bluuebunny/crossref_metadata_2025 huggingface dataset:
Fuel Costs Minimization on a Steel Billet Reheating Furnace Using Genetic Algorithms
Authors: Santos Harley S. O. , Almeida Paulo E. M. , Cardoso Rodrigo T. N.
Published: June 2017

Metallurgy industries often use steel billets, at a proper temperature, to achieve the desired metallurgical, mechanical, and dimensional properties of manufactured products. Optimal operation of steel billet reheating furnaces requires the minimization of fuel consumption while maintaining a homogeneous material thermal soak. In this study, the operation of a reheating furnace is modeled as a nonlinear optimization problem with the goal of minimizing fuel cost while satisfying a desired discharge temperature. For this purpose, a genetic algorithms approach is developed. Computational simulation results show that it is possible to minimize costs for different charge temperatures and production rates using the implemented method. Additionally, practical results are validated with actual data, in a specific scenario, showing a reduction of 3.36% of fuel consumption.
Photoluminescence Enhancement Effect of the Layered MoS2 Film Grown by CVD
Authors: Li H. , Zhang X. H. , Tang Z. K.
Published: June 2017

The layered MoS2 films have been prepared by the chemical vapor deposition (CVD) method, which shows numerous MoS2 convex flakes (i.e., MoS2 nanosheets) on SiO2/Si substrates. The convex flake islands form a uniform layered film and the single flake corresponds to one small piece of monolayer MoS2 film; they show a strong photoluminescence (PL) radiation as a whole. The thickness of the layered MoS2 films increases with the increases of growth time, the effect of diverse growth time on the properties of layered MoS2 films has been discussed, and the PL enhancement effect is due to the PL intensity accumulation from each of the convex flakes. The strong PL radiation has been found by annealing the samples and the reason has been analyzed. The layered MoS2 films could provide more photon energy than both the monolayer MoS2 film and the bulk MoS2. This work provides a fundamental study about the device fabrication based on layered MoS2 films. The optoelectronic devices based on this study will be more energy efficient.
Protective Effects of Wogonin against Alzheimer’s Disease by Inhibition of Amyloidogenic Pathway
Authors: Huang Ding-Siang , Yu Yu-Chen , Wu Chung-Hsin , Lin Jung-Yaw
Published: June 2017

One of the pathogenic systems of Alzheimer’s disease (AD) is the formation of β‐amyloid plaques in the brains of patients, and amyloidogenic activity becomes one of the therapeutic targets. Here, we report wogonin, one of the major active constituting components in Scutellaria baicalensis, which has the neuroprotective effects on amyloid‐β peptides‐ (Aβ‐) induced toxicity. Oral wogonin treatment improved the performance of triple transgenic AD mice (h‐APPswe, h‐Tau P301L, and h‐PS1 M146V) on the Morris water maze, Y‐maze, and novel object recognition. Furthermore, wogonin activated the neurite outgrowth of AD cells by increasing neurite length and complexity of Tet‐On Aβ42‐GFP SH‐SY5Y neuroblastoma cells (AD cells) and attenuated amyloidogenic pathway by decreasing the levels of β‐secretase, APP β‐C‐terminal fragment, Aβ‐aggregation, and phosphorylated Tau. Wogonin also increased mitochondrial membrane potential (∆ψm) and protected against apoptosis by reducing the expression of Bax and cleaved PARP. Collectively, these results conclude that wogonin may be a promising multifunctional drug candidate for AD.
Grain Size Dependence of Elastic Moduli in Nanocrystalline Tungsten
Authors: Valat-Villain P. , Durinck J. , Renault P. O.
Published: June 2017

Using atomistic calculations with a Finnis-Sinclair type potential and molecular statics and dynamics methods, we performed a series of deformation tests on nanocrystallised tungsten samples presenting various microstructures; we calculated the elastic constants of polycrystalline tungsten for average grain diameters ranging from 2.7 to 6.7 nm. The results show that both Young’s and the shear moduli decrease by over 60% as the average grain diameter decreases below 3 nm. This diminution appears to be highly correlated to the grain boundary volume fraction. The results are compared to conclusions from other authors.
FPGA-Based Channel Coding Architectures for 5G Wireless Using High-Level Synthesis
Authors: Mhaske Swapnil , Kee Hojin , Ly Tai , Aziz Ahsan , Spasojevic Predrag
Published: June 2017

We propose strategies to achieve a high-throughput FPGA architecture for quasi-cyclic low-density parity-check codes based on circulant-1 identity matrix construction. By splitting the node processing operation in the min-sum approximation algorithm, we achieve pipelining in the layered decoding schedule without utilizing additional hardware resources. High-level synthesis compilation is used to design and develop the architecture on the FPGA hardware platform. To validate this architecture, an IEEE 802.11n compliant 608 Mb/s decoder is implemented on the Xilinx Kintex-7 FPGA using the LabVIEW FPGA Compiler in the LabVIEW Communication System Design Suite. Architecture scalability was leveraged to accomplish a 2.48 Gb/s decoder on a single Xilinx Kintex-7 FPGA. Further, we present rapidly prototyped experimentation of an IEEE 802.16 compliant hybrid automatic repeat request system based on the efficient decoder architecture developed. In spite of the mixed nature of data processing—digital signal processing and finite-state machines—LabVIEW FPGA Compiler significantly reduced time to explore the system parameter space and to optimize in terms of error performance and resource utilization. A 4x improvement in the system throughput, relative to a CPU-based implementation, was achieved to measure the error-rate performance of the system over large, realistic data sets using accelerated, in-hardware simulation.
Bone Regeneration Using N-Methyl-2-pyrrolidone as an Enhancer for Recombinant Human Bone Morphogenetic Protein-2 in a Rabbit Sinus Augmentation Model
Authors: Lim Hyun-Chang , Thoma Daniel S. , Yoon So-Ra , Cha Jae-Kook , Lee Jung-Seok , Jung Ui-Won
Published: June 2017

