bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of long‐term use of the preferential COX‐2 inhibitor meloxicam on growing pigs
Authors: Gorissen Ben M C , Uilenreef Joost J , Bergmann Wilhelmina , Meijer Ellen , van Rietbergen Bert , van der Staay Franz Josef , van Weeren P René , Wolschrijn Claudia F
Published: October 2017

Meloxicam, a preferential COX‐2 inhibitor, is a commonly used NSAID in pigs. Besides having potential side effects on the gastrointestinal tract, this type of drug might potentially affect osteogenesis and chondrogenesis, processes relevant to growing pigs. Therefore, the effects of long‐term meloxicam treatment on growing pigs were studied. Twelve piglets (n=6 receiving daily meloxicam 0.4 mg/kg orally from 48 until 110 days of age; n=6 receiving only applesauce (vehicle control)) were subjected to visual and objective gait analysis by pressure plate measurements at several time points. Following euthanasia a complete postmortem examination was performed and samples of the talus and distal tibia, including the distal physis, were collected. Trabecular bone microarchitecture was analysed by microCT scanning, bone stiffness by compression testing and growth plate morphology using light microscopy. Animals were not lame and gait patterns did not differ between the groups. Pathological examination revealed no lesions compatible with known side effects of NSAIDs. Trabecular bone microarchitecture and growth plate morphology did not differ between the two groups. The findings of this in vivo study reduce concerns regarding the long‐term use of meloxicam in young, growing piglets.
Use of shrub willows (Salix spp.) to develop soil communities during coal mine restoration
Authors: Sylvain Zachary A. , Mosseler Alex
Published: October 2017

Afforestation or reforestation in highly degraded environments (e.g., surface mines) is often complicated by the total removal of vegetation and severe soil degradation that occurs during mining operations, necessitating revegetation to be undertaken in tandem with the re-establishment of soil developmental processes. Shrub willows (Salix spp.) are effective as colonizer species initiating revegetation dynamics; however, it is unclear if they also serve as nurse plants facilitating the establishment of soil communities such as those of nematodes. We established a study in a former coal mine site in New Brunswick, Canada, to assess whether the presence of willows on otherwise bare, poorly developed soil contributed to nematode community development and to what degree landform design (e.g., slope) may influence these dynamics. Our results demonstrate that willows can facilitate nematode communities at this site, but that slope strongly influences these effects, likely as a consequence of hydrology and overland water flow. These results confirm the beneficial role that willows can play in reforestation of highly degraded environments both for revegetation and for the re-initiation of soil ecosystem processes.
A critical analysis of the carbon neutrality assumption in life cycle assessment of forest bioenergy systems
Authors: Liu Weiguo , Yu Zhen , Xie Xinfeng , von Gadow Klaus , Peng Changhui
Published: October 2017

This study presents a critical analysis regarding the assumption of carbon neutrality in life cycle assessment (LCA) models that assess climate change impacts of bioenergy usage. We identified a complex of problems in the carbon neutrality assumption, especially regarding bioenergy derived from forest residues. In this study, we summarized several issues related to carbon neutral assumptions, with particular emphasis on possible carbon accounting errors at the product level. We analyzed errors in estimating emissions in the supply chain, direct and indirect emissions due to forest residue extraction, biogenic CO2 emission from biomass combustion for energy, and other effects related to forest residue extraction. Various modeling approaches are discussed in detail. We concluded that there is a need to correct accounting errors when estimating climate change impacts and proposed possible remedies. To accurately assess climate change impacts of bioenergy use, greater efforts are required to improve forest carbon cycle modeling, especially to identify and correct pitfalls associated with LCA accounting, forest residue extraction effects on forest fire risk and biodiversity. Uncertainties in accounting carbon emissions in LCA are also highlighted, and associated risks are discussed.
Cancer Metastasis: A Reappraisal of Its Underlying Mechanisms and Their Relevance to Treatment
Authors: Riggi Nicolo , Aguet Michel , Stamenkovic Ivan
Published: October 2017

Metastases are responsible for the vast majority of cancer-related deaths, but, despite intense efforts to understand their underlying mechanisms with the goal of uncovering effective therapeutic targets, treatment of metastatic cancer has progressed minimally. In this review, we examine the biological programs currently proposed to be key drivers of metastasis. On the basis of evidence from a growing body of research, we discuss to what extent the cellular and molecular mechanisms that are suggested to underlie cancer cell dissemination are specific to the metastatic process, as opposed to representing natural primary tumor progression. Our review highlights the contrast between the abundance of insight gained into the events that constitute the metastatic cascade and the paucity of therapeutic options.
Interindividual variability in muscle sympathetic responses to static handgrip in young men: evidence for sympathetic responder types?
Authors: Incognito Anthony V. , Doherty Connor J. , Lee Jordan B. , Burns Matthew J. , Millar Philip J.
Published: October 2017

