bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth and Analysis of NSH and KMNSH Crystals by Slow Evaporation Technique
Authors: Masilamani V. , Shanthi J. , Sheelarani V.
Published: March 2014

Nickel sulphate hexahydrate (NSH) and potassium magnesium nickel sulphate hexahydrate (KMNSH) single crystals were grown by slow evaporation method. The grown NSH crystal was found to crystallize in tetragonal system with space group P41 21 2 and KMNSH in monoclinic system with space group P121/c. The optical band gap energies of the grown crystals using UV-Vis spectral results for the doped and undoped NSH crystals were calculated. The presence of various functional groups in the crystal was identified by FTIR analysis. The thermal behaviour of the grown crystal has been studied by TGA/DTA analysis.
An Energy-Efficient Cooperative Communication Method for Wireless Sensor Networks
Authors: Lee Kyuhong , Lee Heesang
Published: March 2014

Energy efficiency is one of the most important issues for operations of wireless sensor networks. To increase network lifetime and to reduce energy consumption of sensor nodes, many clustering and routing protocols have been studied. In this paper, we propose an energy-efficient cooperative communication method which forms clusters and establishes intercluster routes directly or via relay nodes. Relay nodes selected by the cooperation of adjacent cluster heads along with their cluster members can prevent long-haul transmissions of cluster heads. This can reduce the energy consumption of cluster heads. We show the validity of using relay nodes and then compare the performance of the proposed method with that of a well-known clustering and routing protocol for wireless sensor networks. Our computational experiments demonstrate that network lifetime, energy consumption, and scalability of the proposed method are better than those of the compared method.
N-acetyl-seryl-aspartyl-lysyl-proline Inhibits Diabetes-Associated Kidney Fibrosis and Endothelial-Mesenchymal Transition
Authors: Nagai Takako , Kanasaki Megumi , Srivastava Swayam Prakash , Nakamura Yuka , Ishigaki Yasuhito , Kitada Munehiro , Shi Sen , Kanasaki Keizo , Koya Daisuke
Published: March 2014

Endothelial-to-mesenchymal transition (EndMT) emerges as an important source of fibroblasts. MicroRNA let-7 exhibits anti-EndMT effects and fibroblast growth factor (FGF) receptor has been shown to be an important in microRNA let-7 expression. The endogenous antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is a substrate of angiotensin-converting enzyme (ACE). Here, we found that AcSDKP inhibited the EndMT and exhibited fibrotic effects that were associated with FGF receptor-mediated anti-fibrotic program. Conventional ACE inhibitor plus AcSDKP ameliorated kidney fibrosis and inhibited EndMT compared to therapy with the ACE inhibitor alone in diabetic CD-1 mice. The endogenous AcSDKP levels were suppressed in diabetic animals. Cytokines induced cultured endothelial cells into EndMT; coincubation with AcSDKP inhibited EndMT. Expression of microRNA let-7 family was suppressed in the diabetic kidney; antifibrotic and anti-EndMT effects of AcSDKP were associated with the restoration of microRNA let-7 levels. AcSDKP restored diabetes- or cytokines-suppressed FGF receptor expression/phosphorylation into normal levels both in vivo and in vitro. These results suggest that AcSDKP is an endogenous antifibrotic molecule that has the potential to cure diabetic kidney fibrosis via an inhibition of the EndMT associated with the restoration of FGF receptor and microRNA let-7.
Association between Parathyroid Hormone Levels and Inflammatory Markers among US Adults
Authors: Cheng Shih-Ping , Liu Chien-Liang , Liu Tsang-Pai , Hsu Yi-Chiung , Lee Jie-Jen
Published: March 2014

Background and Aims. High levels of parathyroid hormone (PTH) appear to be associated with an increased mortality. Previous studies concerning the relationship of inflammatory markers with hyperparathyroidism have yielded inconsistent results. This study investigated whether serum PTH concentrations were independently associated with several inflammatory markers among the US adults.Materials and Methods. Using data from the National Health and Nutrition Examination Survey, we examined the relation between serum PTH and C-reactive protein (CRP), red cell distribution width (RDW), and platelet-to-lymphocyte ratio (PLR) levels with weighted linear regression. Additionally, we examined the relation with increased modified Glasgow Prognostic Score (mGPS) by using weighted logistic regression.Results. CRP, RDW, and PLR values increased with increasing serum PTH concentration. After extensively adjusting for covariates, CRP and RDW increased linearly and across PTH categories (allP<0.001), while PLR marginally increased (P=0.190andP=0.095using PTH as a categorical and continuous variable, resp.). The odds ratio of increased mGPS was 1.11 and 1.31 across PTH categories and with increasing PTH levels continuously.Conclusion. These nationally representative data indicate that serum PTH levels are independently associated with several inflammatory markers in the US population. The casual relationship between PTH levels and inflammation remains to be elucidated.
Cross-Layer Optimization Scheme Using Cooperative Diversity for Reliable Data Transfer in Wireless Sensor Networks
Authors: Chen Yongrui , Qin Fei , Xing Yulong , Buranapanichkit Dujdow
Published: March 2014

