bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Interaction between the Cytoplasmic ABC Protein LptB and the Inner Membrane LptC Protein, Components of the Lipopolysaccharide Transport Machinery in Escherichia coli
Authors: Martorana Alessandra M. , Benedet Mattia , Maccagni Elisa A. , Sperandeo Paola , Villa Riccardo , Dehò Gianni , Polissi Alessandra
Published: June 2016

The assembly of lipopolysaccharide (LPS) in the outer leaflet of the outer membrane (OM) requires the transenvelope Lpt (lipopolysaccharide transport) complex, made in
Escherichia coli
of seven essential proteins located in the inner membrane (IM) (LptBCFG), periplasm (LptA), and OM (LptDE). At the IM, LptBFG constitute an unusual ATP binding cassette (ABC) transporter, composed by the transmembrane LptFG proteins and the cytoplasmic LptB ATPase, which is thought to extract LPS from the IM and to provide the energy for its export across the periplasm to the cell surface. LptC is a small IM bitopic protein that binds to LptBFG and recruits LptA via its N- and C-terminal regions, and its role in LPS export is not completely understood. Here, we show that the expression level of
lptB
is a critical factor for suppressing lethality of deletions in the C-terminal region of LptC and the functioning of a hybrid Lpt machinery that carries
Pa
-LptC, the highly divergent LptC orthologue from
Pseudomonas aeruginosa
. We found that LptB overexpression stabilizes C-terminally truncated LptC mutant proteins, thereby allowing the formation of a sufficient amount of stable IM complexes to support growth. Moreover, the LptB level seems also critical for the assembly of IM complexes carrying
Pa
-LptC which is otherwise defective in interactions with the
E. coli
LptFG components. Overall, our data suggest that LptB and LptC functionally interact and support a model whereby LptB plays a key role in the assembly of the Lpt machinery.

IMPORTANCE
The asymmetric outer membrane (OM) of Gram-negative bacteria contains in its outer leaflet an unusual glycolipid, the lipopolysaccharide (LPS). LPS largely contributes to the peculiar permeability barrier properties of the OM that prevent the entry of many antibiotics, thus making Gram-negative pathogens difficult to treat. In
Escherichia coli
the LPS transporter (the Lpt machine) is made of seven essential proteins (LptABCDEFG) that form a transenvelope complex. Here, we show that increased expression of the membrane-associated ABC protein LptB can suppress defects of LptC, which participates in the formation of the periplasmic bridge. This reveals functional interactions between these two components and supports a role of LptB in the assembly of the Lpt machine.
Transcriptome Remodeling Contributes to Epidemic Disease Caused by the Human Pathogen Streptococcus pyogenes
Authors: Beres Stephen B. , Kachroo Priyanka , Nasser Waleed , Olsen Randall J. , Zhu Luchang , Flores Anthony R. , de la Riva Ivan , Paez-Mayorga Jesus , Jimenez Francisco E. , Cantu Concepcion , Vuopio Jaana , Jalava Jari , Kristinsson Karl G. , Gottfredsson Magnus , Corander Jukka , Fittipaldi Nahuel , Di Luca Maria Chiara , Petrelli Dezemona , Vitali Luca A. , Raiford Annessa , Jenkins Leslie , Musser James M.
Published: June 2016

For over a century, a fundamental objective in infection biology research has been to understand the molecular processes contributing to the origin and perpetuation of epidemics. Divergent hypotheses have emerged concerning the extent to which environmental events or pathogen evolution dominates in these processes. Remarkably few studies bear on this important issue. Based on population pathogenomic analysis of 1,200
Streptococcus pyogenes
type
emm
89 infection isolates, we report that a series of horizontal gene transfer events produced a new pathogenic genotype with increased ability to cause infection, leading to an epidemic wave of disease on at least two continents. In the aggregate, these and other genetic changes substantially remodeled the transcriptomes of the evolved progeny, causing extensive differential expression of virulence genes and altered pathogen-host interaction, including enhanced immune evasion. Our findings delineate the precise molecular genetic changes that occurred and enhance our understanding of the evolutionary processes that contribute to the emergence and persistence of epidemically successful pathogen clones. The data have significant implications for understanding bacterial epidemics and for translational research efforts to blunt their detrimental effects.

IMPORTANCE
The confluence of studies of molecular events underlying pathogen strain emergence, evolutionary genetic processes mediating altered virulence, and epidemics is in its infancy. Although understanding these events is necessary to develop new or improved strategies to protect health, surprisingly few studies have addressed this issue, in particular, at the comprehensive population genomic level. Herein we establish that substantial remodeling of the transcriptome of the human-specific pathogen
Streptococcus pyogenes
by horizontal gene flow and other evolutionary genetic changes is a central factor in precipitating and perpetuating epidemic disease. The data unambiguously show that the key outcome of these molecular events is evolution of a new, more virulent pathogenic genotype. Our findings provide new understanding of epidemic disease.
Effective Cytotoxic T Lymphocyte Targeting of Persistent HIV-1 during Antiretroviral Therapy Requires Priming of Naive CD8
+
T Cells
Authors: Smith Kellie N. , Mailliard Robbie B. , Piazza Paolo A. , Fischer Will , Korber Bette T. , Fecek Ronald J. , Ratner Deena , Gupta Phalguni , Mullins James I. , Rinaldo Charles R.
Published: June 2016