The aim of this study was to determine whether N-methyl-2-pyrrolidone (NMP) can decrease the dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) in sinus augmentation of rabbits. In each of 15 rabbits, 2 sinuses were randomly grafted using 1 of 3 treatment modalities: (i) biphasic calcium phosphate (BCP; control), (ii) rhBMP-2-coated BCP (BMP), or (iii) rhBMP-2-coated BCP soaked in NMP solution (BMP/NMP). The rabbits were sacrificed 2 weeks postoperatively. Histologic and histomorphometric analyses were performed. Bone formation in all groups was predominantly located close to the access window and the lateral walls. Newly formed bone within the total augmented area (NBTA) was greatest in BMP/NMP (1.94±0.69 mm2), followed by BMP (1.50±0.72 mm2) and BCP (1.28±0.52 mm2) (P>0.05). In the center of the augmentation (NBROI_C) and the area close to the sinus membrane (NBROI_M), BMP/NMP produced the largest area of NB (NBROI_C: 0.10±0.11 mm2; NBROI_M: 0.17±0.08 mm2); the corresponding NB values for BCP were 0.05±0.05 mm2 and 0.08±0.09 mm2, respectively (P>0.05 for all comparisons). The effect of NMP on bone regeneration was inconsistent between the specimens. Adding NMP as an adjunct to rhBMP-2-coated BCP produced inconsistent effects on bone regeneration, resulting in no significant benefit compared to controls.
Economic Levers for Mitigating Interest Flooding Attack in Named Data Networking
Authors: Wang Licheng , Pan Yun , Dong Mianxiong , Yu Yafang , Wang Kun
Published: June 2017

As a kind of unwelcome, unavoidable, and malicious behavior, distributed denial of service (DDoS) is an ongoing issue in today’s Internet as well as in some newly conceived future Internet architectures. Recently, a first step was made towards assessing DDoS attacks in Named Data Networking (NDN)—one of the promising Internet architectures in the upcoming big data era. Among them, interest flooding attack (IFA) becomes one of the main serious problems. Enlightened by the extensive study on the possibility of mitigating DDoS in today’s Internet by employing micropayments, in this paper we address the possibility of introducing economic levers, say, dynamic pricing mechanism, and so forth, for regulating IFA in NDN.
A Preliminary Study on the IoT-Based Pavement Monitoring Platform Based on the Piezoelectric-Cantilever-Beam Powered Sensor
Authors: Hou Yue , Wang Linbing , Wang Dawei , Yang Hailu , Guo Meng , Ye Zhoujing , Tong Xinlong
Published: June 2017

Green and sustainable power supply for sensors in pavement monitoring system has attracted attentions of civil engineers recently. In this paper, the piezoelectric energy harvesting technology is used to provide the power for the acceleration sensor and Radio Frequency (RF) communication. The developed piezoelectric bimorph cantilever beam is used for collecting the vibrational energy. The energy collection circuit is used to charge the battery, where the power can achieve 1.68 mW and can meet the power need of acceleration sensor for data collection and transmission in one operation cycle, that is, 32.8 seconds. Based on the piezoelectric-cantilever-beam powered sensor, the preliminary study on the IoT-based pavement monitoring platform is suggested, which provides a new applicable approach for civil infrastructure health monitoring.
The Proliferation Enhancing Effects of Salidroside on Schwann Cells In Vitro
Authors: Liu Hui , Lv Peizhen , Wu Huayu , Zhang Kun , Xu Fuben , Zheng Li , Zhao Jinmin
Published: June 2017

Derived from Rhodiola rosea L., which is a popular plant in Eastern Europe and Asia, salidroside has pharmacological properties including antiviral, anticancer, hepatoprotective, antidiabetic, and antioxidative effects. Recent studies show that salidroside has neurotrophic and neuroprotective effects. However, the effect of salidroside on Schwann cells (SCs) and the underlying mechanisms of the salidroside‐induced neurotrophin secretion have seldom been studied. In this study, the effect of salidroside on the survival, proliferation, and gene expression of Schwann cells lineage (RSC96) was studied through the examinations of the cell viability, proliferation, morphology, and expression of neurotrophic factor related genes including BDNF, GDNF, and CDNF at 2, 4, and 6 days, respectively. These results showed that salidroside significantly enhanced survival and proliferation of SCs. The underlying mechanism might involve that salidroside affected SCs growth through the modulation of several neurotrophic factors including BDNF, GDNF, and CDNF. As for the concentration, 0.4 mM, 0.2 mM, and 0.1 mM of salidroside were recommended, especially 0.2 mM. This investigation indicates that salidroside is capable of enhancing SCs survival and function in vitro, which highlights the possibility that salidroside as a drug agent to promote nerve regeneration in cellular nerve scaffold through salidroside‐induced neurotrophin secretion in SCs.
Donor Selection for Allogenic Hemopoietic Stem Cell Transplantation: Clinical and Ethical Considerations
Authors: Riezzo Irene , Pascale Natascha , La Russa Raffaele , Liso Arcangelo , Salerno Monica , Turillazzi Emanuela
Published: June 2017

