bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quasirandom rumor spreading
Authors: Doerr Benjamin , Friedrich Tobias , Künnemann Marvin , Sauerwald Thomas 
Published: October 2012

We empirically analyze two versions of the well-known “randomized rumor spreading” protocol to disseminate a piece of information in networks. In the classical model, in each round, each informed node informs a random neighbor. In the recently proposed quasirandom variant, each node has a (cyclic) list of its neighbors. Once informed, it starts at a random position of the list, but from then on informs its neighbors in the order of the list.
While for sparse random graphs a better performance of the quasirandom model could be proven, all other results show that, independent of the structure of the lists, the same asymptotic performance guarantees hold as for the classical model.
In this work, we compare the two models experimentally. Not only does this show that the quasirandom model generally is faster, but it also shows that the runtime is more concentrated around the mean. This is surprising given that much fewer random bits are used in the quasirandom process.
These advantages are also observed in a lossy communication model, where each transmission does not reach its target with a certain probability, and in an asynchronous model, where nodes send at random times drawn from an exponential distribution. We also show that typically the particular structure of the lists has little influence on the efficiency.
Languages as libraries
Authors: Tobin-Hochstadt Sam , St-Amour Vincent , Culpepper Ryan , Flatt Matthew , Felleisen Matthias 
Published: October 2012

Programming language design benefits from constructs for extending the syntax and semantics of a host language. While C's string-based macros empower programmers to introduce notational shorthands, the parser-level macros of Lisp encourage experimentation with domain-specific languages. The Scheme programming language improves on Lisp with macros that respect lexical scope.
The design of Racket---a descendant of Scheme---goes even further with the introduction of a full-fledged interface to the static semantics of the language. A Racket extension programmer can thus add constructs that are indistinguishable from "native" notation, large and complex embedded domain-specific languages, and even optimizing transformations for the compiler backend. This power to experiment with language design has been used to create a series of sub-languages for programming with first-class classes and modules, numerous languages for implementing the Racket system, and the creation of a complete and fully integrated typed sister language to Racket's untyped base language.
This paper explains Racket's language extension API via an implementation of a small typed sister language. The new language provides a rich type system that accommodates the idioms of untyped Racket. Furthermore, modules in this typed language can safely exchange values with untyped modules. Last but not least, the implementation includes a type-based optimizer that achieves promising speedups. Although these extensions are complex, their Racket implementation is just a library, like any other library, requiring no changes to the Racket implementation.
Digest of ACM educational activities
Authors: McGettrick Andrew , Timanovsky Yan 
Published: October 2012

Welcome to the third installment of EduBits, your quarterly pipeline to new and exciting happenings in the world of ACM education. Starting with this March issue of ACM Inroads, we are introducing a new thread that will highlight principal educational activities within ACM and affiliated organizations. Starting with this issue, you'll find a special focus on an ACM Special Interest Group (SIG) engaged in educational activities. News summaries will also include updates from task groups and committees of the ACM Education Council and within the institution itself.
This issue also features a status report from the CS2013 curricula revision task force and highlights of the many educational activities within SIGGRAPH, ACM's Special Interest Group on Computer Graphics and Interactive Techniques. In the spirit of community inclusiveness and broadening participation that permeates the Education Council, these pieces come straight from the people leading these important educational efforts. We trust you'll find their words informative and engaging and welcome your feedback. Enjoy.
We begin with a dedicated group of volunteers guiding a major revision of undergraduate computer science curricula recommendations: CS2013.
A real-time remote rendering system for interactive mobile graphics
Authors: Shi Shu , Nahrstedt Klara , Campbell Roy 
Published: October 2012