Curing HIV-1 infection will require elimination of persistent cellular reservoirs that harbor latent virus in the face of combination antiretroviral therapy (cART). Proposed immunotherapeutic strategies to cure HIV-1 infection include enhancing lysis of these infected cells by cytotoxic T lymphocytes (CTL). A major challenge in this strategy is overcoming viral immune escape variants that have evaded host immune control. Here we report that naive CD8
+
T cells from chronic HIV-1-infected participants on long-term cART can be primed by dendritic cells (DC). These DC must be mature, produce high levels of interleukin 12p70 (IL-12p70), be responsive to CD40 ligand (CD40L), and be loaded with inactivated, autologous HIV-1. These DC-primed CD8
+
T cell responders produced high levels of gamma interferon (IFN-γ) in response to a broad range of both conserved and variable regions of Gag and effectively killed CD4
+
T cell targets that were either infected with the autologous latent reservoir-associated virus or loaded with autologous Gag peptides. In contrast, HIV-1-specific memory CD8
+
T cells stimulated with autologous HIV-1-loaded DC produced IFN-γ in response to a narrow range of conserved and variable Gag peptides compared to the primed T cells and most notably, displayed significantly lower cytolytic function. Our findings highlight the need to selectively induce new HIV-1-specific CTL from naive precursors while avoiding activation of existing, dysfunctional memory T cells in potential curative immunotherapeutic strategies for HIV-1 infection.

IMPORTANCE
Current immunotherapeutic approaches aim to enhance antiviral immunity against the HIV-1 reservoir; however, it has yet to be shown whether T cells from persons on cART can recognize and eliminate virus-infected cells. We show that in persons on cART a personalized medicine approach using their dendritic cells to stimulate their naive T cells induces potent effector CTL
in vitro
that recognize and eradicate HIV-1-infected CD4
+
T cells. Additionally, we show that the same stimulation of existing memory T cells results in cytokine secretion but limited effector function. Our study demonstrates that the naive T cell repertoire can recognize persistent HIV-1 during cART and supports immunotherapy strategies for an HIV-1 cure that targets naive T cells, rather than existing, dysfunctional, memory T cells.
Contribution of the Ade Resistance-Nodulation-Cell Division-Type Efflux Pumps to Fitness and Pathogenesis of Acinetobacter baumannii
Authors: Yoon Eun-Jeong , Balloy Viviane , Fiette Laurence , Chignard Michel , Courvalin Patrice , Grillot-Courvalin Catherine
Published: June 2016

Overexpression of chromosomal resistance-nodulation-cell division (RND)-type efflux systems with broad substrate specificity contributes to multidrug resistance (MDR) in
Acinetobacter baumannii
. We have shown that modulation of expression of the structural genes for the efflux systems AdeABC and AdeIJK confers MDR and results in numerous alterations of membrane-associated cellular functions, in particular biofilm formation. However, the contribution of these RND pumps to cell fitness and virulence has not yet been studied. The biological cost of an antibiotic resistance mechanism is a key parameter in determining its stability and dissemination. From an entirely sequenced susceptible clinical isolate, we have generated a set of isogenic derivatives having single point mutations resulting in overexpression of each efflux system or with every pump deleted by allelic replacement. We found that overproduction of the pumps results in a significant decrease in fitness of the bacterial host when measured by competition experiments
in vitro
. Fitness and virulence were also evaluated
in vivo
both in systemic and pulmonary infection models in immunocompetent mice. A diminished competitiveness of the AdeABC-overexpressing mutant was observed only after intraperitoneal inoculation, but not after intranasal inoculation, the latter mimicking the most frequent type of human
A. baumannii
infection. However, in mice infected intranasally, this mutant was more virulent and stimulated an enhanced neutrophil activation in the lungs. Altogether, these data account for the observation that
adeABC
overexpression is common in MDR
A. baumannii
frequently found in ventilator-associated pneumonia.

IMPORTANCE
Overproduction of the RND AdeABC efflux system is observed with a high incidence in multidrug-resistant
Acinetobacter baumannii
and results in increased resistance to several antibiotics of choice for the treatment of infections caused by this nosocomial pathogen. It was therefore important to study the biological cost of the overexpression of the
adeABC
structural operon which is normally tightly regulated. Fitness diminution of an overexpressing mutant detected
in vitro
and
in vivo
in a model that mimics sepsis was not observed in a pulmonary infection model in which the mutant was more virulent. This points out that increased virulence can occur independently from prolonged persistence in the infected organ and can account for the elevated incidence of this resistance mechanism in clinical isolates. The study also indicates that transposon libraries will identify only virulence genes that are expressed under physiological conditions but not those that are tightly regulated.
Targeting Mycobacterium tuberculosis Tumor Necrosis Factor Alpha-Downregulating Genes for the Development of Antituberculous Vaccines
Authors: Olsen Aaron , Chen Yong , Ji Qingzhou , Zhu Guofeng , De Silva Aruna Dharshan , Vilchèze Catherine , Weisbrod Torin , Li Weimin , Xu Jiayong , Larsen Michelle , Zhang Jinghang , Porcelli Steven A. , Jacobs William R. , Chan John
Published: June 2016

