bluuebunny/crossref_metadata_2025 huggingface dataset:
KLF2 mediates enhanced chemoreflex sensitivity, disordered breathing and autonomic dysregulation in heart failure
Authors: Marcus Noah J. , Del Rio Rodrigo , Ding Yanfeng , Schultz Harold D.
Published: October 2017

Key points

Enhanced carotid body chemoreflex activity contributes to development of disordered breathing patterns, autonomic dysregulation and increases in incidence of arrhythmia in animal models of reduced ejection fraction heart failure.

Chronic reductions in carotid artery blood flow are associated with increased carotid body chemoreceptor activity.

Krüppel‐like Factor 2 (KLF2) is a shear stress‐sensitive transcription factor that regulates the expression of enzymes which have previously been shown to play a role in increased chemoreflex sensitivity.

We investigated the impact of restoring carotid body KLF2 expression on chemoreflex control of ventilation, sympathetic nerve activity, cardiac sympatho‐vagal balance and arrhythmia incidence in an animal model of heart failure.

The results indicate that restoring carotid body KLF2 in chronic heart failure reduces sympathetic nerve activity and arrhythmia incidence, and improves cardiac sympatho‐vagal balance and breathing stability. Therapeutic approaches that increase KLF2 in the carotid bodies may be efficacious in the treatment of respiratory and autonomic dysfunction in heart failure.

Oscillatory breathing and increased sympathetic nerve activity (SNA) are associated with increased arrhythmia incidence and contribute to mortality in chronic heart failure (CHF). Increased carotid body chemoreflex (CBC) sensitivity plays a role in this process and can be precipitated by chronic blood flow reduction. We hypothesized that downregulation of a shear stress‐sensitive transcription factor, Krüppel‐like Factor 2 (KLF2), mediates increased CBC sensitivity in CHF and contributes to associated autonomic, respiratory and cardiac sequelae. Ventilation (Ve), renal SNA (RSNA) and ECG were measured at rest and during CBC activation in sham and CHF rabbits. Oscillatory breathing was quantified as the apnoea–hypopnoea index (AHI) and respiratory rate variability index (RRVI). AHI (control 6 ± 1/h, CHF 25 ± 1/h), RRVI (control 9 ± 3/h, CHF 29 ± 3/h), RSNA (control 22 ± 2% max, CHF 43 ± 5% max) and arrhythmia incidence (control 50 ± 10/h, CHF 300 ± 100/h) were increased in CHF at rest ( 21%), as were CBC responses (Ve, RSNA) to 10% (all P < 0.05 vs. control). In vivo adenoviral transfection of KLF2 to the carotid bodies in CHF rabbits restored KLF2 expression, and reduced AHI (7 ± 2/h), RSNA (18 ± 2% max) and arrhythmia incidence (46 ± 13/h) as well as CBC responses to hypoxia (all P < 0.05 vs. CHF empty virus). Conversely, lentiviral KLF2 siRNA in the carotid body decreased KLF2 expression, increased chemoreflex sensitivity, and increased AHI (6 ± 2/h vs. 14 ± 3/h), RRVI (5 ± 3/h vs. 20 ± 3/h) and RSNA (24 ± 4% max vs. 34 ± 5% max) relative to scrambled‐siRNA rabbits. In conclusion, down‐regulation of KLF2 in the carotid body increases CBC sensitivity, oscillatory breathing, RSNA and arrhythmia incidence during CHF.
Oxidative phosphorylation: regulation and role in cellular and tissue metabolism
Authors: Wilson David F.
Published: October 2017

Oxidative phosphorylation provides most of the ATP that higher animals and plants use to support life and is responsible for setting and maintaining metabolic homeostasis. The pathway incorporates three consecutive near equilibrium steps for moving reducing equivalents between the intramitochondrial [NAD+]/[NADH] pool to molecular oxygen, with irreversible reduction of oxygen to bound peroxide at cytochrome c oxidase determining the net flux. Net flux (oxygen consumption rate) is determined by demand for ATP, with feedback by the energy state ([ATP]/[ADP][Pi]) regulating the pathway. This feedback affects the reversible steps equally and independently, resulting in the rate being coupled to ([ATP]/[ADP][Pi])3. With increasing energy state, oxygen consumption decreases rapidly until a threshold is reached, above which there is little further decrease. In most cells, [ATP] and [Pi] are much higher than [ADP] and change in [ADP] is primarily responsible for the change in energy state. As a result, the rate of ATP synthesis, plotted against [ADP], remains low until [ADP] reaches about 30 μm and then increases rapidly with further increase in [ADP]. The dependencies on energy state and [ADP] near the threshold can be fitted by the Hill equation with a Hill coefficients of about −2.6 and 4.2, respectively. The homeostatic set point for metabolism is determined by the threshold, which can be modulated by the and intramitochondrial [NAD+]/[NADH]. The ability of oxidative phosphorylation to precisely set and maintain metabolic homeostasis is consistent with it being permissive of, and essential to, development of higher plants and animals.

