bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive muscle plasticity of a remaining agonist following denervation of its close synergists in a model of complete spinal cord injury
Authors: Dambreville Charline , Charest Jérémie , Thibaudier Yann , Hurteau Marie-France , Kuczynski Victoria , Grenier Guillaume , Frigon Alain
Published: June 2016

Complete spinal cord injury (SCI) alters the contractile properties of skeletal muscle, and although exercise can induce positive changes, it is unclear whether the remaining motor system can produce adaptive muscle plasticity in response to a subsequent peripheral nerve injury. To address this, the nerve supplying the lateral gastrocnemius (LG) and soleus muscles was sectioned unilaterally in four cats that had recovered hindlimb locomotion after spinal transection. In these spinal cats, kinematics and electromyography (EMG) were collected before and for 8 wk after denervation. Muscle histology was performed on LG and medial gastrocnemius (MG) bilaterally in four spinal and four intact cats. In spinal cats, cycle duration for the hindlimb ipsilateral or contralateral to the denervation could be significantly increased or decreased compared with predenervation values. Stance duration was generally increased and decreased for the contralateral and ipsilateral hindlimbs, respectively. The EMG amplitude of MG was significantly increased bilaterally after denervation and remained elevated 8 wk after denervation. In spinal cats the ipsilateral LG was significantly smaller than the contralateral LG, whereas the ipsilateral MG weighed significantly more than the contralateral MG. Histological characterizations revealed significantly larger fiber areas for type IIa fibers of the ipsilateral MG in three of four spinal cats. Microvascular density in the ipsilateral MG was significantly higher than in the contralateral MG. In intact cats, no differences were found for muscle weight, fiber area, or microvascular density between homologous muscles. Therefore, the remaining motor system after complete SCI retains the ability to produce adaptive muscle plasticity.
RESH: A Secure Authentication Algorithm Based on Regeneration Encoding Self-Healing Technology in WSN
Authors: Liang Wei , Ruan Zhiqiang , Wang Yuntao , Chen Xiaoyan
Published: June 2016

In the real application environment of wireless sensor networks (WSNs), the uncertain factor of data storage makes the authentication information be easily forged and destroyed by illegal attackers. As a result, it is hard for secure managers to conduct forensics on transmitted information in WSN. This work considers the regeneration encoding self-healing and secret sharing techniques and proposes an effective scheme to authenticate data in WSN. The data is encoded by regeneration codes and then distributed to other redundant nodes in the form of fragments. When the network is attacked, the scheme has the ability against tampering attack or collusion attack. Furthermore, the damaged fragments can be restored as well. Parts of fragments, encoded by regeneration code, are required for secure authentication of the original distributed data. Experimental results show that the proposed scheme reduces hardware communication overhead by five percent in comparison. Additionally, the performance of local recovery achieves ninety percent.
Mechanism Analysis and Parameter Optimization of Mega-Sub-Isolation System
Authors: Li Xiangxiu , Tan Ping , Li Xiaojun , Liu Aiwen
Published: June 2016

The equation of motion of mega-sub-isolation system is established. The working mechanism of the mega-sub-isolation system is obtained by systematically investigating its dynamic characteristics corresponding to various structural parameters. Considering the number and location of the isolated substructures, a procedure to optimally design the isolator parameters of the mega-sub-isolation system is put forward based on the genetic algorithm with base shear as the optimization objective. The influence of the number and locations of isolated substructures on the control performance of mega-sub-isolation system has also been investigated from the perspective of energy. Results show that, with increase in substructure mass, the working mechanism of the mega-sub-isolation system is changed from tuned vibration absorber and energy dissipation to seismic isolation. The locations of the isolated substructures have little influence on the optimal frequency ratio but have great influence on the optimal damping ratio, while the number of isolated substructures shows great impact on both the optimal frequency ratio and damping ratio. When the number of the isolated substructures is determined, the higher the isolated substructures, the more the energy that will be consumed by the isolation devices, and with the increase of the number of isolated substructures, the better control performance can be achieved.
Twist-Shaped CuO Nanowires as Anode Materials for Lithium Ion Batteries
Authors: Liu Hongdong , Lin Ye , Hu Zhongli , Hu Rong , Ruan Haibo , Zhang Lei
Published: June 2016

