bluuebunny/crossref_metadata_2025 huggingface dataset:
Intimate citizenship and the tightening of migration controls in the United Kingdom
Authors: Nehring Daniel , Sealey Clive
Published: August 2019

This article examines recent changes in British family migration policy. It explores the reasons for these policy changes. It highlights the fact that these changes have affected the legal, financial, social, and lived experiences of transnational couples. It uses primary research to exemplify these changes. For example, it highlights the fact that the changes in policy have had some negative impacts on the ability of transnational families to have intimate relationships with each other. Some of these changes have led to the separation of couples. Other changes have led to what couples outline as an involuntary separation from the United Kingdom. This research has current and future relevance in the context of the focus of the current government and the likelihood that policy will be tightened even further in the aftermath of Britain leaving the EU, post‐Brexit.
Genetic control of α‐farnesene production in apple fruit and its role in fungal pathogenesis
Authors: Souleyre Edwige J. F. , Bowen Joanna K. , Matich Adam J. , Tomes Sumathi , Chen Xiuyin , Hunt Martin B. , Wang Mindy Y. , Ileperuma Nadeesha R. , Richards Kate , Rowan Daryl D. , Chagné David , Atkinson Ross G.
Published: August 2019

Terpenes are important compounds in plant trophic interactions. A meta‐analysis of GC‐MS data from a diverse range of apple (Malus × domestica) genotypes revealed that apple fruit produces a range of terpene volatiles, with the predominant terpene being the acyclic branched sesquiterpene (E,E)‐α‐farnesene. Four quantitative trait loci (QTLs) for α‐farnesene production in ripe fruit were identified in a segregating ‘Royal Gala’ (RG) × ‘Granny Smith’ (GS) population with one major QTL on linkage group 10 co‐locating with the MdAFS1 (α‐farnesene synthase‐1) gene. Three of the four QTLs were derived from the GS parent, which was consistent with GC‐MS analysis of headspace and solvent‐extracted terpenes showing that cold‐treated GS apples produced higher levels of (E,E)‐α‐farnesene than RG. Transgenic RG fruit downregulated for MdAFS1 expression produced significantly lower levels of (E,E)‐α‐farnesene. To evaluate the role of (E,E)‐α‐farnesene in fungal pathogenesis, MdAFS1 RNA interference transgenic fruit and RG controls were inoculated with three important apple post‐harvest pathogens [Colletotrichum acutatum, Penicillium expansum and Neofabraea alba (synonym Phlyctema vagabunda)]. From results obtained over four seasons, we demonstrate that reduced (E,E)‐α‐farnesene is associated with decreased disease initiation rates of all three pathogens. In each case, the infection rate was significantly reduced 7 days post‐inoculation, although the size of successful lesions was comparable with infections on control fruit. These results indicate that (E,E)‐α‐farnesene production is likely to be an important factor involved in fungal pathogenesis in apple fruit.
Effects of Using the Learning Stations Technique to Teach the Electrical Current Topic on Students’ Physics Subject Performance
Authors: Batman Demet , Saka Ahmet Zeki , Kan Sabri , Saka Tolga
Published: August 2019

The purpose of this study is to determine the effects of using the learning stations technique in teaching about the electrical current on students’ physics course achievement. The sample of the experimental study designed with a pretest-posttest model consists of 50 10th grade students studying in a Science High School in Trabzon, in the 2016-2017 academic year. A multiple-choice achievement test with .80 reliability coefficient was used as the data collection tool. The obtained data were analyzed by applying the Wilcoxon Signed Ranks test in SPSS 20.00 program and a statistically significant difference was found between the experimental and control group achievement test scores in favor of the experimental group, which indicates that the learning stations technique practices performed to teach about the electrical current are effective in increasing the 10th grade students’ physics course achievements.
Perceptions of High School Students about University
Authors: Hayırsever Fahriye
Published: August 2019

This study aims to determine the perceptions of the high school students about the university and the underlying reasons for these perceptions. The model of this study is descriptive, and it is designed based on qualitative research methodology. The sample of the study consists of 70 students from different high schools located in the city center of Duzce, in Turkey. Maximum variation sampling method, one of the purposive sampling methods, was used to determine the sample of the study. The sample consists of 11th grade students from the selected high schools. The data of the research was collected by interview method. The data of the research was analyzed by content analysis method. According to results of this study, students' perceptions about the university were categorized under two main themes. These themes are “Future and Career” and “Freedom and Autonomy”. Within the first main theme, “Future and Career”, the sub-theme with the highest frequency is “future”. This sub-theme is also important in terms of having the highest frequency among all other sub-themes. Students perceive the university as a turning point in their future lives and think that their future lives will be changed and shaped only by the university. Within the second main theme, two sub-themes with the highest frequency are “being free” and “having an independent life”. According to the students, it is also important to be free, socially and personally empowered, and to have the ability to live their own lives during and after university education.
Highly-reactive haloester surface initiators for ARGET ATRP readily prepared by radio frequency glow discharge plasma
Authors: Mecwan Marvin M. , Taylor Michael J. , Graham Daniel J. , Ratner Buddy D.
Published: August 2019

