bluuebunny/crossref_metadata_2025 huggingface dataset:
Cartesian Mesh Linearized Euler Equations Solver for Aeroacoustic Problems around Full Aircraft
Authors: Fukushima Yuma , Sasaki Daisuke , Nakahashi Kazuhiro
Published: April 2015

The linearized Euler equations (LEEs) solver for aeroacoustic problems has been developed on block-structured Cartesian mesh to address complex geometry. Taking advantage of the benefits of Cartesian mesh, we employ high-order schemes for spatial derivatives and for time integration. On the other hand, the difficulty of accommodating curved wall boundaries is addressed by the immersed boundary method. The resulting LEEs solver is robust to complex geometry and numerically efficient in a parallel environment. The accuracy and effectiveness of the present solver are validated by one-dimensional and three-dimensional test cases. Acoustic scattering around a sphere and noise propagation from the JT15D nacelle are computed. The results show good agreement with analytical, computational, and experimental results. Finally, noise propagation around fuselage-wing-nacelle configurations is computed as a practical example. The results show that the sound pressure level below the over-the-wing nacelle (OWN) configuration is much lower than that of the conventional DLR-F6 aircraft configuration due to the shielding effect of the OWN configuration.
Trigger Point Dry Needling and Proprioceptive Exercises for the Management of Chronic Ankle Instability: A Randomized Clinical Trial
Authors: Salom-Moreno Jaime , Ayuso-Casado Blanca , Tamaral-Costa Beatriz , Sánchez-Milá Zacarías , Fernández-de-las-Peñas César , Alburquerque-Sendín Francisco
Published: April 2015

Objective.To compare the effects of combined trigger point dry needling (TrP-DN) and proprioceptive/strengthening exercises to proprioceptive/strengthening exercises on pain and function in ankle instability.Methods.Twenty-seven (44% female, mean age:33±3years) individuals with unilateral ankle instability were randomly assigned to an experimental group who received proprioceptive/strengthening exercises combined with TrP-DN into the lateral peroneus muscle and a comparison group receiving the same proprioceptive/strengthening exercise program alone. Outcome included function assessed with the Foot and Ankle Ability Measure (FAAM) and ankle pain intensity assessed with a numerical pain rate scale (NPRS). They were captured at baseline and 1-month follow-up after the intervention.Results.The ANOVAs found significant Group∗Time Interactions for both subscales of the FAAM (ADL:F=8.211;P=0.008; SPORTS:F=13.943;P<0.001) and for pain (F=44.420;P<0.001): patients receiving TrP-DN plus proprioceptive/strengthening exercises experienced greater improvements in function and pain than those receiving the exercise program alone. Between-groups effect sizes were large in all outcomes (SMD > 2.1) in favor of the TrP-DN group.Conclusions.This study provides evidence that the inclusion of TrP-DN within the lateral peroneus muscle into a proprioceptive/strengthening exercise program resulted in better outcomes in pain and function 1 month after the therapy in ankle instability.
Late Stage of Corneal Decompensation Caused by Progressive Keratoconus: Can We Treat It and Save the Cornea?
Authors: Knezović Igor , Belovari Višnjić Mirna , Raguž Hrvoje
Published: April 2015

Aim. To report a case of 40-year-old male with progressive bilateral keratoconus who had undergone transepithelial phototherapeutic keratectomy (TE-PTK) and corneal collagen cross-linking (CXL) using hypoosmolar riboflavin solution in a same day procedure.Methods. Eye examination showed that UCDVA on both eyes was 0,01 according to Snellen charts, and slit lamp biomicroscopy showed paracentral diffuse intrastromal corneal haze. Anterior OCT marked stromal hyperreflective zones and localized paracentral thinning of the cornea. Scheimpflug tomography noted keratoconus stages III-IV on both eyes. After 40/35 microns TE-PTK, a CXL was performed for 30 minutes using hypoosmolar riboflavin solution. The left eye was treated first and the right eye 1 month after. Follow-up period was 10 months.Results. One month after the treatment both eyes showed improvement in corneal topography and the UCDVA was better. Eight months after the treatment BSCVA improved to 0,6 in both eyes using Rose K2 contact lenses and remained stable.Conclusion. TE-PTK and CXL using hypotonic riboflavin solution as a same day procedure have been shown to be a safe and promising method in this case of progressive keratoconus. It was necessary to consider certain parameters that could influence the safety and the final outcome of this combined protocol.
Development ofIn SituSensors for Chlorophyll Concentration Measurement
Authors: Zeng Lihua , Li Daoliang
Published: April 2015

Chlorophyll fluorescence measurement is a sensitive and effective method to quantify and analyze freshwater and sea water phytoplanktonin situ. Major improvements in optical design, electronic technology, and calibration protocol have increased the accuracy and reliability of the fluorometer. This review briefly describes the improvement of probe design, excitation light sources, detectors, and calibrations ofin situfluorometers. Firstly, various optical designs for increasing the efficiency of fluorescence measurement are discussed. Next, the development of electronic technology to meet and improvein situmeasurement, including various light sources, detectors, and corresponding measurement protocols, is described. In addition, various calibration materials, procedures, and methods are recommended for different kinds of water. The conclusion discusses key trends and future perspectives forin situfluorescence sensors.
A New Method Based on TOPSIS and Response Surface Method for MCDM Problems with Interval Numbers
Authors: Wang Peng , Li Yang , Wang Yong-Hu , Zhu Zhou-Quan
Published: April 2015