Twist-shaped CuO nanowires were synthesized by two-step method consisting of solution reaction and then heat treatment. The as-synthesized samples were characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). When evaluated as anode materials for lithium ion batteries, twist-shaped CuO nanowires showed a high initial discharge capacity of 983 mAh g−1and maintained a reversible capacity of 320 mAh g−1over 50 cycles at the current density of 100 mA g−1. Thus, 1D twist-shaped CuO nanowires provide a new insight into the development of anode materials for next-generation high performance lithium ion batteries.
Fractional-Derivative Maxwell Kelvin Model for “5+4” Viscoelastic Damping Wall Subjected to Large Deformation
Authors: Xu Junhong , Li Aiqun , Shen Yang
Published: June 2016

Considering the larger vibration amplitude and several viscoelastic material layers, a fractional-derivative Maxwell Kelvin (FDMK) viscoelastic mechanical model is proposed for “5+4” viscoelastic damping wall, which is used for vibration control of building structures. The development of the model is based on in-parallel combination of fractional Maxwell model and fractional Kelvin model. The proposed model is experimentally validated and very good agreement between predicted and experimental results was obtained. The results confirm that the FDMK model is accurate in simulating the hysteresis properties of the “5+4” viscoelastic damping wall under large deformation. From the areas of the experimental and theoretical hysteresis loops, under 300% strain, the predicted result is the most accurate in prediction of the energy dissipation and the second is the prediction under 450% strain. Moreover, from the comparisons of dynamic properties (storage modulus, loss modulus, etc.), the FDMK model works satisfactorily. The FDMK model is more sensitive in energy dissipation than in energy storage.
A Novel Application of Ti-Substituted Polyoxometalates: Anti-Inflammatory Activity in OVA-Induced Asthma Murine Model
Authors: Li Dong , Gao Xiuzhu , Gu Jingmin , Tian Yuan , Liu Yaqing , Jin Zheng , Yan Dongmei , Chen Ya-Guang , Zhu Xun
Published: June 2016

Objective. Asthma is a chronic inflammatory disorder. Despite extensive researches into the treatment and management of it, current treatments and management strategies are still limited. The search for a novel approach to its treatments is urgently needed. Researches on the potential medical use of polyoxometalates (POMs) have already shown it has antiviral and antitumor bioactivities. But the effects of POM in immune systems are still largely unknown.Methods. In order to investigate the role of POM in the asthmatic disease, we used OVA-induced asthma murine model and observed the pathological changes between mice that received three different Ti-substituted POMs (0.3 μg per mouse per dose) when challenged with OVA. We also measured the type 2 cytokine expressions to reveal the potential mechanism.Results and Conclusions. Our results showed that two Ti-substituted POMs, K5H2[FeW11TiO40]·17H2O and K5H[H2ZnW11TiO40]·35H2O, could reduce OVA-induced lung inflammation, serum IgE level (around 2000 ng/mL to less than 1000 ng/mL), leukocytes infiltration in the lung, and cytokines levels (including IL-4, IL-5, IL-13, and TNF-α) but Ti-centered POM K4[TiW12O40]·10H2O did not. Thus, Ti-substituted POMs may have pharmaceutical values especially in treatments for asthmatic diseases.
Effects of Extruded Soy Protein on the Quality of Chinese Steamed Bread
Authors: Du Zhenya , Chen Fusheng , Liu Kunlun , Lai Shaojuan , Zhang Lifen , Bu Guanhao , Gao Xueli , Liu Shaobo
Published: June 2016

Five different extruded soy protein isolates (ESPIs) were obtained by extrusion and denoted by IVD1, IVD2, IVD3, IVD4, and IVD5. Then the SDS-PAGE results showed that the subunits of SPI decreased after extrusion, especially the subunits of 90.8, 32.8, and 31.3 kDa, whereas no isopeptide bond was formed. Although SPI improved both the development time (DT) and stability (S) of dough, ESPIs increasedSbut the DT decreased from 4.3 min to 1.8–2.0 min. Texture profile analysis (TPA) results showed that the hardness and chewiness of Chinese steamed bread (CSB) decreased in the order wheat flour+IVD2 (WF+IVD2), WF+SPI, WF+IVD4, WF+IVD1, WF+IVD3, WF, and WF+IVD5. As regards color, the total colorΔEdecreased except for the WF+IVD1 (56.22); its positive and negative trends ofL⁎andb⁎were invariant with the SPI or ESPIs mixture, whereasa⁎showed a positive trend. The sensory score increased from 82.7 to 83.4 with 3% of SPI addition and up to 87.8 when the substitution was IVD1. Therefore, SPI treated by extrusion may significantly improve the quality of CSB.
Investigation on a Novel Capacitive Electrode for Geophysical Surveys
Authors: Wang Zhiyu , Wang Shun , Fang Guangyou , Zhang Qunying
Published: June 2016

