bluuebunny/crossref_metadata_2025 huggingface dataset:
Defects in Phosphate Acquisition and Storage Influence Virulence of Cryptococcus neoformans
Authors: Kretschmer Matthias , Reiner Ethan , Hu Guanggan , Tam Nicola , Oliveira Debora L. , Caza Melissa , Yeon Ju Hun , Kim Jeongmi , Kastrup Christian J. , Jung Won Hee , Kronstad James W.
Published: April 2014

Nutrient acquisition and sensing are critical aspects of microbial pathogenesis. Previous transcriptional profiling indicated that the fungal pathogen
Cryptococcus neoformans
, which causes meningoencephalitis in immunocompromised individuals, encounters phosphate limitation during proliferation in phagocytic cells. We therefore tested the hypothesis that phosphate acquisition and polyphosphate metabolism are important for cryptococcal virulence. Deletion of the high-affinity uptake system interfered with growth on low-phosphate medium, perturbed the formation of virulence factors (capsule and melanin), reduced survival in macrophages, and attenuated virulence in a mouse model of cryptococcosis. Additionally, analysis of nutrient sensing functions for
C. neoformans
revealed regulatory connections between phosphate acquisition and storage and the iron regulator Cir1, cyclic AMP (cAMP)-dependent protein kinase A (PKA), and the calcium-calmodulin-activated protein phosphatase calcineurin. Deletion of the
VTC4
gene encoding a polyphosphate polymerase blocked the ability of
C. neoformans
to produce polyphosphate. The
vtc4
mutant behaved like the wild-type strain in interactions with macrophages and in the mouse infection model. However, the fungal load in the lungs was significantly increased in mice infected with
vtc4
deletion mutants. In addition, the mutant was impaired in the ability to trigger blood coagulation
in vitro
, a trait associated with polyphosphate. Overall, this study reveals that phosphate uptake in
C. neoformans
is critical for virulence and that its regulation is integrated with key signaling pathways for nutrient sensing.
Immunosuppressive Compounds Exhibit Particular Effects on Functional Properties of Human Anti-Aspergillus T
H
1 Cells
Authors: Tramsen Lars , Schmidt Stanislaw , Roeger Frauke , Schubert Ralf , Salzmann-Manrique Emilia , Latgé Jean-Paul , Klingebiel Thomas , Lehrnbecher Thomas
Published: April 2014

Allogeneic hematopoietic stem cell transplant (HSCT) recipients are at high risk for invasive aspergillosis. Whereas adoptive immunotherapy transferring donor-derived anti-
Aspergillus
T
H
1 cells has been shown to be beneficial for HSCT recipients suffering from invasive aspergillosis, little is known about the impact of commonly used immunosuppressants on the functional properties of anti-
Aspergillus
T
H
1 cells. Anti-
Aspergillus
T
H
1 cells were coincubated with different concentrations of methylprednisolone, cyclosporine (CsA), mycophenolic acid (MPA), the active component of mycophenolate mofetil, and rapamycin. Immunosuppressants were tested in concentrations reflecting common target levels in serum and in significantly lower and higher concentrations. Apoptosis of anti-
Aspergillus
T
H
1 cells, as well as proliferation and production of gamma interferon (IFN-γ) and CD154 upon restimulation, was evaluated in the presence and absence of immunosuppressive compounds. All dosages of CsA, MPA, and methylprednisolone significantly decreased the number of viable anti-
Aspergillus
T
H
1 cells in the cell culture, which was due partly to an impaired proliferative capacity of the cells and partly to an increased rate of apoptosis. In addition, CsA significantly decreased the number of IFN-γ-producing cells and had the highest impact of all immunosuppressants on IFN-γ levels in the supernatant. CsA also significantly decreased the expression of CD154 by anti-
Aspergillus
T
H
1 cells. Variant dosages of immunosuppressants exhibit particular effects on essential functional properties of anti-
Aspergillus
T
H
1 cells. Our findings may have an important impact on the design of clinical trials evaluating the therapeutic benefit of anti-
Aspergillus
T
H
1 cells in allogeneic HSCT recipients suffering from invasive aspergillosis.
Insulin supersensitivity and normoinsulinaemic hypoglycaemia in uncontrolled type 2 diabetes mellitus: clinical usefulness of 3 h assessment in the 75 g oral glucose tolerance test
Authors: Sugiyama Seigo , Jinnouchi Hideaki , Hieshima Kunio , Jinnouchi Tomio
Published: April 2014

A 60-year-old man with uncontrolled type 2 diabetes mellitus (DM) (glycated haemoglobin 11%) had the unusual symptoms of palpitations and sweating after drinking an excessive amount of soft drinks. Three-hour data in the 75-g oral glucose tolerance test (75g-OGTT) repeatedly showed normoinsulinaemic hypoglycaemia. His diabetic disorder was based on a delayed insulin secretory response to hyperglycaemia and daily excessive intake of glucose from a high caloric diet and soft drinks. However, we paradoxically observed increased insulin sensitivity evaluated by a hyperinsulinaemic-euglycaemic clamp (glucose infusion rate: 64.83 μmol/kg/min). We considered that insulin supersensitivity might be involved in the pathogenic mechanisms of his clinical normoinsulinaemic hypoglycaemia. He was successfully treated by diet and exercise therapy without any hypoglycaemic medications or insulin. Assessment after the 75g-OGTT is useful for investigating the pathogenesis of DM. Insulin supersensitivity and normoinsulinaemic hypoglycaemia might play a role in clinical manifestation and pathogenesis of type 2 DM.
Constipation: take it seriously
Authors: Faruqi Uzma , Lynch Joanna , Husada Glen
Published: April 2014

