bluuebunny/crossref_metadata_2025 huggingface dataset:
Crimean-Congo Hemorrhagic Fever Virus Nucleocapsid Protein Augments mRNA Translation
Authors: Jeeva Subbiah , Cheng Erdong , Ganaie Safder S. , Mir Mohammad A.
Published: May 2017

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne Nairovirus of the
Bunyaviridae
family, causing severe illness with high mortality rates in humans. Here, we demonstrate that CCHFV nucleocapsid protein (CCHFV-NP) augments mRNA translation. CCHFV-NP binds to the viral mRNA 5′ untranslated region (UTR) with high affinity. It facilitates the translation of reporter mRNA both
in vivo
and
in vitro
with the assistance of the viral mRNA 5′ UTR. CCHFV-NP equally favors the translation of both capped and uncapped mRNAs, demonstrating the independence of this translation strategy on the 5′ cap. Unlike the canonical host translation machinery, inhibition of eIF4F complex, an amalgam of three initiation factors, eIF4A, eIF4G, and eIF4E, by the chemical inhibitor 4E1RCat did not impact the CCHFV-NP-mediated translation mechanism. However, the proteolytic degradation of eIF4G alone by the human rhinovirus 2A protease abrogated this translation strategy. Our results demonstrate that eIF4F complex formation is not required but eIF4G plays a critical role in this translation mechanism. Our results suggest that CCHFV has adopted a unique translation mechanism to facilitate the translation of viral mRNAs in the host cell cytoplasm where cellular transcripts are competing for the same translation apparatus.

IMPORTANCE
Crimean-Congo hemorrhagic fever, a highly contagious viral disease endemic to more than 30 countries, has limited treatment options. Our results demonstrate that NP favors the translation of a reporter mRNA harboring the viral mRNA 5′ UTR. It is highly likely that CCHFV uses an NP-mediated translation strategy for the rapid synthesis of viral proteins during the course of infection. Shutdown of this translation mechanism might selectively impact viral protein synthesis, suggesting that an NP-mediated translation strategy is a target for therapeutic intervention against this viral disease.
Spontaneous and Vaccine-Induced Clearance of Mus Musculus Papillomavirus 1 Infection
Authors: Jiang Rosie T. , Wang Joshua W. , Peng Shiwen , Huang Tsui-Chin , Wang Chenguang , Cannella Fabiana , Chang Yung-Nien , Viscidi Raphael P. , Best Simon R. A. , Hung Chien-Fu , Roden Richard B. S.
Published: May 2017

Mus musculus papillomavirus 1 (MmuPV1/MusPV1) induces persistent papillomas in immunodeficient mice but not in common laboratory strains. To facilitate the study of immune control, we sought an outbred and immunocompetent laboratory mouse strain in which persistent papillomas could be established. We found that challenge of SKH1 mice (Crl:SKH1-Hrhr) with MmuPV1 by scarification on their tail resulted in three clinical outcomes: (i) persistent (>2-month) papillomas (∼20%); (ii) transient papillomas that spontaneously regress, typically within 2 months (∼15%); and (iii) no visible papillomas and viral clearance (∼65%). SKH1 mice with persistent papillomas were treated by using a candidate preventive/therapeutic naked-DNA vaccine that expresses human calreticulin (hCRT) fused in frame to MmuPV1 E6 (mE6) and mE7 early proteins and residues 11 to 200 of the late protein L2 (hCRTmE6/mE7/mL2). Three intramuscular DNA vaccinations were delivered biweekly viain vivoelectroporation, and both humoral and CD8 T cell responses were mapped and measured. Previously persistent papillomas disappeared within 2 months after the final vaccination. Coincident virologic clearance was confirmed byin situhybridization and a failure of disease to recur after CD3 T cell depletion. Vaccination induced strong mE6 and mE7 CD8+T cell responses in all mice, although they were significantly weaker in mice that initially presented with persistent warts than in those that spontaneously cleared their infection. A human papillomavirus 16 (HPV16)-targeted version of the DNA vaccine also induced L2 antibodies and protected mice from vaginal challenge with an HPV16 pseudovirus. Thus, MmuPV1 challenge of SKH1 mice is a promising model of spontaneous and immunotherapy-directed clearances of HPV-related disease.

IMPORTANCEHigh-risk-type human papillomaviruses (hrHPVs) cause 5% of all cancer cases worldwide, notably cervical, anogenital, and oropharyngeal cancers. Since preventative HPV vaccines have not been widely used in many countries and do not impact existing infections, there is considerable interest in the development of therapeutic vaccines to address existing disease and infections. The strict tropism of HPV requires the use of animal papillomavirus models for therapeutic vaccine development. However, MmuPV1 failed to grow in common laboratory strains of mice with an intact immune system. We show that MmuPV1 challenge of the outbred immunocompetent SKH1 strain produces both transient and persistent papillomas and that vaccination of the mice with a DNA expressing an MmuPV1 E6E7L2 fusion with calreticulin can rapidly clear persistent papillomas. Furthermore, an HPV16-targeted version of the DNA can protect against vaginal challenge with HPV16, suggesting the promise of this approach to both prevent and treat papillomavirus-related disease.
Delaying ACL reconstruction and treating with exercise therapy alone may alter prognostic factors for 5-year outcome: an exploratory analysis of the KANON trial
Authors: Filbay Stephanie R , Roos Ewa M , Frobell Richard B , Roemer Frank , Ranstam Jonas , Lohmander L Stefan
Published: May 2017

Aim

Identify injury-related, patient-reported and treatment-related prognostic factors for 5-year outcomes in acutely ACL-ruptured individuals managed with early reconstruction plus exercise therapy, exercise therapy plus delayed reconstruction or exercise therapy alone.

