemia compared with CMR was sensitivity, 95%; specificity, 96%; PPV, 95%; and NPV, 96% (per vessel). In 25 patients who underwent invasive angiography, the accuracy of CTA for detection of stenosis >70% was (per segment): sensitivity, 96%; specificity, 88%; PPV, 67%; and NPV, 98.9%. The accuracy improved from 84% to 95% after adding stress CTP to CTA. Radiation exposure of the entire stress/rest CT protocol was only 2.5 mSv.

Conclusions—
Adenosine-induced stress 128-slice dual-source high-pitch myocardial CTP allows for simultaneously assessment of reversible myocardial ischemia and coronary stenosis, with good diagnostic accuracy as compared with CMR and invasive angiography, at a very low radiation exposure.
Meteorological Conditions at Racetrack Playa, Death Valley National Park: Implications for Rock Production and Transport
Authors: Lorenz Ralph D. , Jackson Brian K. , Barnes Jason W. , Spitale Joseph N. , Radebaugh Jani , Baines Kevin H. 
Published: August 2011

AbstractThree decades of weather records at meteorological stations near Death Valley National Park are analyzed in an attempt to gauge the frequency of conditions that might form and erase the famous trails of wind-blown rocks in the mud of Racetrack Playa. Trail formation requires the playa to be wet, followed by strong winds and/or freezing conditions. Weather records are compared with a limited set of meteorological data that were acquired in situ at the playa over three winters and that indicate freezing on 50, 29, and 15 nights during the winters of 2007/08–09/10, respectively, as well as with the hydrological condition of the playa as determined by time-lapse cameras that observed flooding over ~1, ~5, and ~40 days, respectively, during those winters. Measurements at the nearby Panamint and Hunter Mountain stations are found to be a useful, if imperfect (~50%), indicator of Racetrack Playa conditions and give some features of Racetrack Playa’s micrometeorological behavior. Wind speed probability distributions suggest that winds that are fast enough to cause unassisted rock motion are rare and therefore that freezing of water on the playa has a role in a significant fraction of movement events.
Observed Decadal North Atlantic Tripole SST Variability. Part II: Diagnosis of Mechanisms
Authors: Schneider Edwin K. , Fan Meizhu 
Published: August 2011

Abstract
In Part I of this study, the atmospheric weather noise for 1951–2000 was inferred from an atmospheric analysis in conjunction with SST-forced AGCM simulations and used to force interactive ensemble coupled GCM simulations of the North Atlantic SST variability. Here, results from those calculations are used in conjunction with a simple stochastically forced coupled model of the decadal time scale North Atlantic tripole SST variability to examine the mechanisms associated with the tripole SST variability. The diagnosed tripole variability is found to be characterized by damped, delayed oscillator dynamics, similar to what has been found by other investigators. However, major differences here, affecting the signs of two of the crucial parameters of the simple model, are that the atmospheric heat flux feedback damps the tripole pattern and that a counterclockwise intergyre gyre-like circulation enhances the tripole pattern. Delayed oscillator dynamics are still obtained because the sign of the dynamically important parameter, proportional to the product of these two parameters, is unchanged. Another difference with regard to the dynamical processes included in the simple model is that the major contribution to the ocean’s dynamical heat flux response to the weather noise wind stress is through a delayed modulation of the mean gyres, rather than from the simultaneous intergyre gyre response. The power spectrum of a revised simple model forced by white noise has a less prominent decadal peak using the parameter values and dynamics diagnosed here than in previous investigations. Decadal time scale retrospective predictions made with this version of the simple model are no better than persistence.
Turbulence Regimes and Turbulence Intermittency in the Stable Boundary Layer during CASES-99
Authors: Sun Jielun , Mahrt Larry , Banta Robert M. , Pichugina Yelena L. 
Published: August 2011

