bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on the Multi-Energy Management Strategy of the Electric Drive System of a Tracked Bulldozer
Authors: Pan Ming , Yan Jun , Tu Qunzhang , Jiang Chengming
Published: March 2016

The multi-energy management strategy of electric drive system of tracked bulldozer was researched. Firstly, based on power requirement of typical working condition of a tracked bulldozer, the power distribution strategy for three energy sources in the front power chain was proposed by using wavelet theory and fuzzy control theory. Secondly, the electric drive system simulation platform was built in MATLAB/Simulink. At last, a driver-controller based HILS (hardware-in-the-loop simulation) platform was built and the multi-energy management strategy was verified. The HILS result shows that front power chain’s power output can meet the back power chain’s requirement, the engine-generator set works near the best fuel consumption curve, and the battery pack’s charge-discharge frequency and current are low. Thus the designed multi-energy management strategy can be used in real-time control of electric drive bulldozer.
Contrast Medium Induced Nephropathy after Endovascular Stent Graft Placement: An Examination of Its Prevalence and Risk Factors
Authors: Kawatani Yohei , Nakamura Yoshitsugu , Mochida Yoshihiko , Yamauchi Naoya , Hayashi Yujiro , Taneichi Tetsuyoshi , Ito Yujiro , Kurobe Hirotsugu , Suda Yuji , Hori Takaki
Published: March 2016

Endovascular stent graft placement has become a major treatment for thoracic and abdominal aneurysms. While endovascular therapy is less invasive than open surgery, it involves the use of a contrast medium. Contrast media can cause renal impairment, a condition termed as contrast-induced nephropathy (CIN). This study sought to evaluate the incidence and risk factors of CIN following endovascular stent graft placement for aortic aneurysm repair. The study included 167 consecutive patients who underwent endovascular stent graft placement in our hospital from October 2013 to June 2014. CIN was diagnosed using the European Society of Urogenital Radiology criteria. Patients with and without CIN were compared. Chi-squared tests,t-tests, and multivariate logistic regression analyses were performed. Thirteen patients (7.8%) developed CIN. Left ventricular dysfunction and intraoperative blood transfusion were significantly more frequent in the CIN group (P=0.017andP=0.032, resp.). Multivariate analysis showed that left ventricular dysfunction had the strongest influence on CIN development (odds ratio 9.34,P=0.018, and 95% CI = 1.46–59.7). Patients with CIN also experienced longer ICU and hospital stays. Measures to improve renal perfusion flow should be considered for patients with left ventricular dysfunction who are undergoing endovascular stent graft placement.
Estimation of Reversed Flow in Long Pipeline Based on Axial Vibration Model of Dense Paste
Authors: Lyu Fuyan , Zhang Minjun , Qu Yuanyuan , Gao Jie , Jia Xuankai , Hao Xuedi , Wu Miao
Published: March 2016

Intense axial vibration of the paste and the reversed flow make damage to the transportation system and lag the transport progress. This paper analyzed the axial vibration of the paste by building the vibration model according to the working situations of the system. The amount of the reversed flow share is then estimated based on the formed axial vibration model. The estimation of the reversed flow is carried out by counting the amount of the decompressed paste in certain time, which is being relative to the displacement in a single process of the vibration in numerical. The estimation of the reversed flow share of coal slime paste under certain transportation conditions was given and compared with the result based on the wave velocity method. It is evident that the introduction of axial vibration model into the study of the pipeline transportation system is feasible and reasonable, which also supplements the theoretical foundation for the analysis of dense paste vibrations in pipeline transportation system and its impacts on the system.
Axial Length of the Eyeball Is Important in Secondary Dislocation of the Intraocular Lens, Capsular Bag, and Capsular Tension Ring Complex
Authors: Klysik Anna , Kaszuba-Bartkowiak Katarzyna , Jurowski Piotr
Published: March 2016

Purpose. To analyze the patients with secondary dislocation of CTR and IOL within 5 years from cataract surgery, to determine predisposing factors.Methods. 16 eyes of 15 patients aged66.2±6.7(from 49 to 82) with CTR/IOL complex dislocation within 5 years from cataract surgery were compared with 26 patients aged67.1±7.2(from 53 to 85), implanted with CTR during cataract surgery to manage zonule dehiscence and did not dislocate for at least 5 years, in respect of cause, axial length and IOL power, refraction, coexistent pathology, and trauma.Results. Axial length of the eyeball was23.8±1.3(from 21 to 29) in the group of patients with CTR/IOL dislocation and20.7±1.2(from 19 to 24) in patients with no dislocation present (p=0.008). Crystalline lens dislocation was diagnosed before surgery in 13 of 16 patients with CTR/IOL complex dislocation as opposed to 7 of 26 eyes in the control group (p=0.01). Pseudoexfoliation was present in 50% and 58% in both groups, respectively. Traumatic dislocation was present in 8 patients, none of them with CTR/IOL dislocation (p=0.04).Conclusion. Longer axial length may contribute to the failure of the CTR to prevent in-the-bag IOL dislocation. Traumatic dislocation appears to be well fixed with the CTR.
Papillary Thyroid Cancer in a Child with Progressive Transformation of Germinal Centers
Authors: Mohan Suresh , DeNardo Bradley , Stachurski Dariusz , Greene Welch Jennifer , Groblewski Jan C.
Published: March 2016

