bluuebunny/crossref_metadata_2025 huggingface dataset:
A Polymerization-Associated Structural Switch in FtsZ That Enables Treadmilling of Model Filaments
Authors: Wagstaff James M. , Tsim Matthew , Oliva María A. , García-Sanchez Alba , Kureisaite-Ciziene Danguole , Andreu José Manuel , Löwe Jan
Published: May 2017

Bacterial cell division in many organisms involves a constricting cytokinetic ring that is orchestrated by the tubulin-like protein FtsZ. FtsZ forms dynamic filaments close to the membrane at the site of division that have recently been shown to treadmill around the division ring, guiding septal wall synthesis. Here, using X-ray crystallography of
Staphylococcus aureus
FtsZ (SaFtsZ), we reveal how an FtsZ can adopt two functionally distinct conformations, open and closed. The open form is found in SaFtsZ filaments formed in crystals and also in soluble filaments of
Escherichia coli
FtsZ as deduced by electron cryomicroscopy. The closed form is found within several crystal forms of two nonpolymerizing SaFtsZ mutants and corresponds to many previous FtsZ structures from other organisms. We argue that FtsZ’s conformational switch is polymerization-associated, driven by the formation of the longitudinal intersubunit interfaces along the filament. We show that such a switch provides explanations for both how treadmilling may occur within a single-stranded filament and why filament assembly is cooperative.

IMPORTANCE
The FtsZ protein is a key molecule during bacterial cell division. FtsZ forms filaments that organize cell membrane constriction, as well as remodeling of the cell wall, to divide cells. FtsZ functions through nucleotide-driven filament dynamics that are poorly understood at the molecular level. In particular, mechanisms for cooperative assembly (nonlinear dependency on concentration) and treadmilling (preferential growth at one filament end and loss at the other) have remained elusive. Here, we show that most likely all FtsZ proteins have two distinct conformations, a “closed” form in monomeric FtsZ and an “open” form in filaments. The conformational switch that occurs upon polymerization explains cooperativity and, in concert with polymerization-dependent nucleotide hydrolysis, efficient treadmilling of FtsZ polymers.
The Fitness of
Pseudomonas aeruginosa
Quorum Sensing Signal Cheats Is Influenced by the Diffusivity of the Environment
Authors: Mund Anne , Diggle Stephen P. , Harrison Freya
Published: May 2017

Experiments examining the social dynamics of bacterial quorum sensing (QS) have focused on mutants which do not respond to signals and the role of QS-regulated exoproducts as public goods. The potential for QS signal molecules to themselves be social public goods has received much less attention. Here, we analyze how signal-deficient (
lasI
) mutants of the opportunistic pathogen
Pseudomonas aeruginosa
interact with wild-type cells in an environment where QS is required for growth. We show that when growth requires a “private” intracellular metabolic mechanism activated by the presence of QS signal,
lasI
mutants act as social cheats and outcompete signal-producing wild-type bacteria in mixed cultures, because they can exploit the signals produced by wild-type cells. However, reducing the ability of signal molecules to diffuse through the growth medium results in signal molecules becoming less accessible to mutants, leading to reduced cheating. Our results indicate that QS signal molecules can be considered social public goods in a way that has been previously described for other exoproducts but that spatial structuring of populations reduces exploitation by noncooperative signal cheats.

IMPORTANCE
Bacteria communicate via signaling molecules to regulate the expression of a whole range of genes. This process, termed quorum sensing (QS), moderates bacterial metabolism under many environmental conditions, from soil and water (where QS-regulated genes influence nutrient cycling) to animal hosts (where QS-regulated genes determine pathogen virulence). Understanding the ecology of QS could therefore yield vital clues to how we might modify bacterial behavior for environmental or clinical gains. Here, we demonstrate that QS signals act as shareable public goods. This means that their evolution, and therefore population-level responses to interference with QS, will be constrained by population structure. Further, we show that environmental structure (constraints on signal diffusion) alters the accessibility of QS signals and demonstrates that we need to consider population and environmental structure to help us further our understanding of QS signaling systems.
HIV Exploits Antiviral Host Innate GCN2-ATF4 Signaling for Establishing Viral Replication Early in Infection
Authors: Jiang Guochun , Santos Rocha Clarissa , Hirao Lauren A. , Mendes Erica A. , Tang Yuyang , Thompson George R. , Wong Joseph K. , Dandekar Satya
Published: May 2017

Antiviral innate host defenses against acute viral infections include suppression of host protein synthesis to restrict viral protein production. Less is known about mechanisms by which viral pathogens subvert host antiviral innate responses for establishing their replication and dissemination. We investigated early innate defense against human immunodeficiency virus (HIV) infection and viral evasion by utilizing human CD4
+
T cell cultures
in vitro
and a simian immunodeficiency virus (SIV) model of AIDS
in vivo
. Our data showed that early host innate defense against the viral infection involves GCN2-ATF4 signaling-mediated suppression of global protein synthesis, which is exploited by the virus for supporting its own replication during early viral infection and dissemination in the gut mucosa. Suppression of protein synthesis and induction of protein kinase GCN2-ATF4 signaling were detected in the gut during acute SIV infection. These changes diminished during chronic viral infection. HIV replication induced by serum deprivation in CD4
+
T cells was linked to the induction of ATF4 that was recruited to the HIV long terminal repeat (LTR) to promote viral transcription. Experimental inhibition of GCN2-ATF4 signaling either by a specific inhibitor or by amino acid supplementation suppressed the induction of HIV expression. Enhancing ATF4 expression through selenium administration resulted in reactivation of latent HIV
in vitro
as well as
ex vivo
in the primary CD4
+
T cells isolated from patients receiving suppressive antiretroviral therapy (ART). In summary, HIV/SIV exploits the early host antiviral response through GCN2-ATF4 signaling by utilizing ATF4 for activating the viral LTR transcription to establish initial viral replication and is a potential target for HIV prevention and therapy.