Allogenic hematopoietic progenitor cell transplantation (allo-HSCT) is an established treatment for many diseases. Stem cells may be obtained from different sources: mobilized peripheral blood stem cells, bone marrow, and umbilical cord blood. The progress in transplantation procedures, the establishment of experienced transplant centres, and the creation of unrelated adult donor registries and cord blood banks gave those without an human leucocyte antigen- (HLA-) identical sibling donor the opportunity to find a donor and cord blood units worldwide. HSCT imposes operative cautions so that the entire donation/transplantation procedure is safe for both donors and recipients; it carries with it significant clinical, moral, and ethical concerns, mostly when donors are minors. The following points have been stressed: the donation should be excluded when excessive risks for the donor are reasonable, donors must receive an accurate information regarding eventual adverse events and health burden for the donors themselves, a valid consent is required, and the recipient’s risks must be outweighed by the expected benefits. The issue of conflict of interest, when the same physician has the responsibility for both donor selection and recipient care, is highlighted as well as the need of an adequate insurance protection for all the parties involved.
Immunotherapy for Patients with Advanced Urothelial Cancer: Current Evidence and Future Perspectives
Authors: Zichi Clizia , Tucci Marcello , Leone Gianmarco , Buttigliero Consuelo , Vignani Francesca , Pignataro Daniele , Scagliotti Giorgio V. , Di Maio Massimo
Published: June 2017

In recent years, immunotherapy has produced encouraging results in a rapidly increasing number of solid tumors. The responsiveness of bladder cancer to immunotherapy was first established in nonmuscle invasive disease in 1976 with intravesical instillations of bacillus Calmette-Guérin (BCG). Very recently immune checkpoint inhibitors demonstrated good activity and significant efficacy in metastatic disease. In particular the best results were obtained with programmed death-ligand-1 (PD-L1) and programmed death-1 (PD-1) inhibitors, but many other immune checkpoint inhibitors, including anti-cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) antibodies, are currently under investigation in several trials. Simultaneously other therapeutic strategies which recruit an adaptive immune response against tumoral antigens or employ externally manipulated tumor infiltrating lymphocytes might change the natural history of bladder cancer in the near future. This review describes the rationale for the use of immunotherapy in bladder cancer and discusses recent and ongoing clinical trials with checkpoint inhibitors and other novel immunotherapy agents.
Study of Chemical and Enzymatic Hydrolysis of Cellulosic Material to Obtain Fermentable Sugars
Authors: Amezcua-Allieri Myriam A. , Sánchez Durán Teresa , Aburto Jorge
Published: June 2017

The objective of this study was to evaluate the chemical and enzymatic hydrolysis using a factorial experimental design (23) in order to obtain fermentable sugars from cellulose-based material (CBM) usually used as pet litter. In assessing chemical hydrolysis, we studied the effect of temperature, in addition to H2SO4 concentration and reaction time, on the production of total sugars, reducing sugars, soluble lignin, carbohydrate profile, furfural (F), and hydroxymethyl furfural (HMF). We performed a response surface analysis and found that, at 100°C, 1% acid concentration, and 60 min reaction time, the yields of 0.0033 g reducing sugar/g biomass and 0.0852 g total sugars/g biomass were obtained. Under the above conditions, F is not generated, while HMF is generated in such a concentration that does not inhibit fermentation. We pretreated the CBM with H2SO4, NaOH, CaO, or ozonolysis, in order to evaluate the effectiveness of the enzymatic hydrolysis from the pretreated biomass, using an enzymatic cocktail. Results showed that CBM with acid was susceptible to enzymatic attack, obtaining a concentration of 0.1570 g reducing sugars/g biomass and 0.3798 g total sugars/g biomass. We concluded that acid pretreatment was the best to obtain fermentable sugars from CBM.
The Interaction of Selectins and PSGL-1 as a Key Component in Thrombus Formation and Cancer Progression
Authors: Kappelmayer János , Nagy Béla
Published: June 2017

Cellular interaction is inevitable in the pathomechanism of human disease. Formation of heterotypic cellular aggregates, between distinct cells of hematopoietic and nonhematopoietic origin, may be involved in events leading to inflammation and the complex process of cancer progression. Among adhesion receptors, the family of selectins with their ligands have been considered as one of the major contributors to cell-cell interactions. Consequently, the inhibition of the interplay between selectins and their ligands may have potential therapeutic benefits. In this review, we focus on the current evidence on the selectins as crucial modulators of inflammatory, thrombotic, and malignant disorders. Knowing that there is promiscuity in selectin binding, we outline the importance of a key protein that serves as a ligand for all selectins. This dimeric mucin, the P-selectin glycoprotein ligand 1 (PSGL-1), has emerged as a major player in inflammation, thrombus, and cancer development. We discuss the interaction of PSGL-1 with various selectins in physiological and pathological processes with particular emphasis on mechanisms that lead to severe disease.
Sapium ellipticum(Hochst.) Pax Ethanol Leaf Extract Maintains Lipid Homeostasis in Streptozotocin-Induced Diabetic Rats
Authors: Ighodaro Osasenaga Mcdonald , Akinloye Oluseyi Adeboye , Ugbaja Regina Ngozi , Omotainse Samuel Olatunbosun
Published: June 2017

Dyslipidemia is a common metabolic disorder especially in diabetes mellitus (DM). In this study, the ability ofSapium ellipticum(SE) leaf extract to restore lipid homeostasis in streptozotocin-induced diabetes was examined. DM was induced in experimental rats (Wistar strains) using single intraperitoneal dose (55 mg/kg body weightBW) of streptozotocin (STZ). Treatment of diabetic rats with SE was oral (p.o), at doses of 400 and 800 mg kg−1BW, twice daily at 8 h interval for 21 days. Lipid parameters were analyzed in the serum of rats using test kits. SE caused a significant (P≤0.05) reduction in STZ-induced hypercholesterolemia in a dose dependent pattern (13.7 and 17.89%). These effects were comparable to that provided by metformin (15.45%), a standard antidiabetic drug. Similar pattern was noted with serum triglycerides (TG) (10.63 and 19.06%) and LDL (31.47 and 25.97%). Adipose tissue TG level was improved to near normal. Besides, the cardiovascular risk predictors in terms of atherogenic index of plasma (AIP) and LDL/HDL ratio were lowered by 57.85 and 44.12%, respectively. However, the extract failed to significantly reverse the STZ-induced decline in serum HDL. Overall, with AIP value of 0.28 and LDL/HDL ratio of 0.91, SE demonstrated the potential to maintain lipid homeostasis in the diabetics.
Performance Improvement of Spaceborne SAR Using Antenna Pattern Synthesis Based on Quantum-Behaved Particle Swarm Optimization
Authors: Won Young-Jin , Lee Kyun Ho , Lee Jae-Hyun
Published: June 2017