A case report of a young, healthy female who presented as an emergency with large bowel obstruction secondary to a rectosigmoid tumour. Acute presentation was preceded by a progressive history of change in bowel habit managed medically in the community with laxative treatment. The family history of note included breast cancer of an identical triplet aged 41 years. An emergency Hartman's procedure was successfully performed the same day as presentation due to the high risk of perforation. The patient was discharged home within a week. Histology confirmed adenocarcinoma, Dukes’ Stage C and oncologists have now taken over care of the patient. Discussion points explore whether it is appropriate to refer a young healthy patient presenting with a change in bowel habit if she is resistant to medical management in the community and in the absence of other red flag symptoms. The family history of malignancy and genetic associations are also considered.
Rapidly progressive coronary artery disease as the first manifestation of antiphospholipid syndrome
Authors: Abdullah Abdullah Sayied , Yagoub Hatim , Kiernan Thomas J , Daly Caroline
Published: April 2014

Antiphospholipid syndrome (APS) is an autoimmune multisystem disorder characterised by high incidence of arterial and venous thrombosis. Cardiovascular manifestations also include valvular heart disease, ventricular thrombi and higher risk for coronary artery disease (CAD). In this case report, we describe a 61-year-old woman who had no significant risk factors for CAD, and presented with aggressive disease in native and graft vessels that required multiple coronary interventions. The extent of her aggressive CAD could not be explained by her risk factors profile. Therefore autoantibodies screening was carried out and showed a strongly positive anticardiolipin and β2glycoprotein-I antibody, and hence a diagnosis of antiphospholipid syndrome was made.
Determinants Of Oral corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY): protocol for a prospective multicentre cohort study of children with acute moderate-to-severe asthma exacerbations
Authors: Ducharme F M , Zemek R , Gravel J , Chalut D , Poonai N , Laberge S , Quach C , Krajinovic M , Guimont C , Lemière C , Guertin M C
Published: April 2014

Introduction

Oral corticosteroids are the cornerstone of acute asthma management in the emergency department. Recent evidence has raised doubts about the efficacy of this treatment in preschool-aged children with viral-induced wheezing and in smoking adults. The aims of the study were to: (1) document the magnitude of response to oral corticosteroids in children presenting to the emergency department with moderate or severe asthma; (2) quantify potential determinants of response to corticosteroids and (3) explore the role of gene polymorphisms associated with the responsiveness to corticosteroids.

Methods and analysis

The design is a prospective cohort study of 1008 children aged 1–17 years meeting a strict definition of asthma and presenting with a clinical score of ≥4 on the validated Pediatric Respiratory Assessment Measure. All children will receive standardised severity-specific treatment with prednisone/prednisolone and cointerventions (salbutamol with/without ipratropium bromide). Determinants, namely viral aetiology, environmental tobacco smoke and single nucleotide polymorphism, will be objectively documented. The primary efficacy endpoint is the failure of emergency department (ED) management within 72 h of the ED visit. Secondary endpoints include other measures of asthma severity and time to recovery within 7 days of the index visit. The study has 80% power for detecting a risk difference of 7.5% associated with each determinant from a baseline risk of 21%, at an α of 0.05.

Ethics and dissemination

Ethical approval has been obtained from all participating institutions. An impaired response to systemic steroids in certain subgroups will challenge the current standard of practice and call for the immediate search for better approaches. A potential host–environment interaction will broaden our understanding of corticosteroid responsiveness in children. Documentation of similar effectiveness of corticosteroids across determinants will provide the needed reassurance regarding current treatment recommendations.

Results

Results will be disseminated at international conferences and manuscripts targeted at emergency physicians, paediatricians, geneticists and respirologists.

Trial registration number

This study is registered at Clinicaltrials.gov (NCT02013076).
Fat-soluble vitamin deficiency in children and adolescents with cystic fibrosis
Authors: Rana Malay , Wong-See Denise , Katz Tamarah , Gaskin Kevin , Whitehead Bruce , Jaffe Adam , Coakley John , Lochhead Alistair
Published: April 2014

Aims

Determine the prevalence of fat-soluble vitamin deficiency in children with cystic fibrosis (CF) aged ≤18 years in New South Wales (NSW), Australia, from 2007 to 2010.

Methods

A retrospective analysis of fat-soluble vitamin levels in children aged ≤18 years who lived in NSW and attended any of the three paediatric CF centres from 2007 to 2010. An audit of demographic and clinical data during the first vitamin level measurement of the study period was performed.

