bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progressive Genomic Instability in the FVB/KrasLA2 Mouse Model of Lung Cancer
Authors: To Minh D. , Quigley David A. , Mao Jian-Hua , Del Rosario Reyno , Hsu Jeff , Hodgson Graeme , Jacks Tyler , Balmain Allan 
Published: August 2011

Abstract
Alterations in DNA copy number contribute to the development and progression of cancers and are common in epithelial tumors. We have used array Comparative Genomic Hybridization (aCGH) to visualize DNA copy number alterations across the genomes of lung tumors in the KrasLA2 model of lung cancer. Copy number gain involving the Kras locus, as focal amplification or whole chromosome gain, is the most common alteration in these tumors and with a prevalence that increased significantly with increasing tumor size. Furthermore, Kras amplification was the only major genomic event among the smallest lung tumors, suggesting that this alteration occurs early during the development of mutant Kras-driven lung cancers. Recurring gains and deletions of other chromosomes occur progressively more frequently among larger tumors. These results are in contrast to a previous aCGH analysis of lung tumors from KrasLA2 mice on a mixed genetic background, in which relatively few DNA copy number alterations were observed regardless of tumor size. Our model features the KrasLA2 allele on the inbred FVB/N mouse strain, and in this genetic background, there is a highly statistically significant increase in level of genomic instability with increasing tumor size. These data suggest that recurring DNA copy alterations are important for tumor progression in the KrasLA2 model of lung cancer and that the requirement for these alterations may be dependent on the genetic background of the mouse strain. Mol Cancer Res; 9(10); 1339–45. ©2011 AACR.
In Vitro Characterization of the Mechanisms Responsible for Functional Tricuspid Regurgitation
Authors: Spinner Erin M. , Shannon Patrick , Buice Dana , Jimenez Jorge H. , Veledar Emir , del Nido Pedro J. , Adams David H. , Yoganathan Ajit P. 
Published: August 2011

Background—
Functional tricuspid regurgitation (TR) is increasingly recognized as a source of morbidity. Current repair strategies focus on annular remodeling because annular dilatation is common in patients with TR. Although papillary muscle (PM) displacement is recognized in functional mitral regurgitation, its role in TR is less well characterized. The objective of this in vitro study was to further clarify the mechanisms by which TR occurs as an effect of annular dilatation and PM displacement.

Methods and Results—

Porcine tricuspid valves (n=16) were studied in an in vitro right heart simulator. The valve dynamics were quantified with isolated annular dilatation starting with a normal annular size (6 cm
2
) and incrementally dilated up to 100%, isolated PM displacement, and a combination of the 2. All valves lost competence at 40% dilatation, resulting in a TR of 7.9±3.4 mL (
P
≤0.05) compared with baseline and central residual leaflet length of 0.5±0.2 cm. Multidirectional displacement of the anterior and posterior/septal PMs and all PMs significantly (
P
≤0.05) increased TR, with normal annular area. Malcoaptation was observed where the 3 leaflets joined with all significant levels of TR. The anterior leaflet had the greatest percent change in residual leaflet length, whereas PM displacement caused a reduction in residual leaflet length for the septal leaflet for all conditions.

Conclusions—
This study shows that although annular dilatation alone leads to TR, isolated PM displacement can also cause TR; annular remodeling strategies should be tailored in the setting of severe PM displacement.
Genetic Variation in Titin in Arrhythmogenic Right Ventricular Cardiomyopathy–Overlap Syndromes
Authors: Taylor Matthew , Graw Sharon , Sinagra Gianfranco , Barnes Carl , Slavov Dobromir , Brun Francesca , Pinamonti Bruno , Salcedo Ernesto E. , Sauer William , Pyxaras Stylianos , Anderson Brian , Simon Bernd , Bogomolovas Julius , Labeit Siegfried , Granzier Henk , Mestroni Luisa 
Published: August 2011

Background—

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited genetic myocardial disease characterized by fibrofatty replacement of the myocardium and a predisposition to cardiac arrhythmias and sudden death. We evaluated the cardiomyopathy gene titin (
TTN
) as a candidate ARVC gene because of its proximity to an ARVC locus at position 2q32 and the connection of the titin protein to the transitional junction at intercalated disks.