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Structural and compositional characterization of RF magnetron cosputtered lithium silicate films: From Li2Si2O5 to lithium-rich Li8SiO6
Authors: Coyle Jaclyn , Apblett Christopher , Brumbach Michael , Ohlhausen James , Stoldt Conrad
Published: October 2017

In this study, the structure and composition of lithium silicate thin films deposited by radio-frequency magnetron cosputtering are investigated. Five compositions ranging from Li2Si2O5 to Li8SiO6 were confirmed by inductively coupled plasma-optical emission spectroscopy, and structural analysis on the evolution of nonbridging oxygens in the thin films was conducted using Fourier transform infrared spectroscopy. It was found that nonbridging oxygens increased as the silicate network breaks apart with the increasing lithium content, which agrees with previous studies on lithium silicates. Thin film impurities were examined using x-ray photoelectron spectroscopy and time of flight secondary ion mass spectroscopy and traced back to target synthesis. This study utilizes a unique synthesis technique for lithium silicate thin films that can be used to model the lithium silicates formed on the surface of silicon anodes in lithium ion batteries and can bridge the understanding between this layer and the influence of silicates on ionic conductivity of the silicon interphase layer.
Individual variability as a window on production-perception interactions in speech motor control
Authors: Franken Matthias K. , Acheson Daniel J. , McQueen James M. , Eisner Frank , Hagoort Peter
Published: October 2017

An important part of understanding speech motor control consists of capturing the interaction between speech production and speech perception. This study tests a prediction of theoretical frameworks that have tried to account for these interactions: If speech production targets are specified in auditory terms, individuals with better auditory acuity should have more precise speech targets, evidenced by decreased within-phoneme variability and increased between-phoneme distance. A study was carried out consisting of perception and production tasks in counterbalanced order. Auditory acuity was assessed using an adaptive speech discrimination task, while production variability was determined using a pseudo-word reading task. Analyses of the production data were carried out to quantify average within-phoneme variability, as well as average between-phoneme contrasts. Results show that individuals not only vary in their production and perceptual abilities, but that better discriminators have more distinctive vowel production targets—that is, targets with less within-phoneme variability and greater between-phoneme distances—confirming the initial hypothesis. This association between speech production and perception did not depend on local phoneme density in vowel space. This study suggests that better auditory acuity leads to more precise speech production targets, which may be a consequence of auditory feedback affecting speech production over time.
High-density lipoprotein delivered after myocardial infarction increases cardiac glucose uptake and function in mice
Authors: Heywood Sarah E. , Richart Adele L. , Henstridge Darren C. , Alt Karen , Kiriazis Helen , Zammit Claire , Carey Andrew L. , Kammoun Helene L. , Delbridge Lea M. , Reddy Medini , Chen Yi-Ching , Du Xiao-Jun , Hagemeyer Christoph E. , Febbraio Mark A. , Siebel Andrew L. , Kingwell Bronwyn A.
Published: October 2017

One dose of rHDL after myocardial ischemia increases both cardiac glucose uptake and heart function in healthy and insulin-resistant mice.
The science of love in ASD and ADHD
Authors: Novarino Gaia
Published: October 2017

Genetic variations in the oxytocin receptor gene affect patients with ASD and ADHD differently.
Transgenerational Diapause as an Avoidance Strategy against Bacterial Pathogens in
Caenorhabditis elegans
Authors: Palominos M. Fernanda , Verdugo Lidia , Gabaldon Carolaing , Pollak Bernardo , Ortíz-Severín Javiera , Varas Macarena A. , Chávez Francisco P. , Calixto Andrea
Published: October 2017

The dynamic response of organisms exposed to environmental pathogens determines their survival or demise, and the outcome of this interaction depends on the host’s susceptibility and pathogen-dependent virulence factors. The transmission of acquired information about the nature of a pathogen to progeny may ensure effective defensive strategies for the progeny’s survival in adverse environments. Environmental RNA interference (RNAi) is a systemic and heritable mechanism and has recently been linked to antibacterial and antifungal defenses in both plants and animals. Here, we report that the second generation of
Caenorhabditis elegans
living on pathogenic bacteria can avoid bacterial infection by entering diapause in an RNAi pathway-dependent mechanism. Furthermore, we demonstrate that the information encoding this survival strategy is transgenerationally transmitted to the progeny via the maternal germ line.

IMPORTANCE
Bacteria vastly influence physiology and behavior, and yet, the specific mechanisms by which they cause behavioral changes in hosts are not known. We use
C. elegans
as a host and the bacteria they eat to understand how microbes trigger a behavioral change that helps animals to survive. We found that animals faced with an infection for two generations could enter a hibernationlike state, arresting development by forming dauer larvae. Dauers have closed mouths and effectively avoid infection. Animals accumulate information that is transgenerationally transmitted to the next generations to form dauers. This work gives insight on how bacteria communicate in noncanonical ways with their hosts, resulting in long-lasting effects providing survival strategies to the community.
Comparative Metabolomics of Mycoplasma bovis and Mycoplasma gallisepticum Reveals Fundamental Differences in Active Metabolic Pathways and Suggests Novel Gene Annotations
Authors: Masukagami Y. , De Souza D. P. , Dayalan S. , Bowen C. , O’Callaghan S. , Kouremenos K. , Nijagal B. , Tull D. , Tivendale K. A. , Markham P. F. , McConville M. J. , Browning G. F. , Sansom F. M.
Published: October 2017