New surface initiators for ARGET ATRP (activators regenerated by electron transfer atomic transfer radical polymerization) have been prepared by the plasma deposition of haloester monomers. Specifically, methyl 3-bromopropionate (M3BP), methyl 2-chloropropionate, and ethyl 2-fluoropropionate (E2FP) were plasma deposited onto glass discs using RF glow discharge plasma. This technique creates surface coatings that are resistant to delamination and rich in halogen species making them good candidates for surface initiators for ARGET ATRP. Of all the plasma polymerized surface coatings, M3BP showed the highest halogen content and was able to grow 2-hydroxyethyl methacrylate (HEMA) polymer brushes on its surface via ARGET ATRP in as little as 15 min as confirmed by XPS. Surprisingly, E2FP, a fluoroester, was also able to grow HEMA polymer brushes despite fluorine being a poor leaving group for ARGET ATRP. The versatility of RF glow discharge plasma offers a clear advantage over other techniques previously used to immobilize ARGET ATRP surface initiators.
DprA-Dependent Exit from the Competent State Regulates Multifaceted Streptococcus pneumoniae Virulence
Authors: Lin Jingjun , Lau Gee W.
Published: August 2019

Streptococcus pneumoniae
(pneumococcus) causes multiple infectious diseases. The pneumococcal competence system facilitates genetic transformation, spreads antibiotic resistance, and contributes to virulence. DNA-processing protein A (DprA) regulates the exit of pneumococcus from the competent state. Previously, we have shown that DprA is important in both bacteremia and pneumonia infections. Here, we examined the mechanisms of virulence attenuation in a Δ
dprA
mutant.
Chylous ascites during peritoneal dialysisin a toddler: a rare complication
Authors: Bhattacharya Deepanjan , Indla Ravi Teja , Tiewsoh Karalanglin , Rathore Vinay
Published: August 2019

Chylous ascites is a rare complication of peritoneal dialysis (PD) and is often mistaken for peritonitis. It usually resolves following conservative management and does not pose any risk to the dialysis procedure. We report the case of a 2-year-old boy, who developed chylous ascites at 36 hours of PD and spontaneously resolved within the next 48 hours.
In transition: current health challenges and priorities in Sudan
Authors: Charani Esmita , Cunnington Aubrey J , Yousif AlaEldin H A , Seed Ahmed Mohammed , Ahmed Ammar E M , Babiker Souad , Badri Shahinaz , Buytaert Wouter , Crawford Michael A , Elbashir Mustafa I , Elhag Kamal , Elsiddig Kamal E , Hakim Nadey , Johnson Mark R , Miras Alexander D , Swar Mohamed O , Templeton Michael R , Taylor-Robinson Simon David
Published: August 2019

A recent symposium and workshop in Khartoum, the capital of the Republic of Sudan, brought together broad expertise from three universities to address the current burden of communicable and non-communicable diseases facing the Sudanese healthcare system. These meetings identified common challenges that impact the burden of diseases in the country, most notably gaps in data and infrastructure which are essential to inform and deliver effective interventions. Non-communicable diseases, including obesity, type 2 diabetes, renal disease and cancer are increasing dramatically, contributing to multimorbidity. At the same time, progress against communicable diseases has been slow, and the burden of chronic and endemic infections remains considerable, with parasitic diseases (such as malaria, leishmaniasis and schistosomiasis) causing substantial morbidity and mortality. Antimicrobial resistance has become a major threat throughout the healthcare system, with an emerging impact on maternal, neonatal and paediatric populations. Meanwhile, malnutrition, micronutrient deficiency and poor perinatal outcomes remain common and contribute to a lifelong burden of disease. These challenges echo the United Nations (UN) sustainable development goals and concentrating on them in a unified strategy will be necessary to address the national burden of disease. At a time when the country is going through societal and political transition, we draw focus on the country and the need for resolution of its healthcare needs.
Anthropometric, physiological characteristics and rugby-specific game skills discriminating Zimbabwean under-16 male adolescent rugby players by level of competition
Authors: Chiwaridzo Matthew , Ferguson Gillian D , Smits-Engelsman Bouwien C M
Published: August 2019

Objectives

Despite growing popularity of adolescent rugby in Zimbabwean schools, little is known about qualities or skills of schoolboy rugby players and how they differ by competitive level. Therefore, the aim of the current study was to identify anthropometric, physiological characteristics and rugby-specific game skills capable of discriminating under-16 (U16) RU players across three proficiency levels.

Methods

Following development of School Clinical Rugby Measure test battery, elite rugby players (n=41), subelite rugby players (n=30) and non-rugby players (n=29) were enrolled and tested for height, sitting height, body mass, skinfolds, speed, agility, upper and lower muscular strength and power, prolonged high-intensity intermittent running ability, tackling, passing and catching in a cross-sectional study.

Results

Elite rugby players displayed significantly better scores for all physiological tests and game skills compared with either subelite or non-rugby players, except for Sit-and-Reach, 20 m speed and L-run tests. However, only vertical jump (VJ) and Yo-Yo Intermittent Recovery Test Level 1 (Yo-Yo IRT L1) significantly improved with increasing competitive level. In addition, elite rugby players showed significantly better scores for tackling (p<0.001) and catching (p<0.001) compared with subelites. No statistical differences were observed across competitive levels for height (p=0.43), sum of seven skinfolds (p=0.26) and passing (p=0.27).

Conclusion

Since VJ and Yo-Yo IRT L1 improved with increasing playing standard, these findings possibly highlight physiological attributes important in elite schoolboy rugby in Zimbabwe. Additionally, development and training of tackling and catching skills in U16 schoolboy rugby is important since they are linked to higher playing standard.
Impact of the caller’s emotional state and cooperation on out-of-hospital cardiac arrest recognition and dispatcher-assisted cardiopulmonary resuscitation
Authors: Chien Cheng-Yu , Chien Wei-Che , Tsai Li-Heng , Tsai Shang-Li , Chen Chen-Bin , Seak Chen-June , Chou Yu-Shao , Ma Matthew , Weng Yi-Ming , Ng Chip-Jin , Lin Cheng-Yu , Tzeng I-Shiang , Lin Chi-Chun , Huang Chien Hsiung
Published: August 2019

Objective

This study determined the impact of the caller’s emotional state and cooperation on out-of-hospital cardiac arrest (OHCA) recognition and dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) performance metrics.