Objectives. To describe the presentation and management of a child with Progressive Transformation of Germinal Centers (PTGC), an uncommon condition characterized by significant persistent lymphadenopathy, who developed papillary thyroid carcinoma and to explore and review potential links between PTGC and neoplastic processes in the head and neck.Methods. Case presentation and literature review are used.Results. A 10-year-old female presented with a right parotid mass and cervical lymphadenopathy. Multiple biopsies revealed PTGC without malignancy. Two years later, she developed fatigue and weight gain, and a thyroid nodule was found. Fine needle aspiration was strongly suggestive of papillary thyroid carcinoma. The patient underwent total thyroidectomy and central neck dissection without surgical management of the longstanding right lateral neck lymphadenopathy. Final pathology confirmed papillary thyroid carcinoma. She was treated with radioactive iodine therapy postoperatively and remains free of disease at three years of follow-up.Conclusions. PTGC is considered a benign condition but has previously been associated with Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL). This is the first reported case of papillary thyroid cancer in a child with preexisting cervical PTGC and no defined risk factors for thyroid malignancy. No link has been established with thyroid carcinoma, but patients with PTGC may have a defect in immune surveillance that predisposes them to malignancy.
Dual Effects of Cellular Immunotherapy in Inhibition of Virus Replication and Prolongation of Survival in HCV-Positive Hepatocellular Carcinoma Patients
Authors: Qian Lei , Wang Nanya , Tian Huimin , Jin Haofan , Zhao Hengjun , Niu Chao , He Hua , Ge Tingwen , Han Wei , Hu Jifan , Li Dan , Han Fujun , Xu Jianting , Ding Xiao , Chen Jingtao , Li Wei , Cui Jiuwei
Published: March 2016

Immune cells play an important role in the development and progression of hepatitis C virus (HCV) and hepatocellular carcinoma (HCC). We conducted a retrospective study to evaluate the influence of adoptive cellular immunotherapy (CIT) on viral load and progression-free survival (PFS) for HCC patients infected with HCV. Patients (n=104) were divided into a control group (conventional therapy,n=73) and study group (combination of CIT and conventional therapy,n=31). Autologous mononuclear cells were induced into natural killer,γδT, and cytokine-induced killer cells and infused intravenously to study group patients. More patients had shown viral load decrease or were stable in study group (100% versus 75%) (p=0.014). The median PFS of the study group and control group was 16 and 10 months, respectively (p=0.0041), and only CIT was an independent prognostic factor for PFS (hazard ratio, 0.422;p=0.005). Three patients developed transient moderate fever after infusion, and there were no significant differences in alanine aminotransferase and aspartate aminotransferase levels before and after treatment in both groups. Our results show that CIT contributes to improvement of prognosis and inhibition of viral replication in HCV-related HCC patients, without impairment of liver function.
Unhealthy Phenotype as Indicated by Salivary Biomarkers: Glucose, Insulin, VEGF-A, and IL-12p70 in Obese Kuwaiti Adolescents
Authors: Hartman Mor-Li , Goodson J. Max , Shi Ping , Vargas Jorel , Yaskell Tina , Stephens Danielle , Cugini Maryann , Hasturk Hatice , Barake Roula , Alsmadi Osama , Al-Mutawa Sabiha , Ariga Jitendra , Soparkar Pramod , Behbehani Jawad , Behbehani Kazem , Welty Francine
Published: March 2016

Objective. Here, we investigated the relationships between obesity and the salivary concentrations of insulin, glucose, and 20 metabolic biomarkers in Kuwaiti adolescents. Previously, we have shown that certain salivary metabolic markers can act as surrogates for blood concentrations.Methods. Salivary samples of whole saliva were collected from 8,317 adolescents. Salivary glucose concentration was measured by a high-sensitivity glucose oxidase method implemented on a robotic chemical analyzer. The concentration of salivary insulin and 20 other metabolic biomarkers was assayed in 744 randomly selected saliva samples by multiplexed bead-based immunoassay.Results. Obesity was seen in 26.5% of the adolescents. Salivary insulin predicting hyperinsulinemia occurred in 4.3% of normal-weight adolescents, 8.3% of overweight adolescents, and 25.7% of obese adolescents (p<0.0001). Salivary glucose predicting hyperglycemia was found in only 3% of obese children and was not predictive (p=0.89). Elevated salivary glucose and insulin occurring together was associated with elevated vascular endothelial growth factor and reduced salivary interleukin-12.Conclusion.Considering the surrogate nature of salivary insulin and glucose, this study suggests that elevated insulin may be a dominant sign of metabolic disease in adolescent populations. It also appears that a proangiogenic environment may accompany elevated glucose in obese adolescents.
Naringin Stimulates Osteogenic Differentiation of Rat Bone Marrow Stromal Cells via Activation of the Notch Signaling Pathway
Authors: Yu Guo-yong , Zheng Gui-zhou , Chang Bo , Hu Qin-xiao , Lin Fei-xiang , Liu De-zhong , Wu Chu-cheng , Du Shi-xin , Li Xue-dong
Published: March 2016

Naringin is a major flavonoid found in grapefruit and is an active compound extracted from the Chinese herbal medicine Rhizoma Drynariae. Naringin is a potent stimulator of osteogenic differentiation and has potential application in preventing bone loss. However, the signaling pathway underlying its osteogenic effect remains unclear. We hypothesized that the osteogenic activity of naringin involves the Notch signaling pathway. Rat bone marrow stromal cells (BMSCs) were cultured in osteogenic medium containing‐naringin, with or without DAPT (an inhibitor of Notch signaling), the effects on ALP activity, calcium deposits, osteogenic genes (ALP, BSP, and cbfa1), adipogenic maker gene PPARγ2 levels, and Notch expression were examined. We found that naringin dose‐dependently increased ALP activity and Alizarin red S staining, and treatment at the optimal concentration (50 μg/mL) increased mRNA levels of osteogenic genes and Notch1 expression, while decreasing PPARγ2 mRNA levels. Furthermore, treatment with DAPT partly reversed effects of naringin on BMSCs, as judged by decreases in naringin‐induced ALP activity, calcium deposits, and osteogenic genes expression, as well as upregulation of PPARγ2 mRNA levels. These results suggest that the osteogenic effect of naringin partly involves the Notch signaling pathway.
Serotonin-Related Gene Polymorphisms and Asymptomatic Neurocognitive Impairment in HIV-Infected Alcohol Abusers
Authors: Villalba Karina , Dévieux Jessy G. , Rosenberg Rhonda , Cadet Jean Lud
Published: March 2016