Methods

Exploratory analysis of the Knee Anterior Cruciate Ligament, Nonsurgical versus Surgical Treatment (KANON) trial (ISRCTN84752559). Relationships between prognostic factors (baseline cartilage, meniscus and osteochondral damage, baseline extension deficit, baseline patient-reported outcomes, number of rehabilitation visits, graft/contralateral ACL rupture, non-ACL surgery and ACL treatment strategy) and 5-year Knee Injury and Osteoarthritis Outcome Score (KOOS) pain, symptoms, sport/recreation and quality of life (QOL) scores were explored using multivariable linear regression. Estimates were adjusted for sex, age, body mass index, preinjury activity level, education and smoking.

Results

For all participants (n=118), graft/contralateral ACL rupture, non-ACL surgery and worse baseline 36-item Short-Form Mental Component Scores were associated with worse outcomes. Treatment with exercise therapy alone was a prognostic factor forlessknee symptoms compared with early reconstruction plus exercise therapy (regression coefficient 10.1, 95% CI 2.3 to 17.9). Baseline meniscus lesion was associated with worse sport/recreation function (−14.4, 95% CI −27.6 to –1.3) and osteochondral lesions were associated with worse QOL (−12.3, 95% CI −24.3 to –0.4) following early reconstruction plus exercise therapy. In the same group, undergoing additional non-ACL surgery and worse baseline KOOS scores were prognostic for worse outcome on all KOOS subscales. Following delayed reconstruction, baseline meniscus damage was a prognostic factor forlesspain (14.3, 95% CI 0.7 to 27.9). Following exercise therapy alone, undergoing non-ACL surgery was prognostic for worse pain.

Conclusions

Treatment-dependent differences in prognostic factors for 5-year outcomes may support individualised treatment after acute ACL rupture in young active individuals.

Trial registration number

Current Controlled TrialsISRCTN84752559.
For a healthier future: a virtuous cycle for reducing exposure to persistent organic pollutants
Authors: Mori Chisato , Todaka Emiko
Published: May 2017

In the modern society, people are exposed to various pollutants during their lifetime. Worldwide, the status of children's health has changed in recent decades. Some studies have attempted to identify the causes of these changes and whether they relate to pollutant exposure; however, such attempts have faced major challenges because human life is complex, involving many social and environmental factors. Several long-term cohort studies are being conducted to determine the relationship between diseases and social and environmental factors in children. Even before we establish complete proof of adverse effects, we should attempt to decrease risk to future generations by adopting precautionary principles. Environmental exposure to persistent organic pollutants can be reduced throughout the stages of life—the fetal period, newborn and infant periods, childhood, adolescence and adulthood (preconception) by individuals as well as by society as a whole. Through reducing environmental exposure to pollutants, adverse health effects can also be reduced, which will contribute to healthier future generations. Here, we suggest a virtuous cycle for improving the health of future generations through reduced exposure to persistent pollutants.
Rosie's diary
Authors: Perrett Rose
Published: May 2017

Every month, Vet Record Careers checks in with third‐year vet student, Rosie Perrett.
Effects of Viola mandshurica on Atherosclerosis and Hepatic Steatosis in ApoE−∕− via the AMPK Pathway
Authors: Park Sun Haeng , Sung Yoon-Young , Nho Kyoung jin , Kim Dong Sun , Kim Ho Kyoung
Published: May 2017

Atherosclerosis was previously thought to be a disease that primarily involves lipid accumulation in the arterial wall. In this report, we investigated the effect of Viola mandshurica W. Becker (V. mandshurica) water extract on atherosclerosis in apolipoprotein E deficient (ApoE[Formula: see text]) mice. The administration of V. mandshurica to high-fat diet-fed mice reduced body weight, liver weight, and serum levels of lipids (total cholesterol, low-density lipoprotein-cholesterol, triglycerides), glucose, alanine transaminase, and aspartate transaminase. Histopathologic analyses of the aorta and liver revealed that V. mandshurica attenuated atherosclerotic lesions and reduced lipid accumulation, inflammatory responses and fatty acid synthesis. V. mandshurica also increased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), thereby reducing acetyl-CoA carboxylase (ACC) in liver tissue and inhibiting sterol regulatory element-binding protein 1c (SREBP-1c). V. mandshurica reduced protein expression levels of adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin) as well as ACC, fatty acid synthase, and SREBP-1c. In addition, quantitative analysis of V. mandshurica by high-performance liquid chromatography revealed the presence of esculetin and scopoletin. Esculetin and scopoletin reduced adhesion molecules in human aortic smooth muscle cells. Our results indicate that the anti-atherosclerotic effects of V. mandshurica may be associated with activation of the AMPK pathway. Therefore, AMPK-dependent phosphorylation of SREBP-1c by V. mandshurica may be an effective therapeutic strategy for combatting atherosclerosis and hepatic steatosis.
ASSOUAD-MINIMALITY OF MORAN SETS UNDER QUASI-LIPSCHITZ MAPPINGS
Authors: XI LIFENG , DENG JUAN , WEN ZHIYING
Published: May 2017