IMPORTANCE
Understanding how HIV overcomes host antiviral innate defense response in order to establish infection and dissemination is critical for developing prevention and treatment strategies. Most investigations focused on the viral pathogenic mechanisms leading to immune dysfunction following robust viral infection and dissemination. Less is known about mechanisms that enable HIV to establish its presence despite rapid onset of host antiviral innate response. Our novel findings provide insights into the viral strategy that hijacks the host innate response of the suppression of protein biosynthesis to restrict the virus production. The virus leverages transcription factor ATF4 expression during the GCN2-ATF4 signaling response and utilizes it to activate viral transcription through the LTR to support viral transcription and production in both HIV and SIV infections. This unique viral strategy is exploiting the innate response and is distinct from the mechanisms of immune dysfunction after the critical mass of viral loads is generated.
Chlamydia
Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning
Authors: Wesolowski Jordan , Weber Mary M. , Nawrotek Agata , Dooley Cheryl A. , Calderon Mike , St. Croix Claudette M. , Hackstadt Ted , Cherfils Jacqueline , Paumet Fabienne
Published: May 2017

The intracellular bacterium
Chlamydia trachomatis
develops in a parasitic compartment called the inclusion. Posttranslationally modified microtubules encase the inclusion, controlling the positioning of Golgi complex fragments around the inclusion. The molecular mechanisms by which
Chlamydia
coopts the host cytoskeleton and the Golgi complex to sustain its infectious compartment are unknown. Here, using a genetically modified
Chlamydia
strain, we discovered that both posttranslationally modified microtubules and Golgi complex positioning around the inclusion are controlled by the chlamydial inclusion protein CT813/CTL0184/InaC and host ARF GTPases. CT813 recruits ARF1 and ARF4 to the inclusion membrane, where they induce posttranslationally modified microtubules. Similarly, both ARF isoforms are required for the repositioning of Golgi complex fragments around the inclusion. We demonstrate that CT813 directly recruits ARF GTPases on the inclusion membrane and plays a pivotal role in their activation. Together, these results reveal that
Chlamydia
uses CT813 to hijack ARF GTPases to couple posttranslationally modified microtubules and Golgi complex repositioning at the inclusion.

IMPORTANCE
Chlamydia trachomatis
is an important cause of morbidity and a significant economic burden in the world. However, how
Chlamydia
develops its intracellular compartment, the so-called inclusion, is poorly understood. Using genetically engineered
Chlamydia
mutants, we discovered that the effector protein CT813 recruits and activates host ADP-ribosylation factor 1 (ARF1) and ARF4 to regulate microtubules. In this context, CT813 acts as a molecular platform that induces the posttranslational modification of microtubules around the inclusion. These cages are then used to reposition the Golgi complex during infection and promote the development of the inclusion. This study provides the first evidence that ARF1 and ARF4 play critical roles in controlling posttranslationally modified microtubules around the inclusion and that
Chlamydia trachomatis
hijacks this novel function of ARF to reposition the Golgi complex.
Invasive meningococcal disease in the Veneto region of Italy: a capture-recapture analysis for assessing the effectiveness of an integrated surveillance system
Authors: Baldovin Tatjana , Lazzari Roberta , Cocchio Silvia , Furlan Patrizia , Bertoncello Chiara , Saia Mario , Russo Francesca , Baldo Vincenzo
Published: May 2017

Background

Epidemiology ofNeisseria meningitidishas been changing since the introduction of universal vaccination programmes against meningococcal serogroup C (MenC) and meningococcal serogroup B (MenB) has now become dominant. This study aimed to analyse the cases reported in institutional data recording systems to estimate the burden of invasive meningococcal diseases (IMDs) and assess the effectiveness of surveillance in Veneto region (Italy).

Methods

Analysis was performed from 2007 to 2014 on data recorded in different systems: Mandatory Notification System, National Surveillance of Invasive Bacterial Diseases System and Laboratories Surveillance System (LSS), which were pooled into a combined surveillance system (CSS) and hospital discharge records (HDRs). A capture-recapture method was used and completeness of each source estimated. Number of cases with IMD by source of information and year, incidence of IMD by age group, case fatality rate (CFR) and distribution of meningococcal serogroups by year were also analysed.

Results

Combining the four data systems enabled the identification of 179 confirmed cases with IMD, achieving an overall sensitivity of 94.7% (95% CI: 90.8% to 98.8%), while it was 76.7% (95% CI: 73.6% to 80.1%) for CSS and 77.2% (95% CI: 74.1% to 80.6%) for HDRs. Typing of isolates was done in 80% of cases, and 95.2% of the typed cases were provided by LSS. Serogroup B was confirmed in 50.3% of cases. The estimated IMD notification rate (cases with IMD diagnosed and reported to the surveillance systems) was 0.48/100 000 population, and incidence peaked at 6.2/100 000 in children aged <1 year old (60.9% due to MenB), and increased slightly in the age group between 15 and 19 years (1.1/100 000). A CFR of 14% was recorded (8.7% in paediatric age).

