bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD11c Controls Herpes Simplex Virus 1 Responses To Limit Virus Replication during Primary Infection
Authors: Allen Sariah J. , Mott Kevin R. , Chentoufi Aziz A. , BenMohamed Lbachir , Wechsler Steven L. , Ballantyne Christie M. , Ghiasi Homayon 
Published: July 2011

ABSTRACTCD11c is expressed on the surface of dendritic cells (DCs) and is one of the main markers for identification of DCs. DCs are the effectors of central innate immune responses, but they also affect acquired immune responses to infection. However, how DCs influence the efficacy of adaptive immunity is poorly understood. Here, we show that CD11c+DCs negatively orchestrate both adaptive and innate immunity against herpes simplex virus type 1 (HSV-1) ocular infection. The effectiveness and quantity of virus-specific CD8+T cell responses are increased in CD11c-deficient animals. In addition, the levels of CD83, CD11b, alpha interferon (IFN-α), and IFN-β, but not IFN-γ, were significantly increased in CD11c-deficient animals. Higher levels of IFN-α, IFN-β, and CD8+T cells in the CD11c-deficient mice may have contributed to lower virus replication in the eye and trigeminal ganglia (TG) during the early period of infection than in wild-type mice. However, the absence of CD11c did not influence survival, severity of eye disease, or latency. Our studies provide for the first time evidence that CD11c expression may abrogate the ability to reduce primary virus replication in the eye and TG via higher activities of type 1 interferon and CD8+T cell responses.
APOBEC1-Mediated Editing and Attenuation of Herpes Simplex Virus 1 DNA Indicate That Neurons Have an Antiviral Role during Herpes Simplex Encephalitis
Authors: Gee Peter , Ando Yoshinori , Kitayama Hiroko , Yamamoto Seiji P. , Kanemura Yuka , Ebina Hirotaka , Kawaguchi Yasushi , Koyanagi Yoshio 
Published: July 2011

ABSTRACT
APOBEC1 (A1) is a cytidine deaminase involved in the regulation of lipids in the small intestine. Herpes simplex virus 1 (HSV-1) is a ubiquitous pathogen that is capable of infecting neurons in the brain, causing encephalitis. Here, we show that A1 is induced during encephalitis in neurons of rats infected with HSV-1. In cells stably expressing A1, HSV-1 infection resulted in significantly reduced virus replication compared to that in control cells. Infectivity could be restored to levels comparable to those observed for control cells if A1 expression was silenced by specific A1 short hairpin RNAs (shRNA). Moreover, cytidine deaminase activity appeared to be essential for this inhibition and led to an impaired accumulation of viral mRNA transcripts and DNA copy numbers. The sequencing of viral gene UL54 DNA, extracted from infected A1-expressing cells, revealed G-to-A and C-to-T transitions, indicating that A1 associates with HSV-1 DNA. Taken together, our results demonstrate a model in which A1 induction during encephalitis in neurons may aid in thwarting HSV-1 infection.
Tempo and Mode of Plant RNA Virus Escape from RNA Interference-Mediated Resistance
Authors: Lafforgue Guillaume , Martínez Fernando , Sardanyés Josep , de la Iglesia Francisca , Niu Qi-Wen , Lin Shih-Shun , Solé Ricard V. , Chua Nam-Hai , Daròs José-Antonio , Elena Santiago F. 
Published: July 2011

