bluuebunny/crossref_metadata_2025 huggingface dataset:
FAWN
Authors: Andersen David G. , Franklin Jason , Kaminsky Michael , Phanishayee Amar , Tan Lawrence , Vasudevan Vijay
Published: June 2011

This paper presents a fast array of wimpy nodes---FAWN---an approach for achieving low-power data-intensive data-center computing. FAWN couples low-power processors to small amounts of local flash storage, balancing computation and I/O capabilities. FAWN optimizes for per node energy efficiency to enable efficient, massively parallel access to data.

The key contributions of this paper are the principles of the FAWN approach and the design and implementation of FAWN-KV---a consistent, replicated, highly available, and high-performance key-value storage system built on a FAWN prototype. Our design centers around purely log-structured datastores that provide the basis for high performance on flash storage, as well as for replication and consistency obtained using chain replication on a consistent hashing ring. Our evaluation demonstrates that FAWN clusters can handle roughly 350 key-value
queries per Joule
of energy---two orders of magnitude more than a disk-based system.
Future Tense: My office mate
Authors: Rucker Rudy
Published: June 2011

Future Tense, one of the revolving features on this page, presents stories and essays from the intersection of computational science and technological speculation, their boundaries limited only by our ability to imagine what will and could be.

I became a biocomputational zombie for science…and for love
.
A Fast Corpus-Based Stemmer
Authors: Paik Jiaul H. , Parui Swapan K.
Published: June 2011

Stemming is a mechanism of word form normalization that transforms the variant word forms to their common root. In an Information Retrieval system, it is used to increase the system’s performance, specifically the recall and desirably the precision. Although its usefulness is shown to be mixed in languages such as English, because morphologically complex languages stemming produces a significant performance improvement. A number of linguistic rule-based stemmers are available for most European languages which employ a set of rules to get back the root word from its variants. But for Indian languages which are highly inflectional in nature, devising a linguistic rule-based stemmer needs some additional resources which are not available. We present an approach which is purely corpus based and finds the equivalence classes of variant words in an unsupervised manner. A set of experiments on four languages using FIRE, CLEF, and TREC test collections shows that our approach provides comparable results with linguistic rule-based stemmers for some languages and gives significant performance improvement for resource constrained languages such as Bengali and Marathi.
Visually and Phonologically Similar Characters in Incorrect Chinese Words
Authors: Liu C.-L. , Lai M.-H. , Tien K.-W. , Chuang Y.-H. , Wu S.-H. , Lee C.-Y.
Published: June 2011

Information about students’ mistakes opens a window to an understanding of their learning processes, and helps us design effective course work to help students avoid replication of the same errors. Learning from mistakes is important not just in human learning activities; it is also a crucial ingredient in techniques for the developments of student models. In this article, we report findings of our study on 4,100 erroneous Chinese words. Seventy-six percent of these errors were related to the phonological similarity between the correct and the incorrect characters, 46% were due to visual similarity, and 29% involved both factors. We propose a computing algorithm that aims at replication of incorrect Chinese words. The algorithm extends the principles of decomposing Chinese characters with the Cangjie codes to judge the visual similarity between Chinese characters. The algorithm also employs empirical rules to determine the degree of similarity between Chinese phonemes. To show its effectiveness, we ran the algorithm to select and rank a list of about 100 candidate characters, from more than 5,100 characters, for the incorrectly written character in each of the 4,100 errors. We inspected whether the incorrect character was indeed included in the candidate list and analyzed whether the incorrect character was ranked at the top of the candidate list. Experimental results show that our algorithm captured 97% of incorrect characters for the 4,100 errors, when the average length of the candidate lists was 104. Further analyses showed that the incorrect characters ranked among the top 10 candidates in 89% of the phonologically similar errors and in 80% of the visually similar errors.
Detecting Locally Distributed Predicates
Authors: De Rosa Michael , Goldstein Seth Copen , Lee Peter , Campbell Jason , Pillai Padmanabhan S.
Published: June 2011

In this article, we formalize
locally distributed predicates
, a concept previously introduced to address specific challenges associated with modular robotics and distributed debugging. A locally distributed predicate (LDP) is a novel construction for representing and detecting distributed properties in sparse-topology systems. Our previous work on LDPs presented empirical validation; here we show a formal model for two variants of the LDP algorithm, LDP-Basic and LDP-Snapshot, and establish performance bounds for these variants. We prove that LDP-Basic can detect strong stable predicates, that LDP-Snapshot can detect all stable predicates, and discuss their applicability to various distributed programming domains and to spatial computing in general. LDP detection in bounded-degree networks is shown to be scale-free, making the approach particularly attractive for specific topologies, even though LDPs are less efficient than snapshot algorithms in general distributed systems.
Spatial Coordination of Pervasive Services through Chemical-Inspired Tuple Spaces
Authors: Viroli Mirko , Casadei Matteo , Montagna Sara , Zambonelli Franco
Published: June 2011

