bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Characterization of an Isoform-Selective Inhibitor of PI3K-p110β as a Potential Anticancer Agent
Authors: Ni Jing , Liu Qingsong , Xie Shaozhen , Carlson Coby , Von Thanh , Vogel Kurt , Riddle Steve , Benes Cyril , Eck Michael , Roberts Thomas , Gray Nathanael , Zhao Jean 
Published: April 2012

Abstract
Genetic approaches have shown that the p110β isoform of class Ia phosphatidylinositol-3-kinase (PI3K) is essential for the growth of PTEN-null tumors. Thus, it is desirable to develop p110β-specific inhibitors for cancer therapy. Using a panel of PI3K isoform-specific cellular assays, we screened a collection of compounds possessing activities against kinases in the PI3K superfamily and identified a potent and selective p110β inhibitor: KIN-193. We show that KIN-193 is efficacious specifically in blocking AKT signaling and tumor growth that are dependent on p110β activation or PTEN loss. Broad profiling across a panel of 422 human tumor cell lines shows that the PTEN mutation status of cancer cells strongly correlates with their response to KIN-193. Together, our data provide the first pharmacologic evidence that PTEN-deficient tumors are dependent on p110β in animals and suggest that KIN-193 can be pursued as a drug to treat tumors that are dependent on p110β while sparing other PI3K isoforms.
Significance: We report the first functional characterization of a p110β-selective inhibitor, KIN-193, that is efficacious as an antitumor agent in mice. We show that this class of inhibitor holds great promise as a pharmacologic agent that could be used to address the potential therapeutic benefit of treating p110β-dependent PTEN-deficient human tumors. Cancer Discov; 2(5); 425–33. ©2012 AACR.
Read the Commentary on this article by Shepherd and Denny, p. 393.
This article is highlighted in the In This Issue feature, p. 377.
Inhibition of Development of Abdominal Aortic Aneurysm by Glycolysis Restriction
Authors: Tsuruda Toshihiro , Hatakeyama Kinta , Nagamachi Shigeki , Sekita Yoko , Sakamoto Sumiharu , Endo George J. , Nishimura Masanori , Matsuyama Masakazu , Yoshimura Koichi , Sato Yuko , Onitsuka Toshio , Imamura Takuroh , Asada Yujiro , Kitamura Kazuo 
Published: April 2012

Objective—
The mechanisms underlying abdominal aortic aneurysm development remain unknown. We hypothesized that acceleration of glucose metabolism with the upregulation of glucose transporters is associated with abdominal aortic aneurysm development.

Methods and Results—

Enhanced accumulation of the modified glucose analogue 18 fluoro-deoxyglucose by positron emission tomography imaging in the human abdominal aortic aneurysm was associated with protein expressions of glucose transporters-1 and -3, assessed by Western blot. The magnitude of glucose transporter-3 expression was correlated with zymographic matrix metalloproteinase-9 activity. Intraperitoneal administration of glycolysis inhibitor with 2-deoxyglucose significantly attenuated the dilatation of abdominal aorta induced by periaortic application of CaCl
2
in C57BL/6J male mice or reduced the aneurysmal formation in angiotensin II-infused apolipoprotein E knockout male mice. In monocytic cell line induced by phorbol 12-myristate 13-acetate or ex vivo culture obtained from human aneurysmal tissues, 2-deoxyglucose abrogated the matrix metalloproteinase-9 activity and interleukin-6 expression in these cells/tissues. Moreover, 2-deoxyglucose attenuated the survival/proliferation of monocytes and the adherence of them to vascular endothelial cells.

Conclusion—
This study suggests that the enhanced glycolytic activity in aortic wall contributes to the pathogenesis of aneurysm development. In addition, pharmacological intervention in glycolytic activity might be a potential therapeutic target for the disorder.
High-Resolution Versus Standard-Resolution Cardiovascular MR Myocardial Perfusion Imaging for the Detection of Coronary Artery Disease
Authors: Motwani Manish , Maredia Neil , Fairbairn Timothy A. , Kozerke Sebastian , Radjenovic Aleksandra , Greenwood John P. , Plein Sven 
Published: April 2012

Background—
Although accelerated high-spatial-resolution cardiovascular MR (CMR) myocardial perfusion imaging has been shown to be clinically feasible, there has not yet been a direct comparison with standard-resolution methods. We hypothesized that higher spatial resolution detects more subendocardial ischemia and leads to greater diagnostic accuracy for the detection coronary artery disease. This study compared the diagnostic accuracy of high-resolution and standard-resolution CMR myocardial perfusion imaging in patients with suspected coronary artery disease.

