bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prooncogenic Factors miR-23b and miR-27b Are Regulated by Her2/Neu, EGF, and TNF-α in Breast Cancer
Authors: Jin Lianjin , Wessely Oliver , Marcusson Eric G. , Ivan Cristina , Calin George A. , Alahari Suresh K. 
Published: January 2013

Abstract
miRNAs (miR) are a critical class of small (21–25 nucleotides) noncoding endogenous RNAs implicated in gene expression regulation. We identified miR-23b and miR-27b as miRNAs that are highly upregulated in human breast cancer. We found that engineered knockdown of miR-23b and miR-27b substantially repressed breast cancer growth. Nischarin (NISCH) expression was augmented by knockdown of miR-23b as well as miR-27b. Notably, these miRNAs and Nischarin were inversely expressed in human breast cancers, underscoring their biologic relevance. We showed the clinical relevance of the expression of these miRNAs and showed that high expression of miR-23b and miR-27b correlates with poor outcome in breast cancer. Moreover, intraperitoneally delivered anti-miR-27b restored Nischarin expression and decreased tumor burden in a mouse xenograft model of human mammary tumor. Also, we report for the first time that HER2/neu (ERBB2), EGF, and TNF-α promote miR-23b/27b expression through the AKT/NF-κB signaling cascade. Nischarin was found to regulate miR-27b/23b expression through a feedback loop mechanism by suppressing NF-κB phosphorylation. Because anti-miR-27b compounds that suppress miR-27b inhibit tumor growth, the anti-miR-27b seems to be a good candidate for the development of new antitumor therapies. Cancer Res; 73(9); 2884–96. ©2013 AACR.
Diffuse Large B-cell Lymphoma in the Elderly: A Review of Potential Difficulties
Authors: Sarkozy Clémentine , Coiffier Bertrand 
Published: January 2013

Abstract
Half of patients with diffuse large B-cell lymphoma (DLBCL) are more than 65 years old. These elderly patients frequently have other diseases, some of them severe, which may alter their ability to receive standard curative therapy. However, these associated diseases are heterogeneous and only a few contraindicate chemotherapy treatments. We reviewed all potential difficulties, such as the evaluation of comorbidities, the heterogeneous functional status of this population, and the consequences of the aging process that might be associated with treating these patients, and now propose solutions. As standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy may cure the majority of patients, it must always be the first proposed option. With this approach, elderly patients with DLBCL treated with a curative intent can reach a complete remission and have a similar outcome as younger patients. Reduced dose intensity must be applied for very elderly patients or those unfit for full-dose anthracycline. The critical question for a physician is why these patients cannot be treated with the standard regimen, namely R-CHOP. Clin Cancer Res; 19(7); 1660–9. ©2013 AACR.
Antitumor Effect of SIRT1 Inhibition in Human HCC Tumor Models In Vitro and In Vivo
Authors: Portmann Simone , Fahrner René , Lechleiter Antje , Keogh Adrian , Overney Sarah , Laemmle Alexander , Mikami Kei , Montani Matteo , Tschan Mario P. , Candinas Daniel , Stroka Deborah 
Published: January 2013

Abstract
Sirtuins (SIRT1-7) are a highly conserved family of NAD+-dependent enzymes that control the activity of histone and nonhistone regulatory proteins. SIRT1 is purposed to promote longevity and to suppress the initiation of some cancers. Nevertheless, SIRT1 is reported to function as a tumor suppressor as well as an oncogenic protein. Our data show that compared with normal liver or surrounding tumor tissue, SIRT1 is strongly overexpressed in human hepatocellular carcinoma (HCC). In addition, human HCC cell lines (Hep3B, HepG2, HuH7, HLE, HLF, HepKK1, skHep1) were screened for the expression of the sirtuin family members and only SIRT1 was consistently overexpressed compared with normal hepatocytes. To determine its effect on HCC growth, SIRT1 activity was inhibited either with lentiviruses expressing short hairpin RNAs or with the small molecule inhibitor, cambinol. Knockdown or inhibition of SIRT1 activity had a cytostatic effect, characterized by an altered morphology, impaired proliferation, an increased expression of differentiation markers, and cellular senescence. In an orthotopic xenograft model, knockdown of SIRT1 resulted in 50% fewer animals developing tumors and cambinol treatment resulted in an overall lower tumor burden. Taken together, our data show that inhibition of SIRT1 in HCC cells impairs their proliferation in vitro and tumor formation in vivo. These data suggest that SIRT1 expression positively influences the growth of HCC and support further studies aimed to block its activity alone or in combination as a novel treatment strategy. Mol Cancer Ther; 12(4); 499–508. ©2013 AACR.
Novel Inhibitors of Rad6 Ubiquitin Conjugating Enzyme: Design, Synthesis, Identification, and Functional Characterization
Authors: Sanders Matthew A. , Brahemi Ghali , Nangia-Makker Pratima , Balan Vitaly , Morelli Matteo , Kothayer Hend , Westwell Andrew D. , Shekhar Malathy P.V. 
Published: January 2013

