bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Algorithm for Reconstructing Two-Dimensional Temperature Distribution by Ultrasonic Thermometry
Authors: Shen Xuehua , Xiong Qingyu , Shi Weiren , Liang Shan , Shi Xin , Wang Kai
Published: February 2015

Temperature, especially temperature distribution, is one of the most fundamental and vital parameters for theoretical study and control of various industrial applications. In this paper, ultrasonic thermometry to reconstruct temperature distribution is investigated, referring to the dependence of ultrasound velocity on temperature. In practical applications of this ultrasonic technique, reconstruction algorithm based on least square method is commonly used. However, it has a limitation that the amount of divided blocks of measure area cannot exceed the amount of effective travel paths, which eventually leads to its inability to offer sufficient temperature information. To make up for this defect, an improved reconstruction algorithm based on least square method and multiquadric interpolation is presented. And then, its reconstruction performance is validated via numerical studies using four temperature distribution models with different complexity and is compared with that of algorithm based on least square method. Comparison and analysis indicate that the algorithm presented in this paper has more excellent reconstruction performance, as the reconstructed temperature distributions will not lose information near the edge of area while with small errors, and its mean reconstruction time is short enough that can meet the real-time demand.
Ultrasonographic and Scintigraphic Findings of Thyroid Hemiagenesis in a Child: Report of a Rare Male Case
Authors: Ayaz Ümit Yaşar , Ayaz Sevin , Döğen Mehmet Ercüment , Api Arman
Published: February 2015

Thyroid hemiagenesis is a rare congenital anomaly in which one lobe of thyroid gland fails to develop. It is much rarer in males. There is a higher incidence of associated thyroid disorders in patients with thyroid hemiagenesis; therefore early and prompt diagnosis is important for children. We present the ultrasonographic and scintigraphic findings of thyroid hemiagenesis in an eight-year-old-boy. On ultrasonography (US), left lobe of the thyroid gland could not be demonstrated and the right lobe showed minimal hyperplasia. Its echogenicity was normal and no nodule was seen. On thyroid scintigraphy, left lobe of thyroid gland or any ectopic thyroid tissue could not be demonstrated, while the right lobe showed minimal hyperplasia. Without performing any invasive procedure, we enrolled the child in a follow-up program with the guidance of US and scintigraphy, which were effective both in making the final diagnosis of thyroid hemiagenesis and in evaluating the current status of the present thyroid tissue. In conclusion, if only one thyroid lobe is detected in a pediatric case initially with US or scintigraphy, the diagnosis of thyroid hemiagenesis should be suggested and, before any unnecessary or invasive attempt, the other complementary method (scintigraphy/US) should be performed.
Risk Factors and Medico-Economic Effect of Pancreatic Fistula after Pancreaticoduodenectomy
Authors: Huang Renping , Liu Bing , Chen Hua , Bai Xuewei , Kong Rui , Wang Gang , Wang Yongwei , Sun Bei , Guan Yinghui
Published: February 2015

The study aimed to uncover the risk factors for the new defined pancreatic fistula (PF) and clinical related PF (CR-PF) after pancreaticoduodenectomy (PD) surgery and to evaluate the medico-economic effect of patients. A total of 412 patients were classified into two groups according to different criteria, PF and NOPF according to PF occurrence: CR-PF (grades B and C) and NOCR-PF (grade A) based on PF severity. A total of 28 factors were evaluated by univariate and multivariate logistic regression test. Hospital charges and stays of these patients were assessed. The results showed that more hospital stages and charges are needed for patients in PF and CR-PF groups than in NOPF and NOCR-PF groups (P<0.05). The excessive drinking, soft remnant pancreas, preoperative albumin, and intraoperative blood transfusion are risk factors affecting both PF and CR-PF incidence. More professional surgeons can effectively reduce the PF and CR-PF incidence. Patients with PF and CR-PF need more hospital costs and stages than that in NOPF and NOCR-PF groups. It is critical that surgeons know the risk factors related to PF and CR-PF so as to take corresponding therapeutic regimens for each patient.
The COMRADE System for Multirobot Autonomous Landmine Detection in Postconflict Regions
Authors: Dasgupta Prithviraj , Baca José , Guruprasad K. R. , Muñoz-Meléndez Angélica , Jumadinova Janyl
Published: February 2015

We consider the problem of autonomous landmine detection using a team of mobile robots. Previous research on robotic landmine detection mostly employs a single robot equipped with a landmine detection sensor to detect landmines. We envisage that the quality of landmine detection can be significantly improved if multiple robots are coordinated to detect landmines in a cooperative manner by incrementally fusing the landmine-related sensor information they collect and then use that information to visit locations of potential landmines. Towards this objective, we describe a multirobot system called COMRADES to address different aspects of the autonomous landmine detection problem including distributed area coverage to detect and locate landmines, information aggregation to fuse the sensor information obtained by different robots, and multirobot task allocation (MRTA) to enable different robots to determine a suitable sequence to visit locations of potential landmines while reducing the time required and battery expended. We have used commercially available all-terrain robots called Coroware Explorer that are customized with a metal detector to detect metallic objects including landmines, as well as indoor Corobot robots, both in simulation and in physical experiments, to test the different techniques in COMRADES.
Unilateral Oral Mucous Membrane Pemphigoid: Refractory Atypical Presentation Successfully Treated with Intravenous Immunoglobulins
Authors: Laureano André , Cardoso Jorge
Published: February 2015