Negative and positive muscle sympathetic nerve activity (MSNA) responders have been observed during mental stress. We hypothesized that similar MSNA response patterns could be identified during the first minute of static handgrip and contribute to the interindividual variability throughout exercise. Supine measurements of multiunit MSNA (microneurography) and continuous blood pressure (Finometer) were recorded in 29 young healthy men during the first (HG1) and second (HG2) minute of static handgrip (30% maximal voluntary contraction) and subsequent postexercise circulatory occlusion (PECO). Responders were identified on the basis of differences from the typical error of baseline total MSNA: 7 negative, 12 positive, and 10 nonresponse patterns. Positive responders demonstrated larger total MSNA responses during HG1 ( P < 0.01) and HG2 ( P < 0.0001); however, the increases in blood pressure throughout handgrip exercise were similar between all groups, as were the changes in heart rate, stroke volume, cardiac output, total vascular conductance, and respiration (all P > 0.05). Comparing negative and positive responders, total MSNA responses were similar during PECO ( P = 0.17) but opposite from HG2 to PECO (∆40 ± 46 vs. ∆-21 ± 62%, P = 0.04). Negative responders also had a shorter time-to-peak diastolic blood pressure during HG1 (20 ± 20 vs. 44 ± 14 s, P < 0.001). Total MSNA responses during HG1 were associated with responses to PECO ( r = 0.39, P < 0.05), the change from HG2 to PECO ( r = −0.49, P < 0.01), and diastolic blood pressure time to peak ( r = 0.50, P < 0.01). Overall, MSNA response patterns during the first minute of static handgrip contribute to interindividual variability and appear to be influenced by differences in central command, muscle metaboreflex activation, and rate of loading of the arterial baroreflex.
Dexamethasone enhances vasopressin-induced aquaporin-2 gene expression in the mpkCCD cells
Authors: Kuo Kuang-Ting , Yang Chan-Wei , Yu Ming-Jiun
Published: October 2017

The mouse cortical collecting duct cell (mpkCCD) has been an instrumental cell model for studying vasopressin-mediated aquaporin-2 regulation. This cell line was first developed by Vandewalle’s group from a transgenic mouse carrying the transforming SV40 antigens driven by the pyruvate kinase promoter. To immortalize the cells, four hormone supplements (dexamethasone, epidermal growth factor, insulin, and triiodothyronine) were used to enhance SV40 antigen expression; however, these hormones appear to have various effects on aquaporin-2 gene expression in the cells. Here, we evaluated the effects of each hormone supplement and found that dexamethasone enhanced vasopressin-induced aquaporin-2 gene expression at both mRNA and protein levels in a dose- and time-dependent manner, without affecting mRNA or protein stability. The effects of dexamethasone were attributed largely to enhanced aquaporin-2 mRNA transcription in association with an enhanced aquaporin-2 promoter activity. Dexamethasone did not affect vasopressin-regulated aquaporin-2 phosphorylation and trafficking. In summary, we optimized the conditions to enhance vasopressin-induced endogenous aquaporin-2 gene expression in the mpkCCD cells. By increasing the amount of aquaporin-2 protein in the cells, our method will facilitate the study of aquaporin-2 cell physiology regulated by vasopressin.
miR-34c-5p and CaMKII are involved in aldosterone-induced fibrosis in kidney collecting duct cells
Authors: Park Eui-Jung , Jung Hyun Jun , Choi Hyo-Jung , Cho Jeong-In , Park Hye-Jeong , Kwon Tae-Hwan
Published: October 2017

Mineralocorticoids trigger a profibrotic process in the kidney. In mouse cortical collecting duct cells, the present study addressed two main questions: 1) what are microRNAs (miRNAs) and their target genes that are changed by aldosterone? and 2) what do miRNAs, in response to aldosterone, regulate regarding signaling pathways related to fibrosis? A microarray chip assay was done in cells in the absence or presence of aldosterone treatment (10−6M; 3 days). The candidate miRNAs were identified by the criteria of >30% of fold change among the significantly changed miRNAs ( P < 0.05). Twenty-nine miRNAs were upregulated (>1.3-fold), and 27 miRNAs were downregulated (<0.7-fold). Putative target genes of identified miRNAs were associated with 74 Kyoto Encyclopedia of Genes and Genomes pathways. Among them, the wingless-related integration site (Wnt) signaling pathway was highly ranked, where 15 mature miRNAs were observed. These miRNAs were further analyzed by real-time quantitative PCR, and among them, miR-130b-3p, miR-34c-5p, and miR-146a-5p were selected. Through the identification of putative target genes of these three miRNAs, mRNA and protein expression of the Ca2+/calmodulin-dependent protein kinase type II β-chain ( Camk2b) gene (a target gene of miR-34c-5p) were found to be increased significantly in aldosterone-treated cells, where fibronectin (FN) and α-smooth muscle actin were induced. When CaMKIIβ small interfering RNA or the miR-34c-5p mimic was transfected, aldosterone-induced FN expression was significantly attenuated, along with reduced CaMKIIβ protein expression. A luciferase reporter assay revealed a decrease of CaMKIIβ translation in cells transfected with miRNA mimics of miR-34c-5p. In conclusion, aldosterone-induced downregulation of miR-34c-5p in the Wnt signaling pathway and a consequent increase of CaMKIIβ expression are likely to be involved in aldosterone-induced fibrosis.
Saphenous nerve stimulation normalizes bladder underactivity induced by tibial nerve stimulation in cats
Authors: Li Shun , Li Xing , Theisen Katherine , Browning Jeffery , Shen Bing , Wang Jicheng , Roppolo James R. , de Groat William C. , Tai Changfeng
Published: October 2017