HIV-infected individuals continue to experience neurocognitive deterioration despite virologically successful treatments. While the cause remains unclear, evidence suggests that HIV-associated neurocognitive disorders (HAND) may be associated with neurobehavioral dysfunction. Genetic variants have been explored to identify risk markers to determine neuropathogenesis of neurocognitive deterioration. Memory deficits and executive dysfunction are highly prevalent among HIV-infected adults. These conditions can affect their quality of life and HIV risk-taking behaviors. Single nucleotide polymorphisms in the SLC6A4, TPH2, and GALM genes may affect the activity of serotonin and increase the risk of HAND. The present study explored the relationship between SLC6A4, TPH2, and GALM genes and neurocognitive impairment in HIV-infected alcohol abusers. A total of 267 individuals were genotyped for polymorphisms in SLC6A4 5-HTTLPR, TPH2 rs4570625, and GALM rs6741892. To assess neurocognitive functions, the Short Category and the Auditory Verbal Learning Tests were used. TPH2 SNP rs4570625 showed a significant association with executive function in African American males (odds ratio 4.8, 95% CI, 1.5–14.8; P=0.005). Similarly, GALM SNP rs6741892 showed an increased risk with African American males (odds ratio 2.4, 95% CI, 1.2–4.9; P=0.02). This study suggests that TPH2 rs4570625 and GALM rs6741892 polymorphisms may be risk factors for HAND.
A New Method for Optimal Regularization Parameter Determination in the Inverse Problem of Load Identification
Authors: Gao Wei , Yu Kaiping , Wu Ying
Published: March 2016

According to the regularization method in the inverse problem of load identification, a new method for determining the optimal regularization parameter is proposed. Firstly, quotient function (QF) is defined by utilizing the regularization parameter as a variable based on the least squares solution of the minimization problem. Secondly, the quotient function method (QFM) is proposed to select the optimal regularization parameter based on the quadratic programming theory. For employing the QFM, the characteristics of the values of QF with respect to the different regularization parameters are taken into consideration. Finally, numerical and experimental examples are utilized to validate the performance of the QFM. Furthermore, the Generalized Cross-Validation (GCV) method and theL-curve method are taken as the comparison methods. The results indicate that the proposed QFM is adaptive to different measuring points, noise levels, and types of dynamic load.
Resveratrol Enhances Autophagic Flux and Promotes Ox‐LDL Degradation in HUVECs via Upregulation of SIRT1
Authors: Zhang Yanlin , Cao Xueqin , Zhu Wawa , Liu Zhihua , Liu Huihui , Zhou Yande , Cao Yongjun , Liu Chunfeng , Xie Ying
Published: March 2016

Oxidized low‐density lipoprotein‐ (Ox‐LDL‐) induced autophagy dysfunction in human vascular endothelial cells contributes to the development of atherosclerosis (AS). Resveratrol (RSV) protects against Ox‐LDL‐induced endothelium injury. The objective of this study was to determine the mechanisms underlying Ox‐LDL‐induced autophagy dysfunction and RSV‐mediated protection in human umbilical vein endothelial cells (HUVECs). The results showed that Ox‐LDL suppressed the expression of sirtuin 1 (SIRT1) and increased LC3‐II and sequestosome 1 (p62) protein levels without altering p62 mRNA levels in HUVECs. Pretreatment with bafilomycin A1 (BafA1) to inhibit lysosomal degradation abrogated the Ox‐LDL‐induced increase in LC3‐II protein level. Ox‐LDL increased colocalization of GFP and RFP puncta in mRFP‐GFP‐tandem fluorescent LC3‐ (tf‐LC3‐) transfected cells. Moreover, Ox‐LDL decreased the expression of mature cathepsin D and attenuated cathepsin D activity. Pretreatment with RSV increased the expression of SIRT1 and LC3‐II and increased p62 protein degradation. RSV induced RFP‐LC3 aggregation more than GFP‐LC3 aggregation. RSV restored lysosomal function and promoted Ox‐LDL degradation in HUVECs. All the protective effects of RSV were blocked after SIRT1 was knocked down. These findings demonstrated that RSV upregulated the expression of SIRT1, restored lysosomal function, enhanced Ox‐LDL‐induced impaired autophagic flux, and promoted Ox‐LDL degradation through the autophagy‐lysosome degradation pathway in HUVECs.
Correlation of Serum Soluble Interleukin-7 Receptor and Anti-C1q Antibody in Patients with Systemic Lupus Erythematosus
Authors: Chi Shuhong , Xue Jing , Li Feng , Zhu Caixia , Yu Yunxia , Li Haibo , Wang Xuemei , Zhang Yurong , Yang Jijuan , Zhou Shaolan , Yang Lijuan , Ji Chen , Liu Xiaoming
Published: March 2016