The quasi-Lipschitz mappings, weaker than the bi-Lipschitz mappings, preserve Hausdorff, packing and box dimensions, but change Assouad dimension [Formula: see text]. In this paper, for Moran fractals, we investigate the change of their Assouad dimension under the quasi-Lipschitz mappings. We study a class of Moran set which is quasi-Lipschitz Assouad-minimal, i.e. for any [Formula: see text] in the class, [Formula: see text] for all quasi-Lipschitz mappings [Formula: see text] defined on [Formula: see text]. For another class of Moran sets, we prove that for any [Formula: see text] in the class, [Formula: see text] where the infimum is taken over all quasi-Lipschitz mappings [Formula: see text] defined on [Formula: see text], and [Formula: see text] is the quasi-Assouad dimension introduced in [F. Lü and L. F. Xi, Quasi-Assouad dimension of fractals, J. Fractal Geom. 3 (2016) 187–215].
A Social-Based DTN Routing in Cooperative Vehicular Sensor Networks
Authors: Wang Tong , Zhou Yongzhe , Wang Xibo , Cao Yue
Published: May 2017

As a cooperative information system, vehicles in Vehicular Sensor Networks deliver messages based on collaboration. Due to the high speed of vehicles, the topology of the network is highly dynamic, and the network may be disconnected frequently. So how to transfer large files in such network is worth considering. The encountering nodes which never meet before flood messages blindly cause tremendous network overhead. We address this challenge by introducing the Encounter Utility Rank Router (EURR) based on social metrics. EURR includes three cases: Utility Replication Strategy, Lifetime Replication Strategy and SocialRank Replication Strategy. The Lifetime Replication is promising and complements Utility Replication. It enhances the delivery ratio by relaying the copy via the remaining lifetime. Considering the network overhead, the SocialRank Replication replicates a copy according to the SocialRank when two communicating nodes have not met before. The routing mechanism explores the utility of history encounter information and social opportunistic forwarding. The results under the scenario show an advantage of the proposed EURR over the compared algorithms in terms of delivery ratio, average delivery latency and overhead ratio.
ANALYTICAL SOLUTION OF HYPERBOLIC BIOHEAT EQUATION IN SPHERICAL COORDINATES APPLIED IN RADIOFREQUENCY HEATING
Authors: TALAEE MOHAMMAD REZA , KABIRI ALI
Published: May 2017

This paper presents an analytical solution for the hyperbolic bioheat equation in spherical coordinates under nonuniform distributed heat source term, which is theoretically modeling the Radiofrequency Heating (RFH) technique. In RFH technique a spherical electrode is inserted into the diseased tissue which leads to the heat generation there due to the imposed electromagnetic field. Because of the non-Fourier behavior of biological tissues, the hyperbolic Penne’s equation is adopted as perfused thermal model. The equation has been solved using Eigenvalue method and the closed form solutions are introduced. The temperature profiles are determined for a sample RFH procedure in cornea and liver and the effect of perfusion term in Penne’s bioheat equation is shown. The effective parameters in the RFH process such as electrode radius, power and different material are studied analytically too. The derived solution can play a role of verification basis of other numerical ones in this area.
NUMERICAL INVESTIGATIONS OF THE FLEXIBILITY OF INTRAVASCULAR BRAIDED STENT
Authors: FU WENYU , CHENG GUANG , YAN RUOBING , QIAO AIKE
Published: May 2017

Braided stents are commonly used to treat cerebral aneurysm, but there is little information about the bending characteristic of braided stent used for cerebral aneurysm. This paper investigates how geometrical parameters of braided stent influence its flexibility. Eight groups of braided stent models with different geometries (i.e., nominal diameter, length, braiding angle, number of wires, diameter of wire, frictional coefficient among wires and porosity) were constructed. Parametric analyses of these models were carried out by using Abaqus/Explicit. When the nominal diameter varied from 2[Formula: see text]mm to 5.5[Formula: see text]mm, the forces required for flexural deformation decrease from [Formula: see text][Formula: see text]N to [Formula: see text][Formula: see text]N; when the axial length varied from 10[Formula: see text]mm to 40[Formula: see text]mm, the forces required for flexural deformation decrease from [Formula: see text][Formula: see text]N to [Formula: see text][Formula: see text]N; when the braiding angle increases from 30[Formula: see text] to 75[Formula: see text] (the number of wires is 48 and the diameter of the wire is 0.026[Formula: see text]mm), the forces required for bending deformation decrease from [Formula: see text][Formula: see text]N to [Formula: see text][Formula: see text]N; when the diameter of wires increases from 0.026[Formula: see text]mm to 0.052[Formula: see text]mm (the number of wires is 24 and the braiding angle is 60[Formula: see text]), the forces required for flexural deformation increase from [Formula: see text][Formula: see text]N to [Formula: see text][Formula: see text]N; and when the number of wires increases from 14 to 48 (the braiding angle is 75[Formula: see text] and the diameter of the wire is 0.026[Formula: see text]mm), the forces required for flexural deformation increase from [Formula: see text][Formula: see text]N to [Formula: see text][Formula: see text]N. From the data above it can be seen that the diameter of wires, the number of wires and braiding angle have a larger impact on bending characteristics of braided stent; and the axial length and nominal diameter have a smaller impact on bending characteristics of braided stent. Results of the present study may provide theoretical guidance for the design of self-expanding braided stent and its clinical practice.
Synthesis and characterization of two new triads with ferrocene and C60 connected by triple bonds to the beta-positions of meso-tetraphenylporphyrin
Authors: Limosani Francesca , Possanza Fabio , Ciotta Erica , Pepi Federico , Salvitti Chiara , Tagliatesta Pietro , Pizzoferrato Roberto
Published: May 2017