Methods

This was a retrospective study using data from November 2015 to October 2016 from the emergency medical service dispatching centre in northern Taiwan. Audio recordings of callers contacting the centre regarding adult patients with non-traumatic OHCA were reviewed. The reviewers assigned an emotional content and cooperation score (ECCS) to the callers. ECCS 1–3 callers were graded as cooperative and ECCS 4–5 callers as uncooperative and highly emotional. The relation between ECCS and OHCA recognition, time to key events and DA-CPR delivery were investigated.

Results

Of the 367 cases, 336 (91.6%) callers were assigned ECCS 1–3 with a good inter-rater reliability (k=0.63). Dispatchers recognised OHCA in 251 (68.4%) cases. Compared with callers with ECCS 1, callers with ECCS 2 and 3 were more likely to give unambiguous responses about the patient’s breathing status (adjusted OR (AOR)=2.6, 95% CI 1.1 to 6.4), leading to a significantly higher rate of OHCA recognition (AOR=2.3, 95% CI 1.1 to 5.0). Thirty-one callers were rated uncooperative (ECCS 4–5) but had shorter median times to OHCA recognition and chest compression (29 and 122 s, respectively) compared with the cooperative caller group (38 and 170 s, respectively). Nevertheless, those with ECCS 4–5 had a significantly lower DA-CPR delivery rate (54.2% vs 85.9%) due to ‘caller refused’ or ‘overly distraught’ factors.

Conclusions

The caller’s high emotional state is not a barrier to OHCA recognition by dispatchers but may prevent delivery of DA-CPR instruction. However, DA-CPR instruction followed by first chest compression is possible despite the caller’s emotional state if dispatchers are able to skilfully reassure the emotional callers.
Cardiovascular effects of psychotic illnesses and antipsychotic therapy
Authors: Howell Sandra , Yarovova Ekaterina , Khwanda Ahmad , Rosen Stuart D
Published: August 2019

Mortality from cardiovascular disease is increased in people with mental health disorders in general and schizophrenia in particular. The causes are multifactorial, but it is known that antipsychotic medication can cause cardiac side-effects beyond the traditional coronary risk factors. Schizophrenia itself is a contributor to an increased risk of cardiovascular mortality via cardiac autonomic dysfunction and a higher prevalence of metabolic syndrome, both contributing to a reduced life expectancy. The pro-arrhythmic impact of traditional antipsychotics, especially via the hERG-potassium channel, has been known for several years. Newer antipsychotics have a reduced pro-arrhythmic profile but might contribute to higher cardiac death rates by worsening the metabolic profile. Clozapine-induced cardiomyopathy, which is dose independent, is a further concern and continuous monitoring of these patients is required. Prophylaxis with angiotensin-converting enzyme inhibitors is currently under review. Overall, management of cardiovascular risk within this population group must be multifaceted and nuanced to allow the most effective treatment of serious mental illness to be conducted within acceptable parameters of cardiovascular risk; some practical measures are presented for the clinical cardiologist.
Impact of a community-based cardiovascular disease service intervention in a highly deprived area
Authors: Downing Jennifer , Rose Tanith C , Saini Pooja , Matata Bashir , McIntosh Zoe , Comerford Terence , Wilson Keith , Pemberton Allan , Harper Lesley M , Shaw Matthew , Daras Konstantinos , Barr Ben
Published: August 2019

Objective

To examine the effects on emergency hospital admissions, length of stay and emergency re-admissions of providing a consultant-led, community-based cardiovascular diagnostic, treatment and rehabilitation service, based in a highly deprived area in the North West of England.

Methods

A longitudinal matched controlled study using difference-in-differences analysis compared the change in outcomes in the intervention population, to the change in outcomes in a matched comparison population that had not received the intervention, 5 years before and after implementation. The outcomes were emergency hospitalisations, length of inpatient stay and re-admission rates for cardiovascular disease (CVD).

Results

Findings show that the intervention was associated with 66 fewer emergency CVD admissions per 100 000 population per year (95% CI 22.13 to 108.98) in the post-intervention period, relative to the control group. No significant measurable effects on length of stay or emergency re-admission rates were observed.

Conclusion

This consultant-led, community-based cardiovascular diagnostic, treatment and rehabilitation service was associated with a lower rate of emergency hospital admissions in a highly disadvantaged population. Similar approaches could be an effective component of strategies to reduce unplanned hospital admissions.
Progress in reducing inequalities in cardiovascular disease mortality in Europe
Authors: Di Girolamo Chiara , Nusselder Wilma J , Bopp Matthias , Brønnum-Hansen Henrik , Costa Giuseppe , Kovács Katalin , Leinsalu Mall , Martikainen Pekka , Pacelli Barbara , Rubio Valverde José , Mackenbach Johan P
Published: August 2019

Objective

To assess whether recent declines in cardiovascular mortality have benefited all socioeconomic groups equally and whether these declines have narrowed or widened inequalities in cardiovascular mortality in Europe.

Methods

In this prospective registry-based study, we determined changes in cardiovascular mortality between the 1990s and the early 2010s in 12 European populations by gender, educational level and occupational class. In order to quantify changes in the magnitude of differences in mortality, we calculated both ratio measures of relative inequalities and difference measures of absolute inequalities.