This study in α-chloralose-anesthetized cats aimed at investigating the bladder responses to saphenous nerve stimulation (SNS). A urethral catheter was used to infuse the bladder with saline and to record changes in bladder pressure. With the bladder fully distended, SNS at 1-Hz frequency and an intensity slightly below the threshold (T) for inducing an observable motor response of the hindlimb muscles induced large amplitude (40–150 cmH2O) bladder contractions. Application of SNS (1 Hz, 2–4T) during cystometrograms (CMGs), when the bladder was slowly (1–3 ml/min) infused with saline, significantly ( P < 0.05) increased the duration of the micturition contraction to >200% of the control without changing bladder capacity or contraction amplitude. Repeated application (1–8 times) of intense (4–8T intensity) 30-min tibial nerve stimulation (TNS) produced prolonged post-TNS inhibition that significantly ( P < 0.01) increased bladder capacity to 135.9 ± 7.6% and decreased the contraction amplitude to 44.1 ± 16.5% of the pre-TNS control level. During the period of post-TNS inhibition, SNS (1 Hz, 2–4T) applied during CMGs completely restored the bladder capacity and the contraction amplitude to the pre-TNS control level and almost doubled the duration of the micturition contraction. These results indicate that SNS at 1 Hz can facilitate the normal micturition reflex and normalize the reflex when it is suppressed during post-TNS inhibition. This study provides an opportunity to develop a novel neuromodulation therapy for underactive bladder using SNS.
The Kölliker-Fuse nucleus orchestrates the timing of expiratory abdominal nerve bursting
Authors: Barnett William H. , Jenkin Sarah E. M. , Milsom William K. , Paton Julian F. R. , Abdala Ana P. , Molkov Yaroslav I. , Zoccal Daniel B.
Published: October 2017

Coordination of respiratory pump and valve muscle activity is essential for normal breathing. A hallmark respiratory response to hypercapnia and hypoxia is the emergence of active exhalation, characterized by abdominal muscle pumping during the late one-third of expiration (late-E phase). Late-E abdominal activity during hypercapnia has been attributed to the activation of expiratory neurons located within the parafacial respiratory group (pFRG). However, the mechanisms that control emergence of active exhalation, and its silencing in restful breathing, are not completely understood. We hypothesized that inputs from the Kölliker-Fuse nucleus (KF) control the emergence of late-E activity during hypercapnia. Previously, we reported that reversible inhibition of the KF reduced postinspiratory (post-I) motor output to laryngeal adductor muscles and brought forward the onset of hypercapnia-induced late-E abdominal activity. Here we explored the contribution of the KF for late-E abdominal recruitment during hypercapnia by pharmacologically disinhibiting the KF in in situ decerebrate arterially perfused rat preparations. These data were combined with previous results and incorporated into a computational model of the respiratory central pattern generator. Disinhibition of the KF through local parenchymal microinjections of gabazine (GABAA receptor antagonist) prolonged vagal post-I activity and inhibited late-E abdominal output during hypercapnia. In silico, we reproduced this behavior and predicted a mechanism in which the KF provides excitatory drive to post-I inhibitory neurons, which in turn inhibit late-E neurons of the pFRG. Although the exact mechanism proposed by the model requires testing, our data confirm that the KF modulates the formation of late-E abdominal activity during hypercapnia.

NEW & NOTEWORTHY The pons is essential for the formation of the three-phase respiratory pattern, controlling the inspiratory-expiratory phase transition. We provide functional evidence of a novel role for the Kölliker-Fuse nucleus (KF) controlling the emergence of abdominal expiratory bursts during active expiration. A computational model of the respiratory central pattern generator predicts a possible mechanism by which the KF interacts indirectly with the parafacial respiratory group and exerts an inhibitory effect on the expiratory conditional oscillator.
Central pattern generators in the turtle spinal cord: selection among the forms of motor behaviors
Authors: Stein Paul S. G.
Published: October 2017

Neuronal networks in the turtle spinal cord have considerable computational complexity even in the absence of connections with supraspinal structures. These networks contain central pattern generators (CPGs) for each of several behaviors, including three forms of scratch, two forms of swim, and one form of flexion reflex. Each behavior is activated by a specific set of cutaneous or electrical stimuli. The process of selection among behaviors within the spinal cord has multisecond memories of specific motor patterns. Some spinal cord interneurons are partially shared among several CPGs, whereas other interneurons are active during only one type of behavior. Partial sharing is a proposed mechanism that contributes to the ability of the spinal cord to generate motor pattern blends with characteristics of multiple behaviors. Variations of motor patterns, termed deletions, assist in characterization of the organization of the pattern-generating components of CPGs. Single-neuron recordings during both normal and deletion motor patterns provide support for a CPG organizational structure with unit burst generators (UBGs) whose members serve a direction of a specific degree of freedom of the hindlimb, e.g., the hip-flexor UBG, the hip-extensor UBG, the knee-flexor UBG, the knee-extensor UBG, etc. The classic half-center hypothesis that includes all the hindlimb flexors in a single flexor half-center and all the hindlimb extensors in a single extensor half-center lacks the organizational complexity to account for the motor patterns produced by turtle spinal CPGs. Thus the turtle spinal cord is a valuable model system for studies of mechanisms responsible for selection and generation of motor behaviors.