Cooperative diversity has been shown to provide significant performance gains in wireless networks where communication is impeded by channel fading. In resource constraint networks, the advantages of cooperation can be further exploited by optimally allocating the energy and bandwidth resources among users in a cross-layer way. In this paper, we investigate the problem of transmission power minimization and network lifetime maximization using cooperative diversity for wireless sensor networks, under the constraint of a target end-to-end transmission reliability and a given transmission rate. By utilizing a cross-layer optimization scheme, distributive algorithms which jointly consider routing, relay selection, and power allocation strategies are proposed for the reliability constraint wireless sensor networks. We demonstrate through simulations that the proposed cross-layer cooperative strategies achieve significant energy savings and prolong the network lifetime considerably.
Assessment of a Human Cadaver Model for Training Emergency Medicine Residents in the Ultrasound Diagnosis of Pneumothorax
Authors: Adhikari Srikar , Zeger Wesley , Wadman Michael , Walker Richard , Lomneth Carol
Published: March 2014

Objectives. To assess a human cadaver model for training emergency medicine residents in the ultrasound diagnosis of pneumothorax.Methods. Single-blinded observational study using a human cadaveric model at an academic medical center. Three lightly embalmed cadavers were used to create three “normal lungs” and three lungs modeling a “pneumothorax.” The residents were blinded to the side and number of pneumothoraces, as well as to each other’s findings. Each resident performed an ultrasound examination on all six lung models during ventilation of cadavers. They were evaluated on their ability to identify the presence or absence of the sliding-lung sign and seashore sign.Results. A total of 84 ultrasound examinations (42-“normal lung,” 42-“pneumothorax”) were performed. A sliding-lung sign was accurately identified in 39 scans, and the seashore sign was accurately identified in 34 scans. The sensitivity and specificity for the sliding-lung sign were 93% (95% CI, 85–100%) and 90% (95% CI, 81–99%), respectively. The sensitivity and specificity for the seashore sign were 80% (95% CI, 68–92%) and 83% (95% CI, 72–94%), respectively.Conclusions. Lightly embalmed human cadavers may provide an excellent model for mimicking the sonographic appearance of pneumothorax.
Design Optimization of a Transonic-Fan Rotor Using Numerical Computations of the Full Compressible Navier-Stokes Equations and Simplex Algorithm
Authors: Aziz M. A. , Owis Farouk M. , Abdelrahman M. M.
Published: March 2014

The design of a transonic-fan rotor is optimized using numerical computations of the full three-dimensional Navier-Stokes equations. The CFDRC-ACE multiphysics module, which is a pressure-based solver, is used for the numerical simulation. The code is coupled with simplex optimization algorithm. The optimization process is started from a suitable design point obtained using low fidelity analytical methods that is based on experimental correlations for the pressure losses and blade deviation angle. The fan blade shape is defined by its stacking line and airfoil shape which are considered the optimization parameters. The stacking line is defined by lean, sweep, and skews, while blade airfoil shape is modified considering the thickness and camber distributions. The optimization has been performed to maximize the rotor total pressure ratio while keeping the rotor efficiency and surge margin above certain required values. The results obtained are verified with the experimental data of Rotor 67. In addition, the results of the optimized fan indicate that the optimum design is found to be leaned in the direction of rotation and has a forward sweep from the hub to mean section and backward sweep to the tip. The pressure ratio increases from 1.427 to 1.627 at the design speed and mass flow rate.
Research of Compound Control for DC Motor System Based on Global Sliding Mode Disturbance Observer
Authors: Zhang He , Ge Liang , Shi Mingjiang , Yang Qing
Published: March 2014

Aiming at the problems of modeling errors, parameter variations, and load moment disturbances in DC motor control system, one global sliding mode disturbance observer (GSMDO) is proposed based on the global sliding mode (GSM) control theory. The output of GSMDO is used as the disturbance compensation in control system, which can improve the robust performance of DC motor control system. Based on the designed GSMDO in inner loop, one compound controller, composed of a feedback controller and a feedforward controller, is proposed in order to realize the position tracking of DC motor system. The gains of feedback controller are obtained by means of linear quadratic regulator (LQR) optimal control theory. Simulation results present that the proposed control scheme possesses better tracking properties and stronger robustness against modeling errors, parameter variations, and friction moment disturbances. Moreover, its structure is simple; therefore it is easy to be implemented in engineering.
Resveratrol Oligomers for the Prevention and Treatment of Cancers
Authors: Xue You-Qiu , Di Jin-Ming , Luo Yun , Cheng Ke-Jun , Wei Xing , Shi Zhi
Published: March 2014

Resveratrol (3,4′,5-trihydroxystilbene) is a naturally derived phytoalexin stilbene isolated from grapes and other plants, playing an important role in human health and is well known for its extensive bioactivities, such as antioxidation, anti-inflammatory, anticancer. In addition to resveratrol, scientists also pay attention to resveratrol oligomers, derivatives of resveratrol, which are characterized by the polymerization of two to eight, or even more resveratrol units, and are the largest group of oligomeric stilbenes. Resveratrol oligomers have multiple beneficial properties, of which some are superior in activity, stability, and selectivity compared with resveratrol. The complicated structures and diverse biological activities are of significant interest for drug research and development and may provide promising prospects as cancer preventive and therapeutical agents. This review presents an overview on preventive or anticancer properties of resveratrol oligomers.
Empirical Research on Decoupling Relationship between Energy-Related Carbon Emission and Economic Growth in Guangdong Province Based on Extended Kaya Identity
Authors: Wang Wenxiu , Kuang Yaoqiu , Huang Ningsheng , Zhao Daiqing
Published: March 2014

