bluuebunny/crossref_metadata_2025_split huggingface dataset:
Indexing for summary queries
Authors: Yi Ke , Wang Lu , Wei Zhewei 
Published: February 2014

Database queries can be broadly classified into two categories: reporting queries and aggregation queries. The former retrieves a collection of records from the database that match the query's conditions, while the latter returns an aggregate, such as count, sum, average, or max (min), of a particular attribute of these records. Aggregation queries are especially useful in business intelligence and data analysis applications where users are interested not in the actual records, but some statistics of them. They can also be executed much more efficiently than reporting queries, by embedding properly precomputed aggregates into an index.
However, reporting and aggregation queries provide only two extremes for exploring the data. Data analysts often need more insight into the data distribution than what those simple aggregates provide, and yet certainly do not want the sheer volume of data returned by reporting queries. In this article, we design indexing techniques that allow for extracting a statistical summary of all the records in the query. The summaries we support include frequent items, quantiles, and various sketches, all of which are of central importance in massive data analysis. Our indexes require linear space and extract a summary with the optimal or near-optimal query cost. We illustrate the efficiency and usefulness of our designs through extensive experiments and a system demonstration.
Pufferfish
Authors: Kifer Daniel , Machanavajjhala Ashwin 
Published: February 2014

In this article, we introduce a new and general privacy framework called Pufferfish. The Pufferfish framework can be used to create new privacy definitions that are customized to the needs of a given application. The goal of Pufferfish is to allow experts in an application domain, who frequently do not have expertise in privacy, to develop rigorous privacy definitions for their data sharing needs. In addition to this, the Pufferfish framework can also be used to study existing privacy definitions.
We illustrate the benefits with several applications of this privacy framework: we use it to analyze differential privacy and formalize a connection to attackers who believe that the data records are independent; we use it to create a privacy definition called hedging privacy, which can be used to rule out attackers whose prior beliefs are inconsistent with the data; we use the framework to define and study the notion of composition in a broader context than before; we show how to apply the framework to protect unbounded continuous attributes and aggregate information; and we show how to use the framework to rigorously account for prior data releases.
Approximating Markov Processes by Averaging
Authors: Chaput Philippe , Danos Vincent , Panangaden Prakash , Plotkin Gordon 
Published: February 2014

Normally, one thinks of probabilistic transition systems as taking an initial probability distribution over the state space into a new probability distribution representing the system after a transition. We, however, take a dual view of Markov processes as transformers of bounded measurable functions. This is very much in the same spirit as a “predicate-transformer” view, which is dual to the state-transformer view of transition systems. We redevelop the theory of labelled Markov processes from this viewpoint; in particular, we explore approximation theory. We obtain three main results.
(i) It is possible to define bisimulation on general measure spaces and show that it is an equivalence relation. The logical characterization of bisimulation can be done straightforwardly and generally.
(ii) A new and flexible approach to approximation based on averaging can be given. This vastly generalizes and streamlines the idea of using conditional expectations to compute approximations.
(iii) We show that there is a minimal process bisimulation-equivalent to a given process, and this minimal process is obtained as the limit of the finite approximants.
Distributed programming framework for fast iterative optimization in networked cyber-physical systems
Authors: Balani Rahul , Wanner Lucas F. , Srivastava Mani B. 
Published: February 2014

Large-scale coordination and control problems in cyber-physical systems are often expressed within the networked optimization model. While significant advances have taken place in optimization techniques, their widespread adoption in practical implementations has been impeded by the complexity of internode coordination and lack of programming support for the same. Currently, application developers build their own elaborate coordination mechanisms for synchronized execution and coherent access to shared resources via distributed and concurrent controller processes. However, they typically tend to be error prone and inefficient due to tight constraints on application development time and cost. This is unacceptable in many CPS applications, as it can result in expensive and often irreversible side-effects in the environment due to inaccurate or delayed reaction of the control system.
This article explores the design of a distributed shared memory (DSM) architecture that abstracts the details of internode coordination. It simplifies application design by transparently managing routing, messaging, and discovery of nodes for coherent access to shared resources. Our key contribution is the design of provably correct locality-sensitive synchronization mechanisms that exploit the spatial locality inherent in actuation to drive faster and scalable application execution through opportunistic data parallel operation. As a result, applications encoded in the proposed Hotline Application Programming Framework are error free, and in many scenarios, exhibit faster reactions to environmental events over conventional implementations.
Relative to our prior work, this article extends Hotline with a new locality-sensitive coordination mechanism for improved reaction times and two tunable iteration control schemes for lower message costs. Our extensive evaluation demonstrates that realistic performance and cost of applications are highly sensitive to the prevalent deployment, network, and environmental characteristics. This highlights the importance of Hotline, which provides user-configurable options to trivially tune these metrics and thus affords time to the developers for implementing, evaluating, and comparing multiple algorithms.
Querying Regular Graph Patterns
Authors: Barceló Pablo , Libkin Leonid , Reutter Juan L. 
Published: February 2014

