bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pacman
Authors: Brock Jacob , Gu Xiaoming , Bao Bin , Ding Chen 
Published: December 2013

As caches become larger and shared by an increasing number of cores, cache management is becoming more important. This paper explores collaborative caching, which uses software hints to influence hardware caching. Recent studies have shown that such collaboration between software and hardware can theoretically achieve optimal cache replacement on LRU-like cache.
This paper presents Pacman, a practical solution for collaborative caching in loop-based code. Pacman uses profiling to analyze patterns in an optimal caching policy in order to determine which data to cache and at what time. It then splits each loop into different parts at compile time. At run time, the loop boundary is adjusted to selectively store data that would be stored in an optimal policy. In this way, Pacman emulates the optimal policy wherever it can. Pacman requires a single bit at the load and store instructions. Some of the current hardware has partial support. This paper presents results using both simulated and real systems, and compares simulated results to related caching policies.
A Genetic Mouse Model of Invasive Endometrial Cancer Driven by Concurrent Loss of Pten and Lkb1 Is Highly Responsive to mTOR Inhibition
Authors: Cheng Hailing , Liu Pixu , Zhang Fan , Xu Erbo , Symonds Lynn , Ohlson Carolynn E. , Bronson Roderick T. , Maira Sauveur-Michel , Di Tomaso Emmanuelle , Li Jane , Myers Andrea P. , Cantley Lewis C. , Mills Gordon B. , Zhao Jean J. 
Published: December 2013

Abstract
Signals from the tumor suppressors PTEN and LKB1 converge on mTOR to negatively regulate its function in cancer cells. Notably, both of these suppressors are attenuated in a significant fraction of human endometrial tumors. In this study, we generated a genetic mouse model of endometrial cancer driven by concomitant loss of these suppressors to gain pathophysiological insight into this disease. Dual loss of Pten and Lkb1 in the endometrial epithelium led to rapid development of advanced endometrioid endometrial tumors with 100% penetrance and short host survival. The tumors displayed dysregulated phosphatidylinositol 3-kinase (PI3K)/Akt and Lkb1/Ampk signaling with hyperactivation of mTOR signaling. Treatment with a dual PI3K/mTOR inhibitor, BEZ235, extended the time before tumor onset and prolonged overall survival. The PI3K inhibitor GDC-0941 used as a single agent reduced the growth rate of primary tumor implants in Pten/Lkb1-deficient mice, and the mTOR inhibitor RAD001 was unexpectedly as effective as BEZ235 in triggering tumor regression. In parallel, we also found that ectopic expression of LKB1 in PTEN/LKB1-deficient human endometrial cancer cells increased their sensitivity to PI3K inhibition. Together, our results demonstrated that Pten/Lkb1-deficient endometrial tumors rely strongly on deregulated mTOR signaling, and they provided evidence that LKB1 status may modulate the response of PTEN-deficient tumors to PI3K or mTOR inhibitors. Cancer Res; 74(1); 15–23. ©2013 AACR.
Colon Cancer Cells Escape 5FU Chemotherapy-Induced Cell Death by Entering Stemness and Quiescence Associated with the c-Yes/YAP Axis
Authors: Touil Yasmine , Igoudjil Wassila , Corvaisier Matthieu , Dessein Anne-Frédérique , Vandomme Jérôme , Monté Didier , Stechly Laurence , Skrypek Nicolas , Langlois Carole , Grard Georges , Millet Guillaume , Leteurtre Emmanuelle , Dumont Patrick , Truant Stéphanie , Pruvot François-René , Hebbar Mohamed , Fan Fan , Ellis Lee M. , Formstecher Pierre , Van Seuningen Isabelle , Gespach Christian , Polakowska Renata , Huet Guillemette 
Published: December 2013