Methods and Results—

All 312 titin exons known to be expressed in human cardiac titin and the complete 3′ untranslated region were sequenced in 38 ARVC families. Eight unique
TTN
variants were detected in 7 families, including a prominent Thr2896Ile mutation that showed complete segregation with the ARVC phenotype in 1 large family. The Thr2896IIe mutation maps within a highly conserved immunoglobulin-like fold (Ig10 domain) located in the spring region of titin. Native gel electrophoresis, nuclear magnetic resonance, intrinsic fluorescence, and proteolysis assays of wild-type and mutant Ig10 domains revealed that the Thr2896IIe exchange reduces the structural stability and increases the propensity for degradation of the Ig10 domain. The phenotype of
TTN
variant carriers was characterized by a history of sudden death (5 of 7 families), progressive myocardial dysfunction causing death or heart transplantation (8 of 14 cases), frequent conduction disease (11 of 14), and incomplete penetrance (86%).

Conclusions—
Our data provide evidence that titin mutations can cause ARVC, a finding that further expands the origin of the disease beyond desmosomal proteins. Structural impairment of the titin spring is a likely cause of ARVC and constitutes a novel mechanism underlying myocardial remodeling and sudden cardiac death.
Cardiac Resynchronization Therapy as a Therapeutic Option in Patients With Moderate-Severe Functional Mitral Regurgitation and High Operative Risk
Authors: van Bommel Rutger J. , Marsan Nina Ajmone , Delgado Victoria , Borleffs C. Jan Willem , van Rijnsoever Eva P.M. , Schalij Martin J. , Bax Jeroen J. 
Published: August 2011

Background—
Functional mitral regurgitation (MR) is a common finding in heart failure patients with dilated cardiomyopathy and has important prognostic implications. However, the increased operative risk of these patients may result in low referral or high denial rate for mitral valve surgery. Cardiac resynchronization therapy (CRT) has been shown to have a favorable effect on MR. Aims of this study were to (1) evaluate CRT as a therapeutic option in heart failure patients with functional MR and high operative risk and (2) investigate the effect of MR improvement after CRT on prognosis.

Methods and Results—

A total of 98 consecutive patients with moderate-severe functional MR and high operative risk underwent CRT according to current guidelines. Echocardiography was performed at baseline and 6-month follow-up; severity of MR was graded according to a multiparametric approach. Significant improvement of MR was defined as a reduction ≥1 grade. All-cause mortality was assessed during follow-up (median 32 [range 6.0 to 116] months). Thirteen patients (13%) died before 6-months follow-up. In the remaining 85 patients, significant reduction in MR was observed in all evaluated parameters. In particular, 42 patients (49%) improved ≥1 grade of MR and were considered MR improvers. Survival was superior in MR improvers compared to MR nonimprovers (log rank
P
<0.001). Mitral regurgitation improvement was an independent prognostic factor for survival (hazard ratio 0.35, confidence interval 0.13 to 0.94;
P
=0.043).

Conclusions—
Cardiac resynchronization therapy is a potential therapeutic option in heart failure patients with moderate-severe functional MR and high risk for surgery. Improvement in MR results in superior survival after CRT.
Potential Vorticity of the Madden–Julian Oscillation
Authors: Zhang Chidong , Ling Jian 
Published: August 2011

Abstract
This study explores the extent to which the dynamical structure of the Madden–Julian oscillation (MJO), its evolution, and its connection to diabatic heating can be described in terms of potential vorticity (PV). The signature PV structure of the MJO is an equatorial quadrupole of cyclonic and anticyclonic PV that tilts westward and poleward. This PV quadrupole is closely related to positive and negative anomalies in precipitation that are in a swallowtail pattern extending eastward along the equator and splitting into off-equatorial branches westward. Two processes dominate the generation of MJO PV. One is linear, involving MJO diabatic heating alone. The other is nonlinear, involving diabatic heating and relative vorticity of perturbations spectrally outside the MJO domain but spatially constrained to the MJO convective envelope. The MJO is thus partially a self-sustaining system and partially a consequence of scale interaction of MJO-constrained stochastic processes. Convective initiation of the MJO over the Indian Ocean features a swallowtail pattern of negative anomalous precipitation and associated anticyclonic PV anomalies at the early stage, and increasing cyclonic PV generation straddling the equator in the midtroposphere due to increasing positive anomalies in precipitation. These lead to the swallowtail pattern in positive anomalous precipitation and the associated PV quadrupole that signifies the fully developed MJO. The equatorial Kelvin and Rossby waves bear PV structures distinct from that of the MJO. They contribute insignificantly to the structure and generation of MJO PV. Solely based on the PV analysis, a hypothesis is proposed that the fundamental dynamics of the MJO depends on neither Kelvin nor Rossby waves.
Surface Track Discontinuity of Tropical Cyclones Crossing Taiwan: A Statistical Study
Authors: Peng L. , Wang S.-T. , Shieh S.-L. , Cheng M.-D. , Yeh T.-C. 
Published: August 2011