Graph data appears in a variety of application domains, and many uses of it, such as querying, matching, and transforming data, naturally result in incompletely specified graph data, that is, graph patterns. While queries need to be posed against such data, techniques for querying patterns are generally lacking, and properties of such queries are not well understood.
Our goal is to study the basics of querying graph patterns. The key features of patterns we consider here are node and label variables and edges specified by regular expressions. We provide a classification of patterns, and study standard graph queries on graph patterns. We give precise characterizations of both data and combined complexity for each class of patterns. If complexity is high, we do further analysis of features that lead to intractability, as well as lower-complexity restrictions. Since our patterns are based on regular expressions, query answering for them can be captured by a new automata model. These automata have two modes of acceptance: one captures queries returning nodes, and the other queries returning paths. We study properties of such automata, and the key computational tasks associated with them. Finally, we provide additional restrictions for tractability, and show that some intractable cases can be naturally cast as instances of constraint satisfaction problems.
UTX and MLL4 Coordinately Regulate Transcriptional Programs for Cell Proliferation and Invasiveness in Breast Cancer Cells
Authors: Kim Jae-Hwan , Sharma Amrish , Dhar Shilpa S. , Lee Sung-Hun , Gu Bingnan , Chan Chia-Hsin , Lin Hui-Kuan , Lee Min Gyu 
Published: February 2014

Abstract
Histone methyltransferases and demethylases reversibly modulate histone lysine methylation, which is considered a key epigenetic mark associated with gene regulation. Recently, aberrant regulation of gene expression by histone methylation modifiers has emerged as an important mechanism for tumorigenesis. However, it remains largely unknown how histone methyltransferases and demethylases coregulate transcriptional profiles for cancer cell characteristics. Here, we show that in breast cancer cells, the histone H3 lysine 27 (H3K27) demethylase UTX (also known as KDM6A) positively regulates gene expression programs associated with cell proliferation and invasion. The majority of UTX-controlled genes, including a cohort of oncogenes and prometastatic genes, are coregulated by the H3K4 methyltransferase mixed lineage leukemia 4 (MLL4, also called ALR, KMT2D, and MLL2). UTX interacted with a C-terminal region of MLL4. UTX knockdown resulted in significant decreases in the proliferation and invasiveness of breast cancer cells in vitro and in a mouse xenograft model. Such defective cellular characteristics of UTX-depleted cells were phenocopied by MLL4 knockdown cells. UTX-catalyzed demethylation of trimethylated H3K27 and MLL4-mediated trimethylation at H3K4 occurred interdependently at cotarget genes of UTX and MLL4. Clinically, high levels of UTX or MLL4 were associated with poor prognosis in patients with breast cancer. Taken together, these findings uncover that coordinated regulation of gene expression programs by a histone methyltransferase and a histone demethylase is coupled to the proliferation and invasion of breast cancer cells. Cancer Res; 74(6); 1705–17. ©2014 AACR.
Positron Emission Tomography Imaging with 18F-Labeled ZHER2:2891 Affibody for Detection of HER2 Expression and Pharmacodynamic Response to HER2-Modulating Therapies
Authors: Trousil Sebastian , Hoppmann Susan , Nguyen Quang-Dé , Kaliszczak Maciej , Tomasi Giampaolo , Iveson Peter , Hiscock Duncan , Aboagye Eric O. 
Published: February 2014

