bluuebunny/crossref_metadata_2025_split huggingface dataset:
Online privacy; replicating research results
Authors: Reed Daniel , Chi Ed H. 
Published: September 2012

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Daniel Reed offers three ideas about the future of personal online information management. Ed H. Chi writes about replication of experiments and how experiments are often the beginning, rather than the end, of a scientific inquiry.
The only constant is change
Authors: Xie Di , Ding Ning , Hu Y. Charlie , Kompella Ramana 
Published: September 2012

In multi-tenant datacenters, jobs of different tenants compete for the shared datacenter network and can suffer poor performance and high cost from varying, unpredictable network performance. Recently, several virtual network abstractions have been proposed to provide explicit APIs for tenant jobs to specify and reserve virtual clusters (VC) with both explicit VMs and required network bandwidth between the VMs. However, all of the existing proposals reserve a fixed bandwidth throughout the entire execution of a job.
In the paper, we first profile the traffic patterns of several popular cloud applications, and find that they generate substantial traffic during only 30%-60% of the entire execution, suggesting existing simple VC models waste precious networking resources. We then propose a fine-grained virtual network abstraction, Time-Interleaved Virtual Clusters (TIVC), that models the time-varying nature of the networking requirement of cloud applications. To demonstrate the effectiveness of TIVC, we develop Proteus, a system that implements the new abstraction. Using large-scale simulations of cloud application workloads and prototype implementation running actual cloud applications, we show the new abstraction significantly increases the utilization of the entire datacenter and reduces the cost to the tenants, compared to previous fixed-bandwidth abstractions.
CarSpeak
Authors: Kumar Swarun , Shi Lixin , Ahmed Nabeel , Gil Stephanie , Katabi Dina , Rus Daniela 
Published: September 2012

This paper introduces CarSpeak, a communication system for autonomous driving. CarSpeak enables a car to query and access sensory information captured by other cars in a manner similar to how it accesses information from its local sensors. CarSpeak adopts a content-centric approach where information objects -- i.e., regions along the road -- are first class citizens. It names and accesses road regions using a multi-resolution system, which allows it to scale the amount of transmitted data with the available bandwidth. CarSpeak also changes the MAC protocol so that, instead of having nodes contend for the medium, contention is between road regions, and the medium share assigned to any region depends on the number of cars interested in that region.
CarSpeak is implemented in a state-of-the-art autonomous driving system and tested on indoor and outdoor hardware testbeds including an autonomous golf car and 10 iRobot Create robots. In comparison with a baseline that directly uses 802.11, CarSpeak reduces the time for navigating around obstacles by 2.4x, and reduces the probability of a collision due to limited visibility by 14x.
Basal but not Luminal Mammary Epithelial Cells Require PI3K/mTOR Signaling for Ras-Driven Overgrowth
Authors: Plichta Kristin A. , Mathers Jessica L. , Gestl Shelley A. , Glick Adam B. , Gunther Edward J. 
Published: September 2012

Abstract
The mammary ducts of humans and mice are comprised of two main mammary epithelial cell (MEC) subtypes: a surrounding layer of basal MECs and an inner layer of luminal MECs. Breast cancer subtypes show divergent clinical behavior that may reflect properties inherent in their MEC compartment of origin. How the response to a cancer-initiating genetic event is shaped by MEC subtype remains largely unexplored. Using the mouse mammary gland, we designed organotypic three-dimensional culture models that permit challenge of discrete MEC compartments with the same oncogenic insult. Mammary organoids were prepared from mice engineered for compartment-restricted coexpression of oncogenic H-RASG12V together with a nuclear fluorescent reporter. Monitoring of H-RASG12V-expressing MECs during extended live cell imaging permitted visualization of Ras-driven phenotypes via video microscopy. Challenging either basal or luminal MECs with H-RASG12V drove MEC proliferation and survival, culminating in aberrant organoid overgrowth. In each compartment, Ras activation triggered modes of collective MEC migration and invasion that contrasted with physiologic modes used during growth factor–initiated branching morphogenesis. Although basal and luminal Ras activation produced similar overgrowth phenotypes, inhibitor studies revealed divergent use of Ras effector pathways. Blocking either the phosphoinositide 3-kinase or the mammalian target of rapamycin pathway completely suppressed Ras-driven invasion and overgrowth of basal MECs, but only modestly attenuated Ras-driven phenotypes in luminal MECs. We show that MEC subtype defines signaling pathway dependencies downstream of Ras. Thus, cells-of-origin may critically determine the drug sensitivity profiles of mammary neoplasia. Cancer Res; 72(22); 5856–66. ©2012 AACR.
Inactivation of the Dlc1 Gene Cooperates with Downregulation of p15INK4b and p16Ink4a, Leading to Neoplastic Transformation and Poor Prognosis in Human Cancer
Authors: Qian Xiaolan , Durkin Marian E. , Wang Dunrui , Tripathi Brajendra K. , Olson Lyra , Yang Xu-Yu , Vass William C. , Popescu Nicholas C. , Lowy Douglas R. 
Published: September 2012