Abstract
Protein ubiquitination is important for cell signaling, DNA repair, and proteasomal degradation, and it is not surprising that alterations in ubiquitination occur frequently in cancer. Ubiquitin-conjugating enzymes (E2) mediate ubiquitination by selective interactions with ubiquitin-activating (E1) and ubiquitin ligase (E3) enzymes, and thus selective E2 small molecule inhibitor (SMI) will provide specificity unattainable with proteasome inhibitors. Here we describe synthesis and functional characterization of the first SMIs of human E2 Rad6B, a fundamental component of translesion synthesis DNA repair. A pharmacophore model for consensus E2 ubiquitin-binding sites was generated for virtual screening to identify E2 inhibitor candidates. Twelve triazine (TZ) analogs screened in silico by molecular docking to the Rad6B X-ray structure were verified by their effect on Rad6B ubiquitination of histone H2A. TZs #8 and 9 docked to the Rad6B catalytic site with highest complementarity. TZs #1, 2, 8, and 9 inhibited Rad6B-ubiquitin thioester formation and subsequent ubiquitin transfer to histone H2A. SMI #9 inhibition of Rad6 was selective as BCA2 ubiquitination by E2 UbcH5 was unaffected by SMI #9. SMI #9 more potently inhibited proliferation, colony formation, and migration than SMI #8, and induced MDA-MB-231 breast cancer cell G2–M arrest and apoptosis. Ubiquitination assays using Rad6 immunoprecipitated from SMI #8- or 9-treated cells confirmed inhibition of endogenous Rad6 activity. Consistent with our previous data showing Rad6B-mediated polyubiquitination stabilizes β-catenin, MDA-MB-231 treatment with SMIs #8 or 9 decreased β-catenin protein levels. Together these results describe identification of the first Rad6 SMIs. Mol Cancer Ther; 12(4); 373–83. ©2013 AACR.
Nuclear Expression of β-Catenin Promotes RB Stability and Resistance to TNF-Induced Apoptosis in Colon Cancer Cells
Authors: Han Jinbo , Soletti Rossana C. , Sadarangani Anil , Sridevi Priya , Ramirez Michael E. , Eckmann Lars , Borges Helena L. , Wang Jean Y.J. 
Published: January 2013

Abstract
Tumor necrosis factor (TNF)-α promotes tumor development under chronic inflammation. Because TNF also activates caspase-8, selective inhibition of TNF-induced extrinsic apoptosis would be required for inflammation-associated tumor growth. In a mouse model of inflammation-associated colon carcinogenesis, we found nuclear expression of β-catenin in tumors of wild-type, but not mutant, mice that were made resistant to TNF-induced apoptosis by a germline mutation blocking caspase cleavage of the retinoblastoma (RB) protein, despite similar frequencies of β-catenin exon-3 mutations in these two genetic backgrounds. TNF-induced apoptosis was also attenuated in human colon cancer cell lines with genetically activated β-catenin. However, we found that HCT116 cells, which contain an activated allele of β-catenin but do not express nuclear β-catenin, were sensitive to TNF-induced apoptosis. In HCT116 cells, TNF stimulated efficient RB cleavage that preceded chromatin condensation. In contrast, TNF did not induce RB cleavage in colon cancer cells expressing nuclear β-catenin and these cells could be sensitized to basal and/or TNF-induced apoptosis by the knockdown of β-catenin or RB. In the apoptosis-resistant colon cancer cells, knockdown of β-catenin led to a reduction in the RB protein without affecting RB mRNA. Furthermore, ectopic expression of the caspase-resistant, but not the wild-type, RB re-established resistance to TNF-induced caspase activation in colon cancer cells without β-catenin. Together, these results suggest that nuclear β-catenin–dependent RB stabilization suppresses TNF-induced apoptosis in caspase-8–positive colon cancer cells.
Visual Overview: http://mcr.aacrjournals.org/content/11/3/207/F1.large.jpg.
Mol Cancer Res; 11(3); 207–18. ©2012 AACR.
A Self-Organized Neural Comparator
Authors: Ludueña Guillermo A. , Gros Claudius 
Published: January 2013