Results

Cardiovascular mortality has declined rapidly among lower and higher socioeconomic groups. Relative declines (%) were faster among higher socioeconomic groups; absolute declines (deaths per 100 000 person-years) were almost uniformly larger among lower socioeconomic groups. Therefore, although relative inequalities increased over time, absolute inequalities often declined substantially on all measures used. Similar trends were seen for ischaemic heart disease and cerebrovascular disease mortality separately. Best performer was England and Wales, which combined large declines in cardiovascular mortality with large reductions in absolute inequalities and stability in relative inequalities in both genders. In the early 2010s, inequalities in cardiovascular mortality were smallest in Southern Europe, of intermediate magnitude in Northern and Western Europe and largest in Central-Eastern European and Baltic countries.

Conclusions

Lower socioeconomic groups have experienced remarkable declines in cardiovascular mortality rates over the last 25 years, and trends in inequalities can be qualified as favourable overall. Nevertheless, further reducing inequalities remains an important challenge for European health systems and policies.
A strengthened data processing inequality for the Belavkin–Staszewski relative entropy
Authors: Bluhm Andreas , Capel Ángela
Published: August 2019

In this work, we provide a strengthening of the data processing inequality for the relative entropy introduced by Belavkin and Staszewski (BS-entropy). This extends previous results by Carlen and Vershynina for the relative entropy and other standard [Formula: see text]-divergences. To this end, we provide two new equivalent conditions for the equality case of the data processing inequality for the BS-entropy. Subsequently, we extend our result to a larger class of maximal [Formula: see text]-divergences. Here, we first focus on quantum channels which are conditional expectations onto subalgebras and use the Stinespring dilation to lift our results to arbitrary quantum channels.
PORTFOLIO RHO-PRESENTATIVITY
Authors: FROIDURE TRISTAN , JALALZAI KHALID , CHOUEIFATY YVES
Published: August 2019

Given an investment universe, we consider the vector [Formula: see text] of correlations of all assets to a portfolio with weights [Formula: see text]. This vector offers a representation equivalent to [Formula: see text] and leads to the notion of [Formula: see text]-presentative portfolio, that has a positive correlation, or exposure, to all assets. This class encompasses well-known portfolios, and complements the notion of representative portfolio, that has positive amounts invested in all assets (e.g. the market-cap index). We then introduce the concept of maximally [Formula: see text]-presentative portfolios, that maximize under no particular constraint an aggregate exposure [Formula: see text] to all assets, as measured by some symmetric, increasing and concave real-valued function [Formula: see text]. A basic characterization is established and it is shown that these portfolios are long-only, diversified and form a finite union of polytopes that satisfies a local regularity condition with respect to changes of the covariance matrix of the assets. Despite its small size, this set encompasses many well-known and possibly constrained long-only portfolios, bringing them together in a common framework. This also allowed us characterizing explicitly the impact of maximum weight constraints on the minimum variance portfolio. Finally, several theoretical and numerical applications illustrate our results.
A Fuzzy Logic-Based Gain Scheduling Method for Online Feedback Path Modeling and Neutralization in Active Noise Control Systems
Authors: Haseeb Abdul , Tufail Muhammad , Ahmed Shakeel , Rehan Muhammad , Majid Amna , Ahmed Waqas
Published: August 2019

Acoustic feedback is the main problem associated with (broadband) active noise control (ANC) in feed-forward configuration. To solve this problem, auxiliary noise is injected into the ANC system to have accurate model of the feedback path. The conventional approaches substantially model the feedback path at the cost of degradation in the noise reduction performance (NRP) and vice versa. Here, we propose a fuzzy logic-based gain scheduling (of auxiliary noise) for online feedback path modeling and neutralization (FBPMN). The fuzzy controller computes the instantaneous gain for auxiliary noise based on two inputs, the first input gives information about modeling status of FBPMN filter while the second input gives information regarding variance of the disturbance signal for the adaptive FBPMN filter. Furthermore, variable step-size (VSS) is used for the adaptation of FBPMN filter that uses a larger value of step-size during modeling (phase) of FBPMN filter for fast adaptation and a smaller value when the feedback path has been (adequately) modeled. Fuzzy gain scheduler together with VSS in FBPMN filter improves both the NRP and feedback path modeling characteristics. Moreover, the proposed method does not require initial offline modeling of the feedback path thereby demonstrating complete online operation. To make the system computationally efficient, a look-up table-based approach is also proposed in this paper. Simulations results are presented to demonstrate the effectiveness of the proposed method.
Extracellular Nucleotides and P2 Receptors in Renal Function
Authors: Vallon Volker , Unwin Robert , Inscho Edward W. , Leipziger Jens , Kishore Bellamkonda K.
Published: August 2019

