bluuebunny/crossref_metadata_2025 huggingface dataset:
Housing Complexity Alters GFAP-Immunoreactive Astrocyte Morphology in the Rat Dentate Gyrus
Authors: Salois Garrick , Smith Jeffrey S.
Published: February 2016

Rats used in research are typically housed singly in cages with limited sensory stimulation. There is substantial evidence that housing rats in these conditions lead to numerous neuroanatomical and behavioral abnormalities. Alternatively, rats can be housed in an enriched environment in which rats are housed in groups and given room for exercise and exploration. Enriched environments result in considerable neuroplasticity in the rodent brain. In the dentate gyrus of the hippocampus, enriched environments evoke especially profound neural changes, including increases in the number of neurons and the number of dendritic spines. However, whether changes in astrocytes, a type of glia increasingly implicated in mediating neuroplasticity, are concurrent with these neural changes remains to be investigated. In order to assess morphological changes among astrocytes of the rat dentate gyrus, piSeeDB was used to optically clear 250 μm sections of tissue labeled using GFAP immunohistochemistry. Confocal imaging and image analysis were then used to measure astrocyte morphology. Astrocytes from animals housed in EE demonstrated a reduced distance between filament branch points. Furthermore, the most complex astrocytes were significantly more complex among animals housed in EE compared to standard environments.
Studies on Liquefaction Time and Proteins Involved in the Improvement of Seminal Characteristics in Dromedary Camels (Camelus dromedarius)
Authors: Mal Gorakh , Vyas Sumant , Srinivasan Alagiri , Patil Nitin Vasant Rao , Pathak Krishan Murari Lal
Published: February 2016

Semen was collected from six dromedary camels using artificial vagina during rutting season. Liquefaction of the viscous semen occurred in23.89±1.49 h. During liquefaction, proteins with molecular masses of 24.55 kDa and 22.07 kDa appeared in conjunction with the disappearance of intact 26.00 kDa protein after 18–24 h. These proteins were identified asβ-nerve growth factors (β-NGFs) in liquefied camel semen. Guanidine-HCL improves the rheological characteristics of dromedary camel semen along with significant (P<0.01) increase in sperm motility. No significant differences were found in viability of spermatozoa indicating no visible detrimental effects on spermatozoa. The cause of semen viscosity, as well as proteins that are present in liquefied dromedary camel seminal plasma, is described for the first time.
Serum Fatty Acids, Traditional Risk Factors, and Comorbidity as Related to Myocardial Injury in an Elderly Population with Acute Myocardial Infarction
Authors: Laake Kristian , Seljeflot Ingebjørg , Schmidt Erik B. , Myhre Peder , Tveit Arnljot , Arnesen Harald , Solheim Svein
Published: February 2016

Background.Epidemiological and randomized clinical trials indicate that marine polyunsaturated n-3 fatty acids (n-3 PUFAs) may have cardioprotective effects.Aim.Evaluate the associations between serum fatty acid profile, traditional risk factors, the presence of cardiovascular diseases (CVD), and peak Troponin T (TnT) levels in elderly patients with an acute myocardial infarction (AMI).Materials and Methods.Patients (n=299) consecutively included in the ongoing Omega-3 fatty acids in elderly patients with myocardial infarction (OMEMI) trial were investigated. Peak TnT was registered during the hospital stay. Serum fatty acid analysis was performed 2–8 weeks later.Results.No significant correlations between peak TnT levels and any of the n-3 PUFAs were observed. However, patients with a history of atrial fibrillation had significantly lower docosahexaenoic acid levels than patients without. Significantly lower peak TnT levels were observed in patients with a history of hyperlipidemia, angina, MI, atrial fibrillation, intermittent claudication, and previous revascularization (allp<0.02).Conclusions.In an elderly population with AMI, no association between individual serum fatty acids and estimated myocardial infarct size could be demonstrated. However, a history of hyperlipidemia and the presence of CVD were associated with lower peak TnT levels, possibly because of treatment with cardioprotective medications.
Two Traditional Chinese Medicines Curcumae Radix and Curcumae Rhizoma: An Ethnopharmacology, Phytochemistry, and Pharmacology Review
Authors: Zhou Yang , Xie Meng , Song Yan , Wang Wenping , Zhao Haoran , Tian Yuxin , Wang Yan , Bai Shaojuan , Zhao Yichen , Chen Xiaoyi , She Gaimei
Published: February 2016

Curcumae Rhizoma, known as Ezhu (Chinese: 莪术), and Curcumae Radix, known as Yujin (Chinese: 郁金), are different plant parts coming from three same species according to China Pharmacopoeia. Actually, they are used in different ways in TCM clinical treatment. Curcumae Rhizoma is mainly used as antitumor drug, while Curcumae Radix has been used as antidepressant and cholagogue. Curcumae Rhizoma and Curcumae Radix are confused in variety and source, even in clinical trials by some nonprofessional workers. So it is important for us to make them clear. This review is aimed at summarizing the ethnopharmacology, phytochemical, and pharmacological differences between Curcumae Radix and Curcumae Rhizoma by SciFinder, CNKI, and so on, to use them exactly and clearly. Further studies on Curcumae Rhizoma and Curcumae Radix can lead to the development of new drugs and therapeutics for various diseases on the basis of the TCM theory.
Growing-Related Changes in Arterial Properties of Healthy Children, Adolescents, and Young Adults Nonexposed to Cardiovascular Risk Factors: Analysis of Gender-Related Differences
Authors: Curcio S. , García-Espinosa V. , Arana M. , Farro I. , Chiesa P. , Giachetto G. , Zócalo Y. , Bia D.
Published: February 2016