Abstract
Learning algorithms need generally the ability to compare several streams of information. Neural learning architectures hence need a unit, a comparator, able to compare several inputs encoding either internal or external information, for instance, predictions and sensory readings. Without the possibility of comparing the values of predictions to actual sensory inputs, reward evaluation and supervised learning would not be possible.
Comparators are usually not implemented explicitly. Necessary comparisons are commonly performed by directly comparing the respective activities one-to-one. This implies that the characteristics of the two input streams (like size and encoding) must be provided at the time of designing the system. It is, however, plausible that biological comparators emerge from self-organizing, genetically encoded principles, which allow the system to adapt to the changes in the input and the organism. We propose an unsupervised neural circuitry, where the function of input comparison emerges via self-organization only from the interaction of the system with the respective inputs, without external influence or supervision.
The proposed neural comparator adapts in an unsupervised form according to the correlations present in the input streams. The system consists of a multilayer feedforward neural network, which follows a local output minimization (anti-Hebbian) rule for adaptation of the synaptic weights. The local output minimization allows the circuit to autonomously acquire the capability of comparing the neural activities received from different neural populations, which may differ in population size and the neural encoding used. The comparator is able to compare objects never encountered before in the sensory input streams and evaluate a measure of their similarity even when differently encoded.
Wave Activity for Large-Amplitude Disturbances Described by the Primitive Equations on the Sphere
Authors: Methven John 
Published: January 2013

Abstract
Pseudomomentum and pseudoenergy are both measures of wave activity for disturbances in a fluid, relative to a notional background state. Together they give information on the propagation, growth, and decay of disturbances. Wave activity conservation laws are most readily derived for the primitive equations on the sphere by using isentropic coordinates. However, the intersection of isentropic surfaces with the ground (and associated potential temperature anomalies) is a crucial aspect of baroclinic wave evolution. A new expression is derived for pseudoenergy that is valid for large-amplitude disturbances spanning isentropic layers that may intersect the ground. The pseudoenergy of small-amplitude disturbances is also obtained by linearizing about a zonally symmetric background state. The new expression generalizes previous pseudoenergy results for quasigeostrophic disturbances on the β plane and complements existing large-amplitude results for pseudomomentum.
The pseudomomentum and pseudoenergy diagnostics are applied to an extended winter from the European Centre for Medium-Range Weather Forecasts Interim Re-Analysis data. The time series identify distinct phenomena such as a baroclinic wave life cycle where the wave activity in boundary potential temperature saturates nonlinearly almost two days before the peak in wave activity near the tropopause. The coherent zonal propagation speed of disturbances at tropopause level, including distinct eastward, westward, and stationary phases, is shown to be dictated by the ratio of total hemispheric pseudoenergy to pseudomomentum. Variations in the lower-boundary contribution to pseudoenergy dominate changes in propagation speed; phases of westward progression are associated with stronger boundary potential temperature perturbations.
Asymmetry in the IOD and ENSO Teleconnection in a CMIP5 Model Ensemble and Its Relevance to Regional Rainfall
Authors: Weller Evan , Cai Wenju 
Published: January 2013