Results

Deficiency of one or more fat-soluble vitamins was present in 240/530 children (45%) on their first vitamin level test in the study period. The prevalence of vitamins D and E deficiency fell from 22.11% in 2007 to 15.54% in 2010, and 20.22% to 13.89%, respectively. The prevalence of vitamin A deficiency increased from 11.17% to 13.13%. Low vitamin K was present in 29% in 2007, and prevalence of prolonged prothrombin time increased from 19.21% to 22.62%. Fat-soluble vitamin deficiency is present in 10%–35% of children with pancreatic insufficiency, but only a very small proportion of children who are pancreatic-sufficient.

Conclusions

This is one of few studies of fat-soluble vitamin deficiency in children with CF in Australia. Fat-soluble vitamin testing is essential to identify deficiency in pancreatic-insufficient children who may be non-compliant to supplementation or require a higher supplement dose, and pancreatic-sufficient children who may be progressing to insufficiency. Testing of vitamin K-dependent factors needs consideration. Further studies are needed to monitor rates of vitamin deficiency in the CF community.
In situ LA–ICP–MS dating of monazite from aluminous gneisses: insights on the tectono-metamorphic history of a granulite-facies domain in the central Grenville Province
Authors: Lasalle Stephanie , Dunning Greg , Indares Aphrodite
Published: April 2014

In situ U–Pb dating of monazite from granulite-facies anatectic aluminous gneisses of the hinterland of the Grenville Province (Manicouagan area) is used to constrain the age of metamorphic events. Matrix grains in these rocks show complex internal textures consistent with extensive corrosion and overgrowths which are attributed to partial dissolution of earlier monazite in anatectic melt followed by new growth during melt crystallization or subsequent fluid infiltration. The new monazite data show the following: (i) inherited “pre-Grevillian” ages up to ca. 1400 Ma in some rocks; (ii) “main Grenvillian” ages in the general range of ca. 1070–1020 Ma, with a variable spread in individual samples and a general cluster at 1070–1050 Ma; and (iii) “late Grenvillian” ages at ca. 1010–990 Ma, mostly restricted to backscatter electron (BSE)-bright rims of matrix grains. The wide age range of the main Grenvillian metamorphism suggests episodic growth of monazite over a wide time span, consistent with protracted residence of the host rocks under high-temperature conditions. The clusters in the age distribution likely represent major episodes of melt crystallization in the respective rocks, following the granulite-facies metamorphism. In contrast, the growth of the late Grenvillian monazite at ca. 1000 Ma is attributed to late fluid infiltration of the host rocks under greenschist-facies conditions, coeval with ultrapotassic magmatism. It is the first report of a late Grenvillian metamorphic overprint on granulite-facies mineral assemblages in the hinterland and is consistent with the model of extensional collapse of the orogen.
Trade-offs between growth and reproduction in wild Atlantic cod
Authors: Folkvord Arild , Jørgensen Christian , Korsbrekke Knut , Nash Richard D.M. , Nilsen Trygve , Skjæraasen Jon Egil
Published: April 2014

Animals partition and trade off their resources between competing needs such as growth, maintenance, and reproduction. Over a lifetime, allocation strategies should result in distinct trajectories for growth, survival, and reproduction, but such longitudinal individual data are difficult to reconstruct for wild animals and especially marine fish. We were able to reconstruct two of these trajectories in wild-caught Northeast Arctic cod (Gadus morhua) females: size-at-age was back-calculated from otolith growth increments, and recent spawning history was reconstructed from postovulatory follicles and present oocyte development. Our findings indicate distinct trade-offs between length growth and reproduction. Fish that sexually matured early had attained a larger size at age 3 than immatures, but onset of reproduction caused slower growth compared with immatures. We found that 6- and 7-year-old females skipping spawning grew significantly more in the year of missed spawning than females spawning for the second consecutive year. The latter tentatively supports the hypothesis that skipped spawning may occur as an adaptive life-history strategy, given the potential future fecundity gain with increased size.
Targeting angiotensin-converting enzyme 2 as a new therapeutic target for cardiovascular diseases
Authors: Parajuli Nirmal , Ramprasath Tharmarajan , Patel Vaibhav B. , Wang Wang , Putko Brendan , Mori Jun , Oudit Gavin Y.
Published: April 2014

Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that metabolizes several vasoactive peptides, including angiotensin II (Ang-II; a vasoconstrictive/proliferative peptide), which it converts to Ang-(1–7). Ang-(1–7) acts through the Mas receptor to mediate vasodilatory/antiproliferative actions. The renin–angiotensin system involving the ACE–Ang-II–Ang-II type-1 receptor (AT1R) axis is antagonized by the ACE2–Ang-(1–7)–Mas receptor axis. Loss of ACE2 enhances adverse remodeling and susceptibility to pressure and volume overload. Human recombinant ACE2 may act to suppress myocardial hypertrophy, fibrosis, inflammation, and diastolic dysfunction in heart failure patients. The ACE2–Ang-(1–7)–Mas axis may present a new therapeutic target for the treatment of heart failure patients. This review is mainly focused on the analysis of ACE2, including its influence and potentially positive effects, as well as the potential use of human recombinant ACE2 as a novel therapy for the treatment cardiovascular diseases, such as hypertension and heart failure.
Quantum state transfer through a thermal spin channel
Authors: Su Xiao Qiang , Wang An Min , Yang Guo Hui
Published: April 2014