The understanding of the nucleotide/P2 receptor system in the regulation of renal hemodynamics and transport function has grown exponentially over the last 20 yr. This review attempts to integrate the available data while also identifying areas of missing information. First, the determinants of nucleotide concentrations in the interstitial and tubular fluids of the kidney are described, including mechanisms of cellular release of nucleotides and their extracellular breakdown. Then the renal cell membrane expression of P2X and P2Y receptors is discussed in the context of their effects on renal vascular and tubular functions. Attention is paid to effects on the cortical vasculature and intraglomerular structures, autoregulation of renal blood flow, tubuloglomerular feedback, and the control of medullary blood flow. The role of the nucleotide/P2 receptor system in the autocrine/paracrine regulation of sodium and fluid transport in the tubular and collecting duct system is outlined together with its role in integrative sodium and fluid homeostasis and blood pressure control. The final section summarizes the rapidly growing evidence indicating a prominent role of the extracellular nucleotide/P2 receptor system in the pathophysiology of the kidney and aims to identify potential therapeutic opportunities, including hypertension, lithium-induced nephropathy, polycystic kidney disease, and kidney inflammation. We are only beginning to unravel the distinct physiological and pathophysiological influences of the extracellular nucleotide/P2 receptor system and the associated therapeutic perspectives.
An Approach to Rapid Determination of Tween-80 for the Quality Control of Traditional Chinese Medicine Injection by Partial Least Squares Regression in Near-Infrared Spectral Modeling
Authors: Ma Jin-Fang , Chen Tian-Ling , Zhang Xiang-Dong , Xiao Xue , Ge Fa-Huan
Published: August 2019

This study established an approach to rapidly determine the Tween-80 in traditional Chinese medicine (TCM) injection by using near-infrared (NIR) spectroscopy. Totally 133 standard solutions of Tween-80 were prepared and randomly divided into calibration set and validation set, containing 109 and 24 samples, respectively. Spectral data were preprocessed and then subjected to establish a predictive model using partial least-squares (PLS). The standard error of cross validation (SECV), standard deviation of calibration (SEC), and the determination coefficient (R) of the established model were 0.0561, 0.0526, and 0.9986, respectively. The model was successfully applied to determine Tween-80 contents in 25XBJ Injectionsand 40FFSX Injections, and it produced satisfactory quantitative analysis results with average relative deviations 0.60% and 0.16%, respectively, for 25XBJ Injectionsand 40FFSX Injections, and the maximum relative deviations 8.57% and 7.60%, respectively. This work shows that NIR model displayed quite good predictive ability for Tween-80 quantitative analysis, which could potentially be applied to rapid determination of Tween-80 in the production process of TCM injections and other TCM products.
Notch Signaling Inhibition by LY411575 Attenuates Osteoblast Differentiation and Decreased Ectopic Bone Formation Capacity of Human Skeletal (Mesenchymal) Stem Cells
Authors: AlMuraikhi Nihal , Ali Dalia , Vishnubalaji Radhakrishnan , Manikandan Muthurangan , Atteya Muhammad , Siyal Abdulaziz , Alfayez Musaad , Aldahmash Abdullah , Kassem Moustapha , Alajez Nehad M.
Published: August 2019

Background. Chemical biology approaches using small molecule inhibitors targeting specific signaling pathways are useful tools to dissect the molecular mechanisms governing stem cell differentiation and for their possible use in therapeutic interventions. Methods. Stem cell signaling small molecule library functional screen was performed employing human bone marrow skeletal (mesenchymal) stem cells (hBMSCs). Alkaline phosphatase (ALP) activity and formation of mineralized matrix visualized by Alizarin red staining were employed as markers for osteoblastic differentiation. Global gene expression profiling was conducted using the Agilent microarray platform, and data normalization and bioinformatics were performed using GeneSpring software. Pathway analyses were conducted using the Ingenuity Pathway Analysis (IPA) tool. In vivo ectopic bone formation was performed using hBMSC mixed with hydroxyapatite–tricalcium phosphate granules that were implanted subcutaneously in 8-week-old female nude mice. Hematoxylin and eosin staining and Sirius red staining were performed to identify bone formation in vivo. Results. Among the tested molecules, LY411575, a potent γ-secretase and Notch signaling inhibitor, exhibited significant inhibitory effects on osteoblastic differentiation of hBMSCs manifested by reduced ALP activity, mineralized matrix formation, and decreased osteoblast-specific gene expression as well as in vivo ectopic bone formation. Global gene expression profiling of LY411575-treated cells revealed changes in multiple signaling pathways, including focal adhesion, insulin, TGFβ, IL6, and Notch signaling, and decreased the expression of genes associated with functional categories of tissue development. Among the affected signaling networks were TGFβ1, SPP1, and ERK regulatory networks. Conclusions. We identified γ-secretase inhibitor (LY411575) as a potent regulator of osteoblastic differentiation of hBMSC that may be useful as a therapeutic option for treating conditions associated with ectopic bone formation.
Shaking Table Test Study on Seismic Performance of Hollow Rectangular Piers
Authors: Shen Yanli , Wei Bo
Published: August 2019

To study the seismic performance of hollow reinforced concrete piers under dynamic loads, nine hollow pier specimens with different stirrup ratios, reinforcement ratios, and axial compression ratios are designed and manufactured. The El Centro wave, Taft wave, and artificial Lanzhou wave are selected as seismic excitation for the shaking table test. The effects of the reinforcement ratio, stirrup ratio, and axial compression ratio on the failure mode, period, damping, acceleration and displacement response, dynamic magnification factor, ductility, and energy dissipation of specimens under different working conditions are studied. The results show that all the nine reinforced concrete piers have good seismic performance. Subjected to ground motion excitation, horizontal through cracks appeared on the pier surface. With the increase of ground motion excitation, the period of piers increases but the maximum period does not exceed 0.62 s, and the damping ratio increases as well and ranges from 0.02 to 0.064. With the increase of the ground motion excitation, the acceleration response of pier specimens increases, the dynamic magnification factor decreases, the displacement ductility coefficient decreases, and the energy dissipation of the specimens increases. The reinforcement ratio, stirrup ratio, and axial compression ratio have different effects on the above parameters. The test results can provide reference for seismic design of hollow rectangular piers and have certain engineering significance and value.
Effects of Fe3+ on Acute Toxicity and Regeneration of Planarian (Dugesia japonica) at Different Temperatures
Authors: Ding Xue , Song Linxia , Han Yahong , Wang Yingbo , Tang Xiaowang , Cui Guicai , Xu Zhenbiao
Published: August 2019