This study improves the performance of a spaceborne synthetic aperture radar (SAR) system using an antenna mask design method and antenna pattern synthesis algorithms for an active phased array SAR system. The SAR antenna is an important component that affects the SAR system performance because it is closely related to the antenna pattern. This study proposes a method for antenna mask design that is based on several previous studies as well as the antenna pattern synthesis algorithm, which is based on quantum-behaved particle swarm optimization (QPSO) for an active phased array SAR system. The performance of the designed antenna masks and synthesized patterns demonstrate that the proposed mask design method and antenna pattern synthesis algorithm based on QPSO can be used to improve the SAR system performance for spaceborne applications.
Cadmium Removal from Contaminated Water Using Polyelectrolyte-Coated Industrial Waste Fly Ash
Authors: Olabemiwo Fatai A. , Tawabini Bassam S. , Patel Faheemuddin , Oyehan Tajudeen A. , Khaled Mazen , Laoui Tahar
Published: June 2017

Fly ash (FA) is a major industrial waste generated from power stations that add extra cost for proper disposal. Recent research efforts have consequently focused on developing ways to make use of FA in environmentally sound applications. This study, therefore, investigates the potential ability of raw fly ash (RFA) and polyelectrolyte-coated fly ash (PEFA) to remove cadmium (Cd) from polluted water. Using layer-by-layer approach, functionalized fly ash was coated with 20 layers from 0.03% (v/v) of cationic poly(diallyldimethylammonium chloride) (PDADMAC) and anionic polystyrene sulfonate (PSS) solutions. Both surface morphology and chemical composition of the adsorbent (PEFA) were characterized using Field-Emission Scanning Electron Microscope (FE-SEM), X-Ray Diffraction (XRD), Fourier-Transform Infrared (FTIR), and X-Ray Fluorescence (XRF) techniques. The effects of pH, adsorbent dosage, contact time, initial contaminant concentration, and mixing rate of the adsorption of Cd were also studied in batch mode experiments. Results of the study revealed that a 4.0 g/L dosage of PEFA removed around 99% of 2.0 mg/L of Cd in 15 min at 150 rpm compared to only 27% Cd removal achieved by RFA under the same conditions. Results also showed that adsorption by PEFA followed both Langmuir and Freundlich models with correlation coefficients of 98% and 99%, respectively.
Requirements Elicitation and Prototyping of a Fully Immersive Virtual Reality Gaming System for Upper Limb Stroke Rehabilitation in Saudi Arabia
Authors: AlMousa Maram , Al-Khalifa Hend S. , AlSobayel Hana
Published: June 2017

Stroke rehabilitation plays an important role in recovering the lifestyle of stroke survivors. Although existing research proved the effectiveness and engagement of nonimmersive virtual reality- (VR-) based rehabilitation systems, limited research is available on the applicability of fully immersive VR-based rehabilitation systems. In this paper, we present the elicited requirements of a fully immersive VR-based rehabilitation system that will be designed for domestic upper limb stroke patients; we will also provide an initial conceptual prototype of the proposed system.
Abnormal Functional Connectivity of Ventral Anterior Insula in Asthmatic Patients with Depression
Authors: Zhang Yuqun , Yang Yuan , Bian Rongrong , Yin Yingying , Hou Zhenghua , Yue Yingying , Xu Zhi , Yuan Yonggui
Published: June 2017

Objective. To explore the underlying mechanism of depression in asthmatic patients, the ReHo in the insula and its FC was used to probe the differences between depressed asthmatic (DA) and nondepressed asthmatic (NDA) patients. Methods. 18 DA patients, 24 NDA patients, and 60 healthy controls (HCs) received resting-state fMRI scan, severity of depression, and asthma control assessment. Results. DA patients showed increased FC between the left ventral anterior insula (vAI) and the left middle temporal gyrus compared with both NDA and HC groups. In addition, compared with HCs, the DA and NDA patients both exhibited increased FC between the left vAI and the right anterior cingulate cortex (ACC), decreased FC between the left vAI and the bilateral parietal lobe, and increased FC between the right vAI and the left putamen and the right caudate, respectively. Furthermore, the increased FC between the left vAI and the right ACC could differentiate HCs from both DA and NDA patients, and the increased FC between the right vAI and both the left putamen and the right caudate could separate NDA patients from HCs. Conclusions. This study confirmed that abnormal vAI FC may be involved in the neuropathology of depression in asthma. The increased FC between the left vAI and the left MTG could distinguish DA from the NDA and HC groups.
Delay‐Dependent Stability Analysis of TS Fuzzy Switched Time‐Delay Systems
Authors: Aoun Nawel , Kermani Marwen , Sakly Anis
Published: June 2017