The dynamics of quantum state transfer through a thermal spin chain with Heisenberg interaction is discussed by numerically calculating the maximal fidelity in a finite transfer time for the chains with several numbers of sites. We find that the maximal fidelity does not decrease monotonously with the increase in the temperature, but depends on the maximal allowed transfer time. Finally, we compare the results of thermal channel with the transfer through ground state channel.
Renormalization group method for kink dynamics in a perturbed sine-Gordon equation
Authors: Wang Li , Tu Tao , Guo Ping-Guo , Guo Guang-Can
Published: April 2014

In this paper, we show that renormalization group theory can be used to give a systematic description of the evolution of the kink in a perturbed sine-Gordon equation. The present method gives the same results as inverse scattering theory and other approaches, which may provide a new insight into the soliton dynamics of perturbed equations.
Clausius' entropy revisited
Authors: Cohen E. G. D. , Merlino R. L.
Published: April 2014

Conventional nonequilibrium thermodynamics is mainly concerned with systems in local equilibrium and their entropy production, due to the irreversible processes which take place in these systems. In this paper, fluids will be considered in a state of local equilibrium. We argue that the main feature of such systems is not the entropy production, but the organization of the flowing currents in such systems. These currents do not only have entropy production, but must also have an organization needed to flow in a certain direction. It is the latter, which is the source of the equilibrium entropy, when the fluid goes from a local equilibrium state to an equilibrium state. This implies a transmutation of the local equilibrium currents' organization into the equilibrium entropy. Alternatively, when a fluid goes from an equilibrium state to a local equilibrium state, its entropy transmutes into the organization of the currents of that state.
Causality constraints on hadron production in high energy collisions
Authors: Castorina Paolo , Satz Helmut
Published: April 2014

For hadron production in high energy collisions, causality requirements lead to the counterpart of the cosmological horizon problem: the production occurs in a number of causally disconnected regions of finite space-time size. As a result, globally conserved quantum numbers (charge, strangeness, baryon number) must be conserved locally in spatially restricted correlation clusters. This provides a theoretical basis for the observed suppression of strangeness production in elementary interactions (pp, e+e-). In contrast, the space-time superposition of many collisions in heavy ion interactions largely removes these causality constraints, resulting in an ideal hadronic resonance gas in full equilibrium.
Coherent control of tunable entanglement between two resonators in superconducting circuits
Authors: Zhong Wen-Xue , Cheng Guang-Ling , Chen Ai-Xi
Published: April 2014

We present an efficient method to generate Einstein–Podolsky–Rosen (EPR) entanglement of two microwave photons with different frequencies in two superconducting resonators. Our scheme is based on the sideband couplings of two resonators with a single gap-tunable superconducting quantum circuits driven by a controlled field. By the proper choice of the physical parameters, the nonlinear interaction of parametric down-conversion occurs between two resonators while the superconducting qubit remains in the original state, which is responsible for the entanglement generation. The present scheme would provide a promising alternative approach to scalable quantum information processing in solid-state systems.
Investigation of axial ligand effects on catalytic activity of manganese porphyrin, evidence for the importance of hydrogen bonding in cytochrome-P450 model reactions
Authors: Mesbahi Elnaz , Safari Nasser , Gheidi Mahin
Published: April 2014

Various nitrogenous bases, such as imidazoles, pyridines and amines were employed as axial ligands in epoxidation reaction of cyclooctene bytetra-n-butylammonium hydrogen monopersulfate (n- Bu 4 NHSO 5), in the presence of Mn ( III )-tetrakis(2,3-dimethoxyphenyl)porphyrin-acetate ( T (2,3- OMeP ) PorMnOAc ). T (2,3- OMeP ) PorMnOAc is a fairly stable catalyst, with the ability of producing hydrogen bonding. High epoxidation yield of 85 ± 6% was obtained in the presence of imidazole axial ligand with 100% selectivity in 30 min. Higher conversion of around 100% was obtained by pyridine axial base, while selectivity was reduced to 69%. Further epoxidation reactions were also performed using Mn ( III )-Tetrakis(2,3-dihydroxyphenyl)porphyrin-acetate ( T (2,3- OHP ) PorMnOAc ) as catalyst. In addition to the usual electronic and steric effects, it is proposed that the catalytic activity depends on the existence and kind of hydrogen bonding between the axial base and the ortho-methoxy or hydroxy groups on the phenyl rings of manganese porphyrin. The cis to trans ratio of cis-stilbene oxide formed by imidazole and pyridine axial bases were obtained as 7.5 and 2.5 respectively. In addition GC-Ms and UV-vis studies were employed to find the nature of active species and product formation. Our DFT calculations disclosed that pyridine hydrogen bonding with moiety of the macrocycle rings strongly affects the relative energies of S/Q spin states in [ T (2,3- OMeP ) PorMn V ( O )( Py )]+, in that it results in the longer Mn – O bond and reactivity toward substrates.
Self-sealing barriers of sand/clay mixtures – lessons learnt from
in situ
experiment and retrospective modelling
Authors: Czaikowski O. , Miehe R. , Rothfuchs T.
Published: April 2014