To support and engineer the spatial coordination of distributed pervasive services, we propose a chemical-inspired model, which extends tuple spaces with the ability of evolving tuples mimicking chemical systems, that is, in terms of reaction and diffusion rules that apply to tuples modulo semantic match. The suitability of this model is studied by considering a self-adaptive display infrastructure providing people nearby with several visualization services (advertisements, news, personal and social content). The key result of this article is that general-purpose chemical reactions inspired by population dynamics can be used in pervasive applications to enact spatial computing patterns of competition and gradient-based interaction.
Infrastructureless Spatial Storage Algorithms
Authors: Fernandez-Marquez Jose Luis , Di Marzo Serugendo Giovanna , Arcos Josep Lluis
Published: June 2011

This article defines and analyzes a collection of algorithms for persistent storage of data at specific geographical zones exploiting the memory of mobile devices located in these areas. Contrarily to other approaches for data dissemination, our approach uses a viral programming model. Data performs an active role in the storage process. It acts as a virus or a mobile agent, finding its own storage and relocating when necessary. We consider geographical areas of any shape and size. Simulation results show that our algorithms are scalable and converge quickly, even though none of them outperform the others for all performance metrics considered.
PRE-BUD
Authors: Manzanares Adam , Qin Xiao , Ruan Xiaojun , Yin Shu
Published: June 2011

A critical problem with parallel I/O systems is the fact that disks consume a significant amount of energy. To design economically attractive and environmentally friendly parallel I/O systems, we propose an energy-aware prefetching strategy (PRE-BUD) for parallel I/O systems with disk buffers. We introduce a new architecture that provides significant energy savings for parallel I/O systems using buffer disks while maintaining high performance. There are two buffer disk configurations: (1) adding an extra buffer disk to accommodate prefetched data, and (2) utilizing an existing disk as the buffer disk. PRE-BUD is not only able to reduce the number of power-state transitions, but also to increase the length and number of standby periods. As such, PRE-BUD conserves energy by keeping data disks in the standby state for increased periods of time. Compared with the first prefetching configuration, the second configuration lowers the capacity of the parallel disk system. However, the second configuration is more cost-effective and energy-efficient than the first one. Finally, we quantitatively compare PRE-BUD with both disk configurations against three existing strategies. Empirical results show that PRE-BUD is able to reduce energy dissipation in parallel disk systems by up to 50 percent when compared against a non-energy aware approach. Similarly, our strategy is capable of conserving up to 30 percent energy when compared to the dynamic power management technique.
Towards a framework of publics
Authors: Lindtner Silvia , Chen Judy , Hayes Gillian R. , Dourish Paul
Published: June 2011

Design and evaluation of user-generated media production and sharing in Human-Computer Interaction (HCI) often focus on formal and informal media sharing, such as communication within social networks, automatic notifications of activities, and the exchange of digital artifacts. However, conceptual tools for understanding how people relate to the audiences they reach through these systems are limited. The increasing interest in user-generated content in HCI demands the infusion of new methods and theories that explicitly engage the construction and use of media within and among large groups of individuals and systems. In this paper, we suggest that the notion of “publics,” drawn from media theory, provides useful insights into user-driven, social, and cultural forms of technology use and digital content creation. We illustrate this by employing the notion of publics to the findings from a two-month deployment of a mobile photo sharing platform in a youth housing community. The results of this empirical work coupled with a theoretical examination of publics stimulate reflection on prevailing interpretations of user-designer-reader roles. The paper provides an outlook for potentially new and productive ways of understanding interdependencies within those activities. Implications that can be drawn from this work concern the role of digital media creation and sharing for the formation of collectives and how people position themselves collectively in relation to larger social groups and societal norms. The analysis suggests fruitful crossovers among HCI, Media Theory and New Media Research by approaching the user as both consumer and producer of digital content.
Measuring multitasking behavior with activity-based metrics
Authors: Benbunan-Fich Raquel , Adler Rachel F. , Mavlanova Tamilla
Published: June 2011

Multitasking is the result of time allocation decisions made by individuals faced with multiple tasks. Multitasking research is important in order to improve the design of systems and applications. Since people typically use computers to perform multiple tasks at the same time, insights into this type of behavior can help develop better systems and ideal types of computer environments for modern multitasking users. In this paper, we define multitasking based on the principles of task independence and performance concurrency and develop a set of metrics for computer-based multitasking. The theoretical foundation of this metric development effort stems from an application of key principles of Activity Theory and a systematic analysis of computer usage from the perspective of the user, the task and the technology. The proposed metrics, which range from a lean dichotomous variable to a richer measure based on switches, were validated with data from a sample of users who self-reported their activities during a computer usage session. This set of metrics can be used to establish a conceptual and methodological foundation for future multitasking studies.
Iris
Authors: Li Zheng , Mohamed Moustafa , Chen Xi , Zhou Hongyu , Mickelson Alan , Shang Li , Vachharajani Manish
Published: June 2011

On-chip communication, including short, often-multicast, latency-critical coherence and synchronization messages, and long, unicast, throughput-sensitive data transfers, limits the power efficiency and performance scalability of many-core chip-multiprocessor systems. This article analyzes on-chip communication challenges and studies the characteristics of existing electrical and emerging nanophotonic interconnect. Iris, a CMOS-compatible high-performance low-power nanophotonic on-chip network, is thus introduced. Iris's circuit-switched subnetwork supports throughput-sensitive data transfer. Iris's optical-antenna-array-based broadcast--multicast subnetwork optimizes latency-critical traffic and supports the path setup of circuit-switched communication. Overall, the proposed nanophotonic network design offers an on-chip communication backplane that is power efficient while demonstrating low latency and high throughput.
Online Sexual Harassment Training Just Makes Sense
Authors: Lindenberger Judith
Published: June 2011