Background.Serum concentrations of soluble interleukin-7 receptor (sIL-7R) and anti-C1q antibody have recently been identified as unique serological markers for lupus nephritis (LN) in patients with systemic lupus erythematosus (SLE). In this study, we evaluated the correlation of serum sIL-7R and anti-C1q in SLE patients.Methods.Sera from 134 patients with SLE and 84 healthy cohorts were tested for levels of sIL-7R and anti-C1q antibodies in terms of ELISA. Correlations of the sIL-7R and anti-C1q autoantibodies were evaluated.Results.The serum concentrations of sIL-7R and anti-C1q antibodies were significantly higher in SLE patients and LN patients in comparison with healthy individuals/controls and SLE patients with non-LN, respectively. In addition, both sIL-7R and anti-C1q concentrations were found to significantly correlate with the SLE disease activity as evaluated by SLEDAI scores. Interestingly, the serum sIL-7R concentration was strongly correlated with the level of anti-C1q antibodies (r=0.2871,p=0.0008) but not statistically correlated with other serological markers, including the anti-dsDNA and complements C3 and C4 concentrations in SLE patients.Conclusion.Both serum sIL-7R and anti-C1q antibodies were strongly associated with disease activity and LN in SLE patients, suggesting that they may be reliable serological markers for identification of SLE patients with active diseases and LN.
Ni-Based Ohmic Contacts ton-Type 4H-SiC: The Formation Mechanism and Thermal Stability
Authors: Kuchuk A. V. , Borowicz P. , Wzorek M. , Borysiewicz M. , Ratajczak R. , Golaszewska K. , Kaminska E. , Kladko V. , Piotrowska A.
Published: March 2016

The fabrication of low-resistance and thermal stable ohmic contacts is important for realization of reliable SiC devices. For then-type SiC, Ni-based metallization is most commonly used for Schottky and ohmic contacts. Many experimental studies have been performed in order to understand the mechanism of ohmic contact formation and different models were proposed to explain the Schottky to ohmic transition for Ni/SiC contacts. In the present review, we summarize the last key results on the matter and post open questions concerning the unclear issues of ohmic contacts ton-type SiC. Analysis of the literature data and our own experimental observations have led to the conclusion that the annealing at high temperature leads to the preferential orientation of silicide at the heterointerface (0001)SiC//(013)δ-Ni2Si. Moreover, we may conclude that onlyδ-Ni2Si grains play a key role in determining electrical transport properties at the contact/SiC interface. Finally, we show that the diffusion barriers with free diffusion path microstructure can improve thermal stability of metal-SiC ohmic contacts for high-temperature electronics.
A Novel Microstrip-to-Microstrip Vertical Via Transition in X-Band Multilayer Packages
Authors: Yu M. X.
Published: March 2016

This paper investigates a novel X-band microstrip-to-microstrip vertical via transition with matching pads loaded signal via. This design has been proposed for a multilayer substrate package. The matching pads, which are located in the center of the signal via on each ground layer, are adopted to further improve the impedance matching level and thus attain better signal transition performance. A physics-based equivalent circuit modeling approach has been employed for this research. The right angle MS-to-MS via transition was also designed using this technique. The simulatedS-parameters indicate that the match-pad design made a breakthrough in achieving an approximate −15 dB wide-band return loss reduction. The measuredS-parameter of MS-to-MS transition showed that return loss with the matching pads is better than that without the matching pads.
Enhancement of Mycophenolate Mofetil Permeation for Topical Use by Eucalyptol and N-Methyl-2-pyrrolidone
Authors: Amnuaikit Thanaporn , Songkram Chalermkiat , Pinsuwan Sirirat
Published: March 2016

Mycophenolate mofetil (MMF) is a prodrug of mycophenolic acid (MPA) which can be metabolized by esterase. MMF has been approved by the United States Food and Drug Administration (USFDA) for treatment of psoriasis patient with skin symptoms. However, it remains unclear whether MMF is efficiently effective to treat skin symptoms developed from psoriasis. The insufficient amount of MMF penetrating through the skin results in the treatment failure due to the difficulty in MMF penetration through the stratum corneum. Skin permeation enhancers such as eucalyptol (EUL) and N-methyl-2-pyrrolidone (NMP) potentially aid in increasing skin penetration. This study aimed to investigate the effects of a concentration ratio (% w/v) between two enhancers (EUL and NMP). The results showed that EUL enhanced MMF permeation with an enhancement ratio (ER) of 3.44 while NMP was not able to promote the penetration of MMF. Interestingly, the synergistic effect of the two enhancers was observed with a suitable ratio given that the ER was 8.21. EUL and NMP are promising enhancers for the development of MMF based skin product.
Insights into the Biology and Therapeutic Applications of Neural Stem Cells
Authors: Harris Lachlan , Zalucki Oressia , Piper Michael , Heng Julian Ik-Tsen
Published: March 2016

The cerebral cortex is essential for our higher cognitive functions and emotional reasoning. Arguably, this brain structure is the distinguishing feature of our species, and yet our remarkable cognitive capacity has seemingly come at a cost to the regenerative capacity of the human brain. Indeed, the capacity for regeneration and neurogenesis of the brains of vertebrates has declined over the course of evolution, from fish to rodents to primates. Nevertheless, recent evidence supporting the existence of neural stem cells (NSCs) in the adult human brain raises new questions about the biological significance of adult neurogenesis in relation to ageing and the possibility that such endogenous sources of NSCs might provide therapeutic options for the treatment of brain injury and disease. Here, we highlight recent insights and perspectives on NSCs within both the developing and adult cerebral cortex. Our review of NSCs during development focuses upon the diversity and therapeutic potential of these cells for use in cellular transplantation and in the modeling of neurodevelopmental disorders. Finally, we describe the cellular and molecular characteristics of NSCs within the adult brain and strategies to harness the therapeutic potential of these cell populations in the treatment of brain injury and disease.
Identification of Mithramycin Analogues with Improved Targeting of the EWS-FLI1 Transcription Factor
Authors: Osgood Christy L. , Maloney Nichole , Kidd Christopher G. , Kitchen-Goosen Susan , Segars Laura , Gebregiorgis Meti , Woldemichael Girma M. , He Min , Sankar Savita , Lessnick Stephen L. , Kang Min , Smith Malcolm , Turner Lisa , Madaj Zachary B. , Winn Mary E. , Núñez Luz-Elena , González-Sabín Javier , Helman Lee J. , Morís Francisco , Grohar Patrick J.
Published: March 2016

Purpose: The goal of this study was to identify second-generation mithramycin analogues that better target the EWS-FLI1 transcription factor for Ewing sarcoma. We previously established mithramycin as an EWS-FLI1 inhibitor, but the compound's toxicity prevented its use at effective concentrations in patients.