Conclusions

Quality of surveillance systems relies on case ascertainment based on serological characterisation of the circulating strains by microbiology laboratories. All available sources should be routinely combined to improve the epidemiology of IMD and the information used by public health departments to conduct timely preventive measures.
REDucing Unnecessary Coagulation Testing in the Emergency Department (REDUCED)
Authors: Fralick Michael , Hicks Lisa K , Chaudhry Hina , Goldberg Nicola , Ackery Alun , Nisenbaum Rosane , Sholzberg Michelle
Published: May 2017

The PT/INR (prothrombin time/international normalized ratio) and aPTT (activated partial thromboplastin time) were tests developed in the early 20th century for specific and unique indications. Despite this, they are often ordered together routinely. The objective of this study was to determine if a multimodal intervention could reduce PT/INR and aPTT testing in the emergency department (ED). This was a prospective multi-pronged quality improvement study at St. Michael's Hospital. The initiative involved stakeholder engagement, uncoupling of PT/INR and aPTT testing, teaching, and most importantly a revision to the ED order panels. After changes to order panels, weekly rates of PT/INR and aPTT testing per 100 ED patients decreased (17.2 vs 38.4, rate ratio=0.45 (95% CI 0.43-0.47), p<0.001; 16.6 vs 37.8, rate ratio=0.44 (95% CI 0.42-0.46), p<0.001, respectively). Rate of creatinine testing per 100 ED patients, our internal control, increased during the same period (54.0 vs 49.7, rate ratio=1.09 (95% CI 1.06-1.12); p<0.0001) while the weekly rate per 100 ED patients receiving blood transfusions slightly decreased (0.5 vs 0.7, rate ratio=0.66 (95% CI 0.49-0.87), p=0.0034). We found that a simple process change to order panels was associated with meaningful reductions in coagulation testing without obvious adverse effects.
Characteristics associated with requests by pathologists for second opinions on breast biopsies
Authors: Geller Berta M , Nelson Heidi D , Weaver Donald L , Frederick Paul D , Allison Kimberly H , Onega Tracy , Carney Patricia A , Tosteson Anna N A , Elmore Joann G
Published: May 2017

Aims

Second opinions in pathology improve patient safety by reducing diagnostic errors, leading to more appropriate clinical treatment decisions. Little objective data are available regarding the factors triggering a request for second opinion despite second opinion consultations being part of the diagnostic system of pathology. Therefore we sought to assess breast biopsy cases and interpreting pathologists characteristics associated with second opinion requests.

Methods

Collected pathologist surveys and their interpretations of 60 test set cases were used to explore the relationships between case characteristics, pathologist characteristics and case perceptions, and requests for second opinions. Data were evaluated by logistic regression and generalised estimating equations.

Results

115 pathologists provided 6900 assessments; pathologists requested second opinions on 70% (4827/6900) of their assessments 36% (1731/4827) of these would not have been required by policy. All associations between case characteristics and requesting second opinions were statistically significant, including diagnostic category, breast density, biopsy type, and number of diagnoses noted per case. Exclusive of institutional policies, pathologists wanted second opinions most frequently for atypia (66%) and least frequently for invasive cancer (20%). Second opinion rates were higher when the pathologist had lower assessment confidence, in cases with higher perceived difficulty, and cases with borderline diagnoses.

Conclusions

Pathologists request second opinions for challenging cases, particularly those with atypia, high breast density, core needle biopsies, or many co-existing diagnoses. Further studies should evaluate whether the case characteristics identified in this study could be used as clinical criteria to prompt system-level strategies for mandating second opinions.
A case of canine idiopathic eosinophilic meningoencephalitis with serial MRI scans, CSF analyses and histopathology
Authors: Cowan Allison , Bibevski Jennifer , Axlund Todd
Published: May 2017

A six‐year‐old labrador retriever mix was evaluated for behaviour change, hyperaesthesia and inappropriate urination. Neurological examination was consistent with a multifocal localisation. Multiple MRI scans, cerebrospinal fluid (CSF) analyses, infectious disease titres and a cerebral biopsy were performed over the course of nine months, confirming the diagnosis of idiopathic eosinophilic meningoencephalitis. The patient was treated with immunomodulatory medications, antibiotics, anthelminthics and anticonvulsant medications. Resolution of meningoencephalitis was achieved; however, permanent neurological deficits remained and seizures became more difficult to control. The patient’s neurological status was followed until her death approximately six years following initial presentation. This is the first and only reported case of idiopathic eosinophilic meningoencephalitis to have had multiple MRI scans and CSF analyses performed. This report allows for visual tracking of disease progression and correlates it with CSF characteristics and clinical signs. Furthermore, this report demonstrates the persistent long‐term ramifications of the disease, even after successful treatment.
Improving release efficiency of cod (Gadus morhua) and haddock (Melanogrammus aeglefinus) in the Barents Sea demersal trawl fishery by stimulating escape behaviour
Authors: Grimaldo Eduardo , Sistiaga Manu , Herrmann Bent , Larsen Roger B. , Brinkhof Jesse , Tatone Ivan
Published: May 2017