Mobile devices are gradually changing people's computing behaviors. However, due to the limitations of physical size and power consumption, they are not capable of delivering a 3D graphics rendering experience comparable to desktops. Many applications with intensive graphics rendering workloads are unable to run on mobile platforms directly. This issue can be addressed with the idea of remote rendering: the heavy 3D graphics rendering computation runs on a powerful server and the rendering results are transmitted to the mobile client for display. However, the simple remote rendering solution inevitably suffers from the large interaction latency caused by wireless networks, and is not acceptable for many applications that have very strict latency requirements.In this article, we present an advanced low-latency remote rendering system that assists mobile devices to render interactive 3D graphics in real-time. Our design takes advantage of an image based rendering technique: 3D image warping, to synthesize the mobile display from the depth images generated on the server. The research indicates that the system can successfully reduce the interaction latency while maintaining the high rendering quality by generating multiple depth images at the carefully selected viewpoints. We study the problem of viewpoint selection, propose a real-time reference viewpoint prediction algorithm, and evaluate the algorithm performance with real-device experiments.
Stromal Progenitor Cells from Endogenous Adipose Tissue Contribute to Pericytes and Adipocytes That Populate the Tumor Microenvironment
Authors: Zhang Yan , Daquinag Alexes C. , Amaya-Manzanares Felipe , Sirin Olga , Tseng Chieh , Kolonin Mikhail G. 
Published: October 2012

Abstract
Epidemiologic studies associate cancer with obesity, but the pathophysiologic connections remain obscure. In this study, we show that obesity facilitates tumor growth in mice irrespective of concurrent diet, suggesting a direct effect of excess white adipose tissue (WAT). When transplanted into mice, adipose stromal cells (ASC) can serve as perivascular adipocyte progenitors that promote tumor growth, perhaps helping explain the obesity–cancer link. In developing this hypothesis, we showed that ASCs are expanded in obesity and that they traffic from endogenous WAT to tumors in several mouse models of cancer. Strikingly, a comparison of circulating and tumor-infiltrating cell populations in lean, and obese mice revealed that cancer induces a six-fold increase of ASC frequency in the systemic circulation. We obtained evidence that ASCs mobilized in this way can be recruited into tumors, where they can be incorporated into blood vessels as pericytes and they can differentiate into adipocytes in an obesity-dependent manner. Extending this evidence, we found that increased tumor vascularization (reflected by changes in tumor vascular morphology and a two-fold increase in vascular density) was associated with intratumoral adipocytes and elevated proliferation of neighboring malignant cells. Taken together, our results suggest that ASCs recruited from endogenous adipose tissue can be recruited by tumors to potentiate the supportive properties of the tumor microenvironment. Cancer Res; 72(20); 5198–208. ©2012 AACR.
The CRTC1-NEDD9 Signaling Axis Mediates Lung Cancer Progression Caused by LKB1 Loss
Authors: Feng Yan , Wang Ye , Wang Zuoyun , Fang Zhaoyuan , Li Fei , Gao Yijun , Liu Hongyan , Xiao Tian , Li Fuming , Zhou Yang , Zhai Qiwei , Liu Xiaolong , Sun Yihua , Bardeesy Nabeel , Wong Kwok-kin , Chen Haiquan , Xiong Zhi-qi , Ji Hongbin 
Published: October 2012

Abstract
Somatic mutation of the tumor suppressor gene LKB1 occurs frequently in lung cancer where it causes tumor progression and metastasis, but the underlying mechanisms remain mainly unknown. Here, we show that the oncogene NEDD9 is an important downstream mediator of lung cancer progression evoked by LKB1 loss. In de novo mouse models, RNAi-mediated silencing of Nedd9 inhibited lung tumor progression, whereas ectopic NEDD9 expression accelerated this process. Mechanistically, LKB1 negatively regulated NEDD9 transcription by promoting cytosolic translocation of CRTC1 from the nucleus. Notably, ectopic expression of either NEDD9 or CRTC1 partially reversed the inhibitory function of LKB1 on metastasis of lung cancer cells. In clinical specimens, elevated expression of NEDD9 was associated with malignant progression and metastasis. Collectively, our results decipher the mechanism through which LKB1 deficiency promotes lung cancer progression and metastasis, and provide a mechanistic rationale for therapeutic attack of these processes. Cancer Res; 72(24); 6502–11. ©2012 AACR.
EGFR/JIP-4/JNK2 Signaling Attenuates Cetuximab-Mediated Radiosensitization of Squamous Cell Carcinoma Cells
Authors: Eke Iris , Schneider Lydia , Förster Claudia , Zips Daniel , Kunz-Schughart Leoni A. , Cordes Nils 
Published: October 2012