The decoupling elasticity decomposition quantitative model of energy-related carbon emission in Guangdong is established based on the extended Kaya identity and Tapio decoupling model for the first time, to explore the decoupling relationship and its internal mechanism between energy-related carbon emission and economic growth in Guangdong. Main results are as follows. (1) Total production energy-related carbon emissions in Guangdong increase from4128×104 tC in 1995 to14396×104 tC in 2011. Decoupling elasticity values of energy-related carbon emission and economic growth increase from 0.53 in 1996 to 0.85 in 2011, and its decoupling state turns from weak decoupling in 1996–2004 to expansive coupling in 2005–2011. (2) Land economic output and energy intensity are the first inhibiting factor and the first promoting factor to energy-related carbon emission decoupling from economic growth, respectively. The development speeds of land urbanization and population urbanization, especially land urbanization, play decisive roles in the change of total decoupling elasticity values. (3) Guangdong can realize decoupling of energy-related carbon emission from economic growth effectively by adjusting the energy mix and industrial structure, coordinating the development speed of land urbanization and population urbanization effectively, and strengthening the construction of carbon sink.
Colorectal Cancer: Prevention and Management of Metastatic Disease
Authors: Sugarbaker Paul H.
Published: March 2014

This paper compared the similarities and differences of the two most common types of colorectal cancer metastases. The treatment of liver metastases by surgery combined with systemic chemotherapy was explained. The different natural history of liver metastases as compared to peritoneal metastases and the possibility for prevention of peritoneal metastases were emphasized. Perioperative cancer chemotherapy or second-look surgery must be considered as individualized treatments of selected patients who have small volume peritoneal metastases or who are known to be at risk for subsequent disease progression on peritoneal surfaces. However, the fact that peritoneal metastases, when diagnosed in the follow-up of colorectal cancer patients, can be cured with a combination of cytoreductive surgery and hyperthermic perioperative chemotherapy cannot be ignored. Careful follow-up and timely intervention in colorectal cancer patients with progressive disease are a necessary part of the management strategies recommended by the multidisciplinary team. After a critical evaluation of the data currently available, these strategies for prevention and management of colorectal metastases are presented as the author’s recommendations for a high standard of care. As more information becomes available, modifications may be necessary.
Reduced Renshaw Recurrent Inhibition after Neonatal Sciatic Nerve Crush in Rats
Authors: Shu Liang , Su Jingjing , Jing Lingyan , Huang Ying , Di Yu , Peng Lichao , Liu Jianren
Published: March 2014

Renshaw recurrent inhibition (RI) plays an important gated role in spinal motion circuit. Peripheral nerve injury is a common disease in clinic. Our current research was designed to investigate the change of the recurrent inhibitory function in the spinal cord after the peripheral nerve crush injury in neonatal rat. Sciatic nerve crush was performed on 5-day-old rat puppies and the recurrent inhibition between lateral gastrocnemius-soleus (LG-S) and medial gastrocnemius (MG) motor pools was assessed by conditioning monosynaptic reflexes (MSR) elicited from the sectioned dorsal roots and recorded either from the LG-S and MG nerves by antidromic stimulation of the synergist muscle nerve. Our results demonstrated that the MSR recorded from both LG-S or MG nerves had larger amplitude and longer latency after neonatal sciatic nerve crush. The RI in both LG-S and MG motoneuron pools was significantly reduced to virtual loss (15–20% of the normal RI size) even after a long recovery period upto 30 weeks after nerve crush. Further, the degree of the RI reduction after tibial nerve crush was much less than that after sciatic nerve crush indicatig that the neuron-muscle disconnection time is vital to the recovery of the spinal neuronal circuit function during reinnervation. In addition, sciatic nerve crush injury did not cause any spinal motor neuron loss but severally damaged peripheral muscle structure and function. In conclusion, our results suggest that peripheral nerve injury during neonatal early development period would cause a more sever spinal cord inhibitory circuit damage, particularly to the Renshaw recurrent inhibition pathway, which might be the target of neuroregeneration therapy.
Rain Height Statistics Based on 0°C Isotherm Height Using TRMM Precipitation Data for Earth-Space Satellite Links in Nigeria
Authors: Ojo Joseph Sunday
Published: March 2014

In the prediction of attenuation due to precipitation related phenomena, the 0°C isotherm height plays a vital role. In this paper, 2 years of precipitation data obtained from the Tropical Rain Measuring Mission (TRMM) satellite had been analyzed to establish the distribution of rain height based on 0°C isotherm heights over six locations in Nigeria. Probability of exceedance of rain heights in each of the locations was compared between the two seasons in Nigeria. Rain heights distribution was also compared with the ITU-R P.839 recommendation. The overall results show seasonal, rainfall type’s dependence and overestimation of the rain height predicted by the ITU for Nigeria.
Invariant Statistical Convergence of Sequences of Sets with respect to a Modulus Function
Authors: Pancaroglu Nimet , Nuray Fatih
Published: March 2014

We introduce and study the concept of invariant convergence for sequences of sets with respect to modulus functionfand give some inclusion relations.
A Second Trimester Caesarean Scar Pregnancy
Authors: Sikka Pooja , Suri Vanita , Chopra Seema , Aggarwal Neelam
Published: March 2014