Abstract
Surface tracks of some cross-Taiwan tropical cyclones were discontinuous as a result of the blockage of the north-northeast–south-southwest-oriented Central Mountain Range (CMR). This paper tries to identify the variables that may be used to diagnose track continuity in advance. The track records of 131 westbound cross-Taiwan tropical cyclones between 1897 and 2009 are examined. It is found that the track continuity of a westbound cross-Taiwan tropical cyclone depends mostly upon the landfall location (YLF), the approaching direction (ANG), and the maximum wind (VMX) of the cyclone. According to the empirical probability of track continuity estimated from the data, the dependence on YLF, which is nonlinear and remarkably asymmetric with respect to the midpoint of the east coast, may be well approximated by a quadratic function of YLF. The nonlinearity and asymmetry can be interpreted in terms of the length scale of the CMR and the north–south antisymmetry of the cyclonic flow. The estimated dependence of track continuity on cyclone intensity and size may be approximated by a linear function of VMX. The estimated dependence of track continuity on ANG may be approximated by a single term of the modified variable DIR (=|ANG − 110|, where 110 is the direction, in degrees, perpendicular to the CMR’s long axis).
Using the 64 tracks between 1944 and 1996 as the training sample, a logistic regression equation model, built in terms of YLF, YLF square, DIR, and VMX gives an overall accuracy score of 89%. As to the probability estimates of individual tracks, 49 of the 64 tracks have estimated probabilities outside the (0.5 − 0.127, 0.5 + 0.127) RMS error range and are correctly classified. A prediction test using another set of 67 tracks not included in the model-training sample, scores a success rate of 82%. As to the probability predictions for individual tracks, 49 of the 67 tracks have predicted probabilities outside the RMS error range and are correctly predicted. These results confirm the appropriateness of the model and moreover demonstrate that the three parameters, YLF, DIR, and VMX, primarily control the surface track continuity of a westbound tropical cyclone crossing Taiwan.
Outcomes of Transoral Robotic Surgery
Authors: Hurtuk Agnes , Agrawal Amit , Old Matthew , Teknos Theodoros N. , Ozer Enver 
Published: August 2011

ObjectiveTo report a single institution’s experience with transoral robotic surgery (TORS) and its clinical outcomes.Study DesignPreliminary clinical data from a prospective TORS study.SettingUniversity tertiary care facility.Subjects and MethodsPatients who underwent TORS at The Ohio State University Medical Center. Demographic, intraoperative, clinicopathological, and follow‐up functional data were collected.ResultsSixty‐four patients underwent TORS with a median age of 56.9 years. A total of 113 TORS procedures were performed. Fifty‐four patients with squamous cell cancer (SCCA) were included in the final analysis. Mean follow‐up time was 11.8 months (range, 2‐29). There was a trend toward longer TORS setup time, operative time, estimated blood loss, and hospital length of stay with advanced (T3) compared with early‐stage tumors (T1‐2). There were no major intraoperative complications, and none of the procedures were aborted because of inability to remove the tumor. Negative resection margins were achieved in 93% of cases of SCCA. No patients experienced immediate postoperative complications, and all of the patients tolerated an oral diet without any airway compromise on the day of surgery. Forty‐nine patients (91%) underwent adjuvant radiation therapy (RT), with 11 patients requiring gastrostomy tube placement during RT. Addition of TORS to overall management of head and neck SCCA spared adjuvant RT or combined chemotherapy and RT (CRT) in 50% of stage I/II tumors and spared chemotherapy in 34% of stage III/IV tumors.ConclusionTORS is a safe procedure with minimal complications and favorable clinical and functional outcomes. It is a promising future alternative surgical treatment for laryngopharyngeal tumors.
Using mixed methods to develop and evaluate complex interventions in palliative care research
Authors: Farquhar Morag C , Ewing Gail , Booth Sara 
Published: August 2011