ABSTRACT

A biotechnological application of artificial microRNAs (amiRs) is the generation of plants that are resistant to virus infection. This resistance has proven to be highly effective and sequence specific. However, before these transgenic plants can be deployed in the field, it is important to evaluate the likelihood of the emergence of resistance-breaking mutants. Two issues are of particular interest: (i) whether such mutants can arise in nontransgenic plants that may act as reservoirs and (ii) whether a suboptimal expression level of the transgene, resulting in subinhibitory concentrations of the amiR, would favor the emergence of escape mutants. To address the first issue, we experimentally evolved independent lineages of
Turnip mosaic virus
(TuMV) (family
Potyviridae
) in fully susceptible wild-type
Arabidopsis thaliana
plants and then simulated the spillover of the evolving virus to fully resistant
A. thaliana
transgenic plants. To address the second issue, the evolution phase took place with transgenic plants that expressed the amiR at subinhibitory concentrations. Our results show that TuMV populations replicating in susceptible hosts accumulated resistance-breaking alleles that resulted in the overcoming of the resistance of fully resistant plants. The rate at which resistance was broken was 7 times higher for TuMV populations that experienced subinhibitory concentrations of the antiviral amiR. A molecular characterization of escape alleles showed that they all contained at least one nucleotide substitution in the target sequence, generally a transition of the G-to-A and C-to-U types, with many instances of convergent molecular evolution. To better understand the viral population dynamics taking place within each host, as well as to evaluate relevant population genetic parameters, we performed
in silico
simulations of the experiments. Together, our results contribute to the rational management of amiR-based antiviral resistance in plants.
Gainfully employed? An inquiry into bidi-dependent livelihoods in Bangladesh
Authors: Roy Anupom , Efroymson Debra , Jones Lori , Ahmed Saifuddin , Arafat Islam , Sarker Rashmi , FitzGerald Sian 
Published: July 2011

ObjectivesThis study sought to increase government, civil society and media attention to the tobacco–poverty connection in Bangladesh, particularly as it relates to bidi-dependent livelihoods.Data sourcesThis study consisted of a literature review that examined the socioeconomic impacts of tobacco farming, the working conditions of tobacco workers and the impact of tobacco on consumers, and a primary research study among bidi workers and users. The research included in-depth and semistructured interviews and focus group discussions among bidi workers and a closed-ended quantitative survey among bidi users.Data synthesisMost bidi worker families earn about $6.40 per 7-day work week, leaving them below the poverty line. The majority of bidi workers are women and children, classified as unpaid assistants, who toil long hours in toxic environments. Bidi users are primarily low-income earners who spend up to 10% of their daily income on bidis; the average proportion of income spent on bidis decreased as income increased. If bidi expenditures were reduced and spent instead on food or local transportation, many higher value jobs could be created. This could also mean better health and nutrition for those currently engaged in bidi work.ConclusionsThe results of this study illustrate the linkages between tobacco and poverty. Tobacco control is not simply about health and the environment, but also about the living conditions of the poorest of the poor. If we are to improve the lives of the poor, we must address the root causes of poverty, which include the production and use of tobacco.
Stonebraker on NoSQL and enterprises
Authors: Stonebraker Michael 
Published: July 2011

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish selected posts or excerpts.

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Follow us on Twitter at http://twitter.com/blogCACM
http://cacm.acm.org/blogs/blog-cacm
Michael Stonebraker discusses several reasons why NoSQL has not caught on with enterprise users.
Virtual machine monitor-based lightweight intrusion detection
Authors: Azmandian Fatemeh , Moffie Micha , Alshawabkeh Malak , Dy Jennifer , Aslam Javed , Kaeli David 
Published: July 2011

As virtualization technology gains in popularity, so do attempts to compromise the security and integrity of virtualized computing resources. Anti-virus software and firewall programs are typically deployed in the guest virtual machine to detect malicious software. These security measures are effective in detecting known malware, but do little to protect against new variants of intrusions. Intrusion detection systems (IDSs) can be used to detect malicious behavior. Most intrusion detection systems for virtual execution environments track behavior at the application or operating system level, using virtualization as a means to isolate themselves from a compromised virtual machine.
In this paper, we present a novel approach to intrusion detection of virtual server environments which utilizes only information available from the perspective of the virtual machine monitor (VMM). Such an IDS can harness the ability of the VMM to isolate and manage several virtual machines (VMs), making it possible to provide monitoring of intrusions at a common level across VMs. It also offers unique advantages over recent advances in intrusion detection for virtual machine environments. By working purely at the VMM-level, the IDS does not depend on structures or abstractions visible to the OS (e.g., file systems), which are susceptible to attacks and can be modified by malware to contain corrupted information (e.g., the Windows registry). In addition, being situated within the VMM provides ease of deployment as the IDS is not tied to a specific OS and can be deployed transparently below different operating systems.
Due to the semantic gap between the information available to the VMM and the actual application behavior, we employ the power of data mining techniques to extract useful nuggets of knowledge from the raw, low-level architectural data. We show in this paper that by working entirely at the VMM-level, we are able to capture enough information to characterize normal executions and identify the presence of abnormal malicious behavior. Our experiments on over 300 real-world malware and exploits illustrate that there is sufficient information embedded within the VMM-level data to allow accurate detection of malicious attacks, with an acceptable false alarm rate.
Virtualization in the age of heterogeneous machines
Authors: Bacon David F. 
Published: July 2011