Abstract
EGF receptor (EGFR) promotes tumor growth as well as radio- and chemoresistance in various human malignancies including squamous cell carcinomas (SCC). In addition to deactivation of prosurvival signaling, cetuximab-mediated EGFR targeting might concomitantly induce self-attenuating signaling bypasses. Identification of such bypass mechanisms is key to improve the efficacy of targeted approaches. Here, we show great similarity of EGFR signaling and radiation survival in cetuximab-treated SCC cells grown in a more physiologic three-dimensional extracellular matrix and as tumor xenografts in contrast to conventional monolayer cell cultures. Using phosphoproteome arrays, we observed strong induction of JNK2 phosphorylation potentially resulting from cetuximab-inhibited EGFR through c-jun-NH2-kinase (JNK)-interacting protein-4 (JIP-4), which was identified using an immunoprecipitation-mass spectrometric approach. Inhibition of this signaling bypass by JIP-4 or JNK2 knockdown or pharmacologic JNK2 inhibition enhanced cetuximab efficacy and tumor cell radiosensitivity. Our findings add new facets to EGFR signaling and indicate signaling bypass possibilities of cancer cells to improve their survival on cetuximab treatment. By deactivation of cetuximab–self-attenuating JNK2-dependent signaling, the cytotoxicity, and radiosensitizing potential of cetuximab can be augmented. Cancer Res; 73(1); 297–306. ©2012 AACR.
miR-23b Represses Proto-oncogene Src Kinase and Functions as Methylation-Silenced Tumor Suppressor with Diagnostic and Prognostic Significance in Prostate Cancer
Authors: Majid Shahana , Dar Altaf A. , Saini Sharanjot , Arora Sumit , Shahryari Varahram , Zaman Mohd Saif , Chang Inik , Yamamura Soichiro , Tanaka Yuichiro , Deng Guoren , Dahiya Rajvir 
Published: October 2012

AbstractThe miRNAs have great potential as biomarkers and therapeutic agents owing to their ability to control multiple genes and potential to influence cellular behavior. Here, we identified that miR-23b is a methylation-silenced tumor suppressor in prostate cancer. We showed that miR-23b expression is controlled by promoter methylation and has great promise as a diagnostic and prognostic biomarker in prostate cancer. High levels of miR-23b expression are positively correlated with higher overall and recurrence-free survival in patients with prostate cancer. Furthermore, we elucidated the tumor suppressor role of miR-23b using in vitro and in vivo models. We showed that proto-oncogene Src kinase and Akt are direct targets of miR-23b. Increased expression of miR-23b inhibited proliferation, colony formation, migration/invasion, and triggered G0–G1 cell-cycle arrest and apoptosis in prostate cancer. Overexpression of miR-23b inhibited epithelial-to-mesenchymal transition (EMT) causing a decline in mesenchymal markers Vimentin and Snail and increasing the epithelial marker, E-cadherin. Depletion of Src by RNA interference conferred similar functional effects as that of miR-23b reconstitution. miR-23b expression caused a dramatic decrease in tumor growth in nude mice and attenuated Src expression in excised tumors compared with a control miR. These findings suggest that miR-23b is a methylation-silenced tumor suppressor that may be a useful biomarker in prostate cancer. Loss of miR-23b may confer proliferative advantage and promote prostate cancer migration and invasion, and reexpression of miR-23b may contribute to the epigenetic therapy for prostate cancer. Cancer Res; 72(24); 6435–46. ©2012 AACR.
Pyruvate Kinase M2: Multiple Faces for Conferring Benefits on Cancer Cells
Authors: Tamada Mayumi , Suematsu Makoto , Saya Hideyuki 
Published: October 2012

Abstract
The M2 splice isoform of pyruvate kinase (PKM2), an enzyme that catalyzes the later step of glycolysis, is a key regulator of aerobic glycolysis (known as the Warburg effect) in cancer cells. Expression and low enzymatic activity of PKM2 confer on cancer cells the glycolytic phenotype, which promotes rapid energy production and flow of glycolytic intermediates into collateral pathways to synthesize nucleic acids, amino acids, and lipids without the accumulation of reactive oxygen species. PKM2 enzymatic activity has also been shown to be negatively regulated by the interaction with CD44 adhesion molecule, which is a cell surface marker for cancer stem cells. In addition to the glycolytic functions, nonglycolytic functions of PKM2 in cancer cells are of particular interest. PKM2 is induced translocation into the nucleus, where it activates transcription of various genes by interacting with and phosphorylating specific nuclear proteins, endowing cancer cells with a survival and growth advantage. Therefore, inhibitors and activators of PKM2 are well underway to evaluate their anticancer effects and suitability for use as novel therapeutic strategies. Clin Cancer Res; 18(20); 5554–61. ©2012 AACR.
c-Myc and Cancer Metabolism
Authors: Miller Donald M. , Thomas Shelia D. , Islam Ashraful , Muench David , Sedoris Kara 
Published: October 2012