Background: there is increasing interest in combining qualitative and quantitative research methods to provide comprehensiveness and greater knowledge yield. Mixed methods are valuable in the development and evaluation of complex interventions. They are therefore particularly valuable in palliative care research where the majority of interventions are complex, and the identification of outcomes particularly challenging. Aims: this paper aims to introduce the role of mixed methods in the development and evaluation of complex interventions in palliative care, and how they may be used in palliative care research. Content: the paper defines mixed methods and outlines why and how mixed methods are used to develop and evaluate complex interventions, with a pragmatic focus on design and data collection issues and data analysis. Useful texts are signposted and illustrative examples provided of mixed method studies in palliative care, including a detailed worked example of the development and evaluation of a complex intervention in palliative care for breathlessness. Key challenges to conducting mixed methods in palliative care research are identified in relation to data collection, data integration in analysis, costs and dissemination and how these might be addressed. Conclusions: the development and evaluation of complex interventions in palliative care benefit from the application of mixed methods. Mixed methods enable better understanding of whether and how an intervention works (or does not work) and inform the design of subsequent studies. However, they can be challenging: mixed method studies in palliative care will benefit from working with agreed protocols, multidisciplinary teams and engaging staff with appropriate skill sets.
Self-adaptive uniform differential evolution for optimizing the initial integral point of the Earth–Moon low-energy transfer
Authors: Peng L , Dai G , Wang M , Hu H , Chang Y , Chen F 
Published: August 2011

Low-energy transfer trajectory is of growing interest in the space community. It is important to choose the patch point of the unstable manifold of the Lyapunov orbit around Sun–Earth L2 and the stable manifold of the Lyapunov orbit around Earth–Moon L2. The main contributions of this study are two areas: (a) designing the optimization model and using evolutionary algorithms to optimize the initial condition and (b) developing effective algorithms for this problem. In this article, an improved differential evolution (DE) algorithm, named adaptive uniform design differential evolution (AUDE), is proposed to solve the Earth–Moon low-energy transfer optimization problem. It incorporates the uniform design technology and the self-adaptive parameter control method into standard DE to accelerate its convergence speed and improve the stability and calculation accuracy. To verify the performance of AUDE, the Earth–Moon low-energy transfer optimization problem and 15 benchmark functions with diverse complexities are employed. The experiment results indicate that the authors' approach is able to find the better one, or at least comparably, in terms of the quality and stability of the final solutions than the other three algorithms. Moreover, it proves that the application of DE algorithm in the Earth–Moon low-energy transfer optimization problem is effective.
Discovery of serum biomarkers of alcoholic fatty liver in a rodent model: C-reactive protein
Authors: Liu Shu-Lin , Cheng Chun-Chia , Chang Chun-Chao , Mai Fu-Der , Wang Chia-Chi , Lee Shui-Cheng , Ho Ai-Sheng , Chen Ling-Yun , Chang Jungshan 
Published: August 2011

Abstract

Background
Excessive consumption of alcohol contributes to alcoholic liver disease. Fatty liver is the early stage of alcohol-related liver disease. The aim of this study was to search for specific serological biomarkers of alcoholic fatty liver (AFL) compared to healthy controls, non-alcoholic fatty liver (NAFL) and liver fibrosis in a rodent model.

Methods
Serum samples derived from animals with AFL, NAFL, or liver fibrosis were characterized and compared using two-dimensional differential gel electrophoresis. A matrix-assisted laser desorption ionization-time of flight tandem mass spectrometer in conjunction with mascot software was used for protein identification. Subsequently, Western blotting and flexible multi-analyte profiling were used to measure the expressions of the putative biomarkers present in the serum of animals and clinical patients.

Results
Eight differential putative biomarkers were identified, and the two most differentiated proteins, including upregulated C-reactive protein (CRP) and downregulated haptoglobin (Hp), were further investigated. Western blotting validated that CRP was dramatically higher in the serum of AFL compared to healthy controls and other animals with liver disease of NAFL or liver fibrosis (p < 0.05). Moreover, we found that CRP and Hp were both lower in liver fibrosis of TAA-induced rats and clinical hepatitis C virus-infected patients.