Nonpolarizable electrodes are applied widely in the electric field measurement for geophysical surveys. However, there are two major problems: (1) systematic errors caused by poor electrical contact in the high resistive terrains and (2) environmental damage associated with using nonpolarizable electrodes. A new alternative structure of capacitive electrode, which is capable of sensing surface potential through weak capacitive coupling, is presented to solve the above problems. A technique is introduced to neutralize distributed capacitance and input capacitance of the detection circuit. With the capacitance neutralization technique, the transmission coefficient of capacitive electrode remains stable when environmental conditions change. The simulation and field test results indicate that the new capacitive electrode has an operating bandwidth range from 0.1 Hz to 1 kHz. The capacitive electrodes have a good prospect of the applications in geophysical prospecting, especially in resistive terrains.
Application of Probabilistic Method to Stability Analysis of Gravity Dam Foundation over Multiple Sliding Planes
Authors: Wang Gang , Ma Zhenyue
Published: June 2016

The current challenge to the engineering profession is to carry out probabilistic methods in practice. The design point method in generalized random space (DPG method) associated with the method of divided difference can be utilized to deal with the complex problem of probability calculation of implicit performance function with nonnormal and correlated variables. For a practical concrete gravity dam, the suggested method is performed to calculate the instability probability of the dam foundation over multiple sliding places. The general conclusions drawn in the paper are identical to those in other research and the method is proved to be feasible, accurate, and efficient. As the same analysis principle, the method can also be used in other similar fields, such as in fields of slopes, earth-rock dams, levees, and embankments.
Ens-PPI: A Novel Ensemble Classifier for Predicting the Interactions of Proteins Using Autocovariance Transformation from PSSM
Authors: Gao Zhen-Guo , Wang Lei , Xia Shi-Xiong , You Zhu-Hong , Yan Xin , Zhou Yong
Published: June 2016

Protein-Protein Interactions (PPIs) play vital roles in most biological activities. Although the development of high-throughput biological technologies has generated considerable PPI data for various organisms, many problems are still far from being solved. A number of computational methods based on machine learning have been developed to facilitate the identification of novel PPIs. In this study, a novel predictor was designed using the Rotation Forest (RF) algorithm combined with Autocovariance (AC) features extracted from the Position-Specific Scoring Matrix (PSSM). More specifically, the PSSMs are generated using the information of protein amino acids sequence. Then, an effective sequence-based features representation, Autocovariance, is employed to extract features from PSSMs. Finally, the RF model is used as a classifier to distinguish between the interacting and noninteracting protein pairs. The proposed method achieves promising prediction performance when performed on the PPIs ofYeast,H.pylori, andindependent datasets. The good results show that the proposed model is suitable for PPIs prediction and could also provide a useful supplementary tool for solving other bioinformatics problems.
Lateralization Technique and Inferior Alveolar Nerve Transposition
Authors: Pimentel Angélica Castro , Sanches Marco Antonio , Ramalho Gabriel Cardoso , Roman-Torres Caio Vinicius , Manzi Marcello Roberto , Sendyk Wilson Roberto
Published: June 2016

Bone resorption of the posterior mandible can result in diminished bone edge and, therefore, the installation of implants in these regions becomes a challenge, especially in the presence of the mandibular canal and its contents, the inferior alveolar nerve. Several treatment alternatives are suggested: the use of short implants, guided bone regeneration, appositional bone grafting, distraction osteogenesis, inclined implants tangential to the mandibular canal, and the lateralization of the inferior alveolar nerve. The aim was to elucidate the success rate of implants in the lateralization technique and in inferior alveolar nerve transposition and to determine the most effective sensory test. We conclude that the success rate is linked to the possibility of installing implants with long bicortical anchor which favors primary stability and biomechanics.
Quadrupedal Robot Locomotion: A Biologically Inspired Approach and Its Hardware Implementation
Authors: Espinal A. , Rostro-Gonzalez H. , Carpio M. , Guerra-Hernandez E. I. , Ornelas-Rodriguez M. , Puga-Soberanes H. J. , Sotelo-Figueroa M. A. , Melin P.
Published: June 2016