Experimental Design: We screened a panel of mithralogs to establish their ability to inhibit EWS-FLI1 in Ewing sarcoma. We compared the IC50 with the MTD established in mice to determine the relationship between efficacy and toxicity. We confirmed the suppression of EWS-FLI1 at the promoter, mRNA, gene signature, and protein levels. We established an improved therapeutic window by using time-lapse microscopy to model the effects on cellular proliferation in Ewing sarcoma cells relative to HepG2 control cells. Finally, we established an improved therapeutic window using a xenograft model of Ewing sarcoma.

Results: EC-8105 was found to be the most potent analogue and was able to suppress EWS-FLI1 activity at concentrations nontoxic to other cell types. EC-8042 was substantially less toxic than mithramycin in multiple species but maintained suppression of EWS-FLI1 at similar concentrations. Both compounds markedly suppressed Ewing sarcoma xenograft growth and inhibited EWS-FLI1 in vivo.

Conclusions: These results provide a basis for the continued development of EC-8042 and EC-8105 as EWS-FLI1 inhibitors for the clinic. Clin Cancer Res; 22(16); 4105–18. ©2016 AACR.
Is There a Future for AKT Inhibitors in the Treatment of Cancer?
Authors: Jansen Valerie M. , Mayer Ingrid A. , Arteaga Carlos L.
Published: March 2016

An AKT inhibitor plus an antiestrogen exhibited no significant clinical activity in patients with ER+/HER2− breast cancer despite laboratory studies supporting an antitumor effect for both drugs combined. These results raise concerns about the development of AKT inhibitors in unselected patients whose tumors have unknown dependence on the PI3K/AKT pathway. Clin Cancer Res; 22(11); 2599–601. ©2016 AACR.

See related article by Ma et al., p. 2650
Expression of the MHC Class II Pathway in Triple-Negative Breast Cancer Tumor Cells Is Associated with a Good Prognosis and Infiltrating Lymphocytes
Authors: Forero Andres , Li Yufeng , Chen Dongquan , Grizzle William E. , Updike Katherine L. , Merz Natalie D. , Downs-Kelly Erinn , Burwell Todd C. , Vaklavas Christos , Buchsbaum Donald J. , Myers Richard M. , LoBuglio Albert F. , Varley Katherine E.
Published: March 2016

Triple-negative breast cancer (TNBC) is a subtype with heterogeneous patient outcomes. Approximately 40% of patients experience rapid relapse, while the remaining patients have long-term disease-free survival. To determine if there are molecular differences between primary tumors that predict prognosis, we performed RNA-seq on 47 macrodissected tumors from newly diagnosed patients with TNBC (n = 47; 22 relapse, 25 no relapse; follow-up median, 8 years; range, 2–11 years). We discovered that expression of the MHC class II (MHC II) antigen presentation pathway in tumor tissue was the most significant pathway associated with progression-free survival (HR, 0.36; log-rank P = 0.0098). The association between MHC II pathway expression and good prognosis was confirmed in a public gene expression database of 199 TNBC cases (HR, 0.28; log-rank P = 4.5 × 10–8). Further analysis of immunohistochemistry, laser-capture microdissected tumors, and TNBC cell lines demonstrated that tumor cells, in addition to immune cells, aberrantly express the MHC II pathway. MHC II pathway expression was also associated with B-cell and T-cell infiltration in the tumor. Together, these data support the model that aberrant expression of the MHC II pathway in TNBC tumor cells may trigger an antitumor immune response that reduces the rate of relapse and enhances progression-free survival. Cancer Immunol Res; 4(5); 390–9. ©2016 AACR.
Loss of Maspardin Attenuates the Growth and Maturation of Mouse Cortical Neurons
Authors: Davenport Anne , Bivona Alexis , Latson Will , Lemanski Larry F. , Cheriyath Venugopalan
Published: March 2016

Background: Mast syndrome, an autosomal recessive, progressive form of hereditary spastic paraplegia, is associated with mutations in SPG21 loci that encode maspardin protein. Although SPG21-/- mice exhibit lower limb dysfunction, the role of maspardin loss in mast syndrome is unclear. Objective: To test the hypothesis that loss of maspardin attenuates the growth and maturation of cortical neurons in SPG21-/- mice. Methods and Results: In a randomized experimental design SPG21-/- mice demonstrated significantly less agility and coordination compared to wild-type mice in beam walk, ledge, and hind limb clasp tests for assessing neuronal dysfunction (p ≤ 0.05). The SPG21-/- mice exhibited symptoms of mast syndrome at 6 months which worsened in 12-month-old cohort, suggesting progressive dysfunction of motor neurons. Ex vivo, wild-type cortical neurons formed synapses, ganglia and aggregates at 96 h, whereas SPG21-/- neurons exhibited attenuated growth with markedly less axonal branches. Additionally, epidermal growth factor markedly promoted the growth and maturation of SPG21+/+ cortical neurons but not SPG21-/- neurons. Consequently, quantitative RT-PCR identified a significant reduction in the expression of a subset of EGF-EGFR signaling targets. Conclusions: Our current study uncovered a direct role for maspardin in normal and EGF-induced growth and maturation of primary cortical neurons. The loss of maspardin resulted in attenuated growth, axonal branching, and attenuation of EGF signaling. Reinstating the functions of maspardin may reverse hind limb impairment associated with neuronal dysfunction in mast syndrome patients.
Parques urbanos: fragilidade na aplicação de legislação específica no município de Chapecó-SC
Authors: Favaretto Angela , Rammé Juliana , Afonso Sonia
Published: March 2016