Tumor necrosis factor alpha (TNF) plays a critical role in the control ofMycobacterium tuberculosis, in part by augmenting T cell responses through promoting macrophage phagolysosomal fusion (thereby optimizing CD4+T cell immunity by enhancing antigen presentation) and apoptosis (a process that can lead to cross-priming of CD8+T cells).M. tuberculosiscan evade antituberculosis (anti-TB) immunity by inhibiting host cell TNF production via expression of specific mycobacterial components. We hypothesized thatM. tuberculosismutants with an increased capacity to induce host cell TNF production (TNF-enhancing mutants) and thus with enhanced immunogenicity can be useful for vaccine development. To identify mycobacterial genes that regulate host cell TNF production, we used a TNF reporter macrophage clone to screen an H37RvM. tuberculosiscosmid library constructed inM. smegmatis. The screen has identified a set of TNF-downregulating mycobacterial genes that, when deleted in H37Rv, generate TNF-enhancing mutants. Analysis of mutants disrupted for a subset of TNF-downregulating genes, annotated to code for triacylglycerol synthases and fatty acyl-coenzyme A (acyl-CoA) synthetase, enzymes that concern lipid biosynthesis and metabolism, has revealed that these strains can promote macrophage phagolysosomal fusion and apoptosis better than wild-type (WT) bacilli. Immunization of mice with the TNF-enhancingM. tuberculosismutants elicits CD4+and CD8+T cell responses that are superior to those engendered by WT H37Rv. The results suggest that TNF-upregulatingM. tuberculosisgenes can be targeted to enhance the immunogenicity of mycobacterial strains that can serve as the substrates for the development of novel anti-TB vaccines.

IMPORTANCEOne way to control tuberculosis (TB), which remains a major global public health burden, is by immunization with an effective vaccine. The efficacy ofMycobacterium bovisBCG, the only currently approved TB vaccine, is inconsistent. Tumor necrosis factor alpha (TNF) is a cytokine that plays an important role in controlling TB.M. tuberculosis, the causative agent of TB, can counter this TNF-based defense by decreasing host cell TNF production. This study identifiedM. tuberculosisgenes that can mediate inhibition of TNF production by macrophage (an immune cell critical to the control of TB). We have knocked out a number of these genes to generateM. tuberculosismutants that can enhance macrophage TNF production. Immunization with these mutants in mice triggered a T cell response stronger than that elicited by the parental bacillus. Since T cell immunity is pivotal in controllingM. tuberculosis, the TNF-enhancing mutants can be used to develop novel TB vaccines.
Aspergillus
Cell Wall Chitin Induces Anti- and Proinflammatory Cytokines in Human PBMCs via the Fc-γ Receptor/Syk/PI3K Pathway
Authors: Becker K. L. , Aimanianda V. , Wang X. , Gresnigt M. S. , Ammerdorffer A. , Jacobs C. W. , Gazendam R. P. , Joosten L. A. B. , Netea M. G. , Latgé J. P. , van de Veerdonk F. L.
Published: June 2016

Chitin is an important cell wall component of
Aspergillus fumigatus
conidia, of which hundreds are inhaled on a daily basis. Previous studies have shown that chitin has both anti- and proinflammatory properties; however the exact mechanisms determining the inflammatory signature of chitin are poorly understood, especially in human immune cells. Human peripheral blood mononuclear cells were isolated from healthy volunteers and stimulated with chitin from
Aspergillus fumigatus
. Transcription and production of the proinflammatory cytokine interleukin-1β (IL-1β) and the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1Ra) were measured from the cell culture supernatant by quantitative PCR (qPCR) or enzyme-linked immunosorbent assay (ELISA), respectively. Chitin induced an anti-inflammatory signature characterized by the production of IL-1Ra in the presence of human serum, which was abrogated in immunoglobulin-depleted serum. Fc-γ-receptor-dependent recognition and phagocytosis of IgG-opsonized chitin was identified as a novel IL-1Ra-inducing mechanism by chitin. IL-1Ra production induced by chitin was dependent on Syk kinase and phosphatidylinositol 3-kinase (PI3K) activation. In contrast, costimulation of chitin with the pattern recognition receptor (PRR) ligands lipopolysaccharide, Pam3Cys, or muramyl dipeptide, but not β-glucan, had synergistic effects on the induction of proinflammatory cytokines by human peripheral blood mononuclear cells (PBMCs). In conclusion, chitin can have both pro- and anti-inflammatory properties, depending on the presence of pathogen-associated molecular patterns and immunoglobulins, thus explaining the various inflammatory signatures reported for chitin.

IMPORTANCE
Invasive aspergillosis and allergic aspergillosis are increasing health care problems. Patients get infected by inhalation of the airborne spores of
Aspergillus fumigatus
. A profound knowledge of how
Aspergillus
and its cell wall components are recognized by the host cell and which type of immune response it induces is necessary to develop target-specific treatment options with less severe side effects than the treatment options to date. There is controversy in the literature about the receptor for chitin in human cells. We identified the Fc-γ receptor and Syk/PI3K pathway via which chitin can induce anti-inflammatory immune responses by inducing IL-1 receptor antagonist in the presence of human immunoglobulins but also proinflammatory responses in the presence of bacterial components. This explains why
Aspergillus
does not induce strong inflammation just by inhalation and rather fulfills an immune-dampening function. While in a lung coinfected with bacteria,
Aspergillus
augments immune responses by shifting toward a proinflammatory reaction.
Does revision ACL reconstruction measure up to primary surgery? A meta-analysis comparing patient-reported and clinician-reported outcomes, and radiographic results
Authors: Grassi Alberto , Ardern Clare L , Marcheggiani Muccioli Giulio Maria , Neri Maria Pia , Marcacci Maurilio , Zaffagnini Stefano
Published: June 2016

Purpose

To compare patient-reported and clinician-reported outcomes, and radiographic results between patients who had had revision ACL reconstruction and those who had had primary ACL reconstruction.