Sexual harassment is a difficult topic to teach and requires the ability to be professional, open, and clear. Employees want to spend less time in training, companies want easier ways to schedule training, and employers are looking at new ways to incorporate traditional workplace training. The solution, elearning.
Avoiding the Trap of Clicky-Clicky Bling-Bling
Authors: Bean Cammy
Published: June 2011

Bling makes it easy to overlook a poorly designed elearning solution. How do you create long lasting, intriguing programs that are visually pleasing without sacrificing the needs of learners? In part one of a two-part series on clicky-click bling-bling, learn how to create good design while avoiding the "seductive-details effect."
Make Your Designs Shine from the Inside
Authors: Bean Cammy
Published: June 2011

Good design doesn't mean over accessorizing. Part two explores how to add graphics that enhance, not distract from the learning experience; incorporate interactive elements that are useful; and find that "inner bling."
Toward online hybrid systems model checking of cyber-physical systems' time-bounded short-run behavior
Authors: Bu Lei , Wang Qixin , Chen Xin , Wang Linzhang , Zhang Tian , Zhao Jianhua , Li Xuandong
Published: June 2011

Many
Cyber-Physical Systems
(CPS) are highly nondeterministic. This often makes it impractical to model and predict the complete system behavior. To address this problem, we propose that instead of offline modeling and verification, many CPS systems should be modeled and verified online, and we shall focus on the system's
time-bounded behavior in short-run future
, which is more describable and predictable. Meanwhile, as the system model is generated/updated online, the verification has to be fast. It is meaningless to tell an online model is unsafe when it is already out-dated. To demonstrate the feasibility of our proposal, we study two cases of our ongoing projects, one on the modeling and verification of a train control system, and the other on a
Medical Device Plug-and-Play
(MDPnP) application. Both cases are about safety-critical CPS systems. Through these two cases, we exemplify how to build online models that describe the time-bounded short-run behavior of CPS systems; and we show that fast online modeling and verification is possible.
Toward autonomous vehicle safety verification from mobile cyber-physical systems perspective
Authors: Kandula Sailesh , Mukherjee Tridib , Gupta Sandeep K. S.
Published: June 2011

Safety certification of Autonomous Vehicles (AVs) require guarantees on AVs' safety at design time. To this effect, this paper proposes modeling abstractions that allow architectural representation of AVs and their surroundings, i.e. representation of different components, and enable safety analysis from such representation without requiring any expertise on formal methods. Toward this direction, AVs are considered as Cyber-Physical Systems with Mobile computing nodes (MCPS), where each node (i.e. an AV) can have intentional (as determined by AVs' controller) and unintentional (e.g., in case of skids) motion characteristics depending on the physical environment (e.g. road condition). The modeling abstractions are used to analyze safety of passengers in an AV that collides with guard rail due to skid along a curved segment on the AZ-83 highway.
Serum Metabolic Profile in Multiple Sclerosis Patients
Authors: Tavazzi Barbara , Batocchi Anna Paola , Amorini Angela Maria , Nociti Viviana , D'Urso Serafina , Longo Salvatore , Gullotta Stefano , Picardi Marika , Lazzarino Giuseppe
Published: June 2011

Multiple sclerosis (MS) is a progressive demyelinating process considered as an autoimmune disease, although the causes of this pathology have not been yet fully established. Similarly to other neurodegenerations, MS is characterized by a series of biochemical changes affecting to different extent neuronal functions; great attention has been given to oxidative/nitrosative stress and to alterations in mitochondrial functions. According to previous data, MS patients show significant changes in the circulating concentrations of different metabolites, although it is still unclear whether uric acid undergoes to decrease, increase, or no change under this pathological condition. In this study, we report the serum metabolic profile in terms of purines, pyrimidines, creatinine, malondialdehyde, ascorbic acid, nitrite, and nitrate in a group of 170 MS patients. The results show increase in circulating uric acid and other oxypurines (hypoxanthine and xanthine), as well as in uridine and β-pseudouridine. The concomitant increase in circulating creatinine, malondialdehyde, nitrite, and nitrate, and decrease in ascorbic acid, demonstrates that MS induces alteration in energy metabolism and in oxidants/antioxidants balance that can be monitored in serum of MS patients.
Segmentation of Endothelial Cell Boundaries of Rabbit Aortic Images Using a Machine Learning Approach
Authors: Iftikhar Saadia , Bond Andrew R. , Wagan Asim I. , Weinberg Peter D. , Bharath Anil A.
Published: June 2011