Abstract
Recent studies have shown that the impact of the Indian Ocean dipole (IOD) on southern Australia occurs via equivalent barotropic Rossby wave trains triggered by convective heating in the tropical Indian Ocean. Furthermore, the El Niño–Southern Oscillation (ENSO) influence on southern Australian climate is exerted through the same pathway during austral spring. It is also noted that positive phase [positive IOD (pIOD) and El Niño] events have a much larger impact associated with their respective skewness. These phenomena play a significant role in the region's rainfall reduction in recent decades, and it is essential that climate models used for future projections simulate these features. Here, the authors demonstrate that climate models do indeed simulate a greater climatic impact on Australia for pIOD events than for negative IOD (nIOD) events, but this asymmetric impact is distorted by an exaggerated influence of La Niña emanating from the Pacific. The distortion results from biases in the Pacific in two respects. First, the tropical and extratropical response to La Niña is situated unrealistically too far westward and hence too close to Australia, leading to an overly strong impact on southeast Australia that shows up through the nIOD–La Niña coherence. Second, the majority of models simulate a positive sea surface temperature skewness in the eastern Pacific that is too weak, overestimating the impact of La Niña relative to that of El Niño. As such, the impact of the positive asymmetry in the IOD only becomes apparent when the impact of ENSO is removed. This model bias needs to be taken into account when analyzing projections of regional Australian climate change.
Impact of ASCAT Scatterometer Wind Observations on the High-Resolution Limited-Area Model (HIRLAM) within an Operational Context
Authors: de Haan Siebren , Marseille Gert-Jan , de Valk Paul , de Vries John 
Published: January 2013

Abstract
Denial experiments, also denoted observing system experiments (OSEs), are used to determine the impact of an observing system on the forecast quality of a numerical weather prediction (NWP) model. When the impact is neutral or positive, new observations from this observing system may be admitted to an operational forecasting system based on that NWP model. A drawback of the method applied in most denial experiments is that it neglects the operational time constraint on the delivery of observations. In a 10-week twin experiment with the operational High-Resolution Limited-Area Model (HIRLAM) at KNMI, the impact of additional ocean surface wind observations from the Advanced Scatterometer (ASCAT) on the forecast quality of the model has been verified under operational conditions. In the experiment, the operational model was used as reference, parallel to an augmented system in which the ASCAT winds were assimilated actively. Objective verification of the forecast with independent wind observations from moored buoys and ASCAT winds revealed a slight improvement in forecast skill as measured by a decrease in observation-minus-forecast standard deviation in the wind components for the short range (up to 24 h). A subjective analysis in a case study showed a realistic deepening of a low pressure system over the North Atlantic near the coast of Ireland through the assimilation of scatterometer data that were verified with radiosonde observations over Ireland. Based on these results, the decision was made to include ASCAT in operations at the next upgrade of the forecasting system.
Changes in Criminal Offending around the Time of Marriage
Authors: Lyngstad Torkild Hovde , Skardhamar Torbjørn 
Published: January 2013

Objectives: The authors investigate whether the argument from life-course criminology that marriage leads to reduction in crime or whether the mechanisms leading to lower crime rates might take effect in a period of courtship before the transition to marriage. Method: Using data from population-wide, longitudinal Norwegian administrative registers, the authors estimate within-individual offending propensities before and after marriage for all men marrying in Norway 1997–2001. This approach allows for studying how offending develops over a decade around the time of marriage, for those men who actually marry. Results: The propensity to offend declines sharply prior to marriage. After marriage, there is a small increase in offending. This holds both for all offenses and when the analysis is restricted to felony offenses. Conclusions: The analysis provides no evidence for an effect of marriage on offending. Rather, the results suggest that the lower offending rates of marrieds develop over the years prior to marriage rather than as a consequence of the marriage.
Effects of 1.8 GHz radiofrequency radiation on protein expression in human lens epithelial cells
Authors: Zhang Y. , Yao K. , Yu Y. , Ni S. , Zhang L. , Wang W. , Lai K. 
Published: January 2013