Abstract
The processes of cellular growth regulation and cellular metabolism are closely interrelated. The c-Myc oncogene is a “master regulator” which controls many aspects of both of these processes. The metabolic changes which occur in transformed cells, many of which are driven by c-Myc overexpression, are necessary to support the increased need for nucleic acids, proteins, and lipids necessary for rapid cellular proliferation. At the same time, c-Myc overexpression results in coordinated changes in level of expression of gene families which result in increased cellular proliferation. This interesting duality of c-Myc effects places it in the mainstream of transformational changes and gives it a very important role in regulating the “transformed phenotype.” The effects induced by c-Myc can occur either as a “primary oncogene” which is activated by amplification or translocation or as a downstream effect of other activated oncogenes. In either case, it appears that c-Myc plays a central role in sustaining the changes which occur with transformation. Although efforts to use c-Myc as a therapeutic target have been quite frustrating, it appears that this may change in the next few years. Clin Cancer Res; 18(20); 5546–53. ©2012 AACR.
IDH1andIDH2Mutations in Tumorigenesis: Mechanistic Insights and Clinical Perspectives
Authors: Yang Hui , Ye Dan , Guan Kun-Liang , Xiong Yue 
Published: October 2012

AbstractGenes encoding for isocitrate dehydrogenases 1 and 2, IDH1 and IDH2, are frequently mutated in multiple types of human cancer. Mutations targeting IDH1 and IDH2 result in simultaneous loss of their normal catalytic activity, the production of α-ketoglutarate (α-KG), and gain of a new function, the production of 2-hydroxyglutarate (2-HG). 2-HG is structurally similar to α-KG, and acts as an α-KG antagonist to competitively inhibit multiple α-KG–dependent dioxygenases, including both lysine histone demethylases and the ten-eleven translocation family of DNA hydroxylases. Abnormal histone and DNA methylation are emerging as a common feature of tumors with IDH1 and IDH2 mutations and may cause altered stem cell differentiation and eventual tumorigenesis. Therapeutically, unique features of IDH1 and IDH2 mutations make them good biomarkers and potential drug targets. Clin Cancer Res; 18(20); 5562–71. ©2012 AACR.
Combretastatin A-4 Phosphate Affects Tumor Vessel Volume and Size Distribution as Assessed Using MRI-Based Vessel Size Imaging
Authors: Nielsen Thomas , Bentzen Lise , Pedersen Michael , Tramm Trine , Rijken Paul F.J.W. , Bussink Johan , Horsman Michael R. , Østergaard Leif 
Published: October 2012

Abstract
Purpose: Combretastatin A-4 disodium phosphate (CA4P) is a promising vascular disrupting agent (VDA) in clinical trials. As CA4P acts on dividing endothelial cells, we hypothesize that CA4P affects vessels of certain sizes. The aim of this study was to evaluate the effect of CA4P by the MRI-based vessel size imaging (VSI).
Experimental Design: C3H mammary carcinomas were grown to 200 mm3 in the right rear foot of female CDF1 mice. A control group of mice received no treatment, and a treatment group had CA4P administered intraperitoneally at a dose of 250 mg/kg. VSI was conducted on a 3 Tesla MR scanner to estimate the tumor blood volume (ζ0) and mean vessel radius (R). Vascularization was also estimated histologically by endothelial and Hoechst 33342 staining.
Results: ζ 0 and R showed different spatial heterogeneity. Tumor median and quartile values of ζ0 were all significantly reduced by about 35% in the CA4P-treated group as compared with the control group, and the median and upper quartile of R were significantly increased. Histograms of ζ0 and R showed a general decrease in ζ0 following treatment, and values of R in a certain range (≈20–30 μm) were decreased in the treatment group. The drug-induced change in ζ0 was in agreement with histology and our previous dynamic contrast enhanced MRI (DCE-MRI) data.
Conclusions: Tumor blood volume and mean vessel radius showed a clear response following treatment with CA4P. VSI may prove valuable in estimation of tumor angiogenesis and prediction of response to VDAs. Clin Cancer Res; 18(23); 6469–77. ©2012 AACR.
SuperTAG Methylation-specific Digital Karyotyping Reveals Uremia-induced Epigenetic Dysregulation of Atherosclerosis-Related Genes
Authors: Zawada Adam M. , Rogacev Kyrill S. , Hummel Björn , Grün Oliver S. , Friedrich Annika , Rotter Björn , Winter Peter , Geisel Jürgen , Fliser Danilo , Heine Gunnar H. 
Published: October 2012