This paper proposes a new approach to deal with the problem of stability under arbitrary switching of continuous‐time switched time‐delay systems represented by TS fuzzy models. The considered class of systems, initially described by delayed differential equations, is first put under a specific state space representation, called arrow form matrix. Then, by constructing a pseudo‐overvaluing system, common to all fuzzy submodels and relative to a regular vector norm, we can obtain sufficient asymptotic stability conditions through the application of Borne and Gentina practical stability criterion. The stability criterion, hence obtained, is algebraic, is easy to use, and permits avoiding the problem of existence of a common Lyapunov‐Krasovskii functional, considered as a difficult task even for some low‐order linear switched systems. Finally, three numerical examples are given to show the effectiveness of the proposed method.
Risk Factors of Mortality from All Asbestos-Related Diseases: A Competing Risk Analysis
Authors: Abós-Herràndiz Rafael , Rodriguez-Blanco Teresa , Garcia-Allas Isabel , Rosell-Murphy Isabel-Magdalena , Albertí-Casas Constança , Tarrés Josep , Krier-Günther Illona , Martinez-Artés Xavier , Orriols Ramon , Grimau-Malet Isidre , Canela-Soler Jaume
Published: June 2017

Background. The mortality from all malignant and nonmalignant asbestos-related diseases remains unknown. The authors assessed the incidence and risk factors for all asbestos-related deaths. Methods. The sample included 544 patients from an asbestos-exposed community in the area of Barcelona (Spain), between Jan 1, 1970, and Dec 31, 2006. Competing risk regression through a subdistribution hazard analysis was used to estimate risk factors for the outcomes. Results. Asbestos-related deaths were observed in 167 (30.7%) patients and 57.5% of these deaths were caused by some type of mesothelioma. The incidence rate after diagnosis was 3,600 per 100,000 person-years. In 7.5% of patients death was non-asbestos-related, while pleural and peritoneal mesothelioma were identified in 87 (16.0%) and 18 (3.3%) patients, respectively. Conclusions. Age, sex, household exposure, cumulative nonmalignant asbestos-related disease, and single malignant pathology were identified as risk factors for asbestos-related death. These findings suggest the need to develop a preventive approach to the community and to improve the clinical follow-up process of these patients.
Near-Infrared Photoimmunotherapy Targeting Prostate Cancer with Prostate-Specific Membrane Antigen (PSMA) Antibody
Authors: Nagaya Tadanobu , Nakamura Yuko , Okuyama Shuhei , Ogata Fusa , Maruoka Yasuhiro , Choyke Peter L. , Kobayashi Hisataka
Published: June 2017

Prostate-specific membrane antigen (PSMA) is a membrane protein that is overexpressed manifold in prostate cancer and provides an attractive target for molecular therapy. Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photoabsorber conjugate (APC). Here, we describe the efficacy of NIR-PIT, using a fully human IgG1 anti-PSMA monoclonal antibody (mAb), conjugated to the photoabsorber, IR700DX, in a PSMA-expressing PC3 prostate cancer cell line. Anti-PSMA-IR700 showed specific binding and cell-specific killing was observed after exposure of the cells to NIR light in vitro. In the in vivo study, anti-PSMA-IR700 showed high tumor accumulation and high tumor–background ratio. Tumor-bearing mice were separated into 4 groups: (i) no treatment; (ii) 100 μg of anti-PSMA-IR700 i.v.; (iii) NIR light exposure; (iv) 100 μg of anti-PSMA-IR700 i.v., NIR light exposure was administered. These were performed every week for up to 3 weeks. Tumor growth was significantly inhibited by NIR-PIT treatment compared with the other control groups (P < 0.001), and significantly prolonged survival was achieved (P < 0.0001 vs. other control groups). More than two thirds of tumors were cured with NIR-PIT. In conclusion, the anti-PSMA antibody is suitable as an APC for NIR-PIT. Furthermore, NIR-PIT with the anti-PSMA-IR700 antibody is a promising candidate of the treatment of PSMA-expressing tumors and could be readily translated to humans.

Implications: NIR-infrared photoimmunotherapy (NIR-PIT) using a fully human anti-PSMA-IR700 conjugate showed potential therapeutic effects against a PSMA-expressing prostate cancer that is readily translated to humans. Mol Cancer Res; 15(9); 1153–62. ©2017 AACR.
Intravesical BCG Induces CD4+ T-Cell Expansion in an Immune Competent Model of Bladder Cancer
Authors: Kates Max , Nirschl Thomas , Sopko Nikolai A. , Matsui Hotaka , Kochel Christina M. , Reis Leonardo O. , Netto George J. , Hoque Mohammad O. , Hahn Noah M. , McConkey David J. , Baras Alex S. , Drake Charles G. , Bivalacqua Trinity J.
Published: June 2017

Intravesical bacillus Calmette–Guérin (BCG) immunotherapy is the standard of care in treating non–muscle-invasive bladder cancer, yet its mechanism of action remains elusive. Both innate and adaptive immune responses have been implicated in BCG activity. Although prior research has indirectly demonstrated the importance of T cells and shown a rise in CD4+ T cells in bladder tissue after BCG, T-cell subpopulations have not been fully characterized. We investigated the relationship between effector and regulatory T cells in an immune competent, clinically relevant rodent model of bladder cancer. Our data demonstrate that cancer progression in the N-methyl-N-nitrosourea (MNU) rat model of bladder cancer was characterized by a decline in the CD8/FoxP3 ratio, consistent with decreased adaptive immunity. In contrast, treatment with intravesical BCG led to a large, transient rise in the CD4+ T-cell population in the urothelium and was both more effective and immunogenic compared with intravesical chemotherapy. Whole-transcriptome expression profiling of posttreatment intravesical CD4+ and CD8+ T cells revealed minimal differences in gene expression after BCG treatment. Together, our results suggest that although BCG induces T-cell recruitment to the bladder, the T-cell phenotype does not markedly change, implying that combining T-cell–activating agents with BCG might improve clinical activity. Cancer Immunol Res; 5(7); 594–603. ©2017 AACR.
Are the Polyomaviruses BK and JC Associated with Opportunistic Infections, Graft-versus-Host Disease, or Worse Outcomes in Adult Patients Receiving Their First Allogeneic Stem Cell Transplantation with Low-Dose Alemtuzumab?
Authors: Schneidewind Laila , Neumann Thomas , Knoll Florian , Zimmermann Kathrin , Smola Sigrun , Schmidt Christian Andreas , Krüger William
Published: June 2017

