bluuebunny/crossref_metadata_2025_split huggingface dataset:
A first look at cellular machine-to-machine traffic
Authors: Shafiq Muhammad Zubair , Ji Lusheng , Liu Alex X. , Pang Jeffrey , Wang Jia 
Published: July 2012

Cellular network based Machine-to-Machine (M2M) communication is fast becoming a market-changing force for a wide spectrum of businesses and applications such as telematics, smart metering, point-of-sale terminals, and home security and automation systems. In this paper, we aim to answer the following important question: Does traffic generated by M2M devices impose new requirements and challenges for cellular network design and management? To answer this question, we take a first look at the characteristics of M2M traffic and compare it with traditional smartphone traffic. We have conducted our measurement analysis using a week-long traffic trace collected from a tier-1 cellular network in the United States. We characterize M2M traffic from a wide range of perspectives, including temporal dynamics, device mobility, application usage, and network performance.
Our experimental results show that M2M traffic exhibits significantly different patterns than smartphone traffic in multiple aspects. For instance, M2M devices have a much larger ratio of uplink to downlink traffic volume, their traffic typically exhibits different diurnal patterns, they are more likely to generate synchronized traffic resulting in bursty aggregate traffic volumes, and are less mobile compared to smartphones. On the other hand, we also find that M2M devices are generally competing with smartphones for network resources in co-located geographical regions. These and other findings suggest that better protocol design, more careful spectrum allocation, and modified pricing schemes may be needed to accommodate the rise of M2M devices.
Understanding performance anomalies of SSDs and their impact in enterprise application environment
Authors: Hu Jian , Jiang Hong , Manden Prakash 
Published: July 2012

SSD is known to have the erase-before-write and out-of-place update properties. When the number of invalidated pages is more than a given threshold, a process referred to as garbage collection (GC) is triggered to erase blocks after valid pages in these blocks are copied somewhere else. GC degrades both the performance and lifetime of SSD significantly because of the read-write-erase operation sequence.
In this paper, we conduct intensive experiments on a 120GB Intel 320 SATA SSD and a 320GB Fusion IO ioDrive PCI-E SSD to show and analyze the following important performance issues and anomalies.
The commonly accepted knowledge that the performance drops sharply as more data is being written is not always true. This is because GC efficiency, a more important factor affecting SSD performance, has not been carefully considered. It is defined as the percentage of invalid pages of a GC erased block. It is possible to avoid the performance degradation by managing the addressable LBA range.
Estimating the residual lifetime of an SSD is a very challenging problem because it involves several interdependent and mutually interacting factors such as FTL, GC, wear leveling, workload characteristics, etc. We develop an analytical model to estimate the residual lifetime of a given SSD.
The high random-read performance is widely accepted as one of the advantages of SSD. We will show that this is not true if the GC efficiency is low.
HSP90 Inhibitor 17-AAG Selectively Eradicates Lymphoma Stem Cells
Authors: Newman Bryan , Liu Yan , Lee Hsiu-Fang , Sun Duxin , Wang Yin 
Published: July 2012

Abstract
Cancer stem cells (CSC; also called tumor-initiating cells) comprise tumor cell subpopulations that preserve the properties of quiescence, self-renewal, and differentiation of normal stem cells. In addition, CSCs are therapeutically important because of their key contributions toward drug resistance. The hypoxia-inducible transcription factor HIF1α is critical for CSC maintenance in mouse lymphoma. In this study, we showed that low concentrations of the HSP90 inhibitor 17-AAG eliminate lymphoma CSCs in vitro and in vivo by disrupting the transcriptional function of HIF1α, a client protein of HSP90. 17-AAG preferentially induced apoptosis and eliminated the colony formation capacity of mouse lymphoma CSCs and human acute myeloid leukemia (AML) CSCs. However, low concentrations of 17-AAG failed to eliminate highly proliferative lymphoma and AML cells (non-CSCs), in which the AKT-GSK3 signaling pathway is constitutively active. The heat shock transcription factor HSF1 is highly expressed in non-CSCs, but it was weakly expressed in lymphoma CSCs. However, siRNA-mediated attenuation of HSF1 abrogated the colony formation ability of both lymphoma and AML CSCs. This study supports the use of 17-AAG as a CSC targeting agent and, in addition, shows that HSF1 is an important target for elimination of both CSCs and non-CSCs in cancer. Cancer Res; 72(17); 4551–61. ©2012 AACR.
Strain-Specific Variation in Murine Natural Killer Gene Complex Contributes to Differences in Immunosurveillance for Urethane-Induced Lung Cancer
Authors: Kreisel Daniel , Gelman Andrew E. , Higashikubo Ryuji , Lin Xue , Vikis Haris G. , White J. Michael , Toth Kelsey A. , Deshpande Charuhas , Carreno Beatriz M. , You Ming , Taffner Samantha M. , Yokoyama Wayne M. , Bui Jack D. , Schreiber Robert D. , Krupnick Alexander S. 
Published: July 2012