Abstract
Purpose: Metastasis and drug resistance are the major limitations in the survival and management of patients with cancer. This study aimed to identify the mechanisms underlying HT29 colon cancer cell chemoresistance acquired after sequential exposure to 5-fluorouracil (5FU), a classical anticancer drug for treatment of epithelial solid tumors. We examined its clinical relevance in a cohort of patients with colon cancer with liver metastases after 5FU-based neoadjuvant chemotherapy and surgery.
Results: We show that a clonal 5F31 cell population, resistant to 1 μmol/L 5FU, express a typical cancer stem cell–like phenotype and enter into a reversible quiescent G0 state upon reexposure to higher 5FU concentrations. These quiescent cells overexpressed the tyrosine kinase c-Yes that became activated and membrane-associated upon 5FU exposure. This enhanced signaling pathway induced the dissociation of the Yes/YAP (Yes-associated protein) molecular complex and depleted nuclear YAP levels. Consistently, YES1 silencing decreased nuclear YAP accumulation and induced cellular quiescence in 5F31 cells cultured in 5FU-free medium. Importantly, YES1 and YAP transcript levels were higher in liver metastases of patients with colon cancer after 5FU-based neoadjuvant chemotherapy. Moreover, the YES1 and YAP transcript levels positively correlated with colon cancer relapse and shorter patient survival (P &lt; 0.05 and P &lt; 0.025, respectively).
Conclusions: We identified c-Yes and YAP as potential molecular targets to eradicate quiescent cancer cells and dormant micrometastases during 5FU chemotherapy and resistance and as predictive survival markers for colon cancer. Clin Cancer Res; 20(4); 837–46. ©2013 AACR.
p53/mdm2 Feedback Loop Sustains miR-221 Expression and Dictates the Response to Anticancer Treatments in Hepatocellular Carcinoma
Authors: Fornari Francesca , Milazzo Maddalena , Galassi Marzia , Callegari Elisa , Veronese Angelo , Miyaaki Hisamitsu , Sabbioni Silvia , Mantovani Vilma , Marasco Elena , Chieco Pasquale , Negrini Massimo , Bolondi Luigi , Gramantieri Laura 
Published: December 2013

Abstract
The overexpression of microRNA-221 (miR-221) is reported in several human cancers including hepatocellular carcinoma, and its targeting by tailored treatments has been proposed. The evidence supporting the role of miR-221 in cancer is growing and has been mainly focused on the discovery of miR-221 targets as well as on its possible therapeutic exploitations. However, the mechanism sustaining miR-221 aberrant expression remains to be elucidated. In this study, MDM2 (E3 ubiquitin-protein ligase homolog), a known p53 (TP53) modulator, is identified as a direct target of miR-221, and a feed-forward loop is described that sustains miR-221 aberrant expression. Interestingly, miR-221 can activate the p53/mdm2 axis by inhibiting MDM2 and, in turn, p53 activation contributes to miR-221 enhanced expression. Moreover, by modulating the p53 axis, miR-221 impacts cell-cycle progression and apoptotic response to doxorubicin in hepatocellular carcinoma–derived cell lines. Finally, CpG island methylation status was assessed as a causative event associated with miR-221 upregulation in hepatocellular carcinoma cells and primary tumor specimens. In hepatocellular carcinoma–derived cell lines, pharmacologically induced DNA hypomethylation potentiated a significant increase in miR-221 expression. These data were confirmed in clinical specimens of hepatocellular carcinoma in which elevated miR-221 expression was associated with the simultaneous presence of wild-type p53 and DNA hypomethylation.
Implications: These findings reveal a novel miR-221–sustained regulatory loop that determines a p53-context-specific response to doxorubicin treatment in hepatocellular carcinoma. Mol Cancer Res; 12(2); 203–16. ©2013 AACR.
A Systems Biology Approach to Personalizing Therapeutic Combinations
Authors: Kwong Lawrence N. , Heffernan Timothy P. , Chin Lynda 
Published: December 2013

Abstract
Summary: The identification of evidence-based, efficacious drug combinations for each cancer, among thousands of potential permutations, is a daunting task. In this perspective, we propose a systematic approach to defining such combinations by molecularly benchmarking a drug against a desired state of efficacy using model systems. Cancer Discov; 3(12); 1339–44. ©2013 AACR.
Soluble Tumor Necrosis Factor Receptors and Heart Failure Risk in Older Adults
Authors: Marti Catherine N. , Khan Hassan , Mann Douglas L. , Georgiopoulou Vasiliki V. , Bibbins-Domingo Kirsten , Harris Tamara , Koster Annemarie , Newman Anne , Kritchevsky Stephen B. , Kalogeropoulos Andreas P. , Butler Javed 
Published: December 2013

Background—
Tumor necrosis factor (TNF) levels are associated with risk for heart failure (HF). The soluble TNF type 1 (sTNF-R1) and type 2 (sTNF-R2) receptors are elevated in patients with manifest HF, but whether they are associated with risk for incident HF is unclear.