Objetivou-se investigar a relação entre a legislação federal, os Planos Diretores aprovados em Chapecó entre os anos de 1990 e 2014 e os parques urbanos, buscando compreender as diretrizes e as ações para a implantação destes. Foram utilizados métodos qualitativos: pesquisa bibliográfica e de campo com análise de conteúdo e análise histórico-estrutural, com apoio do Sistema de Informações Geográficas (SIG). Identificou-se que, nesse período, foram aprovados dois Planos Diretores (1990 e 2004) e que em ambos são estudadas áreas ambientais destinadas ao lazer. No entanto, somente em 2004 foram incluídos os parques como diretrizes e estratégias ambientais. No tocante aos mesmos, considera-se que os Planos Diretores não foram implementados e tampouco tem havido a gestão e a fiscalização do uso e da ocupação do solo. Detectaram-se, ainda, divergências entre a redação das leis dos Planos Diretores e os mapas temáticos anexos, em função das modificações realizadas por meio de leis complementares, sobretudo no que diz respeito ao gravame dos parques.
Fibrosis of the Neonatal Mouse Heart After Cryoinjury Is Accompanied by Wnt Signaling Activation and Epicardial‐to‐Mesenchymal Transition
Authors: Mizutani Makiko , Wu Joseph C. , Nusse Roeland
Published: March 2016

Background

The adult mammalian heart responds to cardiac injury by formation of persistent fibrotic scar that eventually leads to heart failure. In contrast, the neonatal mammalian heart reacts to injury by the development of transient fibrotic tissue that is eventually replaced by regenerated cardiomyocytes. How fibrosis occurs in the neonatal mammalian heart remains unknown. To start elucidating the molecular underpinnings of neonatal cardiac fibrosis, we investigated Wnt signaling in the neonatal heart after cryoinjury.

Methods and Results

Using expression of the Wnt target gene Axin2 as an indicator of Wnt/β‐catenin signaling activation, we discovered that epicardial cells in the ventricles are responsive to Wnt in the uninjured neonatal heart. Lineage‐tracing studies of these Wnt‐responsive epicardial cells showed that they undergo epithelial‐to‐mesenchymal transition and infiltrate into the subepicardial space and exhibit fibroblast phenotypes after injury. In addition, we showed that—similar to adult ischemic injury—neonatal cryoinjury results in activation of Wnt signaling in cardiac fibroblasts near injured areas. Furthermore, through in situ hybridization of all 19 Wnt ligands in injured neonatal hearts, we observed upregulation of Wnt ligands (Wnt2b, Wnt5a, and Wnt9a) that had not been implicated in the adult cardiac injury response.

Conclusions

These results demonstrate that cryoinjury in neonatal heart leads to the formation of fibrotic tissue that involves Wnt‐responsive epicardial cells undergoing epithelial‐to‐mesenchymal transition to give rise to fibroblasts and activation of Wnt signaling in resident cardiac fibroblasts.
Long‐Term Outcomes Among Elderly Survivors of Out‐of‐Hospital Cardiac Arrest
Authors: Chan Paul S. , McNally Bryan , Nallamothu Brahmajee K. , Tang Fengming , Hammill Bradley G. , Spertus John A. , Curtis Lesley H.
Published: March 2016

Background

Most studies on out‐of‐hospital cardiac arrest have focused on immediate survival. However, little is known about long‐term outcomes and resource use among survivors.

Methods and Results

Within the national
CARES
registry, we identified 16 206 adults 65 years or older with an out‐of‐hospital cardiac arrest between 2005 and 2010. Among 1127 patients who were discharged alive, we evaluated whether 1‐year mortality, cumulative readmission incidence, and follow‐up inpatient costs differed according to patients’ race, sex, initial cardiac arrest rhythm, bystander delivery of cardiopulmonary resuscitation, discharge neurological status, and functional status (hospital discharge disposition). Overall 1‐year mortality after hospital discharge was 31.8%. Among survivors, there were no long‐term mortality differences by sex, race, or initial cardiac arrest rhythm, but worse functional status and severe neurological disability at discharge were associated with higher mortality. Moreover, compared with first responders, cardiopulmonary resuscitation delivered by bystanders was associated with 23% lower mortality (hazard ratio 0.77 [confidence interval 0.58–1.02]). Besides mortality, 638 (56.6%) patients were readmitted within the first year, and the cumulative readmission incidence was 197 per 100 patient‐years. Mean 1‐year inpatient costs were $23 765±41 002. Younger age, black race, severe neurological disability at discharge, and hospital disposition to a skilled nursing or rehabilitation facility were each associated with higher 1‐year inpatient costs (
P
for all <0.05).

Conclusion

Among elderly survivors of out‐of‐hospital cardiac arrest, nearly 1 in 3 patients die within the first year. Long‐term mortality and inpatient costs differed substantially by certain demographic factors, whether cardiopulmonary resuscitation was initiated by a bystander, discharge neurological status, and hospital disposition.
Coronary Microvascular Function and Cardiovascular Risk Factors in Women With Angina Pectoris and No Obstructive Coronary Artery Disease: The iPOWER Study
Authors: Mygind Naja Dam , Michelsen Marie Mide , Pena Adam , Frestad Daria , Dose Nynne , Aziz Ahmed , Faber Rebekka , Høst Nis , Gustafsson Ida , Hansen Peter Riis , Hansen Henrik Steen , Bairey Merz C. Noel , Kastrup Jens , Prescott Eva
Published: March 2016

Background

The majority of women with angina‐like chest pain have no obstructive coronary artery disease when evaluated with coronary angiography. Coronary microvascular dysfunction is a possible explanation and associated with a poor prognosis. This study evaluated the prevalence of coronary microvascular dysfunction and the association with symptoms, cardiovascular risk factors, psychosocial factors, and results from diagnostic stress testing.