Caesarean scar pregnancy, where conceptus is implanted on previous scar, is a rare entity. We present one such case of scar pregnancy presenting to us in the second trimester and was managed with methotrexate and uterine artery embolization, followed by hysterotomy. Uterus could be conserved and hysterectomy could be avoided.
Ultrastructure of Intervertebral Disc and Vertebra-Disc Junctions Zones as a Link in Etiopathogenesis of Idiopathic Scoliosis
Authors: Burger Evalina L. , Noshchenko Andriy , Patel Vikas V. , Lindley Emily M. , Bradford Andrew P.
Published: March 2014

Background Context. There is no general accepted theory on the etiology of idiopathic scoliosis (IS). An important role of the vertebrae endplate physes (VEPh) and intervertebral discs (IVD) in spinal curve progression is acknowledged, but ultrastructural mechanisms are not well understood.Purpose. To analyze the current literature on ultrastructural characteristics of VEPh and IVD in the context of IS etiology.Study Design/Setting. A literature review.Results. There is strong evidence for multifactorial etiology of IS. Early wedging of vertebra bodies is likely due to laterally directed appositional bone growth at the concave side, caused by a combination of increased cell proliferation at the vertebrae endplate and altered mechanical properties of the outer annulus fibrosus of the adjacent IVD. Genetic defects in bending proteins necessary for IVD lamellar organization underlie altered mechanical properties. Asymmetrical ligaments, muscular stretch, and spine instability may also play roles in curve formation.Conclusions. Development of a reliable, cost effective method for identifying patients at high risk for curve progression is needed and could lead to a paradigm shift in treatment options. Unnecessary anxiety, bracing, and radiation could potentially be minimized and high risk patient could receive surgery earlier, rendering better outcomes with fewer fused segments needed to mitigate curve progression.
Regulating Inflammation Using Acid-Responsive Electrospun Fibrous Scaffolds for Skin Scarless Healing
Authors: Yuan Ziming , Zhao Jingwen , Chen Yigang , Yang Zhili , Cui Wenguo , Zheng Qi
Published: March 2014

Skin injury in adult mammals brings about a series of events and inflammation in the wounded area is initiated first and provides lots of inflammatory factors, which is critical for the final scar formation. While the postinjured skin of fetus and nude mice heals scarlessly owing to the absence of inflammation or immunodeficient, we designed a feasible acid-responsive ibuprofen-loaded poly(L-lactide) (PLLA) fibrous scaffolds via doping sodium bicarbonate to prevent excessive inflammation and achieve scarless healing finally. The morphological results of in vivo experiments revealed that animals treated with acid-responsive ibuprofen-loaded PLLA fibrous scaffolds exhibited alleviative inflammation, accelerated healing process, and regulated collagen deposition via interference in the collagen distribution, theα-smooth muscle actin (α-SMA), and the basic fibroblast growth factor (bFGF) expression. The lower ratios of collagen I/collagen III and TGF-β1/TGF-β3 and higher ratio of matrix metalloproteinase-1 (MMP-1)/tissue inhibitor of metalloproteinase-1 (TIMP-1) in acid-responsive ibuprofen-loaded PLLA fibrous scaffolds group were confirmed by real-time qPCR as well. These results suggest that inhibiting the excessive inflammation will result in regular collagen distribution and appropriate ratio between the factors, which promote or suppress the scar formation, then decrease the scar area, and finally achieve the scarless healing.
Utilization of a Continuous External Tissue Expansion System to Assist in Primary Closure of a Large Anterolateral Thigh Donor Site Defect
Authors: Silver Andrew G. , Baynosa Richard C.
Published: March 2014

Primary closure of a large anterolateral thigh (ALT) flap donor site defect with the assistance of an external tissue expansion system is presented. The dimensions of this donor site (12 cm × 40 cm) and its percentage of leg circumference (34%) would make this site likely to require skin grafting or further flap coverage based on the results of previously published literature.
Existence and Uniqueness Theorems for Impulsive Fractional Differential Equations with the Two-Point and Integral Boundary Conditions
Authors: Mardanov M. J. , Mahmudov N. I. , Sharifov Y. A.
Published: March 2014

We study a boundary value problem for the system of nonlinear impulsive fractional differential equations of orderα  0<α≤1involving the two-point and integral boundary conditions. Some new results on existence and uniqueness of a solution are established by using fixed point theorems. Some illustrative examples are also presented. We extend previous results even in the integer caseα=1.
Kolaviron Improved Resistance to Oxidative Stress and Inflammation in the Blood (Erythrocyte, Serum, and Plasma) of Streptozotocin-Induced Diabetic Rats
Authors: Ayepola Omolola R. , Brooks Nicole L. , Oguntibeju Oluwafemi O.
Published: March 2014

Aims.Bitter kola seed (Garcinia kola, family:Guttiferae) has been used as a social masticatory agent in Africa for several years and is believed to possess many useful medicinal properties. The present study evaluates the antioxidative, anti-inflammatory, and antilipidemic effects of kolaviron (an extract from theGarcinia kolaseeds) in the blood of streptozotocin- (STZ) induced diabetic rats.Methods.Diabetic rats were treated with kolaviron (100 mg/kg b·wt) orally, five times a week for a period of six weeks. Serum glucose andHBA1Cconcentrations were estimated in experimental groups. The activities of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) (in erythrocytes) as well as plasma concentration of malondialdehyde (MDA), a product of lipid peroxidation, oxygen radical absorbing capacity (ORAC) and ferric-reducing antioxidant power (FRAP) were investigated. Serum levels of proinflammatory cytokines and growth factor: interleukin- (IL-) 1, monocyte chemotactic protein-1 (MCP-1), and vascular endothelial growth factor (VEGF), respectively, were also analyzed.Results.Kolaviron treatment markedly improved antioxidant status and abated inflammatory response evidenced by reduction in the levels of proinflammatory cytokines and growth factor, lipid peroxidation product, and the restoration of activities of erythrocyte antioxidant enzymes in the blood of diabetic rats.Conclusion.Kolaviron improved antioxidant status, reduced inflammation, and protected against hyperglycemic-induced oxidative damage in the blood of diabetic rats.
A Uniform Clustering Mechanism for Wireless Sensor Networks
Authors: Enam Rabia Noor , Qureshi Rehan , Misbahuddin Syed
Published: March 2014