Background: The association of polyomaviruses BK and JC with other opportunistic infections and graft-versus-host disease (GvHD) in allogeneic stem cell transplantation is controversially discussed. Methods: We conducted a retrospective study of 64 adult patients who received their first allogeneic stem cell transplantation between March 2010 and December 2014; the follow-up time was 2 years. Results: Acute leukemia was the most frequent underlying disease (45.3%), and conditioning included myeloablative (67.2%) and nonmyeloablative protocols (32.8%). All patients received 10 mg of alemtuzumab on day -2 (20 mg in case of mismatch) as GvHD prophylaxis. Twenty-seven patients (41.5%) developed cytomegalovirus (CMV) reactivation. BKPyV-associated hemorrhagic cystitis was diagnosed in 10 patients (15.6%). Other opportunistic infections caused by viruses or protozoa occurred rarely (<10%). There was no association of BKPyV or JCPyV with CMV reactivation, Epstein-Barr virus reactivation, human herpes virus 6, or parvovirus B19 infection requiring treatment. There was a significant correlation of BKPyV-associated hemorrhagic cystitis with toxoplasmosis (p = 0.013). Additionally, there was a significant link of simultaneous BKPyV and JCPyV viruria with toxoplasmosis (p = 0.047). BKPyV and JCPyV were not associated with GvHD, relapse, or death. Conclusion: We found no association of BKPyV or JCPyV with viral infections or GvHD. Only the correlation of both polyomaviruses with toxoplasmosis was significant. This is a novel and interesting finding.
Crosstalk between Stem and Progenitor Cellular Mediators with Special Emphasis on Vasculogenesis
Authors: Rohban Rokhsareh , Prietl Barbara , Pieber Thomas R.
Published: June 2017

The cellular components and molecular processes of signaling during vasculogenesis have been investigated for decades. Considerable efforts have been made to unravel regulatory mechanisms of vasculogenesis through crosstalk between vasculogenic playmakers located in the vascular niche, namely hematopoietic stem cells, endothelial progenitor cells, and mesenchymal stem and progenitor cells. Recent studies have increased the knowledge about signaling events within vascular microenvironment that leads to vasculogenesis. Findings from these recent studies indicate the impact of cellular crosstalk through signaling pathways such as vascular endothelial growth factor signaling, wingless and Notch signaling in vasculogenesis and vascular development. In this review, we highlight the signaling signature between stem and progenitor cellular mediators during vasculogenesis. We further focus on hematopoietic stem cell-endothelial progenitor cell crosstalk during vasculogenesis and discuss their potential implications and benefits for therapeutic interventions and regenerative therapy.
Different Approaches for Catheter Ablation of Para-Hisian Accessory Pathways
Authors: Liang Ming , Wang Zulu , Liang Yanchun , Yang Guitang , Jin Zhiqing , Sun Mingyu , Han Yaling
Published: June 2017

Background—

Catheter ablation of para-Hisian accessory pathways (APs) can be challenging because of adjacent conduction tissue. Some different approaches for ablation, including the inferior vena cava approach (IVC-A), the noncoronary cusp approach (NCC-A), or the superior vena cava approach (SVC-A), have been reported. However, when should para-Hisian APs be mapped and ablated by the IVC-A, NCC-A, or SVC-A is not well established.

Methods and Results—

This study included 55 consecutive patients (mean age, 53±11 years, 36 males) with para-Hisian APs. On the basis of the approach resulting in successful ablation, patients were divided into IVC-A, NCC-A, and SVC-A groups. The clinical characteristics, surface ECG, intracardiac electrogram findings, and response to ablation were analyzed. Para-Hisian APs were eliminated by IVC-A in 48 of the 55 (87%) patients. The rates of para-Hisian APs requiring NCC-A (4/55 patients, 7%) and SVC-A (3/55 patients, 6%) were relatively low. During mapping at the para-Hisian region, the local ventricular and atrial potentials were well fused during retrograde AP conduction in 45 of the 48 patients in IVC-A group, 0 of the 4 patients in NCC-A group, and 1 of the 3 patients in SVC-A group, respectively. There was no significant difference in the preexcitation characteristics among the 3 groups.

Conclusion—

Most para-Hisian APs can be safely and effectively ablated by IVC-A, and ablation in the NCC is not an initial or a preferred approach. The degree of local ventriculoatrial fusion in the para-Hisian region during retrograde AP conduction can differentiate or predict the successful ablation site.
The AMP-Related Kinase (AMPK) Induces Ca
2+
-Independent Dilation of Resistance Arteries by Interfering With Actin Filament Formation
Authors: Schubert Kai Michael , Qiu Jiehua , Blodow Stephanie , Wiedenmann Margarethe , Lubomirov Lubomir T. , Pfitzer Gabriele , Pohl Ulrich , Schneider Holger
Published: June 2017

Rationale:

Decreasing Ca
2+
sensitivity of vascular smooth muscle (VSM) allows for vasodilation without lowering of cytosolic Ca
2+
. This may be particularly important in states requiring maintained dilation, such as hypoxia. AMP-related kinase (AMPK) is an important cellular energy sensor in VSM. Regulation of Ca
2+
sensitivity usually is attributed to myosin light chain phosphatase activity, but findings in non-VSM identified changes in the actin cytoskeleton. The potential role of AMPK in this setting is widely unknown.

Objective:

To assess the influence of AMPK on the actin cytoskeleton in VSM of resistance arteries with regard to potential Ca
2+
desensitization of VSM contractile apparatus.