Design

Systematic review and meta-analysis

Data sources

The MEDLINE, CINAHL, EMBASE and SPORTDiscus electronic databases were searched on 6 August 2015, using 3 main concepts: (1) revision ACL reconstruction, (2) primary ACL reconstruction and (3) treatment outcomes.

Eligibility criteria for selecting studies

Articles that compared patient-reported or clinician-reported outcomes or radiographic results between patients who had had revision ACL reconstruction and those who had had primary surgery with a minimum of 2 years follow-up were included. The outcomes evaluated were the Lysholm Knee Scoring Scale, objective International Knee Documentation Committee (IKDC) classification, Tegner Activity Scale, side-to-side difference in anterior tibial translation measured with KT-1000/2000 arthrometer, pivot shift test, tibiofemoral osteoarthritis grading on plain radiographs and subsequent knee surgeries.

Results

8 studies (300 revision ACL reconstructions and 413 primary ACL reconstructions) were included in the meta-analysis. Patients who had had revision surgery reported inferior Lysholm Knee Scoring Scale scores (mean difference: 7.8 points), had inferior clinician-reported knee function as assessed with the objective IKDC classification (IKDC category A: 27% vs 57%; IKDC category C or D: 22% vs 8%) and pivot shift test (grade II or III: 7% vs 2%), and more radiographic evidence of tibiofemoral osteoarthritis (50% vs 25%) compared with patients who had had primary surgery.

Conclusions

Revision ACL reconstruction restored similar anterior-posterior knee laxity compared with primary ACL reconstruction. Patients who had had revision surgery reported inferior Lysholm Knee Scoring Scale scores, had inferior clinician-reported knee function and more radiographic signs of tibiofemoral osteoarthritis compared with patients with primary ACL reconstruction.
Symptoms and risk factors of depression during and after the football career of elite female players
Authors: Prinz Birgit , Dvořák Jiří , Junge Astrid
Published: June 2016

Background

The mental health of elite athletes has received increasing attention in recent years, but no study has evaluated the career–time prevalence of depression, and very few have analysed risk factors of mental health problems during or after the career.

Methods

157 (response rate 64.1%) female players who played in the German First League answered an anonymous online survey on details of their football career, stressful and helpful conditions, depression and need of psychotherapeutic support during and after the football career.

Results

The career–time prevalence of depression symptoms was 32.3%. Significant differences in the average depression score were observed for playing positions (F=2.75; p<0.05) and levels of play (F=3.53; p<0.01). About half of the players (49.7%) stated ‘conflicts with coach/management’ as an important reason for their low in moods, followed by ‘low in performance/injury’ (48.4%) and ‘too little support/acknowledgement by the coach’ (40.0%). ‘Psychological strain/stress’ (46.5%) was (after injury) the second most important reason for lows in performance. During their career, almost 40% of players wanted or needed psychological support, but only 10% received it. After their career, the percentage of players wanting or needing psychological support decreased to 24%, of whom 90% received it.

Conclusions

The high prevalence of depression symptoms in combination with low use of psychotherapy during the career shows the need for de-stigmatisation of mental health issues in elite football. Furthermore, it seems very important to educate coaches, physicians, physiotherapists and club managers to recognise and prevent mental health problems of their players.
Surveying traffic congestion based on the concept of community structure of complex networks
Authors: Ma Lili , Zhang Zhanli , Li Meng
Published: June 2016

In this paper, taking the traffic of Beijing city as an instance, we study city traffic states, especially traffic congestion, based on the concept of network community structure. Concretely, using the floating car data (FCD) information of vehicles gained from the intelligent transport system (ITS) of the city, we construct a new traffic network model which is with floating cars as network nodes and time-varying. It shows that this traffic network has Gaussian degree distributions at different time points. Furthermore, compared with free traffic situations, our simulations show that the traffic network generally has more obvious community structures with larger values of network fitness for congested traffic situations, and through the GPSspg web page, we show that all of our results are consistent with the reality. Then, it indicates that network community structure should be an available way for investigating city traffic congestion problems.
Fluid structure interaction model for biological systems in the presence of magnetic field
Authors: Aziz Asim , Shoaib Muhammad
Published: June 2016

In the present paper a one-dimensional mathematical model of a cerebral aneurysm is considered. The model combines the interaction between the arterial wall structure, blood pressure and the cerebral spinal fluid (CSF) that is around the aneurysm. CSF is considered electrically conducting in the presence of a uniform magnetic field. Therefore, it may be possible to control pressure and its flow behavior by using an appropriate magnetic field. Hence, such studies have potential for the treatment of Cerebral aneurysms, diseases of heart and blood vessels. The modeled mathematical equations are solved algebraically and the displacement of the arterial wall is plotted to visualize the wall movement. It is evident from the graphs the inclusion of magnetic field reduce the movement of the arterial wall and in turn prevent the rupture of the cerebral aneurysm. The solution is also investigated using computational tools for various other parameters involve in the model.
Proxy Bits for Low Cost Floating-Point Fused Multiply–Add Unit
Authors: Kim Hyunpil , Moon Sangook
Published: June 2016