The aims of our work were to determine normal aging rates for structural and functional arterial parameters in healthy children, adolescents, and young adults and to identify gender-related differences in these aging rates.Methods. 161 subjects (mean: 15 years (range: 4–28 years), 69 females) were studied. Subjects included had no congenital or chronic diseases, nor had they been previously exposed to traditional cardiovascular risk factors. Arterial parameters assessed were (1) central blood pressure (BP) and aortic pulse wave analysis, (2) arterial local (pressure-strain elastic modulus) and regional (pulse wave velocity, PWV) stiffness, and (3) arterial diameters and carotid intima-media thickness (CIMT). Simple linear regression models (age as the independent variable) were obtained for all the parameters and the resulting rates of change were compared between genders.Results. No gender-related differences were found in mean values of arterial structural and functional parameters in prepubertal ages (4–8 years), but they started to appear at ~15 years. Boys showed a greater rate of change for central systolic BP, central pulse pressure, CIMT, and carotid-femoral PWV.Conclusion.Gender-related differences in arterial characteristics of adults can be explained on the basis of different growing-related patterns between boys and girls, with no existing differences in prepubertal ages.
Radiotherapy Suppresses Bone Cancer Pain through Inhibiting Activation of cAMP Signaling in Rat Dorsal Root Ganglion and Spinal Cord
Authors: Zhu Guiqin , Dong Yanbin , He Xueming , Zhao Ping , Yang Aixing , Zhou Rubing , Ma Jianhua , Xie Zhong , Song Xue-Jun
Published: February 2016

Radiotherapy is one of the major clinical approaches for treatment of bone cancer pain. Activation of cAMP-PKA signaling pathway plays important roles in bone cancer pain. Here, we examined the effects of radiotherapy on bone cancer pain and accompanying abnormal activation of cAMP-PKA signaling. Female Sprague-Dawley rats were used and received tumor cell implantation (TCI) in rat tibia (TCI cancer pain model). Some of the rats that previously received TCI treatment were treated with X-ray radiation (radiotherapy). Thermal hyperalgesia and mechanical allodynia were measured and used for evaluating level of pain caused by TCI treatment. PKA mRNA expression in dorsal root ganglion (DRG) was detected by RT-PCR. Concentrations of cAMP, IL-1β, and TNF-αas well as PKA activity in DRG and the spinal cord were measured by ELISA. The results showed that radiotherapy significantly suppressed TCI-induced thermal hyperalgesia and mechanical allodynia. The level of PKA mRNA in DRG, cAMP concentration and PKA activity in DRG and in the spinal cord, and concentrations of IL-1βand TNF-αin the spinal cord were significantly reduced by radiotherapy. In addition, radiotherapy also reduced TCI-induced bone loss. These findings suggest that radiotherapy may suppress bone cancer pain through inhibition of activation of cAMP-PKA signaling pathway in DRG and the spinal cord.
Mechanism of Xinfeng Capsule on Adjuvant-Induced Arthritis via Analysis of Urinary Metabolomic Profiles
Authors: Jiang Hui , Liu Jian , Wang Ting , Gao Jia-rong , Sun Yue , Huang Chuan-bing , Meng Mei , Qin Xiu-juan
Published: February 2016

We aimed to explore the potential effects of Xinfeng capsule (XFC) on urine metabolic profiling in adjuvant-induced arthritis (AA) rats by using gas chromatography time-of-flight mass spectrometry (GC-TOF/MS). GC-TOF/MS technology was combined with multivariate statistical approaches, such as principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal projections to latent structures discriminant analysis (OPLS-DA). These methods were used to distinguish the healthy group, untreated group, and XFC treated group and elucidate potential biomarkers. Nine potential biomarkers such as hippuric acid, adenine, and L-dopa were identified as potential biomarkers, indicating that purine metabolism, fat metabolism, amino acid metabolism, and energy metabolism were disturbed in AA rats. This study demonstrated that XFC is efficacious for RA and explained its potential metabolomics mechanism.
Robust Observer for a Class of Nonlinear SISO Dynamical Systems
Authors: Rosas David , Alvarez Joaquin , Rosas Patricia , Rascon Raul
Published: February 2016

A procedure to design an asymptotically stable second-order sliding mode observer for a class of single input single output (SISO) nonlinear systems in normal form is presented. The observer converges to the system state in spite of the existence of bounded disturbances and parameter uncertainties affecting the system dynamics. At the same time, the observer estimates the disturbances without the use of an additional filter to recover the equivalent control. The observer design is modular; each module of the observer is applied to each equation of state of the plant. Because of this, the proposed observer can be applied to a broader class of dynamic systems. The performance of the observer is illustrated in numerical and experimental form.
Orthogonal Analysis Based Performance Optimization for Vertical Axis Wind Turbine
Authors: Song Lei , Liu Hong-Zhao , Yang Zong-Xiao
Published: February 2016