In wireless sensor networks with dynamic clustering, the cluster heads are usually not selected on the basis of their locations. This causes irregular distribution of cluster heads and highly variable number of nodes in the clusters. Also, some of the clusters are spread over large areas within the network, causing limited spatial correlation between associated sensor nodes. These irregularities in cluster placements and dimensions negatively impact the efficiency of a wireless sensor network. For example, for a cooperative data aggregation, it necessitates variable or large sized packets while the aggregations, based on spatial correlation of sensor nodes, cannot be exploited easily. In this paper, we have developed a Distributed Uniform Clustering Algorithm (DUCA) for cluster based WSN. In DUCA, cluster formation mechanism is based on a virtual-grid system and sensing ranges of nodes that provide even distribution of clusters, homogenized cluster sizes, and reduced energy consumption. Simulation results show that DUCA improves the distribution of cluster heads by more than 2 times and reduces the energy consumption within a range of 15% to 50% as compared to the existing protocols.
Trajectory-Based Road-Geometry and Crash-Risk Estimation with Smartphone-Assisted Sensor Networks
Authors: Lee Dongwook , Kim Ilmin , Hahn Minsoo
Published: March 2014

As mobile devices came into wide use, it became practical to collect travel data in personal logs. Many studies have been conducted to extract meaningful information from this trend. In this study, we present a system for monitoring road-geometry and crash-risk estimation, based on trajectories created using a smartphone-aided sensor network. The proposed system consists of a number of node vehicles with smartphone applications for GPS data collection and a map server which aggregates the collected GPS trajectories and estimates road conditions. In order to estimate road geometry and crash risk information, the trajectories were segmented and categorized into groups according to their headings. Based on the processed trajectories, the geometry of the road section was estimated using the principal curve method. The crash risk of the road section was estimated from the constructed road geometry and the density map of the trajectories. Our system was evaluated using bicycle trajectories collected from segregated bicycle tracks in Seoul, Korea. Constructed geometry and crash-risk information of the track was compared with real track geometry and crash data. As a result, the estimated road geometry showed over 74% similarity and the calculated crash risk (61%) matched the real crash data.
Cellular Players in Skeletal Muscle Regeneration
Authors: Ceafalan Laura Cristina , Popescu Bogdan Ovidiu , Hinescu Mihail Eugen
Published: March 2014

Skeletal muscle, a tissue endowed with remarkable endogenous regeneration potential, is still under focused experimental investigation mainly due to treatment potential for muscle trauma and muscular dystrophies. Resident satellite cells with stem cell features were enthusiastically described quite a long time ago, but activation of these cells is not yet controlled by any medical interventions. However, after thorough reports of their existence, survival, activation, and differentiation there are still many questions to be answered regarding the intimate mechanism of tissue regeneration. This review delivers an up-to-date inventory of the main known key players in skeletal muscle repair, revealed by various models of tissue injuries in mechanical trauma, toxic lesions, and muscular dystrophy. A better understanding of the spatial and temporal relationships between various cell populations, with different physical or paracrine interactions and phenotype changes induced by local or systemic signalling, might lead to a more efficient approach for future therapies.
Molecular Pathways: Adaptive Kinome Reprogramming in Response to Targeted Inhibition of the BRAF–MEK–ERK Pathway in Cancer
Authors: Johnson Gary L. , Stuhlmiller Timothy J. , Angus Steven P. , Zawistowski Jon S. , Graves Lee M.
Published: March 2014

The central role of the BRAF–MEK–ERK pathway in controlling cell fate has made this pathway a primary target for deregulated activation in cancer. BRaf is activated by Ras proteins allowing Ras oncogenes to constitutively activate the pathway. Activating BRaf mutations are also frequent in several cancers, being the most common oncogenic mutation in thyroid carcinoma and melanoma. There are currently two inhibitors, vemurafenib and dabrafenib, approved for treatment of malignant melanoma having activating BRaf mutations. Concurrent administration of BRAF and MAP–ERK kinase (MEK) inhibitor (trametinib) is significantly more active in patients with BRAF-mutant melanoma than either single agent alone, but progression to resistance ultimately occurs by different mechanisms that increase the activation of extracellular signal–regulated kinase (ERK). Such adaptive changes in tumor cell signaling networks allow bypass of targeted oncoprotein inhibition. This is true with targeted inhibitors for BRaf and MEK as well as specific inhibitors for AKT, mTOR, and many receptor tyrosine kinases such as EGF receptor (EGFR) and HER2. It is this adaptive response to targeted kinase inhibitors that contributes to the failure of single-agent kinase inhibitors to have durable responses. This failure is seen in virtually all cancers treated with single-agent kinase inhibitors, most of which are not as dependent on a single signaling pathway such as BRaf–MEK–ERK in melanoma. Thus, understanding the breadth of adaptive reprogramming responses to specific targeted kinase inhibition will be critical to develop appropriate combination therapies for durable clinical responses. Clin Cancer Res; 20(10); 2516–22. ©2014 AACR.
A Functional Fetal HSD11B2[CA]n Microsatellite Polymorphism is Associated with Maternal Serum Cortisol Concentrations in Pregnant Women
Authors: Li Jian , Chen You-Peng , Wang Zi-Neng , Liu Tie-Bin , Chen Dan , Dong Yun-Peng , Hocher Berthold
Published: March 2014