Conclusion
The results suggest that increased levels of CRP are an early sign of AFL in rats. The abnormally elevated CRP induced by ethanol can be used as a biomarker to distinguish AFL from normal or otherwise diseased livers.
Link-based quantitative methods to identify differentially coexpressed genes and gene Pairs
Authors: Yu Hui , Liu Bao-Hong , Ye Zhi-Qiang , Li Chun , Li Yi-Xue , Li Yuan-Yuan 
Published: August 2011

Abstract

Background
Differential coexpression analysis (DCEA) is increasingly used for investigating the global transcriptional mechanisms underlying phenotypic changes. Current DCEA methods mostly adopt a gene connectivity-based strategy to estimate differential coexpression, which is characterized by comparing the numbers of gene neighbors in different coexpression networks. Although it simplifies the calculation, this strategy mixes up the identities of different coexpression neighbors of a gene, and fails to differentiate significant differential coexpression changes from those trivial ones. Especially, the correlation-reversal is easily missed although it probably indicates remarkable biological significance.

Results
We developed two link-based quantitative methods, DCp and DCe, to identify differentially coexpressed genes and gene pairs (links). Bearing the uniqueness of exploiting the quantitative coexpression change of each gene pair in the coexpression networks, both methods proved to be superior to currently popular methods in simulation studies. Re-mining of a publicly available type 2 diabetes (T2D) expression dataset from the perspective of differential coexpression analysis led to additional discoveries than those from differential expression analysis.

Conclusions
This work pointed out the critical weakness of current popular DCEA methods, and proposed two link-based DCEA algorithms that will make contribution to the development of DCEA and help extend it to a broader spectrum.
NMD and microRNA expression profiling of the HPCX1 locus reveal MAGEC1 as a candidate prostate cancer predisposition gene
Authors: Mattila Henna , Schindler Martin , Isotalo Jarkko , Ikonen Tarja , Vihinen Mauno , Oja Hannu , Tammela Teuvo LJ , Wahlfors Tiina , Schleutker Johanna 
Published: August 2011

Abstract

Background
Several predisposition loci for hereditary prostate cancer (HPC) have been suggested, including HPCX1 at Xq27-q28, but due to the complex structure of the region, the susceptibility gene has not yet been identified.

Methods
In this study, nonsense-mediated mRNA decay (NMD) inhibition was used for the discovery of truncating mutations. Six prostate cancer (PC) patients and their healthy brothers were selected from a group of HPCX1-linked families. Expression analyses were done using Agilent 44 K oligoarrays, and selected genes were screened for mutations by direct sequencing. In addition, microRNA expression levels in the lymphoblastic cells were analyzed to trace variants that might alter miRNA expression and explain partly an inherited genetic predisposion to PC.

Results
Seventeen genes were selected for resequencing based on the NMD array, but no truncating mutations were found. The most interesting variant was MAGEC1 p.Met1?. An association was seen between the variant and unselected PC (OR = 2.35, 95% CI = 1.10-5.02) and HPC (OR = 3.38, 95% CI = 1.10-10.40). miRNA analysis revealed altogether 29 miRNAs with altered expression between the PC cases and controls. miRNA target analysis revealed that 12 of them also had possible target sites in the MAGEC1 gene. These miRNAs were selected for validation process including four miRNAs located in the X chromosome. The expressions of 14 miRNAs were validated in families that contributed to the significant signal differences in Agilent arrays.

Conclusions
Further functional studies are needed to fully understand the possible contribution of these miRNAs and MAGEC1 start codon variant to PC.
Some results on a general iterative method for k-strictly pseudo-contractive mappings
Authors: Jung Jong Soo 
Published: August 2011

AbstractLet H be a Hilbert space, C be a closed convex subset of H such that C ± C ⊂ C, and T : C → H be a k-strictly pseudo-contractive mapping with F(T) ≠ ∅ for some 0 ≤ k < 1. Let F : C → C be a κ-Lipschitzian and η-strongly monotone operator with κ > 0 and η > 0 and f : C → C be a contraction with the contractive constant α ∈ (0, 1). Let "Equation missing", "Equation missing" and τ < 1. Let {α
n
} and {β
n
} be sequences in (0, 1). It is proved that under appropriate control conditions on {α
n
} and {β
n
}, the sequence {x
n
} generated by the iterative scheme xn+1= α
n
γf(x
n
) + β
n
x
n
+ ((1 - β
n
)I - α
n
μF)P
C
Sx
n
, where S : C → H is a mapping defined by Sx = kx + (1 - k)Tx and P
C
is the metric projection of H onto C, converges strongly to q ∈ F(T), which solves the variational inequality 〈μFq - γf(q), q - p〉 ≤ 0 for p ∈ F(T).MSC: 47H09, 47H05, 47H10, 47J25, 49M05