Objective. To investigate the effects of different concentrations of Fe3+ on the acute toxicity and regeneration of planarian at different temperatures. Method. The planarians were treated with 40 mg/l, 50 mg/l, 60 mg/l, and 70 mg/l Fe3+ solution and placed in 15°C, 20°C, and 25°C, respectively, to observe the mortality and the poisoning pattern of the planarian. In addition, the planarians were cut into three parts of head, trunk, and tail, then placed in Fe3+ solution at concentrations of 10 mg/l, 15 mg/l, 20 mg/l, and 30 mg/l, and placed in 15°C, 20°C, and 25°C respectively, and the regeneration rate of the planarian was investigated. Results. At the same temperature, in the concentration of Fe3+ from 40 mg/l to 70 mg/l, the mortality of the planarian increased with the increasing of the concentration of Fe3+; at the same concentration and different temperatures, the death speed of the planarian is the fastest at 20°C, the next at 25°C, and the lowest at 15°C, indicating that the toxic effect of Fe3+ can be accelerated at a suitable temperature of 20°C. At the same temperature, in the low concentration of Fe3+ from 10 mg/l to 30 mg/l, the regeneration rate of the planarian gradually decreased with the increasing of the concentration of Fe3+; at the same concentration and different temperature, the regeneration rate of planarian was faster at 20°C and 25°C, but the difference between 20°C and 25°C was small, and the slowest at 15°C, indicating that the low temperature significantly affects the planarian regeneration speed. The study also found the regeneration rates of the head, trunk, and tail of the planarian were different; the head regeneration was the fastest, the trunk was the second, and the tail was the slowest. Conclusion. Fe3+ had obvious toxic effects on the survival and regeneration of planarian; the planarian is sensitive to Fe3+ and may be used to detect Fe3+ water pollution; in addition, temperature can affect the toxic effects of Fe3+ and thus affect the survival and regeneration of the planarian. Therefore, the temperature should be taken into consideration when detecting water Fe3+ pollution.
Adaptive Sliding Mode Fixed‐Time Tracking Control Based on Fixed‐Time Sliding Mode Disturbance Observer with Dead‐Zone Input
Authors: Wang Hongbin , Su Bo , Wang Yueling , Gao Jing
Published: August 2019

Aiming at the problem of fixed‐time trajectory tracking control for high‐order dynamic systems with external time‐varying disturbance and input dead‐zone, an adaptive fixed‐time sliding mode control algorithm is proposed by employing a fixed‐time sliding mode disturbance observer (FTSMDO) and high‐order fixed‐time sliding mode algorithm. Firstly, a FTSMDO is presented for the problem that estimating the compound disturbance is composed of input dead‐zone and time‐varying external disturbance in the higher‐order dynamic system, which cannot be measured accurately. Furthermore, for the case that the total disturbance of the system has an unknown upper bound, the corresponding adaptive law is designed to estimate the unknown upper bound, and the fixed‐time controller is designed based on FTSMDO algorithm to make all state variables converge in a fixed‐time. Based on Lyapunov technique, the fixed‐time convergence performance of the proposed algorithm is proved. The effectiveness of the presented fixed‐time control algorithm is verified by simulating the depth tracking control of the underactuated underwater vehicle.
Longitudinal Modeling and Control of Tailed Flapping-Wings Micro Air Vehicles near Hovering
Authors: Jiang Tao , Yang Xiaosong , Wang Hongwei , Gai Wen , Cui Long
Published: August 2019

Compared with the tailless flapping wing micro air vehicle (FMAV), the tailed FMAV has a simpler structure and is easier to control. However, although biplane FMAVs with tails have been used for flight control in practice for a long time, a theoretical model of the tailed FMAV has not previously been established. In this paper, we report modeling of the longitudinal dynamics of a tailed biplane FMAV using the Newton‐Euler equations. In this study, the vehicle was trimmed and linearized near its hovering equilibrium, assuming small disturbances. Then the stability of the hovering FMAV was analyzed with a modal analysis method. A state feedback controller was synthesized to stabilize the disturbance. Finally, we investigated the flight control of the tailed biplane FMAV with different control signals. Our results show that the natural‐motion mode determines the oscillation divergence characteristics of the tailed FMAV, a mode that can be suppressed with the state feedback controller by real‐time modulation of the tail. The tail can also be used to achieve different flight modes with different control‐signal functions. The tailed FMAV cruises in a line when the tail is controlled with a step function and spirals in an elliptical trajectory in the longitudinal plane when the tail is controlled by a sinusoidal function. Our longitudinal‐ dynamics model provides an analytical basis for further dynamic analyses of the tailed FMAV, as well as the corresponding controller synthesis. Moreover, the proposed attitude stabilization and flight control schemes for the vehicle near hovering provide a basis for developing practical uses of the tailed FMAV.
DHA-SBT-1214 Taxoid Nanoemulsion and Anti–PD-L1 Antibody Combination Therapy Enhances Antitumor Efficacy in a Syngeneic Pancreatic Adenocarcinoma Model
Authors: Ahmad Gulzar , Mackenzie Gerardo G. , Egan James , Amiji Mansoor M.
Published: August 2019