Background—
Accelerated atherosclerosis is a hallmark of chronic kidney disease (CKD). Although the role of epigenetic dysregulation in atherosclerosis is increasingly appreciated, only a few studies focused on epigenetics in CKD-associated cardiovascular disease, virtually all of which assessed epigenetic dysregulation globally. We hypothesized that gene-specific epigenetic dysregulation in CKD exists, affecting genes pertinent to inflammation and atherosclerosis.

Methods and Results—

Ten clinically stable patients undergoing hemodialysis therapy and 10 healthy age- and sex-matched controls were recruited. Genome-wide analysis of DNA methylation was performed by SuperTAG methylation-specific digital karyotyping, in order to identify genes differentially methylated in CKD. Analysis of 27 043 436 tags revealed 4288 genomic loci with differential DNA methylation (
P
<10
–10
) between hemodialysis patients and control subjects. Annotation of UniTags to promoter databases allowed us to identify 52 candidate genes associated with cardiovascular disease and 97 candidate genes associated with immune/infection diseases. These candidate genes could be classified to distinct proatherogenic processes, including lipid metabolism and transport (eg,
HMGCR
,
SREBF1
,
LRP5
,
EPHX2
, and
FDPS
), cell proliferation and cell-cycle regulation (eg,
MIK67
,
TP53
, and
ALOX12
), angiogenesis (eg,
ANGPT2
,
ADAMTS10
, and
FLT4
), and inflammation (eg,
TNFSF10
,
LY96
,
IFNGR1
,
HSPA1A
, and
IL12RB1
).

Conclusions—
We provide a comprehensive analysis of genome-wide epigenetic alterations in CKD, identifying candidate genes associated with proatherogenic and inflammatory processes. These results may spur further research in the field of epigenetics in kidney disease and point to new therapeutic strategies in CKD-associated atherosclerotic disease.
Cardiac Structural and Sarcomere Genes Associated With Cardiomyopathy Exhibit Marked Intolerance of Genetic Variation
Authors: Pan Stephen , Caleshu Colleen A. , Dunn Kyla E. , Foti Marcia J. , Moran Maura K. , Soyinka Oretunlewa , Ashley Euan A. 
Published: October 2012

Background—
The clinical significance of variants in genes associated with inherited cardiomyopathies can be difficult to determine because of uncertainty regarding population genetic variation and a surprising amount of tolerance of the genome even to loss-of-function variants. We hypothesized that genes associated with cardiomyopathy might be particularly resistant to the accumulation of genetic variation.

Methods and Results—

We analyzed the rates of single nucleotide genetic variation in all known genes from the exomes of >5000 individuals from the National Heart, Lung, and Blood Institute’s Exome Sequencing Project, as well as the rates of structural variation from the Database of Genomic Variants. Most variants were rare, with over half unique to 1 individual. Cardiomyopathy-associated genes exhibited a rate of nonsense variants, about 96.1% lower than other Mendelian disease genes. We tested the ability of
in silico
algorithms to distinguish between a set of variants in
MYBPC3
,
MYH7
, and
TNNT2
with strong evidence for pathogenicity and variants from the Exome Sequencing Project data. Algorithms based on conservation at the nucleotide level (genomic evolutionary rate profiling, PhastCons) did not perform as well as amino acid-level prediction algorithms (Polyphen-2, SIFT). Variants with strong evidence for disease causality were found in the Exome Sequencing Project data at prevalence higher than expected.

Conclusions—
Genes associated with cardiomyopathy carry very low rates of population variation. The existence in population data of variants with strong evidence for pathogenicity suggests that even for Mendelian disease genetics, a probabilistic weighting of multiple variants may be preferred over the single gene causality model.