NEW & NOTEWORTHY The concept of the central pattern generator (CPG) is a major tenet in motor neuroethology that has influenced the design and interpretations of experiments for over a half century. This review concentrates on the turtle spinal cord and describes studies from the 1970s to the present responsible for key developments in understanding the CPG mechanisms responsible for the selection and production of coordinated motor patterns during turtle hindlimb motor behaviors.
Exploration of the Association between Nurses’ Moral Distress and Secondary Traumatic Stress Syndrome: Implications for Patient Safety in Mental Health Services
Authors: Christodoulou-Fella Maria , Middleton Nicos , Papathanassoglou Elizabeth D. E. , Karanikola Maria N. K.
Published: October 2017

Work-related moral distress (MD) and secondary traumatic stress syndrome (STSS) may be associated with compromised health status among health professionals, reduced productivity, and inadequate safety of care. We explored the association of MD with the severity of STSS symptoms, along with the mediating role of mental distress symptoms. Associations with emotional exhaustion and professional satisfaction were also assessed. This cross-sectional survey conducted in 206 mental health nurses (MHNs) was employed across public sector community and hospital settings in Cyprus. The analysis revealed that MD (measured by the modified Moral Distress Scale) was positively associated with both STSS (measured by the Secondary Traumatic Stress Scale) and mental distress symptoms (assessed by the General Health Questionnaire-28). The association of MD with STSS symptoms was partially mediated by mental distress symptoms. This association remained largely unchanged after adjusting for gender, age, education, rank, and intention to quit the job. Our findings provide preliminary evidence on the association between MD and STSS symptomatology in MHNs. Situations that may lead health professionals to be in moral distress seem to be mainly related to the work environment; thus interventions related to organizational empowerment of MHNs need to be developed.
Difficult to Treat Focal, Stiff Person Syndrome of the Left Upper Extremity
Authors: Esplin Nathan E. , Stelzer John W. , Legare Timothy B. , Ali Sayed K.
Published: October 2017

Background. Stiff person syndrome (SPS) is a rare neurologic disorder characterized by muscle rigidity. It is a disorder of reduced GABA activity leading to increased muscle tone and often painful spasms. It generally presents in the axial musculature but rarely can involve only one limb, typically a lower extremity. In rare cases it can be paraneoplastic which generally resolves on treatment of the underlying neoplasm. Case Report. A 46-year-old male with a history of Hodgkin’s Lymphoma in remission presented with left upper extremity pain secondary to a diagnosis of Stiff Person Syndrome limited to his left upper extremity. He had previously benefitted from plasmapheresis and was on diazepam and baclofen at home with relatively good control of his symptoms. SPS had previously been diagnosed with EMG and anti-GAD-65 antibody titers and was confirmed by an elevated anti-GAD-65 antibody titer. He was treated with plasmapheresis and maximum doses of medical treatment including botulinum toxin with only transient mild improvement in his symptoms. Conclusion. This case represents a case of a rare disease that was refractory to all known therapies. It outlines the need for further understanding of this disorder in order to provide better symptomatic treatment or potentially more definitive care.
Immune and Inflammatory Responses of the Intestinal Mucosa following Extended Liver Radiofrequency Ablation
Authors: Ypsilantis Petros , Lambropoulou Maria , Evagellou Antonios , Papadopoulos Nikolaos , Simopoulos Constantinos
Published: October 2017

Background and Aim. Extended liver radiofrequency ablation (RFA) has been shown to disrupt gut barrier integrity with subsequent bacterial translocation. The aim of the present project was to study the immune and inflammatory responses of the intestinal mucosa after extended RFA of the liver.Methods. Twelve Wistar rats were either subjected to RFA of the left lateral hepatic lobe (approximately 30% of the liver mass) after midline laparotomy (group RFA,n=6) or sham operation (group Sham,n=6). Forty-eight hours later, ileal tissue specimens were excised for immunohistochemical assessment of CD68+macrophages, CD4+T-lymphocytes, CD8+T-lymphocytes, mucosal addressin cell adhesion molecule-1 (MAdCAM-1), tumor necrosis factor-α(TNFα), interleukin-6 (IL-6), and nuclear factor-κB (NFκB) expression.Results. Immune response biomarkers were upregulated in the RFA group. Expression of CD4+and CD8+T-lymphocytes was moderate, while that of CD68+macrophages and MAdCAM-1 was high. Inflammatory response biomarkers were also upregulated in the RFA group. TNFα, IL-6, and NFκB expression was low, moderate, and high, respectively.Conclusions. Extended liver RFA evokes both immune and inflammatory responses of the gut mucosa.
Methods for the Evaluation of Waste Treatment Processes
Authors: Gehrmann Hans-Joachim , Hiebel Markus , Simon Franz-Georg
Published: October 2017

Decision makers for waste management are confronted with the problem of selecting the most economic, environmental, and socially acceptable waste treatment process. This paper elucidates evaluation methods for waste treatment processes for the comparison of ecological and economic aspects such as material flow analysis, statistical entropy analysis, energetic and exergetic assessment, cumulative energy demand, and life cycle assessment. The work is based on the VDI guideline 3925. A comparison of two thermal waste treatment plants with different process designs and energy recovery systems was performed with the described evaluation methods. The results are mainly influenced by the type of energy recovery, where the waste-to-energy plant providing district heat and process steam emerged to be beneficial in most aspects. Material recovery options from waste incineration were evaluated according to sustainability targets, such as saving of resources and environmental protection.
Inhibitors of Histone Deacetylases Are Weak Activators of the FMR1 Gene in Fragile X Syndrome Cell Lines
Authors: Dolskiy Alexander A. , Pustylnyak Vladimir O. , Yarushkin Andrey A. , Lemskaya Natalya A. , Yudkin Dmitry V.
Published: October 2017