Abstract
Non–small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide and results from a complex interaction between carcinogen exposure and inherent susceptibility. Despite its prevalence, genetic factors that predispose to the development of lung cancer remain elusive. Inbred mouse models offer a unique and clinically relevant tool to study genetic factors that contribute to lung carcinogenesis due to the development of tumors that resemble human adenocarcinoma and broad strain-specific variation in cancer incidence after carcinogen administration. Here, we set out to investigate whether strain-specific variability in tumor immunosurveillance contributes to differences in lung cancer. Using bone marrow transplantation, we determined that hematopoietic cells from lung cancer–resistant mice could significantly impede the development of cancer in a susceptible strain. Furthermore, we show that this is not due to differences in tumor-promoting inflammatory changes or variability in immunosurveillance by the adaptive immune system but results from strain-specific differences in natural killer (NK) cell cytotoxicity. Using a newly discovered congenic strain of mice, we show a previously unrecognized role for strain-specific polymorphisms in the natural killer gene complex (NKC) in immunosurveillance for carcinogen-induced lung cancer. Because polymorphisms in the NKC are highly prevalent in man, our data may explain why certain individuals without obvious risk factors develop lung cancer whereas others remain resistant to the disease despite heavy environmental carcinogen exposure. Cancer Res; 72(17); 4311–7. ©2012 AACR.
Copper Chelation Enhances Antitumor Efficacy and Systemic Delivery of Oncolytic HSV
Authors: Yoo Ji Young , Pradarelli Jason , Haseley Amy , Wojton Jeffrey , Kaka Azeem , Bratasz Anna , Alvarez-Breckenridge Christopher A. , Yu Jun-Ge , Powell Kimerly , Mazar Andrew P. , Teknos Theodoros N. , Chiocca E. Antonio , Glorioso Joseph C. , Old Matthew , Kaur Balveen 
Published: July 2012

Abstract
Purpose: Copper in serum supports angiogenesis and inhibits replication of wild-type HSV-1. Copper chelation is currently being investigated as an antiangiogenic and antineoplastic agent in patients diagnosed with cancer. Herpes simplex virus–derived oncolytic viruses (oHSV) are being evaluated for safety and efficacy in patients, but several host barriers limit their efficacy. Here, we tested whether copper inhibits oHSV infection and replication and whether copper chelation would augment therapeutic efficacy of oHSV.
Experimental Design: Subcutaneous and intracranial tumor-bearing mice were treated with oHSV ± ATN-224 to evaluate tumor burden and survival. Virus replication and cell killing was measured in the presence or absence of the copper chelating agent ATN-224 and in the presence or absence of copper in vitro. Microvessel density and changes in perfusion were evaluated by immunohistochemistry and dynamic contrast enhanced MRI (DCE-MRI). Serum stability of oHSV was measured in mice fed with ATN-224. Tumor-bearing mice were injected intravenously with oHSV; tumor burden and amount of virus in tumor tissue were evaluated.
Results: Combination of systemic ATN-224 and oHSV significantly reduced tumor growth and prolonged animal survival. Immunohistochemistry and DCE-MRI imaging confirmed that ATN-224 reduced oHSV-induced blood vessel density and vascular leakage. Copper at physiologically relevant concentrations inhibited oHSV replication and glioma cell killing, and this effect was rescued by ATN-224. ATN-224 increased serum stability of oHSV and enhanced the efficacy of systemic delivery.
Conclusion: This study shows that combining ATN-224 with oHSV significantly increased serum stability of oHSV and greatly enhanced its replication and antitumor efficacy. Clin Cancer Res; 18(18); 4931–41. ©2012 AACR.
BRCA2 Deep Intronic Mutation Causing Activation of a Cryptic Exon: Opening toward a New Preventive Therapeutic Strategy
Authors: Anczuków Olga , Buisson Monique , Léoné Mélanie , Coutanson Christine , Lasset Christine , Calender Alain , Sinilnikova Olga M. , Mazoyer Sylvie 
Published: July 2012