Methods and Results:

AMPK induced a slowly developing dilation at unchanged cytosolic Ca
2+
levels in potassium chloride–constricted intact arteries isolated from mouse mesenteric tissue. This dilation was not associated with changes in phosphorylation of myosin light chain or of myosin light chain phosphatase regulatory subunit. Using ultracentrifugation and confocal microscopy, we found that AMPK induced depolymerization of F-actin (filamentous actin). Imaging of arteries from LifeAct mice showed F-actin rarefaction in the midcellular portion of VSM. Immunoblotting revealed that this was associated with activation of the actin severing factor cofilin. Coimmunoprecipitation experiments indicated that AMPK leads to the liberation of cofilin from 14-3-3 protein.

Conclusions:

AMPK induces actin depolymerization, which reduces vascular tone and the response to vasoconstrictors. Our findings demonstrate a new role of AMPK in the control of actin cytoskeletal dynamics, potentially allowing for long-term dilation of microvessels without substantial changes in cytosolic Ca
2+
.
Predictors and Association With Clinical Outcomes of the Changes in Exercise Capacity After Transcatheter Aortic Valve Replacement
Authors: Abdul-Jawad Altisent Omar , Puri Rishi , Regueiro Ander , Chamandi Chekrallah , Rodriguez-Gabella Tania , del Trigo Maria , Campelo-Parada Francisco , Couture Thomas , Marsal Josep Ramon , Côté Mélanie , Paradis Jean-Michel , DeLarochellière Robert , Doyle Daniel , Mohammadi Siamak , Dumont Eric , Rodés-Cabau Josep
Published: June 2017

Background:

At present, there are no objective data specifically examining the clinical impact of variations in exercise capacity post–transcatheter aortic valve replacement (TAVR). We describe the changes in exercise capacity between baseline and 6 months post-TAVR, and ascertain factors associated with and clinical implications of a lack of improvement in exercise capacity post-TAVR.

Methods:

A total of 305 patients (mean age, 79±9 years; 44% men; Society of Thoracic Surgeons predicted risk mortality score, 6.7±4.2%) undergoing TAVR completed both baseline and follow-up exercise capacity assessments at 6 months post-TAVR. Exercise capacity was evaluated by the 6-minute walk test (6MWT). Clinical outcomes were compared between patients displaying greater than (n=152; improving group) versus less than (n=153; nonimproving group) the median percentage change in distance walked between baseline and 6-month follow-up examinations. The primary outcome measure was clinical event rates, measured from the 6-month post-TAVR period onward. Further dichotomization according to baseline 6MWT distance (less than versus more than median walking distance, or slow walker versus fast walker) was also assessed.

Results:

The mean overall distances walked pre- and post-TAVR (6 months post-TAVR) were 204±119 and 263±116 m, respectively (Δ6MWT=60±106 m), with 219 (72%) patients demonstrating an increase in their walking distance (median percentage increase of the entire population was 20% [interquartile range, 0%–80%]). Factors independently correlated with reduced exercise capacity improvement included a range of baseline clinical characteristics (older age, female sex, chronic obstructive pulmonary disease;
P
<0.05 for all), periprocedural major or life-threatening bleeding (
P
=0.009) and new-onset anemia at 6 months post-TAVR (
P
=0.009). Failure to improve the 6MWT distance by at least 20% was independently associated with all-cause mortality (
P
=0.002) and cardiovascular death or rehospitalization for cardiovascular causes (
P
=0.001). Baseline slow walkers who were able to improve the 6MWT distance presented with significantly better outcomes than nonimprovers (
P
=0.01 for all-cause mortality;
P
=0.001 for cardiovascular end point).

Conclusions:

Approximately one-third of patients undergoing TAVR did not improve their exercise capacity postprocedure. The lack of functional improvement post-TAVR was predicted by a mix of baseline and periprocedural factors translating into poorer clinical outcomes. These results suggest that systematically implementing exercise capacity assessment pre- and post-TAVR may help to improve patient risk stratification.
Plasminogen Activator Inhibitor Type I Controls Cardiomyocyte Transforming Growth Factor-β and Cardiac Fibrosis
Authors: Flevaris Panagiotis , Khan Sadiya S. , Eren Mesut , Schuldt Adam J. T. , Shah Sanjiv J. , Lee Daniel C. , Gupta Sweta , Shapiro Amy D. , Burridge Paul W. , Ghosh Asish K. , Vaughan Douglas E.
Published: June 2017

Background:

Fibrosis is the pathological consequence of stress-induced tissue remodeling and matrix accumulation. Increased levels of plasminogen activator inhibitor type I (PAI-1) have been shown to promote fibrosis in multiple organ systems. Paradoxically, homozygous genetic deficiency of PAI-1 is associated with spontaneous age-dependent, cardiac-selective fibrosis in mice. We have identified a novel PAI-1-dependent mechanism that regulates cardiomyocyte-derived fibrogenic signals and cardiac transcriptional pathways during injury.

Methods:

Cardiac fibrosis in subjects with homozygous mutation in
SERPINE-1
was evaluated with late gadolinium-enhanced cardiac magnetic resonance imaging. A murine cardiac injury model was performed by subcutaneous infusion of either saline or Angiotensin II by osmotic minipumps. We evaluated blood pressure, cardiac function (by echocardiography), fibrosis (with Masson Trichrome staining), and apoptosis (with TUNEL staining), and we performed transcriptome analysis (with RNA sequencing). We further evaluated fibrotic signaling in isolated murine primary ventricular myocytes.