As the preference of design maker (DM) is always ambiguous, we have to face many multiple criteria decision-making (MCDM) problems with interval numbers in our daily life. Though there have been some methods applied to solve this sort of problem, it is always complex to comprehend and sometimes difficult to implement. The calculation processes are always ineffective when a new alternative is added or removed. In view of the weakness like this, this paper presents a new method based on TOPSIS and response surface method (RSM) for MCDM problems with interval numbers, RSM-TOPSIS-IN for short. The key point of this approach is the application of deviation degree matrix, which ensures that the DM can get a simple response surface (RS) model to rank the alternatives. In order to demonstrate the feasibility and effectiveness of the proposed method, three illustrative MCMD problems with interval numbers are analysed, including (a) selection of investment program, (b) selection of a right partner, and (c) assessment of road transport technologies. The contrast of ranking results shows that the RSM-TOPSIS-IN method is in good agreement with those derived by earlier researchers, indicating it is suitable to solve MCDM problems with interval numbers.
Whole Exome Sequencing Reveals the Order of Genetic Changes during Malignant Transformation and Metastasis in a Single Patient with NF1-plexiform Neurofibroma
Authors: Hirbe Angela C. , Dahiya Sonika , Miller Christopher A. , Li Tiandao , Fulton Robert S. , Zhang Xiaochun , McDonald Sandra , DeSchryver Katherine , Duncavage Eric J. , Walrath Jessica , Reilly Karlyne M. , Abel Haley J. , Pekmezci Melike , Perry Arie , Ley Timothy J. , Gutmann David H.
Published: April 2015

Purpose: Malignant peripheral nerve sheath tumors (MPNST) occur at increased frequency in individuals with neurofibromatosis type 1 (NF1), where they likely arise from benign plexiform neurofibroma precursors. While previous studies have used a variety of discovery approaches to discover genes associated with MPNST pathogenesis, it is currently unclear what molecular events are associated with the evolution of MPNST from plexiform neurofibroma.

Experimental Design: Whole-exome sequencing was performed on biopsy materials representing plexiform neurofibroma (n = 3), MPNST, and metastasis from a single individual with NF1 over a 14-year period. Additional validation cases were used to assess candidate genes involved in malignant progression, while a murine MPNST model was used for functional analysis.

Results: There was an increasing proportion of cells with a somatic NF1 gene mutation as the tumors progressed from benign to malignant, suggesting a clonal process in MPNST development. Copy number variations, including loss of one copy of the TP53 gene, were identified in the primary tumor and the metastatic lesion, but not in benign precursor lesions. A limited number of genes with nonsynonymous somatic mutations (βIII-spectrin and ZNF208) were discovered, several of which were validated in additional primary and metastatic MPNST samples. Finally, increased βIII-spectrin expression was observed in the majority of MPNSTs, and shRNA-mediated knockdown reduced murine MPNST growth in vivo.

Conclusions: Collectively, the ability to track the molecular evolution of MPNST in a single individual with NF1 offers new insights into the sequence of genetic events important for disease pathogenesis and progression for future mechanistic study. Clin Cancer Res; 21(18); 4201–11. ©2015 AACR.
Tiam1-Rac1 Axis Promotes Activation of p38 MAP Kinase in the Development of Diabetic Retinopathy: Evidence for a Requisite Role for Protein Palmitoylation
Authors: Veluthakal Rajakrishnan , Kumar Binit , Mohammad Ghulam , Kowluru Anjaneyulu , Kowluru Renu A.
Published: April 2015

Background/Aims: Evidence in multiple tissues, including retina, suggests generation of reactive oxygen species (ROS) and the ensuing oxidative stress as triggers for mitochondrial defects and cell apoptosis. We recently reported novel roles for Tiam1-Rac1-Nox2 axis in retinal mitochondrial dysfunction and cell death leading to the development of diabetic retinopathy. Herein, we tested the hypothesis that activation of p38 MAP kinase, a stress kinase, represents the downstream signaling event to Rac1-Nox2 activation in diabetes-induced metabolic stress leading to capillary cell apoptosis. Methods: Activation of p38 MAP kinase was quantified by Western blotting in retinal endothelial cells incubated with high glucose (20 mM) for up to 96 hours, a duration where mitochondrial dysfunction and capillary cell apoptosis can be observed. NSC23766 and 2-bromopalmitate (2-BP) were used to assess the roles of Tiam1-Rac1 and palmitoylation pathways, respectively. Results: Activation of p38 MAP kinase was observed as early as 3 hours after high glucose exposure, and continued until 96 hours. Consistent with this, p38 MAP kinase activation was significantly higher in the retina from diabetic mice compared to age-matched normal mice. NSC23766 markedly attenuated hyperglycemia-induced activation of p38 MAP kinase. Lastly, 2-BP inhibited glucose-induced Rac1, Nox2 and p38 MAP kinase activation in endothelial cells. Conclusions: Tiam1-Rac1-mediated activation of Nox2 and p38 MAP kinase constitutes early signaling events leading to mitochondrial dysfunction and the development of diabetic retinopathy. Our findings also provide the first evidence to implicate novel roles for protein palmitoylation in this signaling cascade.
Pig BMSCs Transfected with Human TFPI Combat Species Incompatibility and Regulate the Human TF Pathway in Vitro and in a Rodent Model
Authors: Ji Hongchen , Li Xiao , Yue Shuqiang , Li Junjie , Chen Hui , Zhang Zhuochao , Ma Ben , Wang Jing , Pu Meng , Zhou Liang , Feng Chong , Wang Desheng , Duan Juanli , Pan Dengke , Tao Kaishan , Dou Kefeng
Published: April 2015