This paper presents an automatic detection method for thin boundaries of silver-stained endothelial cells (ECs) imaged using light microscopy of endothelium mono-layers from rabbit aortas. To achieve this, a segmentation technique was developed, which relies on a rich feature space to describe the spatial neighbourhood of each pixel and employs a Support Vector Machine (SVM) as a classifier. This segmentation approach is compared, using hand-labelled data, to a number of standard segmentation/thresholding methods commonly applied in microscopy. The importance of different features is also assessed using the method of minimum Redundancy, Maximum Relevance (mRMR), and the effect of different SVM kernels is also considered. The results show that the approach suggested in this paper attains much greater accuracy than standard techniques; in our comparisons with manually labelled data, our proposed technique is able to identify boundary pixels to an accuracy of 93%. More significantly, out of a set of 56 regions of image data, 43 regions were binarised to a useful level of accuracy. The results obtained from the image segmentation technique developed here may be used for the study of shape and alignment of ECs, and hence patterns of blood flow, around arterial branches.
Adiabatic Gasification and Pyrolysis of Coffee Husk Using Air‐Steam for Partial Oxidation
Authors: Rodriguez Catalina , Gordillo Gerardo
Published: June 2011

Colombian coffee industry
produces about 0.6 million tons of husk (CH) per year
which could serve as feedstock for thermal
gasification to produce gaseous and liquid fuels. The
current paper deals with: (i) CH adiabatic gasification
modeling using air‐steam blends for partial oxidation
and (ii) experimental thermogravimetric analysis to
determine the CH activation energy (E). The Chemical
Equilibrium with Applications Program (CEA), developed
by NASA, was used to estimate the effect of
equivalence ratio (ER) and steam to fuel ratio (S : F)
on equilibrium temperature and gas composition of ~150
species. Also, an atom balance model was developed for
comparison purposes. The results showed that increased
ER and (S : F) ratios produce mixtures that are rich in
H2 and CO2 but poor in CO. The
value for the activation energy was estimated to be
221 kJ/kmol.
A Generic Current Mode Design for Multifunction Grounded Capacitor Filters Employing Log-Domain Technique
Authors: Shah N. A. , Khanday F. A.
Published: June 2011

A generic design (GD) for realizing annth order log-domain multifunction filter (MFF), which can yield four possible stable filter configurations, each offering simultaneously lowpass (LP), highpass (HP), and bandpass (BP) frequency responses, is presented. The features of these filters are very simple, consisting of merely a few exponential transconductor cells and capacitors; all grounded elements, capable of absorbing the shunt parasitic capacitances, responses are electronically tuneable, and suitable for monolithic integration. Furthermore, being designed using log-domain technique, it offers all its advantages. As an example, 5th-order MFFs are designed in each case and their performances are evaluated through simulation. Lastly, a comparative study of the MFFs is also carried, which helps in selecting better high-order MFF for a given application.
Current Mode Biquad Filter with Minimum Component Count
Authors: Chaturvedi Bhartendu , Maheshwari Sudhanshu
Published: June 2011

The paper presents a new current mode biquadratic filter with one input and three outputs using differential voltage current conveyor (DVCC) and four passive components. The proposed circuit can simultaneously realize low-pass, band-pass, and high-pass filter functions without changing the circuit topology and passive elements. The circuit exhibits a good frequency performance and low-sensitivity figures. PSPICE simulation using 0.5 μm CMOS parameters are given to validate the proposed circuit. The circuit provides a simple yet novel solution to the current-mode filtering after appropriate incorporation of current sensing elements in form of current buffers.
Study of Allergic Rhinitis in Childhood
Authors: Balatsouras Dimitrios G. , Koukoutsis George , Ganelis Panayotis , Fassolis Alexandros , Korres George S. , Kaberos Antonis
Published: June 2011

Allergic rhinitis is common among children and quite often represents a stage of the atopic march. Although sensitization to food and airborne allergens may appear in infancy and early childhood, symptoms of the disease are usually present after age 3. The aim of this study was to determine the most frequent food and indoor and outdoor respiratory allergens involved in allergic rhinitis in children in the region of Piraeus. The study was performed in the outpatient clinic of otolaryngologic allergy of a general hospital. Fifty children (ranged 6–14 ) with symptoms of allergic rhinitis and positive radioallergosorbent test (RAST) for IgE antibodies or skin prick tests were included in the study. Thirty six (72%) of the subjects of the study had intermittent allergic rhinitis. The most common aeroallergens determined were grass pollens and Parietaria, whereas egg and milk were the food allergens identified. The detection of indoor and outdoor allergens in the region of Piraeus, based on skin prick tests and RAST tests, showed high incidence of grasses and food allergens, which is similar to other Mediterranean countries.
Sequential Load Transport in Grass-Cutting Ants (Atta vollenweideri): Maximization of Plant Delivery Rate or Improved Information Transfer?
Authors: Röschard Jacqueline , Roces Flavio
Published: June 2011