A new floating-point fused multiply–add (FMA) unit is proposed in this paper. We observed a group of redundant bits that have no effect on the effective results of the floating-point FMA arithmetic, and figured out that two proxy bits can replace the redundant bits. We proved the existence of the proxy bits using binary arithmetic keeping track of the negligible bits. Using proxy bits, the proposed FMA unit achieves improvement in terms of cost, power consumption, and performance. The results show that the proposed FMA unit reduces the total area and latency by approximately 17.0% and 32% respectively, compared with a current widely used FMA unit.
The nonconforming virtual element method for plate bending problems
Authors: Zhao Jikun , Chen Shaochun , Zhang Bei
Published: June 2016

We develop the nonconforming virtual element method for linear plate bending problems. A class of nonconforming virtual elements is constructed, which is [Formula: see text]-continuous. Like the classical nonconforming plate elements, it relaxes the continuity requirement for the function space to some extent. Further, the virtual element is constructed for any order of accuracy and adapts to complicate element geometries. We present a general framework on the error analysis for the nonconforming virtual element method, highlighting the main difference with the conforming one.
Global weak entropy solutions to the Euler–Poisson system with spherical symmetry
Authors: Xiao Jingjing
Published: June 2016

In this paper, we study the initial boundary value problem for the isentropic Euler–Poisson system in an exterior domain with spherical symmetry. The initial data is supposed to be bounded and satisfy other suitable assumptions. Using a fractional step Godunov scheme, we construct the approximate solutions and prove the uniform [Formula: see text] estimates for the approximate solutions. Then the compensated compactness argument implies the convergence of the solutions. The weak entropy solution also satisfies the initial value and boundary value in the sense of trace.
Inequality and risk aversion in economies open to altruistic attitudes
Authors: Perversi Eleonora , Regazzini Eugenio
Published: June 2016

This paper attempts to find a relationship between agents’ risk aversion and inequality of incomes. Specifically, a model is proposed for the evolution in time of surplus/deficit distribution, and the long-time distributions are characterized almost completely. They turn out to be weak Pareto laws with exponent linked to the relative risk aversion index which, in turn, is supposed to be the same for every agent. On the one hand, the aforesaid link is expressed by an affine transformation. On the other hand, the level of the relative risk aversion index results from a frequency distribution of observable quantities stemming from how agents interact in an economic sense. Combination of these facts is conducive to the specification of qualitative and quantitative characteristics of actions fit for the control of income concentration.
Analysis of a chemotaxis system modeling ant foraging
Authors: Alonso Ricardo , Amorim Paulo , Goudon Thierry
Published: June 2016

In this paper, we analyze a system of PDEs recently introduced in [P. Amorim, Modeling ant foraging: A chemotaxis approach with pheromones and trail formation, J. Theor. Biol. 385 (2015) 160–173], in order to describe the dynamics of ant foraging. The system is made of convection–diffusion–reaction equations, and the coupling is driven by chemotaxis mechanisms. We establish the well-posedness for the model, and investigate the regularity issue for a large class of integrable data. Our focus is on the (physically relevant) two-dimensional case with boundary conditions, where we prove that the solutions remain bounded for all times. Further, we prove a hypercontractivity result (instantaneous formation of all [Formula: see text]-norms, [Formula: see text]). The proofs involve a series of fine a priori estimates in Lebesgue spaces and a De Giorgi level set technique.
Vibration of Nonuniform Beams Under Moving Point Loads: An Approximate Analytical Solution in Time Domain
Authors: Sudheesh Kumar C. P. , Sujatha C. , Shankar K.
Published: June 2016

The forced-free responses of nonuniform beams under moving point loads are analyzed in this paper. Simple approximate analytical formulae for the forced responses of undamped nonuniform beams, derived using the fundamental mode by the Rayleigh–Ritz (R–R) method, are presented. The responses of both simply supported and clamped–clamped beams are analyzed. The responses are also determined by the finite element method (FEM) in which nonuniform elements are used for fast convergence. It is found that the present method yields results that are very close to those obtained by the FEM. As this method does not require time integration, it is faster and computationally more efficient. Though the single-mode analysis of forced vibration of uniform beams under moving loads has been done by several researchers, its application to nonuniform beams has not been reported.
Contextual Fuzzy-Based Decision Support System Through Opinion Analysis: A Case Study at University of the Salerno
Authors: De Maio Carmen , Tommasetti Aurelio , Troisi Orlando , Vesci Massimiliano , Fenza Giuseppe , Loia Vincenzo
Published: June 2016