In the framework of the SB experiment (‘Self-sealing barriers of sand/clay mixtures’), a series of small
in situ
tests in several vertical boreholes were installed in October 2005 at the underground rock laboratory at Mont Terri. The boreholes were backfilled with sand/clay mixtures at different ratios as well as pure MX-80 bentonite. At the GRS laboratory the experimental setup was installed in advance and has run under nearly the same boundary conditions since March 2005. Sand/clay mixtures exhibit a high permeability to gas in the dry state and a low gas entry pressure and moderate permeability to gas in the saturated state, while the permeability to water is comparable to that of the undisturbed host rock. Therefore, gaseous corrosion products will be preferentially conducted through the seal, mitigating the risk of opening new pathways (fractures) in the host rock. The main objective of the SB experiment presented here is to test and demonstrate that the advantageous sealing properties of clay/sand mixtures determined in the laboratory can technically be achieved and maintained under repository-relevant
in situ
conditions.
Earth tidal and barometric responses observed in the Callovo-Oxfordian clay Formation at Andra Meuse/Haute-Marne Underground Research Laboratory
Authors: Delcourt-Honorez M. , Scholz E.
Published: April 2014

Fluid pressures were recorded over 6.5 years in borehole EST207 located at the Andra Meuse/Haute-Marne Underground Research Laboratory in Bure (France). The borehole is equipped with a multipacker system monitoring 11 intervals, including 8 in the Callovo-Oxfordian clay Formation, 2 in the Dogger Formation and 1 at the Oxfordian base. Pressure data were analysed for responses to Earth tides and barometric pressure in the 11intervals. Fourier analyses on the pressure data revealed some of the Earth tidal components. Use of ETERNA software determined a better estimate of Earth tidal wave parameters (amplitudes, phases and their standard deviations) and barometric efficiency. Estimates of the tidal parameters K1, O1, P1, S1 and M2, N2, S2, K2 were made before and after barometric correction. It is suggested that in the Callovo-Oxfordian clay, the greater the clay content of the formation, the greater the barometric efficiency values. A barometric and tidal responses classification using four groups as a function of the 11 borehole intervals is in good agreement with the geological configuration. This preliminary geological interpretation will allow both the estimation of poroelastic and hydrogeological parameters of the clay formation from Earth tidal and barometric responses without classical pump test experiments, and the monitoring of these properties over a long period.
Two-phase-flow pore-size simulations in Opalinus clay by the Lattice Boltzmann Method
Authors: Dymitrowska M. , Pazdniakou A. , Adler Pierre M.
Published: April 2014

The experimental determination of transport properties of low permeability clay rocks, especially of relative permeabilities and capillary pressure curves for water and gas, is a very challenging issue, in particular at high water saturation (very low gas permeability resulting in long equilibration times) and for gaseous hydrogen (due to the high pressures involved and the resulting explosion risk). Navier-Stokes equations are solved inside a porous medium on the pore scale, so as to derive the absolute and relative (two-phase-flow) permeabilities. For this purpose microtomography data of Opalinus clay samples acquired in the Mont Terri Ventilation Experiment are used to visualize the pore space in 3D at a micrometric scale (porosity size >0.7 µm). The corresponding percolating porosity is mainly composed of micrometric cracks parallel to the bedding and attributed to shrinkage. Two-phase flow is calculated in the percolating cracks by an immiscible Lattice Boltzmann (LBM) code. In addition, some validation results of the LBM model for three-phase systems (liquid-gas-solid) are presented.
A taxonomy for requirements engineering and software test alignment
Authors: Unterkalmsteiner M. , Feldt R. , Gorschek T.
Published: April 2014

Requirements Engineering and Software Testing are mature areas and have seen a lot of research. Nevertheless, their interactions have been sparsely explored beyond the concept of traceability. To fill this gap, we propose a definition of requirements engineering and software test (REST) alignment, a taxonomy that characterizes the methods linking the respective areas, and a process to assess alignment. The taxonomy can support researchers to identify new opportunities for investigation, as well as practitioners to compare alignment methods and evaluate alignment, or lack thereof. We constructed the REST taxonomy by analyzing alignment methods published in literature, iteratively validating the emerging dimensions. The resulting concept of an information dyad characterizes the exchange of information required for any alignment to take place. We demonstrate use of the taxonomy by applying it on five in-depth cases and illustrate angles of analysis on a set of thirteen alignment methods. In addition, we developed an assessment framework (REST-bench), applied it in an industrial assessment, and showed that it, with a low effort, can identify opportunities to improve REST alignment. Although we expect that the taxonomy can be further refined, we believe that the information dyad is a valid and useful construct to understand alignment.
Required behavior of sequence diagrams
Authors: Lu Lunjin , Kim Dae-Kyoo
Published: April 2014