Abstract
An investigation of nocturnal intermittent turbulence during the Cooperative Atmosphere–Surface Exchange Study in 1999 (CASES-99) revealed three turbulence regimes at each observation height: 1) regime 1, a weak turbulence regime when the wind speed is less than a threshold value; 2) regime 2, a strong turbulence regime when the wind speed exceeds the threshold value; and 3) regime 3, a moderate turbulence regime when top-down turbulence sporadically bursts into the otherwise weak turbulence regime. For regime 1, the strength of small turbulence eddies is correlated with local shear and weakly related to local stratification. For regime 2, the turbulence strength increases systematically with wind speed as a result of turbulence generation by the bulk shear, which scales with the observation height. The threshold wind speed marks the transition above which the boundary layer approaches near-neutral conditions, where the turbulent mixing substantially reduces the stratification and temperature fluctuations. The preference of the turbulence regimes during CASES-99 is closely related to the existence and the strength of low-level jets. Because of the different roles of the bulk and local shear with regard to turbulence generation under different wind conditions, the relationship between turbulence strength and the local gradient Richardson number varies for the different turbulence regimes. Turbulence intermittency at any observation height was categorized in three ways: turbulence magnitude oscillations between regimes 1 and 2 as wind speed varies back and forth across its threshold value, episodic turbulence enhancements within regime 1 as a result of local instability, and downbursts of turbulence in regime 3.
Influence of Mean Flow on the ENSO–Vertical Wind Shear Relationship over the Northern Tropical Atlantic
Authors: Zhu Xiaojie , Saravanan R. , Chang Ping 
Published: August 2011

Abstract
Vertical wind shear over the tropical Atlantic Ocean plays an important role in mediating hurricane activity. The vertical shear variability over the main development region for Atlantic hurricanes is affected by local factors as well as by the remote influence of the El Niño–Southern Oscillation (ENSO) phenomenon, as indicated by observational and climate modeling analyses. Climate model simulations of the ENSO–shear relationship are compared with observations. It is shown that there is a strong influence of background mean flow on the ENSO–shear relationship, because of the inherently nonlinear nature of vertical wind shear. In particular, the simulation of zonal flow over the tropical Atlantic is shown to play a critical role in how the remote influence of ENSO modulates the shear. Even with realistic simulations of the ENSO-induced westerly anomaly in the upper troposphere, overestimated easterly background flow in the model simulations can alter the relationship between ENSO and vertical wind shear, resulting in decreased vertical wind shear during warm ENSO events. This nonlinear superposition has important implications for the assessment of trends in large-scale environmental factors affecting tropical cyclogenesis in climate change simulations.
Intracellular trafficking as a determinant of AS-DACA cytotoxicity in rhabdomyosarcoma cells
Authors: Wolf Steven J , Huynh Tony , Bryce Nicole S , Hambley Trevor W , Wakelin Laurence PG , Stewart Bernard W , Catchpoole Daniel R 
Published: August 2011

Abstract

Background
Rhabdomyosarcoma (RMS) is a malignant soft tissue sarcoma derived from skeletal muscle precursor cells, which accounts for 5-8% of all childhood malignancies. Disseminated RMS represents a major clinical obstacle, and the need for better treatment strategies for the clinically aggressive alveolar RMS subtype is particularly apparent. Previously, we have shown that the acridine-4-carboxamide derivative AS-DACA, a known topoisomerase II poison, is potently cytotoxic in the alveolar RMS cell line RH30, but is 190-fold less active in the embryonal RMS cell line RD. Here, we investigate the basis for this selectivity, and demonstrate in these RMS lines, and in an AS-DACA- resistant subclone of RH30, that AS-DACA-induced cytotoxicity correlates with the induction of DNA double strand breaks.

Results
We show that inhibition of the multidrug-resistance associated protein (MRP1) has no effect on AS-DACA sensitivity. By exploiting the pH-dependent fluorescence properties of AS-DACA, we have characterized its intracellular distribution, and show that it concentrates in the cell nucleus, as well as in acidic vesicles of the membrane trafficking system. We show that fluorescence microscopy can be used to determine the localization of AS-DACA to the nuclear and cytoplasmic compartments of RMS cells grown as spheroids, penetrance being much greater in RH30 than RD spheroids, and that the vesicular signal leads the way into the spheroid mass. EEA1 and Rab5 proteins, molecular markers expressed on early-endosomal vesicles, are reduced by > 50% in the sensitive cell lines.

Conclusion
Taking the evidence as a whole, suggests that endosomal vesicle trafficking influences the toxicity of AS-DACA in RMS cells.