We tested the ability of stimulators to improve the release efficiency of cod (Gadus morhua) and haddock (Melanogrammus aeglefinus) through the meshes of a square mesh section installed in a trawl. The section was tested in three different configurations: without any stimulation device, with a mechanical stimulation device, and with LED light stimulation devices. We analysed and compared the behaviour of cod and haddock in all three configurations based on release results and underwater recordings. Parallel to the fishing trials, we carried out fall-through tests to determine the upper physical size limits for cod and haddock to be able to escape through the square meshes in the section. This enabled us to infer whether lack of release efficiency was due to fish behaviour or release potential of the square meshes in the section. The results showed that the escape behaviour of haddock can be triggered by mechanical stimulation. In contrast, cod did not react significantly to the presence of mechanical stimulators. LED light stimulation had some effect on the behaviour of haddock, but not on cod.
The novel combination of theophylline and bambuterol as a potential treatment of hypoxemia in humans
Authors: Strand Trond-Eirik , Khiabani Hasse Z. , Boico Alina , Radiloff Daniel , Zhao Yulin , Hamilton Karyn L. , Christians Uwe , Klawitter Jelena , Noveck Robert J. , Piantadosi Claude A. , Bell Christopher , Irwin David , Schroeder Thies
Published: May 2017

Hypoxemia can be life-threatening, both acutely and chronically. Because hypoxemia causes vascular dysregulation that further restricts oxygen availability to tissue, it can be pharmacologically addressed. We hypothesized that theophylline can be safely combined with the β2-adrenergic vasodilator bambuterol to improve oxygen availability in hypoxemic patients. Ergogenicity and hemodynamic effects of bambuterol and theophylline were measured in rats under hypobaric and normobaric hypoxia (12% O2). Feasibility in humans was assessed using randomized, double-blind testing of the influence of combined slow-release theophylline (300 mg) and bambuterol (20 mg) on adverse events (AEs), plasma K+, pulse, blood pressure, and drug interaction. Both drugs and their combination significantly improved hypoxic endurance in rats. In humans, common AEs were low K+(<3.5 mmol/L; bambuterol: 12, theophylline: 4, combination: 13 episodes) and tremors (10, 0, 14 episodes). No exacerbation or serious AE occurred when drugs were combined. A drop in plasma K+coincided with peak bambuterol plasma concentrations. Bambuterol increased heart rate by approximately 13 bpm. Drug interaction was present but small. We report promise, feasibility, and relative safety of combined theophylline and bambuterol as a treatment of hypoxemia in humans. Cardiac safety and blood K+will be important safety endpoints when testing these drugs in hypoxemic subjects.
Semantic Trajectory Knowledge Discovery: A Promising Way to Extract Meaningful Patterns from Spatiotemporal Data
Authors: Chakri Sana , Raghay Said , El Hadaj Salah
Published: May 2017

Spatiotemporal data mining studies the field of discovering interesting patterns from large spatiotemporal databases. Although these databases generate a huge volume of data daily from satellite images and mobile sensors like GPS, among these data we find first spatiotemporal and geographical data; secondly, the trajectories browsed by moving objects in some time intervals. Combination of these types of data leads to producing semantic trajectory data. Enriching trajectories with semantic geographical information leads to ease queries, analysis, and mining, in order to give more meaning to behaviors potentially extracted from trajectories. Therefore, applying mining techniques on semantic trajectories continue to prove to be a success story in discovering useful and nontrivial behavioral patterns of moving objects. The purpose of this paper is to make an overview of spatiotemporal knowledge discovery (STKD) and techniques recently used to extract knowledge from spatiotemporal data based on analysis of recent literature. Then leading towards a deeper analysis about semantic trajectory knowledge discovery as a specified field from STKD that integrates trajectory sample points with geographical data before applying mining techniques in order to extract behavioral knowledge from semantic trajectories which can be more useful and significant for the application users.
Preparation of 0.055BaZrO3–0.935(K0.45Na0.5Li0.05)NbO3–0.01(Bi0.5Na0.5)TiO3 piezoelectric thin films from precursor solution by Pechini method
Authors: Liu Liqiang , Karaki Tomoaki , Fujii Tadashi , Sakai Yuichi
Published: May 2017

Lead-free piezoelectric thin films of 0.055BaZrO3–0.935(K[Formula: see text]Na[Formula: see text]Li[Formula: see text])NbO3–0.01(Bi[Formula: see text]Na[Formula: see text])TiO3 (BZ–KNLN–BNT) were fabricated on (100)-LaNiO3/SiO2/Si substrates. The Pechini (polymeric precursor) method was carried out to prepare the complicated multi-component precursor solution. This method was suited for controlling the complex components accurately. The films crystallized at 700[Formula: see text]C showed a (100)pc-oriented perovskite structure, whose grain size was about 200[Formula: see text]nm and thickness was about 700[Formula: see text]nm. The Curie temperature [Formula: see text]c of the films was 292[Formula: see text]C that was near to that of the bulk ceramics. The preparation method used in this work provided a possibility for the application of multi-component lead-free piezoelectric films.
Enhanced brain responses to color during smooth-pursuit eye movements
Authors: Chen Jing , Valsecchi Matteo , Gegenfurtner Karl R.
Published: May 2017

We constantly move our eyes when we explore the world. Eye movements alter visual perception in various ways. The smooth-pursuit eye movements have been shown to boost color sensitivity. We recorded steady-state visually evoked potentials to equiluminant chromatic flickering stimuli and observed increased steady-state visually evoked potentials when participants smoothly pursued a moving target compared with when they maintained fixation. This work provides direct neurophysiological evidence for the parvocellular boost by smooth-pursuit eye movements in humans.
Cerebellar patients do not benefit from cerebellar or M1 transcranial direct current stimulation during force-field reaching adaptation
Authors: Hulst Thomas , John Liane , Küper Michael , van der Geest Jos N. , Göricke Sophia L. , Donchin Opher , Timmann Dagmar
Published: May 2017