Abstract
Purpose: Diagnostic screening of the BRCA1/2 genes in breast cancer families is mostly done on genomic DNA. For families with a very strong family history and no mutation identified in the coding sequences or the exon–intron boundaries, BRCA1/2 transcripts' analysis is an efficient approach to uncover gene inversion and pre-mRNA splicing defaults missed by conventional DNA-based protocols.
Experimental Design: We analyzed RNA from patients of negative BRCA families by reverse transcriptase PCR and identified an insertion in one family that we characterized by sequencing and by using a minigene splicing assay. More than 2,000 additional BRCA1/2 negative families were subsequently screened for this mutation using a dedicated PCR approach.
Results: Nine families were found to harbor a BRCA2 mutant transcript containing a 95-nucleotide cryptic exon between exons 12 and 13. This cryptic exon results from a new mutation located deep into intron 12, c.6937+594T &gt; G, which reinforces the strength of a preexisting 5′ splice site, turning it into a perfect consensus sequence. It is systematically included in transcripts produced by the mutant allele in cells from mutation carriers or produced by a mutant splicing reporter minigene. The inclusion of the cryptic exon was prevented when we cotransfected the minigene with antisense oligonucleotides complementary to the 3′ or mutated 5′ splice sites.
Conclusion: This first deep intronic BRCA mutation emphasizes the importance of analyzing RNA to provide comprehensive BRCA1/2 diagnostic tests and opens the possibility of using antisense therapy in the future as an alternative strategy for cancer prevention. Clin Cancer Res; 18(18); 4903–9. ©2012 AACR.
Killing of Kras-Mutant Colon Cancer Cells via Rac-Independent Actin Remodeling by the βGBP Cytokine, a Physiological PI3K Inhibitor Therapeutically Effective In Vivo
Authors: Mallucci Livio , Shi Dong-yun , Davies Derek , Jordan Peter , Nicol Alastair , Lotti Lavinia , Mariani-Costantini Renato , Verginelli Fabio , Wells Valerie , Zicha Daniel 
Published: July 2012

Abstract
Activating mutations in Kras are the most frequent mutations in human cancer. They define a subset of patients who do not respond to current therapies and for whom prognosis is poor. Oncogenic Kras has been shown to deregulate numerous signaling pathways of which the most intensively studied are the Ras/extracellular signal–regulated kinase cascade and the phosphoinositide 3-kinase (PI3K)/Akt cascade. However, to date, there are no effective targeted therapies in the clinic against Kras-mutant cancers. Here, we report that the β-galactoside–binding protein (βGBP) cytokine, a physiologic inhibitor of class I PI3Ks, is a potent activator of apoptosis in Kras-mutant colorectal cancer cells, even when coharboring mutant-activated PIK3CA. Our study unveils an elective route to intrinsic and extrinsic apoptosis, which involves the cytoskeleton. Early events are inhibition of PI3K activity and Rac-independent actin rearrangement assignable to phosphoinositide changes at the plasma membrane. Cyclin E deregulation, arrest of DNA synthesis, and checkpoint kinase 2 activation underscore events critical to the activation of an intrinsic apoptotic program. Clustering of CD95/Fas death receptors underscore events critical to the activation of extrinsic apoptosis. In nude mice, we present the first evidence that xenograft tumor development is strongly inhibited by Hu-r-βGBP. Taken together, our results open a new therapeutic opportunity to a subset of patients refractive to current treatments. This first demonstration of therapeutic efficacy against Kras-mutant colon cancer suggests that Hu-r-βGBP may also be therapeutically effective against other cancers harboring activating Ras mutations as well as PIK3CA mutations. Mol Cancer Ther; 11(9); 1884–93. ©2012 AACR.
Induction of the Transcriptional Repressor ZBTB4 in Prostate Cancer Cells by Drug-Induced Targeting of MicroRNA-17-92/106b-25 Clusters
Authors: Kim KyoungHyun , Chadalapaka Gayathri , Pathi Satya S. , Jin Un-Ho , Lee Ju-Seog , Park Yun-Yong , Cho Sung-Gook , Chintharlapalli Sudhakar , Safe Stephen 
Published: July 2012