Mycoplasmas are pathogenic bacteria that cause serious chronic infections in production animals, resulting in considerable losses worldwide, as well as causing disease in humans. These bacteria have extremely reduced genomes and are thought to have limited metabolic flexibility, even though they are highly successful persistent parasites in a diverse number of species. The extent to which different
Mycoplasma
species are capable of catabolizing host carbon sources and nutrients, or synthesizing essential metabolites, remains poorly defined. We have used advanced metabolomic techniques to identify metabolic pathways that are active in two species of
Mycoplasma
that infect distinct hosts (poultry and cattle). We show that these species exhibit marked differences in metabolite steady-state levels and carbon source utilization. This information has been used to functionally characterize previously unknown genes in the genomes of these pathogens. These species-specific differences are likely to reflect important differences in host nutrient levels and pathogenic mechanisms.
Use of a dynamic gait trainer for a child with thoracic level spinal cord injury
Authors: Altizer Wendy , Noritz Garey , Paleg Ginny
Published: October 2017

Paediatric spinal cord injury (SCI) can result in permanent mobility impairment with consequences for activity, participation and quality of life. This case documents the effect of an overground supported stepping intervention using a dynamic gait trainer. To our knowledge, there are no published studies on this intervention for children with SCI and similar interventions have only been reported in children at American Spinal Injury Association Impairment Scale (AIS) levels B and C.

A child with a T10 (thoracic level, vertebra 10), AIS level A injury, sustained at 2 years of age, continued to make gains in all areas including participation, activity, body structure and function over the following 4 years. Use of a dynamic gait trainer improved the participant’s ability to be active and participate despite lack of further neuromuscular recovery. This novel approach with a commonly available device allowed the child to be active and participate in the absence of neural recovery.
Prevalence and associated factors of active smoking among individuals living with hypertension and/or diabetes in Africa: a systematic review and meta-analysis protocol
Authors: Wafeu Guy S , Tankeu Aurel T , Endomba Francky Teddy A , Nansseu Jobert Richie , Kaze Arnaud D , Bigna Jean Joel , Noubiap Jean Jacques
Published: October 2017

Introduction

Tobacco use significantly increases cardiovascular complications in people living with hypertension and/or diabetes. We aim to summarise data on the prevalence and factors associated with active smoking in these conditions in Africa.

Method and analysis

We will search PubMed, Embase, Google Scholar and African Journals Online for relevant abstracts of studies on active smoking in individuals living with diabetes and/or hypertension published from 1 January 2000 to 31 December 2016, with no language restriction. Additionally, relevant unpublished papers and conference proceedings will be checked, as well as references of included articles. Two investigators will independently screen, select studies, extract data and assess the risk of bias in each study. Data will be analysed using Stata software (Stata V.14, Texas, USA). The study-specific estimates will be pooled through a random-effects meta-analysis model to obtain an overall summary estimate of the prevalence of smoking across studies. Also, we will assess factors associated to smoking. Heterogeneity of studies will be evaluated by the χ2 test on Cochrane’s Q statistic. Funnel plots analysis and Egger’s test will be done to detect publication bias. Results will be presented by geographic region (central, eastern, northern, southern and western Africa). A p value less than 0.05 will be considered significant for factors associated to smoking.

Ethics and dissemination

This study is based on published data, and therefore ethical approval is not a requirement. This systematic review and meta-analysis is expected to serve as a basis for designing cost-effective interventions to reduce and prevent smoking in patients with diabetes and/or hypertension, and as a guide for future research based on the remaining gaps. The final report of this study in the form of a scientific paper will be published in peer-reviewed journals. Findings will further be presented at conferences and submitted to relevant health authorities.
Improving the completeness of acute kidney injury follow-up information in hospital electronic discharge letters
Authors: Reschen Michael Edward , Vaux Emma
Published: October 2017

Objectives

Acute kidney injury (AKI) is common in hospitalised patients, often mandates changes to regular medications and can be unresolved at hospital discharge. General practitioners (GPs) require apposite AKI-related information in electronic discharge letters (EDLs). In 2015 NHS England introduced a care quality standard that all EDLs should include four items of information for patients with AKI. We performed a 12-month quality improvement project (QIP) aimed at achieving above 90% compliance with the quality standard.

Methods

Hospital-wide episodes of AKI were detected using the nationally approved electronic AKI alerts system. 25 patient AKI episodes were audited per month for 12 months using the electronic patient record. The target compliance rate was staggered at 35%, 65% and 90% for each subsequent 3-month block. Baseline compliance was 22%. Measures taken to improve compliance included email information, grand rounds, ward-level meetings, computer screensavers, nurse support, clinical governance meetings, and face-to-face rapid education. Annotation of AKI within the computer EDL system was progressively enhanced such that in the final quarter the presence of an AKI-alert mandated the user to complete the AKI annotation before the EDL could be signed off.

Results

The completion rate improved to 37% in the second quarter, 51% in the third quarter and 92% in the fourth quarter. This change has been sustained in the 14 months since.

Conclusions

By the end of the study, omissions relating to AKI information were reduced from 78% to less than 10%, indicating our QIP was highly effective—meeting the quality standard. The single most important factor in improving documentation was to mandate user review of AKI aftercare in patients with electronic AKI alerts. Our study encompassed hospital-wide inpatients, and our results could be replicated at other acute hospitals that have implemented an EDL system connected to an AKI alert system.
Improving combined contraceptive pill/oral contraceptives prescribing in general practice
Authors: Russell Sophie , Wiles Helen
Published: October 2017

Introduction

Eighty per cent of contraceptive care occurs in the general practice setting. UK Medical Eligibility Criteria provides clear guidelines for the safe provision of appropriate contraception. The Faculty of Sexual and Reproductive Health and the National Institute for Health and Care Excellence offer further recommendations for initiation and continuation of the combined contraceptive pill/oral contraceptives.