Transcranial direct current stimulation (tDCS) has been identified as a potential tool in the rehabilitation of cerebellar disease. We investigated whether tDCS of the cerebellum and primary motor cortex could alleviate motor impairments of subjects with cerebellar degeneration. The present study did not find stimulation effects of tDCS in young controls, aging controls, and individuals with cerebellar degeneration during reach adaptation. Our results require a re-evaluation of the clinical potential of tDCS in cerebellar patients.
Global Dynamics of Rational Difference Equations xn+1=xn+xn-1/q+ynyn-1 and yn+1=yn+yn-1/p+xnxn-1
Authors: Liu Keying , Li Peng , Zhong Weizhou
Published: May 2017

Global dynamics of a system of nonlinear difference equations was investigated, which had five kinds of equilibria including isolated points and a continuum of nonhyperbolic equilibria along the coordinate axes. The local stability of these equilibria was analyzed which led to nine regions in the parameters space. The solution of the system converged to the equilibria or the boundary point (+∞,0) or (0,+∞) in each region depending on nonnegative initial conditions. These results completely described the behavior of the system.
Cancer Is to Embryology as Mutation Is to Genetics: Hypothesis of the Cancer as Embryological Phenomenon
Authors: Cofre Jaime , Abdelhay Eliana
Published: May 2017

Despite numerous advances in cell biology, genetics, and developmental biology, cancer origin has been attributed to genetic mechanisms primarily involving mutations. Embryologists have expressed timidly cancer embryological origin with little success in leveraging the discussion that cancer could involve a set of conventional cellular processes used to build the embryo during morphogenesis. Thus, this “cancer process” allows the harmonious and coherent construction of the embryo structural base, and its implementation as the embryonic process involves joint regulation of differentiation, proliferation, cell invasion, and migration, enabling the human being recreation of every generation. On the other hand, “cancer disease” is the representation of an abnormal state of the cell that might happen in the stem cells of an adult person, in which the mechanism for joint gene regulating of differentiation, proliferation, cell invasion, and migration could be reactivated in an entirely inappropriate context.
The Effect of Masterbatch Recipes on the Homogenization Properties of Injection Molded Parts
Authors: Zsíros László , Török Dániel , Kovács József Gábor
Published: May 2017

Appearance is a key factor in most injection molding applications. Unfortunately, there is no widespread method to objectively test visual appearance, such as color inhomogeneity of the parts or other surface defects. We developed an evaluation method to characterize the color inhomogeneity of injection molded parts. First, we examined manufacturing conditions and masterbatch recipes and then the individual effects of the components and their interactions on homogeneity.
Interluekin-35 in Asthma and Its Potential as an Effective Therapeutic Agent
Authors: Gao Peng , Su Zhenzhong , Lv Xuejiao , Zhang Jie
Published: May 2017

Interleukin- (IL-) 35 is a member of the IL-12 cytokine family and a heterodimeric protein formed by Epstein-Barr-induced gene 3 (EBI3) and IL-12p35. Emerging evidence shows that IL-35 is a key player in the regulation of cellular communication, differentiation, and inflammation. Altered IL-35 expression has been found in disease conditions such as cancer, rheumatoid arthritis, and, more recently, asthma. In cancer, IL-35 is involved in the regulation of tumorigenesis, cancer progression, and metastasis. In rheumatoid arthritis, IL-35 acts as a negative regulator of inflammation. Similarly, IL-35 also appears to suppress allergic inflammation in asthma. In an in vivo murine model of asthma, transfer of adenovirus-mediated IL-35 markedly reduced the degree of airway hyperresponsiveness (AHR) and inflammatory cell infiltration. Many studies have shown the involvement of IL-35 in a number of aspects of allergic inflammation, such as eosinophil and neutrophil recruitment as well as inhibition of inflammatory mediators of the Th2 subtype. However, the exact molecular mechanisms underlying the role of IL-35 in human asthma have yet to be fully elucidated. This review describes the current evidence regarding the role of IL-35 in the pathophysiology of asthma and evaluates the potential of IL-35 as a biomarker for airway inflammation and a therapeutic target for the treatment of asthma.
High Isolation Dual-Polarized Patch Antenna with Hybrid Ring Feeding
Authors: Lin Xian-Jing , Xie Ze-Ming , Zhang Pei-Sheng
Published: May 2017

This paper presents a hybrid ring feeding dual-polarized patch antenna with high isolation in a wide working band. The proposed antenna consists of a circular radiating patch printed on the upper horizontal substrate, two pairs of Γ shaped strips printed on two vertical substrates, and a hybrid ring feeding network printed on the lower two horizontal substrates. The proposed antenna adopts Γ shape strips coupled feeding structure to achieve a wide operating band. Furthermore, a hybrid ring feeding structure with high isolation in a wide bandwidth, which is firstly proposed, is applied as feeding network. When one port is excited, the feeding network can realize twice the power cancellation. Thus, high ports isolation characteristics can be obtained. A prototype of the proposed antenna is fabricated and measured. Measured results show that the 10 dB reflection coefficient bandwidths of the two ports are both about 38.7%, with port isolation higher than 40 dB through most of the band, and the cross-polarizations are below −24 dB.
Synthesis of Disentangled Ultra-High Molecular Weight Polyethylene: Influence of Reaction Medium on Material Properties
Authors: Forte Giuseppe , Ronca Sara
Published: May 2017