The 2,12 pyrrole positions of meso-tetraphenylporphyrin were functionalized through triple carbon–carbon bonds by C60 and ferrocene giving new electron donor–acceptor triads which have been characterized and studied by photophysical methods. The fluorescence spectra of the new compounds have been compared to those previously reported for similar compounds giving as a result an increase of the quantum efficiency based on the larger separation of fullerene from the porphyrin ring. On the contrary the efficiency decreases with the presence of a phenylene spacer between ferrocene and the macrocycle.
The Impact of Iceberg Orders in Limit Order Books
Authors: Frey Stefan , Sandås Patrik
Published: May 2017

We examine the impact of iceberg orders on the price and order flow dynamics in limit order books. Iceberg orders allow traders to simultaneously hide a large portion of their order size and signal their interest in trading to the market. We show that when market participants detect iceberg orders they tend to strongly respond by submitting matching market orders consistent with iceberg orders facilitating the search for latent liquidity. The greater the fraction of an iceberg order that is executed, the smaller is its price impact consistent with liquidity rather than informed trading. The presence of iceberg orders is associated with increased trading consistent with a positive liquidity externality, but the reduced order book transparency associated with iceberg orders also creates an adverse selection cost for limit orders that may partly offset any gains.
Semantics and Efficient Simulation Algorithms of an Expressive Multilevel Modeling Language
Authors: Helms Tobias , Warnke Tom , Maus Carsten , Uhrmacher Adelinde M.
Published: May 2017

The domain-specific modeling and simulation language ML-Rules is aimed at facilitating the description of cell biological systems at different levels of organization. Model states are chemical solutions that consist of dynamically nested, attributed entities. The model dynamics are described by rules that are constrained by arbitrary functions, which can operate on the entities’ attributes, (nested) solutions, and the reaction kinetics. Thus, ML-Rules supports an expressive hierarchical, variable structure modeling of cell biological systems. The formal syntax and semantics of ML-Rules show that it is firmly rooted in continuous-time Markov chains. In addition to a generic stochastic simulation algorithm for ML-Rules, we introduce several specialized algorithms that are able to handle subclasses of ML-Rules more efficiently. The algorithms are compared in a performance study, leading to conclusions on the relation between expressive power and computational complexity of rule-based modeling languages.
Some steps to improve software information
Authors: Heinle Albert , Koepf Wolfram , Sperber Wolfram
Published: May 2017

Mathematical software plays an increasing role in mathematics and key technologies. But to find and get information about software is expensive. Missing metadata standards, e.g., the citation of software, are one of the reasons. In the following some recent developmentsare described how the community can contribute to a better information system for mathematical software.
Linearization of a specific family of Bézout matrices
Authors: Sevyeri Leili Rafiee , Corless Robert M.
Published: May 2017

We want to investigate on the sequence of minimal polynomials of the sequence below.
AskConstants proposes concise non-floats close to floats
Authors: Stoutemyer David R.
Published: May 2017

This poster presentation is an opportunity to try the downloadable AskConstants program. This copy of some posters is a sequence of images of the program in operation.
Regulation of ATP production: dependence on calcium concentration and respiratory state
Authors: Fink Brian D. , Bai Fan , Yu Liping , Sivitz William I.
Published: May 2017

Nanomolar free calcium enhances oxidative phosphorylation. However, the effects over a broad concentration range, at different respiratory states, or on specific energy substrates are less clear. We examined the action of varying [Ca2+] over respiratory states ranging 4 to 3 on skeletal muscle mitochondrial respiration, potential, ATP production, and H2O2 production using ADP recycling to clamp external [ADP]. Calcium at 450 nM enhanced respiration in mitochondria energized by the complex I substrates, glutamate/malate (but not succinate), at [ADP] of 4–256 µM, but more substantially at intermediate respiratory states and not at all at state 4. Using varied [Ca2+], we found that the stimulatory effects on respiration and ATP production were most prominent at nanomolar concentrations, but inhibitory at 10 µM or higher. ATP production decreased more than respiration at 10 µM calcium. However, potential continued to increase up to 10 µM; suggesting a calcium-induced inability to utilize potential for phosphorylation independent of opening of the mitochondrial permeability transition pore (MTP). This effect of 10 µM calcium was confirmed by direct determination of ATP production over a range of potential created by differing substrate concentrations. Consistent with past reports, nanomolar [Ca2+] had a stimulatory effect on utilization of potential for phosphorylation. Increasing [Ca2+] was positively and continuously associated with H2O2 production. In summary, the stimulatory effect of calcium on mitochondrial function is substrate dependent and most prominent over intermediate respiratory states. Calcium stimulates or inhibits utilization of potential for phosphorylation dependent on concentration with inhibition at higher concentration independent of MTP opening.
Decreased phosphatase PTEN amplifies PI3K signaling and enhances proinflammatory cytokine release in COPD
Authors: Yanagisawa Satoru , Baker Jonathan R. , Vuppusetty Chaitanya , Fenwick Peter , Donnelly Louise E. , Ito Kazuhiro , Barnes Peter J.
Published: May 2017