Fragile X syndrome is the most common cause of inherited intellectual disability in humans. It is a result of CGG repeat expansion in the 5′ untranslated region (5′ UTR) of the FMR1 gene. This gene encodes the FMRP protein that is involved in neuronal development. Repeat expansion leads to heterochromatinization of the promoter, gene silencing, and the subsequent absence of FMRP. To date, there is no specific therapy for the syndrome. All treatments in clinic practice provide symptomatic therapy. The development of drug therapy for Fragile X syndrome treatment is connected with the search for inhibitors of enzymes that are responsible for heterochromatinization. Here, we report a weak transcriptional activity of the FMR1 gene and the absence of FMRP protein after Fragile X syndrome cell lines treatment with two FDA approved inhibitors of histone deacetylases, romidepsin and vorinostat. We demonstrate that romidepsin, an inhibitor of class I histone deacetylases, does not activate FMR1 expression in patient cell cultures, whereas vorinostat, an inhibitor of classes I and II histone deacetylases, activates a low level of FMR1 expression in some patient cell lines.
The Immediate Analgesic Effect of Acupuncture for Pain: A Systematic Review and Meta‐Analysis
Authors: Xiang Anfeng , Cheng Ke , Shen Xueyong , Xu Ping , Liu Sheng
Published: October 2017

Although acupuncture is gaining popularity for the treatment of nonspecific pain, the immediate analgesic effect of acupuncture has never been reviewed. We conducted a systematic review and meta‐analysis of randomized controlled trials (RCTs) on disease‐related pain to critically evaluate the immediate effect of acupuncture for pain relief. The PubMed and Cochrane Central Register of Controlled Trials databases as well as three Chinese databases including the China National Knowledge Infrastructure (CNKI), Wanfang, and VIP platforms were searched through November 2016. The outcome was the extent of pain relief from baseline within 30 min of the first acupuncture treatment. We evaluated all RCTs comparing acupuncture with other interventions for disease‐related pain. Real acupuncture showed statistically significantly greater pain relief effect compared to sham acupuncture (SMD, −0.56; 95% confidence interval [CI], −1.00 to −0.12; 9 RCTs) and analgesic injection (SMD, −1.33; 95% CI, −1.94 to −0.72; 3 RCTs). No serious adverse events were documented. Acupuncture was associated with a greater immediate pain relief effect compared to sham acupuncture and analgesic injections. Further RCTs with stricter design and methodologies are warranted to evaluate the immediate pain relief effect of acupuncture for more disease‐related pain.
Site Specific Stem Volume Models for Pinus patula and Pinus oocarpa
Authors: Malata Herbert , Ngulube Elisha S. , Missanjo Edward
Published: October 2017

Sustainable management of timber forests requires availability and adequacy of models for accurate estimation of tree volumes. This study was conducted to develop site specific models for estimating individual total tree stem volume of Pinus patula and Pinus oocarpa at Chongoni Timber Plantation in Central Malawi. A total of 32 trees from Pinus patula compartment and 48 trees from Pinus oocarpa compartment were destructively sampled. Various predictors including diameter at breast height (dbh) and height (ht) were run against total stem volume using a nonlinear mixed-effects modelling approach. The results indicate that the developed site specific models showed a significant association between total stem volume and the predictors (dbh and ht). The developed volume models accounted for at least 99% of the total variation in the total stem volume data. This suggests that application of the developed site specific models is highly recommended when accurate results are required. The appropriateness of the developed models was also supported by the fact that the total relative errors (TRE) of these models were lower (range: −0.04% to 0.06%) than the TRE of some previously developed models (range: −12.40% to 41.70%) tested on the present data.
Mitigation of Ground Vibration due to Collapse of a Large-Scale Cooling Tower with Novel Application of Materials as Cushions
Authors: Lin Feng , Zhong Qiheng
Published: October 2017

Ground vibration induced by the collapse of large-scale cooling towers in nuclear power plants (NPPs) has recently been realized as a potential secondary disaster to adjacent nuclear-related facilities with demands for vibration mitigation. The previous concept to design cooling towers and nuclear-related facilities operating in a containment as isolated components in NPPs is inappropriate in a limited site which is the cases for inland NPPs in China. This paper presents a numerical study on the mitigation of ground vibration in a “cooling tower-soil-containment” system via a novel application of two materials acting as cushions underneath cooling towers, that is, foamed concrete and a “tube assembly.” Comprehensive “cooling tower-cushion-soil” models were built with reasonable cushion material models. Computational cases were performed to demonstrate the effect of vibration mitigation using seven earthquake waves. Results found that collapse-induced ground vibrations at a point with a distance of 300 m were reduced in average by 91%, 79%, and 92% in radial, tangential, and vertical directions when foamed concrete was used, and the vibrations at the same point were reduced by 53%, 32%, and 59% when the “tube assembly” was applied, respectively. Therefore, remarkable vibration mitigation was achieved in both cases to enhance the resilience of the “cooling tower-soil-containment” system against the secondary disaster.
The Controller Design of the Epilepsy Therapy Apparatus
Authors: Li Ning , Sun Haiyi , Zhang Qingling
Published: October 2017

Deep brain stimulation (DBS) is one of the effective treatments of epilepsy. Based on the Lyapunov stability theory combined with the method of the periodically intermittent control and adaptive control, the abnormal synchronization neural network models with high frequency oscillation are achieved with multilag synchronization in this paper. Some simple criteria are derived for the multilag synchronization of the coupled neural networks with coupling delays. The adaptive periodically intermittent control which we have obtained can cut down control cost. The sufficient conditions of this paper for abnormal neural network multilag synchronization are less conservative and can be applied in a wider area. Finally, simulation results show the effectiveness of the proposed control strategy. The design of controllers and control strategy may provide a potential electrical stimulation therapy on neurological diseases caused by abnormal synchronization. And they can provide technical support for epilepsy treatment apparatus research and development.
Low-Cost GPS Receivers for the Monitoring of Sunflower Cover Dynamics
Authors: Zribi Mehrez , Motte Erwan , Fanise Pascal , Zouaoui Walid
Published: October 2017