Method and analysis

Using the Egton Medical Information Systems database of an inner city, average size general practice we performed a retrospective analysis of combined contraceptive pill/oral contraceptives consultations to identify areas of substandard prescribing. Through three subsequent improvement cycles we demonstrated that the safety of combined contraceptive pill/oral contraceptives prescribing could be enhanced by consistent application of UK Medical Eligibility Criteria. By encouraging general practitioners to promote safe sex and use local long-acting reversible contraception options we were able to enhance the quality of consultations as dictated by national guidelines. Regular education and use of an amended EMIS template (to include UK Medical Eligibility Criteria) enabled us to improve both the safety and quality of community-combined contraceptive pill/oral contraceptives prescribing in a sustainable fashion.
Improvement in patient and physician notification of cardiac rhythm device report transmissions
Authors: Czosek Richard J , Brown James , Proctor Diane , Koch Paula , Martin Michelle , Rust Mary , Anderson Jeffrey B
Published: October 2017

BackgroundCardiac rhythm devices (CRD) require complex management to identify potential device or patient issues. While easy to obtain, report processing is complex and time consuming. In our population, a majority of reports were performed outside of institutional protocols and no method for electrophysiology (EP) notification for unscheduled reports existed. These process breakdowns led to potential issues with safety and associated loss of work efficiency.

ObjectiveOur aim was to decrease the percentage of reports without EP notification from 30% to 10% over a 9-month time period.

MethodsWe created a detailed process map of in-office and home device reporting. Failure mode and effects analysis (FMEA)/Pareto charts were used to determine the mechanistic underpinnings of notification failures and identify areas for process improvement. Multiple interventions were implemented using the Plan-Do-Study-Act (PDSA) technique. Process run charts and control charts were used to evaluate ongoing changes.

ResultsOur FMEA identified failures related to (1) lack of physician understanding of the device reporting system, (2) lack of an easy to use method of EP notification and (3) lack of patient understanding of report notification. Pareto charts identified the most frequent failures to be associated with specific cardiology subspecialties as well as reports sent from home. We performed multiple interventions including(1) creation of an easy to use method of EP notification used by patients and medical staff, (2) physician education and (3) patient education. Compared with baseline reporting, there was a decrease from 30% to <10% of device reports obtained without EP notification. This process improvement additionally resulted in a 34% reduction in time required for device processing.

ConclusionsDevelopment of a unified EP reporting system and quality improvement methodology resulted in improved CRD report notification and improved efficiency for staff. These process changes resulted in improvement across differing cardiac subspecialty providers and patients.
The ocean lifeguard drowning prevention paradigm: how and where do lifeguards intervene in the drowning process?
Authors: Koon William , Rowhani-Rahbar Ali , Quan Linda
Published: October 2017

Drowning is a global health problem that can be addressed with multiple strategies including utilisation of lifeguards in recreational swim areas. However, few studies have described lifeguard prevention activities. We conducted a retrospective analysis using lifeguard activity data collected in real time with a Computer-Aided-Dispatch (CAD) system to characterise the nature of lifeguard primary and secondary drowning prevention at a popular ocean beach in California. Preventative actions constituted the majority (232 065/423 071; 54.8%) of lifeguard activities, while rescues represented 1.9%. Most preventative actions and rescues occurred during summer months, weekends and afternoons. Statistically significant geographical clusters of preventative actions were identified all over the beach, while rescue clusters were primarily restricted to two sites. Using the most reliable and valid collection system to date, these data show spatial and temporal patterns for ocean lifeguard provision of primary prevention as well as secondary drowning prevention (rescue).
Rnf43
Authors: Serra Stefano , Chetty Runjan
Published: October 2017

RNF43 (E3 ubiquitin-protein ligase RNF43 or RING-type E3 ubiquitin transferase RNF43) functions as a tumor suppressor, by exerting a predominant negative feedback mechanism in the Wnt/β-catenin signaling pathway. RNF43 inhibits Wnt/beta-catenin signaling by ubiquitinating Frizzled receptor and targeting it to the lysosomal pathway for degradation. Loss of function of RNF43 results in decrease/lack of degradation of Frizzled with enhancement of Wnt/β-catenin signaling pathway. Mutations of RNF43 have been reported in different cancers. We describe the structure of RNF43, its function and most frequent mutations in different cancers.
Clinical utility of amyloid PET imaging with (18)F-florbetapir: a retrospective study of 100 patients
Authors: Carswell Christopher James , Win Zarni , Muckle Kirsty , Kennedy Angus , Waldman Adam , Dawe Gemma , Barwick Tara D , Khan Sameer , Malhotra Paresh A , Perry Richard J
Published: October 2017

Background and objective

Amyloid-positron emission tomography (PET) imaging (API) detects amyloid-beta pathology early in the course of Alzheimer’s disease (AD) with high sensitivity and specificity. (18)F-florbetapir (Amyvid) is an amyloid-binding PET ligand with a half-life suitable for clinical use outside of the research setting. How API affects patient investigation and management in the ‘real-world’ arena is unknown. To address this, we retrospectively documented the effect of API in patients in the memory clinic.

Methods

We reviewed the presenting clinical features, the pre-API and post-API investigations, diagnosis and outcomes for the first 100 patients who had API as part of their routine work-up at the Imperial Memory Centre, a tertiary referral clinic in the UK National Health Service.