Geometrical shape of a vertical axis wind turbine (VAWT) is composed of multiple structural parameters. Since there are interactions among the structural parameters, traditional research approaches, which usually focus on one parameter at a time, cannot obtain performance of the wind turbine accurately. In order to exploit overall effect of a novel VAWT, we firstly use a single parameter optimization method to obtain optimal values of the structural parameters, respectively, by Computational Fluid Dynamics (CFD) method; based on the results, we then use an orthogonal analysis method to investigate the influence of interactions of the structural parameters on performance of the wind turbine and to obtain optimization combination of the structural parameters considering the interactions. Results of analysis of variance indicate that interactions among the structural parameters have influence on performance of the wind turbine, and optimization results based on orthogonal analysis have higher wind energy utilization than that of traditional research approaches.
Supply Chain Coordination with Variable Backorder, Inspections, and Discount Policy for Fixed Lifetime Products
Authors: Sarkar Biswajit
Published: February 2016

This paper illustrates a channel coordination and quantity discounts between a vendor and a buyer with single-setup multi-delivery (SSMD) strategy to reduce the joint total cost among supply chain players. The benefit of the coordination between a buyer and a vendor is considered as the vendor requests to the buyer for changing the ordering quantity such that the vendor can be benefited from lower inventory costs. After accepting the buyer’s condition, the vendor compensates the buyer for his increased inventory cost and gives consent for additional savings by offering a quantity discount. The centralized decision making is examined for the effect of this strategy with the presence of backorder for buyer and inspection cost for the vendor. The quantity discount strategy, with the presence of variable backorder and inspections, can allow more savings for all players of supply chain. Some numerical examples, sensitivity analysis, and graphical representations are given to illustrate more savings from existing literature and comparisons between the several demand values.
A New Integral Inequality and Delay-Decomposition with Uncertain Parameter Approach to the Stability Analysis of Time-Delay Systems
Authors: Zhang Haiyang , Xiong Lianglin , Miao Qing , Wang Yanmeng , Peng Chen
Published: February 2016

This paper is concerned with the problem of delay-dependent stability of time-delay systems. Firstly, it introduces a new useful integral inequality which has been proved to be less conservative than the previous inequalities. Next, the inequality combines delay-decomposition approach with uncertain parameters applied to time-delay systems, based on the new Lyapunov-Krasovskii functionals and new stability criteria for system with time-delay have been derived and expressed in terms of LMIs. Finally, a numerical example is provided to show the effectiveness and the less conservative feature of the proposed method compared with some recent results.
School Absenteeism due to Toothache among Secondary School Students Aged 16–18 Years in the Ha’il Region of Saudi Arabia
Authors: Shaikh Sameer , Siddiqui Ammar Ahmed , Aljanakh Mohammad
Published: February 2016

Objective. This study assessed the impact of toothache on school attendance among secondary school students in the Ha’il Region, Saudi Arabia. Methods. A cross-sectional, paper based survey was conducted among 16–18-year-old students of public sector secondary schools in the Ha’il Region, Saudi Arabia. Results. Of the 510 students selected from the participating schools, 480 were analyzed (94.1%). Of the sample, 50.4% were boys. Among the participants in the study, 86 students reported school absence due to toothache in the six months prior to the survey. Consequently, the prevalence of absenteeism due to toothache in this study was of 18%. Conclusion. The prevalence of school absenteeism due to toothache among students in the Ha’il Region was low. Yet, still, missed school days due to toothache may have implications for students also in the Ha’il Region, Saudi Arabia, as school absenteeism leads to missed opportunities for learning and academic advancement.
Research on Resistor-Loaded Half-Ellipse Antenna System for GPR Application
Authors: Li Xueping , Shao Jinjin , Zhang Yu
Published: February 2016

A resistor-loaded half-ellipse antenna system mounted on a vehicle as a candidate for the exploration of the lunar subsurface is investigated. The antenna system includes two identical half-ellipse antennas, one is used for transmission, and the other is for reception. A resistive loading technique for broadening the bandwidth and improving impulse radiation is introduced. The performance of the proposed antenna with different height above ground surface is studied, and the influence of the vehicle on the antenna is analyzed. Then the antenna is manufactured and mounted on a vehicle as some tests are done. The simulated and measured antenna VSWR and radiation patterns are compared together, and good agreements between them are achieved.
Energy-Aware Low-Power CMOS LNA with Process-Variations Management
Authors: González Jorge Luis , Moreno Robson Luiz , Cruz Juan Carlos , Vázquez Diego
Published: February 2016

A reconfigurable low-noise amplifier (LNA) with digitally controllable gain and power consumption is presented. This architecture allows increasing power consumption only when required, that is, to improve LNA’s radiofrequency performance at extreme communication-channel conditions and/or to counteract the effect of process, voltage, and temperature variations. The proposed design leads to significant power saving when a relaxed operation is acceptable. The LNA is implemented in a 130 nm 1.2 V CMOS technology for a 2.4 GHz IEEE-802.15.4 application. Simulated LNA performance (taking into account the worst cases under process variations) is comparable to recently published works.
Antiobesity and Antidiabetes Effects of aCudrania tricuspidataHydrophilic Extract Presenting PTP1B Inhibitory Potential
Authors: Kim Dae Hoon , Lee Sooung , Chung Youn Wook , Kim Byeong Mo , Kim Hanseul , Kim Kunhong , Yang Kyung Mi
Published: February 2016