A 57-year-old male presented with a 6-month history of blisters and painful erosions on the right buccal mucosa. No skin or other mucosal involvement was seen. The findings of histopathological and direct immunofluorescence examinations were sufficient for the diagnosis of oral mucous membrane pemphigoid in the context of adequate clinical correlation. No response was seen after topical therapies and oral corticosteroids or dapsone. Intravenous immunoglobulin was started and repeated every three weeks. Complete remission was achieved after three cycles and no recurrence was seen after two years of follow-up. The authors report a rare unilateral presentation of oral mucous membrane pemphigoid on the right buccal and hard palate mucosa, without additional involvement during a period of five years. Local trauma or autoimmune factors are possible etiologic factors for this rare disorder, here with unique presentation.
Study on the Identification ofRadix Bupleurifrom Its Unofficial Varieties Based on Discrete Wavelet Transformation Feature Extraction of ATR-FTIR Spectroscopy Combined with Probability Neural Network
Authors: Jin Wenying , Wan Chayan , Cheng Cungui
Published: February 2015

The attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) was employed to acquire the infrared spectra ofRadix Bupleuriand its unofficial varieties: the root ofBupleurum smithiiWolff and the root ofBupleurum bicauleHelm. The infrared spectra and spectra of Fourier self-deconvolution (FSD), discrete wavelet transform (DWT), and probability neural network (PNN) of these species were analyzed. By the method of FSD, there were conspicuous differences of the infrared absorption peak intensity of different types betweenRadix Bupleuriand its unofficial varieties. But it is hard to tell the differences between the root ofBupleurum smithiiWolff and the root ofBupleurum bicaule. The differences could be shown more clearly when the DWT was used. The research result shows that by the DWT technology it is easier to identifyRadix Bupleurifrom its unofficial varieties the root ofBupleurum smithiiWolff and the root ofBupleurum bicaule.
Myofibroblast Expression in Skin Wounds Is Enhanced by Collagen III Suppression
Authors: Al-Qattan Mohammed M. , Abd-Elwahed Mervat M. , Hawary Khalid , Arafah Maha M. , Shier Medhat K.
Published: February 2015

Generally speaking, the excessive expression of myofibroblasts is associated with excessive collagen production. One exception is seen in patients and animal models of Ehlers-Danlos syndrome type IV in which theCOL3A1gene mutation results in reduced collagen III but with concurrent increased myofibroblast expression. This paradox has not been examined with the use of external drugs/modalities to prevent hypertrophic scars. In this paper, we injected the rabbit ear wound model of hypertrophic scarring with two doses of a protein called nAG, which is known to reduce collagen expression and to suppress hypertrophic scarring in that animal model. The higher nAG dose was associated with significantly less collagen III expression and concurrent higher degree of myofibroblast expression. We concluded that collagen III content of the extracellular matrix may have a direct or an indirect effect on myofibroblast differentiation. However, further research is required to investigate the pathogenesis of this paradoxical phenomenon.
Combination Therapy with Oleanolic Acid and Metformin as a Synergistic Treatment for Diabetes
Authors: Wang Xue , Chen Yupeng , Abdelkader Daoud , Hassan Waseem , Sun Hongbin , Liu Jun
Published: February 2015

Aims and Background. Type 2 diabetes is a chronic disease that cannot be treated adequately using the known monotherapies, especially when the disease progresses to an advanced stage. In this study, we explore the possibility of treating the disease with a novel combination approach of oleanolic acid (OA), a glycogen phosphorylase (GP) inhibitor, and metformin.Methods. Db/db mice were randomly divided into four groups: a db/db control group, db/db mice treated with OA (250 mg/kg), db/db mice treated with metformin (100 mg/kg), and db/db mice treated with a combination of OA and metformin. All mice were treated for four weeks. The effects of the treatments on glucose homeostasis were measured using an OGTT, an assessment of insulin sensitivity and signaling in the liver, and the hepatic glucose production.Results. Combination therapy with OA and metformin significantly reduced the blood glucose and insulin levels and improved the liver pathology compared with that for the monotherapy in the db/db diabetic mouse model. We also found that the combination therapy significantly increased the mRNA expression of glycogen synthesis and decreased the GP, PGC-1α, PEPCK1, and G-6-Pase levels. In addition, the combination therapy with OA and metformin significantly increased the phosphorylation of AKT, PI3K, AMPK, and ACC and decreased the protein expression levels of G-6-Pase, PEPCK1, and TORC compared with those for either monotherapy. The combination therapy also reduced the phosphorylation of mTOR and CREB.Conclusions. Our results suggest that the combination therapy with OA and metformin has synergistic effects on the symptoms of db/db diabetic mice by improving glucose and insulin homeostasis.
Physical Exercise and Redox Balance in Type 2 Diabetics: Effects of Moderate Training on Biomarkers of Oxidative Stress and DNA Damage Evaluated through Comet Assay
Authors: Pittaluga Monica , Sgadari Antonio , Dimauro Ivan , Tavazzi Barbara , Parisi Paolo , Caporossi Daniela
Published: February 2015

Objective.Hyperglycemia leads to increased production of reactive oxygen species (ROS) in type 2 diabetes, which reduces cellular antioxidant defenses and induces DNA lesions. The aim of this study was to investigate the effects on redox homeostasis and DNA oxidative damage of exercise training in patients with type 2 diabetes compared with nondiabetic individuals.Methods and Results.12 sedentary type 2 diabetic males (62.1 ± 4.3 yrs) and 12 sedentary healthy males (61.7 ± 3.9 yrs) were exposed to 4-month moderate training, 3 times per week, to evaluate the effect on plasma biomarkers of oxidative stress malondialdehyde and antioxidant status (GSSG, GSH/GSSG, and ascorbic acid) as well as basal and H2O2-induced DNA damage trough alkaline comet assay in peripheral blood lymphocytes. After training, glutathione and ascorbic acid levels increased in both groups, but only in diabetics the malondialdehyde as well as the DNA damage decreased.Conclusion.Our study demonstrates for the first time that moderate exercise training is not only effective in improving the redox homeostasis, through an increase of the endogenous antioxidant defences in healthy as well as in diabetic patients, but also, specifically in diabetic patients, effective in lowering the susceptibility to oxidative DNA damage and the lipid peroxidation levels.
A Hybrid Technique for Order Preference in Decision-Making
Authors: Beg Ismat , Rashid Tabasam
Published: February 2015