Background/Aims: Cortisol plays an important role during pregnancy. It controls maternal glucose metabolism and fetal development. Cortisol metabolism is partially controlled by the 11b-HSD2. This enzyme is expressed in the kidney and human placenta. The activity of the enzyme is partially controlled by functional polymorphisms: the HSD11B2[CA]n microsatellite polymorphism. The impact of this functional gene polymorphism on cortisol metabolism and potential effects on the newborn's is unknown so far. Methods: In the current prospective birth cohort study in southern Asia, we analyzed the association of the HSD11B2[CA]n microsatellite polymorphisms in 187 mothers and their newborn's on maternal and newborn's serum cortisol concentrations. Results: Using multivariable regression analyses considering known confounding (gestational age, newborn's gender, the labor uterine contraction states and the timing during the day of blood taking), we showed that the fetal HSD11B2[CA]n microsatellite polymorphisms in the first intron was related to maternal cortisol concentration (R2=0.26, B=96.27, p=0.007), whereas as the newborn's cortisol concentrations were independent of fetal and maternal HSD11B2[CA]n microsatellite polymorphism. Conclusions: Our study showed for the first time that the fetal HSD11B2[CA]n microsatellite polymorphism of the HSD11B2 gene in healthy uncomplicated human pregnancy is associated with maternal cortisol concentration. This indicates that fetal genes controlling cortisol metabolism may affect maternal cortisol concentration and hence physiology in healthy pregnant women.
Silent Atrial Fibrillation after Ischemic Stroke or Transient Ischemic Attack: Interest of Continuous ECG Monitoring
Authors: Fernandez Vanessa , Béjot Yannick , Zeller Marianne , Hamblin Joëlle , Daubail Benoit , Jacquin Agnes , Maza Maud , Touzery Claude , Cottin Yves , Giroud Maurice
Published: March 2014

Background: Since atrial fibrillation (AF) may be undiagnosed when asymptomatic and paroxysmal, we aimed to investigate the incidence and determinants of silent AF in patients with acute ischemic stroke or transient ischemic attack (TIA). Methods: Consecutive patients admitted to the Stroke Unit of the University Hospital of Dijon, France, for acute ischemic stroke or TIA were prospectively enrolled from March to December 2012. Silent AF was assessed by continuous electrocardiography (ECG) monitoring for 24 h after admission. An echocardiography was performed at day 2 ± 1 to measure left ventricular ejection fraction (LVEF) and left auricular (LA) dimensions. Results: Among the 187 patients included, 19 (10%) developed silent AF. Patients with silent AF were markedly older (76 vs. 66 years, p < 0.002), with lower creatinine levels (90 vs. 80 µmol/l, p = 0.030) and were less often smokers (5 vs. 24%, p = 0.058) than patients without silent AF. They also showed a trend towards more frequent hypertension and a recent history of infection. Patients with silent AF had a larger indexed LA volume (37.4 vs. 30.8 ml/m3, p = 0.057) and LA diameter (23.2 vs. 20.8 mm/m2, p = 0.059). LVEF in the two groups was similar. In multivariate analysis, only age remained an independent estimate of silent AF. Conclusion: Silent AF detected by continuous ECG monitoring is common and closely associated with older age. Further studies are needed to investigate the interest of systematically screening for silent AF for secondary prevention after ischemic stroke/TIA.
Extreme Deep White Matter Hyperintensity Volumes Are Associated with African American Race
Authors: Nyquist Paul A. , Bilgel Murat S. , Gottesman Rebecca , Yanek Lisa R. , Moy Taryn F. , Becker Lewis C. , Cuzzocreo Jennifer , Prince Jerry , Yousem David M. , Becker Diane M. , Kral Brian G. , Vaidya Dhananjay
Published: March 2014