Abstract
The tumor suppressor gene deleted in liver cancer-1 (DLC1), which encodes a protein with strong RhoGAP (GTPase activating protein) activity and weak Cdc42GAP activity, is inactivated in various human malignancies. Following Dlc1 inactivation, mouse embryo fibroblasts (MEF) with a conditional Dlc1 knockout allele reproducibly underwent neoplastic transformation. In addition to inactivation of Dlc1 and increased activity of Rho and Cdc42, transformation depended on the subsequent decreased expression of the Cdk4/6 inhibitors p15Ink4b and p16Ink4a together with increased expression and activation of Cdk4/6. The level of expression of these cell-cycle regulatory genes was relevant to human tumors with low DLC1 expression. Analysis of publicly available annotated datasets of lung and colon cancer with gene expression microarray profiles indicated that, in pairwise comparisons, low DLC1 expression occurred frequently together (P &lt; 0.01) with downregulation of p15Ink4b or p16Ink4a or upregulation of CDK4 or CDK6. In addition, an unfavorable prognosis (P &lt; 0.05) was associated with low DLC1 and low p15Ink4b in lung cancer and colon cancer, low DLC1 and low p16Ink4a in lung cancer, low DLC1 and high CDK4 in lung cancer, and low DLC1 and high CDK6 in colon cancer. Thus, several genes and biochemical activities collaborate with the inactivation of DLC1 to give rise to cell transformation in MEFs, and the identified genes are relevant to human tumors with low DLC1 expression. Cancer Res; 72(22); 5900–11. ©2012 AACR.
Decent citizenship, justice and trust as cornerstones of legitimation: tensions between generations in Finland
Authors: Salminen Ari , Lähdesmäki Kirsi , Ikola-Norrbacka Rinna 
Published: September 2012

The aim of this article is to analyze ethical issues related to the problem of legitimation. The article discusses the tensions of legitimation in light of three ethical topics: decent citizenship, trust, and justice and equality. Citizens’ assessments of ethics and tensions of legitimation are described and discussed in the context of Finnish society. Special attention is paid to the question of whether generational gaps matter. Are the perceptions of the three different generations (age-groups) distinctive and can these perceptions be explained by the gap between generations? The results of this study show that there are ethical considerations where the generation seems to make a difference. The youth, in particular, differ very significantly in their attitudes and opinions from the other two age-groups. Thus explanations based on the generational factor have proven relatively strong. The differences between the generations were evident in many ethical statements which are presented in more detail in the article. The empirical evidence of the study is based on two large batches of empirical data. Both are surveys implemented in Finland in 2008 and 2009. The first one is a citizen survey of 5000 Finnish citizens. The second survey is a youth survey of 1130 Finnish school students. Points for practitioners The article will be of interest to practitioners in describing Finnish citizens’ current perceptions about such ethical issues as decent citizenship, justice and equality as well as trust. The study reveals the differences in ethical valuations between the three age-groups. The article also provides a theoretical framework which can help in understanding tensions of legitimation through chosen ethical values.
On bureaucratic centre formation in government institutions: lessons from the European Commission
Authors: Trondal Jarle 
Published: September 2012

Identifying and explaining bureaucratic centre formation within government institutions – such as the European Commission (Commission) – is essential for understanding political order and the potential and limitations for public sector governance. Benefiting from a new body of interview data this article adds two key observations: First, bureaucratic centre formation in the Commission does not profoundly penetrate the Commission as a whole. Comparing officials from the Secretariat General and DG Trade, this study suggests that bureaucratic centre formation is primarily happening within the Secretariat General and only marginally penetrating DG Trade. Two behavioural logics tend to coexist within the Commission administration, albeit embedded and layered within different organizational sub-units. Variation in bureaucratic centre formation is associated with two key variables: (i) the accumulation of relevant organizational capacities at the bureaucratic centre, and (ii) the vertical and horizontal specialization of the Commission administration. Third, these findings hold when ‘controlling for’ recent managerial reforms inside the Commission. The article illustrates that despite recent Commission reforms, some core behavioural logics among Commission officials are not profoundly transformed. Points for practitioners The administration of the European Commission is seen as increasingly steered from the executive centre – that is from the President and the Secretariat General. This study, however, makes two main observations: First, it shows that the strengthening of the executive centre inside the Commission administration (the Secretariat General) is not echoed throughout the services of the Commission. The ambition to make the Secretariat General the service centre for the Commission President is currently not greatly penetrating and transforming the everyday activities of the Directors General (DGs). Second, the study shows that despite historic administrative reforms of the Commission, the everyday behaviour of Commission officials remains basically unaffected.
Visualizing clinical predictors of febrile neutropenia in Asian cancer patients receiving myelosuppressive chemotherapy
Authors: Chen Chao , Chan Alexandre , Yap Kevin 
Published: September 2012