Background: The activation of tissue factor (TF) is one of the major reasons for coagulation dysregulation after pig-to-primate xenotransplantation. Tissue factor pathway inhibitor (TFPI) is the most important inhibitor of TF. Studies have demonstrated species incompatibility between pig TFPI and human TF. Methods: A pig-to-macaque heterotopic auxiliary liver transplantation model was established to determine the origin of activated TF. Chimeric proteins of human and pig TFPI were constructed to assess the role of Kunitz domains in species incompatibility. Immortalised pig bone marrow mesenchymal stem cells transfected with human TFPI were tested for their ability to inhibit clotting in vitro. Results: TF from recipient was activated early after liver xenotransplantation. Pig TFPI Kunitz domain 2 bound human FXa, but Kunitz domain 1 did not effectively inhibit human TF/FVIIa. Immortalised pig bone marrow mesenchymal cells (BMSCs) transfected with human TFPI showed a prolonged recalcification time in vitro and in a rodent model. Conclusion: Recipient TF is relevant to dysregulated coagulation after xenotransplantation. Kunitz domain 1 plays the most important role in species incompatibility between pig TFPI and human TF, and clotting can be inhibited by human TFPI-transfected pig BMSCs. Our study shows a possible way to resolve the incompatibility of pig TFPI.
17β-Estradiol and/or Estrogen Receptor β Attenuate the Autophagic and Apoptotic Effects Induced by Prolonged Hypoxia Through HIF-1α-Mediated BNIP3 and IGFBP-3 Signaling Blockage
Authors: Hsieh Dennis Jine-Yuan , Kuo Wei-Wen , Lai Yi-Ping , Shibu Marthandam Asokan , Shen Chia-Yao , Pai Peiying , Yeh Yu-Lan , Lin Jing-Ying , Viswanadha Vijaya Padma , Huang Chih-Yang
Published: April 2015

Background/Aims: The risk of heart disease is higher in males than in females. However, this advantage of females declines with increasing age, presumably a consequence of decreased estrogen secretion and malfunctioning of the estrogen receptor. We previously demonstrated that 17β-estradiol (E2) prevents cardiomyocyte hypertrophy, autophagy and apoptosis via estrogen receptor α (ERα), but the effects of ERβ on myocardial injury remained elusive. The present paper thus, investigated the cardioprotective effects of estrogen (E2) and ERβ against hypoxia-induced cell death. Methods: Transient transfection of Tet-On ERβ gene construct was used to overexpress ERβ in hypoxia-treated H9c2 cardiomyoblast cells. Results: Our data revealed that IGF1R, Akt phosphorylation and Bcl-2 expression are enhanced by ERβ in H9c2 cells. Moreover, ERβ overexpression reduced accumulation of hypoxia-related proteins, autophagy-related proteins and mitochondria-apoptotic proteins and enhanced the protein levels of Bcl-2, pAkt and Bad under hypoxic condition. In neonatal rat ventricular myocytes (NRVMs), we observed that hypoxia induced cell apoptosis as measured by TUNEL staining, and E2 and/or ERβ could totally abolish hypoxia-induced apoptosis. The suppressive effects of E2 and/or ERβ in hypoxia-treated NRVMs were totally reversed by ER antagonist, ICI. Taken together, E2 and/or ERβ exert the protective effect through repressed hypoxia-inducible HIF-1α, BNIP3 and IGFBP-3 levels to restrain the hypoxia-induced autophagy and apoptosis effects in H9c2 cardiomyoblast cells. Conclusion: The results suggest that females probably could tolerate better prolonged hypoxia condition than males, and E2/ERβ treatment could be a potential therapy to prevent hypoxia-induced heart damage.”
Vitamin D and Lung Cancer Risk: A Comprehensive Review and Meta-Analysis
Authors: Zhang Liqun , Wang Sihai , Che Xiaoyu , Li Xuehui
Published: April 2015

Background/Aim: Vitamin D has been suggested to have important roles against cancer development. There were several published studies on the association between vitamin D and lung cancer risk, but not conclusive results were available. Methods: To clarify the role of vitamin D in lung carcinogenesis, we performed a comprehensive review of the literature and a meta-analysis to evaluate the association of serum vitamin D levels and dietary vitamin D intake with lung cancer risk. Twelve studies (9 prospective cohort and 3 nested case-control studies) with a total of 288,778 individuals were included. The summary relative risk (RR) with 95% confidence interval (CI) was used to assess lung cancer risk. Results: Meta-analysis of total 12 studies showed that RR for the association of high vitamin D status with lung cancer was 0.84 (95%CI 0.78-0.90, P < 0.001). The RR of lung cancer for the highest versus lowest quintile of serum vitamin D levels was 0.83 (95%CI 0.77-0.90, P < 0.001). The RR of lung cancer for the highest versus lowest quintile of vitamin D intake was 0.89 (95%CI 0.74-1.06, P = 0.184). Conclusion: Current data suggest an inverse association between serum vitamin D and lung cancer risk. Further studies are needed to investigate the effect of vitamin D intake on lung cancer risk and to evaluate whether vitamin D supplementation can prevent lung cancer.
Clinical and Instrumental Evaluation of the Efficacy of a New Depigmenting Agent Containing a Combination of a Retinoid, a Phenolic Agent and an Antioxidant for the Treatment of Solar Lentigines
Authors: Cameli Norma , Abril Elva , Agozzino Marina , Mariano Maria
Published: April 2015