The polymerization of ethylene to Ultra-High Molecular Weight Polyethylene (UHMWPE) in certain reaction conditions allows synthesis of nascent powders with a considerably lower amount of entanglements: the material obtained is of great interest from both academic and industrial viewpoints. From an academic point of view, it is interesting to follow the evolution of the metastable melt state with the progressive entanglements formation. Industrially, it is valuable to have a solvent-free processing route for the production of high modulus, high strength tapes. Since the polymer synthesis is performed in the presence of a solvent, it is interesting to investigate the influence that the reaction medium can have on the catalyst activity, resultant molecular characteristics, and polymer morphology at the macroscopic as wells as microscopic level. In this paper, we present the effect that two typical polymerization solvents, toluene and heptane, and mixtures of them, have on the catalytic performance and on the polymer properties. The observations are that an unexpected increase of catalyst activity, accompanied by a significant improvement in mechanical properties, is found when using a carefully chosen mixture of solvents. A tentative explanation is given on the basis of the presented results.
Numerical Simulations of Restrained Shrinkage Cracking in Glass Fibre Reinforced Shotcrete Slabs
Authors: Sjölander Andreas , Ansell Anders
Published: May 2017

Modern tunnels in hard rock are usually constructed by drill and blast with the rock reinforced by shotcrete (sprayed concrete) in combination with rock bolts. The irregular rock surface and the projection method of shotcrete lead to a tunnel lining of varying thickness with unevenly distributed stresses that affect the risk of cracking during shrinkage of the young and hardening material. Depending on water conditions, shotcrete is sprayed directly either onto the rock surface or over a drainage system, creating a fully restrained or an end-restrained structural system. In this paper, a method for nonlinear numerical simulations has been demonstrated, for the study of differences in stress build-up and cracking behaviour of restrained shotcrete slabs subjected to shrinkage. Special focus was given to the effects of the irregular shape and varying thickness of the shotcrete. The effects of glass fibre reinforcement and bond were implemented in the study by changing the fracture energy in bending and in the interaction between shotcrete and the substrate. The study verifies that an end-restrained shotcrete slab is prone to shrinkage induced cracking and shows the importance of a continuous bond to avoid wide shrinkage cracks when shotcrete is sprayed directly onto the rock.
Asymptomatic Brain Edema after Hemodialysis Initiation in a Patient with Severe Uremia
Authors: Fujisaki Kiichiro , Nakagawa Kaneyasu , Nagae Hiroshi , Nakano Toshiaki , Taniguchi Masatomo , Masutani Kosuke , Kitazono Takanari , Tsuruya Kazuhiko
Published: May 2017

A 66-year-old man with severe renal insufficiency presented with mild confusion associated with uremia. Cranial magnetic resonance imaging (MRI) showed no remarkable changes. The patient was placed on short-duration hemodialysis (2 hours) with smaller surface area and low blood flow (100 mL/min) to avoid dialysis disequilibrium syndrome (DDS). His consciousness gradually improved and he did not develop apparent DDS symptoms. However, T2-weighted FLAIR MRI showed increased signal intensities bilaterally in the cortical and subcortical areas of the occipital lobe on day 15. In other words, cranial MRI showed cerebral edema, indicating asymptomatic DDS. On day 29, cranial MRI showed a return to findings on admission. In this case, because the patient did not have apparent DDS symptoms despite MRI changes, we diagnosed asymptomatic cerebral edema. The patient was discharged on regular intermittent HD without any neurological deficits. No further neurological disturbances were noted during 1-year follow-up. MRI findings in ESKD patients without DDS symptoms help to clarify the diagnosis of cerebral edema. In this case, the patient did not have apparent DDS symptoms and was therefore diagnosed with asymptomatic cerebral edema.
Effect of Graphite Nanosheets on Properties of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)
Authors: Montagna Larissa Stieven , Montanheiro Thaís Larissa do Amaral , Machado João Paulo Barros , Passador Fábio Roberto , Lemes Ana Paula , Rezende Mirabel Cerqueira
Published: May 2017

The influence of different contents, 0.25, 0.50, and 1.00 wt%, of graphite nanosheets (GNS) on the properties of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanocomposites obtained by solution casting method has been studied. GNS were prepared by three steps: intercalation (chemical exfoliation), expansion (thermal treatment), and the GNS obtainment (physical treatment by ultrasonic exfoliation). X-ray diffraction (XRD), Raman spectroscopy, and field emission gun-scanning electron microscopy (FE-SEM) showed that the physical, chemical, and thermal treatments preserved the graphite sheets structure. XRD and Raman results also showed that GNS were dispersed in the PHBV matrix. The degree of crystallinity (Xc) of the nanocomposites did not change when the graphite nanosheets were added. However, the GNS acted as nucleation agent for crystallization; that is, in the second heating the samples containing GNS showed two melting peaks. The addition the GNS did not change the thermal stability of the PHBV.
Experimental Research on Longitudinal Steel Bar Bond Properties in Modified Recycled Aggregate Concrete Beam-Column Interior Joint under Cyclic Loading
Authors: Fu Jia-Li , Liu Bing-Kang , Ma Jun-Wei
Published: May 2017