Purpose: Febrile neutropenia is a serious complication among cancer patients receiving myelosuppressive chemotherapy. Patient-specific risk factors, chemotherapy-related and disease-related characteristics can affect the clinical outcome and management of febrile neutropenia. Although many factors have been identified, they vary among different patient populations. We identified clinically-relevant febrile neutropenia predictors in Asian cancer patients through visualization of these factors. Methods: A single-centered, retrospective study was conducted from May to July 2011 at a local cancer center. Demographics and risk factor data were collated from electronic health records and four cancer registries. Data were summarized using descriptive statistics. Additionally, potential febrile neutropenia predictors were identified using categorical principal component and multiple correspondence analyses. Results: A total of 583 patients were analyzed. Majority was females (79%), Chinese (75%) and diagnosed with breast cancers (60%). Six risk factors were identified as potential predictors: types of cancer (16.9–19.8% of variance), chemotherapy regimen (anthracycline-based 11.8–12.9%, taxane-based 8.1%), liver function tests (alanine transaminase 8.6%, alkaline phosphatase 4.0%), renal function tests (serum creatinine 3.1%), prior granulocyte colony stimulating factor use (5.6%) and diabetes mellitus (6.6–6.9%). In terms of cancer types, lymphomas were more predictive than breast cancers. Conclusion: From our knowledge, this is the first study that has identified clinically-relevant febrile neutropenia predictors in Asian cancer patients through visualization of their risk factors. The use of these predictors to identify patients at risk for adverse reactions, such as FN, can allow clinicians to optimize prophylactic granulocyte colony stimulating factor usage in these patients.
Smelt was the likely beneficiary of an antifreeze gene laterally transferred between fishes
Authors: Graham Laurie A , Li Jieying , Davidson William S , Davies Peter L 
Published: September 2012

Abstract

Background
Type II antifreeze protein (AFP) from the rainbow smelt, Osmerus mordax, is a calcium-dependent C-type lectin homolog, similar to the AFPs from herring and sea raven. While C-type lectins are ubiquitous, type II AFPs are only found in a few species in three widely separated branches of teleost fishes. Furthermore, several other non-homologous AFPs are found in intervening species. We have previously postulated that this sporadic distribution has resulted from lateral gene transfer. The alternative hypothesis, that the AFP evolved from a lectin present in a shared ancestor and that this gene was lost in most species, is not favored because both the exon and intron sequences are highly conserved.

Results
Here we have sequenced and annotated a 160 kb smelt BAC clone containing a centrally-located AFP gene along with 14 other genes. Quantitative PCR indicates that there is but a single copy of this gene within the smelt genome, which is atypical for fish AFP genes. The corresponding syntenic region has been identified and searched in a number of other species and found to be devoid of lectin or AFP sequences. Unlike the introns of the AFP gene, the intronic sequences of the flanking genes are not conserved between species. As well, the rate and pattern of mutation in the AFP gene are radically different from those seen in other smelt and herring genes.

Conclusions
These results provide stand-alone support for an example of lateral gene transfer between vertebrate species. They should further inform the debate about genetically modified organisms by showing that gene transfer between ‘higher’ eukaryotes can occur naturally. Analysis of the syntenic regions from several fishes strongly suggests that the smelt acquired the AFP gene from the herring.
Advances in genome-wide RNAi cellular screens: a case study using the Drosophila JAK/STAT pathway
Authors: Fisher Katherine H , Wright Victoria M , Taylor Amy , Zeidler Martin P , Brown Stephen 
Published: September 2012

Abstract

Background
Genome-scale RNA-interference (RNAi) screens are becoming ever more common gene discovery tools. However, whilst every screen identifies interacting genes, less attention has been given to how factors such as library design and post-screening bioinformatics may be effecting the data generated.

Results
Here we present a new genome-wide RNAi screen of the Drosophila JAK/STAT signalling pathway undertaken in the Sheffield RNAi Screening Facility (SRSF). This screen was carried out using a second-generation, computationally optimised dsRNA library and analysed using current methods and bioinformatic tools. To examine advances in RNAi screening technology, we compare this screen to a biologically very similar screen undertaken in 2005 with a first-generation library. Both screens used the same cell line, reporters and experimental design, with the SRSF screen identifying 42 putative regulators of JAK/STAT signalling, 22 of which verified in a secondary screen and 16 verified with an independent probe design. Following reanalysis of the original screen data, comparisons of the two gene lists allows us to make estimates of false discovery rates in the SRSF data and to conduct an assessment of off-target effects (OTEs) associated with both libraries. We discuss the differences and similarities between the resulting data sets and examine the relative improvements in gene discovery protocols.