Sequential transport of plant fragments was studied in the grass-cutting antAtta vollenweideri. Two competing hypotheses concerning its occurrence were tested. Based on the “economic-transport hypothesis," sequential transport occurs because of a mismatch between load size and ant body size, and it is therefore considered a way to improve size-matching and so the plant delivery rate. Alternatively, the “information-transfer hypothesis" states that sequential transport improves the information flow during foraging. By transferring its load, a worker may return earlier to the foraging site so as to intensify chemical recruitment. To distinguish between these two competing hypotheses, standardized paper fragments that differed either in size or in quality were presented to workers of a field colony, and sequential transport was quantified. Neither an increase in fragment mass nor in fragment length influenced the occurrence of transport chains. Sequential transport took longer than transport by a single carrier. However, the occurrence of sequential transport increased with increasing fragment quality. High-quality fragments were transferred more frequently and after shorter distances than less-attractive fragments. Taken together, these results strongly support the hypothesis that sequential load transport has been favoured during evolution because of an improvement in the information flow during foraging.
The Efficacy and Safety of Propiverine Hydrochloride in Patients with Overactive Bladder Symptoms Who Poorly Responded to Previous Anticholinergic Agents
Authors: Masumori Naoya , Miyamoto Shintaro , Tsukamoto Taiji , Furuya Seiji , Iwasawa Akihiko , Sato Takashi , Itoh Naoki , Shibuya Akihiko , Oda Toshiro
Published: June 2011

Objectives. To prospectively examine the efficacy and safety of propiverine hydrochloride in patients with overactive bladder (OAB) symptoms who poorly responded to previous treatment with solifenacin, tolterodine or imidafenacin.Methods. Patients aged ≥20 with persisting OAB symptoms (≥6 in OAB symptom score (OABSS)) even after at least 4-week treatment using solifenacin, tolterodine or imidafenacin were enrolled. Propiverine 20 mg/day was administered for 12 weeks to 70 patients who desired the further improvement of OAB symptoms and 3 who had intolerable adverse events of previous drugs. The OABSS and postvoid residual urine volume (PVR) were determined before and at 4 and 12 weeks of treatment.Results. Of 73 patients enrolled (29 males and 44 females, median age 71 years), 52 completed the protocol treatment. The OABSS was significantly improved by propiverine treatment (9.0 at baseline, 6.2 at 4 weeks, 6.3 at 12 weeks (P<0.001)). The scores of OAB symptoms (nighttime frequency, urgency and urge incontinence) except daytime frequency also improved significantly. No increase in PVR was observed. The most frequent adverse event was dry mouth (13.7%), followed by constipation (6.8%).Conclusions. Propiverine is useful to improve OAB for patients who poorly respond to solifenacin, tolterodine or imidafenacin.
Beyond the Expanders
Authors: Bolla Marianna
Published: June 2011

Expander graphs are widely used in communication problems and construction of error
correcting codes. In such graphs, information gets through very quickly. Typically, it is not true for social or biological networks, though we may find a partition of the vertices such that the induced subgraphs on them and the bipartite subgraphs between any pair of them exhibit regular behavior of information flow within or between the vertex subsets. Implications between spectral and regularity properties are discussed.
The Eigenfunction Expansion for a Dirichlet Problem with Explosive Factor
Authors: El-Raheem Zaki F. A. , Nasser A. H.
Published: June 2011

We prove the eigenfunction expansion formula for a Dirichlet problem with explosive factor by two ways, first by standard method and second by proving a convergence in some metric space L2(0, π; ρ(x)).
Evaluating the Reliability of Anatomic Landmarks in Safe Lumbar Puncture Using Magnetic Resonance Imaging: Does Sex Matter?
Authors: Rahmani Maryam , Bozorg Seyed Mehran Vaziri , Esfe Ahmad Reza Ghasemi , Morteza Afsaneh , Khalilzadeh Omid , Pedarzadeh Elham , Shakiba Madjid
Published: June 2011

Aim. To determine the level of the conus medullaris-Tuffier's line, and conus medullaris-Tuffier's line distance using imaging and evaluate their relation to age and gender.Methods. We performed a cross-sectional study of 189 adult participants, who underwent MR imaging of lumbosacral spine. Each vertebra was divided into 3 equal segments (upper, middle, and lower), and intervertebral disc space was also assumed as one segment. All segments from T12 upper segment to L5S1 intervertebral disc were numbered consecutively. The position of conus medullaris and Tuffier's line was determined by the vertebral segment or intervertebral disc space at the same level. The patients were stratified into high/low conus medullaris position (cutpoint: L1 middle segment) and short/long conus-Tuffier's distance (cutpoint: 14 segments).Results. Women with low conus were significantly more than men, in patients older than 50 years old (72.7% in females versus 55.3% in males; ), whereas there was not such a sexual dimorphism in patients younger than 50 years old. Similarly, short conus-Tuffier's distance was more frequent among women than men in patients older than 50 years old (59.7% in females versus 39.5% in males; ), whereas there was not any gender difference in patients younger than 50 years old. Conus-Tuffier's distance was negatively correlated with age (, ) in all studied population.Conclusion. Anatomical landmarks vary according to age and gender, with a lower end of conus medullaris in women, so clinicians should use more caution on the identification of the appropriate site for lumbar puncture, particularly in elderly women.
A PEDF-Derived Peptide Inhibits Retinal Neovascularization and Blocks Mobilization of Bone Marrow-Derived Endothelial Progenitor Cells
Authors: Longeras Richard , Farjo Krysten , Ihnat Michael , Ma Jian-Xing
Published: June 2011