Background: Solar lentigines are common benign macular hyperpigmented lesions localized on sun-exposed areas. Objective: To evaluate the efficacy and safety of a new depigmenting agent containing a retinoid (retinaldehyde), a new phenolic agent (4-(1-phenylethyl)-resorcinol) and a reducing agent (δ-tocopheryl-β-D-glucopyranoside) in the topical treatment of solar lentigines. Patients and Methods: Twenty patients with solar lentigines of the face and hands applied the depigmenting agent on each lentigo once daily for 12 weeks. The outcome was evaluated at 45 days (T1) and 3 months (T2) after the end of treatment compared to baseline (T0) by means of clinical evaluation, Mexameter® and Visioface devices for digital and ultraviolet computerized image analysis of skin color as well as in vivo reflectance confocal microscopy. Results: Image analysis and confocal laser reflectance microscopy showed that hyperpigmentation was significantly reduced at T2 compared to baseline and to controls. Conclusion: The study treatment was well tolerated and showed significant improvement in the depigmentation of solar lentigines.
Risk Factors for Haemorrhage during Suction Curettage after Uterine Artery Embolization for Treating Caesarean Scar Pregnancy: A Case-Control Study
Authors: Du Yong Jiang , Zhang Xiao Hui , Wang Li Quan
Published: April 2015

Aims: To investigate the potential risk factors for haemorrhage during suction curettage after uterine artery embolization (UAE) in the treatment of caesarean scar pregnancy (CSP). Methods: A case-control study was executed including 35 patients with CSP and haemorrhage during suction curettage after UAE and 140 controls without haemorrhage. The data collected included gestational age, the distance between the gestational mass and the bladder, and the volume of vaginal bleeding. Results: Six patients with UAE needed blood transfusions and two had a hysterectomy, while no patient in the control group needed these interventions. Multivariate analysis showed that both gestational age and the distance between the gestational mass and the bladder were associated with haemorrhage in the CSP group. The odds ratio (OR) of gestational age between cases and controls was 1.579 (95% confidence interval [CI] 1.291-1.933), and the OR of the distance between the gestational mass and the bladder was 0.208 (95% CI 0.082-0.531). Conclusion: Increased gestational age might be an important risk factor for haemorrhage during suction curettage after UAE in the treatment of patients with CSP, and a distance of >0.2 cm between the gestational mass and the bladder was protective against haemorrhage.
Deletion of UNC5B in Kidney Epithelium Exacerbates Diabetic Nephropathy in Mice
Authors: Ranganathan Punithavathi , Mohamed Riyaz , Jayakumar Calpurnia , Brands Michael W. , Ramesh Ganesan
Published: April 2015

Background: Guidance cue netrin-1 was shown to have protective effects in diabetic nephropathy. However, the role of its receptor UNC5B in diabetic kidney disease is unknown. Moreover, whether netrin-1 is protective against diabetic kidney disease in a genetic model of nephropathy and in the nephropathy prone DBA background is also unknown. The aim of this study was to determine the significance of UNC5B in tubular epithelial cells in chronic kidney disease due to diabetes and evaluate whether netrin-1 is also protective in the case of a nephropathy-prone mouse. Methods: Proximal tubular epithelium-specific UNC5B knockout mice as well as heterozygous UNC5B knockout mice were used to determine the roles of UNC5B in nephropathy. Diabetes was induced in these tissue-specific knockout, heterozygous and WT mice, and albuminuria was then monitored. Results: WT and heterozygous diabetic mice developed significant albuminuria at 8 weeks after induction of diabetes as compared to buffer-treated control mice. However, albuminuria was significantly more pronounced in mice with proximal tubule specific deletion of UNC5B. Transgenic overexpression of netrin-1 in proximal tubules in the DBA background and administration of recombinant netrin-1 to Ins2Akita mice also significantly reduced diabetes-induced albuminuria and suppressed glomerular and interstitial lesions. Conclusion: Our data suggested that netrin-1 signaling in proximal tubular epithelium may play a critical role in the protection of kidney against diabetic kidney disease.
Oncologic Concerns regarding Laparoscopic Cytoreductive Surgery in Patients with Advanced Ovarian Cancer Submitted to Neoadjuvant Chemotherapy
Authors: Favero Giovanni , Macerox Nathalia , Pfiffer Tatiana , Köhler Christhardt , da Costa Miranda Vanessa , Estevez Diz Maria Del Pilar , Fukushima Julia Tizue , Baracat Edmund Chada , Carvalho Jesus Paula
Published: April 2015