Diabetes and obesity represent the major health problems and the most age-related metabolic diseases. Protein-tyrosine phosphatase 1B (PTP1B) has emerged as an important regulator of insulin signal transduction and is regarded as a pharmaceutical target for metabolic disorders. To find novel natural materials presenting therapeutic activities against diabetes and obesity, we screened various herb extracts using a chip screening allowing the determination of PTP1B inhibitory effects of the tested compounds using insulin receptor (IR) as the substrate.Cudrania tricuspidataleaves (CTe) had a strong inhibitory effect on PTP1B activity and substantially inhibited fat accumulation in 3T3-L1 cells. CTe was orally administrated to diet-induced obesity (DIO) mice once daily for 3 weeks after which changes in glucose, insulin metabolism, and fat accumulation were examined. Hepatic enzyme markers (aspartate aminotransferase, AST, and alanine aminotransferase, ALT) and total fat mass and triglyceride levels decreased in CTe-treated mice, whereas body weight and total cholesterol concentration slightly decreased. CTe increased the phosphorylation of IRS-1 and Akt in liver tissue. Furthermore, CTe treatment significantly lowered blood glucose levels and improved insulin secretion in DIO mice. Our results strongly suggest that CTe may represent a promising therapeutic substance against diabetes and obesity.
Low-Cost Rotating Experimentation in Compressor Aerodynamics Using Rapid Prototyping
Authors: Michaud Mathias , Milan Petro Jr. , Vo Huu Duc
Published: February 2016

With the rapid evolution of additive manufacturing, 3D printed parts are no longer limited to display purposes but can also be used in structural applications. The objective of this paper is to show that 3D prototyping can be used to produce low-cost rotating turbomachinery rigs capable of carrying out detailed flow measurements that can be used, among other things, for computational fluid dynamics (CFD) code validation. A fully instrumented polymer two-stage axial-mixed flow compressor test rig was designed and fabricated with stereolithography (SLA) technology by a team of undergraduate students as part of a senior-year design course. Experiments were subsequently performed on this rig to obtain both the overall pressure rise characteristics of the compressor and the stagnation pressure distributions downstream of the blade rows for comparison with CFD simulations. In doing so, this work provides a first-of-a-kind assessment of the use of polymer additive technology for low-cost rotating turbomachinery experimentation with detailed measurements.
Potential of New-Generation Electron Beam Technology in Interface Modification of Cold and HVOF Sprayed MCrAlY Bond Coats
Authors: Cizek J. , Matejkova M. , Kouril J. , Cupera J. , Dlouhy I.
Published: February 2016

Electron beam (EB) technology treatment was carried out on CoNiCrAlY bond coats deposited on Inconel substrates via cold spray and HVOF techniques in dissimilar thicknesses. Such treatment was carried out with regard to the final materials microstructure, composition, surface roughness, and the quality of the coating-substrate interface. Following a multiple-step optimization of the processing parameters (such as beam pattern configuration, accelerating voltage, longitudinal speed, and multiple beam incidence), two final EB modifications were carried out on both coating types. It was found that the optimized EB treatment could lead to a significant alteration of the interface from a distinctive divide into smooth chemical and structural transition between the materials, significant decrease in surface roughness and porosity, and changes in mechanical properties (increase in Young’s modulus and decrease in hardness of the coating).
Obesity and Insulin Resistance Are the Main Determinants of Postprandial Lipoprotein Dysmetabolism in Polycystic Ovary Syndrome
Authors: Kyaw Tun Tommy , McGowan Anne , Phelan Niamh , Correia Neuman , Boran Gerard , O’Connor Anna-Louise , Roche Helen M. , Gibney James
Published: February 2016

Postprandial dyslipidaemia may be a plausible mechanism by which polycystic ovary syndrome (PCOS) increases cardiovascular risk. We sought to investigate whether the postprandial glucose and insulin and lipid and lipoprotein responses, including that of apolipoprotein B-48 (apoB-48) containing chylomicrons, to a mixed meal are different in obese PCOS women when compared to obese control subjects and whether differences, if any, are related to obesity, insulin resistance (IR), hyperandrogenaemia, or PCOS status. 26 women with PCOS (age30.4±1.2years (mean ± SEM), body mass index (BMI)36.8±1.5 kg/m2) and 26 non-PCOS subjects (age34.1±0.9years, BMI31.5±1.0 kg/m2) were studied before and up to 8 hours following a standard mixed meal. AUC-triglyceride (AUC-TG) was higher and AUC-high-density lipoprotein (AUC-HDL) lower in PCOS women. These differences were not apparent when BMI was accounted for. Insulin sensitivity (SI), AUC-apoB-48, and AUC-apolipoprotein B (AUC-apoB) were found to be independent predictors of AUC-TG, accounting for 55% of the variance. Only AUC-insulin remained significantly elevated following adjustment for BMI. Obesity related IR explains postprandial hypertriglyceridaemia and hyperinsulinaemic responses. Management of obesity in premenopausal women with PCOS is likely to reduce their cardiovascular risk burden.
Research Priorities, Measures, and Recommendations for Assessment of Tobacco Use in Clinical Cancer Research
Authors: Land Stephanie R. , Toll Benjamin A. , Moinpour Carol M. , Mitchell Sandra A. , Ostroff Jamie S. , Hatsukami Dorothy K. , Duffy Sonia A. , Gritz Ellen R. , Rigotti Nancy A. , Brandon Thomas H. , Prindiville Sheila A. , Sarna Linda P. , Schnoll Robert A. , Herbst Roy S. , Cinciripini Paul M. , Leischow Scott J. , Dresler Carolyn M. , Fiore Michael C. , Warren Graham W.
Published: February 2016