The phosphatidylinositol 3-kinase (PI3K) pathway is activated in chronic obstructive pulmonary disease (COPD), but the regulatory mechanisms for this pathway are yet to be elucidated. The aim of this study was to determine the expression and role of phosphatase and tensin homolog deleted from chromosome 10 (PTEN), a negative regulator of the PI3K pathway, in COPD. PTEN protein expression was measured in the peripheral lung of COPD patients compared with smoking and nonsmoking controls. The direct influence of cigarette smoke extract (CSE) on PTEN expression was assessed using primary lung epithelial cells and a cell line (BEAS-2B) in the presence or absence of l-buthionine-sulfoximine (BSO) to deplete intracellular glutathione. The impact of PTEN knockdown by RNA interference on cytokine production was also examined. In peripheral lung, PTEN protein was significantly decreased in patients with COPD compared with the subjects without COPD ( P < 0.001) and positively correlated with the severity of airflow obstruction (forced expiratory volume in 1-s percent predicted; r = 0.50; P = 0.0012). Conversely, phosphorylated Akt, as a marker of PI3K activation, showed a negative correlation with PTEN protein levels ( r = −0.41; P = 0.0042). In both primary bronchial epithelial cells and BEAS-2B cells, CSE decreased PTEN protein, which was reversed by N-acetyl cysteine treatment. PTEN knockdown potentiated Akt phosphorylation and enhanced production of proinflammatory cytokines, such as IL-6, CXCL8, CCL2, and CCL5. In conclusion, oxidative stress reduces PTEN protein levels, which may result in increased PI3K signaling and amplification of inflammation in COPD.
Arginase-2 mediates renal ischemia-reperfusion injury
Authors: Raup-Konsavage Wesley M. , Gao Ting , Cooper Timothy K. , Morris Sidney M. , Reeves W. Brian , Awad Alaa S.
Published: May 2017

Novel therapeutic interventions for preventing or attenuating kidney injury following ischemia-reperfusion injury (IRI) remain a focus of significant interest. Currently, there are no definitive therapeutic or preventive approaches available for ischemic acute kidney injury (AKI). Our objective is to determine 1) whether renal arginase activity or expression is increased in renal IRI, and 2) whether arginase plays a role in development of renal IRI. The impact of arginase activity and expression on renal damage was evaluated in male C57BL/6J (wild type) and arginase-2 (ARG2)-deficient ( Arg2−/−) mice subjected to bilateral renal ischemia for 28 min, followed by reperfusion for 24 h. ARG2 expression and arginase activity significantly increased following renal IRI, paralleling the increase in kidney injury. Pharmacological blockade or genetic deficiency of Arg2 conferred kidney protection in renal IRI. Arg2−/−mice had significantly attenuated kidney injury and lower plasma creatinine and blood urea nitrogen levels after renal IRI. Blocking arginases using S-(2-boronoethyl)-l-cysteine (BEC) 18 h before ischemia mimicked arginase deficiency by reducing kidney injury, histopathological changes and kidney injury marker-1 expression, renal apoptosis, kidney inflammatory cell recruitment and inflammatory cytokines, and kidney oxidative stress; increasing kidney nitric oxide (NO) production and endothelial NO synthase (eNOS) phosphorylation, kidney peroxisome proliferator-activated receptor-γ coactivator-1α expression, and mitochondrial ATP; and preserving kidney mitochondrial ultrastructure compared with vehicle-treated IRI mice. Importantly, BEC-treated eNOS-knockout mice failed to reduce blood urea nitrogen and creatinine following renal IRI. These findings indicate that ARG2 plays a major role in renal IRI, via an eNOS-dependent mechanism, and that blocking ARG2 activity or expression could be a novel therapeutic approach for prevention of AKI.
Functional assessment of the diaphragm by speckle tracking ultrasound during inspiratory loading
Authors: Oppersma Eline , Hatam Nima , Doorduin Jonne , van der Hoeven Johannes G. , Marx Gernot , Goetzenich Andreas , Fritsch Sebastian , Heunks Leo M. A. , Bruells Christian S.
Published: May 2017

Assessment of diaphragmatic effort is challenging, especially in critically ill patients in the phase of weaning. Fractional thickening during inspiration assessed by ultrasound has been used to estimate diaphragm effort. It is unknown whether more sophisticated ultrasound techniques such as speckle tracking are superior in the quantification of inspiratory effort. This study evaluates the validity of speckle tracking ultrasound to quantify diaphragm contractility. Thirteen healthy volunteers underwent a randomized stepwise threshold loading protocol of 0–50% of the maximal inspiratory pressure. Electric activity of the diaphragm and transdiaphragmatic pressures were recorded. Speckle tracking ultrasound was used to assess strain and strain rate as measures of diaphragm tissue deformation and deformation velocity, respectively. Fractional thickening was assessed by measurement of diaphragm thickness at end-inspiration and end-expiration. Strain and strain rate increased with progressive loading of the diaphragm. Both strain and strain rate were highly correlated to transdiaphragmatic pressure (strain r2 = 0.72; strain rate r2 = 0.80) and diaphragm electric activity (strain r2 = 0.60; strain rate r2 = 0.66). We conclude that speckle tracking ultrasound is superior to conventional ultrasound techniques to estimate diaphragm contractility under inspiratory threshold loading.

NEW & NOTEWORTHY Transdiaphragmatic pressure using esophageal and gastric balloons is the gold standard to assess diaphragm effort. However, this technique is invasive and requires expertise, and the interpretation may be complex. We report that speckle tracking ultrasound can be used to detect stepwise increases in diaphragmatic effort. Strain and strain rate were highly correlated with transdiaphragmatic pressure, and therefore, diaphragm electric activity and speckle tracking might serve as reliable tools to quantify diaphragm effort in the future.
On the existence of a central respiratory oxygen sensor
Authors: Gourine Alexander V. , Funk Gregory D.
Published: May 2017