Many reusable software artifacts such as design patterns and design aspects make use of UML sequence diagrams to describe interaction behaviors. When a pattern or an aspect is reused in an application, it is important to ensure that the sequence diagrams for the application conform to the corresponding sequence diagrams for the pattern or aspect. Reasoning about conformance relationship between sequence diagrams has not been addressed adequately in literature. In this article, we focus on required behaviors specified by a UML sequence diagram and provide a semantic-based formalization of conformance relationships between sequence diagrams. A novel trace semantics is first given that captures precisely required behaviors. A refinement relation between sequence diagrams is then defined based on the semantics. The refinement relation allows a sequence diagram to be refined by changing its structure so long as its required behaviors are preserved. A conformance relation between sequence diagrams is finally given that includes the refinement relation as a special case. It allows one to introduce and rename lifelines, messages, and system variables when reusing sequence diagrams. Properties of the semantics, refinement, and conformance relations are studied. Two case studies are provided to illustrate the efficacy of semantic-based conformance reasoning.
A survey on concept drift adaptation
Authors: Gama João , Žliobaitė Indrė , Bifet Albert , Pechenizkiy Mykola , Bouchachia Abdelhamid
Published: April 2014

Concept drift primarily refers to an online supervised learning scenario when the relation between the input data and the target variable changes over time. Assuming a general knowledge of supervised learning in this article, we characterize adaptive learning processes; categorize existing strategies for handling concept drift; overview the most representative, distinct, and popular techniques and algorithms; discuss evaluation methodology of adaptive algorithms; and present a set of illustrative applications. The survey covers the different facets of concept drift in an integrated way to reflect on the existing scattered state of the art. Thus, it aims at providing a comprehensive introduction to the concept drift adaptation for researchers, industry analysts, and practitioners.
Shortest-path queries in static networks
Authors: Sommer Christian
Published: April 2014

We consider the
point-to-point (approximate) shortest-path query problem
, which is the following generalization of the classical
single-source (SSSP)
and
all-pairs shortest-path (APSP)
problems: we are first presented with a
network (graph)
. A so-called preprocessing algorithm may compute certain information
(a data structure or index)
to prepare for the next phase. After this preprocessing step, applications may ask shortest-path or distance queries, which should be answered as fast as possible.

Due to its many applications in areas such as transportation, networking, and social science, this problem has been considered by researchers from various communities (sometimes under different names): algorithm engineers construct fast route planning methods; database and information systems researchers investigate
materialization tradeoffs
, query processing on
spatial networks
, and
reachability queries
; and theoretical computer scientists analyze
distance oracles
and
sparse spanners
. Related problems are considered for
compact routing
and
distance labeling
schemes in networking and distributed computing and for
metric embeddings
in geometry as well.

In this survey, we review selected approaches, algorithms, and results on shortest-path queries from these fields, with the main focus lying on the tradeoff between the index size and the query time. We survey methods for general graphs as well as specialized methods for restricted graph classes, in particular for those classes with arguable practical significance such as planar graphs and complex networks.
Interest management for distributed virtual environments
Authors: Liu Elvis S. , Theodoropoulos Georgios K.
Published: April 2014

The past two decades have witnessed an explosion in the deployment of large-scale distributed simulations and distributed virtual environments in different domains, including military and academic simulation systems, social media, and commercial applications such as massively multiplayer online games. As these systems become larger, more data intensive, and more latency sensitive, the optimisation of the flow of data, a paradigm referred to as interest management, has become increasingly critical to address the scalability requirements and enable their successful deployment. Numerous interest management schemes have been proposed for different application scenarios. This article provides a comprehensive survey of the state of the art in the design of interest management algorithms and systems. The scope of the survey includes current and historical projects providing a taxonomy of the existing schemes and summarising their key features. Identifying the primary requirements of interest management, the article discusses the trade-offs involved in the design of existing approaches.
A survey on server-side approaches to securing web applications
Authors: Li Xiaowei , Xue Yuan
Published: April 2014

Web applications are one of the most prevalent platforms for information and service delivery over the Internet today. As they are increasingly used for critical services, web applications have become a popular and valuable target for security attacks. Although a large body of techniques have been developed to fortify web applications and mitigate attacks launched against them, there has been little effort devoted to drawing connections among these techniques and building the big picture of web application security research.

This article surveys the area of securing web applications from the server side, with the aim of systematizing the existing techniques into a big picture that promotes future research. We first present the unique aspects of the web application development that cause inherent challenges in building secure web applications. We then discuss three commonly seen security vulnerabilities within web applications:
input validation vulnerabilities, session management vulnerabilities
, and
application logic vulnerabilities
, along with attacks that exploit these vulnerabilities. We organize the existing techniques along two dimensions: (1) the security vulnerabilities and attacks that they address and (2) the design objective and the phases of a web application during which they can be carried out. These phases are
secure construction of new web applications, security analysis/testing of legacy web applications
, and
runtime protection of legacy web applications
. Finally, we summarize the lessons learned and discuss future research opportunities in this area.
Dynamite
Authors: Moscato Mariano M. , Pombo Carlos G. Lopez , Frias Marcelo F.
Published: April 2014

Automatic analysis of Alloy models is supported by the Alloy Analyzer, a tool that translates an Alloy model to a propositional formula that is then analyzed using off-the-shelf SAT solvers. The translation requires user-provided bounds on the sizes of data domains. The analysis is limited by the bounds and is therefore partial. Thus, the Alloy Analyzer may not be appropriate for the analysis of critical applications where more conclusive results are necessary.