Proliferative diabetic retinopathy is characterized by pathological retinal neovascularization, mediated by both angiogenesis (involving mature endothelial cells) and vasculogenesis (involving bone marrow-derived circulating endothelial progenitor cells (EPCs)). Pigment epithelium-derived factor (PEDF) contains an N-terminal 34-amino acid peptide (PEDF-34) that has antiangiogenic properties. Herein, we present a novel finding that PEDF-34 also possesses antivasculogenic activity. In the oxygen-induced retinopathy (OIR) model using transgenic mice that have Tie2 promoter-driven GFP expression, we quantified Tie2GFP+cells in bone marrow and peripheral blood by fluorescence-activated cell sorting (FACS). OIR significantly increased the number of circulating Tie2-GFP+at P16, correlating with the peak progression of neovascularization. Daily intraperitoneal injections of PEDF-34 into OIR mice decreased the number of Tie2-GFP+cells in the circulation at P16 by 65% but did not affect the number of Tie2-GFP+cells in the bone marrow. These studies suggest that PEDF-34 attenuates EPC mobilization from the bone marrow into the blood circulation during retinal neovascularization.
The ICOS/ICOSL Pathway Is Required for Optimal Antitumor Responses Mediated by Anti–CTLA-4 Therapy
Authors: Fu Tihui , He Qiuming , Sharma Padmanee
Published: June 2011

The anti–CTL-associated antigen 4 (anti–CTLA-4) antibody ipilimumab is the first agent to show improved survival in a randomized phase III trial that enrolled patients with metastatic melanoma. Studies are ongoing to identify mechanisms that elicit clinical benefit in the setting of anti–CTLA-4 therapy. We previously reported that treated patients had an increase in the frequency of T cells expressing the inducible costimulator (ICOS) molecule, a T-cell–specific molecule that belongs to the CD28/CTLA-4/B7 immunoglobulin superfamily. ICOS and its ligand (ICOSL) have been shown to play diverse roles in T-cell responses such as mediating autoimmunity as well as enhancing the development/activity of regulatory T cells. These seemingly opposing roles have made it difficult to determine whether the ICOS/ICOSL pathway is necessary for antitumor responses. To determine whether the ICOS/ICOSL pathway might play a causal role in the antitumor effects mediated by anti–CTLA-4, we conducted studies in ICOS-sufficient and ICOS-deficient mice bearing B16/BL6 melanoma. We show that ICOS+ T cells comprised a population of Th1 cytokine producing and tumor antigen-specific effector cells. Furthermore, in the absence of ICOS, antitumor T-cell responses elicited by anti–CTLA-4 are significantly diminished, thereby impairing tumor rejection. Our findings establish that the ICOS/ICOSL pathway is necessary for the optimal therapeutic effect of anti–CTLA-4, thus implicating this pathway as a target for future combinatorial strategies to improve the efficacy of anti–CTLA-4 therapy. Cancer Res; 71(16); 5445–54. ©2011 AACR.
The GTPase Function of YvcJ and Its Subcellular Relocalization Are Dependent on Growth Conditions in Bacillus subtilis
Authors: Pompeo Frédérique , Luciano Jennifer , Brochier-Armanet Céline , Galinier Anne
Published: June 2011

We have recently shown that the Bacillus subtilis GTPase YvcJ is involved in the phosphorylation of an unidentified cellular component and that the deletion of yvcJ induced a decrease in competence efficiency. In this paper, we report that growth conditions influence both the YvcJ-dependent phosphorylation event and the localization of this protein. More precisely, we have observed that YvcJ can be localized in the cell either as a helical-like pattern or as foci close to the poles and the septa depending on growth phase and on growth medium. In addition, we show that the mutation of the catalytic lysine residue (K22) located in the Walker A motif of YvcJ, and necessary for its GTPase activity, induces a decrease in competence efficiency similar to that observed for the yvcJ null mutant. This mutation also inhibits the YvcJ-dependent phosphorylation event. Furthermore, a phylogenetic analysis of the YvcJ homologues shows that this protein is ancient in Bacteria (being possibly present in their last common ancestor) and has been conserved in a number of major bacterial phyla, suggesting that this protein has an important function in this domain of life. To sum up, even if the precise cellular role of this ancient protein remains unknown, our data show that the GTPase activity of B. subtilis YvcJ and its function in the phosphorylation of a cellular component are influenced by the growth conditions, and are important for the effect of YvcJ on competence efficiency.
Mortality and Readmission of Patients With Heart Failure, Atrial Fibrillation, or Coronary Artery Disease Undergoing Noncardiac Surgery
Authors: van Diepen Sean , Bakal Jeffrey A. , McAlister Finlay A. , Ezekowitz Justin A.
Published: June 2011

Background—

The postoperative risks for patients with coronary artery disease (CAD) undergoing noncardiac surgery are well described. However, the risks of noncardiac surgery in patients with heart failure (HF) and atrial fibrillation (AF) are less well known. The purpose of this study is to compare the postoperative mortality of patients with HF, AF, or CAD undergoing major and minor noncardiac surgery.