The aim of this research is to analyze the potential use of Global Navigation Satellite System (GNSS) signals for the monitoring of in situ vegetation characteristics. An instrument, based on the use of a pair of low-cost receivers and antennas, providing continuous measurements of all the available Global Positioning System (GPS) satellite signals is proposed for the determination of signal attenuation caused by a sunflower cover. Experimental campaigns with this instrument, combined with ground truth measurements of the vegetation, were performed over a nonirrigated sunflower test field for a period of more than two months, corresponding to a significant portion of the vegetation cycle. A method is proposed for the analysis of the signal attenuation data as a function of elevation and azimuth angles. A high correlation is observed between the vegetation’s water content and the GPS signals attenuation, and an empirical modeling is tested for the retrieval of signal behavior as a function of vegetation water content (VWC). The VWC was estimated from GNSS signals on a daily basis, over the full length of the study period.
Challenges in Clock Synchronization for On-Site Coding Digital Beamformer
Authors: Bojja Venkatakrishnan Satheesh , Alwan Elias A. , Volakis John L.
Published: October 2017

Typical radio frequency (RF) digital beamformers can be highly complex. In addition to a suitable antenna array, they require numerous receiver chains, demodulators, data converter arrays, and digital signal processors. To recover and reconstruct the received signal, synchronization is required since the analog-to-digital converters (ADCs), digital-to-analog converters (DACs), field programmable gate arrays (FPGAs), and local oscillators are all clocked at different frequencies. In this article, we present a clock synchronization topology for a multichannel on-site coding receiver (OSCR) using the FPGA as a master clock to drive all RF blocks. This approach reduces synchronization errors by a factor of 8, when compared to conventional digital beamformer.
Genetic Analysis of LRRK2 R1628P in Parkinson’s Disease in Asian Populations
Authors: Zhang Yuan , Sun Qiying , Yi Minhan , Zhou Xun , Guo Jifeng , Xu Qian , Tang Beisha , Yan Xinxiang
Published: October 2017

Although the etiology of Parkinson’s disease (PD) remains unclear, there is increasing evidence of genetic factors contributing to the onset of PD. Various mutations and risk variants of the gene LRRK2 have been reported, but the association between LRRK2 R1628P and PD is still inconsistent. Thus, we conducted a meta-analysis to determine the potential relationship between R1628P and PD. Our study sample was an aggregate of 17 publications, which in total consisted of 9,275 PD patients and 8,114 controls. All of these articles are of high quality according to NOS, and there was no obvious reporting bias or heterogeneity. In a general Asian population, the pooled OR of the risk genotype contrasts was 1.83 (95% CI: 1.57, 2.13). When stratified by ethnicity, the pooled ORs were 1.84 (95% CI: 1.56, 2.18) in a Chinese population and 1.79 (95% CI: 1.27, 2.52) in a non-Chinese population. Our study suggests that LRRK2 R1628P appears to be a risk factor for PD in Asian populations, both Chinese and non-Chinese.
Maxillary Sinus Floor Augmentation Using an Equine-Derived Graft Material: Preliminary Results in 17 Patients
Authors: Rivara F. , Negri M. , Lumetti S. , Parisi L. , Toffoli A. , Calciolari E. , Manfredi E. , Macaluso G. M.
Published: October 2017

Objective. Sinus floor elevation with lateral approach is probably the most frequently performed reconstructive procedure to rehabilitate posterior maxilla when a bone deficiency is present. Different graft materials have been proposed and tested, often with high clinical performances and predictable results. Histological analysis is required when evaluating new materials. We investigated human biopsies retrieved after sinus floor elevation procedure by histomorphometric evaluation to test the performance of an equine-derived bone grafting material.Study Design. Seventeen consecutive patients were enrolled and sinus lift surgeries were performed using an equine bone graft. Six months after surgery, at implant placement, bone samples were collected. Histomorphometry analysis was carried out on decalcified samples.Results. All surgeries were uneventful and no additional grafting was required prior to implant insertion. Forty percent of new bone formation was detected, which represented the most abundant tissue retrieved, followed by the residual graft material (33%) and fibrous tissue (27%). A significant reduction in particles size demonstrates a remodeling activity of the graft material.Conclusion. Within the limitations of this study, this equine-derived bone graft proved to be an effective material to induce new bone formation in the sinus floor elevation procedure.
CD39 Expression Defines Cell Exhaustion in Tumor-Infiltrating CD8+ T Cells
Authors: Canale Fernando P. , Ramello María C. , Núñez Nicolás , Furlan Cintia L. Araujo , Bossio Sabrina N. , Serrán Melisa Gorosito , Boari Jimena Tosello , del Castillo Andrés , Ledesma Marta , Sedlik Christine , Piaggio Eliane , Gruppi Adriana , Rodríguez Eva V. Acosta , Montes Carolina L.
Published: October 2017