Abstract
Androgen-insensitive DU145 and PC3 human prostate cancer cells express high levels of specificity protein (Sp) transcription factors Sp1, Sp3, and Sp4, and treatment of cells with methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate (CDODA-Me) inhibited cell growth and downregulated Sp1, Sp3, and Sp4 expression. CDODA-Me (15 mg/kg/d) was a potent inhibitor of tumor growth in a mouse xenograft model (PC3 cells) and also decreased expression of Sp transcription factors in tumors. CDODA-Me–mediated downregulation of Sp1, Sp3, and Sp4 was due to induction of the transcriptional repressor ZBTB4, which competitively binds and displaces Sp transcription factors from GC-rich sites in Sp1-, Sp3-, Sp4-, and Sp-regulated gene promoters. ZBTB4 levels are relatively low in DU145 and PC3 cells due to suppression by miR paralogs that are members of the miR-17-92 (miR-20a/17-5p) and miR-106b-25 (miR-106b/93) clusters. Examination of publically available prostate cancer patient array data showed an inverse relationship between ZBTB4 and miRs-20a/17-5p/106b/93 expression, and increased ZBTB4 in patients with prostate cancer was a prognostic factor for increased survival. CDODA-Me induces ZBTB4 in prostate cancer cells through disruption of miR–ZBTB4 interactions, and this results in downregulation of pro-oncogenic Sp transcription factors and Sp-regulated genes. Mol Cancer Ther; 11(9); 1852–62. ©2012 AACR.
Genetic Variation That Predicts Platinum Sensitivity Reveals the Role of miR-193b* in Chemotherapeutic Susceptibility
Authors: Ziliak Dana , Gamazon Eric R. , LaCroix Bonnie , Kyung Im Hae , Wen Yujia , Huang Rong Stephanie 
Published: July 2012

Abstract
Platinum agents are the backbone of cancer chemotherapy. Recently, we identified and replicated the role of a single nucleotide polymorphism (SNP, rs1649942) in predicting platinum sensitivity both in vitro and in vivo. Using the CEU samples from the International HapMap Project, we found the same SNP to be a master regulator of multiple gene expression phenotypes, prompting us to investigate whether rs1649942-mediated regulation of miRNAs may in part contribute to variation in platinum sensitivity. To these ends, 60 unrelated HapMap CEU I/II samples were used for our discovery-phase study using high-throughput genome-wide miRNA and gene expression profiling. Examining the relationships among rs1649942, its gene expression targets, genome-wide miRNA expression, and cellular sensitivity to carboplatin and cisplatin, we identified 2 platinum-associated miRNAs (miR-193b* and miR-320) that inhibit the expression of 5 platinum-associated genes (CRIM1, IFIT2, OAS1, KCNMA1, and GRAMD1B). We further replicated the relationship between the expression of miR-193b*, CRIM1, IFIT2, KCNMA1, and GRAMD1B, and platinum sensitivity in a separate HapMap CEU III dataset. We then showed that overexpression of miR-193b* in a randomly selected HapMap cell line results in resistance to both carboplatin and cisplatin. This relationship was also found in 7 ovarian cancer cell lines from NCI60 dataset and confirmed in an OVCAR-3 that overexpression of miR-193b* leads to increased resistance to carboplatin. Our findings highlight a potential mechanism of action for a previously observed genotype-survival outcome association. Further examination of miR-193b* in platinum sensitivity in ovarian cancer is warranted. Mol Cancer Ther; 11(9); 2054–61. ©2012 AACR.
The Hedgehog Receptor Patched Functions in Multidrug Transport and Chemotherapy Resistance
Authors: Bidet Michel , Tomico Amandine , Martin Patrick , Guizouarn Hélène , Mollat Patrick , Mus-Veteau Isabelle 
Published: July 2012

Abstract
Most anticancer drugs fail to eradicate tumors, leading to the development of drug resistance and disease recurrence. The Hedgehog signaling plays a crucial role during embryonic development, but is also involved in cancer development, progression, and metastasis. The Hedgehog receptor Patched (Ptc) is a Hedgehog signaling target gene that is overexpressed in many cancer cells. Here, we show a link between Ptc and resistance to chemotherapy, and provide new insight into Ptc function. Ptc is cleared from the plasma membrane upon interaction with its ligand Hedgehog, or upon treatment of cells with the Hedgehog signaling antagonist cyclopamine. In both cases, after incubation of cells with doxorubicin, a chemotherapeutic agent that is used for the clinical management of recurrent cancers, we observed an inhibition of the efflux of doxorubicin from Hedgehog-responding fibroblasts, and an increase of doxorubicin accumulation in two different cancer cell lines that are known to express aberrant levels of Hedgehog signaling components. Using heterologous expression system, we stringently showed that the expression of human Ptc conferred resistance to growth inhibition by several drugs from which chemotherapeutic agents such as doxorubicin, methotrexate, temozolomide, and 5-fluorouracil. Resistance to doxorubicin correlated with Ptc function, as shown using mutations from Gorlin's syndrome patients in which the Ptc-mediated effect on Hedgehog signaling is lost. Our results show that Ptc is involved in drug efflux and multidrug resistance, and suggest that Ptc contributes to chemotherapy resistance of cancer cells. Mol Cancer Res; 10(11); 1496–508. ©2012 AACR.
Quantitative Analysis of Isolation Area and Rhythm Outcome in Patients With Paroxysmal Atrial Fibrillation After Circumferential Pulmonary Vein Antrum Isolation Using the Pace-and-Ablate Technique
Authors: Kiuchi Kunihiko , Kircher Simon , Watanabe Norikazu , Gaspar Thomas , Rolf Sascha , Arya Arash , Piorkowski Christopher , Hindricks Gerhard , Sommer Philipp 
Published: July 2012