Results:

Cardiac fibrosis was detected in 2 otherwise healthy humans with complete PAI-1 deficiency because of a homozygous frameshift mutation in
SERPINE-1
. In addition to its suppressive role during spontaneous cardiac fibrosis in multiple species, we hypothesized that PAI-1 also regulates fibrosis during cardiac injury. Treatment of young PAI-1
−/−
mice with Angiotensin II induced extensive hypertrophy and fibrotic cardiomyopathy, with increased cardiac apoptosis and both reactive and replacement fibrosis. Although Angiotensin II-induced hypertension was blunted in PAI-1
−/−
mice, cardiac hypertrophy was accelerated. Furthermore, ventricular myocytes were found to be an important source of cardiac transforming growth factor-β (TGF-β) and PAI-1 regulated TGF-β synthesis by cardiomyocytes in vitro as well as in vivo during cardiac injury. Transcriptome analysis of ventricular RNA after Angiotensin II treatment confirmed that PAI-1 deficiency significantly enhanced multiple TGF-β signaling elements and transcriptional targets, including genes for extracellular matrix components, mediators of extracellular matrix remodeling, matricellular proteins, and cardiac integrins compared with wild-type mice.

Conclusions:

PAI-1 is an essential repressor of cardiac fibrosis in mammals. We define a novel cardiomyocyte-specific regulatory mechanism for TGF-β production by PAI-1, which explains the paradoxical effect of PAI-1 deficiency in promoting cardiac-selective fibrosis. Thus, PAI-1 is a molecular switch that controls the cardiac TGF-β axis and its early transcriptional effects that lead to myocardial fibrosis.
In Good Company
Authors: Fraser Heather , Taylor Nik
Published: June 2017

Companion animals play an important role in many human’s lives, including many Australian social workers and clients. Yet Australian social work has been slow to address the burgeoning area of human-animal studies. In this embryonic research, we focus on women’s close relationships with companion animals and some of the broad implications this has for social work practice. We analyze some of the themes expressed by women who participated in three focus groups we conducted: two on a university campus and another in a community welfare agency setting. We also examine how the women interacted with each other as they spoke of “their pets,” as these dynamics point to a potentially important source of inspiration and energy that social workers may wish to harness in their day-to-day work with women.
Examination of the Accuracy and Applicability of Information in Popular Books on Dog Training
Authors: Browne Clare M. , Starkey Nicola J. , Foster T. Mary , McEwan James S.
Published: June 2017

There is a wealth of popular literature available on dog behavior and training; sourcing reliable and trustworthy advice is important to achieving successful training. The aim of this study was to select five best-selling (at that time) dog training books, and review their general content and references to basic learning theory and human communicative cues. An Internet search was performed on three online bookstores’ websites for “best selling” “dog training” books. The books were by Millan and Peltier (2006), Fennell (2002), Stilwell (2005), Pryor (1999), and Monks of New Skete (2002). The results showed marked differences across all books, including inconsistencies in the depth of information provided, and some starkly contrasting training methods were advocated. Overall, these books were not all considered to function as instructional manuals. The persistent popularity of these books suggests that they have likely contributed appreciably to the type of information accessed by dog guardians.
Resistance of Coffea arabica genotypes against Meloidogyne paranaensis and M. incognita under controlled and field conditions
Authors: Peres Ana Catarina J. , Salgado Sonia M.L. , Correa Valdir R. , Santos Marcilene F.A. , Mattos Vanessa S. , Monteiro Jessica M.S. , Carneiro Regina M.D.G.
Published: June 2017

Root-knot nematodes negatively impact on coffee yield worldwide. The use of resistant cultivars is the most effective way to manage these pests. The goal of this study was to identify Coffea arabica genotypes with resistance to Meloidogyne paranaensis and M. incognita race 1. Eighteen C. arabica genotypes (EPAMIG’s Germplasm Bank), previously selected for poor host suitability in a M. paranaensis-infested field, plus a resistant and a susceptible standard, were inoculated with these two Meloidogyne species to determine their resistance using nematode reproduction factor (). Accessions for which were considered resistant, while those for which were considered moderately resistant or susceptible, also according to statistical analysis. Five accessions from crossing ‘Catuaí Vermelho’ × ‘Amphillo MR 2-161’, one from ‘Catuaí Vermelho’ × ‘Amphillo MR 2-474’, two from ‘Timor Hybrid (UFV 408-01)’ and the standard ‘IPR-100’ were resistant to M. incognita race 1 with . Four accessions from ‘Catuaí Vermelho’ × ‘Amphillo MR 2-161’, one from ‘Timor Hybrid (UFV 408-01)’, one from ‘Catuaí Vermelho’ × ‘Amphillo MR 2-474’ and the resistant standard ‘IPR100’ were resistant to M. paranaensis (). Field evaluations with parental genotypes showed that plants that originated from progenies ‘Catuaí Vermelho’ × ‘Amphillo MR 2-161’ were resistant to M. paranaensis and also gave a good yield compared to commercial cultivars, showing promising agronomic traits that can be used in breeding programmes to develop new cultivars of C. arabica.
Soundless Screams: Graffiti and Drawings in the Prisons of the Holy Office in Palermo
Authors: Fiume Giovanna
Published: June 2017

The discovery of graffiti in the early years of the twentieth century by the folklorist Giuseppe Pitré left by prisoners of the tribunal of the Spanish Inquisition in Palermo has been followed by more extensive investigations in recent years. These images and words have added a concrete and particular dimension to Sicily’s position at the crossroads of the Mediterranean. As well as images of saints and naval battles are to be found inscriptions not only in Italian, Sicilian and Latin but also in English and Hebrew. This article cross references this visual and textual evidence with the relevant archives of the tribunal in order to provide a powerful microhistory of suffering and resilience in this most inhospitable of environments. The result adds a new dimension to our understanding of the prison’s organization, judicial proceedings and the impact of the inquisition on the lives and consciences of those people from all over Europe, North Africa and the Middle East, who found themselves unwilling denizens of what must have been perhaps the most international community of prisoners in the early modern Christian world.