Dynamite is an extension of PVS that embeds a complete calculus for Alloy. It also includes extensions to PVS that allow one to improve the proof effort by, for instance, automatically analyzing new hypotheses with the aid of the Alloy Analyzer. Since PVS sequents may get cluttered with unnecessary formulas, we use the Alloy unsat-core extraction feature in order to refine proof sequents. An internalization of Alloy's syntax as an Alloy specification allows us to use the Alloy Analyzer for producing witnesses for proving existentially quantified formulas.

Dynamite complements the partial automatic analysis offered by the Alloy Analyzer with semi-automatic verification through theorem proving. It also improves the theorem proving experience by using the Alloy Analyzer for early error detection, sequent refinement, and witness generation.
A game based passive worm defense model for P2P networks
Authors: Tang Haokun , Huang Jun , Wang Wei
Published: April 2014

Passive worm, a huge hidden trouble to P2P applications, has drawn much attention because of its undetectable, destructive, and wide-ranging features. Existing propagation models for passive worm only noticed its similarity to biological viruses in propagation, ignored the impact of social attributes of P2P nodes on the spread of worms, such as trust relationship, network topology, security awareness and potential profit. Although these models were simple and efficient, they did not match the defense process of passive worm in dynamic environment. This paper proposes a defense model of passive worm in P2P networks. The contributions made in this paper include four aspects. First, we analyze the deficiency of current defense model of passive worm based on mean-field theory in P2P networks. Second, we build a node evaluation system based on trust relationship, by which the resource providers in P2P networks are determined. Third, we develop a defense model based on game theory. Fourth, we provide extensive numerical study and simulation experiments to the impact of some relevant model parameters on the defense of passive worm in P2P networks. The model presented in this paper is applicable for defending against passive worms in P2P networks.
MOOC experience
Authors: Liyanagunawardena Tharindu R.
Published: April 2014

In this article the author reflects on the experiences of three Massive Open Online Courses (MOOCs): Edfuture (CHFE), Learning Design for 21st Century Curriculum (OLDS-MOOC), and Open Education (H817). Discussion draws on the perceived differences between OERs and MOOCs and questions the definitions of 'success', 'engagement', 'completion', and 'drop out' in a MOOC. Some lessons learnt as a participant are also discussed.
What's yours is mine and what's mine's my own
Authors: Adams A. A. , Williams S. A.
Published: April 2014

Many online services assume that they each account will only be accessed by one person, ever. This is even enshrined in the terms and conditions for some. However, our identities are bound up with others in various ways, in both life and death, legally and socially. A basic classification system for multiple ownership of accounts is proposed, based on fictionalised accounts of real world problems encountered by the authors and their acquaintances.
Ipb-frame adaptive mapping mechanism for video transmission over IEEE 802.11e WLANs
Authors: Yao Xin-Wei , Wang Wan-Liang , Yang Shuang-Hua , Cen Yue-Feng , Yao Xiao-Min , Pan Tie-Qiang
Published: April 2014

This paper proposed an IPB-frame Adaptive Mapping Mechanism (AMM) to improve the video transmission quality over IEEE 802.11e Wireless Local Area Networks (WLANs). Based on the frame structure of hierarchical coding technology, the probability of each frame allocated to the most appropriate Access Category (AC) was dynamically updated according to its importance and traffic load of each AC. Simulation results showed the superior performance of the proposed AMM by comparing with three other existing mechanisms in terms of three objective metrics.
Using peeringDB to understand the peering ecosystem
Authors: Lodhi Aemen , Larson Natalie , Dhamdhere Amogh , Dovrolis Constantine , claffy kc
Published: April 2014

In this study we mine one of the few sources of public data available about the interdomain peering ecosytem: PeeringDB [1], an online database where participating networks contribute information about their peering policies, traffic volumes and presence at various geographic locations. Although established to support the practical needs of operators, this data also provides a valuable source of information to researchers. Using BGP data to cross-validate three years of PeeringDB snapshots, we find that PeeringDB membership is reasonably representative of the Internet's transit, content, and access providers in terms of business types and geography of participants, and PeeringDB data is generally up-to-date. We find strong correlations among different measures of network size -- BGP-advertised address space, PeeringDB-reported traffic volume and presence at peering facilities, and between these size measures and advertised peering policies.
Rekindling network protocol innovation with user-level stacks
Authors: Honda Michio , Huici Felipe , Raiciu Costin , Araujo Joao , Rizzo Luigi
Published: April 2014

Recent studies show that more than 86% of Internet paths allow well-designed TCP extensions, meaning that it is still possible to deploy transport layer improvements despite the existence of middleboxes in the network. Hence, the blame for the slow evolution of protocols (with extensions taking many years to nbecome widely used) should be placed on end systems.

In this paper, we revisit the case for moving protocols stacks up into user space in order to ease the deployment of new protocols, extensions, or performance optimizations. We present MultiStack, operating system support for user-level protocol stacks. MultiStack runs within commodity operating systems, can concurrently host a large number of isolated stacks, has a fall-back path to the legacy host stack, and is able to process packets at rates of 10Gb/s.