The goal of this study was to evaluate combination of a novel taxoid, DHA-SBT-1214 chemotherapy, in modulating immune checkpoint marker expression and ultimately in improving antibody-based checkpoint blockade therapy in pancreatic adenocarcinoma (PDAC). DHA-SBT-1214 was encapsulated in an oil-in-water nanoemulsion and administered systemically in Panc02 syngeneic PDAC-bearing C57BL/6 mice. Following treatment with DHA-SBT-1214, expression levels of PD-L1 were measured and anti–PD-L1 antibody was administered in combination. The effects of combination therapy on efficacy and the molecular basis of synergistic effects were evaluated. PD-L1 expression was lower on Panc02 pancreatic tumor cells in vitro, which significantly increased after exposure to different chemotherapy drugs. Administration of DHA-SBT-1214, gemcitabine, and PD-L1 antibody alone failed to increase CD8+ T-cell infiltration inside tumors. However, combination of anti–PD-L1 therapy with a novel chemotherapy drug DHA-SBT-1214 in nanoemulsion (NE-DHA-SBT-1214) significantly enhanced CD8+ T-cell infiltration and the therapeutic effects of the anti–PD-L1 antibody. Furthermore, in the Panc02 syngeneic model, the NE-DHA-SBT-1214 combination therapy group reduced tumor growth to a higher extend than paclitaxel, nab-paclitaxel (Abraxane), gemcitabine, or single anti–PD-L1 antibody therapy groups. Our results indicate that NE-DHA-SBT-1214 stimulated immunogenic potential of PDAC and provided an enhanced therapeutic effect with immune checkpoint blockade therapy, which warrants further evaluation.
Immunopathologic Stratification of Colorectal Cancer for Checkpoint Blockade Immunotherapy
Authors: Llosa Nicolas J. , Luber Brandon , Siegel Nicholas , Awan Anas H. , Oke Teniola , Zhu Qingfeng , Bartlett Bjarne R. , Aulakh Laveet K. , Thompson Elizabeth D. , Jaffee Elizabeth M. , Durham Jennifer N. , Sears Cynthia L. , Le Dung T. , Diaz Luis A. , Pardoll Drew M. , Wang Hao , Housseau Franck , Anders Robert A.
Published: August 2019

Mismatch-repair deficiency in solid tumors predicts their response to PD-1 blockade. Based on this principle, pembrolizumab is approved as standard of care for patients with unresectable or metastatic microsatellite instability–high (MSI-H) cancer. Despite this success, a large majority of metastatic colorectal cancer patients are not MSI-H and do not benefit from checkpoint blockade treatment. Predictive biomarkers to develop personalized medicines and guide clinical trials are needed for these patients. We, therefore, asked whether immunohistologic stratification of metastatic colorectal cancer based on primary tumor PD-L1 expression associated with the presence or absence of extracellular mucin defines a subset of metastatic colorectal cancer patients who exhibit a preexisting antitumor immune response and who could potentially benefit from the checkpoint blockade. To address this, we studied 26 advanced metastatic colorectal cancer patients treated with pembrolizumab (NCT01876511). To stratify patients, incorporation of histopathologic characteristics (percentage of extracellular mucin) and PD-L1 expression at the invasive front were used to generate a composite score, the CPM (composite PD-L1 and mucin) score, which discriminated patients who exhibited clinical benefit (complete, partial, or stable disease) from those patients with progressive disease. When validated in larger cohorts, the CPM score in combination with MSI testing may guide immunotherapy interventions for colorectal cancer patient treatment.
Impact of Cigarette Smoking and Head and Neck Squamous Cell Carcinoma on Circulating Inflammatory Biomarkers
Authors: Andersson Bengt-Åke , Löfgren Sture , Lewin Freddi , Nilsson Mats , Laytragoon-Lewin Nongnit
Published: August 2019

Introduction: Smoking induces inflammation and an immune response. A cancer-related inflammatory response has been seen in smoking and nonsmoking head and neck squamous cell carcinoma (HNSCC) patients. Objectives: The aim of this study was to analyze the possible separated effects of smoking or HNSCC on 18 inflammatory or immune regulatory biomarkers. Methods: Fifty-one nonsmoking and 36 smoking pretreated HNSCC patients and 101 nonsmoking and 39 smoking controls were included in this study. The levels of 18 inflammatory or immune regulatory biomarkers were analyzed. A multivariable linear regression model was used to predict the impact of smoking and HNSCC on the levels of the biomarkers. Results: Smoking had the highest impact on total WBC, IFN-γ, and MCP-1 levels. The highest impact of HNSCC was found on neutrophils, neutrophil-to-lymphocyte ratio, HsCRP, MIP-1b, and TNF-α levels. Conclusion: IdentifyingHNSCC or smoking-related inflammatory biomarkers might contribute to the understanding of the immune response in HNSCC patients. This study could provide information of inflammatory biomarkers in HNSCC patients.
МЕТОДИ ІДЕНТИФІКАЦІЇ ДИНАМІЧНОЇ МОДЕЛІ РЕАКЦІЇ СЕРЦЕВО-СУДИННОЇ СИСТЕМИ НА ФІЗИЧНЕ НАВАНТАЖЕННЯ У ХВОРИХ НА ІНФАРКТ МІОКАРДА В ПРОЦЕСІ РЕАБІЛІТАЦІЇ
Authors: Levytska L. V. , Vovkodav O. V.
Published: August 2019

Прогнозування динаміки пульсу та артеріального тиску під дією фізичного навантаження є ключовим завданням при плануванні процесу реабілітації пацієнта після перенесених серцево-судинних подій, і, в першу чергу, інфаркту міокарда. На сьогоднішній день її розв'язують емпірично, однак, розроблення адекватної математичної моделі прогнозування основних гемодинамічних показників дозволила б уникнути суб'єктивізму оцінок і підвищити надійність прогнозу, безпеку та ефективність реабілітаційної технології.