A bioinspired locomotion system for a quadruped robot is presented. Locomotion is achieved by a spiking neural network (SNN) that acts as a Central Pattern Generator (CPG) producing different locomotion patterns represented by their raster plots. To generate these patterns, the SNN is configured with specific parameters (synaptic weights and topologies), which were estimated by a metaheuristic method based on Christiansen Grammar Evolution (CGE). The system has been implemented and validated on two robot platforms; firstly, we tested our system on a quadruped robot and, secondly, on a hexapod one. In this last one, we simulated the case where two legs of the hexapod were amputated and its locomotion mechanism has been changed. For the quadruped robot, the control is performed by the spiking neural network implemented on an Arduino board with 35% of resource usage. In the hexapod robot, we used Spartan 6 FPGA board with only 3% of resource usage. Numerical results show the effectiveness of the proposed system in both cases.
Transcriptional Targeting of Mature Dendritic Cells with Adenoviral Vectors via a Modular Promoter System for Antigen Expression and Functional Manipulation
Authors: Knippertz Ilka , Deinzer Andrea , Dörrie Jan , Schaft Niels , Nettelbeck Dirk M. , Steinkasserer Alexander
Published: June 2016

To specifically target dendritic cells (DCs) to simultaneously express different therapeutic transgenes for inducing immune responses against tumors, we used a combined promoter system of adenoviral vectors. We selected a 216 bp short Hsp70B′ core promoter induced by a mutated, constitutively active heat shock factor (mHSF) 1 to drive strong gene expression of therapeutic transgenes MelanA, BclxL, and IL-12p70 in HeLa cells, as well as in mature DCs (mDCs). As this involves overexpressing mHSF1, we first evaluated the resulting effects on DCs regarding upregulation of heat shock proteins and maturation markers, toxicity, cytokine profile, and capacity to induce antigen-specific CD8+T cells. Second, we generated the two-vector-based “modular promoter” system, where one vector contains the mHSF1 under the control of the human CD83 promoter, which is specifically active only in DCs and after maturation. mHSF1, in turn, activates the Hsp70B′ core promotor-driven expression of transgenes MelanA and IL-12p70 in the DC-like cell line XS52 and in human mature and hence immunogenic DCs, but not in tolerogenic immature DCs. Thesein vitroexperiments provide the basis for anin vivotargeting of mature DCs for the expression of multiple transgenes. Therefore, this modular promoter system represents a promising tool for future DC-based immunotherapiesin vivo.
Bioartificial Therapy of Sepsis: Changes of Norepinephrine-Dosage in Patients and Influence on Dynamic and Cell Based Liver Tests during Extracorporeal Treatments
Authors: Sauer Martin , Altrichter Jens , Haubner Cristof , Pertschy Annette , Wild Thomas , Doß Fanny , Mencke Thomas , Thomsen Maren , Ehler Johannes , Henschel Jörg , Doß Sandra , Koch Stephanie , Richter Georg , Nöldge-Schomburg Gabriele , Mitzner Steffen R.
Published: June 2016

Purpose.Granulocyte transfusions have been used to treat immune cell dysfunction in sepsis. A granulocyte bioreactor for the extracorporeal treatment of sepsis was tested in a prospective clinical study focusing on the dosage of norepinephrine in patients and influence on dynamic and cell based liver tests during extracorporeal therapies.Methods and Patients.Ten patients with severe sepsis were treated twice within 72 h with the system containing granulocytes from healthy donors. Survival, physiologic parameters, extended hemodynamic measurement, and the indocyanine green plasma disappearance rate (PDR) were monitored. Plasma of patients before and after extracorporeal treatments were tested with a cell based biosensor for analysis of hepatotoxicity.Results.The observed mortality rate was 50% during stay in hospital. During the treatments, the norepinephrine-dosage could be significantly reduced while mean arterial pressure was stable. In the cell based analysis of hepatotoxicity, the viability and function of sensor-cells increased significantly during extracorporeal treatment in all patients and the PDR-values increased significantly between day 1 and day 7 only in survivors.Conclusion.The extracorporeal treatment with donor granulocytes showed promising effects on dosage of norepinephrine in patients, liver cell function, and viability in a cell based biosensor. Further studies with this approach are encouraged.
Evaluating a Nationwide Recreational Football Intervention: Recruitment, Attendance, Adherence, Exercise Intensity, and Health Effects
Authors: Fløtum Liljan av , Ottesen Laila S. , Krustrup Peter , Mohr Magni
Published: June 2016