According to the literature about customer satisfaction and loyalty, it is possible to define knowledge-based system to support management decision-making in the organizations. Nevertheless, the problem as to how much the context impacts on correlation has not been investigated in the literature. This paper focuses on developing of Decision Support System (DSS) taking into account correlations among statistical factors, i.e., expert knowledge, and customers’ opinions depending on several contextual features, e.g., culture, location, in order to build context-sensitive simulation environment. The proposed work defines a general system design workflow to tailor knowledge-based DSS by using a fuzzy model to quantify correlations among variables in a given context. We explore ontologies to represent correlations among statistical factors, e.g., Calculative Commitment, Quality of Service. We apply fuzzy data analysis techniques to train fuzzy classifier on the customer’s opinions collected by survey. Finally, synergistic usage of Description Logic and Fuzzy Theory allows the implementation of a simulation environment that supports the management team to tune business strategies. The framework has been instantiated for a case study to support public administration at the University of the Salerno.
Glucose uptake saturation explains glucose kinetics profiles measured by different tests
Authors: Bizzotto Roberto , Natali Andrea , Gastaldelli Amalia , Muscelli Elza , Krssak Martin , Brehm Attila , Roden Michael , Ferrannini Ele , Mari Andrea
Published: June 2016

It is known that for a given insulin level glucose clearance depends on glucose concentration. However, a quantitative representation of the concomitant effects of hyperinsulinemia and hyperglycemia on glucose clearance, necessary to describe heterogeneous tests such as euglycemic and hyperglycemic clamps and oral tests, is lacking. Data from five studies (123 subjects) using a glucose tracer and including all the above tests in normal and diabetic subjects were collected. A mathematical model was developed in which glucose utilization was represented as a Michaelis-Menten function of glucose with constant Kmand insulin-controlled Vmax, consistently with the basic notions of glucose transport. Individual values for the model parameters were estimated using a population approach. Tracer data were accurately fitted in all tests. The estimated Kmwas 3.88 (2.83–5.32) mmol/l [median (interquartile range)]. Median model-derived glucose clearance at 600 pmol/l insulin was reduced from 246 to 158 ml·min−1·m−2when glucose was raised from 5 to 10 mmol/l. The model reproduced the characteristic lack of increase in glucose clearance when moderate hyperinsulinemia was accompanied by hyperglycemia. In all tests, insulin sensitivity was inversely correlated with BMI, as expected ( R2= 0.234, P = 0.0001). In conclusion, glucose clearance in euglycemic and hyperglycemic clamps and oral tests can be described with a unifying model, consistent with the notions of glucose transport and able to reproduce the suppression of glucose clearance due to hyperglycemia observed in previous studies. The model may be important for the design of reliable glucose homeostasis simulators.
Dynamics of glucagon secretion in mice and rats revealed using a validated sandwich ELISA for small sample volumes
Authors: Wewer Albrechtsen Nicolai J. , Kuhre Rune E. , Windeløv Johanne A. , Ørgaard Anne , Deacon Carolyn F. , Kissow Hannelouise , Hartmann Bolette , Holst Jens J.
Published: June 2016

Glucagon is a metabolically important hormone, but many aspects of its physiology remain obscure, because glucagon secretion is difficult to measure in mice and rats due to methodological inadequacies. Here, we introduce and validate a low-volume, enzyme-linked immunosorbent glucagon assay according to current analytical guidelines, including tests of sensitivity, specificity, and accuracy, and compare it, using the Bland-Altman algorithm and size-exclusion chromatography, with three other widely cited assays. After demonstrating adequate performance of the assay, we measured glucagon secretion in response to intravenous glucose and arginine in anesthetized mice (isoflurane) and rats (Hypnorm/midazolam). Glucose caused a long-lasting suppression to very low values (1–2 pmol/l) within 2 min in both species. Arginine stimulated secretion 8- to 10-fold in both species, peaking at 1–2 min and returning to basal levels at 6 min (mice) and 12 min (rats). d-Mannitol (osmotic control) was without effect. Ketamine/xylazine anesthesia in mice strongly attenuated ( P < 0.01) α-cell responses. Chromatography of pooled plasma samples confirmed the accuracy of the assay. In conclusion, dynamic analysis of glucagon secretion in rats and mice with the novel accurate sandwich enzyme-linked immunosorbent assay revealed extremely rapid and short-lived responses to arginine and rapid and profound suppression by glucose.
Differential regulation of lipid and protein metabolism in obese vs. lean subjects before and after a 72-h fast
Authors: Bak Ann Mosegaard , Møller Andreas Buch , Vendelbo Mikkel Holm , Nielsen Thomas Svava , Viggers Rikke , Rungby Jørgen , Pedersen Steen Bønløkke , Jørgensen Jens Otto Lunde , Jessen Niels , Møller Niels
Published: June 2016

Increased availability of lipids may conserve muscle protein during catabolic stress. Our study was designed to define 1) intracellular mechanisms leading to increased lipolysis and 2) whether this scenario is associated with decreased amino acid and urea fluxes, and decreased muscle amino acid release in obese subjects under basal and fasting conditions. We therefore studied nine lean and nine obese subjects twice, after 12 and 72 h of fasting, using measurements of mRNA and protein expression and phosphorylation of lipolytic and protein metabolic signaling molecules in fat and muscle together with whole body and forearm tracer techniques. Obese subjects displayed increased whole body lipolysis, decreased urea production rates, and decreased forearm muscle protein breakdown per 100 ml of forearm tissue, differences that persisted after 72 h of fasting. Lipolysis per fat mass unit was reduced in obese subjects and, correspondingly, adipose tissue hormone-sensitive lipase (HSL) phosphorylation and mRNA and protein levels of the adipose triglyceride lipase (ATGL) coactivator CGI58 were decreased. Fasting resulted in higher HSL phosphorylations and lower protein levels of the ATGL inhibitor G0S2. Muscle protein expressions of mammalian target of rapamycin (mTOR) and 4EBP1 were lower in obese subjects, and MuRf1 mRNA was higher with fasting in lean but not obese subjects. Phosphorylation and signaling of mTOR decreased with fasting in both groups, whereas ULK1 protein and mRNA levels increased. In summary, obese subjects exhibit increased lipolysis due to a large fat mass with blunted prolipolytic signaling, together with decreased urea and amino acid fluxes both in the basal and 72-h fasted state; this is compatible with preservation of muscle and whole body protein.
Formoterol decreases muscle wasting as well as inflammation in the rat model of rheumatoid arthritis
Authors: Gómez-SanMiguel Ana Belén , Gomez-Moreira Carolina , Nieto-Bona María Paz , Fernández-Galaz Carmen , Villanúa Maria Ángeles , Martín Ana Isabel , López-Calderón Asunción
Published: June 2016

Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that is associated with body weight loss and muscle wasting. β2-adrenergic receptor agonists are powerful anabolic agents that trigger skeletal muscle hypertrophy and have been proposed as a promising treatment for muscle wasting in human patients. The aim of this work was to determine whether formoterol, a selective β2-adrenoreceptor agonist, is able to ameliorate muscle wasting in arthritic rats. Arthritis was induced in male Wistar rats by intradermal injection of Freund's adjuvant. Control and arthritic rats were injected daily with 50 μg/kg sc formoterol or saline for 12 days. Body weight change, food intake, and arthritis index were analyzed. After euthanasia, in the gastrocnemius mRNA was analyzed by PCR, and proteins were analyzed by Western blotting. Arthritis decreased gastrocnemius weight, cross-sectional area, and myofiber size, whereas formoterol increased those variables in both arthritic and control rats. Formoterol decreased the external signs of arthritis as well as NF-κB(p65) activation, TNFα, and COX-2 levels in the gastrocnemius of arthritic and control rats. Those effects of formoterol were associated with a decreased expression of myostatin, atrogin-1, and MuRF1 and in LC3b lipidation. Arthritis increased the expression of MyoD, myogenin, IGF-I, and IGFBP-3 and -5 in the gastrocnemius. In control and in arthritic rats, treatment with formoterol increased Akt phosphorylation and myogenin levels, whereas it decreased IGFBP-3 expression in the gastrocnemius. These data suggest that formoterol has an anti-inflammatory effect and decreases muscle wasting in arthritic rats through increasing Akt activity and myogenin and decreasing myostatin, the p-NF-κB(p65)/TNF pathway, and IGFBP-3.
Feature-based attention and spatial selection in frontal eye fields during natural scene search
Authors: Ramkumar Pavan , Lawlor Patrick N. , Glaser Joshua I. , Wood Daniel K. , Phillips Adam N. , Segraves Mark A. , Kording Konrad P.
Published: June 2016

When we search for visual objects, the features of those objects bias our attention across the visual landscape (feature-based attention). The brain uses these top-down cues to select eye movement targets (spatial selection). The frontal eye field (FEF) is a prefrontal brain region implicated in selecting eye movements and is thought to reflect feature-based attention and spatial selection. Here, we study how FEF facilitates attention and selection in complex natural scenes. We ask whether FEF neurons facilitate feature-based attention by representing search-relevant visual features or whether they are primarily involved in selecting eye movement targets in space. We show that search-relevant visual features are weakly predictive of gaze in natural scenes and additionally have no significant influence on FEF activity. Instead, FEF activity appears to primarily correlate with the direction of the upcoming eye movement. Our result demonstrates a concrete need for better models of natural scene search and suggests that FEF activity during natural scene search is explained primarily by spatial selection.
Consistent Approximations of the Zeno Behaviour in Affine-Type Switched Dynamic Systems
Authors: Azhmyakov Vadim
Published: June 2016

This paper proposes a new theoretic approach to a specific interaction of continuous and discrete dynamics in switched control systems known as a Zeno behaviour. We study executions of switched control systems with affine structure that admit infinitely many discrete transitions on a finite time interval. Although the real world processes do not present the corresponding behaviour, mathematical models of many engineering systems may be Zeno due to the used formal abstraction. We propose two useful approximative approaches to the Zeno dynamics, namely, an analytic technique and a variational description of this phenomenon. A generic trajectory associated with the Zeno dynamics can finally be characterized as a result of a specific projection or/and an optimization procedure applied to the original dynamic model. The obtained analytic and variational techniques provide an effective methodology for constructive approximations of the general Zeno-type behaviour. We also discuss shortly some possible applications of the proposed approximation schemes.
Disordered and Multiple Destinations Path Planning Methods for Mobile Robot in Dynamic Environment
Authors: Dong Yong-feng , Xia Hong-mei , Zhou Yan-cong
Published: June 2016

In the smart home environment, aiming at the disordered and multiple destinations path planning, the sequencing rule is proposed to determine the order of destinations. Within each branching process, the initial feasible path set is generated according to the law of attractive destination. A sinusoidal adaptive genetic algorithm is adopted. It can calculate the crossover probability and mutation probability adaptively changing with environment at any time. According to the cultural-genetic algorithm, it introduces the concept of reducing turns by parallelogram and reducing length by triangle in the belief space, which can improve the quality of population. And the fallback strategy can help to jump out of the “U” trap effectively. The algorithm analyses the virtual collision in dynamic environment with obstacles. According to the different collision types, different strategies are executed to avoid obstacles. The experimental results show that cultural-genetic algorithm can overcome the problems of premature and convergence of original algorithm effectively. It can avoid getting into the local optimum. And it is more effective for mobile robot path planning. Even in complex environment with static and dynamic obstacles, it can avoid collision safely and plan an optimal path rapidly at the same time.
Dynamic Model and Fault Feature Research of Dual-Rotor System with Bearing Pedestal Looseness
Authors: Wang Nanfei , Xu Hongzhi , Jiang Dongxiang
Published: June 2016