A commonly held view that dominates both the scientific and educational literature is that in terrestrial mammals the central nervous system lacks a physiological hypoxia sensor capable of triggering increases in lung ventilation in response to decreases in Po2 of the brain parenchyma. Indeed, a normocapnic hypoxic ventilatory response has never been observed in humans following bilateral resection of the carotid bodies. In contrast, almost complete or partial recovery of the hypoxic ventilatory response after denervation/removal of the peripheral respiratory oxygen chemoreceptors has been demonstrated in many experimental animals when assessed in an awake state. In this essay we review the experimental evidence obtained using in vitro and in vivo animal models, results of human studies, and discuss potential mechanisms underlying the effects of CNS hypoxia on breathing. We consider experimental limitations and discuss potential reasons why the recovery of the hypoxic ventilatory response has not been observed in humans. We review recent experimental evidence suggesting that the lower brain stem contains functional oxygen sensitive elements capable of stimulating respiratory activity independently of peripheral chemoreceptor input.
A model for in vivo analysis of sudomotor sympathetic C-fiber activation and human sweat gland output
Authors: Mack Gary W.
Published: May 2017

Quantitative assessment of small-fiber peripheral neuropathy often involves an evaluation of the interaction between the C-fiber sudomotor nerve and local sweat rate (SR). Typically, some sort of quantitative sudomotor axon reflex test (QSART) is performed to aid in diagnosing small-fiber dysfunction. The currently used QSART demonstrates only moderate test-retest reliability and therefore limits its usefulness in tracking small-fiber dysfunction. A new experimental model to examine small C-fiber function in the skin using intradermal electrical stimulation and simultaneous monitoring of SR is proposed. Using intradermal electrical stimulation (1.5 and 2.5 mA) and varying stimulus frequency from 0.2 to 64 Hz, a quantitative relationship between the area under the SR–time curve and log10 stimulus frequency is modeled using a four-parameter logistic equation, providing the following parameters: baseline, plateau, EC50, and Hill slope. The model has good to excellent repeatability within the same day (ICC = 0.98), on different days at the same skin site (ICC = 0.80), and when comparing two different skin sites (ICC = 0.78) with a small bias estimate and the line of identity always lying within the 95% limits of agreement. Atropine sulfate (0.1 mg/ml) blocked 90 ± 5% of the electrically induced sweating. Overall, the model provides control over sudomotor nerve activity and a quantitative assessment of SR. Finally, the ability to reproduce the quantitative stimulus-response curve on different days allows for a robust assessment of the relationship between the activation of a sympathetic C-fiber and local SR.

NEW & NOTEWORTHY A model for quantitative assessment of C-fiber function in human skin using intradermal electrical stimulation and local sweat rate measurements has been developed. This new electrically induced sweating model is nonpainful and allows for a complete stimulus-response curve plotting the area under the local sweat rate-time curve vs. the log10 stimulus frequency. The model has good reproducibility and should provide a means of assessing the progression of small C-fiber peripheral neuropathy in humans.
Terminal Guidance Law for UAV Based on Receding Horizon Control Strategy
Authors: Wu Zhenglong , Guan Zhenyu , Yang Chengwei , Li Jie
Published: May 2017

Terminal guidance law against the maneuvering target is always the focal point. Most of the literatures focus on estimating the acceleration of target and time to go in guidance law, which are difficult to acquire. This paper presents a terminal guidance law based on receding horizon control strategy. The proposed guidance law adopts the basic framework of receding horizon control, and the guidance process is divided into several finite time horizons. Then, optimal control theory and target motion prediction model are used to derive guidance law for minimum time index function with continuous renewal of original conditions at the initial time of each horizon. Finally, guidance law performs repeated iteration until intercepting the target. The guidance law is of subprime optimal type, requiring less guidance information, and does not need to estimate the acceleration of target and time to go. Numerical simulation has verified that the proposed guidance law is more effective than traditional methods on constant and sinusoidal target with bounded acceleration.
The Association between Age-Related Macular Degeneration and the Risk of Mortality
Authors: Wang Peipei , Wang Jie , Ma Jun , Jin Ge , Guan Xueqiang
Published: May 2017

Studies have investigated the association between age-related macular degeneration (AMD) and subsequent risks of mortality, but results have been equivocal. We conducted a comprehensive analysis of prospective cohort studies to assess the association of AMD and the risk of mortality in the general population. We searched PubMed and EMBASE for trials published from 1980 to 2016. We included 11 cohort studies that reported relative risks with 95% confidence intervals for the association of AMD and mortality, involving 57,069 participants. In a random-effects model, the adjusted RR (95% confidence interval) associated with AMD was 1.09 (1.02–1.17) for all-cause mortality. Findings from this research provide support that persons with AMD had a higher subsequent risk of mortality than persons without AMD.
GLT: Grouping Based Location Tracking for Object Tracking Sensor Networks
Authors: Hawbani Ammar , Wang Xingfu , Karmoshi Saleem , Kuhlani Hassan , Ghannami Aiman , Abudukelimu Adili , Ghoul Rafia
Published: May 2017

The use of wireless sensor networks (WSN) in tracking applications is growing rapidly. In these applications, the nodes detect, monitor, and track a target, object, or event. In this paper, we consider the problem of tracking mobile objects in wireless sensor networks (WSN). We present a novel tracking model, named Grouping based Location Tracking (GLT), scaling well with the number of nodes and the number of mobile objects. GLT is based on the Grouping Hierarchy Structure, GHS. In GHS, nodes are partitioned into groups (not clusters) according to their maximum covered region (MCR) such that each group contains a number of nodes and a number of leaders. GLT consists of two tiers. The first tier, which is called the Notification Tree (NT), enhances the activation mechanism, the data cleaning mechanism, and the energy balancing mechanism. On the other hand, the second tier, which is called the Hierarchical Spanning Tree (HST), supports the data reporting mechanism and the lifetime prolonging mechanism. Simulations results show that GLT reduces the communication node selections overhead without diminishing object tracking accuracy and achieves a significant energy consumption reduction and network lifetime extension compared with the state-of-the-art approaches.
Chebyshev Bandpass Filter Using Resonator of Tunable Active Capacitor and Inductor
Authors: Wang Yu , Chen Jian , Chen Chien-In Henry
Published: May 2017