Three recycled aggregate concrete (RAC) beam-column interior-joint specimens (including two modified recycled aggregate concrete interior joints with replacement of fly ash ratio of 15%) were tested under cyclic loading in order to study the bond behavior of the longitudinal steel bar at RAC joint. The tests obtained load-strain hysteresis curves of longitudinal bars. The relative bond strength of longitudinal bar in characteristic stages was calculated. The test results indicated that the longitudinal steel bar in RAC joint is able to supply a stable bond stress both in the full crack stage and in the ultimate stage, meaning that the requirements of stress transferring and displacement coordinating between RAC and reinforcements can be satisfied. The larger the diameter of steel bar, the more serious the bond strength degradation. The RAC with fly ash can improve the interface compactness and bond strength of recycled aggregate in full crack stage. When beam-column interface of concrete compression zone reaches ultimate strain, the compressive stress of the longitudinal reinforcement cannot be exerted. The bond stress of the steel bar cannot realize the pull and compressive stress conversion in the length of the core area of the joint owing to the stress hysteresis of the compression rebars.
Capsular Polysaccharide is a Main Component ofMycoplasma ovipneumoniaein the Pathogen-Induced Toll-Like Receptor-Mediated Inflammatory Responses in Sheep Airway Epithelial Cells
Authors: Jiang Zhongjia , Song Fuyang , Li Yanan , Xue Di , Deng Guangcun , Li Min , Liu Xiaoming , Wang Yujiong
Published: May 2017

Mycoplasma ovipneumoniae(M. ovipneumoniae) is characterized as an etiological agent of primary atypical pneumonia that specifically infects sheep and goat. In an attempt to better understand the pathogen-host interaction between the invadingM. ovipneumoniaeand airway epithelial cells, we investigated the host inflammatory responses against capsular polysaccharide (designated as CPS) ofM. ovipneumoniaeusing sheep bronchial epithelial cells cultured in an air-liquid interface (ALI) model. Results showed that CPS derived fromM. ovipneumoniaecould activate toll-like receptor- (TLR-) mediated inflammatory responses, along with an elevated expression of nuclear factor kappa B (NF-κB), activator protein-1 (AP-1), and interferon regulatory factor 3 (IRF3) as well as various inflammatory-associated mediators, representatively including proinflammatory cytokines, such as IL1β, TNFα, and IL8, and anti-inflammatory cytokines such as IL10 and TGFβof TLR signaling cascade. Mechanistically, the CPS-induced inflammation was TLR initiated and was mediated by activations of both MyD88-dependent and MyD88-independent signaling pathways. Of importance, a blockage of CPS with specific antibody led a significant reduction ofM. ovipneumoniae-induced inflammatory responses in sheep bronchial epithelial cells. These results suggested that CPS is a key virulent component ofM. ovipneumoniae, which may play a crucial role in the inflammatory response induced byM. ovipneumoniaeinfections.
Treating Hepatitis C in Patients with Renal Failure
Authors: Lens Sabela , Rodriguez-Tajes Sergio , Llovet Laura-Patricia , Maduell Francisco , Londoño Maria-Carlota
Published: May 2017

Background: There is a strong relationship between hepatitis C virus (HCV) infection and the kidney. Approximately 10-16% of the patients with HCV infection develop renal disease, and the prevalence of HCV infection in patients with renal dysfunction is higher than that of the general population (9.5 vs. 1.6%). Moreover, HCV-positive patients on hemodialysis (HD) have higher mortality rates as compared to HCV-negative patients also on HD, not only due to liver-related complications but also owing to cardiovascular disease. Key Messages: In the interferon era, the treatment of HCV infection in patients on HD was hampered due to a significant number of treatment-related adverse events (predominately anemia and infectious complications). The development of direct-acting antivirals (DAAs) has revolutionized the field allowing viral eradication in these very sick patients. Two recently published clinical trials assessed the efficacy and safety of DAAs in patients with end-stage renal disease (ESRD). The combination of grazoprevir and elbasvir has been studied in the C-SURFER trial with 94% of the patients achieving sustained virological response (SVR). Adverse events were mild and only a small number of patients discontinued therapy early due to adverse events. The 3D regimen was evaluated in the RUBY-I trial. Here, a 90% SVR rate was achieved in 20 patients with ESRD, most of them on HD. Although sofosbuvir is eliminated by the kidney and its use in patients with glomerular filtration rate <30 mL/min is not recommended, real-life data have shown good results for this drug in terms of efficacy and safety. Conclusions: The use of DAAs has safely permitted the treatment of patients with renal dysfunction with excellent efficacy results.
Distinct Distribution of Immunocytes in a Retropharyngeal Lymphadenopathy Associated with Kawasaki Disease: A Case Study Compared with Tonsillitis
Authors: Okada Seigo , Kobayashi-Fujiwara Yuki , Oga Atsunori , Furuta Takashi , Ikemoto Kenzo , Fujii Hironori , Sakata Yasufumi , Suzuki Yasuo , Hasegawa Shunji , Kusuda Takeshi , Itoh Hiroshi , Yamashita Hiroshi , Ohga Shouichi
Published: May 2017

Objectives: Retropharyngeal lesions are often associated with Kawasaki disease (KD). A 4-year-old male first presented a peritonsillar and retropharyngeal abscess-like lesion. Surgical tonsillectomy was performed to avoid a risk of mediastinal abscess, but he fulfilled the diagnostic criteria of KD after the operation. This prompted us to perform a histological study on the KD tonsils. Methods: The histopathology of the KD tonsil specimens were compared with hypertrophic tonsils obtained from 4 patients with chronic tonsillitis unrelated to KD assessed by the immunostainings. Results: KD tonsils showed small lymphatic follicles and neutrophil infiltration in the peritonsillar muscle layer, with no evidence of vasculitis or abscess formation. The KD tonsils exclusively showed (1) predominant activated CD4+ T cells in the perifollicular interstitium, (2) sparse scattering of CD68+ monocytes/macrophages in the lymphatic follicles, and (3) polyclonal carcinoembryonic antigen-positive cells in the lymphatic follicles and venules with the high endothelial cells. Conclusions: The uniquely distributed immunocytes suggest the inflammatory process of KD involving the pathogen-associated molecules.
Neointimal Healing Evaluated by Optical Coherence Tomography after Drug-Eluting Absorbable Metal Scaffold Implantation in de novo Native Coronary Lesions: Rationale and Design of the Magmaris-OCT Study
Authors: Karjalainen Pasi , Paana Tuomas , Sia Jussi , Nammas Wail
Published: May 2017