Methods and Results—

A total of 111 patients were recruited to undergo 2 separate perfusion-CMR studies at 1.5 T, 1 with standard-resolution (2.5×2.5 mm in-plane) and 1 with high-resolution (1.6×1.6 mm in-plane) acquisition. High-resolution acquisition was facilitated by 8-fold
k-t
broad linear speed-up technique acceleration. Two observers visually graded perfusion in each myocardial segment on a 4-point scale. Segmental scores were summed to produce a perfusion score for each patient. All patients underwent invasive coronary angiography and coronary artery disease was defined as stenosis ≥50% luminal diameter (quantitative coronary angiography). CMR data were successfully obtained in 100 patients. In patients with coronary artery disease (n=70), more segments were determined to have subendocardial ischemia with high-resolution than with standard-resolution acquisition (279 versus 108;
P
<0.001). High-resolution acquisition had a greater diagnostic accuracy than standard resolution for identifying single-vessel disease (area under the curve, 0.88 versus 0.73;
P
<0.001) or multivessel disease (area under the curve, 0.98 versus 0.91;
P
=0.002) and overall (area under the curve, 0.93 versus 0.83;
P
<0.001).

Conclusions—
High-resolution perfusion-CMR has greater overall diagnostic accuracy than standard-resolution acquisition for the detection of coronary artery disease in both single- and multivessel disease and detects more subendocardial ischemia.
Understanding mechanisms of vitiligo development in Smyth line of chickens by transcriptomic microarray analysis of evolving autoimmune lesions
Authors: Shi Fengying , Kong Byung-Whi , Song Joon Jin , Lee Jeong Yoon , Dienglewicz Robert L , Erf Gisela F 
Published: April 2012

AbstractBackgroundThe Smyth line (SL) of chicken is an excellent avian model for human autoimmune vitiligo. The etiology of vitiligo is complicated and far from clear. In order to better understand critical components leading to vitiligo development, cDNA microarray technology was used to compare gene expression profiles in the target tissue (the growing feather) of SL chickens at different vitiligo (SLV) states.ResultsCompared to the reference sample, which was from Brown line chickens (the parental control), 395, 522, 524 and 526 out of the 44 k genes were differentially expressed (DE) (P ≤ 0.05) in feather samples collected from SL chickens that never developed SLV (NV), from SLV chickens prior to SLV onset (EV), during active loss of pigmentation (AV), and after complete loss of melanocytes (CV). Comparisons of gene expression levels within SL samples (NV, EV, AV and CV) revealed 206 DE genes, which could be categorized into immune system-, melanocyte-, stress-, and apoptosis-related genes based on the biological functions of their corresponding proteins. The autoimmune nature of SLV was supported by predominant presence of immune system related DE genes and their remarkably elevated expression in AV samples compared to NV, EV and/or CV samples. Melanocyte loss was confirmed by decreased expression of genes for melanocyte related proteins in AV and CV samples compared to NV and EV samples. In addition, SLV development was also accompanied by altered expression of genes associated with disturbed redox status and apoptosis. Ingenuity Pathway Analysis of DE genes provided functional interpretations involving but not limited to innate and adaptive immune response, oxidative stress and cell death.ConclusionsThe microarray results provided comprehensive information at the transcriptome level supporting the multifactorial etiology of vitiligo, where together with apparent inflammatory/innate immune activity and oxidative stress, the adaptive immune response plays a predominant role in melanocyte loss.
Phytochemical studies and antioxidant activity of two South African medicinal plants traditionally used for the management of opportunistic fungal infections in HIV/AIDS patients
Authors: Otang Wilfred Mbeng , Grierson Donald Scott , Ndip Roland Ndip 
Published: April 2012