The ability of CD8+ T lymphocytes to eliminate tumors is limited by their ability to engender an immunosuppressive microenvironment. Here we describe a subset of tumor-infiltrating CD8+ T cells marked by high expression of the immunosuppressive ATP ecto-nucleotidase CD39. The frequency of CD39highCD8+ T cells increased with tumor growth but was absent in lymphoid organs. Tumor-infiltrating CD8+ T cells with high CD39 expression exhibited features of exhaustion, such as reduced production of TNF and IL2 and expression of coinhibitory receptors. Exhausted CD39+CD8+ T cells from mice hydrolyzed extracellular ATP, confirming that CD39 is enzymatically active. Furthermore, exhausted CD39+CD8+ T cells inhibited IFNγ production by responder CD8+ T cells. In specimens from breast cancer and melanoma patients, CD39+CD8+ T cells were present within tumors and invaded or metastatic lymph nodes, but were barely detectable within noninvaded lymph nodes and absent in peripheral blood. These cells exhibited an exhausted phenotype with impaired production of IFNγ, TNF, IL2, and high expression of coinhibitory receptors. Although T-cell receptor engagement was sufficient to induce CD39 on human CD8+ T cells, exposure to IL6 and IL27 promoted CD39 expression on stimulated CD8+ T cells from human or murine sources. Our findings show how the tumor microenvironment drives the acquisition of CD39 as an immune regulatory molecule on CD8+ T cells, with implications for defining a biomarker of T-cell dysfunction and a target for immunotherapeutic intervention.

Significance: The tumor microenvironment elicits a subset of functionally exhausted CD8+ T cells by creating conditions that induce cell surface expression of CD39, an immunosuppressive molecule that can be therapeutically targeted to restore effector T-cell function. Cancer Res; 78(1); 115–28. ©2017 AACR.
Evidence for Kaposi Sarcoma Originating from Mesenchymal Stem Cell through KSHV-induced Mesenchymal-to-Endothelial Transition
Authors: Li Yuqing , Zhong Canrong , Liu Dawei , Yu Wenjing , Chen Weikang , Wang Yan , Shi Songtao , Yuan Yan
Published: October 2017

The major transmission route for Kaposi sarcoma–associated herpesvirus (KSHV) infection is the oral cavity through saliva. Kaposi sarcoma (KS) frequently occurs in the oral cavity in HIV-positive individuals and is often the first presenting sign of AIDS. However, the oral target cells for KSHV infection and the cellular origin of Kaposi sarcoma remain unknown. Here we present clinical and experimental evidences that Kaposi sarcoma spindle cells may originate from virally modified oral mesenchymal stem cells (MSC). AIDS-KS spindle cells expressed neuroectodermal stem cell marker (Nestin) and oral MSC marker CD29, suggesting an oral/craniofacial MSC lineage of AIDS-associated Kaposi sarcoma. Furthermore, oral MSCs were highly susceptible to KSHV infection, and infection promoted multilineage differentiation and mesenchymal-to-endothelial transition (MEndT). KSHV infection of oral MSCs resulted in expression of a large number of cytokines, a characteristic of Kaposi sarcoma, and upregulation of Kaposi sarcoma signature and MEndT-associated genes. These results suggest that Kaposi sarcoma may originate from pluripotent MSC and KSHV infection transforms MSC to Kaposi sarcoma–like cells through MEndT.

Significance: These findings indicate that Kaposi sarcomas, which arise frequently in AIDS patients, originate from neural crest-derived mesenchymal stem cells, with possible implications for improving the clnical treatment of this malignancy. Cancer Res; 78(1); 230–45. ©2017 AACR.
T-cell Localization, Activation, and Clonal Expansion in Human Pancreatic Ductal Adenocarcinoma
Authors: Stromnes Ingunn M. , Hulbert Ayaka , Pierce Robert H. , Greenberg Philip D. , Hingorani Sunil R.
Published: October 2017

Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy resistant to most therapies, including immune checkpoint blockade. To elucidate mechanisms of immunotherapy resistance, we assessed immune parameters in resected human PDA. We demonstrate significant interpatient variability in T-cell number, localization, and phenotype. CD8+ T cells, Foxp3+ regulatory T cells, and PD-1+ and PD-L1+ cells were preferentially enriched in tertiary lymphoid structures that were found in most tumors compared with stroma and tumor cell nests. Tumors containing more CD8+ T cells also had increased granulocytes, CD163+ (M2 immunosuppressive phenotype) macrophages, and FOXP3+ regulatory T cells. PD-L1 was rare on tumor cells, but was expressed by CD163+ macrophages and an additional stromal cell subset commonly found clustered together adjacent to tumor epithelium. The majority of tumoral CD8+ T cells did not express molecules suggestive of recent T-cell receptor (TCR) signaling. However, 41BB+PD-1+ T cells were still significantly enriched in tumors compared with circulation. Tumoral CD8+PD-1+ T cells commonly expressed additional inhibitory receptors, yet were mostly T-BEThi and EOMESlo, consistent with a less terminally exhausted state. Analysis of gene expression and rearranged TCR genes by deep sequencing suggested most patients have a limited tumor-reactive T-cell response. Multiplex immunohistochemistry revealed variable T-cell infiltration based on abundance and location, which may result in different mechanisms of immunotherapy resistance. Overall, the data support the need for therapies that either induce endogenous, or provide engineered, tumor-specific T-cell responses, and concurrently relieve suppressive mechanisms operative at the tumor site. Cancer Immunol Res; 5(11); 978–91. ©2017 AACR.
The TiLOOP® Male Sling: Did We Forejudge
Authors: Hüsch Tanja , Kretschmer Alexander , Thomsen Frauke , Kronlachner Dominik , Kurosch Martin , Obaje Alice , Anding Ralf , Kirschner-Hermanns Ruth , Pottek Tobias , Rose Achim , Olianas Roberto , Friedl Alexander , Hübner Wilhelm , Homberg Roland , Pfitzenmaier Jesco , Grein Ulrich , Queissert Fabian , Naumann Carsten Maik , Schweiger Josef , Wotzka Carola , Nyarangi-Dix Joanne , Brehmer Bernhard , Ulm Kurt , Bauer Ricarda M. , Haferkamp Axel ,   Debates On Male Incontinence (DOMINO)-Project 8
Published: October 2017