Results

API was primarily used to investigate patients with atypical clinical features (56 cases) or those that were young at onset (42 cases). MRI features of AD did not always predict positive API (67%), and 6 of 23 patients with MRIs reported as normal were amyloid-PET positive. There were significantly more cases categorised as non-AD dementia post-API (from 11 to 23). Patients investigated when API was initially available had fewer overall investigations and all patients had significantly fewer investigations in total post-API.

Conclusions

API has a clear impact on the investigation of young-onset or complex dementia while reducing the overall burden of investigations. It was most useful in younger patients, atypical presentations or individuals with multiple possible causes of cognitive impairment.
A pilot study of surgical telementoring for leg fasciotomy
Authors: Talbot Max , Harvey E J , Berry G K , Reindl R , Tien H , Stinner D J , Slobogean G
Published: October 2017

Introduction

Acute extremity compartment syndrome requires rapid decompression. In remote locations, distance, weather and logistics may delay the evacuation of patients with extremity trauma beyond the desired timeline for compartment release. The aim of this study was to establish the feasibility of performing telementored surgery for leg compartment release and to identify methodological issues relevant for future research.

Methods

Three anaethetists and one critical care physician were recruited as operators. They were directed to perform a two-incision leg fasciotomy on a Thiel-embalmed cadaver under the guidance of a remotely located orthopaedic surgeon. The operating physician and the surgeon (mentor) were connected through software that allows for real-time supervision and the use of a virtual pointer overlaid onto the surgical field. Two experienced orthopaedic traumatologists independently assessed the adequacy of compartment decompression and the presence of iatrogenic complications.

Results

14 of 16 compartments (in four leg specimens) were felt to have been completely released. The first evaluator considered that the deep posterior compartment was incompletely released in two specimens. The second evaluator considered that the superficial posterior compartment was incompletely released in two specimens. The only complication was a large laceration of the soleus muscle that occurred during a period of blurred video signal attributed to a drop in bandwidth.

Conclusions

This study suggests that surgical telementoring may enable physicians to safely perform two-incision leg fasciotomy in remote environments. This could improve the chances of limb salvage when compartment syndrome occurs far from surgical care. We found interobserver variation in the assessment of compartment release, which should be considered in the design of future research protocols.
COMPARATIVE ANALYSIS ON NONLINEAR MODELS FOR RON GASOLINE BLENDING USING NEURAL NETWORKS
Authors: AGUILERA R. CARREÑO , YU WEN , RODRÍGUEZ J. C. TOVAR , MOSQUEDA M. ELENA ACEVEDO , ORTIZ M. PATIÑO , JUAREZ J. J. MEDEL , BAUTISTA D. PACHECO
Published: October 2017

The blending process always being a nonlinear process is difficult to modeling, since it may change significantly depending on the components and the process variables of each refinery. Different components can be blended depending on the existing stock, and the chemical characteristics of each component are changing dynamically, they all are blended until getting the expected specification in different properties required by the customer. One of the most relevant properties is the Octane, which is difficult to control in line (without the component storage). Since each refinery process is quite different, a generic gasoline blending model is not useful when a blending in line wants to be done in a specific process. A mathematical gasoline blending model is presented in this paper for a given process described in state space as a basic gasoline blending process description. The objective is to adjust the parameters allowing the blending gasoline model to describe a signal in its trajectory, representing in neural networks extreme learning machine method and also for nonlinear autoregressive-moving average (NARMA) in neural networks method, such that a comparative work be developed.
Unmasking the Relationships Between Exchange Rate Exposure and Its Determinants: A More Complete Picture from Quantile Regressions
Authors: Lin Luke , Lee Chun I
Published: October 2017

Largely ignored, empirical evidence is mixed regarding the sign of the relationships between exchange rate exposure and its determinants. Employing quantile regressions, we resolve the conflicting findings for S&P 500 firms by demonstrating that the culprit is the inherent limitations of the ordinary least squares (OLS) approach used in previous studies. Instead of the conflicting partial views of the picture of the mean depicted in previous OLS results, we present a clearer fuller picture of the spectrum of the relationships. Specifically, across the range of exchange rate exposure — extremely negative to extremely positive — the sign of the relationships change systematically for foreign sales, size, and debt ratio, while it remains consistently negative for quick ratio and positive for book-to-market. Test results further show significant differences in the coefficient estimates between high and low quantiles, indicating an asymmetric effect of the determinants on the exposure.
EFFECTS OF POROSITY IN A SEEPAGE MODEL ON HEMODYNAMICS
Authors: HE FAN , HUA LU , GAO LIJIAN
Published: October 2017