The paper presents a finite element model of dual-rotor system with pedestal looseness stemming from loosened bolts. Dynamic model including bearing pedestal looseness is established based on the dual-rotor test rig. Three-degree-of-freedom (DOF) planar rigid motion of loose bearing pedestal is fully considered and collision recovery coefficient is also introduced in the model. Based on the Timoshenko beam elements, using the finite element method, rigid body kinematics, and the Newmark-βalgorithm for numerical simulation, dynamic characteristics of the inner and outer rotors and the bearing pedestal plane rigid body motion under bearing pedestal looseness condition are studied. Meanwhile, the looseness experiments under two different speed combinations are carried out, and the experimental results are basically the same. The simulation results are compared with the experimental results, indicating that vibration displacement waveforms of loosened rotor have “clipping” phenomenon. When the bearing pedestal looseness fault occurs, the inner and outer rotors vibration spectrum not only contains the difference and sum frequency of the two rotors’ fundamental frequency but also contains2Xand3Xcomponent of rotor with loosened support, and so forth; low frequency spectrum is more, containing dividing component, and so forth; the rotor displacement spectrums also contain fewer combination frequency components, and so forth; when one side of the inner rotor bearing pedestal is loosened, the inner rotor axis trajectory is drawn into similar-ellipse shape.
Medical Management for the Treatment of Nontuberculous Mycobacteria Infection of the Parotid Gland: Avoiding Surgery May Be Possible
Authors: Kay-Rivest Emily , Bouhabel Sarah , Oughton Matthew Thomas , Hier Michael Peter
Published: June 2016

Infection with nontuberculous mycobacteria (NTM) is uncommon in the head and neck; therefore there is no clear consensus on treating these infections. Our objective was to report our experience with a unique case of NTM infection of the parotid in an immunocompetent patient, in order to determine appropriate management through our experience with this pathology. A 57-year-old man, known for numerous comorbid diseases, presented to our institution complaining of right parotid swelling and pain. A computed tomography (CT) of the neck showed a multiloculated collection in the inferior portion of the right parotid gland, compatible with abscess formation. This abscess was drained by interventional radiology (IR) but required repeat drainage twice due to lack of initial improvement. He was treated with several antibiotics as culture results initially indicated Gram-positive bacilli and thenMycobacteriumspecies, with final identification by a reference laboratory asMycobacterium abscessus. Imipenem was initiated with amikacin and clarithromycin. His infection clinically and radiologically resolved after 5 months of antibiotherapy. In our case, the patient improved following intravenous antibiotic therapy. Our experience demonstrates that appropriate antibiotherapy can lead to resolution ofMycobacterium abscessusinfection in the parotid without the risks associated with surgical intervention.
Influence of Annealing Methods on the Magnetic Properties and Flexural Strength of Iron-OER Soft Magnetic Composites
Authors: Xiao Ling , Li Ming , Cheng Wenjie , Fan Hongwei , Chen Xingzhou , Sun Yanhua , Ding Chunhua , Yu Lie
Published: June 2016

This study aims at investigating high flexural strength iron-OER soft magnetic composites (SMCs) for active magnetic bearings (AMBs). Iron powders were firstly coated with oxide layer by the passivation process at room temperature. The effect of annealing methods on the static performance, magnetic properties, and flexural strength of SMCs was studied. The results showed that the significant improvements of permeability, magnetic loss, and flexural strength were presented by increasing the bonding number between iron surface and resin and using the two-step annealing method. In addition, the effect of pore shape and angle on the behavior of material fracture has been studied by FEM and the analysis was validated by experimental results.
Mitigation of Effects of Occlusion on Object Recognition with Deep Neural Networks through Low-Level Image Completion
Authors: Chandler Benjamin , Mingolla Ennio
Published: June 2016

Heavily occluded objects are more difficult for classification algorithms to identify correctly than unoccluded objects. This effect is rare and thus hard to measure with datasets like ImageNet and PASCAL VOC, however, owing to biases in human-generated image pose selection. We introduce a dataset that emphasizes occlusion and additions to a standard convolutional neural network aimed at increasing invariance to occlusion. An unmodified convolutional neural network trained and tested on the new dataset rapidly degrades to chance-level accuracy as occlusion increases. Training with occluded data slows this decline but still yields poor performance with high occlusion. Integrating novel preprocessing stages to segment the input and inpaint occlusions is an effective mitigation. A convolutional network so modified is nearly as effective with more than 81% of pixels occluded as it is with no occlusion. Such a network is also more accurate on unoccluded images than an otherwise identical network that has been trained with only unoccluded images. These results depend on successful segmentation. The occlusions in our dataset are deliberately easy to segment from the figure and background. Achieving similar results on a more challenging dataset would require finding a method to split figure, background, and occluding pixels in the input.