We propose a hybrid technique by merging fuzzy version of the classical technique for order preference by similarity to ideal solution and decision-making trial and evaluation laboratory technique for trapezoidal fuzzy numbers, where interaction phenomena among the decision-making problem and weights are taken into account. The feasibility of this new method is demonstrated by applying it to an example.
Phase II Study of Nilotinib in Melanoma Harboring KIT Alterations Following Progression to Prior KIT Inhibition
Authors: Carvajal Richard D. , Lawrence Donald P. , Weber Jeffrey S. , Gajewski Thomas F. , Gonzalez Rene , Lutzky Jose , O'Day Steven J. , Hamid Omid , Wolchok Jedd D. , Chapman Paul B. , Sullivan Ryan J. , Teitcher Jerrold B. , Ramaiya Nikhil , Giobbie-Hurder Anita , Antonescu Cristina R. , Heinrich Michael C. , Bastian Boris C. , Corless Christopher L. , Fletcher Jonathan A. , Hodi F. Stephen
Published: February 2015

Purpose: Although durable responses can be achieved with tyrosine kinase inhibitors such as imatinib in melanomas harboring KIT mutations, the efficacy of alternative inhibitors after progression to imatinib and the activity of these agents on brain metastases are unknown.

Experimental Design: We conducted a phase II study of nilotinib 400 mg twice a day in two cohorts of patients with melanomas harboring KIT mutations or amplification: (A) those refractory or intolerant to a prior KIT inhibitor; and (B) those with brain metastases. The primary endpoint was 4-month disease control rate. Secondary endpoints included response rate, time-to-progression (TTP), and overall survival (OS). A Simon two-stage and a single-stage design was planned to assess for the primary endpoint in cohorts A and B, respectively.

Results: Twenty patients were enrolled and 19 treated (11 in cohort A; 8 in cohort B). Three patients on cohort A [27%; 95% confidence interval (CI), 8%–56%] and 1 on cohort B (12.5%; 90% CI, 0.6%–47%) achieved the primary endpoint. Two partial responses were observed in cohort A (18.2%; 90% CI, 3%–47%); none were observed in cohort B. The median TTP and OS was 3.3 (90% CI, 2.1–3.9 months) and 9.1 months (90% CI, 4.3–14.2 months), respectively, in all treated patients.

Conclusions: Nilotinib may achieve disease control in patients with melanoma harboring KIT alterations and whose disease progressed after imatinib therapy. The efficacy of this agent in KIT-altered melanoma with brain metastasis is limited. Clin Cancer Res; 21(10); 2289–96. ©2015 AACR.
Tumor-Infiltrating Lymphocytes Genetically Engineered with an Inducible Gene Encoding Interleukin-12 for the Immunotherapy of Metastatic Melanoma
Authors: Zhang Ling , Morgan Richard A. , Beane Joal D. , Zheng Zhili , Dudley Mark E. , Kassim Sadik H. , Nahvi Azam V. , Ngo Lien T. , Sherry Richard M. , Phan Giao Q. , Hughes Marybeth S. , Kammula Udai S. , Feldman Steven A. , Toomey Mary Ann , Kerkar Sid P. , Restifo Nicholas P. , Yang James C. , Rosenberg Steven A.
Published: February 2015

Purpose: Infusion of interleukin-12 (IL12) can mediate antitumor immunity in animal models, yet its systemic administration to patients with cancer results in minimal efficacy and severe toxicity. Here, we evaluated the antitumor activity of adoptively transferred human tumor-infiltrating lymphocytes (TILs) genetically engineered to secrete single-chain IL12 selectively at the tumor site.

Experimental Design: Thirty-three patients with metastatic melanoma were treated in a cell dose–escalation trial of autologous TILs transduced with a gene encoding a single-chain IL12 driven by a nuclear factor of the activated T cells promoter (NFAT.IL12). No IL2 was administered.

Results: The administration of 0.001 to 0.1 × 109 NFAT.IL12–transduced TILs to 17 patients resulted in a single, objective response (5.9%). However, at doses between 0.3 and 3 × 109 cells, 10 of 16 patients (63%) exhibited objective clinical responses. The responses tended to be short, and the administered IL12-producing cells rarely persisted at 1 month. Increasing cell doses were associated with high serum levels of IL12 and IFNγ as well as clinical toxicities, including liver dysfunction, high fevers, and sporadic life-threatening hemodynamic instability.