Since their invention over 40 years ago, virtual machines have been used to virtualize one or more von Neumann processors and their associated peripherals. System virtual machines provide the illusion that the user has their own instance of a physical machine with a given instruction set architecture (ISA). Process virtual machines provide the illusion of running on a synthetic architecture independent of the underlying ISA, generally for the purpose of supporting a high-level language.
To continue the historical trend of exponential increase in computational power in the face of limits on clock frequency scaling, we must find ways to harness the inherent parallelism of billions of transistors. I contend that multi-core chips are a fatally flawed approach - instead, maximum performance will be achieved by using heterogeneous chips and systems that combine customized and customizable computational substrates that achieve very high performance by closely matching the computational and communications structures of the application at hand.
Such chips might look like a mashup of a conventional multicore, a GPU, an FPGA, some ASICs, and a DSP. But programming them with current technologies would be nightmarishly complex, portability would be lost, and innovation between chip generations would be severely limited.
The answer (of course) is virtualization, and at both the device level and the language level.
In this talk I will illustrate some challenges and potential solutions in the context of IBM's Liquid Metal project, in which we are designing a new high-level language (Lime) and compiler/runtime technology to virtualize the underlying computational devices by providing a uniform semantic model.
I will also discuss problems (and opportunities) that this raises at the operating system and data center levels, particularly with computational elements like FPGAs for which "context switching" is currently either extremely expensive or simply impossible.
Modulating Microtubule Stability Enhances the Cytotoxic Response of Cancer Cells to Paclitaxel
Authors: Ahmed Ahmed Ashour , Wang Xiaoyan , Lu Zhen , Goldsmith Juliet , Le Xiao-Feng , Grandjean Geoffrey , Bartholomeusz Geoffrey , Broom Bradley , Bast Robert C. 
Published: July 2011

Abstract
The extracellular matrix protein TGFBI enhances the cytotoxic response of cancer cells to paclitaxel by affecting integrin signals that stabilize microtubules. Extending the implications of this knowledge, we tested the more general hypothesis that cancer cell signals which increase microtubule stability before exposure to paclitaxel may increase its ability to stabilize microtubules and thereby enhance its cytotoxicity. Toward this end, we carried out an siRNA screen to evaluate how genetic depletion affected microtubule stabilization, cell viability, and apoptosis. High content microscopic analysis was carried out in the absence or presence of paclitaxel. Kinase knockdowns that stabilized microtubules strongly enhanced the effects of paclitaxel treatment. Conversely, kinase knockdowns that enhanced paclitaxel-mediated cytotoxicity sensitized cells to microtubule stabilization by paclitaxel. The siRNA screen identified several genes that have not been linked previously to microtubule regulation or paclitaxel response. Gene shaving and Bayesian resampling used to classify these genes suggested three pathways of paclitaxel-induced cell death related to apoptosis and microtubule stability, apoptosis alone, or neither process. Our results offer a functional classification of the genetic basis for paclitaxel sensitivity and they support the hypothesis that stabilizing microtubules prior to therapy could enhance antitumor responses to paclitaxel treatment. Cancer Res; 71(17); 5806–17. ©2011 AACR.
Hedgehog Signaling: Networking to Nurture a Promalignant Tumor Microenvironment
Authors: Harris Lillianne G. , Samant Rajeev S. , Shevde Lalita A. 
Published: July 2011