Methods and Results—

Population-based data were used to create 4 cohorts of consecutive patients with either nonischemic HF (NIHF; n=7700), ischemic HF (IHF; n=12 249), CAD (n=13 786), or AF (n=4312) who underwent noncardiac surgery between April 1, 1999, and September 31, 2006, in Alberta, Canada. The main outcome was 30-day postoperative mortality. The unadjusted 30-day postoperative mortality was 9.3% in NIHF, 9.2% in IHF, 2.9% in CAD, and 6.4% in AF (each versus CAD,
P
<0.0001). Among patients undergoing minor surgical procedures, the 30-day postoperative mortality was 8.5% in NIHF, 8.1% in IHF, 2.3% in CAD, and 5.7% in AF (
P
<0.0001). After multivariable adjustment, postoperative mortality remained higher in NIHF, IHF, and AF patients than in those with CAD (NIHF versus CAD: odds ratio 2.92; 95% confidence interval 2.44 to 3.48; IHF versus CAD: odds ratio 1.98; 95% confidence interval 1.70 to 2.31; AF versus CAD: odds ratio 1.69; 95% confidence interval 1.34 to 2.14).

Conclusions—

Although current perioperative risk prediction models place greater emphasis on CAD than HF or AF, patients with HF or AF have a significantly higher risk of postoperative mortality than patients with CAD, and even minor procedures carry a risk higher than previously appreciated.
Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID)
Authors: Jessup Mariell , Greenberg Barry , Mancini Donna , Cappola Thomas , Pauly Daniel F. , Jaski Brian , Yaroshinsky Alex , Zsebo Krisztina M. , Dittrich Howard , Hajjar Roger J.
Published: June 2011

Background—

Adeno-associated virus type 1/sarcoplasmic reticulum Ca
2+
-ATPase was assessed in a randomized, double-blind, placebo-controlled, phase 2 study in patients with advanced heart failure.

Methods and Results—

Thirty-nine patients received intracoronary adeno-associated virus type 1/sarcoplasmic reticulum Ca
2+
-ATPase or placebo. Seven efficacy parameters were assessed in 4 domains: symptoms (New York Heart Association class, Minnesota Living With Heart Failure Questionnaire), functional status (6-minute walk test, peak maximum oxygen consumption), biomarker (N-terminal prohormone brain natriuretic peptide), and left ventricular function/remodeling (left ventricular ejection fraction, left ventricular end-systolic volume), plus clinical outcomes. The primary end point success criteria were prospectively defined as achieving efficacy at 6 months in the group-level (concordant improvement in 7 efficacy parameters and no clinically significant worsening in any parameter), individual-level (total score for predefined clinically meaningful changes in 7 efficacy parameters), or outcome end points (cardiovascular hospitalizations and time to terminal events). Efficacy in 1 analysis had to be associated with at least a positive trend in the other 2 analyses. This combination of requirements resulted in a probability of success by chance alone of 2.7%. The high-dose group versus placebo met the prespecified criteria for success at the group-level, individual-level, and outcome analyses (cardiovascular hospitalizations) at 6 months (confirmed at 12 months) and demonstrated improvement or stabilization in New York Heart Association class, Minnesota Living With Heart Failure Questionnaire, 6-minute walk test, peak maximum oxygen consumption, N-terminal prohormone brain natriuretic peptide levels, and left ventricular end-systolic volume. Significant increases in time to clinical events and decreased frequency of cardiovascular events were observed at 12 months (hazard ratio=0.12;
P
=0.003), and mean duration of cardiovascular hospitalizations over 12 months was substantially decreased (0.4 versus 4.5 days;
P
=0.05) on high-dose treatment versus placebo. There were no untoward safety findings.

Conclusions—

The Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) study demonstrated safety and suggested benefit of adeno-associated virus type 1/sarcoplasmic reticulum Ca
2+
-ATPase in advanced heart failure, supporting larger confirmatory trials.

Clinical Trial Registration—

http://www.clinicaltrials.gov
. Unique identifier: NCT00454818.
Utility of Absolute and Relative Changes in Cardiac Troponin Concentrations in the Early Diagnosis of Acute Myocardial Infarction
Authors: Reichlin Tobias , Irfan Affan , Twerenbold Raphael , Reiter Miriam , Hochholzer Willibald , Burkhalter Hanna , Bassetti Stefano , Steuer Stephan , Winkler Katrin , Peter Federico , Meissner Julia , Haaf Philip , Potocki Mihael , Drexler Beatrice , Osswald Stefan , Mueller Christian
Published: June 2011

Background—

Current guidelines for the diagnosis of acute myocardial infarction (AMI), among other criteria, also require a rise and/or fall in cardiac troponin (cTn) levels. It is unknown whether absolute or relative changes in cTn have higher diagnostic accuracy and should therefore be preferred.