Conclusions: In this first-in-man trial, administration of TILs transduced with an inducible IL12 gene mediated tumor responses in the absence of IL2 administration using cell doses 10- to 100-fold lower than conventional TILs. However, due to toxicities, likely attributable to the secreted IL12, further refinement will be necessary before this approach can be safely used in the treatment of cancer patients. Clin Cancer Res; 21(10); 2278–88. ©2015 AACR.
Phase I Study of Vorinostat as a Radiation Sensitizer with 131I-Metaiodobenzylguanidine (131I-MIBG) for Patients with Relapsed or Refractory Neuroblastoma
Authors: DuBois Steven G. , Groshen Susan , Park Julie R. , Haas-Kogan Daphne A. , Yang Xiaodong , Geier Ethan , Chen Eugene , Giacomini Kathy , Weiss Brian , Cohn Susan L. , Granger M. Meaghan , Yanik Gregory A. , Hawkins Randall , Courtier Jesse , Jackson Hollie , Goodarzian Fariba , Shimada Hiroyuki , Czarnecki Scarlett , Tsao-Wei Denice , Villablanca Judith G. , Marachelian Araz , Matthay Katherine K.
Published: February 2015

Purpose: 131I-metaiodobenzylguanidine (MIBG) is a radiopharmaceutical with activity in neuroblastoma. Vorinostat is a histone deacetylase inhibitor that has radiosensitizing properties. The goal of this phase I study was to determine the MTDs of vorinostat and MIBG in combination.

Experimental Design: Patients ≤ 30 years with relapsed/refractory MIBG-avid neuroblastoma were eligible. Patients received oral vorinostat (dose levels 180 and 230 mg/m2) daily days 1 to 14. MIBG (dose levels 8, 12, 15, and 18 mCi/kg) was given on day 3 and peripheral blood stem cells on day 17. Alternating dose escalation of vorinostat and MIBG was performed using a 3+3 design.

Results: Twenty-seven patients enrolled to six dose levels, with 23 evaluable for dose escalation. No dose-limiting toxicities (DLT) were seen in the first three dose levels. At dose level 4 (15 mCi/kg MIBG/230 mg/m2 vorinostat), 1 of 6 patients had DLT with grade 4 hypokalemia. At dose level 5 (18 mCi/kg MIBG/230 mg/m2 vorinostat), 2 patients had dose-limiting bleeding (one grade 3 and one grade 5). At dose level 5a (18 mCi/kg MIBG/180 mg/m2 vorinostat), 0 of 6 patients had DLT. The most common toxicities were neutropenia and thrombocytopenia. The response rate was 12% across all dose levels and 17% at dose level 5a. Histone acetylation increased from baseline in peripheral blood mononuclear cells collected on days 3 and 12 to 14.

Conclusions: Vorinostat at 180 mg/m2/dose is tolerable with 18 mCi/kg MIBG. A phase II trial comparing this regimen to single-agent MIBG is ongoing. Clin Cancer Res; 21(12); 2715–21. ©2015 AACR.
Radiosensitization of Primary Human Glioblastoma Stem-like Cells with Low-Dose AKT Inhibition
Authors: Mehta Monal , Khan Atif , Danish Shabbar , Haffty Bruce G. , Sabaawy Hatem E.
Published: February 2015

Glioblastoma (GBM) is the most frequent and lethal brain cancer. The lack of early detection methods, the presence of rapidly growing tumor cells, and the high levels of recurrence due to chemo- and radioresistance make this cancer an extremely difficult disease to treat. Emerging studies have focused on inhibiting AKT activation; here, we demonstrate that in primary GBM tumor samples, full-dose inhibition of AKT activity leads to differential responses among samples in the context of cell death and self-renewal, reinforcing the notion that GBM is a heterogeneous disease. In contrast, low-dose AKT inhibition when combined with fractionation of radiation doses leads to a significant apoptosis-mediated cell death of primary patient–derived GBM cells. Therefore, low-dose–targeted therapies might be better for radiosensitization of primary GBM cells and further allow for reducing the clinical toxicities often associated with targeting the AKT/PI3K/mTOR pathway. This work emphasizes the discrepancies between cell lines and primary tumors in drug testing, and indicates that there are salient differences between patients, highlighting the need for personalized medicine in treating high-grade glioma. Mol Cancer Ther; 14(5); 1171–80. ©2015 AACR.
A Novel Neutralizing Antibody Targeting Pregnancy-Associated Plasma Protein-A Inhibits Ovarian Cancer Growth and Ascites Accumulation in Patient Mouse Tumorgrafts
Authors: Becker Marc A. , Haluska Paul , Bale Laurie K. , Oxvig Claus , Conover Cheryl A.
Published: February 2015

The majority of ovarian cancer patients acquire resistance to standard platinum chemotherapy and novel therapies to reduce tumor burden and ascites accumulation are needed. Pregnancy-associated plasma protein-A (PAPP-A) plays a key role in promoting insulin-like growth factor (IGF) pathway activity, which directly correlates to ovarian cancer cell transformation, growth, and invasiveness. Herein, we evaluate PAPP-A expression in tumors and ascites of women with ovarian cancer, and determine the antitumor efficacy of a neutralizing monoclonal PAPP-A antibody (mAb-PA) in ovarian cancer using primary patient ovarian tumorgrafts (“Ovatars”). PAPP-A mRNA expression in patient ovarian tumors correlated with poor outcome and was validated as a prognostic surrogate in Ovatar tumors. Following confirmation of mAb-PA bioavailability and target efficacy in vivo, the antitumor efficacy of mAb-PA in multiple Ovatar tumor models was examined and the response was found to depend on PAPP-A expression. Strikingly, the addition of mAb-PA to standard platinum chemotherapy effectively sensitized platinum-resistant Ovatar tumors. PAPP-A protein in ascites was also assessed in a large cohort of patients and very high levels were evident across the entire sample set. Therefore, we evaluated targeted PAPP-A inhibition as a novel approach to managing ovarian ascites, and found that mAb-PA inhibited the development, attenuated the progression, and induced the regression of Ovatar ascites. Together, these data indicate PAPP-A as a potential palliative and adjunct therapeutic target for women with ovarian cancer. Mol Cancer Ther; 14(4); 973–81. ©2015 AACR.
Biomarker Signatures Correlate with Clinical Outcome in Refractory Metastatic Colorectal Cancer Patients Receiving Bevacizumab and Everolimus
Authors: Liu Yingmiao , Starr Mark D. , Brady John C. , Rushing Christel , Bulusu Anuradha , Pang Herbert , Honeycutt Wanda , Amara Anthony , Altomare Ivy , Uronis Hope E. , Hurwitz Herbert I. , Nixon Andrew B.
Published: February 2015