There is strong evidence that cigarette smoking causes adverse outcomes in people with cancer. However, more research is needed regarding those effects and the effects of alternative tobacco products and of secondhand smoke, the effects of cessation (before diagnosis, during treatment, or during survivorship), the biologic mechanisms, and optimal strategies for tobacco dependence treatment in oncology. Fundamentally, tobacco is an important source of variation in clinical treatment trials. Nevertheless, tobacco use assessment has not been uniform in clinical trials. Progress has been impeded by a lack of consensus regarding tobacco use assessment suitable for cancer patients. The NCI-AACR Cancer Patient Tobacco Use Assessment Task Force identified priority research areas and developed recommendations for assessment items and timing of assessment in cancer research. A cognitive interview study was conducted with 30 cancer patients at the NIH Clinical Center to evaluate and improve the measurement items. The resulting Cancer Patient Tobacco Use Questionnaire (C-TUQ) includes “Core” items for minimal assessment of tobacco use at initial and follow-up time points, and an “Extension” set. Domains include the following: cigarette and other tobacco use status, intensity, and past use; use relative to cancer diagnosis and treatment; cessation approaches and history; and secondhand smoke exposure. The Task Force recommends that assessment occur at study entry and, at a minimum, at the end of protocol therapy in clinical trials. Broad adoption of the recommended measures and timing protocol, and pursuit of the recommended research priorities, will help us to achieve a clearer understanding of the significance of tobacco use and cessation for cancer patients. Clin Cancer Res; 22(8); 1907–13. ©2016 AACR.
Feasibility and Acute Hemodynamic Effect of Left Ventricular Septal Pacing by Transvenous Approach Through the Interventricular Septum
Authors: Mafi-Rad Masih , Luermans Justin G.L.M. , Blaauw Yuri , Janssen Michel , Crijns Harry J. , Prinzen Frits W. , Vernooy Kevin
Published: February 2016

Background—

Left ventricular septal (LVS) pacing reduces ventricular dyssynchrony and improves cardiac function relative to right ventricular apex (RVA) pacing in animals. We aimed to establish permanent placement of an LVS pacing lead in patients using a transvenous approach through the interventricular septum.

Methods and Results—

Ten patients with sinus node dysfunction scheduled for dual-chamber pacemaker implantation were prospectively enrolled. A custom pacing lead with extended helix was introduced via the left subclavian vein and, after positioning against the right ventricular septum (RVS) using a preshaped guiding catheter, driven through the interventricular septum to the LVS. The acute hemodynamic effect of RVA, RVS, and LVS pacing was evaluated by invasive LVdP/dtmax measurements. The lead was successfully delivered to the LVS in all patients. Procedure time and fluoroscopy time shortened with experience. QRS duration was shorter during LVS pacing (144±20 ms) than during RVA (172±33 ms;
P
=0.02 versus LVS) and RVS pacing (165±17 ms;
P
=0.004 versus LVS). RVA and RVS pacing reduced LVdP/dtmax compared with baseline atrial pacing (−7.1±4.1% and −6.9±4.3%, respectively), whereas LVS pacing maintained LVdP/dtmax at baseline level (1.0±4.3%;
P
=0.001 versus RVA and RVS). R-wave amplitude and pacing threshold were 12.2±6.7 mV and 0.5±0.2 V at implant and remained stable during 6-month follow-up without lead-related complications.

Conclusions—

Permanent placement of an LVS pacing lead by transvenous approach through the interventricular septum is feasible in patients. LVS pacing preserves acute left ventricular pump function. This new pacing method could serve as an alternative and hemodynamically preferable approach for antibradycardia pacing.
Microdomains, Inflammation, and Atherosclerosis
Authors: Sorci-Thomas Mary G. , Thomas Michael J.
Published: February 2016

Elevated levels of cholesteryl ester (CE)–enriched apoB containing plasma lipoproteins lead to increased foam cell formation, the first step in the development of atherosclerosis. Unregulated uptake of low-density lipoprotein cholesterol by circulating monocytes and other peripheral blood cells takes place through scavenger receptors and over time causes disruption in cellular cholesterol homeostasis. As lipoproteins are taken up, their CE core is hydrolyzed by liposomal lipases to generate free cholesterol (FC). FC can be either re-esterified and stored as CE droplets or shuttled to the plasma membrane for ATP-binding cassette transporter A1–mediated efflux. Because cholesterol is an essential component of all cellular membranes, some FC may be incorporated into microdomains or lipid rafts. These platforms are essential for receptor signaling and transduction, requiring rapid assembly and disassembly. ATP-binding cassette transporter A1 plays a major role in regulating microdomain cholesterol and is most efficient when lipid-poor apolipoprotein AI (apoAI) packages raft cholesterol into soluble particles that are eventually catabolized by the liver. If FC is not effluxed from the cell, it becomes esterified, CE droplets accumulate and microdomain cholesterol content becomes poorly regulated. This dysregulation leads to prolonged activation of immune cell signaling pathways, resulting in receptor oversensitization. The availability of apoAI or other amphipathic α-helix–rich apoproteins relieves the burden of excess microdomain cholesterol in immune cells allowing a reduction in immune cell proliferation and infiltration, thereby stimulating regression of foam cells in the artery. Therefore, cellular balance between FC and CE is essential for proper immune cell function and prevents chronic immune cell overstimulation and proliferation.
Imaging Atherosclerosis
Authors: Tarkin Jason M. , Dweck Marc R. , Evans Nicholas R. , Takx Richard A.P. , Brown Adam J. , Tawakol Ahmed , Fayad Zahi A. , Rudd James H.F.
Published: February 2016