We validate our design by showing that our mux/demux layer can validate and switch packets at line rate (up to 14.88 Mpps) on a 10 Gbit port using 1-2 cores, and that a proof-of-concept HTTP server running over a basic userspace TCP outperforms by 18-90% both the same server and nginx running over the kernel's stack.
Opportunities and research challenges of hybrid software defined networks
Authors: Vissicchio Stefano , Vanbever Laurent , Bonaventure Olivier
Published: April 2014

Software Defined Networking (SDN) promises to ease design, operation and management of communication networks. However, SDN comes with its own set of challenges, including incremental deployability, robustness, and scalability. Those challenges make a full SDN deployment difficult in the short-term and possibly inconvenient in the longer-term.

In this paper, we explore hybrid SDN models that combine SDN with a more traditional networking approach based on distributed protocols. We show a number of use cases in which hybrid models can mitigate the respective limitations of traditional and SDN approaches, providing incentives to (partially) transition to SDN. Further, we expose the qualitatively diverse tradeoffs that are naturally achieved in hybrid models, making them convenient for different transition strategies and long-term network designs. For those reasons, we argue that hybrid SDN architectures deserve more attention from the scientific community.
Cyber-security research ethics dialogue & strategy workshop
Authors: Kenneally Erin , Bailey Michael
Published: April 2014

The inaugural Cyber-security Research Ethics Dialogue & Strategy Workshop was held on May 23, 2013, in conjunction with the IEEE Security Privacy Symposium in San Francisco, California. CREDS embraced the theme of "ethics-by-design" in the context of cyber security research, and aimed to:

Educate participants about underlying ethics principles and applications;

Discuss ethical frameworks and how they are applied across the various stakeholders and respective communities who are involved;

Impart recommendations about how ethical frameworks can be used to inform policymakers in evaluating the ethical underpinning of critical policy decisions;

Explore cyber security research ethics techniques,tools,standards and practices so researchers can apply ethical principles within their research methodologies; and

Discuss specific case vignettes and explore the ethical implications of common research acts and omissions.
Modeling Replenishment of Ultrathin Liquid Perfluoropolyether Z Films on Solid Surfaces Using Monte Carlo Simulation
Authors: Mayeed M. S. , Kato T.
Published: April 2014

Applying the reptation algorithm to a simplified perfluoropolyether Z off-lattice polymer model an NVT Monte Carlo simulation has been performed. Bulk condition has been simulated first to compare the average radius of gyration with the bulk experimental results. Then the model is tested for its ability to describe dynamics. After this, it is applied to observe the replenishment of nanoscale ultrathin liquid films on solid flat carbon surfaces. The replenishment rate for trenches of different widths (8, 12, and 16 nms for several molecular weights) between two films of perfluoropolyether Z from the Monte Carlo simulation is compared to that obtained solving the diffusion equation using the experimental diffusion coefficients of Ma et al. (1999), with room condition in both cases. Replenishment per Monte Carlo cycle seems to be a constant multiple of replenishment per second at least up to 2 nm replenished film thickness of the trenches over the carbon surface. Considerable good agreement has been achieved here between the experimental results and the dynamics of molecules using reptation moves in the ultrathin liquid films on solid surfaces.
Potentially Ineffective Care: Time for Earnest Reexamination
Authors: Jackson William L. , Sales Joseph F.
Published: April 2014

The rising costs and suboptimal quality throughout the American health care system continue to invite critical inquiry, and practice in the intensive care unit setting is no exception. Due to their relatively large impact, outcomes and costs in critical care are of significant interest to policymakers and health care administrators. Measurement of potentially ineffective care has been proposed as an outcome measure to evaluate critical care delivery, and the Patient Protection and Affordable Care Act affords the opportunity to reshape the care of the critically ill. Given the impetus of the PPACA, systematic formal measurement of potentially ineffective care and its clinical, economic, and societal impact merits timely reconsideration.
Aquaporin-1 Protein Levels Elevated in Fresh Urine of Renal Cell Carcinoma Patients: Potential Use for Screening and Classification of Incidental Renal Lesions
Authors: Sreedharan Shilpa , Petros John A. , Master Viraj A. , Ogan Kenneth , Pattaras John G. , Roberts David L. , Lian Fei , Arnold Rebecca S.
Published: April 2014

Introduction and Objectives. There are over 65,000 new cases of renal cell carcinoma (RCC) each year, yet there is no effective clinical screening test for RCC. A single report claimed no overlap between urine levels of aquaporin-1 (AQP1) in patients with and without RCC (Mayo Clin Proc. 85:413, 2010). Here, we used archived and fresh RCC patient urine to validate this report.Methods. Archived RCC, fresh prenephrectomy RCC, and non-RCC negative control urines were processed for Western blot analysis. Urinary creatinine concentrations were quantified by the Jaffe reaction (Nephron 16:31, 1976). Precipitated protein was dissolved in 1x SDS for a final concentration of 2 μg/µL creatinine.Results. Negative control and archived RCC patient urine failed to show any AQP1 protein by Western blot analysis. Fresh RCC patient urine is robustly positive for AQP1. There was no signal overlap between fresh RCC and negative control, making differentiation straightforward.Conclusions. Our data confirms that fresh urine of patients with RCC contains easily detectable AQP1 protein. However, archival specimens showed an absence of detectable AQP1 indistinguishable from negative control. These findings suggest that a clinically applicable diagnostic test for AQP1 in fresh urine may be useful for detecting RCC.