Abstract
Purpose: Expression of HER2 has profound implications on treatment strategies in various types of cancer. We investigated the specificity of radiolabeled HER2-targeting ZHER2:2891 Affibody, [18F]GE-226, for positron emission tomography (PET) imaging.
Experimental Design: Intrinsic cellular [18F]GE-226 uptake and tumor-specific tracer binding were assessed in cells and xenografts with and without drug treatment. Specificity was further determined by comparing tumor localization of a fluorescently labeled analogue with DAKO HercepTest.
Results: [18F]GE-226 uptake was 11- to 67-fold higher in 10 HER2-positive versus HER2-negative cell lines in vitro independent of lineage. Uptake in HER2-positive xenografts was rapid with net irreversible binding kinetics making possible the distinction of HER2-negative [MCF7 and MCF7-p95HER2: NUV60 (%ID/mL) 6.1 ± 0.7; Ki (mL/cm3/min) 0.0069 ± 0.0014] from HER2-positive tumors (NUV60 and Ki: MCF7-HER2, 10.9 ± 1.5 and 0.015 ± 0.0035; MDA-MB-361, 18.2 ± 3.4 and 0.025 ± 0.0052; SKOV-3, 18.7 ± 2.4 and 0.036 ± 0.0065) within 1 hour. Tumor uptake correlated with HER2 expression determined by ELISA (r2 = 0.78), and a fluorophore-labeled tracer analogue colocalized with HER2 expression. Tracer uptake was not influenced by short-term or continuous treatment with trastuzumab in keeping with differential epitope binding, but reflected HER2 degradation by short-term NVP-AUY922 treatment in SKOV-3 xenografts (NUV60: 13.5 ± 2.1 %ID/mL vs. 9.0 ± 0.9 %ID/mL for vehicle or drug, respectively).
Conclusions: [18F]GE-226 binds with high specificity to HER2 independent of cell lineage. The tracer has potential utility for HER2 detection, irrespective of prior trastuzumab treatment, and to discern HSP90 inhibitor-mediated HER2 degradation. Clin Cancer Res; 20(6); 1632–43. ©2014 AACR.
Phase I Study of Oral Rigosertib (ON 01910.Na), a Dual Inhibitor of the PI3K and Plk1 Pathways, in Adult Patients with Advanced Solid Malignancies
Authors: Bowles Daniel W. , Diamond Jennifer R. , Lam Elaine T. , Weekes Colin D. , Astling David P. , Anderson Ryan T. , Leong Stephen , Gore Lia , Varella-Garcia Marileila , Vogler Brian W. , Keysar Stephen B. , Freas Elizabeth , Aisner Dara L. , Ren Chen , Tan Aik-Chook , Wilhelm Francois , Maniar Manoj , Eckhardt S. Gail , Messersmith Wells A. , Jimeno Antonio 
Published: February 2014

Abstract
Purpose: To determine the pharmacokinetics (PK), maximum tolerated dose (MTD), safety, and antitumor activity of an oral formulation of rigosertib, a dual phosphoinositide 3-kinase (PI3K) and polo-like kinase 1 (Plk1) pathway inhibitor, in patients with advanced solid malignancies.
Experimental Design: Patients with advanced solid malignancies received rigosertib twice daily continuously in 21-day cycles. Doses were escalated until intolerable grade ≥2 toxicities, at which point the previous dose level was expanded to define the MTD. All patients were assessed for safety, PK, and response. Urinary PK were performed at the MTD. Archival tumors were assessed for potential molecular biomarkers with multiplex mutation testing. A subset of squamous cell carcinomas (SCC) underwent exome sequencing.
Results: Forty-eight patients received a median of 2 cycles of therapy at 5 dose levels. Rigosertib exposure increased with escalating doses. Dose-limiting toxicities were hematuria and dysuria. The most common grade ≥2 drug-related toxicities involved urothelial irritation. The MTD is 560 mg twice daily. Activity was seen in head and neck SCCs (1 complete response, 1 partial response) and stable disease for ≥12 weeks was observed in 8 additional patients. Tumors experiencing ≥partial response had PI3K pathway activation, inactivated p53, and unique variants in ROBO3 and FAT1, two genes interacting with the Wnt/β-catenin pathway.
Conclusions: The recommended phase II dose of oral rigosertib is 560 mg twice daily given continuously. Urinary toxicity is the dose-limiting and most common toxicity. Alterations in PI3K, p53, and Wnt/β-catenin pathway signaling should be investigated as potential biomarkers of response in future trials. Clin Cancer Res; 20(6); 1656–65. ©2014 AACR.
Gramicidin A Blocks Tumor Growth and Angiogenesis through Inhibition of Hypoxia-Inducible Factor in Renal Cell Carcinoma
Authors: David Justin M. , Owens Tori A. , Inge Landon J. , Bremner Ross M. , Rajasekaran Ayyappan K. 
Published: February 2014