Abstract
In addition to its role in embryonic development, the Hedgehog pathway has been shown to be an active participant in cancer development, progression, and metastasis. Although this pathway is activated by autocrine signaling by Hedgehog ligands, it can also initiate paracrine signaling with cells in the microenvironment. This creates a network of Hedgehog signaling that determines the malignant behavior of the tumor cells. As a result of paracrine signal transmission, the effects of Hedgehog signaling most profoundly influence the stromal cells that constitute the tumor microenvironment. The stromal cells in turn produce factors that nurture the tumor. Thus, such a resonating cross-talk can amplify Hedgehog signaling, resulting in molecular chatter that overall promotes tumor progression. Inhibitors of Hedgehog signaling have been the subject of intense research. Several of these inhibitors are currently being evaluated in clinical trials. Here, we review the role of the Hedgehog pathway in the signature characteristics of cancer cells that determine tumor development, progression, and metastasis. This review condenses the latest findings on the signaling pathways that are activated and/or regulated by molecules generated from Hedgehog signaling in cancer and cites promising clinical interventions. Finally, we discuss future directions for identifying the appropriate patients for therapy, developing reliable markers of efficacy of treatment, and combating resistance to Hedgehog pathway inhibitors. Mol Cancer Res; 9(9); 1165–74. ©2011 AACR.
PPM1H Is a p27 Phosphatase Implicated in Trastuzumab Resistance
Authors: Lee-Hoeflich Si Tuen , Pham Thinh Q. , Dowbenko Don , Munroe Xander , Lee James , Li Li , Zhou Wei , Haverty Peter M. , Pujara Kanan , Stinson Jeremy , Chan Sara M. , Eastham-Anderson Jeffrey , Pandita Ajay , Seshagiri Somasekar , Hoeflich Klaus P. , Turashvili Gulisa , Gelmon Karen A. , Aparicio Samuel A. , Davis David P. , Sliwkowski Mark X. , Stern Howard M. 
Published: July 2011

Abstract
The HER2 oncogene is overexpressed or amplified in 20% of breast cancers. HER2-positive cancer historically portends a poor prognosis, but the HER2-targeted therapy trastuzumab mitigates this otherwise ominous distinction. Nevertheless, some patients suffer disease recurrence despite trastuzumab, and metastatic disease remains largely incurable due to innate and acquired resistance. Thus, understanding trastuzumab resistance remains an unmet medical need. Through RNA interference screening, we discovered that knockdown of the serine/threonine phosphatase PPM1H confers trastuzumab resistance via reduction in protein levels of the tumor suppressor p27. PPM1H dephosphorylates p27 at threonine 187, thus removing a signal for proteasomal degradation. We further determined that patients whose tumors express low levels of PPM1H trend towards worse clinical outcome on trastuzumab. Identifying PPM1H as a novel p27 phosphatase reveals new insight into how cancer cells destabilize a well-recognized tumor suppressor. Furthermore, low PPM1H expression may identify a subset of HER2-positive tumors that are harder to treat.
Significance: PPM1H is identified as a phosphatase impacting p27 stability. Low expression of PPM1H may be associated with poor outcome in breast cancer. Cancer Discovery; 1(4); 326–337. ©2011 AACR.
Read the Commentary on this article by Aceto and Bentires-Alj, p. 285
This article is highlighted in the In This Issue feature, p. 275
ERα-Dependent E2F Transcription Can Mediate Resistance to Estrogen Deprivation in Human Breast Cancer
Authors: Miller Todd W. , Balko Justin M. , Fox Emily M. , Ghazoui Zara , Dunbier Anita , Anderson Helen , Dowsett Mitch , Jiang Aixiang , Smith R. Adam , Maira Sauveur-Michel , Manning H. Charles , González-Angulo Ana M. , Mills Gordon B. , Higham Catherine , Chanthaphaychith Siprachanh , Kuba Maria G. , Miller William R. , Shyr Yu , Arteaga Carlos L. 
Published: July 2011