In this paper, we numerically investigate the effects of porosity on hemodynamics using a seepage outlet boundary condition. The results with the porosities [Formula: see text] and [Formula: see text] are compared. The comparison of the results shows that there are identical pressure, velocity and wall shear stress distributions in the artery zone; however, the velocities and wall shear stresses in the microcirculation zone with [Formula: see text] are almost as twice as those with [Formula: see text]. This work suggests that the porosity changes do not provoke variations in the artery zone, but they lead to the differences of the velocities and wall shear stresses in the microcirculation zone. The results may be the explanation of syndrome X.
Physiological regulation of the epithelial Na+ channel by casein kinase II
Authors: Berman Jonathan M. , Mironova Elena , Stockand James D.
Published: October 2017

epithelial Na+ channel, ENaC, is the final arbiter of sodium excretion in the kidneys. As such, discretionary control of ENaC by hormones is critical to the fine-tuning of electrolyte and water excretion and, consequently, blood pressure. Casein kinase 2 (CK2) phosphorylates ENaC. Phosphorylation by CK2 is necessary for normal ENaC activity. We tested the physiological importance of CK2 regulation of ENaC as the degree to which ENaC activity is dependent on CK2 phosphorylation in the living organism is unknown. This was addressed using patch-clamp analysis of ENaC in completely split-open collecting ducts and whole animal physiological studies of sodium excretion in mice. We also used ENaC-harboring CK2 phosphorylation site mutations to elaborate the mechanism. We found that ENaC activity in ex vivo preparations of murine collecting duct had a significant decrease in activity in response to selective antagonism of CK2. In whole animal experiments selective antagonism of CK2 caused a natriuresis similar to benzamil, but not additive to benzamil, suggesting an ENaC-dependent mechanism. Regulation of ENaC by CK2 was abolished by mutation of the canonical CK2 phosphorylation sites in beta and gamma ENaC. Together, these results demonstrate that the appropriate regulation of ENaC by CK2 is necessary for the normal physiological role played by this key renal ion channel in the fine-tuning of sodium excretion.
Abdominal Wall Reconstruction after Flap Surgery and the Effect on the Immune System
Authors: Popa F. , Georgescu A. V.
Published: October 2017

Background. The aim of our study was to investigate the impact of abdominal wall reconstruction surgery on tissue anatomy and to explore how flap surgery influences the patient’s immune status. Methods. Experimental abdominal wall defects were created in 8 Sus scrofa (swine) animal models. The animals were divided into two groups: 4 swine were euthanized one month after surgery for the biopsies retrieval purpose and the other 4 swine were kept alive and the collection of blood samples has been done 6 months after surgery. In order to evaluate the relative gene expression in operated-on animal cohorts we compared them with samples from 4 healthy swine used as controls. Results. The inflammatory process was present in all types of repairs. Collagen I deposition was higher in the flap repairs. The expression level for the genes related to immune response after 6 months from surgery was relatively similar to the control group except minor alteration registered in the case of two swine models. Conclusion. Our findings indicate a less pronounced proinflammatory response to surgical trauma in animal models after flap surgery. The postoperative levels of the inflammatory cytokines did not show significant differences after abdominal wall reconstruction using flap surgery.
Stair Climbing Control for 4-DOF Tracked Vehicle Based on Internal Sensors
Authors: Endo Daisuke , Watanabe Atsushi , Nagatani Keiji
Published: October 2017

In search-and-rescue missions, multi-degrees-of-freedom (DOF) tracked robots that are equipped with subtracks are commonly used. These types of robots have superior locomotion performance on rough terrain. However, in teleoperated missions, the performance of tracked robots depends largely on the operators’ ability to control every subtrack appropriately. Therefore, an autonomous traversal function can significantly help in the teleoperation of such robots. In this paper, we propose a planning and control method for 4-DOF tracked robots climbing up/down known stairs automatically based on internal sensors. Experimental results obtained using mockup stairs verify the effectiveness of the proposed method.
The Effects of Aqueous Extract from Nardostachys chinensis Batalin on Blood Pressure and Cardiac Hypertrophy in Two‐Kidney One‐Clip Hypertensive Rats
Authors: Aisa Rayile , Yu Zhaoxia , Zhang Xiangyang , Maimaitiyiming Dilinuer , Huang Lipeng , Hasim Ayshamgul , Jiang Tao , Duan Mingjun
Published: October 2017

Aims. The aim of this study was to investigate the effects of the aqueous extract of Nardostachys chinensis Batalin (NCBAE) on blood pressure and cardiac hypertrophy using two‐kidney one‐clip (2K1C) hypertensive rats. Methods. 2K1C rat models were set up by clipping the left renal artery. Sham‐operated rats underwent the same surgical procedure except for renal arterial clipping. 2K1C hypertensive rats were orally given NCBAE at doses of 210, 420, and 630 mg·kg−1·d−1 for 6 weeks. Twelve weeks after surgery, rat SBP and echocardiographic parameters were measured, cardiac histopathology was assessed, serum NO and LDH were detected, and the expression of Bcl‐2 and caspase‐3 of left ventricular tissue was assessed by western blot. Results. Treatment with NCBAE resulted in a decrease of SBP, LVPWd, LVPWs, IVSd, IVSs, LVW/BW ratio, and cardiomyocyte CSA, an increase of LVEF, and inhibition of 2K1C‐induced reduction in serum NO and elevation of LDH compared with 2K1C group. NCBAE intervention also showed a significant increase of Bcl‐2 expression and reduction of cleaved caspase‐3 level dose‐dependently in left ventricular tissue. Conclusion. Our data demonstrate that NCBAE has an antihypertensive property and protective effect on 2K1C‐induced cardiac hypertrophy especially at the dose of 630 mg·kg−1·d−1.
δ-Primary Hyperideals on Commutative Hyperrings
Authors: Ozel Ay Elif , Yesilot Gürsel , Sonmez Deniz
Published: October 2017