A novel combination of bevacizumab and everolimus was evaluated in refractory colorectal cancer patients in a phase II trial. In this retrospective analysis, plasma samples from 49 patients were tested for over 40 biomarkers at baseline and after one or two cycles of drug administration. Analyte levels at baseline and change on-treatment were correlated with progression-free survival (PFS) and overall survival (OS) using univariate Cox proportional hazard modeling. Multivariable analyses were conducted using Cox modeling. Significant changes in multiple markers were observed following bevacizumab and everolimus treatment. Baseline levels of six markers significantly correlated with PFS and OS, including CRP, Gro-α, IGFBP-1, TF, ICAM-1, and TSP-2 (P < 0.05). At C2D1, changes of IGFBP-3, TGFβ-R3, and IGFBP-2 correlated with PFS and OS. Prognostic models were developed for OS and PFS (P = 0.0002 and 0.004, respectively). The baseline model for OS consisted of CRP, Gro-α, and TF, while the on-treatment model at C2D1 included IGFBP-2, IGFBP-3, and TGFβ-R3. These data demonstrated that multiple biomarkers were significantly modulated in response to bevacizumab and everolimus. Several markers correlated with both PFS and OS. Interestingly, these markers are known to be associated with inflammation and IGF signaling, key modulators of mTOR biology. Mol Cancer Ther; 14(4); 1048–56. ©2015 AACR.
The Temporal Dynamics of Cognitive Reactivity and Their Association with the Depression Risk: An Exploratory Study
Authors: Pfeiffer Nils , Brockmeyer Timo , Zimmermann Johannes , Backenstrass Matthias
Published: February 2015

Background: Cognitive reactivity is the change in depressive thinking in response to negative mood. Previous research indicates that cognitive reactivity is an important variable in the etiology and course of depression. The present study tested which time interval after a negative mood induction is critical for the prediction of the depression risk. Methods: Participants suffering from a major depressive disorder were recruited when entering inpatient treatment. At the end of inpatient treatment they completed an experimental procedure to assess their depressive thinking once before and twice after a negative mood induction. Subsequently, patients were followed up for 26 weeks. Results: The immediate change in depressive thinking in response to the negative mood induction was negatively associated with future depression. The delayed change did not predict the depression risk. Conclusion: The negative association between the immediate change in depressive thinking and the depression risk is not in line with results from previous studies on cognitive reactivity. Previous research on emotion context insensitivity and the avoidance of negative thoughts offers hypotheses which could account for this result. Further research is needed to shed light on the processes underlying cognitive reactivity.
Mitomycin C Induces Apoptosis in Rheumatoid Arthritis Fibroblast-Like Synoviocytes via a Mitochondrial-Mediated Pathway
Authors: Yan Chuqi , Kong Dechao , Ge Dong , Zhang Yanming , Zhang Xishan , Su Changhui , Cao Xiaojian
Published: February 2015

Background/Aims: Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterised by prominent synoviocyte hyperplasia and a potential imbalance between the growth and death of fibroblast-like synoviocytes (FLS). Mitomycin C (MMC) has previously been demonstrated to inhibit fibroblast proliferation and to induce fibroblast apoptosis. However, the effects of MMC on the proliferation and apoptosis of human RA FLS and the potential mechanisms underlying its effects remain unknown. Methods: Cell viability was determined using the Cell Counting Kit-8 assay. Apoptotic cell death was analysed via Annexin V-FITC/PI double staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling. The production of intracellular reactive oxygen species (ROS) was assessed via flow cytometry, and the changes in mitochondrial membrane potential (ΔΨm) were visualized based on JC-1 staining via fluorescence microscopy. The expression of apoptosis-related proteins was determined via Western blot. Results: Treatment with MMC significantly reduced cell viability and induced apoptosis in RA FLS. Furthermore, MMC exposure was found to stimulate the production of ROS and to disrupt the ΔΨm compared to the control treatment. Moreover, MMC increased the release of mitochondrial cytochrome c, the ratio of Bax/Bcl-2, the activation of caspase-9 and caspase-3, and the subsequent cleavage of poly(ADP-ribose) polymerase. Conclusion: Our findings suggest that MMC inhibits cell proliferation and induces apoptosis in RA FLS, and the mechanism underlying this MMC-induced apoptosis may involve a mitochondrial signalling pathway.
Expression and Potential Role of microRNA-29b in Mouse Early Embryo Development
Authors: Zhang Junqiang , Wang Ying , Liu Xiaoguang , Jiang Shenglin , Zhao Chun , Shen Rong , Guo Xirong , Ling Xiufeng , Liu Chang
Published: February 2015