Background: Presently, the use of laparoscopy in advanced ovarian cancer (AOC) is extremely controversial. In the era of neoadjuvant chemotherapy (NACT), endoscopic debulking surgery could be a reasonable alternative for selected patients with primarily unresectable disease. Objectives: To evaluate the feasibility as well as the operative and oncologic safety of laparoscopic debulking surgery in patients with AOC submitted to NACT. Methods: This is a pilot observational study on initially unresectable, high-grade serous ovarian cancer treated with a sequence of 6 cycles of carboplatin and paclitaxel followed by debulking surgery performed by laparoscopy (group 1) or laparotomy (group 2). The inclusion criteria were clinical complete response, CA-125 normalization, imaging without disease in critical areas, and optimal cytoreduction. Results: From January 2011 to March 2014, 21 patients were included. Ten women underwent laparoscopy and 11 laparotomy. No epidemiological or oncologic differences were observed between the groups. No surgery-related casualties, intraoperative complications, conversion to laparotomy, or excessive blood loss or transfusion was detected in the laparoscopic procedures. The mean time of operation was 292 min. The length of hospital stay averaged 3.6 days. Two women in group 1 developed relevant complications. After a mean follow-up of 20 months, the recurrence rates were similar, i.e. 80% in group 1 versus 88% in group 2. Although statistical significance was not reached, the mortality related to cancer was considerably higher (20 vs. 0%; p = 0.086) and the mean chemotherapy-free interval was markedly shorter in group 1 (13.3 vs. 20.5 months; p = 0.288). Conclusion: Laparoscopic optimal debulking surgery after NACT is feasible and effective in selected patients. Nevertheless, laparoscopy was substantially associated with inferior oncologic results. Endoscopic cytoreduction in AOC should be cautiously suggested until larger prospective trials confirm the observed results.
Sublobar Resection, Radiofrequency Ablation or Radiotherapy in Stage I Non-Small Cell Lung Cancer
Authors: Safi Seyer , Rauch Geraldine , op den Winkel Jan , Kunz Josef , Schneider Thomas , Bischof Marc , Heussel Claus Peter , Huber Peter E. , Herth Felix J.F. , Dienemann Hendrik , Hoffmann Hans
Published: April 2015

Background: The best therapy for patients with stage I non-small cell lung cancer (NSCLC) who are medically unfit for lobectomy or prefer not to undergo surgery has not yet been demonstrated. Objectives: We analyzed data from our prospective database to evaluate the recurrence and survival rates and assess the extent to which the type of treatment explains outcome differences. Methods: This study included 116 patients with histologically proven clinical stage I NSCLC who were treated with sublobar resection (SLR; n = 42), radiofrequency ablation (RFA; n = 25) or radiotherapy (RT; n = 49) between 2009 and 2013. The primary end point was the time to primary tumor recurrence (PR). Kaplan-Meier curves and Cox regression were used to compare the recurrence patterns and survivals after adjustments for potential confounders. Results: The SLR patients were younger and exhibited better performance status. The RT patients had larger tumors. After adjusting for age and tumor size, there were differences between the different treatments in terms of the PR rate, but no differences were observed in overall (OS) or disease-free survival. The hazard ratio for PR comparing SLR versus RT adjusted for age and tumor size was 2.73 (95% confidence interval, CI, 0.72-10.27) and that for SLR versus RFA was 7.57 (95% CI 1.94-29.47). Conclusions: Our study suggests that SLR was associated with a higher primary tumor control rate compared to RFA or RT, although the OSs were not different. These results should be confirmed in prospective trials.
Association of Pneumococcal Carriage and Expression of Foxp3+ Regulatory T Cells and Th17 Cells in the Adenoids of Children
Authors: Jiang Xiao-li , Zhang Guang-li , Yang Ting , Yang Bao-hui , Wang Li-jia , Wang Qing-hong , Luo Zheng-xiu , Liu En-mei , Fu Zhou
Published: April 2015

Background: Pneumococcal carriage in the nasopharynx is a primary means of transmission and a necessary prerequisite for pneumococcal disease. Objectives: We analyzed the relationship between expressions of Foxp3+ regulatory T (Treg) cells and Th17 cells, and pneumococcal carriage in the adenoids of children who were either positive or negative for pneumococci. Methods: We collected adenoidal tissue and nasopharyngeal swab samples from children undergoing an adenoidectomy. Adenoidal mononuclear cells were isolated, cultured and then stimulated with culture concentrated supernatant (CCS) obtained from a D39 bacterial strain. Results: Foxp3+ Treg cells were upregulated and Th17 cells were downregulated in populations of adenoidal mononuclear cells obtained from the pneumococcus-positive group. Following CCS stimulation, the increment in Foxp3+ Treg cells in the pneumococcus-positive group was significantly greater than that in the pneumococcus-negative group, while the increment in Th17 cells was less as compared to that in the pneumococcus-negative group. These results were consistent with variations in levels of Foxp3 mRNA and retinoic acid receptor-related orphan receptor-γt mRNA in adenoidal mononuclear cells. Levels of IL-17A and IL-6 in adenoid tissue were higher in the pneumococcus-negative group, and the levels of TGF-β in adenoid tissue were lower in the pneumococcus-negative group compared to the pneumococcus-positive group. Pneumococcal carriage in children was closely associated with the expressions of Foxp3+ Treg and Th17 cells in the adenoid. Conclusion: Upregulation of Foxp3+ Treg cells might downregulate the production of Th17 cells in the adenoid, resulting in decreased scavenging of Streptococcus pneumoniae and chronic pneumococcal carriage.
Physical Status and Variant Analysis of Human Papillomavirus 16 in Women from Shanghai
Authors: Guo Yi , Hu Jiachang , Zhu Liping , Sun Jing , Xie Longxu , Kong Fanfei , Han Lingfei , Li Fang
Published: April 2015