A classic second-order coupled-capacitor Chebyshev bandpass filter using resonator of tunable active capacitor and inductor is presented. The low cost and small size of CMOS active components make the bandpass filter (BPF) attractive in fully integrated CMOS applications. The tunable active capacitor is designed to compensate active inductor’s resistance for resistive match in the resonator. In many design cases, more than 95% resistive loss is cancelled. Meanwhile, adjusting design parameter of the active component provides BPF tunability in center frequency, pass band, and pass band gain. Designed in 1.8 V 180 nanometer CMOS process, the BPF has a tuning frequency range of 758–864 MHz, a controllable pass band of 7.1–65.9 MHz, a quality factor Q of 12–107, a pass band gain of 6.5–18.1 dB, and a stopband rejection of 38–50 dB.
Epidemiological Survey and Phylogenetic Characterization of Cysticercus tenuicollis Isolated from Tibetan Pigs in Tibet, China
Authors: Luo Houqiang , Zhang Hui , Li Kun , Rehman Mujeeb Ur , Mehmood Khalid , Lan Yanfang , Huang Shucheng , Li Jiakui
Published: May 2017

Cysticercus tenuicollis, commonly known as “water bell,” is a larva of Taenia hydatigena, which is the most significant parasite of pigs. However, until now very few information is available regarding the prevalence and genetic characterization of the Cysticercus tenuicollis in Tibetan pigs. Therefore, the aim of this study was to investigate the prevalence and phylogenetic analysis of Cysticercus tenuicollis in Tibetan pigs. For this purpose, the COX2 gene of Cysticercus tenuicollis was amplified and sequenced for the first time in Tibetan pigs. The overall prevalence of Cysticercus tenuicollis was 43.93% in Tibetan pigs, with further distribution of 42.86% in 2014 and 45.35% in 2015. In Tibetan male and female pigs, the prevalence of Cysticercus tenuicollis was 43.39% and 44.56%, respectively. The prevalence of Cysticercus tenuicollis in different growing stages (juveniles, subadults, and adults) varied from 30.20% to 63.79%. The phylogenetic analysis of the Cysticercus tenuicollis isolates showed very close resemblance to 16 reference strains, isolates from Gansu, Hunan, and Sichuan provinces of China. To the best of our knowledge, this is the first report on the prevalence and genetic characterization of Cysticercus tenuicollis derived from Tibetan pigs. The data of present study provides baseline information for controlling cysticerci infections in pigs in Tibetan Plateau, China.
EV-Associated MMP9 in High-Grade Serous Ovarian Cancer Is Preferentially Localized to Annexin V-Binding EVs
Authors: Reiner Agnes T. , Tan Sisareuth , Agreiter Christiane , Auer Katharina , Bachmayr-Heyda Anna , Aust Stefanie , Pecha Nina , Mandorfer Mattias , Pils Dietmar , Brisson Alain R. , Zeillinger Robert , Lim Sai Kiang
Published: May 2017

High-grade serous ovarian cancer (HGSOC) is the most aggressive type of ovarian cancer and is responsible for most deaths caused by gynecological cancers. Numerous candidate biomarkers were identified for this disease in the last decades, but most were not sensitive or specific enough for clinical applications. Hence, new biomarkers for HGSOC are urgently required. This study aimed to identify new markers by isolating different extracellular vesicle (EV) types from the ascites of ovarian cancer patients according to their affinities for lipid-binding proteins and analyzing their protein cargo. This approach circumvents the low signal-to-noise ratio when using biological fluids for biomarker discovery and the issue of contamination by large non-EV complexes. We isolated and analyzed three distinct EV populations from the ascites of patients with ovarian cancer or cirrhosis and observed that Annexin V-binding EVs have higher levels of matrix metalloproteinase 9 in malignant compared to portal-hypertensive ascites. As this protein was not detected in other EV populations, this study validates our approach of using different EV types for optimal biomarker discovery. Furthermore, MMP9 in Annexin V-binding EVs could be a HGSOC biomarker with enhanced specificity, because its identification requires detection of two distinct components, that is, lipid and protein.
All-Trans Retinoic Acid Prevents Osteosarcoma Metastasis by Inhibiting M2 Polarization of Tumor-Associated Macrophages
Authors: Zhou Qian , Xian Miao , Xiang Senfeng , Xiang Danyan , Shao Xuejing , Wang Jincheng , Cao Ji , Yang Xiaochun , Yang Bo , Ying Meidan , He Qiaojun
Published: May 2017