Methods and Results—

Using Cox proportional hazard models, we examined the association between baseline levels of sTNF-R1 and sTNF-R2 with incident HF risk among 1285 participants of the Health, Aging, and Body Composition Study (age, 74.0±2.9 years; 51.4% women; 41.1% black). At baseline, median (interquartile range) of TNF, sTNF-R1, and sTNF-R2 levels was 3.14 (2.42–4.06), 1.46 (1.25–1.76), and 3.43 (2.95–4.02) ng/mL, respectively. During a median follow-up of 11.4 (6.9–11.7) years, 233 (18.1%) participants developed HF. In models controlling for other HF risk factors, TNF (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.02–1.61 per log
2
increase) and sTNF-R1 (HR, 1.68; 95% CI, 1.15–2.46 per log
2
increase), but not sTNF-R2 (HR, 1.15; 95% CI, 0.80–1.63 per log
2
increase), were associated with a higher risk for HF. These associations were consistent across whites and blacks (TNF, sTNF-R1, sTNF-R2; interaction
P
=0.531, 0.091, and 0.795, respectively) and in both sexes (TNF, sTNF-R1, sTNF-R2; interaction
P
=0.491, 0.672, and 0.999, respectively). TNF-R1 was associated with a higher risk for HF with preserved versus reduced ejection fraction (HR, 1.81; 95% CI, 1.03–3.18;
P
=0.038 for preserved versus HR, 0.90; 95% CI, 0.56–1.44;
P
=0.667 for reduced ejection fraction; interaction
P
=0.05).

Conclusions—
In older adults, elevated levels of sTNF-R1 are associated with increased risk for incident HF. However, addition of TNF-R1 to the previously validated Health ABC HF risk model did not demonstrate material improvement in net discrimination or reclassification.
TE-array—a high throughput tool to study transposon transcription
Authors: Gnanakkan Veena P , Jaffe Andrew E , Dai Lixin , Fu Jie , Wheelan Sarah J , Levitsky Hyam I , Boeke Jef D , Burns Kathleen H 
Published: December 2013

AbstractBackgroundAlthough transposable element (TE) derived DNA accounts for more than half of mammalian genomes and initiates a significant proportion of RNA transcripts, high throughput methods are rarely leveraged specifically to detect expression from interspersed repeats.ResultsTo characterize the contribution of transposons to mammalian transcriptomes, we developed a custom microarray platform with probes covering known human and mouse transposons in both sense and antisense orientations. We termed this platform the “TE-array” and profiled TE repeat expression in a panel of normal mouse tissues. Validation with nanoString®and RNAseq technologies demonstrated that TE-array is an effective method. Our data show that TE transcription occurs preferentially from the sense strand and is regulated in highly tissue-specific patterns.ConclusionsOur results are consistent with the hypothesis that transposon RNAs frequently originate within genomic TE units and do not primarily accumulate as a consequence of random ‘read-through’ from gene promoters. Moreover, we find TE expression is highly dependent on the tissue context. This suggests that TE expression may be related to tissue-specific chromatin states or cellular phenotypes. We anticipate that TE-array will provide a scalable method to characterize transposable element RNAs.
Antibiotic resistance, virulence determinants and production of biogenic amines among enterococci from ovine, feline, canine, porcine and human milk
Authors: Jiménez Esther , Ladero Victor , Chico Irene , Maldonado-Barragán Antonio , López María , Martín Virginia , Fernández Leonides , Fernández María , Álvarez Miguel A , Torres Carmen , Rodríguez Juan M 
Published: December 2013

Abstract

Background
Recent studies have shown that mammalian milk represents a continuous supply of commensal bacteria, including enterococci. The objectives of this study were to evaluate the presence of enterococci in milk of different species and to screen them for several genetic and phenotypic traits of clinical significance among enterococci.

Results
Samples were obtained from, at least, nine porcine, canine, ovine, feline and human healthy hosts. Enterococci could be isolated, at a concentration of 1.00 × 102 -1.16 × 103 CFU/ml, from all the porcine samples and, also from 85, 50, 25 and 25% of the human, canine, feline and ovine ones, respectively. They were identified as Enterococcus faecalis, Enterococcus faecium, Enterococcus hirae, Enterococcus casseliflavus and Enterococcus durans. Among the 120 initial enterococcal isolates, 36 were selected on the basis of their different PFGE profiles and further characterized. MLST analysis revealed a wide diversity of STs among the E. faecalis and E. faecium strains, including some frequently associated to hospital infections and novel STs. All the E. faecalis strains possessed some of the potential virulence determinants (cad, ccf, cob, cpd, efaA

fs
, agg2, gelE, cylA, esp

fs
) assayed while the E. faecium ones only harboured the efaA

fm
gene. All the tested strains were susceptible to tigecycline, linezolid and vancomycin, and produced tyramine. Their susceptibility to the rest of the antimicrobials and their ability to produce other biogenic amines varied depending on the strain. Enterococci strains isolated from porcine samples showed the widest spectrum of antibiotic resistance.