Abstract
Ionophores are hydrophobic organic molecules that disrupt cellular transmembrane potential by permeabilizing membranes to specific ions. Gramicidin A is a channel-forming ionophore that forms a hydrophilic membrane pore that permits the rapid passage of monovalent cations. Previously, we found that gramicidin A induces cellular energy stress and cell death in renal cell carcinoma (RCC) cell lines. RCC is a therapy-resistant cancer that is characterized by constitutive activation of the transcription factor hypoxia-inducible factor (HIF). Here, we demonstrate that gramicidin A inhibits HIF in RCC cells. We found that gramicidin A destabilized HIF-1α and HIF-2α proteins in both normoxic and hypoxic conditions, which in turn diminished HIF transcriptional activity and the expression of various hypoxia-response genes. Mechanistic examination revealed that gramicidin A accelerates O2-dependent downregulation of HIF by upregulating the expression of the von Hippel–Lindau (VHL) tumor suppressor protein, which targets hydroxylated HIF for proteasomal degradation. Furthermore, gramicidin A reduced the growth of human RCC xenograft tumors without causing significant toxicity in mice. Gramicidin A–treated tumors also displayed physiologic and molecular features consistent with the inhibition of HIF-dependent angiogenesis. Taken together, these results demonstrate a new role for gramicidin A as a potent inhibitor of HIF that reduces tumor growth and angiogenesis in VHL-expressing RCC. Mol Cancer Ther; 13(4); 788–99. ©2014 AACR.
Aspirin Use in Heart Failure
Authors: Bermingham Margaret , Shanahan Mary Katherine , O’Connell Eoin , Dawkins Ian , Miwa Saki , O’Hanlon Rory , Gilmer John , McDonald Kenneth , Ledwidge Mark 
Published: February 2014

Background—
Aspirin use in heart failure (HF) is controversial. The drug has proven benefit in comorbidities associated with HF; however, retrospective analysis of angiotensin-converting enzyme inhibitor trials and prospective comparisons with warfarin have shown increased risk of morbidity with aspirin use. This study aims to evaluate the association of low-dose aspirin with mortality and morbidity risk in a large community-based cohort.

Methods and Results—
This was a retrospective cohort study of patients attending an HF disease management program. Aspirin use at baseline and its association with mortality and HF hospitalization in the population was examined. Of 1476 patients (mean age, 70.4±12.4 years; 63% men), 892 (60.4%) were prescribed aspirin. Low-dose aspirin (75 mg/d) was prescribed to 828 (92.8%) patients. Median follow-up time was 2.6 (0.8–4.5) years. During the follow-up period, 464 (31.4%) patients died. In adjusted analysis, low-dose aspirin use was associated with reduced mortality risk compared with nonaspirin use (hazard ratio=0.58; 95% confidence interval, 0.46–0.74), and this was confirmed by a propensity-matched subgroup analysis. Low-dose aspirin use was associated with reduced risk of HF hospitalization compared with nonaspirin use in the total population (adjusted hazard ratio=0.70; 95% confidence interval, 0.54–0.90). In adjusted analysis, there was no difference in mortality or HF hospitalization between high-dose aspirin users (>75 mg/d) and nonaspirin users.

Conclusions—
In this study, low-dose aspirin therapy was associated with a significant reduction in mortality and morbidity risk during long-term follow-up. These results suggest that low-dose aspirin may have a continuing role in secondary prevention in HF and underline the need for more trials of low-dose aspirin use in HF.
Echocardiographic Assessment of Pulmonary Artery Systolic Pressure and Outcomes in Ambulatory Heart Failure Patients
Authors: Kalogeropoulos Andreas P. , Siwamogsatham Sarawut , Hayek Salim , Li Song , Deka Anjan , Marti Catherine N. , Georgiopoulou Vasiliki V. , Butler Javed 
Published: February 2014

Background

Pulmonary hypertension (
PH
) in patients with heart failure (
HF
) is associated with worse outcomes and is rapidly being recognized as a therapeutic target. To facilitate pragmatic research efforts, data regarding the prognostic importance of noninvasively assessed pulmonary artery systolic pressure (
PASP
) in stable ambulatory patients with
HF
are needed.