Background: African Americans (AAs) have a higher prevalence of extreme ischemic white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) than do European Americans (EAs) based on the Cardiovascular Health Study (CHS) score. Ischemic white matter disease, limited to the deep white matter, may be biologically distinct from disease in other regions and may reflect a previously observed trend toward an increased risk of subcortical lacunar infarcts in AAs. We hypothesized that extreme deep WMH volume (DWMV) or periventricular volume (PV) may also have a higher prevalence in AAs. Thus, we studied extreme CHS scores and extreme DWMV and PV in a healthy population enriched for cardiovascular disease risk factors. Methods: We imaged the brains of 593 subjects who were first-degree relatives of probands with early onset coronary disease prior to 60 years of age. WMHs were manually delineated on 3-tesla cranial MRI by a trained radiology reader; the location and volume of lesions were characterized using automated software. DWMV and PV were measured directly with automated software, and the CHS score was determined by a neuroradiologist. Volumes were characterized as being in the upper 25% versus lower 75% of total lesion volume. Volumes in the upper versus the remaining quartiles were examined for AA versus EA race using multiple logistic regression (generalized estimating equations adjusted for family relatedness) and adjusted for major vascular disease risk factors including age ≥55 years versus <55, sex, current smoking, obesity, hypertension, diabetes and low-density lipoprotein >160 mg/dl. Results: Participants were 58% women and 37% AAs, with a mean age of 51.5 ± 11.0 years (range, 29-74 years). AAs had significantly higher odds of having extreme DWMVs (odds ratio, OR, 1.8; 95% confidence interval, CI, 1.2-2.9; p = 0.0076) independently of age, sex, hypertension and all other risk factors. AAs also had significantly higher odds of having extreme CHS scores ≥3 (OR, 1.3; 95% CI, 1.1-3.6; p = 0.025). Extreme PV was not significantly associated with AA race (OR, 1.3; 95% CI, 0.81-2.1; p = 0.26). Conclusions: AAs from families with early-onset cardiovascular disease are more likely to have extreme DWMVs (a subclinical form of cerebrovascular disease) and an extreme CHS score, but not extreme PV, independently of age and other cardiovascular disease risk factors. These findings suggest that this AA population is at an increased risk for DWMV and may be at an increased risk for future subcortical stroke. Longitudinal studies are required to see if DWMV is predictive of symptomatic subcortical strokes in this population.
Antenatal Corticosteroids Impact the Inflammatory Rather Than the Antiangiogenic Profile of Women With Preeclampsia
Authors: Nayeri Unzila A. , Buhimschi Irina A. , Laky Christine A. , Cross Sarah N. , Duzyj Christina M. , Ramma Wenda , Sibai Baha M. , Funai Edmund F. , Ahmed Asif , Buhimschi Catalin S.
Published: March 2014

Circulating antiangiogenic factors and proinflammatory cytokines are implicated in the pathogenesis of preeclampsia. This study was performed to test the hypothesis that steroids modify the balance of inflammatory and proangiogenic and antiangiogenic factors that potentially contribute to the patient’s evolving clinical state. Seventy singleton women, admitted for antenatal corticosteroid treatment, were enrolled prospectively. The study group consisted of 45 hypertensive women: chronic hypertension (n=6), severe preeclampsia (n=32), and superimposed preeclampsia (n=7). Normotensive women with shortened cervix (<2.5 cm) served as controls (n=25). Maternal blood samples of preeclampsia cases were obtained before steroids and then serially up until delivery. A clinical severity score was designed to clinically monitor disease progression. Serum levels of angiogenic factors (soluble fms-like tyrosine kinase-1 [sFlt-1], placental growth factor [PlGF], soluble endoglin [sEng]), endothelin-1 (ET-1), and proinflammatory markers (IL-6, C-reactive protein [CRP]) were assessed before and after steroids. Soluble IL-2 receptor (sIL-2R) and total immunoglobulins (IgG) were measured as markers of T- and B-cell activation, respectively. Steroid treatment coincided with a transient improvement in clinical manifestations of preeclampsia. A significant decrease in IL-6 and CRP was observed although levels of sIL-2R and IgG remained unchanged. Antenatal corticosteroids did not influence the levels of angiogenic factors but ET-1 levels registered a short-lived increase poststeroids. Although a reduction in specific inflammatory mediators in response to antenatal steroids may account for the transient improvement in clinical signs of preeclampsia, inflammation is unlikely to be the major contributor to severe preeclampsia or useful for therapeutic targeting.
Aldosterone Dysregulation With Aging Predicts Renal Vascular Function and Cardiovascular Risk
Authors: Brown Jenifer M. , Underwood Patricia C. , Ferri Claudio , Hopkins Paul N. , Williams Gordon H. , Adler Gail K. , Vaidya Anand
Published: March 2014

Aging and abnormal aldosterone regulation are both associated with vascular disease. We hypothesized that aldosterone dysregulation influences the age-related risk of renal vascular and cardiovascular disease. We conducted an analysis of 562 subjects who underwent detailed investigations under conditions of liberal and restricted dietary sodium intake (1124 visits) in the General Clinical Research Center. Aldosterone regulation was characterized by the ratio of maximal suppression to stimulation (supine serum aldosterone on a liberal sodium diet divided by the same measure on a restricted sodium diet). We previously demonstrated that higher levels of this Sodium-modulated Aldosterone Suppression-Stimulation Index (SASSI) indicate greater aldosterone dysregulation. Renal plasma flow (RPF) was determined via
p
-aminohippurate clearance to assess basal renal hemodynamics and the renal vascular responses to dietary sodium manipulation and angiotensin II infusion. Cardiovascular risk was calculated using the Framingham Risk Score. In univariate linear regression, older age (β=−4.60;
P
<0.0001) and higher SASSI (β=−58.63;
P
=0.001) predicted lower RPF and a blunted RPF response to sodium loading and angiotensin II infusion. We observed a continuous, independent, multivariate-adjusted interaction between age and SASSI, where the inverse relationship between SASSI and RPF was most apparent with older age (
P
<0.05). Higher SASSI and lower RPF independently predicted higher Framingham Risk Score (
P
<0.0001) and together displayed an additive effect. Aldosterone regulation and age may interact to mediate renal vascular disease. Our findings suggest that the combination of aldosterone dysregulation and renal vascular dysfunction could additively increase the risk of future cardiovascular outcomes; therefore, aldosterone dysregulation may represent a modifiable mechanism of age-related vascular disease.
Soaring Income Gaps: China in Comparative Perspective
Authors: Whyte Martin King
Published: March 2014