AbstractBackgroundIt has been observed that perturbations in the antioxidant defense systems, and consequently redox imbalance, are present in many tissues of HIV-infected patients. Hence, the exogenous supply of antioxidants, as natural compounds that scavenge free radicals, might represent an important additional strategy for the treatment of HIV infection. The aim of this study was therefore to analyse the phytochemical constituents and antioxidant potential ofGasteria bicolorHaw andPittosporum viridiflorumSims., two South African plants traditionally used for the management of opportunistic fungal infections (OFIs) in AIDS patients.MethodsThein vitroantioxidant properties of the two plants were screened through DPPH (1,1-diphenyl-2-picrylhydrazyl), NO (nitric oxide), H2O2(hydrogen peroxide) radical scavenging effects and reducing power assays. Phytochemical studies were done by spectrophotometric techniques.ResultsThere were no significant differences in the flavonoid and proanthocyanidins contents between the leaves and bark extracts ofGasteria bicolorandPittosporum viridiflorumrespectively, while the total phenolic content of the bark extract ofP. viridiflorumwas significantly higher than that ofG. bicolorleaf. The acetone extracts of both plants indicated strong antioxidant activities.ConclusionThe results from this study indicate that the leaves and stem extracts ofGasteria bicolorandPittosporum viridiflorumrespectively possess antioxidant properties and could serve as free radical inhibitors, acting possibly as primary antioxidants. Since reactive oxygen species are thought to be associated with the pathogenesis of AIDS, and HIV-infected individuals often have impaired antioxidant defenses, the inhibitory effect of the extracts on free radicals may partially justify the traditional use of these plants in the management of OFIs in HIV patients in South Africa.
Reliability and validity of the Chinese version of the Psoriasis Disability Index (PDI) in Chinese patients with psoriasis
Authors: He Zehui , Lu Chuanjian , Ou Aihua , Fang Jiqian , Wang Dongmei , Deng Jingwen , Zhang Zhongzhao , Yu Jingjie 
Published: April 2012

Abstract

Background
The Psoriasis Disability Index (PDI) is a widely used instrument to measure the impact of psoriasis on patients. There has not been psychometric evaluation of the Chinese version of PDI. The aim of this study was to evaluate its reliability and validity among Chinese patients with psoriasis.

Methods
A multi-center, cross-sectional study was conducted at 9 hospitals including patients aged 18 years and over. Reliability was determined by internal consistency using Cronbach’s alpha. Validity was assessed through convergent validity and known groups validity. Dimensionality of the PDI was examined by exploratory factor analysis in working patients and nonworking patients respectively.

Results
In all, 831 patients were studied. Internal consistency of the PDI was satisfactory. Cronbach’s alpha coefficient was 0.91 for the total score and over 0.70 for each subscale of the PDI. Evidence of convergent validity of the PDI was proved by excellent and moderate to good correlations with the Dermatology Life Quality Index (DLQI) and four subscales of the Short Form-36 (SF-36) (role-physical, bodily pain, social functioning, and role-emotional): r = 0.51-0.78. Known groups validity was confirmed that the PDI score discriminated well among patients with different severity of psoriasis. The dimensionality of the PDI was determined by the presence of two-factor structure for working patients and three-factor structure for nonworking patients which accounted for 57.3% and 62.3% of the variance respectively.

Conclusion
The Chinese version of the PDI is a reliable and valid instrument to assess the impact of psoriasis on patients’ lives and could be used in future quality of life assessment of Chinese patients with psoriasis.
Assessing JPEG2000 encryption with key-dependent wavelet packets
Authors: Engel Dominik , Stütz Thomas , Uhl Andreas 
Published: April 2012

Abstract
We analyze and discuss encryption schemes for JPEG2000 based on the wavelet packet transform with a key-dependent subband structure. These schemes have been assumed to reduce the runtime complexity of encryption and compression. In addition to this "lightweight" nature, other advantages like encrypted domain signal processing have been reported. We systematically analyze encryption approaches based on key-dependent subband structures in terms of their impact on compression performance, their computational complexity and the level of security they provide as compared to more classical techniques. Furthermore, we analyze the prerequisites and settings in which the previously reported advantages actually hold and in which settings no advantages can be observed. As a final outcome it has to be stated that the compression integrated encryption approach based on the idea of secret wavelet packets can not be recommended.
Using learned under-sampling pattern for increasing speed of cardiac cine MRI based on compressive sensing principles
Authors: Zamani Pooria , Kayvanrad Mohammad , Soltanian-Zadeh Hamid 
Published: April 2012