The purpose of this paper is to define the hyperideal expansion. Hyperideal expansion is associated with prime hyperideals and primary hyperideals. Then, we define some of their properties. Prime and primary hyperideals’ numerous results can be extended into expansions.
Adaptive Neural Network Sliding Mode Control for Quad Tilt Rotor Aircraft
Authors: Yin Yanchao , Niu Hongwei , Liu Xiaobao
Published: October 2017

A novel neural network sliding mode control based on multicommunity bidirectional drive collaborative search algorithm (M-CBDCS) is proposed to design a flight controller for performing the attitude tracking control of a quad tilt rotors aircraft (QTRA). Firstly, the attitude dynamic model of the QTRA concerning propeller tension, channel arm, and moment of inertia is formulated, and the equivalent sliding mode control law is stated. Secondly, an adaptive control algorithm is presented to eliminate the approximation error, where a radial basis function (RBF) neural network is used to online regulate the equivalent sliding mode control law, and the novel M-CBDCS algorithm is developed to uniformly update the unknown neural network weights and essential model parameters adaptively. The nonlinear approximation error is obtained and serves as a novel leakage term in the adaptations to guarantee the sliding surface convergence and eliminate the chattering phenomenon, which benefit the overall attitude control performance for QTRA. Finally, the appropriate comparisons among the novel adaptive neural network sliding mode control, the classical neural network sliding mode control, and the dynamic inverse PID control are examined, and comparative simulations are included to verify the efficacy of the proposed control method.
Impact on CO2 Uptake of MWCNT after Acid Treatment Study
Authors: Zgrzebnicki Michal , Krauze Nikola , Gęsikiewicz-Puchalska Andżelika , Kapica-Kozar Joanna , Piróg Ewa , Jędrzejewska Anna , Michalkiewicz Beata , Narkiewicz Urszula , Morawski Antoni W. , Wrobel Rafal J.
Published: October 2017

Greenhouse effect is responsible for keeping average temperature of Earth’s atmosphere at level of about 288 K. Its intensification leads to warming of our planet and may contribute to adverse changes in the environment. The most important pollution intensifying greenhouse effect is anthropogenic carbon dioxide. This particular gas absorbs secondary infrared radiation, which in the end leads to an increase of average temperature of Earth’s atmosphere. Main source of CO2 is burning of fossil fuels, like oil, natural gas, and coal. Therefore, to reduce its emission, a special CO2 capture and storage technology is required. Carbonaceous materials are promising materials for CO2 sorbents. Thus multiwalled carbon nanotubes, due to the lack of impurities like ash in activated carbons, were chosen as a model material for investigation of acid treatment impact on CO2 uptake. Remarkable 43% enhancement of CO2 sorption capacity was achieved at 273 K and relative pressure of 0.95. Samples were also thoroughly characterized in terms of texture (specific surface area measurement, transmission electron microscope) and chemical composition (X-ray photoelectron spectroscopy).
A Chinese Herbal Formula, Gengnianchun, Ameliorates β‐Amyloid Peptide Toxicity in a Caenorhabditis elegans Model of Alzheimer’s Disease
Authors: Meng Fanhui , Li Jun , Rao Yanqiu , Wang Wenjun , Fu Yan
Published: October 2017

Alzheimer’s disease (AD) is an age‐related neurodegenerative disorder, and the few drugs that are currently available only treat the symptoms. Traditional medicine or phytotherapy has been shown to protect against AD. In our previous studies, Gengnianchun (GNC), a traditional Chinese medicine formula with a prolongevity effect, protected against Aβ‐induced cytotoxicity in pheochromocytoma cells (PC‐12 cells) and hippocampal cells. Here, we investigated the effects and possible mechanisms by which GNC protected against Aβ toxicity using transgenic Caenorhabditis elegans CL4176. Our results showed that GNC effectively delayed the Aβ toxicity‐triggered body paralysis of CL4176 worms. GNC decreased Aβ by reducing Aβ mRNA levels. Moreover, GNC significantly reduced reactive oxygen species in the AD model worms compared with the controls. In addition, GNC upregulated the daf‐16, sod‐3, hsp‐16.2 genes, and enhanced DAF‐16 translocation from the cytoplasm to the nuclei under oxidative stress conditions. GNC treatment of C. elegans strains lacking DAF‐16 did not affect the paralysis phenotype. Taken together, these findings suggest that GNC could protect against Aβ‐induced toxicity via the DAF‐16 pathway in C. elegans. Further studies are required to analyze its effectiveness in more complex animals.
A Sensor-Based Visual Effect Evaluation of Chevron Alignment Signs’ Colors on Drivers through the Curves in Snow and Ice Environment
Authors: Zhao Wei , Xu Liangjie , Xi Shaoxin , Wang Jizhou , Runge Troy
Published: October 2017

The ability to quantitatively evaluate the visual feedback of drivers has been considered as the primary research for reducing crashes in snow and ice environments. Different colored Chevron alignment signs cause diverse visual effect. However, the effect of Chevrons on visual feedback and on the driving reaction while navigating curves in SI environments has not been adequately evaluated. The objective of this study is twofold: (1) an effective and long-term experiment was designed and developed to test the effect of colored Chevrons on drivers’ vision and vehicle speed; (2) a new quantitative effect evaluation model is employed to measure the effect of different colors of the Chevrons. Fixation duration and pupil size were used to describe the driver’s visual response, and Cohen’s d was used to evaluate the colors’ psychological effect on drivers. The results showed the following: (1) after choosing the proper color for Chevrons, drivers reduced the speed of the vehicle while approaching the curves. (2) It was easier for drivers to identify the road alignment after setting the Chevrons. (3) Cohen’s d related to different colors of Chevrons have different effect sizes. The conclusions provide evident references for freeway warning products and the design of intelligent vehicles.
Polysaccharide Hydrogels Support the Long-Term Viability of Encapsulated Human Mesenchymal Stem Cells and Their Ability to Secrete Immunomodulatory Factors
Authors: Hached Fahd , Vinatier Claire , Pinta Pierre-Gabriel , Hulin Philippe , Le Visage Catherine , Weiss Pierre , Guicheux Jérôme , Billon-Chabaud Aurélie , Grimandi Gaël
Published: October 2017