Methods and Results

We examined the association between echocardiographic
PASP
and outcomes in 417 outpatients with
HF
(age, 54±13 years; 60.7% men; 50.4% whites; 24.9% with preserved ejection fraction). Median
PASP
was 36 mm Hg (interquartile range [
IQR
]: 29, 46). After a median follow‐up of 2.6 years (
IQR
: 1.7, 3.9) there were 72 major events (57 deaths; 9 urgent heart transplants; and 6 ventricular assist device implantations) and 431 hospitalizations for
HF
. In models adjusting for clinical risk factors and therapy, a 10‐mm Hg higher
PASP
was associated with 37% higher risk (95%
CI
: 18, 59;
P
<0.001) for major events, and 11% higher risk (95%
CI
: 1, 23;
P
=0.039) for major events or
HF
hospitalization. The threshold that maximized the likelihood ratio for both endpoints was 48 mm Hg; those with
PASP
≥48 mm Hg (N=84; 20.1%) had an adjusted hazard ratio of 3.33 (95%
CI
: 1.96, 5.65;
P
<0.001) for major events and 1.47 (95%
CI
: 1.02, 2.11;
P
=0.037) for major events or
HF
hospitalization. Reduced right ventricular systolic function had independent prognostic utility over
PASP
for adverse outcomes. Right atrial pressure and transtricuspid gradient both contributed to risk.

Conclusions

Elevated
PASP
, determined by echocardiography, identifies ambulatory patients with
HF
at increased risk for adverse events.
A Modern Paradise
Authors: Mollett Sharlene 
Published: February 2014

On the Honduran North Coast, the Afro-indigenous Garifuna struggle to maintain access to and control of their ancestral lands. Their concerns are due in part to the Honduran state’s long-standing goal of modernizing the North Coast and providing an attractive site for foreign investment in land and tourism. The state’s commitment to improving the country’s development profile by opening coastal land ownership to foreigners often overlooks international and constitutional recognition of communal forms of land tenure. Ethnographic participant observation in the Garifuna community of Tornabé, a fishing and farming village in the Tela Bay region, supplemented by semistructured interviews, historical data collection, discourse analysis, and research on agrarian and environmental policy, suggests that Garifuna displacement is a product of the state’s development imaginaries, which racialize the Garifuna as backward and consider their blackness redeemable only by their labor. En la costa norte de Honduras, los garífunas afro-indígenas luchan por mantener el acceso a y control de sus tierras ancestrales. Sus preocupaciones se deben en parte a la meta de largo plazo del estado hondureño por modernizar la costa norte y hacerla atractiva a la inversión extranjera en tierras y turismo. El compromiso del estado por mejorar el perfil de desarrollo del país accediendo a que exista propiedad extranjera en la región costeña a menudo ignora el reconocimiento constitucional e internacional de formas comunales de tenencia de la tierra. Observación etnográfica participante en la comunidad garífuna de Tornabé, una aldea de pescadores y agricultores en la región de Bahía de Tela, complementada con entrevistas semi-estructuradas, recopilación de datos históricos, análisis del discurso e investigación sobre política agraria y ambiental, sugiere que el desplazamiento forzado garífuna es un producto de imaginarios de desarrollo estatales que los racializan como retrógradas y consideran que su negrura sólo es redimible a través de su trabajo.
Endoscopic Reconstruction of Surgically Created Skull Base Defects: A Systematic Review
Authors: Soudry Ethan , Turner Justin H. , Nayak Jayakar V. , Hwang Peter H. 
Published: February 2014

ObjectivesTo systematically review the literature concerning techniques of closure of endoscopically created skull base defects based on site of skull base defect and flow rate of cerebrospinal fluid (CSF).Data SourcesPubMed, SCOPUS, and Cochrane databases.Review MethodsA comprehensive systematic literature review.ResultsThe literature search produced a total of 1708 studies. Of these, 1585 studies were excluded based on title and/or abstract review. A total of 123 articles remained for full‐text review, 101 of which were subsequently excluded primarily because of lack of detailed information as to the reconstructive techniques used or clinical outcomes. Of the 22 studies remaining for final analysis, all were case series. A total of 673 patients were included in the analysis, with an overall postoperative CSF leak rate of 8.5%. Subgroup analysis was performed based on location of the skull base defect and presence and quality of intraoperative CSF leak.ConclusionsBased on level 4 evidence, in cases of low‐flow intraoperative CSF leaks, skull base reconstruction with multilayered free grafts and synthetic materials offers similar outcomes to vascularized flaps. In cases of high‐flow intraoperative CSF leaks, pedicled vascularized flaps appear to be superior. Location of the defect does not seem to be a significant factor in determining successful closure, with the exception of clival defects. In all other sites, good closure may be achieved by multiple reconstructive approaches. More consistency in data reporting and higher levels of evidence will ultimately be necessary to make definitive recommendations.