Abstract
This article presents a compressive sensing approach for reducing data acquisition time in cardiac cine magnetic resonance imaging (MRI). In cardiac cine MRI, several images are acquired throughout the cardiac cycle, each of which is reconstructed from the raw data acquired in the Fourier transform domain, traditionally called k-space. In the proposed approach, a majority, e.g., 62.5%, of the k-space lines (trajectories) are acquired at the odd time points and a minority, e.g., 37.5%, of the k-space lines are acquired at the even time points of the cardiac cycle. Optimal data acquisition at the even time points is learned from the data acquired at the odd time points. To this end, statistical features of the k-space data at the odd time points are clustered by fuzzy c-means and the results are considered as the states of Markov chains. The resulting data is used to train hidden Markov models and find their transition matrices. Then, the trajectories corresponding to transition matrices far from an identity matrix are selected for data acquisition. At the end, an iterative thresholding algorithm is used to reconstruct the images from the under-sampled k-space datasets. The proposed approaches for selecting the k-space trajectories and reconstructing the images generate more accurate images compared to alternative methods. The proposed under-sampling approach achieves an acceleration factor of 2 for cardiac cine MRI.
Genomic amplification patterns of human telomerase RNA gene and C-MYC in liquid-based cytological specimens used for the detection of high-grade cervical intraepithelial neoplasia
Authors: Chen Shaomin , Yang Ziyan , Zhang Yun , Qiao Yunbo , Cui Baoxia , Zhang Youzhong , Kong Beihua 
Published: April 2012

Abstract

Background
The amplification of oncogenes initiated by high-risk human papillomavirus (HPV) infection is an early event in cervical carcinogenesis and can be used for cervical lesion diagnosis. We measured the genomic amplification rates and the patterns of human telomerase RNA gene (TERC) and C-MYC in the liquid-based cytological specimens to evaluate the diagnostic characteristics for the detection of high-grade cervical lesions.

Methods
Two hundred and forty-three residual cytological specimens were obtained from outpatients aged 25 to 64 years at Qilu Hospital, Shandong University. The specimens were evaluated by fluorescence in situ hybridization (FISH) using chromosome probes to TERC (3q26) and C-MYC (8q24). All of the patients underwent colposcopic examination and histological evaluation. A Chi-square test was used for categorical data analysis.

Results
In the normal, cervical intraepithelial neoplasia grade 1 (CIN1), grade 2 (CIN2), grade 3 (CIN3) and squamous cervical cancer (SCC) cases, the TERC positive rates were 9.2%, 17.2%, 76.2%, 100.0% and 100.0%, respectively; the C-MYC positive rates were 20.7%, 31.0%, 71.4%, 81.8% and 100.0%, respectively. The TERC and C-MYC positive rates were higher in the CIN2+ (CIN2, CIN3 and SCC) cases than in the normal and CIN1 cases (p < 0.01). Compared with cytological analysis, the TERC test showed higher sensitivity (90.0% vs. 84.0%) and higher specificity (89.6% vs. 64.3%). The C-MYC test showed lower sensitivity (80.0% vs. 84.0%) and higher specificity (77.7% vs. 64.3%). Using a cut-off value of 5% or more aberrant cells, the TERC test showed the highest combination of sensitivity and specificity. The CIN2+ group showed more high-level TERC gene copy number (GCN) cells than did the normal/CIN1 group (p < 0.05). For C-MYC, no significant difference between the two histological categories was detected (p > 0.05).

Conclusions
The TERC test is highly sensitive and is therefore suitable for cervical cancer screening. The C-MYC test is not suitable for cancer screening because of its lower sensitivity. The amplification patterns of TERC become more diverse and complex as the severity of cervical diseases increases, whereas for C-MYC, the amplification patterns are similar between the normal/CIN1 and CIN2+ groups.

Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1308004512669913.
Computing evolutionary distinctiveness indices in large scale analysis
Authors: Martyn Iain , Kuhn Tyler S , Mooers Arne O , Moulton Vincent , Spillner Andreas 
Published: April 2012