Methods and Results

After screening 3568 women, 963 women with angina‐like chest pain and a diagnostic coronary angiogram without significant coronary artery stenosis (<50%) were consecutively included. Mean age (
SD
) was 62.1 (9.7). Assessment included demographic and clinical data, blood samples, questionnaires, and transthoracic echocardiography during rest and high‐dose dipyridamole (0.84 mg/kg) with measurement of coronary flow velocity reserve (
CFVR
) by Doppler examination of the left anterior descending coronary artery.
CFVR
was successfully measured in 919 (95%) women. Median (
IQR
)
CFVR
was 2.33 (1.98–2.76), and 241 (26%) had markedly impaired
CFVR
(<2). In multivariable regression analysis, predictors of impaired
CFVR
were age (
P
<0.01), hypertension (
P
=0.02), current smoking (
P
<0.01), elevated heart rate (
P
<0.01), and low high‐density lipoprotein cholesterol (
P
=0.02), but these variables explained only a little of the
CFVR
variation (
r
2
=0.09).
CFVR
was not associated with chest pain characteristics or results from diagnostic stress testing.

Conclusion

Impaired
CFVR
was detected in a substantial proportion, which suggests that coronary microvascular dysfunction plays a role in the development of angina pectoris.
CFVR
was associated with few cardiovascular risk factors, suggesting that
CFVR
is an independent parameter in the risk evaluation of these women. Symptom characteristics and results from stress testing did not identify individuals with impaired
CFVR
.
Intercellular Adhesion Molecule 1 Regulates Left Ventricular Leukocyte Infiltration, Cardiac Remodeling, and Function in Pressure Overload–Induced Heart Failure
Authors: Salvador Ane M. , Nevers Tania , Velázquez Francisco , Aronovitz Mark , Wang Bonnie , Abadía Molina Ana , Jaffe Iris Z. , Karas Richard H. , Blanton Robert M. , Alcaide Pilar
Published: March 2016

Background

Left ventricular dysfunction and heart failure are strongly associated in humans with increased circulating levels of proinflammatory cytokines, T cells, and soluble intercellular cell adhesion molecule 1 (
ICAM
1). In mice, infiltration of T cells into the left ventricle contributes to pathological cardiac remodeling, but the mechanisms regulating their recruitment to the heart are unclear. We hypothesized that
ICAM
1 regulates cardiac inflammation and pathological cardiac remodeling by mediating left ventricular T‐cell recruitment and thus contributing to cardiac dysfunction and heart failure.

Methods and Results

In a mouse model of pressure overload–induced heart failure, intramyocardial endothelial
ICAM
1 increased within 48 hours in response to thoracic aortic constriction and remained upregulated as heart failure progressed.
ICAM
1‐deficient mice had decreased T‐cell and proinflammatory monocyte infiltration in the left ventricle in response to thoracic aortic constriction, despite having numbers of circulating T cells and activated T cells in the heart‐draining lymph nodes that were similar to those of wild‐type mice.
ICAM
1‐deficient mice did not develop cardiac fibrosis or systolic and diastolic dysfunction in response to thoracic aortic constriction. Exploration of the mechanisms regulating
ICAM
1 expression revealed that endothelial
ICAM
1 upregulation and T‐cell infiltration were not mediated by endothelial mineralocorticoid receptor signaling, as demonstrated in thoracic aortic constriction studies in mice with endothelial mineralocorticoid receptor deficiency, but rather were induced by the cardiac cytokines interleukin 1β and 6.

Conclusions

ICAM
1 regulates pathological cardiac remodeling by mediating proinflammatory leukocyte infiltration in the left ventricle and cardiac fibrosis and dysfunction and thus represents a novel target for treatment of heart failure.
Optimal Force–Time Integral for Pulmonary Vein Isolation According to Anatomical Wall Thickness Under the Ablation Line
Authors: Chikata Akio , Kato Takeshi , Sakagami Satoru , Kato Chieko , Saeki Takahiro , Kawai Keiichi , Takashima Shin‐ichiro , Murai Hisayoshi , Usui Soichiro , Furusho Hiroshi , Kaneko Shuichi , Takamura Masayuki
Published: March 2016

Background

Low contact force and force–time integral (
FTI
) during catheter ablation are associated with ineffective lesion formation, whereas excessively high contact force and
FTI
may increase the risk of complications. We sought to evaluate the optimal
FTI
for pulmonary vein (
PV
) isolation based on atrial wall thickness under the ablation line.

Methods and Results

Contact force parameters and
FTI
during anatomical ipsilateral
PV
isolation for atrial fibrillation and atrial wall thickness were assessed retrospectively in 59 consecutive patients for their first
PV
isolation procedure. The
PV
antrum was divided into 8 segments, and the wall thickness of each segment under the ablation line was determined using multidetector computed tomography. The
FTI
for each ablation point was divided by the wall thickness of the
PV
antrum segment where each point was located to obtain
FTI
/wall thickness. In total, 5335 radiofrequency applications were delivered, and 85 gaps in
PV
isolation ablation lines and 15 dormant conductions induced by adenosine were detected. The gaps or dormant conductions were significantly associated with low contact force, radiofrequency duration,
FTI
, and
FTI
/wall thickness. Among them,
FTI
/wall thickness had the best prediction value for gaps or dormant conductions by receiver operating characteristic curve analysis.
FTI
/wall thickness of <76.4 gram‐seconds per millimeter (gs/mm) predicted gaps or dormant conductions with sensitivity (88.0%) and specificity (83.6%), and
FTI
/wall thickness of <101.1 gs/mm was highly predictive (sensitivity 97.0%; specificity 69.6%).