Objective: The aim of the present study was to observe the effects of 1.8 GHz radiofrequency (RF) radiation on the protein expression of human lens epithelial cells (hLECs) in vitro. Methods: The hLECs were exposed and sham-exposed to 1.8 GHz RF radiation (specific absorption rate (SAR) of 4 W/kg) for 2 h. After exposure, the proteins extracted from LECs were loaded on the Ettan MDLC system connected to the LTQ-Orbitrap MS for screening the candidate protein biomarkers induced by RF. The quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the levels of messenger RNA of candidate biomarkers. After the hLECs were exposed to 1.8 GHz RF (SAR of 2, 3 and 4 W/kg) for 2 h, the Western blot assay was utilized to measure the expression levels of the above-screened candidate protein biomarkers. Results: The results of shotgun proteomic analysis indicated that there were eight proteins with differential expression between exposure and sham exposure groups. The results of qRT-PCR showed that there were three genes with expressional differences (valosin containing protein (VCP), ubiquitin specific peptidase 35 (USP35) and signal recognition particle 68 kDa (SRP68)) between exposure and sham exposure groups. The results of Western blot assay exhibited that the expressional levels of VCP and USP35 proteins significantly increased and the expressional level of protein SRP68 significantly decreased in hLECs exposed to 1.8 GHz RF radiation (SAR of 3 and 4 W/kg) for 2 h when compared with the corresponding sham groups ( p < 0.05). Conclusion: The shotgun proteomics technique can be applied to screen the proteins with differential expression between hLECs exposed to 1.8 GHz RF and hLECs sham-exposed to 1.8 GHz RF, and three protein biomarkers associated with RF radiation were validated by Western blot assay.
The Impact of Endograft Surveillance on a Vascular Imaging Service
Authors: Karthikesalingam Alan , Young Mark , Powell Sophie A. , Morshedian Golnaz , Ramachandran Veni , D’Abate Fabrizio , Thompson Matthew M. , Holt Peter J. E. 
Published: January 2013

Background: Surveillance is considered mandatory after endovascular repair (EVR), but its impact on imaging services remains unreported. This study reports the effect of EVR surveillance on imaging resources. Methods: A single-center’s duplex database was interrogated from January 1, 2004 to January 1, 2012. All examinations requested by a vascular surgeon were reported, including preoperative abdominal aortic aneurysms, surveillance after EVR, lower limb arterial and venous duplex, and arteriovenous fistulae. Results: A total of 24 309 patients underwent duplex. The EVR surveillance increased from 192 scans in 2004 to 1325 scans in 2011, 9.5% (192 of 2030) and 34.4% (1325 of 3850) of each year’s examinations. By 2011, EVR surveillance was the most common indication for duplex. Conclusion: Lifelong EVR surveillance creates a rapidly increasing workload for imaging services. Further research should aim to reduce the burden of EVR surveillance. Targeting surveillance to the minority of patients at greatest risk of endograft failure might optimize the usage of imaging resources.
BMO and Lipschitz norm estimates for the composition of Green’s operator and the potential operator
Authors: Dai Zhimin , Xing Yuming , Ding Shusen 
Published: January 2013

Abstract
In this paper, we establish BMO and Lipschitz norm inequalities for the composition of Green’s operator and the potential operator. We also investigate the relationship among the Lipschitz norm, the BMO norm and the

L
p

-norm. Finally, we display some examples for applications.

MSC:35J60, 31B05, 58A10, 46E35.
The gain and loss of chromosomal integron systems in the Treponemaspecies
Authors: Wu Yu-Wei , Doak Thomas G , Ye Yuzhen 
Published: January 2013

Abstract

Background
Integron systems are now recognized as important agents of bacterial evolution and are prevalent in most environments. One of the human pathogens known to harbor chromosomal integrons, the Treponema spirochetes are the only clade among spirochete species found to carry integrons. With the recent release of many new Treponema genomes, we were able to study the distribution of chromosomal integrons in this genus.

Results
We find that the Treponema spirochetes implicated in human periodontal diseases and those isolated from cow and swine intestines contain chromosomal integrons, but not the Treponema species isolated from termite guts. By examining the species tree of selected spirochetes (based on 31 phylogenetic marker genes) and the phylogenetic tree of predicted integron integrases, and assisted by our analysis of predicted integron recombination sites, we found that all integron systems identified in Treponema spirochetes are likely to have evolved from a common ancestor—a horizontal gain into the clade. Subsequent to this event, the integron system was lost in the branch leading to the speciation of T. pallidum and T. phagedenis (the Treponema sps. implicated in sexually transmitted diseases). We also find that the lengths of the integron attC sites shortened through Treponema speciation, and that the integron gene cassettes of T. denticola are highly strain specific.

Conclusions
This is the first comprehensive study to characterize the chromosomal integron systems in Treponema species. By characterizing integron distribution and cassette contents in the Treponema sps., we link the integrons to the speciation of the various species, especially to the pathogens T. pallidum and T. phagedenis.