З метою формування судження про зміну стану пацієнта під дією фізичного навантаження в процесі реабілітації реалізовано систему моделювання рівнів пульсу та артеріального тиску за допомогою пакету прикладних програм для математичного моделювання. Її основними підсистемами є обробка та ідентифікація даних, формування прогнозних даних. Для перевірки адекватності побудованої моделі використано засіб перевірки толерантності до фізичного навантаження. Отримані результати свідчать про адекватність побудованої математичної моделі для аналізованого етапу процесу реабілітації. Максимальний рівень похибок за весь період спостереження склав 9,5 % щодо пульсу та 5,2 % щодо артеріального тиску.

Отже, розроблена математична модель динаміки пульсу та артеріального тиску під дією фізичного навантаження в підгостру фазу реабілітації дозволяє прогнозувати реакцію організму на дозоване фізичне навантаження. Метод ідентифікації сукупності диференціальних рівнянь, що моделюють таку динаміку під дією фізичного навантаження на основі модифікованого градієнтного методу Левенберга-Марквадта, доповненого процедурою вибору початкових значень коефіцієнтів, підтверджує адекватність розробленої математичної моделі.
Trend analysis of leprosy indicators in a hyperendemic Brazilian state, 2001–2015
Authors: Anchieta Jefferson De Jesus Silva , Costa Léa Márcia Melo da , Campos Leonardo Costa , Vieira Maurício Dos Remédios , Mota Osvaldina Silva , Morais Neto Otaliba Libânio , Souza Marta Rovery de , Guimarães Rafael Alves
Published: August 2019

OBJECTIVE: To analyze the temporal trend of leprosy indicators in a hyperendemic state of Brazil, from 2001–2015. METHODS:This is a time-series study of leprosy indicators in the state of Maranhão, Northeastern region of Brazil. The study used data from the Brazilian National System of Reportable Diseases, for the period between 2001 and 2015. The following indicators were evaluated: (i) detection coefficient in the general population; (ii) detection coefficient in people under 15 years old; (iii) rate of cases with grade 2 physical disability in the diagnosis; (iv) rate of examined contacts, and (v) proportion of healing . The Prais-Winsten regression model was used for trend analysis. Analyses were performed for the state and by each health region. RESULTS: 77,697 leprosy cases were analyzed in the general population and 7,599 in individuals under 15 years old. The detection coefficient in the general population ranged from 80.7/100 thousand inhabitants in 2001 to 51.2/100 thousand inhabitants in 2015. The coefficient in the general population presented a downward trend (annual percentage variation [APV] = -2.98; 95%CI -4.15– -1.79). For the population under 15 years old, the rate was 24.9/100 thousand inhabitants in 2001, and 19.9/100 thousand inhabitants in 2015, with downward trend (APV = -3.07; 95%CI -4.95– -1.15). It was observed upward trend in rate of contacts examined (APV = 2.35; 95%CI 0.58–4.15) and rate of cases with grade 2 disability (APV = 2.19; 95%CI 0.23–4.19). Stationary trend was observed in the proportion of healing (APV = -0.10; 95%CI -0.50–0.30). Regional differences were found in the performance of the indicators. CONCLUSIONS: A downward trend for the detection coefficients in the general population and in individuals under 15 years old was found in Maranhão. Despite this result, the rates are still very high, demanding efforts from all spheres of public administration and health professionals to reduce the burden of the disease in the state.
Ceramide 1-Phosphate Protects Endothelial Colony–Forming Cells From Apoptosis and Increases Vasculogenesis In Vitro and In Vivo
Authors: Mena Hebe Agustina , Zubiry Paula Romina , Dizier Blandine , Mignon Virginie , Parborell Fernanda , Schattner Mirta , Boisson-Vidal Catherine , Negrotto Soledad
Published: August 2019

Objective:

Ceramide 1-phosphate (C1P) is a bioactive sphingolipid highly augmented in damaged tissues. Because of its abilities to stimulate migration of murine bone marrow–derived progenitor cells, it has been suggested that C1P might be involved in tissue regeneration. In the present study, we aimed to investigate whether C1P regulates survival and angiogenic activity of human progenitor cells with great therapeutic potential in regenerative medicine such as endothelial colony–orming cells (ECFCs).

Approach and Results:

C1P protected ECFC from TNFα (tumor necrosis factor-α)-induced and monosodium urate crystal–induced death and acted as a potent chemoattractant factor through the activation of ERK1/2 (extracellular signal-regulated kinases 1 and 2) and AKT pathways. C1P treatment enhanced ECFC adhesion to collagen type I, an effect that was prevented by β1 integrin blockade, and to mature endothelial cells, which was mediated by the E-selectin/CD44 axis. ECFC proliferation and cord-like structure formation were also increased by C1P, as well as vascularization of gel plug implants loaded or not with ECFC. In a murine model of hindlimb ischemia, local administration of C1P alone promoted blood perfusion and reduced necrosis in the ischemic muscle. Additionally, the beneficial effects of ECFC infusion after ischemia were amplified by C1P pretreatment, resulting in a further and significant enhancement of leg reperfusion and muscle repair.

Conclusions:

Our findings suggest that C1P may have therapeutic relevance in ischemic disorders, improving tissue repair by itself, or priming ECFC angiogenic responses such as chemotaxis, adhesion, proliferation, and tubule formation, which result in a better outcome of ECFC-based therapy.