Advances in atherosclerosis imaging technology and research have provided a range of diagnostic tools to characterize high-risk plaque in vivo; however, these important vascular imaging methods additionally promise great scientific and translational applications beyond this quest. When combined with conventional anatomic- and hemodynamic-based assessments of disease severity, cross-sectional multimodal imaging incorporating molecular probes and other novel noninvasive techniques can add detailed interrogation of plaque composition, activity, and overall disease burden. In the catheterization laboratory, intravascular imaging provides unparalleled access to the world beneath the plaque surface, allowing tissue characterization and measurement of cap thickness with micrometer spatial resolution. Atherosclerosis imaging captures key data that reveal snapshots into underlying biology, which can test our understanding of fundamental research questions and shape our approach toward patient management. Imaging can also be used to quantify response to therapeutic interventions and ultimately help predict cardiovascular risk. Although there are undeniable barriers to clinical translation, many of these hold-ups might soon be surpassed by rapidly evolving innovations to improve image acquisition, coregistration, motion correction, and reduce radiation exposure. This article provides a comprehensive review of current and experimental atherosclerosis imaging methods and their uses in research and potential for translation to the clinic.
The Success Story of LDL Cholesterol Lowering
Authors: Pedersen Terje R.
Published: February 2016

We can look back at >100 years of cholesterol research that has brought medicine to a stage where people at risk of severe or fatal coronary heart disease have a much better prognosis than before. This progress has not come about without resistance. Perhaps one of the most debated topics in medicine, the cholesterol controversy, could only be brought to rest through the development of new clinical research methods that were capable of taking advantage of the amazing achievements in basic and pharmacological science after the second World War. It was only after understanding the biochemistry and physiology of cholesterol synthesis, transport and clearance from the blood that medicine could take advantage of drugs and diets to reduce the risk of atherosclerotic diseases. This review points to the highlights of the history of low-density lipoprotein-cholesterol lowering, with the discovery of the low-density lipoprotein receptor and its physiology and not only the development of statins as the stellar moments but also the development of clinical trial methodology as an effective tool to provide scientifically convincing evidence.
Vascular Smooth Muscle Cells in Atherosclerosis
Authors: Bennett Martin R. , Sinha Sanjay , Owens Gary K.
Published: February 2016

The historical view of vascular smooth muscle cells (VSMCs) in atherosclerosis is that aberrant proliferation of VSMCs promotes plaque formation, but that VSMCs in advanced plaques are entirely beneficial, for example preventing rupture of the fibrous cap. However, this view has been based on ideas that there is a homogenous population of VSMCs within the plaque, that can be identified separate from other plaque cells (particularly macrophages) using standard VSMC and macrophage immunohistochemical markers. More recent genetic lineage tracing studies have shown that VSMC phenotypic switching results in less-differentiated forms that lack VSMC markers including macrophage-like cells, and this switching directly promotes atherosclerosis. In addition, VSMC proliferation may be beneficial throughout atherogenesis, and not just in advanced lesions, whereas VSMC apoptosis, cell senescence, and VSMC-derived macrophage-like cells may promote inflammation. We review the effect of embryological origin on VSMC behavior in atherosclerosis, the role, regulation and consequences of phenotypic switching, the evidence for different origins of VSMCs, and the role of individual processes that VSMCs undergo in atherosclerosis in regard to plaque formation and the structure of advanced lesions. We think there is now compelling evidence that a full understanding of VSMC behavior in atherosclerosis is critical to identify therapeutic targets to both prevent and treat atherosclerosis.
Surprises From Genetic Analyses of Lipid Risk Factors for Atherosclerosis
Authors: Musunuru Kiran , Kathiresan Sekar
Published: February 2016

Observational epidemiological studies have associated plasma lipid concentrations with risk for coronary heart disease (CHD), but these studies cannot distinguish cause from mere correlation. Human genetic studies, when considered with the results of randomized controlled trials of medications, can potentially shed light on whether lipid biomarkers are causal for diseases. Genetic analyses and randomized trials suggest that low-density lipoprotein is causal for CHD, whereas high-density lipoprotein is not. Surprisingly, human genetic evidence suggests that lipoprotein(a) and triglyceride-rich lipoproteins causally contribute to CHD. Gene variants leading to higher levels of plasma apolipoprotein B-containing lipoproteins [low-density lipoprotein, triglyceride-rich lipoproteins, or lipoprotein(a)] consistently increase risk for CHD. For triglyceride-rich lipoproteins, the most compelling evidence revolves around lipoprotein lipase and its endogenous facilitator (APOA5 [apolipoprotein A-V]) and inhibitory proteins (APOC3 [apolipoprotein C-III], ANGPTL4 [angiopoietin like 4]). Combined, these genetic results anticipate that, beyond low-density lipoprotein, pharmacological lowering of triglyceride-rich lipoproteins or lipoprotein(a) will reduce risk for CHD, but this remains to be proven through randomized controlled trials.
Adaptive Response of T and B Cells in Atherosclerosis
Authors: Ketelhuth Daniel F.J. , Hansson Göran K.
Published: February 2016