Background/Aims: Human papillomavirus type 16 (HPV16) is the cause of more than half of all cases of cervical cancer. Genetic mutations in HPV16 and the integration of HPV16 DNA in the human genome are considered important genetic changes in cervical lesion progression. However, limited data concerning HPV16 lineages and physical integration status have been reported for Shanghai, China. The current study analyzed the genetic mutations in complete HPV16 genomes and the physical integration status of HPV16 DNA. Methods: A total of 30 samples of cervical exfoliated cells from patients with HPV16 infection were collected. The entire HPV16 genome was isolated, amplified by PCR and directly sequenced. The physical integration status was determined by 3′RACE nested PCR. Results: A total of 13 integration sites were identified, including 9 in common fragile sites and 1 not close to any fragile sites. Phylogenetic analysis identified two HPV lineages: the European (E) lineage and the East Asian (EA) lineage. Amino acid changes of D25E and N29S were the most common variations across the genome. The HPV16 early genes E1 and E7 and the late gene L1 tended to be highly conserved, whereas the early genes E2, E4 and E6 were more variable. Furthermore, 10 novel variations were identified in this study, which led to the 3 amino acid changes of S23I in E2 and E244K and T269I in E2/E4. Conclusion: Integrated HPV16 viruses were detected in all stages of cervical samples. Many variants in E2, E4, E7, and the long control region co-varied with E6 variations and helped to define the HPV16 lineages.
Chinese Hypertension Guidelines
Authors: Wang Ji-Guang
Published: April 2015

According to the 4th National Nutrition and Health Survey in 2002, the prevalence of hypertension in China was 18.8%. Although there are no recent updated nationwide data, it is believed that the prevalence of hypertension has increased substantially in the past decade up to more than 200 million hypertensive patients in the populous country of China. To fight against the growing risk of hypertension, three Chinese hypertension guidelines were compiled in the past two decades, in 1999, 2005, and 2011. The current guidance document for the management of hypertension was named ‘2010 Chinese hypertension guideline', but it was actually published in 2011. In this guideline, all five classes of antihypertensive drugs were recommended as possible initial and maintenance therapy. The goal of treatment was a systolic/diastolic blood pressure below 140/90 mm Hg in general, 130/80 mm Hg in various groups of high-risk patients, and 150/90 mm Hg in the elderly (≥65 years). With the recent publication of several national and international hypertension guidelines, the Chinese guideline is now under discussion for updating.
Temozolomide in Advanced Neuroendocrine Neoplasms: Pharmacological and Clinical Aspects
Authors: Koumarianou Anna , Kaltsas Gregory , Kulke Matthew H. , Oberg Kjell , Strosberg Jonathan R. , Spada Francesca , Galdy Salvatore , Barberis Massimo , Fumagalli Caterina , Berruti Alfredo , Fazio Nicola
Published: April 2015

Alkylating agents, such as streptozocin and dacarbazine, have been reported as active in neuroendocrine neoplasms (NENs). Temozolomide (TMZ) is an oral, potentially less toxic derivative of dacarbazine, which has shown activity both as a single agent and in combination with other drugs. Nevertheless, its role in NENs has not been well defined. Several retrospective and prospective phase I-II studies have been published describing its use in a variety of NENs. In a retrospective series, the combination of capecitabine and TMZ was reported to be associated with a particularly high tumour response in pancreatic NENs as a first-line treatment. Although in NENs, determination of the O6-methylguanine-DNA methyltransferase (MGMT) status has been suggested as a predictive biomarker of response, its role still remains investigational, awaiting validation along with the establishment of the optimal detection method. Metronomic schedules have been reported to potentially overcome MGMT-related drug resistance. Toxicity is manageable if well monitored. We reviewed the literature regarding pharmacological and clinical aspects of TMZ, focusing on specific settings of NENs, different schedules, toxicity and safety profiles, and potential predictive biomarkers of response.
Estrogens Suppress Spinal Endomorphin 2 Release in Female Rats in Phase with the Estrous Cycle
Authors: Kumar Arjun , Storman Emiliya M. , Liu Nai-Jiang , Gintzler Alan R.
Published: April 2015

Background/Aims: Male and female rats differ in their ability to utilize spinal endomorphin 2 (EM2; the predominant mu-opioid receptor ligand in spinal cord) and in the mechanisms that underlie spinal EM2 analgesic responsiveness. We investigated the relevance of spinal estrogen receptors (ERs) to the in vivo regulation of spinal EM2 release. Methods: ER antagonists were administered directly to the lumbosacral spinal cord of male and female rats, intrathecal perfusate was collected, and resulting changes in EM2 release were quantified using a plate-based radioimmunoassay. Results: Intrathecal application of an antagonist of either estrogen receptor-α (ERα) or the ER GPR30 failed to alter spinal EM2 release. Strikingly, however, the concomitant blockade of ERα and GPR30 enhanced spinal EM2 release. This effect was sexually dimorphic, being absent in males. Furthermore, the magnitude of the enhancement of spinal EM2 release in females was dependent upon estrous cycle stage, suggesting a relationship with circulating levels of 17β-estradiol. The rapid onset of enhanced EM2 release following intrathecal application of ERα/GPR30 antagonists (within 30-40 min) suggests mediation via ERs in the plasma membrane, not the nucleus. Notably, both ovarian and spinally synthesized estrogens are essential for membrane ER regulation of spinal EM2 release. Conclusion: These findings underscore the importance of estrogens for the regulation of spinal EM2 activity and, by extension, endogenous spinal EM2 antinociception in females. Components of the spinal estrogenic mechanism(s) that suppress EM2 release could represent novel drug targets for improving utilization of endogenous spinal EM2, and thereby pain management in women.
The Operation Sequence Model—Combining N-Gram-Based and Phrase-Based Statistical Machine Translation
Authors: Durrani Nadir , Schmid Helmut , Fraser Alexander , Koehn Philipp , Schütze Hinrich
Published: April 2015