Background/Aims: MicroRNA-29b (miR29b) has been previously identified in early mouse embryos through miRNA microarray analysis. Recent research has indicated that miR29b participates in DNA methylation by regulating DNA methyltransferase 3a/3b (Dnmt3a/3b) expression. However, the expression pattern and biological function of miR29b in mouse preimplantation embryonic development remain unknown. Methods: In this study, we examined the expression patterns of miR29b and Dnmt3a/3b in mouse early embryos at different developmental stages. Subsequently, expression and localization of DNMT3A/3B protein was analyzed in mouse early embryos by immunofluorescence staining. The biological function of miR29b in mouse early embryos was analyzed by microinjection of commercially available miRNA-specific inhibitors and mimics. Results: Our data showed that Dnmt3a/3b mRNA expression is negatively regulated by miR29b in mouse early embryos. Immunofluorescence analysis revealed that DNMT3A/3B protein expression is predominantly localized within the nucleoplasm of embryos. Alterations to the activity of miR29b could change the DNA methylation levels in mouse preimplantation embryos and lead to a developmental blockade, from the morula to the blastocyst stage. Conclusion: These results indicated a role for the miR29b-Dnmt3a/3b-DNA methylation axis in mouse early embryonic development, and we provide evidence that miR29b is indispensable for mouse early embryonic development. This study contributes to a preliminary understanding of the role of miR29b during mouse embryonic development.
PAI-1 modulates cell migration in a LRP1-dependent manner via β-catenin and ERK1/2
Authors: Kozlova Nina , Jensen Jan K. , Franklin Chi Tabughang , Samoylenko Anatoly , Kietzmann Thomas
Published: February 2015

Plasminogen activator inhibitor-1 (PAI-1) is the major and most specific acting urokinase (uPA) and tissue plasminogen activator (tPA) inhibitor. Apart from its function in the fibrinolytic system, PAI-1 was also found to contribute to processes like tissue remodelling, angiogenesis, and tumour progression. However, the role of PAI-1 in those processes remains largely controversial with respect to the influence of PAI-1 on cell signalling pathways. Although PAI-1 does not possess its own cellular receptor, it can be bound to low-density lipoprotein receptor- related protein 1 (LRP1) which was proposed to modulate the β-catenin pathway. Therefore, we used wild-type mouse embryonic fibroblasts (MEFs), and MEFs deficient of LRP1 to study PAI-1 as modulator of the β-catenin pathway. We found that PAI-1 influences MEF proliferation and motility in a LRP1-dependent manner and that β-catenin is important for that response. In addition, expression of β-catenin and β-catenin-dependent transcriptional activity were induced by PAI-1 in wild type MEFs, but not in LRP1-deficient cells. Moreover, PAI-1-induced ERK1/2 activation was more prominent in the LRP1-deficient cells and interestingly knockdown of β-catenin abolished this effect. Together, the data of the current study show that PAI-1 can promote cell migration via LRP1-dependent activation of the β-catenin and ERK1/2 MAPK pathway which may be important in stage-specific treatment of human diseases associated with high PAI-1 levels.
Platelet adhesion to podoplanin under flow is mediated by the receptor CLEC-2 and stabilised by Src/Syk-dependent platelet signalling
Authors: Y. Pollitt Alice , Lowe Kate , Latif Arusa , B. Nash Gerard , P. Watson Steve , Navarro-Núñez Leyre
Published: February 2015

Platelet-specific deletion of CLEC-2, which signals through Src and Syk kinases, or global deletion of its ligand podoplanin results in bloodfilled lymphatics during mouse development. Platelet-specific Syk deficiency phenocopies this defect, indicating that platelet activation is required for lymphatic development. In the present study, we investigated whether CLEC-2-podoplanin interactions could support platelet arrest from blood flow and whether platelet signalling is required for stable platelet adhesion to lymphatic endothelial cells (LECs) and recombinant podoplanin under flow. Perfusion of human or mouse blood over human LEC monolayers led to platelet adhesion and aggregation. Following α∥bβ3 blockade, individual platelets still adhered. Platelet binding occurred at venous but not arterial shear rates. There was no adhesion using CLEC-2-deficient blood or to vascular endothelial cells (which lack podoplanin). Perfusion of human blood over human Fc-podoplanin (hFcPDPN) in the presence of monoclonal antibody IV.3 to block FcγR∥A receptors led to platelet arrest at similar shear rates to those used on LECs. Src and Syk inhibitors significantly reduced global adhesion of human or mouse platelets to LECs and hFcPDPN. A similar result was seen using Syk-deficient mouse platelets. Reduced platelet adhesion was due to a decrease in the stability of binding. In conclusion, our data reveal that CLEC-2 is an adhesive receptor that supports platelet arrest to podoplanin under venous shear. Src/Syk-dependent signalling stabilises platelet adhesion to podoplanin, providing a possible molecular mechanism contributing to the lymphatic defects of Syk-deficient mice.
Journeys Together: Horses and Humans in Partnership
Authors: Birke Lynda , Hockenhull Jo
Published: February 2015

Many living with companion animals hope for “good relationships” based on trust, mutuality, and cooperation. Relationships develop from mutual actions, yet research often overlooks nonhumans as mindful actors within relationships. This is a study of horse/human dyads, using multimethod approaches intended to include horses as participants. We ask: can “good relationships” be observed, especially when the pair know each other well? We studied familiar/unfamiliar pairs, negotiating simple obstacles, to explore qualities of cooperation between pairs. Interviews with human participants elicited perceptions of horses’ “personalities” and reactions. We analyzed video recordings of interactions and also showed them to external observers. We identified differences in attention, tension and coordination: familiar pairs were more coordinated, mutually attentive, and less tense, and they showed less resistance. That is, some relationships displayed discernible qualities of “working together.” We cannot know nonhuman animals’ experiences, but knowing how they behave says something about their agency within interspecies relationships.
Sit Verum Obligationes and Counterfactual Reasoning
Authors: Uckelman Sara L.
Published: February 2015