Conclusions
Enterococci isolated from milk of different mammals showed a great genetic diversity. The wide distribution of virulence genes and/or antibiotic resistance among the E. faecalis and E. faecium isolates indicates that they can constitute a reservoir of such traits and a risk to animal and human health.
Thyroid volume, goiter prevalence, and selenium levels in an iodine-sufficient area: a cross-sectional study
Authors: Liu Yang , Huang Hui , Zeng Jing , Sun Chengjun 
Published: December 2013

Abstract

Background
Selenium (Se) is a necessary element for the biosynthesis of thyroid hormones. We investigated the relationship between selenium status, thyroid volume, and goiter in a cross-sectional study in an iodine-sufficient area.

Methods
We selected residents of Chengdu (over 18 years old and living in the city for more than 5 years) using a stratified cluster sampling technique. Fifteen hundred subjects were selected for the study, which involved a questionnaire survey, physical examination, thyroid ultrasound, serum thyroid function test, and determination of serum selenium level. Thyroid volume was calculated from the thickness, width, length, and a corrective factor for each lobe. Ultimately, 1,205 subjects completed the investigation and were included in our study. Additionally, 80 school-age children were selected to provide urine samples for urinary iodine analysis. We analyzed the data using appropriate nonparametric and parametric statistical tests.

Results
The median urinary iodine value was 184 μg/L in school-age children, indicating iodine sufficiency. The median serum selenium level of the 1,205 subjects was 52.63 (interquartile range [IQR] : 40.40-67.00) μg/L. The median thyroid volume was 9.93 (IQR: 7.71-12.57) mL; both log-transformed serum selenium and log-transformed thyroid volume were Gaussian distributions (P = .638 and P = .046, respectively). The prevalences of goiter and thyroid nodules were 8.8% and 18.6%. The prevalences of positive thyroid autoantibodies, thyroperoxidase autoantibodies and thyroglobulin autoantibodies were 16.7%, 12.0%, and 11.1%, respectively. In the general linear regression model, there were positive associations between serum selenium and age, and body mass index. We found no association between serum selenium and thyroid-stimulating hormone. In simple linear regression analyses, we found no association between thyroid volume and serum selenium. There were no significant differences in serum selenium between persons with or without goiter. Serum selenium was not a risk factor for goiter.

Conclusion
In our study population, serum selenium was neither associated with thyroid volume nor with goiter in an iodine-sufficient area. More studies should be conducted by following non-goitrous persons over time and monitoring their selenium status.
Psychometric properties of the World Health Organization quality of life assessment – brief in methadone patients: a validation study in northern Taiwan
Authors: Fu Tiffany Szu-Ting , Tuan Yung-Change , Yen Muh-Yong , Wu Wei-Hsin , Huang Chun-Wei , Chen Wei-Ti , Li Chiang-Shan R , Lee Tony Szu-Hsien 
Published: December 2013

Abstract

Background
Quality of life (QOL) is an important outcome measure in the treatment of heroin addiction. The Taiwan version of the World Health Organization Quality of Life assessment (WHOQOL-BREF [TW]) has been developed and studied in various groups, but not specifically in a population of injection drug users. The aim of this study was to analyze the psychometric properties of the WHOQOL-BREF (TW) in a sample of injection drug users undergoing methadone maintenance treatment.

Methods
A total of 553 participants were interviewed and completed the instrument. Item-response distributions, internal consistency, corrected item-domain correlation, criterion-related validity, and construct validity through confirmatory factor analysis were evaluated.

Results
The frequency distribution of the 4 domains of the WHOQOL-BREF (TW) showed no floor or ceiling effects. The instrument demonstrated adequate internal consistency (Cronbach’s alpha coefficients were higher than 0.7 across the 4 domains) and all items had acceptable correlation with the corresponding domain scores (r = 0.32-0.73). Correlations (p < 0.01) of the 4 domains with the 2 benchmark items assessing overall QOL and general health were supportive of criterion-related validity. Confirmatory factor analysis yielded marginal goodness-of-fit between the 4-domain model and the sample data.

Conclusions
The hypothesized WHOQOL-BREF measurement model was appropriate for the injection drug users after some adjustments. Despite different patterns found in the confirmatory factor analysis, the findings overall suggest that the WHOQOL-BREF (TW) is a reliable and valid measure of QOL among injection drug users and can be utilized in future treatment outcome studies. The factor structure provided by the study also helps to understand the QOL characteristics of the injection drug users in Taiwan. However, more research is needed to examine its test-retest reliability and sensitivity to changes due to treatment.
Human papillomavirus genotypes in human immunodeficiency virus-positive patients with anal pathology in Madrid, Spain
Authors: García-Espinosa Benjamín , Moro-Rodríguez Ernesto , Álvarez-Fernández Emilio 
Published: December 2013

Abstract

Background
We studied anal specimens to determine the distribution of human papillomavirus (HPV) genotypes and co-infection occurrence. This information will contribute to the knowledge of HPV genotype distributions and provide an estimate of the prevalence of different oncogenic HPV genotypes found in patients in Madrid (Spain).