While therapeutically interesting, the injection of MSCs suffers major limitations including cell death upon injection and a massive leakage outside the injection site. We proposed to entrap MSCs within spherical particles derived from alginate, as a control, or from silanized hydroxypropyl methylcellulose (Si-HPMC). We developed water in an oil dispersion method to produce small Si-HPMC particles with an average size of about 68 μm. We evidenced a faster diffusion of fluorescein isothiocyanate-dextran in Si-HPMC particles than in alginate ones. Human adipose-derived MSCs (hASC) were encapsulated either in alginate or in Si-HPMC, and the cellularized particles were cultured for up to 1 month. Both alginate and Si-HPMC particles supported cell survival, and the average number of encapsulated hASC per alginate and Si-HPMC particle (7102 and 5100, resp.) did not significantly change. The stimulation of encapsulated hASC with proinflammatory cytokines resulted in the production of IDO, PGE2, and HGF whose concentration was always higher when cells were encapsulated in Si-HPMC particles than in alginate ones. We have demonstrated that Si-HPMC and alginate particles support hASC viability and the maintenance of their ability to secrete therapeutic factors.
Construction of an miRNA-Regulated Pathway Network Reveals Candidate Biomarkers for Postmenopausal Osteoporosis
Authors: Shao Min
Published: October 2017

We aimed to identify risk pathways for postmenopausal osteoporosis (PMOP) via establishing an microRNAs- (miRNA-) regulated pathway network (MRPN). Firstly, we identified differential pathways through calculating gene- and pathway-level statistics based on the accumulated normal samples using the individual pathway aberrance score (iPAS). Significant pathways based on differentially expressed genes (DEGs) using DAVID were extracted, followed by identifying the common pathways between iPAS and DAVID methods. Next, miRNAs prediction was implemented via calculating TargetScore values with precomputed input (log fold change (FC), TargetScan context score (TSCS), and probabilities of conserved targeting (PCT)). An MRPN construction was constructed using the common genes in the common pathways and the predicted miRNAs. Using false discovery rate (FDR) < 0.05, 279 differential pathways were identified. Using the criteria of FDR < 0.05 and log⁡FC≥2, 39 DEGs were retrieved, and these DEGs were enriched in 64 significant pathways identified by DAVID. Overall, 27 pathways were the common ones between two methods. Importantly, MAPK signaling pathway and PI3K-Akt signaling pathway were the first and second significantly enriched ones, respectively. These 27 common pathways separated PMOP from controls with the accuracy of 0.912. MAPK signaling pathway and PI3K/Akt signaling pathway might play crucial roles in PMOP.
Intratumoral HPV16-Specific T Cells Constitute a Type I–Oriented Tumor Microenvironment to Improve Survival in HPV16-Driven Oropharyngeal Cancer
Authors: Welters Marij J.P. , Ma Wenbo , Santegoets Saskia J.A.M. , Goedemans Renske , Ehsan Ilina , Jordanova Ekaterina S. , van Ham Vanessa J. , van Unen Vincent , Koning Frits , van Egmond Sylvia I. , Charoentong Pornpimol , Trajanoski Zlatko , van der Velden Lilly-Ann , van der Burg Sjoerd H.
Published: October 2017

Purpose: Human papillomavirus (HPV)–associated oropharyngeal squamous cell cancer (OPSCC) has a much better prognosis than HPV-negative OPSCC, and this is linked to dense tumor immune infiltration. As the viral antigens may trigger potent immunity, we studied the relationship between the presence of intratumoral HPV-specific T-cell responses, the immune contexture in the tumor microenvironment, and clinical outcome.

Experimental Design: To this purpose, an in-depth analysis of tumor-infiltrating immune cells in a prospective cohort of 97 patients with HPV16-positive and HPV16-negative OPSCC was performed using functional T-cell assays, mass cytometry (CyTOF), flow cytometry, and fluorescent immunostaining of tumor tissues. Key findings were validated in a cohort of 75 patients with HPV16-positive OPSCC present in the publicly available The Cancer Genome Atlas database.

Results: In 64% of the HPV16-positive tumors, type I HPV16-specific T cells were present. Their presence was not only strongly related to a better overall survival, a smaller tumor size, and less lymph node metastases but also to a type I–oriented tumor microenvironment, including high numbers of activated CD161+ T cells, CD103+ tissue-resident T cells, dendritic cells (DC), and DC-like macrophages.

Conclusions: The viral antigens trigger a tumor-specific T-cell response that shapes a favorable immune contexture for the response to standard therapy. Hence, reinforcement of HPV16-specific T-cell reactivity is expected to boost this process. Clin Cancer Res; 24(3); 634–47. ©2017 AACR.

See related commentary by Laban and Hoffmann, p. 505