In the early 1980s, Paul V. Spade advanced the thesis that obligational reasoning was counterfactual reasoning, based upon his interpretation of the obligationes of Walter Burley, Richard Kilvington, and Roger Swyneshed. Eleonore Stump in a series of contemporary papers argued against Spade’s thesis with respect to Burley and Swyneshed, provisionally admitting it for Kilvington with the caveat that Kilvington’s theory is by no means clear or non-idiosyncratic. In this paper, we revisit the connection between counterfactual reasoning and obligationes, focusing on one particular treatise, the anonymous early twelfth-century Obligationes Parisienses edited by L.M. de Rijk in the late 70s. We show that while positio in this treatise does not involve counterfactual reasoning, the species sit verum or rei veritas apparently does, and it is precisely this which distinguishes the two species in this treatise.
Peter Auriol on Free Choice and Free Judgment
Authors: Hoffmann Tobias
Published: February 2015

Some medieval authors defend free choice by arguing that, even though human choices are indeed caused by the practical judgment about what is best to do here and now, one is nevertheless able to freely influence that practical judgment’s formation. This paper examines Peter Auriol’s account of free choice, which is a quite elaborate version of this approach and which brings its theoretical problems into focus. I will argue in favor of Auriol’s basic theory, but I will also propose an emendation to his theory in order to respond to some problems he leaves unresolved.
Philip the Chancellor on the Beginning of Time
Authors: Yarbrough Joseph
Published: February 2015

Philip the Chancellor was the first of a new generation of medieval theologians to engage the question of whether the world could have been infinite in past duration. This paper examines Philip’s Summa de bono in order to show, first, how Philip handles the Aristotelian material that seems to prove that past time is infinite in duration, a claim that placed Aristotle in direct conflict with the religious orthodoxy of his day. Second, though Philip himself believed that past time was necessarily finite in a created world, this paper will show how his arguments for this position have weaknesses that allowed later thinkers to build upon Philip’s distinctions between time and eternity to demonstrate the conceptual possibility of a created world infinite in past duration.
Characterisation of an Iberian population of Rhyssocolpus iuventutis Andrássy, 1971 (Dorylaimida: Nordiidae), with a revised taxonomy of the genus
Authors: Peña-Santiago Reyes , Guerrero Pablo , Liébanas Gracia , García María del Carmen , Palomeque Teresa , Lorite Pedro
Published: February 2015

The identity and evolutionary relationships of the genus
Rhyssocolpus are analysed and discussed using an
integrative approach including morphological data and partial SSU-rDNA
sequences. An Iberian population of R. iuventutis is
characterised in detail, providing the first SEM observations of the genus. New
sequences of the genera Enchodelus and
Rhyssocolpus are provided for comparative purposes. Both
morphological and molecular evidence support a separate status for the
aforementioned two genera and Heterodorus, of which the latter
and Rhyssocolpus shared a recent common ancestor, whereas
Enchodelus did not, as had been traditionally assumed,
occupy a close position. The Nordiidae is confirmed to be an artificial taxon.
The taxonomy of Rhyssocolpus is revised and an emended
diagnosis, updated list of species, key to their identification and compendium
of their morphometrics are provided. Some nomenclatorial changes are also
proposed: R. alleni and R. paradoxus are
retained under Eudorylaimus, their original genus, whereas
R. brasiliensis is transferred to
Eudorylaimus as E. brasiliensis (Meyl,
1956) comb. n.
Effect of initial population densities of Ditylenchus destructor and D. dipsaci on potato tuber damage and nematode reproduction
Authors: Mwaura Peter , Niere Björn , Vidal Stefan
Published: February 2015

Glasshouse experiments were conducted to evaluate the effect of initial population densities () of Ditylenchus destructor and D. dipsaci on potato tuber damage and nematode reproduction. Ditylenchus destructor did not influence tuber numbers but influenced tuber weight at high levels. Ditylenchus dipsaci influenced tuber numbers and weights at a level of 14.29 (g growing medium)−1. Tolerance limit estimates according to the Seinhorst model were very low indicating both nematode species have a major impact on potato tuber weight. External and internal tuber rot caused by both species increased with levels. Ditylenchus destructor caused more tuber rot than D. dipsaci at all levels. Reproduction rates of D. destructor were higher at all levels studied compared to D. dipsaci. The equilibrium density of 1.3 and 0.6 for D. destructor and D. dipsaci, respectively, was observed at level of 14.29 (g growing medium)−1.
Evaluation of rhizobacterial colonisation and the ability to induce Globodera pallida hatch
Authors: Lettice Eoin P. , Jones Peter W.
Published: February 2015

Three bacterial isolates, SB13 (Acinetobacter sp.), SB14 (Arthrobacter sp.) and SB15 (Bacillus sp.), were previously isolated from the rhizosphere of sugar beet (Beta vulgaris ssp. vulgaris) plants and shown to increase hatch of potato cyst nematodes in vitro. In this study, the three isolates were assayed for rhizosphere competence. Each isolate was applied to seeds at each of four concentrations (105-108 CFU ml−1) and the inoculated seeds were planted in plastic microcosms containing coarse sand. All three isolates were shown to colonise the rhizosphere, although to differing degrees, with the higher inoculation densities providing significantly better colonisation. The isolates increased sugar beet root and shoot dry weight. Isolates SB14 and SB15 were analysed for their ability to induce in vivo hatch of Globodera pallida in non-sterile soil planted with sugar beet. After 4 and 6 weeks, both isolates had induced significantly greater percentage hatch compared to controls.
Description of Sheraphelenchus parabrevigulonis n. sp. (Nematoda: Aphelenchoididae) in pine wood packaging from Italy and redescription of S. sucus in onion bulbs from South Korea, isolated at Ningbo, China
Authors: Fang Yiwu , Gu Jianfeng , Wang Xuan , Wang Jianglin , Li Hongmei
Published: February 2015