Conclusions

FTI
/wall thickness is a strong predictor of gap and dormant conduction formation in
PV
isolation. An
FTI
/wall thickness ≈100 gs/mm could be a suitable target for effective ablation.
THE HISTORY OF DE
Authors: Chaofen SUN
Published: March 2016

L'auteur décrit l'histoire du mot DE . Dans une première partie, s'appuyant sur des études textuelles, il étudie l'apparition, le développement ou la disparition des différentes structures avec DE : 1) DE verbal, 2) DE - V, 3) V - DE, 4)V - DE - Phrase, 5)V - DE - V. L'évolution sémantique et la grammaticalisation de DE sont également abordées. Dans la deuxième partie, l'auteur s'attache à définir les différents statuts grammaticaux de DE en chinois moderne.
PHONOLOGIE ET LEXIQUE D'UN DIALECTE GAN : SHANGGAO
Authors: Sagart Laurent
Published: March 2016

The synchronie and historical phonology, and, to some extent, the lexicon of Shanggao, a Chinese dialect spoken in the western part of the Poyang plain in Jiangxi, are presented and discussed.
Timing of vessel formation in twigs and trunks in relation to porosity and leaf flushing
Authors: Takahashi Sayaka , Takahashi Erina
Published: March 2016

In order to understand the coordination of leaf phenology and functional xylem anatomy, the timing of vessel wall lignification in twigs and stems in relation to leaf appearance was studied in nine species with different porosity patterns. Cylindrical stem cores and twigs were collected from early spring through late summer from deciduous (Quercus serrata, Liquidambar styraciflua, and Acanthopanax sciadophylloides), and evergreen (Castanopsis cuspidata; Cinnamomum camphora, Ilex pedunculosa, Symplocos prunifolia, Quercus glauca and Quercus myrsinifolia) species in a temperate forest. The first-formed twig vessels lignified at the time of leaf appearance or before in all species. The timing of stem vessel lignification in relation to leaf appearance in semi-ringporous deciduous species was overlapping with that of ring-porous deciduous species and diffuse-porous deciduous species. Evergreen species showed a great variation in the timing of stem vessel lignification, relative to leaf flushing. The main conclusions are that 1) Vessel lignification occurs much earlier in twigs than in trunks of the same trees, with hardly any overlap between the two; 2) Deciduous trees do not differ much from evergreen species, but there is a weak tendency for evergreen species to have later vessel differentiation than deciduous species; 3) The timing of vessel formation shows little relation with porosity patterns and overlaps between diffuse-porous and ring-porous species. This suggests a much greater intergradation of timing of vessel formation in species of different porosity pattern in evergreen and deciduous species than recognized in the literature.
A new species of Cantharellus (Cantharellales, Basidiomycota, Fungi) from subalpine forest in Yunnan, China
Authors: SHAO SHI-CHENG , LIU PEI-GUI , TIAN XIAO-FEI , BUYCK BART , GENG YAN-HONG
Published: March 2016

Cantharellus versicolor is described and illustrated as a new species based on morphological and molecular characters. The most significant features to distinguish the new species from other known Cantharellus are its extremely fleshy, turning gray after injury and with black floccose-fibrillose scales composed of thick-walled and irregular, erect hyphae on the pileus. It is described from the subalpine belt of Shangri-La, northwestern Yunnan, China. Phylogenetic analysis of the transcription elongation factor 1-alpha sequence data further support its systematic position in the subgenus Cantharellus and its description as a new species.
Porcelain crabs from Brazil (Crustacea: Decapoda: Anomura: Porcellanidae)
Authors: FERREIRA LUCIANE AUGUSTO DE AZEVEDO , DE MELO GUSTAVO AUGUSTO SCHMIDT
Published: March 2016

Twenty species of porcelain crabs are reported on the basis of material collected from Brazilian coasts. Considering the lack of systematic studies comprehending the Brazilian porcellanids, the present work presents a review of the regional species based on the current taxonomic information. New records, information about variation between specimens and a taxonomic discussion are given for porcellanid crabs from Brazil.
Two new species of Tricorythus Eaton 1868 (Ephemeroptera, Tricorythidae) from Zambia
Authors: Kluge Nikita J.
Published: March 2016

Larvae, subimagoes, imagoes of both sexes and eggs of Tricorythus furcifer sp.n. and T. tener sp.n. are described based on reared material from Zambia. Larvae of both species closely resemble larvae of T. varicauda (Pictet 1843), while genitals of male imagoes are different, being especially unusual in T. furcifer. A new locality for Tricorythus tinctus Kimmins 1956 is recorded in Zambia.
Plasma Endocan Levels in Patients With Isolated Coronary Artery Ectasia
Authors: Turan Turhan , Akyuz Ali Riza , Aykan Ahmet Cagri , Kul Selim , Cirakoglu Omer Faruk , Aslan Ahmet Oguz , Gul Ilker , Uçar Utku , Demir Selim , Celik Sukru
Published: March 2016

Endocan is a soluble proteoglycan, secreted by human vascular endothelial cells. Endocan is a marker for vascular pathologies and an important mediator of angiogenesis, strongly associated with inflammation, vascular endothelial dysfunction, and atherosclerosis. The relationship between coronary artery ectasia (CAE) and endocan has not been evaluated. We aimed to investigate this association. Fifty-four patients with isolated CAE without coronary stenosis and 30 controls with normal coronary angiogram were included in this study. Endocan plasma concentrations were measured using an enzyme-linked immunosorbent assay. Patients with isolated CAE had significantly higher levels of endocan compared to the controls (18.9 ± 7.3 vs 15.6 ± 3.6 ng/mL; P = .007). There was a significant correlation between endocan levels and severity of isolated CAE according to the Markis classification ( r = −.593, P < .001). Plasma endocan levels may reflect the presence and severity of isolated CAE, suggesting that endocan may be involved in pathogenesis of isolated CAE.