AbstractMost estrogen receptor α (ER)-positive breast cancers initially respond to antiestrogens, but many eventually become estrogen-independent and recur. We identified an estrogen-independent role for ER and the CDK4/Rb/E2F transcriptional axis in the hormone-independent growth of breast cancer cells. ER downregulation with fulvestrant or small interfering RNA (siRNA) inhibited estrogen-independent growth. Chromatin immunoprecipitation identified ER genomic binding activity in estrogen-deprived cells and primary breast tumors treated with aromatase inhibitors. Gene expression profiling revealed an estrogen-independent, ER/E2F-directed transcriptional program. An E2F activation gene signature correlated with a lesser response to aromatase inhibitors in patients' tumors. siRNA screening showed that CDK4, an activator of E2F, is required for estrogen-independent cell growth. Long-term estrogen-deprived cells hyperactivate phosphatidylinositol 3-kinase (PI3K) independently of ER/E2F. Fulvestrant combined with the pan-PI3K inhibitor BKM120 induced regression of ER+ xenografts. These data support further development of ER downregulators and CDK4 inhibitors, and their combination with PI3K inhibitors for treatment of antiestrogen-resistant breast cancers.Significance: ERα retains genomic activity and drives a CDK4/E2F-dependent transcriptional program despite estrogen deprivation therapy. Combined inhibition of ER and PI3K induced regression of ER+ xenografts, supporting further development of strong ER downregulators and CDK4 inhibitors, and their combination with PI3K inhibitors for the treatment of antiestrogen-resistant breast cancers. Cancer Discovery; 1(4); 338–51. ©2011 AACR.Read the Commentary on this article by Van Tine et al., p. 287This article is highlighted in the In This Issue feature, p. 275
Development and Validation of a Predictive Screening Tool for Uninterpretable Coronary CT Angiography Results
Authors: Vanhecke Thomas E. , Madder Ryan D. , Weber James E. , Bielak Lawrence F. , Peyser Patricia A. , Chinnaiyan Kavitha M. 
Published: July 2011

Background—
Coronary CT angiography (CCTA) is an excellent tool for noninvasive assessment of coronary arteries in low- to intermediate-risk individuals. However, the accuracy of CCTA heavily depends on image quality. Our objective was to develop and validate a tool to predict pre-CCTA risk of obtaining an uninterpretable result in symptomatic patients.

Methods and Results—
Among 8585 symptomatic patients, we identified variables independently associated with the presence of at least 1 uninterpretable major coronary segment to create the uninterpretable risk score (URS). This risk score was developed using both clinical variables and patient variables acquired at the time the CCTA was performed (heart rate and coronary calcium). The URS was then prospectively validated among an additional 915 symptomatic patients. The URS was predictive of uninterpretable results in both the development and the validation cohorts. For every 4-point increase in the URS (range, 0 to 12), the rate of at least 1 uninterpretable coronary segment per 100 CCTA studies increased ≈1.5 fold. Increased heart rate and coronary artery calcium score were predictive of uninterpretable CCTA study results. Uninterpretable results were associated with 3-month outcomes in the development cohort.

Conclusions—
The URS can categorize patients who are likely to have at least 1 uninterpretable major coronary segment on CCTA. This may aid in appropriate patient selection for CCTA and avoiding radiation exposure in those likely to have an uninterpretable study.

Clinical Trial Registration—

URL:
http:///www.clinicaltrials.gov
. Unique identifier: NCT00640068.
Steady-state operating performance modelling and prediction for a direct expansion air conditioning system using artificial neural network
Authors: Li Ning , Xia Liang , Shiming Deng , Xu Xiangguo , Chan Ming-Yin 
Published: July 2011

A two-in two-out steady-state artificial neural network (ANN)-based model for an experimental variable speed direct expansion (DX) air conditioning (A/C) system has been developed for simulating its total output cooling capacity and equipment sensible heat ratio under different combinations of compressor and supply fan speeds. Experiments were carried out, and totally 169 sets of experimental data were obtained for ANN training and testing. An ANN-based model having the configuration of 2 neurons in the input layer, 2 neurons in the output layer and 6 neurons in each of the 2 hidden layers, i.e. 2-6-6-2 configuration, was thus developed. The ANN-based model developed can be used to predict the operating performance of the DX A/C system with a higher accuracy. It is expected that the model developed can help design a multivariable-input multivariable-output strategy to simultaneously control indoor air temperature and humidity. Practical applications: The work reported in this paper demonstrates that the operating performance of a DX A/C system under different compressor and supply fan speeds can well be represented using ANN model technique, as an alternative to traditional physical-based modelling techniques, with a higher predicting accuracy and less computational effort. The ANN-based model for the DX A/C system is expected to be very useful in developing an efficient control algorithm for simultaneous indoor temperature and humidity using the ANN technique.