M2-polarized tumor-associated macrophages (TAM) play a critical role in cancer invasion and metastasis. Here, we report that M2 macrophages enhanced metastasis of K7M2 WT osteosarcoma cells to the lungs in mice, thus establishing M2 TAMs as a therapeutic target for blocking osteosarcoma metastasis. We found that all-trans retinoic acid (ATRA) inhibited osteosarcoma metastasis via inhibiting the M2 polarization of TAMs. ATRA suppressed IL13- or IL4-induced M2-type macrophages, and then inhibited migration of osteosarcoma cells as promoted by M2-type macrophages in vitro. ATRA reduced the number of pulmonary metastatic nodes of osteosarcoma and decreased expression of M2-type macrophages in metastatic nodes both in intravenous injection and orthotopic transplantation models. ATRA's effect was independent of conventional STAT3/6 or C/EBPβ signaling, which regulate M2-like polarization of macrophages. Quantitative genomic and functional analyses revealed that MMP12, a macrophage-secreted elastase, was elevated in IL13-skewed TAM polarization, whereas ATRA treatment downregulated IL13-induced secretion of MMP12. This downregulation correlates with the antimetastasis effect of ATRA. Our results show the role of TAM polarization in osteosarcoma metastasis, identify a therapeutic opportunity for antimetastasis treatment, and indicate ATRA treatment as an approach for preventing osteosarcoma metastasis via M2-type polarization intervention. Cancer Immunol Res; 5(7); 547–59. ©2017 AACR.
p16/Ki-67 Immunocytochemistry in Gynecological Cytology: Limitations in Practice
Authors: Ziemke Peter
Published: May 2017

Objective: Immunochemical detection of the protein p16INK4a in cervical cytology is used in combination with Ki-67. Cells positive for both proteins are certain to have been transformed by high-risk HPV. p16/Ki-67 immunocytochemistry provides a significant improvement in specificity over cytology and HPV DNA testing. However, p16/Ki-67 immunocytochemistry also has its limitations. Study Design: The research is based on the follow-up of 1,131 patients for whom p16/Ki-67 immunocytochemistry was performed with cytology. Dependencies on the age of patients with LSIL, number of p16/Ki-67-positive cells, and different results during repeated examinations were analyzed. Results: In LSIL, positive p16/Ki-67 is less specific for ≥CIN2/HSIL for patients younger than 30 years compared to patients aged 30 years or older (61.1 vs. 75.7%, p < 0.013). Using a score of 10 p16/Ki-67-marked cells as a positive result instead of 1 led to significantly higher specificity (89.0 vs. 70.2%, p < 0.001). This modified threshold offers better risk assessment in LSIL. In repeated immunocytochemical investigations, 28.4% of the results deviated from the first examination. Conclusion: The abovementioned discrepancies can be interpreted as hints about the molecular biological causes of suboptimal performance of p16/Ki-67. An efficient and reliable application of p16/Ki-67 immunocytochemistry requires knowledge of its methodological limitations.
Efficacy of an Anatomical Approach in Radiofrequency Catheter Ablation of Idiopathic Ventricular Arrhythmias Originating From the Left Ventricular Outflow Tract
Authors: Yamada Takumi , Yoshida Naoki , Doppalapudi Harish , Litovsky Silvio H. , McElderry H. Thomas , Kay G. Neal
Published: May 2017

Background—

When anatomic obstacles preclude radiofrequency catheter ablation of idiopathic ventricular arrhythmias (VAs) originating from the left ventricular outflow tract (LVOT), an alternative approach from the anatomically opposite side (endocardial versus epicardial or above versus below the aortic valve) may be considered (anatomic ablation). The purpose of this study was to investigate the efficacy of an anatomic ablation in idiopathic LVOT VAs.

Methods and Results—

We studied 229 consecutive patients with idiopathic LVOT VAs. Radiofrequency ablation from the first suitable site was successful in 190 patients, and in the remaining 39 patients, it was unsuccessful or had to be abandoned because of anatomic obstacles. In 22 of these 39 patients, an anatomic ablation was successful, and the VA origins were located in the intramural LVOT in 17 patients, basal left ventricular summit in 4, and LVOT septum near the His bundle in 1. The anatomic ablation was highly successful for idiopathic VAs originating from the intramural LVOT (>75%) and lateral LVOT, whereas it was unlikely to be successful for idiopathic VAs originating from the basal left ventricular summit (25%) and sepal LVOT.

Conclusions—

When a standard catheter ablation targeting the best electrophysiological measure of idiopathic LVOT VAs was unsuccessful or had to be abandoned because of anatomic obstacles, an anatomic ablation was moderately successful. These idiopathic LVOT VAs with a successful anatomic ablation commonly arose from the intramural LVOT among the left coronary cusp, aortomitral continuity, and epicardium, occasionally the basal left ventricular summit, and rarely the LVOT septum near the His bundle.
Soldiers on an Ottoman Island: The Janissaries of Crete, Eighteenth-Early Nineteenth Centuries
Authors: Anastasopoulos Antonis , Spyropoulos Yannis
Published: May 2017

This essay is a contribution to the study of provincial janissaries through the case of Crete. After a brief survey of the history of the janissary corps as the wider framework within which the janissaries of Crete have to be studied, the essay focuses on them, resolving the confusion between janissaries and other military groups, discussing the differences between imperial and local janissaries, and offering an explanation as to why various sources exaggerate the number of janissaries while officially they were relatively few. Finally, it is argued that, from a socio-economic point of view, the janissaries must be seen as inclusive and expansive urban and rural networks that placed their members at an advantageous position over others through legal privilege and access to funds.
Paracrossidius radekcervenkai (Coleoptera: Scarabaeidae: Aphodiinae), a new species from China
Authors: ČERVENKA RADEK , NAKLÁDAL OTO
Published: May 2017

A new species of Paracrossidius Balthasar, 1932 (Coleoptera Scarabaeidae: Aphodiinae) from China is described and compared with similar species. Paracrossidius was originally described as a monotypic subgenus based on the type species Aphodius (Paracrossidius) instigator Balthasar, 1932 from Sichuan Province, China. Paracrossidius is currently considered a genus with 10 previously described species, most of which inhabit various parts of China (Dellacasa et al. 2016).