Methods
We studied a total of 82 anal biopsies from the Hospital General Universitario Gregorio Marañón of Madrid. These included 4 specimens with benign lesions, 52 specimens with low-grade anal squamous intraepithelial lesion, 24 specimens with high-grade anal squamous intraepithelial lesions and 2 specimens with invasive anal carcinoma. HPV genotyping was performed with PCR amplification and reverse dot blot hybridization.

Results
We detected 33 different HPV genotypes, including 16 HPVs associated with a high risk of carcinogenesis, 3 HPVs associated with a highly likely risk of carcinogenesis and 14 HPVs associated with a low-risk of carcinogenesis. In two specimens, an uncharacterized HPV genotype was detected. The most frequent HPV genotypes found were HPV-16 (10.3%; 95% CI: 6.6%-15.1%), HPV-52 (8.5%; 95% CI: 5.2%-13%) and HPV-43/44 (7.6%; 95% CI: 4.5%-11.9%). HPV-18 was only detected in 0.9% (95% CI: 0.1%-3.2%) of the total viruses detected in all lesions. HPV co-infections were found in 83.9% of all types of lesions. The majority of cases (90.2%) were concomitantly infected with the human immunodeficiency virus (HIV).

Conclusion
The prevalence of high-risk carcinogenic genotypes in anal pathological samples was remarkable. Therefore, further studies that include a greater number of samples, particularly invasive carcinoma cases are needed to evaluate the potential influence of these HPV genotypes in the appearance of anal carcinomas. Also, the influence of other accompanying infections should be evaluated clarify the appearance of this type of carcinoma.

Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2075238024106058.
Activation of Linear Alkanes by a Hydrido Triruthenium Cluster and Associated Skeletal Rearrangements
Authors: Takao Toshiro , Suzuki Hiroharu 
Published: December 2013

Abstract
We explored polyhydrido cluster reaction chemistry for over two decades, developing rational syntheses of di-, tri-, tetra-, and pentanuclear clusters of ruthenium. In our study of cluster chemistry, we found that triruthenium pentahydrido complex [{Cp*Ru(µ-H)}3(µ3-H)2] (1) (Cp*: η5-C5Me5) reacts with linear alkanes to exclusively afford a closo-ruthenacyclopentadiene complex 2. The reaction mechanism has been elucidated by the isolation and alternative preparation of several important intermediates by the reaction of 1 with other hydrocarbons, such as alkynes, dienes, and alkenes. The mechanism is shown to consist of two reversible and four irreversible steps involving dihydrogen elimination, where the cooperative interaction of neighboring metal centers with hydrocarbons on the cluster is clearly seen. Facile migration of a hydride from a metal center to the carbon atom is also observed during the reaction, which emphasizes the crucial role of hydrido ligands in the skeletal rearrangement of hydrocarbyl ligands on a polyhydrido cluster. In addition, coupling reaction between two hydrocarbyl ligands placed on each face of the triruthenium core with concomitant partial cleavage of the cluster skeleton has also been observed. Such a flexible cluster skeleton enables unusual transformation of hydrocarbons on the cluster.
Simultaneously Learning and Optimizing Using Controlled Variance Pricing
Authors: den Boer Arnoud V. , Zwart Bert 
Published: December 2013

Price experimentation is an important tool for firms to find the optimal selling price of their products. It should be conducted properly, since experimenting with selling prices can be costly. A firm, therefore, needs to find a pricing policy that optimally balances between learning the optimal price and gaining revenue. In this paper, we propose such a pricing policy, called controlled variance pricing (CVP). The key idea of the policy is to enhance the certainty equivalent pricing policy with a taboo interval around the average of previously chosen prices. The width of the taboo interval shrinks at an appropriate rate as the amount of data gathered gets large; this guarantees sufficient price dispersion. For a large class of demand models, we show that this procedure is strongly consistent, which means that eventually the value of the optimal price will be learned, and derive upper bounds on the regret, which is the expected amount of money lost due to not using the optimal price. Numerical tests indicate that CVP performs well on different demand models and time scales. This paper was accepted by Assaf Zeevi, stochastic models and simulation.