TwoSheraphelenchuspopulations were isolated from pine wood packaging from Italy and onion bulbs from South Korea at Ningbo Port, China, respectively. The former, on the basis of morphology and molecular sequencing, is described asS. parabrevigulonisn. sp., which is characterised by a stylet length of 11 μm, three lines in the lateral field, excretory pore at level with, or slightly posterior to, nerve ring, V = 93.1, and spicules with long condylus and membrane-like rostrum in a shallow triangular shape. The species from onion, also on the basis of morphology and sequence data, was identified asS. sucus, which is characterised by a stylet length of 13 μm (erroneously stated to beca6 μm in the type description), excretory pore at level of, or posterior to, median bulb, and V = 80.9. The phylogeny trees based on rDNA 18S, 28S D2-D3 and ITS1/2 sequences revealed thatS. parabrevigulonisn. sp. andS. sucusclustered into a clear clade and grouped withBursaphelenchusspecies. The study enriched the taxonomic information ofSheraphelenchusand confirmed its status as an independent genus.
Description and molecular characterisation of Xiphinema herakliense n. sp. (Nematoda: Longidoridae) from wild and cultivated olives in Crete
Authors: Tzortzakakis Emmanuel A. , Archidona-Yuste Antonio , Cantalapiedra-Navarrete Carolina , Nasiou Eleni , Palomares-Rius Juan E. , Castillo Pablo
Published: February 2015

Xiphinema herakliensen. sp. from wild olive and cultivated trees in Vathy Rema and other localities, Heraklion province of Crete, Greece, is described based on morphological and molecular characters. The new species is characterised by having differentiation in the tubular part of the uterus, body length 4.1 (3.3-5.5) mm, odontostyle 149 (135-163) μm long, odontophore 85 (71-98) μm long, female tail dorsally convex-conoid with subdigitate peg, and presence of functional males. The polytomous identification code of the new species is: A4, B2 + 3, C5a, D6(5), E5, F4(5), G3, H2, I3, J5, K5, L2. The new species belongs to morphospeciesXiphinemanon-americanumGroup 5 characterised by having two equally developed female genital branches with uterine differentiation, presence of pseudo-Z-organ with small granular bodies plus small spines (in low number) and crystalloid bodies along uterus, and a short, rounded tail ending in a peg.Xiphinema herakliensen. sp. appears closely related toX. barense,X. horvatovicae,X. lanceolatum,X. loteni,X. sphaerocephalumandX. thorneanum, from which it may be differentiated morphologically and/or molecularly. The results of the phylogenetic analyses based on the sequences of the D2-D3 expansion regions of the 28S rRNA gene and ITS1 rRNA genes are also supportive of its specific status.
China’s Informal Participation in the Annex vii Philippines v. China Arbitral Tribunal’s Proceedings
Authors: Yu Mincai
Published: February 2015

The Annex vii arbitral tribunal in The Philippines v. China is set to continue its proceedings after 15 December 2014. China will have to bear the legal consequences arising from its non-participation. With reference to the practice of the absent respondent States in the International Court of Justice’s contentious proceedings, China could participate in the tribunal’s proceedings by way of informal communications or informal appearance. China’s informal participation could help assist the tribunal in relation to its arguments or related evidence. This would help the tribunal address the question as to its jurisdiction and merits of the dispute.
Paspalum chilense (Poaceae, Paspaleae): A new species from southern South America

Authors: Catanzaro María Paz , Bonasora Marisa Graciela , Speranza Pablo Rafael , Medina-Nicolas Marcelo , Valls José F.M. , Rua Gabriel Hugo
Published: February 2015

Paspalum chilense, a new species from Chile belonging to the informal Notata group, is described and illustrated on the basis of morphological, cytological and molecular evidence. Our evidence supports its affinity with P. barretoi and P. nummularium, from Brazil, from which it probably diverged by vicariant speciation. The limited available material of the new species was previously identified as P. pumilum or P. minus. A new key to the species of the core Notata group is provided.
A new species of Uleiorchis (Orchidaceae, Gastrodieae) from the Atlantic Forest of Brazil

Authors: Smidt Eric C , Engels Mathias E. , Bolson Mônica , Berg Cássio Van den
Published: February 2015

A new species from the Brazilian Atlantic Forest, Uleiorchis prataënsis, is described, with illustrations and scanning electron micrographs of pollinaria and seeds. Comments on the new species are presented with a key to the species of the genus. Because the phylogenetic position of Uleiorchis has not been previously evaluated with DNA data, we estimated phylogenetic relationships using nrITS sequence data to confirm that this genus is a member of Gastrodieae. The results indicate with high support in both maximum parsimony and maximum-likelihood analyses that both species of Uleiorchis are sister and members of this tribe. Finding a new species in a relatively well-collected place such as Paraná State supports the status of high diversity hotspot for the Atlantic Forest and demonstrates the need for more fieldwork on orchids and other families.
A polyphasic approach to characterise two novel species of Phoma (Didymellaceae) from China

Authors: Chen Qian , ZHANG KE , ZHANG GUOZHEN , CAI LEI
Published: February 2015

Phoma odoratissimi sp. nov. on Viburnum odoratissimum and Syringa oblate, and Phoma segeticola sp. nov. on Cirsium segetum from China are introduced and described, employing a polyphasic approach characterising morphological characteristics, host association and phylogeny. Both species are the first records of Phoma species on their respective hosts. Multi-locus phylogenetic tree was inferred using combined sequences of the internal transcribed spacer regions 1 & 2 and 5.8S nrDNA (ITS), and partial large subunit 28S nrDNA region (LSU), β-tubulin (TUB) region and RNA polymerase II (RPB2) region. The two new species clustered in two separate and distinct lineages, and are distinct from their allied species.