Abstract
We present optimal linear time algorithms for computing the Shapley values and 'heightened evolutionary distinctiveness' (HED) scores for the set of taxa in a phylogenetic tree. We demonstrate the efficiency of these new algorithms by applying them to a set of 10,000 reasonable 5139-species mammal trees. This is the first time these indices have been computed on such a large taxon and we contrast our finding with an ad-hoc index for mammals, fair proportion (FP), used by the Zoological Society of London's EDGE programme. Our empirical results follow expectations. In particular, the Shapley values are very strongly correlated with the FP scores, but provide a higher weight to the few monotremes that comprise the sister to all other mammals. We also find that the HED score, which measures a species' unique contribution to future subsets as function of the probability that close relatives will go extinct, is very sensitive to the estimated probabilities. When they are low, HED scores are less than FP scores, and approach the simple measure of a species' age. Deviations (like the Solendon genus of the West Indies) occur when sister species are both at high risk of extinction and their clade roots deep in the tree. Conversely, when endangered species have higher probabilities of being lost, HED scores can be greater than FP scores and species like the African elephant Loxondonta africana, the two solendons and the thumbless bat Furipterus horrens can move up the rankings. We suggest that conservation attention be applied to such species that carry genetic responsibility for imperiled close relatives. We also briefly discuss extensions of Shapley values and HED scores that are possible with the algorithms presented here.
Novel use of an exchange catheter to facilitate intubation with an Aintree catheter in a tall patient with a predicted difficult airway: a case report
Authors: Gruenbaum Shaun E , Gruenbaum Benjamin F , Tsaregorodtsev Sergey , Dubilet Michael , Melamed Israel , Zlotnik Alexander 
Published: April 2012

Abstract

Introduction
The Aintree intubating catheter (Cook® Medical Inc., Bloomington, IN, USA) has been shown to successfully facilitate difficult intubations when other methods have failed. The Aintree intubating catheter (Cook® Medical Inc., Bloomington, IN, USA) has a fixed length of 56 cm, and it has been suggested in the literature that it may be too short for safe use in patients who are tall.

Case presentation
We present the case of a 32-year-old, 180 cm tall Caucasian woman with a predicted difficult airway who presented to our facility for an emergency cesarean section. After several failed intubation attempts via direct laryngoscopy, an airway was established with a laryngeal mask airway. After delivery of a healthy baby, our patient's condition necessitated tracheal intubation. A fiber-optic bronchoscope loaded with an Aintree intubating catheter (Cook® Medical Inc., Bloomington, IN, USA) was passed through the laryngeal mask airway into the trachea until just above the carina, but was too short to safely allow for the passage of an endotracheal tube.

Conclusions
We present a novel technique in which the Aintree intubating catheter (Cook® Medical Inc., Bloomington, IN, USA) was replaced with a longer (100 cm) exchange catheter, over which an endotracheal tube was passed successfully into the trachea.
Identification of basepairs within Tn5 termini that are critical sfor H-NS binding to the transpososome and regulation of Tn5 transposition
Authors: Whitfield Crystal R , Shilton Brian H , Haniford David B 
Published: April 2012

Abstract

Background
The H-NS protein is a global regulator of gene expression in bacteria and can also bind transposition complexes (transpososomes). In Tn5 transposition H-NS promotes transpososome assembly in vitro and disruption of the hns gene causes a modest decrease in Tn5 transposition (three- to five-fold). This is consistent with H-NS acting as a positive regulator of Tn5 transposition. Molecular determinants for H-NS binding to the Tn5 transpososome have not been determined, nor has the strength of the interaction been established. There is also uncertainty as to whether H-NS regulates Tn5 transposition in vivo through an interaction with the transposition machinery as disruption of the hns gene has pleiotropic effects on Escherichia coli, the organism used in this study.

Results
In the current work we have further examined determinants for H-NS binding to the Tn5 transpososome through both mutational studies on Tn5 termini (or 'transposon ends') and protein-protein cross-linking analysis. We identify mutations in two different segments of the transposon ends that abrogate H-NS binding and characterize the affinity of H-NS for wild type transposon ends in the context of the transpososome. We also show that H-NS forms cross-links with the Tn5 transposase protein specifically in the transpososome, an observation consistent with the two proteins occupying overlapping binding sites in the transposon ends. Finally, we make use of the end mutations to test the idea that H-NS exerts its impact on Tn5 transposition in vivo by binding directly to the transpososome. Consistent with this possibility, we show that two different end mutations reduce the sensitivity of the Tn5 system to H-NS regulation.

Conclusions
H-NS typically regulates cellular functions through its potent transcriptional repressor function. Work presented here provides support for an alternative mechanism of H-NS-based regulation, and adds to our understanding of how bacterial transposition can be regulated.