Atherosclerosis is a chronic inflammatory disease that is initiated by the retention and accumulation of cholesterol-containing lipoproteins, particularly low-density lipoprotein, in the artery wall. In the arterial intima, lipoprotein components that are generated through oxidative, lipolytic, and proteolytic activities lead to the formation of several danger-associated molecular patterns, which can activate innate immune cells as well as vascular cells. Moreover, self- and non-self-antigens, such as apolipoprotein B-100 and heat shock proteins, can contribute to vascular inflammation by triggering the response of T and B cells locally. This process can influence the initiation, progression, and stability of plaques. Substantial clinical and experimental data support that the modulation of adaptive immune system may be used for treating and preventing atherosclerosis. This may lead to the development of more selective and less harmful interventions, while keeping host defense mechanisms against infections and tumors intact. Approaches such as vaccination might become a realistic option for cardiovascular disease, especially if they can elicit regulatory T and B cells and the secretion of atheroprotective antibodies. Nevertheless, difficulties in translating certain experimental data into new clinical therapies remain a challenge. In this review, we discuss important studies on the function of T- and B-cell immunity in atherosclerosis and their manipulation to develop novel therapeutic strategies against cardiovascular disease.
From Loci to Biology
Authors: Nurnberg Sylvia T. , Zhang Hanrui , Hand Nicholas J. , Bauer Robert C. , Saleheen Danish , Reilly Muredach P. , Rader Daniel J.
Published: February 2016

Genome-wide association studies have provided a rich collection of ≈58 coronary artery disease (CAD) loci that suggest the existence of previously unsuspected new biology relevant to atherosclerosis. However, these studies only identify genomic loci associated with CAD, and many questions remain even after a genomic locus is definitively implicated, including the nature of the causal variant(s) and the causal gene(s), as well as the directionality of effect. There are several tools that can be used for investigation of the functional genomics of these loci, and progress has been made on a limited number of novel CAD loci. New biology regarding atherosclerosis and CAD will be learned through the functional genomics of these loci, and the hope is that at least some of these new pathways relevant to CAD pathogenesis will yield new therapeutic targets for the prevention and treatment of CAD.
Macrophages and Dendritic Cells
Authors: Cybulsky Myron I. , Cheong Cheolho , Robbins Clinton S.
Published: February 2016

Atherosclerosis is a complex chronic disease. The accumulation of myeloid cells in the arterial intima, including macrophages and dendritic cells (DCs), is a feature of early stages of disease. For decades, it has been known that monocyte recruitment to the intima contributes to the burden of lesion macrophages. Yet, this paradigm may require reevaluation in light of recent advances in understanding of tissue macrophage ontogeny, their capacity for self-renewal, as well as observations that macrophages proliferate throughout atherogenesis and that self-renewal is critical for maintenance of macrophages in advanced lesions. The rate of atherosclerotic lesion formation is profoundly influenced by innate and adaptive immunity, which can be regulated locally within atherosclerotic lesions, as well as in secondary lymphoid organs, the bone marrow and the blood. DCs are important modulators of immunity. Advances in the past decade have cemented our understanding of DC subsets, functions, hematopoietic origin, gene expression patterns, transcription factors critical for differentiation, and provided new tools for study of DC biology. The functions of macrophages and DCs overlap to some extent, thus it is important to reassess the contributions of each of these myeloid cells taking into account strict criteria of cell identification, ontogeny, and determine whether their key roles are within atherosclerotic lesions or secondary lymphoid organs. This review will highlight key aspect of macrophage and DC biology, summarize how these cells participate in different stages of atherogenesis and comment on complexities, controversies, and gaps in knowledge in the field.
Epidemiology of Atherosclerosis and the Potential to Reduce the Global Burden of Atherothrombotic Disease
Authors: Herrington William , Lacey Ben , Sherliker Paul , Armitage Jane , Lewington Sarah
Published: February 2016

Atherosclerosis is a leading cause of vascular disease worldwide. Its major clinical manifestations include ischemic heart disease, ischemic stroke, and peripheral arterial disease. In high-income countries, there have been dramatic declines in the incidence and mortality from ischemic heart disease and ischemic stroke since the middle of the 20th century. For example, in the United Kingdom, the probability of death from vascular disease in middle-aged men (35–69 years) has decreased from 22% in 1950 to 6% in 2010. Most low- and middle-income countries have also reported declines in mortality from stroke over the last few decades, but mortality trends from ischemic heart disease have been more varied, with some countries reporting declines and others reporting increases (particularly those in Eastern Europe and Asia). Many major modifiable risk factors for atherosclerosis have been identified, and the causal relevance of several risk factors is now well established (including, but not limited to, smoking, adiposity, blood pressure, blood cholesterol, and diabetes mellitus). Widespread changes in health behaviors and use of treatments for these risk factors are responsible for some of the dramatic declines in vascular mortality in high-income countries. In order that these declines continue and are mirrored in less wealthy nations, increased efforts are needed to tackle these major risk factors, particularly smoking and the emerging obesity epidemic.
Silent Brain Infarction and Risk of Future Stroke
Authors: Gupta Ajay , Giambrone Ashley E. , Gialdini Gino , Finn Caitlin , Delgado Diana , Gutierrez Jose , Wright Clinton , Beiser Alexa S. , Seshadri Sudha , Pandya Ankur , Kamel Hooman
Published: February 2016

Background and Purpose—

Silent brain infarction (SBI) on magnetic resonance imaging has been proposed as a subclinical risk marker for future symptomatic stroke. We performed a systematic review and meta-analysis to summarize the association between magnetic resonance imaging–defined SBI and future stroke risk.