Objectives: We sought to explore neointimal healing assessed by optical coherence tomography (OCT) following implantation of the Magmaris sirolimus-eluting absorbable metal scaffold. Methods: The Magmaris-OCT is a prospective, multicenter, single-arm observational clinical study, intended to enrol 60 consecutive patients with up to 2 de novo native coronary lesions, each located in different major epicardial vessels, with a reference vessel diameter of 2.5-3.5 mm, and a maximum lesion length of 20 mm. Patients will undergo Magmaris scaffold implantation in the target lesion, according to the standard practice. Clinical follow-up will take place at 30 days, and at 3, 6, 9, and 12 months. For invasive-imaging follow-up, patients will be classified into 3 groups: cohort A will be scheduled for follow-up at 3 months, cohort B at 6 months, and cohort C at 12 months. Invasive imaging will include quantitative coronary angiography, OCT evaluation, and coronary flow reserve measurement. The primary end point will be the percentage of uncovered scaffold struts assessed by OCT at the prespecified follow-up. Conclusions: This study will provide insight into the short- and mid-term healing properties following Magmaris scaffold implantation, with special emphasis on the neointimal coverage of scaffold struts.
Adenosine Triphosphate Metabolism Measured by Phosphorus Magnetic Resonance Spectroscopy: A Potential Biomarker for Multiple Sclerosis Severity
Authors: Kauv Paul , Ayache Samar S. , Créange Alain , Chalah Moussa A. , Lefaucheur Jean-Pascal , Hodel Jérôme , Brugières Pierre
Published: May 2017

Background/Aims: Phosphorus magnetic resonance spectroscopy (31P-MRS) has previously shown abnormal changes in energy metabolites in the brain of multiple sclerosis (MS) patients. However, the relationship between these energy metabolites - particularly adenosine triphosphate (ATP) - and the disease severity remains unclear. The objective of this study was to determine whether measuring ATP metabolites can help to predict disease severity in MS patients. Methods:31P-MRS at 3 tesla was performed in 9 relapsing remitting (RRMS), 9 secondary progressive MS patients (SPMS), and 10 age-matched healthy controls. ATP metabolites (expressed as %) in normally appearing white matter of the centrum semiovale were compared between patients and healthy controls. The relationship between Expanded Disability Status Scale (EDSS) and ATP metabolites was evaluated. Results: RRMS and SPMS patients had higher phosphocreatine (PCr) and lower phosphodiesters than healthy controls. In addition, RRMS patients had higher β-ATP% than SPMS patients. β-ATP% was negatively correlated with EDSS in all patients. Conclusion: Our findings suggest a defective PCr metabolism in both patient groups, and a higher state of energy production in RRMS that might reflect a compensatory mechanism in face of the increased needs. The correlation of β-ATP with EDSS makes it a candidate biomarker for assessing MS disease severity.
Negative Effect of Ellagic Acid on Cytosolic pH Regulation and Glycolytic Flux in Human Endometrial Cancer Cells
Authors: Abdelazeem Khalid N. M. , Singh Yogesh , Lang Florian , Salker Madhuri S.
Published: May 2017

Background/Aims: Key properties of tumor cells include enhanced glycolytic flux with excessive consumption of glucose and formation of lactate. As glycolysis is highly sensitive to cytosolic pH, maintenance of glycolysis requires export of H+ ions, which is in part accomplished by Na+/H+ exchangers, such as NHE1. The carrier is sensitive to oxidative stress. Growth of tumor cells could be suppressed by the polyphenol Ellagic acid, which is found in various fruits and vegetables. An effect of Ellagic acid on transport processes has, however, never been reported. The present study thus elucidated an effect of Ellagic acid on cytosolic pH (pHi), NHE1 transcript levels, NHE1 protein abundance, Na+/H+ exchanger activity, and lactate release. Methods: Experiments were performed in Ishikawa cells without or with prior Ellagic acid (20 µM) treatment. NHE1 transcript levels were determined by qRT-PCR, NHE1 protein abundance by Western blotting, pHi utilizing (2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein [BCECF] fluorescence, Na+/H+ exchanger activity from Na+ dependent realkalinization after an ammonium pulse, cell volume from forward scatter in flow cytometry, reactive oxygen species (ROS) from 2’,7’-dichlorodihydrofluorescein fluorescence, glucose uptake utilizing 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose, and lactate concentration in the supernatant utilizing a colorimetric (570 nm)/ fluorometric enzymatic assay. Results: A 48 hour treatment with Ellagic acid (20 µM) significantly decreased NHE1 transcript levels by 75%, NHE1 protein abundance by 95%, pHi from 7.24 ± 0.01 to 7.02 ± 0.01, Na+/H+ exchanger activity by 77%, forward scatter by 10%, ROS by 82%, glucose uptake by 58%, and lactate release by 15%. Conclusion: Ellagic acid (20µM) markedly down-regulates ROS formation and NHE1 expression leading to decreased Na+/H+ exchanger activity, pHi, glucose uptake and lactate release in endometrial cancer cells. Those effects presumably contribute to reprogramming and growth inhibition of tumor cells.