Introduction: To evaluate the safety and efficacy of the TiLOOP® male sling (pfm medical, Cologne, Germany) used in the treatment for male stress urinary incontinence (SUI). Material and Methods: We retrospectively evaluated a total of 34 patients with a TiLOOP® male sling. Perioperative complication rates were assessed and validated questionnaires were prospectively evaluated to assess quality of life and satisfaction rate. Outcome and complication rates were analysed by using descriptive statistics. Correlation of continence outcome and risk factors was performed with the chi-square test. A p value below 0.05 was considered statistically significant. Results: The majority of patients (70.6%) were diagnosed with mild or moderate male SUI. During surgery, one instance (2.9%) of intraoperative urethral injury was observed. There were no immediate postoperative complications. The mean follow-up time was 44.6 months. An improvement of male SUI was reported by 61.9% of the patients and 38.1% reported no change according the Patient Global Impression of Improvement. The mean perineal pain score was 0.5 according to the international index of pain. Conclusions: The TiLOOP® is a safe treatment option for male SUI in our cohort with a low complication rate. However, the functional outcome of the TiLOOP® was inferior when compared to the outcome of the AdVance® male sling.
Expression Profiles of Long Noncoding RNA in UVA-Induced Human Skin Fibroblasts
Authors: Zheng Yue , Xu Qingfang , Peng Yating , Gong Zijian , Chen Haiyan , Lai Wei , Maibach Howard I.
Published: October 2017

Background: Long noncoding RNA (lncRNA) are differentially expressed across stages of differentiation and development, but the role of lncRNA in human skin photoaging mechanisms remains poorly understood. Objective: This study aimed to determine lncRNA expression changes in human dermal fibroblasts (HDF) induced by repeated UVA irradiation and to explore correlations between lncRNA and skin photoaging prognosis. Methods: In the UVA-HDF group, HDF were subjected to repeated UVA irradiation (10 J/cm2 UVA twice daily for 7 days); in the control group, HDF received no irradiation. High-throughput sequencing was used to detect lncRNA expression profiles. Functional annotation analysis and pathway enrichment were preformed via Gene Ontology and KEGG. Predicted lncRNA target genes were identified by bioinformatic analysis. Results: In the UVA-HDF group, 1,730 lncRNA exhibited over 2-fold expression changes compared with the control group: 1,494 were upregulated, and 236 downregulated. Predicted lncRNA targets were associated with matrix metalloproteinases, cathepsin D, mitogen-activated protein kinase and TGF-β signaling pathways, and collagen fiber metabolism following repeated UVA damaging mechanisms. Conclusions: lncRNA profiles were aberrantly expressed in UVA-HDF and might play a key role in skin photoaging. This study provides novel insights into the repeated UVA-damaging pathology and potential targets for treatment of human skin photoaging.
The Systemic Activation of Programmed Death 1-PD-L1 Axis Protects Systemic Lupus Erythematosus Model from Nephritis
Authors: Liao Wenjun , Zheng Hua , Wu Sha , Zhang Yanmei , Wang Wei , Zhang Zili , Zhou Chenfei , Wu Hongjun , Min Jie
Published: October 2017

Background: Systemic lupus erythematosus (SLE) is characterized by abnormal activated T cells, autoreactive B cells, and massive cytokines. The CD4+ T cells determined B-cells differentiation and cytokines production. The programmed death 1 (PD-1) is the checkpoint immunoinhibitory receptor of activated T cells, and its engagement could exhaust T cells. In this study, we investigated the role of PD-1 systemic engagement with PD-L1-Ig in lupus-like nephritis in SLE mice. Methods: The murine PD-L1-Ig was injected into SLE-prone mice. The proteinuria and survival ratio were monitored. The production of anti-dsDNA autoantibodies and cytokines in serum were measured by enzyme-linked immunosorbent assay. The cytokine-producing T cells (interferon-γ, IFN-γ and IL-17α) in kidney and spleen were detected with flowcytometry. The pathological evaluation of the Ig deposition in the glomeruliand was determined with immunofluorescence. Lymphocytes in 24-h urine were detected with flowcytometry. Results: The systemic administration of PD-L1-Ig activated PD-1-PD-L1 axis of CD4+ T lymphocytes, suppressed Th17 formation in many organs, including the spleen and the kidney, demolished abnormal production of cytokines (IFN-γ, IL-17, and IL-10) and anti-dsDNA autoantibodies in serum, inhibited immunoglobulin G deposition in the glomeruli with the decrease of proteinuria, and activated T cells in urine. Accordingly, the systemic conjugation of PD-L1-PD-1 impaired renal autoimmune injure and prolonged survival time. Conclusion: Our research demonstrated that the protective function of systemic activation of PD-1-PD-L1 axis with PD-L1-Ig attenuates the nephritis in SLE-prone mice, which facilitates us to understand the suppressive function of PD-1-PD-L1 axis in the pathogenesis and progress of the lupus nephritis, and to explore a possible effective therapeutic strategy to SLE.