Despite repeated pledges by China's leaders to reduce the gap between rich and poor, income inequality has continued to rise. China's Gini coefficient, a standard measure of income inequality, was higher in 2007 than in the United States, Russia, or most other societies. Why have China's income gaps increased so fast and so far, despite programs designed to promote greater equality? Standard explanations, such as income gaps inevitably rising with rapid economic development or in a post-socialist transition, cannot explain the Chinese case. Paradoxically, the sharp rise in inequality is driven more by the legacy of China's socialist system than by market forces or the global economy. It will not be possible to bring China's soaring income gaps under control unless the new leaders who took power in 2012–2013 are able to make much more fundamental reforms than have been attempted to date.
The Politics of Increasing Religious Diversity in China
Authors: Weller Robert P.
Published: March 2014

China has seen a remarkable growth and pluralization of religious activity over the past thirty years, a development that has rapidly overtaken the incremental and sluggish changes in the relevant regulatory structures. In much of the country, the government has managed the mismatch between religious practice and official rules by governing with “one eye open and one eye closed,” that is, by pretending not to notice violations of the regulations as long as people pretend that they are following the rules. Comparative evidence suggests that such a mode of governance can be long-lasting and effective by encouraging groups to self-censor, by allowing space for contextual experimentation, and by stressing the acceptance of nominal convention over the control of behavior. This situation is likely to continue unless China adopts a new vision of the desired relation between state and society.
Persistent Hemispheric Differences in the Perceptual Selection of Spatial Frequencies
Authors: Piazza Elise A. , Silver Michael A.
Published: March 2014

Previous research has shown that the right hemisphere processes low spatial frequencies more efficiently than the left hemisphere, which preferentially processes high spatial frequencies. These studies have typically measured RTs to single, briefly flashed gratings and/or have directed observers to attend to a particular spatial frequency immediately before making a judgment about a subsequently presented stimulus. Thus, it is unclear whether the hemispheres differ in perceptual selection from multiple spatial frequencies that are simultaneously present in the environment, without bias from selective attention. Moreover, the time course of hemispheric asymmetry in spatial frequency processing is unknown. We addressed both of these questions with binocular rivalry, a measure of perceptual selection from competing alternatives over time. Participants viewed a pair of rivalrous orthogonal gratings with different spatial frequencies, presented either to the left or right of central fixation, and continuously reported which grating they perceived. At the beginning of a trial, the low spatial frequency grating was perceptually selected more often when presented in the left hemifield (right hemisphere) than in the right hemifield (left hemisphere), whereas the high spatial frequency grating showed the opposite pattern of results. This hemispheric asymmetry in perceptual selection persisted for the entire 30-sec stimulus presentation, continuing long after stimulus onset. These results indicate stable differences in the resolution of ambiguity across spatial locations and demonstrate the importance of considering sustained differences in perceptual selection across space when characterizing conscious representations of complex scenes.
New insights into polyphyly of the harpacticoid genus Delavalia (Crustacea, Copepoda) through morphological and molecular study of an unprecedented diversity of sympatric species in a small South Korean bay
Authors: KARANOVIC TOMISLAV , KIM KICHOON
Published: March 2014

Polyphyly of the genus Delavalia Brady, 1869 has been postulated previously based on intuitive methods, but no phylogenetic study was ever conducted. A chance discovery of seven sympatric species of this genus in the highly industrialized Gwangyang Bay in South Korea, in addition to one species each from the closely related genera Stenhelia Boeck, 1865 and Onychostenhelia Itô, 1979, prompted a renewed interest in the phylogenetic relationships within the subfamily Stenheliinae Brady, 1880. Additional surveys along the Korean coast failed to produce Delavalia species, but comparative material was sourced from Posyet Bay in the Russian Far East. Aims of this study were to reconstruct phylogenetic relationships of the newly collected stenheliins using molecular methods, test the hypothesized polyphyly of Delavalia, formally describe any resulting monophyletic units, perform a comparative study of traditional morphological and novel micro-morphological characters, and describe all new Delavalia species. A fragment of the mtCOI gene was successfully PCR-amplified from 23 stenheliin specimens and an additional 300 specimens were studied for morphological characters. All phylogenetic analyses supported the presence of at least eight genetically divergent lineages, most with very high bootstrap values, and the polyphyletic nature of Delavalia is demonstrated. Three new genera, each supported by molecular data and a number of morphological synapomorphies, were erected to accommodate the newly discovered species and some previously described members of Delavalia: Wellstenhelia gen. nov., Itostenhelia gen. nov., and Willenstenhelia gen. nov. The Chinese Wellstenhelia qingdaoensis (Ma & Li, 2011) comb. nov. is recorded for the first time in Korea, and six new species are described from Gwangyang Bay: Wellstenhelia calliope sp. nov., Wellstenhelia clio sp. nov., Wellstenhelia erato sp. nov., Wellstenhelia euterpe sp. nov., Itostenhelia polyhymnia sp. nov., and Willenstenhelia thalia sp. nov. Additonally, Itostenhelia golikovi (Chisleno, 1978) comb. nov. is redescribed from newly collected material from the type locality in Russia and its male described for the first time, while Wellstenhelia melpomene sp. nov., Willenstenhelia urania sp. nov., and Willenstenhelia terpsichore sp. nov. are established as new names for previously reported populations of two presumably widely distributed Delavalia species.