In this article, we present a novel machine translation model, the Operation Sequence Model (OSM), which combines the benefits of phrase-based and N-gram-based statistical machine translation (SMT) and remedies their drawbacks. The model represents the translation process as a linear sequence of operations. The sequence includes not only translation operations but also reordering operations. As in N-gram-based SMT, the model is: (i) based on minimal translation units, (ii) takes both source and target information into account, (iii) does not make a phrasal independence assumption, and (iv) avoids the spurious phrasal segmentation problem. As in phrase-based SMT, the model (i) has the ability to memorize lexical reordering triggers, (ii) builds the search graph dynamically, and (iii) decodes with large translation units during search. The unique properties of the model are (i) its strong coupling of reordering and translation where translation and reordering decisions are conditioned on n previous translation and reordering decisions, and (ii) the ability to model local and long-range reorderings consistently. Using BLEU as a metric of translation accuracy, we found that our system performs significantly better than state-of-the-art phrase-based systems (Moses and Phrasal) and N-gram-based systems (Ncode) on standard translation tasks. We compare the reordering component of the OSM to the Moses lexical reordering model by integrating it into Moses. Our results show that OSM outperforms lexicalized reordering on all translation tasks. The translation quality is shown to be improved further by learning generalized representations with a POS-based OSM.
A review of the New World Coproica (Diptera: Sphaeroceridae) with a description of 8 new species
Authors: BERGERON MATTHEW D. , MARSHALL STEPHEN A. , SWANN JOHN E.
Published: April 2015

The New World species of Coproica Rondani, 1861 (Diptera: Sphaeroceridae) are reviewed on the basis of over 17,000 examined specimens. The genus is divided into three major clades: the C. acutangula, C. vagans, and C. urbana species groups. Eight new species (C. bifurcata, C. bispatha, C. brachystyla, C. diabolica, C. emarginata, C. galapagosensis, C. novacula, and C. testudinea) are described, and redescriptions are provided for eleven additional species. Included are two keys (one for the twenty New World species only and one for all described species), updated New World distribution records, and illustrations of male and female genitalic structures.
Improved Simulation of Regional Climate by Global Models with Higher Resolution: Skill Scores Correlated with Grid Length*
Authors: Watterson I. G.
Published: April 2015

The current generation of climate models, as represented by phase 5 of the Coupled Model Intercomparison Project (CMIP5), has previously been assessed as having more skill in simulating the observed climate than the previous ensemble from phase 3 of CMIP (CMIP3). Furthermore, the skill of models in reproducing seasonal means of precipitation, temperature, and pressure from two observational datasets, quantified by the nondimensional Arcsin–Mielke skill score, appeared to be influenced by model resolution. The analysis is extended to 42 CMIP5 and 24 CMIP3 models. For the combined skill scores for six continents, averaged over the three variables and four seasons, the correlation with model grid length in the 66-model ensemble is −0.73. Focusing on the comparison with ERA-Interim data at higher resolution and with greater regional detail, correlations are nearly as strong for scores over the ocean domain as for land. For the global domain (excluding the Antarctic cap), the correlation of the overall skill score with grid length is −0.61, and it is nearly as strong for each variable. For most tests the improved averaged score of CMIP5 models relative to those from CMIP3 is largely consistent with their increased resolution. However, the improvement for precipitation and the correlations with length are both smaller if rmse is used as a metric. They are smaller again using the GPCP observational data, as the regional detail from a high-resolution model can lead to larger differences when compared to relatively smooth observational fields.
Arctic Radiative Fluxes: Present-Day Biases and Future Projections in CMIP5 Models
Authors: English Jason M. , Gettelman Andrew , Henderson Gina R.
Published: April 2015

Radiative fluxes are critical for understanding the energy budget of the Arctic region, where the climate has been changing rapidly and is projected to continue to change. This work investigates causes of present-day biases and future projections of top-of-atmosphere (TOA) Arctic radiative fluxes in phase 5 of the Coupled Model Intercomparison Project (CMIP5). Compared to Clouds and the Earth’s Radiant Energy System Energy Balanced and Filled (CERES-EBAF), CMIP5 net TOA downward shortwave (SW) flux biases are larger than outgoing longwave radiation (OLR) biases. The primary contributions to modeled TOA SW flux biases are biases in cloud amount and snow cover extent compared to the GCM-Oriented CALIPSO Cloud Product (CALIPSO-GOCCP) and the newly developed Making Earth System Data Records for Use in Research Environments (MEaSUREs) dataset, respectively (with most models predicting insufficient cloud amount and snow cover in the Arctic), and biases with sea ice albedo. Future projections (2081–90) with representative concentration pathway 8.5 (RCP8.5) simulations suggest increasing net TOA downward SW fluxes (+8 W m−2) over the Arctic basin due to a decrease of surface albedo from melting snow and ice, and increasing OLR (+6 W m−2) due to an increase in surface temperatures. The largest contribution to future Arctic net TOA downward SW flux increases is declining sea ice area, followed by declining snow cover area on land, reductions to sea ice albedo, and reductions to snow albedo on land. Cloud amount is not projected to change significantly. These results suggest the importance of accurately representing both the surface area and albedos of sea ice and snow cover as well as cloud amount in order to accurately represent TOA radiative fluxes for the present-day climate and future projections.
MCAC and State Counselor Licensure Laws
Authors: Robinson Kurpius Sharon E. , Keaveny Maureen K. , Kim Charlene S. , Walsh Kelsey J.
Published: April 2015