Conclusions
Our work represents one of the first direct comparisons between first- and second-generation libraries and shows that modern library designs together with methodological advances have had a significant influence on genome-scale RNAi screens.
A pilot randomized controlled trial to improve geriatric frailty
Authors: Chan Ding-Cheng Derrick , Tsou Hsiao-Hui , Yang Rong-Sen , Tsauo Jau-Yih , Chen Ching-Yu , Hsiung Chao Agnes , Kuo Ken N 
Published: September 2012

Abstract

Background
Few randomized controlled trials (RCTs) report interventions targeting improvement of frailty status as an outcome.

Methods
This RCT enrolled 117 older adults (65-79 years of age) in Toufen, Taiwan who scored 3-6 on The Chinese Canadian Study of Health and Aging Clinical Frailty Scale Telephone Version and then score ≥1 on the Cardiovascular Health Study Phenotypic Classification of Frailty (CHS_PCF). With a two by two factorial design, subjects were randomly assigned to interventions (Exercise and nutrition, EN, n = 55 or problem solving therapy, PST, n = 57) or controls (non-EN, n = 62 or non-PST, n = 60). Educational booklets were provided to all. EN group subjects received nutrition consultation and a thrice-weekly exercise-training program while PST group subjects received 6 sessions in 3 month. Subjects were followed at 3, 6, and 12 months. Primary outcome was improvement of the CHS_PCF by at least one category (from pre-frail to robust, or from frail to pre-frail or robust) from baseline assessments. One hundred and one completed final assessments. Intention-to-treat analysis with the generalized estimating equation model was applied with adjustment for time and treatment-by-time interactions.

Results
Mean age was 71.4 ± 3.7 years, with 59% females. Baseline characteristic were generally comparable between groups. EN group subjects had a higher improvement rate on the primary outcome than non-EN group subjects (45% vs 27%, adjusted p = 0.008) at 3 months, but not 6 or 12 months. They also had more increase of serum 25(OH) vitamin D level (4.9 ± 7.7 vs 1.2 ± 5.4, p = 0.006) and lower percentage of osteopenia (74% vs 89% p = 0.042) at 12 months. PST group subjects had better improvement (2.7 ± 6.1 vs 0.2 ± 6.7, p = 0.035, 6-month) and less deterioration (−3.5 ± 9.7 vs −7.1 ± 8.7, p = 0.036, 12-month) of dominant leg extension power than non-PST subjects. Some secondary outcomes were also improved in control groups (non-EN or non-PST). No adverse effects were reported.

Conclusions
The three-month EN intervention resulted in short-term (3-month) frailty status improvement and long-term effect on bone mineral density and serum vitamin D (12-month) among Taiwanese community-dwelling elders. The effect of PST was less pronounce.

Trial registration
ClinicalTrials.gov: EC0970301
A new score predicting the survival of patients with spinal cord compression from myeloma
Authors: Douglas Sarah , Schild Steven E , Rades Dirk 
Published: September 2012

Abstract

Background
This study was performed to create and validate a scoring system for the survival of patients with malignant spinal cord compression (SCC) from myeloma.

Methods
Of the entire cohort (N = 216), 108 patients were assigned to a test group and 108 patients to a validation group. In the test group, nine pre-treatment factors including age, gender, Eastern Cooperative Oncology Group performance status (ECOG-PS), number of involved vertebrae, ambulatory status prior to radiotherapy, other bone lesions, extraosseous lesions, interval from first diagnosis of myeloma to radiotherapy of SCC, and the time developing motor deficits were retrospectively analyzed.

Results
On univariate analysis, improved survival was associated with ECOG-PS 1–2 (p = 0.006), being ambulatory (p = 0.005), and absence of other bone lesions (p = 0.019). On multivariate analysis, ECOG-PS (p = 0.036) and ambulatory status (p = 0.037) were significant; other bone lesions showed a strong trend (p = 0.06). These factors were included in the score. The score for each factor was determined by dividing the 12-month survival rate (in%) by 10. The total risk score was the sum of the three factor scores and ranged from 19 to 24 points. Three prognostic groups were designed with the following 12-month survival rates: 49% for 19–20 points, 74% for 21–23 points, and 93% for 24 points (p = 0.002). In the validation group, the 12-month survival rates were 51%, 80%, and 90%, respectively (p < 0.001).

Conclusions
This score appears reproducible, because the 12-month survival rates of both the test and the validation group were very similar. This new survival score can help personalize the treatment of patients with SCC from myeloma and can be of benefit when counseling patients.