Methods and Results—

In a prospective, observational, multicenter study, we analyzed the diagnostic accuracy of absolute (Δ) and relative (Δ%) changes in cTn in 836 patients presenting to the emergency department with symptoms suggestive of AMI. Blood samples for the determination of high-sensitive cTn T and cTn I ultra were collected at presentation and after 1 and 2 hours in a blinded fashion. The final diagnosis was adjudicated by 2 independent cardiologists. The area under the receiver operating characteristic curve for diagnosing AMI was significantly higher for 2-hour absolute (Δ) versus 2-hour relative (Δ%) cTn changes (area under the receiver operating characteristic curve [95% confidence interval], high-sensitivity cTn T: 0.95 [0.92 to 0.98] versus 0.76 [0.70 to 0.83],
P
<0.001; cTn I ultra: 0.95 [0.91 to 0.99] versus 0.72 [0.66 to 0.79],
P
<0.001). The receiver operating characteristic curve–derived cutoff value for 2-hour absolute (Δ) change was 0.007 μg/L for high-sensitivity cTn T and 0.020 μg/L for cTn I ultra (both cutoff levels are half of the 99th percentile of the respective cTn assay). Absolute changes were superior to relative changes in patients with both low and elevated baseline cTn levels.

Conclusions—

Absolute changes of cTn levels have a significantly higher diagnostic accuracy for AMI than relative changes, and seem therefore to be the preferred criteria to distinguish AMI from other causes of cTn elevations.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00470587.
A medieval book and early-modern law: Bracton 's authority and application in the common law c. 1550–1640
Authors: Williams Ian
Published: June 2011

This article considers the place of the thirteenth-century book known as Bracton in the earlymodern common law. e article examines both the uses made of Bracton and the evidence to be found in the surviving copies of the first printed edition. It addresses the impediments to the use of Bracton, the printing of the first edition, the text's readership and place in the early-modern common-law canon and material in Bracton which seem to have been of particular interest.Bracton was a recognised source for criminal law and there is some evidence of impact on the law of evidence, servitudes and a little for contract law. An examination of the early-modern law of treason shows that Bracton had an important role in changing the concept of treason from a crime against the monarch to something like the classical crimen laesae maiestatis.
Carabid beetles (Coleoptera: Carabidae) of the Midwestern United States: a review and synthesis of recent research
Authors: Lundgren Jonathan , McCravy Kenneth
Published: June 2011

Carabid beetles comprise a diverse and ubiquitous family of insects. Carabids are important in conservation biology and often have close associations with particular habitat types, making them useful biomonitoring organisms. Many carabids are also important biological control agents due to their predatory habits, but feeding habits within the family are quite diverse, and seed-eating or granivorous carabids can play an important role in shaping plant diversity and distributions. These qualities have particular relevance in the highly cultivated and fragmented landscape of the Midwestern U.S., and this region has become a very active one for carabid research in a variety of areas. In this paper, we review the state of carabid research in the Midwestern U.S., focusing on work published since the mid-1990s in carabid biogeography, conservation biology, biological control/pest management, feeding ecology and parasitism/health. Potentially productive directions for future research are discussed.
The Externalization of Peacekeeping: Policy, Responsibility, and Accountability
Authors: Buchan Russell , Jones Henry , White Nigel D.
Published: June 2011

The post-Cold War trend towards the privatization of some of the security and military functions of post-conflict and conflict operations conducted by states is extending to peacekeeping operations undertaken by the UN and other organizations. This article examines the policies behind the increased use of private military and security contractors (PMSCs) in peacekeeping, considers the obstacles to accountability and responsibility caused by this development, and suggests ways of overcoming these obstacles to provide remedies for victims of human rights abuse at the hands of such contractors.
It Takes Two (or More) to Keep the Peace: Multiple Simultaneous Peace Operations
Authors: Balas Alexandru
Published: June 2011

This study introduces the concept of multiple simultaneous peace operations (MSPOs). Two or more peace operations deployed at the same time in the same conflicts are MSPOs. There are numerous conflicts in which a United Nations peace operation works side by side with the peace operations of regional international organizations. The majority (60%) of all peace operations from 1978-2009 are MSPOs. Multiple simultaneous peace operations are also the 21st century’s trend for deployments. This study provides a description of a new dataset on multiple simultaneous peace operations and argues for analyzing peace operations through the lenses of MSPOs. Th is concept is useful for understanding inter-organizational cooperation in peace operations and the eff ectiveness of peace operations. It could also be used to apply an innovative collective principals - multiple agents model to the study of international security organizations. A major contribution of this study is that it provides empirical evidence that African conflicts are initially left to inexperienced regional organizations, while European conflicts receive the best expertise immediately. Using the dataset I also identify the most common type of multiple simultaneous peace operations. Parallel deployments are the dominant type, followed by sequential, and by hybrid operations.
Peacekeeper Impartiality: Standards, Processes, and Operations
Authors: Levine Daniel H.
Published: June 2011

Though UN peacekeeping has changed dramatically since its inception, peacekeepers are still ostensibly committed to the “holy trinity” of consent, impartiality, and minimum use of force. Impartiality has come under special pressure, as peacekeepers are increasingly expected not only to observe the situation, but to take forceful action against “spoiler” groups that threaten the peace or human rights. This essay draws on official statements, outside analysis, and a number of interviews with peacekeepers conducted by the author and his research assistant, to demonstrate that a wide variety of understandings of “impartiality” currently exist, potentially undermining peacekeeping operations. The author attempts to systematize these variations according to how they understand the standard of impartiality, the process for making impartial decisions, and the scope of operations that fall under the concept. Ultimately, the author argues for an understanding of impartiality that is practically focused on achieving peace and includes structured consultations with all parties as a conceptual necessity, not just a helpful technique.