Although all 50 states, as well as Washington DC and Puerto Rico, have passed laws that license master’s-level professional counselors, the American Psychological Association has historically not taken a role in addressing master’s-level education. In 2009, the Council for Accreditation of Counseling and Related Educational Programs (CACREP) initiated standards excluding psychologists as core faculty and has been a driving force with state licensing boards to credential graduates from CACREP-accredited programs exclusively. The Council for Counseling Psychology Training Programs explored the Masters in Counseling Accreditation Committee (MCAC) as an alternative accreditation for master’s counseling programs. This study examined the extent to which MCAC accreditation standards align with state counselor licensure statutes. Content analyses indicated that MCAC is a viable alternative accreditation if programs pay attention to state required credits for a degree, curricular requirements not specified by MCAC, and clinical requirements. Implications of these findings and recommendations are discussed.
Planning to Save the Planet
Authors: Bell Beth T. , Toth Nicola , Little Linda , Smith Michael A.
Published: April 2015

Adolescents are an important population to target with energy-saving interventions: Not only are adolescents high consumers of energy, but they are also the adult consumers of the future. In the present study, an online energy-saving intervention was developed based on implementation intentions, a widely used psychological behavior change technique. A total of 180 adolescents, aged 13 to 15 years, were recruited using purposeful sampling and were allocated to either the intervention or control condition. A significant increase in adolescent’s self-reported energy-saving behavior was found among adolescents who had received the intervention, which was sustained at the 6-week follow-up. However, some adolescents were more affected by the intervention than others; adolescents who already actively engaged in energy saving (as identified by their readiness to change prior to the intervention) reported a significant increase in energy-saving behaviors as a consequence of participation in the intervention, whereas those who were not already saving energy did not.
Insulin Response Genes in Different Stages of Periodontal Disease
Authors: Yu N. , Barros S.P. , Zhang S. , Moss K.L. , Phillips S.T. , Offenbacher S.
Published: April 2015

Bacterial infections are known to alter glucose metabolism within tissues via mechanisms of inflammation. We conducted this study to examine whether insulin response genes are differentially expressed in gingival tissues, comparing samples from experimental gingivitis and periodontitis subjects to those from healthy individuals. Total RNA was extracted from gingival biopsies from 26 participants: 8 periodontally healthy, 9 experimental gingivitis, and 9 periodontitis subjects. Gene expression patterns were evaluated with a polymerase chain reaction array panel to examine 84 candidate genes involved with glucose metabolism, insulin resistance, and obesity. Array data were evaluated with a t test adjusted by the false discover rate ( P < 0.05), and ingenuity pathway analysis was performed for statistical testing of pathways. Although tissue samples were not sufficient to enable protein quantification, we confirmed the upregulation of the key gene using lipopolysaccharide-stimulated primary gingival epithelial cells by Western blot. The mRNA expression patterns of genes that are associated with insulin response and glucose metabolism are markedly different in experimental gingivitis subjects compared with healthy controls. Thirty-two genes are upregulated significantly by at least 2-fold, adjusted for false discover rate ( P < 0.05). Periodontitis subjects show similar but attenuated changes in gene expression patterns, and no genes meet the significance criteria. Ingenuity pathway analysis demonstrates significant activation of the carbohydrate metabolism network in experimental gingivitis but not in periodontitis. G6PD protein increases in response to lipopolysaccharide stimulation in primary gingival epithelial cells, which is in the same direction as upregulated mRNA in tissues. Acute gingival inflammation may be associated with tissue metabolism changes, but these changes are not evident in chronic periodontitis. This study suggests that acute gingival inflammation may induce localized changes that modify tissue insulin/glucose metabolism.
A porcine model: surgical anatomy of the orbit for maxillofacial surgery
Authors: Kyllar Michal , Štembírek Jan , Danek Zdenek , Hodan Radek , Stránský Jiří , Machoň Vladimír , Foltán René
Published: April 2015

Due to its similarity to humans, the pig has proven to be a suitable biomodel for both research purposes and for training medical professionals, particularly in surgical specializations. For example, new implant materials have been tested on pig jaws and pigs have also been used in the development of new surgical techniques. For optimizing the effectiveness of such research or training, detailed data on the anatomy of their particular features are needed. At present, however, only limited information related to surgical and imaging anatomy of the facial and orbital areas of the pig and its comparison to human structures from the experimental surgery point of view is available in the literature. The aim of this study was to obtain such data and to compare the morphological structures of the porcine and human orbital regions and to lay down the foundation for practical use in experimental surgery. Ten pig heads were examined using computed tomography (CT) and magnetic resonance imaging (MRI) and, subsequently, a dissection of the orbit was carried out. Attention was focused on the structure of the orbit (floor, rim and nerves) frequently affected by pathological processes in humans (such as trauma, infection or tumours) and which consequently are frequently the subject of maxillofacial surgery. The porcine orbit is suitable for use in experimental medicine. However, if used in experiments, its anatomical peculiarities must be taken into consideration. Our study presents a foundation of basic knowledge for researchers who plan to use the pig as a biomedical model to investigate alternative treatments in the head region.
The spectre of censorship: media regulation, political anxiety and public contestations in India (2011–2013)
Authors: Rajkhowa Arjun
Published: April 2015

This article focuses on contemporary discussions around media regulation and Internet regulation in India and examines in particular certain events from 2011 to 2013. The aim is to present a composite narrative and historical account, a rendering of the important proposals, arguments and judicial proceedings that came about at a time of political upheaval and increased media ‘activism’. It concludes with a discussion of an August 2013 conference which offers an insight into the latest discursive developments in the field.