Methods—

We searched the medical literature to identify cohort studies involving adults with SBI detected by magnetic resonance imaging who were subsequently followed up for incident clinically defined stroke. Study data and quality assessment were recorded in duplicate with disagreements in data extraction resolved by a third reader. Strength association between magnetic resonance imaging–detected SBI and future symptomatic stroke was measured by an hazard ratio.

Results—

The meta-analysis included 13 studies (14 764 subjects) with a mean follow-up ranging from 25.7 to 174 months. SBI predicted the occurrence of stroke with a random effects crude relative risk of 2.94 (95% confidence interval, 2.24–3.86,
P
<0.001;
Q
=39.65,
P
<0.001). In the 8 studies of 10 427 subjects providing hazard ratio adjusted for cardiovascular risk factors, SBI was an independent predictor of incident stroke (hazard ratio, 2.08 [95% confidence interval, 1.69–2.56;
P
<0.001];
Q
=8.99;
P
=0.25). In a subgroup analysis pooling 9483 stroke-free individuals from large population-based studies, SBI was present in ≈18% of participants and remained a strong predictor of future stroke (hazard ratio, 2.06 [95% confidence interval, 1.64–2.59];
P
<0.01).

Conclusions—

SBI is present in ≈1 in 5 stroke-free older adults and is associated with a 2-fold increased risk of future stroke. Future studies of in-depth stroke risk evaluations and intensive prevention measures are warranted in patients with clinically unrecognized radiologically evident brain infarctions.
Validation of the Chinese names Bischofia racemosa (Euphorbiaceae), Ulmus erythrocarpa and Ulmus multinervis (Ulmaceae)
Authors: DUAN YI-FAN , LI YONG-FU , YANG XIN-XIN , WANG XIAN-RONG
Published: February 2016

While studying the type specimens housed at NF (Nanjing Forestry University Herbarium, Nanjing, China), we found that three names, Bischofia racemosa Cheng & Chu in Cheng et al. (1963: 13) (Euphorbiaceae), Ulmus erythrocarpa Cheng (1958: 72) (Ulmaceae) and U. multinervis Cheng (1958: 70) (Ulmaceae), were not validly published, because two or three gatherings were designated as types for each name (ICN Art. 40.2; McNeill et al. 2012). Here we validate these three names by choosing one specimen as the type for each of them.
Progress in Intra-industry Trade in the Greater Mekong Sub-region
Authors: Nozaki Kenji
Published: February 2016

The Greater Mekong Sub-region (GMS) attracts investors’ interest today and economic linkage in the GMS is strengthening with the creation of a production network. This paper analyzes the division of labour in the production process by industry. Two industrial sectors are chosen, the clothing industry and automobile industry. Two types of analysis were conducted in this study: one is a detailed analysis of trade figures, with calculation of the Grubel and Lloyd indexes and unit trade value, and the other is the estimation of gravity model. Their results are consistent. In the clothing sector, which is a labour-intensive industry, intra-industry trades include items by both horizontal division of labour and vertical division of labour. In contrast, the automobile sector does not exhibit horizontal division of labour, and signs of vertical division of labour between Thailand and Vietnam are observed. As different types of industry involve the different types of production network, further research will be needed.
Facile creation of modified surface possessing the controlled wettability between superamphiphobic and superoleophobic–superhydrophilic characteristics by using perfluorocarboxamides/calcium carbonate/calcium fluoride nanocomposites: Application to the separation of oil and water
Authors: Saito Tomoya , Tsushima Yusei , Honda Tsunetoshi , Kamiya Takeshi , Fujita Masato , Sawada Hideo
Published: February 2016

A variety of perfluoroacyl fluorides such as perfluoro-3-(1-piperidinyl)propionyl fluoride, perfluoro-2-methyl-3-morpholinopropionyl fluoride, perfluoro-3-di- n-propylaminopropionyl fluoride, and perfluoro-3-di- n-butylaminopropionyl fluoride were applied to the nanocomposite reactions with calcium carbonate nanoparticles under alkaline conditions to afford the corresponding perfluorocarboxamides/calcium carbonate/calcium fluoride nanocomposites. The modified glass surfaces treated with the fluorinated nanocomposites, which were prepared by using perfluoro-2-methyl-3-morpholinopropionyl fluoride and perfluoro-3-(1-piperidinyl)propionyl fluoride, afforded an oleophobic–superhydrophilic characteristic. The fluorinated nanocomposites, of whose each preparative feed ratio of perfluoro-3-di- n-propylaminopropionyl fluoride (or PF-DBAPF) and CaCO3 is 0.50 (g/g) (2.50 (mol/mol) ), can provide a superamphiphobic characteristic on the modified surfaces; however, the lower feed ratios: 0.25–0.17 (g/g) (1.25–0.83 (mol/mol)) of the acyl fluorides based on CaCO3 can afford a superoleophobic–superhydrophilic characteristic on the modified surfaces. The similar wettability was observed on the modified filter paper and polyethylene terephthalate fabric surfaces by using the fluorinated nanocomposites, which were prepared with perfluoro-3-di- n-butylaminopropionyl fluoride. Interestingly, these modified filter paper and polyethylene terephthalate fabric swatch were applied to the separation membranes for not only the mixture of oil and water but also the oil-in-water emulsion. The modified filter paper treated with the fluorinated nanocomposites possessing a superamphiphobic characteristic was also applied to the separation membrane for the mixture of fluorocarbon and hydrocarbon.