Background—
We sought to determine the relationship between the size of the left atrial isolated surface area (ISA) after pulmonary vein antrum isolation for paroxysmal atrial fibrillation (AF) and rhythm outcome during a 12-month follow-up.

Methods and Results—

One hundred one consecutive patients with paroxysmal AF (mean age, 59±11 years; median [range] AF history, 36 [24–96] months; mean left atrial size, 42±6 mm) were enrolled. The ISA was defined as the ratio of the total isolated antral surface area excluding the pulmonary veins to the sum of the total isolated antral surface area and the left atrial posterior wall surface area, while considering the individual characteristics of antral anatomy. All surface areas were assessed using the NavX system. Patients were divided into 4 groups according to ISA (group I: <50%; group II: 50 to <60%; group III: 60 to <70%; group IV: ≥70%). The average ISA for all patients was 59.2±11.6%. Subgroup analysis showed that ISA was 42.8±4.2% in group I (n=23), 54.2±3.0% in group II (n=23), 64.3±3.0% in group III (n=33), and 73.9±3.6% in group IV (n=22). After a 12-month follow-up period, 70% of patients in group I, 78% in group II, 97% in group III, and 100% in group IV were free from AF and atrial macroreentrant tachycardia. There was a significant difference between groups I and III, I and IV, II and III, and II and IV but not groups I and II and groups III and IV (log-rank test
P
=0.024, 0.016, 0.037, 0.044, 0.584, and 0.500, respectively). Receiver operating characteristic curve analysis yielded an optimal cutoff value of 55% for ISA.

Conclusions—
After 12 months, a larger ISA was associated with a significantly lower AF and macroreentrant tachycardia recurrence rate. ISA≥55% may thus serve as a predictor for long-term success after pulmonary vein antrum isolation.
Sialendoscopy in the Diagnosis and Treatment of Sialolithiasis
Authors: Zenk Johannes , Koch Michael , Klintworth Nils , König Barbara , Konz Katharina , Gillespie M. Boyd , Iro Heinrich 
Published: July 2012

ObjectiveSialendoscopy and other gland‐preserving techniques such as extracorporeal shockwave lithotripsy (ESWL), transoral stone removal, and combinations of these methods have fundamentally changed the therapeutic approach to salivary stones. Since 2003, all patients presenting with sialolithiasis have been diagnosed and treated with the same algorithm and routine salivary gland endoscopy (SGE).Study DesignCase series with chart review of patients with sialolithiasis treated between 2003 and 2008 using an algorithm for gland preservation.SettingTertiary referral academic medical center.Subjects and MethodsA total of 1154 patients with suspected sialolithiasis were identified and reviewed. Factors analyzed included stone location, size, surgical method, rate of stone clearance, complications, and rate of short‐ and long‐term symptom resolution. Successful treatment was defined as freedom from symptoms at follow‐up.ResultsDiagnostic sialendoscopy confirmed 221 parotid stones and 812 submandibular stones, of which 206 and 736, respectively, were treated. Transoral stone removal was the most frequently used method to remove submandibular stones (92%), with a smaller percentage able to be removed by SGE alone (5%) with long‐term success rates ≥90%. Only 4% (29/736) required submandibular gland removal. Parotid stones were removed by SGE (22%), combined SGE and incisional technique (26%), or ESWL (52%), with long‐term success rates of 98%, 89%, and 79%, respectively. Only 8 of 206 (4%) patients eventually required parotidectomy.ConclusionSalivary gland endoscopy is an important diagnostic and therapeutic tool in the management of sialolithiasis but must be combined with additional techniques to ensure a high rate of stone clearance, symptom resolution, and gland preservation.