The present study evaluated a nationwide exercise intervention with Football Fitness in a small-scale society. In all, 741 adult participants (20–72 yrs) were successfully recruited for Football Fitness training in local football clubs, corresponding to 2.1% of the adult population. A preintervention test battery including resting heart rate (RHR), blood pressure, and body mass measurements along with performance tests (Yo-Yo Intermittent Endurance level 1 (Yo-Yo IE1), the Arrowhead Agility Test, and the Flamingo Balance Test) were performed (n=502). Training attendance (n=310) was 1.6 ± 0.2 sessions per week (range: 0.6–2.9), corresponding to 28.8 ± 1.0 sessions during the 18 wk intervention period. After 18 wks mean arterial pressure (MAP) was −2.7 ± 0.7 mmHg lower (P<0.05;n=151) with even greater (P<0.05) reductions for those with baseline MAP values >99 mmHg (−5.6 ± 1.5 mmHg;n=50). RHR was lowered (P<0.05) by 6 bpm after intervention (77 ± 1 to 71 ± 1 bpm). Yo-Yo IE1 performance increased by 41% (540 ± 27 to 752 ± 45 m), while agility and postural balance were improved (P<0.05) by ~6 and ~45%, respectively. In conclusion, Football Fitness was shown to be a successful health-promoting nationwide training intervention for adult participants with an extraordinary recruitment, a high attendance rate, moderate adherence, high exercise intensity, and marked benefits in cardiovascular health profile and fitness.
A Survey of Strategies to Modulate the Bone Morphogenetic Protein Signaling Pathway: Current and Future Perspectives
Authors: Lowery Jonathan W. , Brookshire Brice , Rosen Vicki
Published: June 2016

Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the TGF‐β family of ligands and are unequivocally involved in regulating stem cell behavior. Appropriate regulation of canonical BMP signaling is critical for the development and homeostasis of numerous human organ systems, as aberrations in the BMP pathway or its regulation are increasingly associated with diverse human pathologies. In this review, we provide a wide‐perspective on strategies that increase or decrease BMP signaling. We briefly outline the current FDA‐approved approaches, highlight emerging next‐generation technologies, and postulate prospective avenues for future investigation. We also detail how activating other pathways may indirectly modulate BMP signaling, with a particular emphasis on the relationship between the BMP and Activin/TGF‐β pathways.
Blasting Vibration Generated by Breaking-Blasting Large Barriers with EBBLB
Authors: Zhen-xiong Wang , Wen-bin Gu , Ting Liang , Jian-qing Liu , Jing-lin Xu , Xin Liu
Published: June 2016

Equipment for breaking and blasting large barriers (EBBLB) is new break-blast equipment, which inevitably induces ground vibration and may cause substantial damage to rock mass and nearby structures as well as human beings. The ground vibration induced by break-blast is one of the inevitable outcomes. By monitoring vibration at measuring points at different distances from blasting center, time history curve of vibrating velocity can be obtained; it can be drawn that blasting seismic waves are generated mainly from the explosion of the precharge. Furthermore, different approaches have been adopted to fit relationship between particle peak velocity (PPV) and distance from blasting center, comparative analysis of which provides the most appropriate relation expression to predict attenuation of PPV of vibration with distance from blasting center. The relation between vibration frequency and distance from blasting center is obtained by Fourier transform. And the research decomposes vibrating signals in vertical direction of different distances from blasting center with Hilbert-Huang Transform (HHT), extracting information of empirical mode components of blasting vibration signals; thus vibrating signals are contracted by spectrum information and energy information, three-dimensional energy, and energy attenuation of vibration with different distances from blasting center. The study can predict ground vibration generated by EBBLB and assess its damaging effects of blasting vibration for security and protection.
Evaluation of Shunt Losses in Industrial Silicon Solar Cells
Authors: Somasundaran P. , Gupta R.
Published: June 2016

Shunting is one of the key issues in industrial silicon solar cells which degrade cell performance. This paper presents an approach for investigation of the performance degradation caused by the presence of ohmic extended shunts at various locations in industrial silicon solar cells. Location, nature, and area of the shunts existing in solar cells have been examined by lock-in infrared thermography (LIT). Based on LIT images and experimental darkI-Vcurves of solar cell, shunted cell has been modeled, from which loss in fill factor and efficiency due to the specific shunt has been obtained. Distributed diode modeling approach of solar cell has been exploited for obtaining simulation results which were supported by experimental measurements. The presented approach is useful to estimate performance reduction due to specific shunts and to quantify losses, which can help in improving the efficiency of solar cell during production by tackling the shunt related problems based on the level of severity and tolerance.
Goal Setting for Cognitive Rehabilitation in Mild to Moderate Parkinson’s Disease Dementia and Dementia with Lewy Bodies
Authors: Watermeyer Tamlyn J. , Hindle John V. , Roberts Julie , Lawrence Catherine L. , Martyr Anthony , Lloyd-Williams Huw , Brand Andrew , Gutting Petra , Hoare Zoe , Edwards Rhiannon Tudor , Clare Linda
Published: June 2016

Alongside the physical symptoms associated with Parkinson’s disease dementia and dementia with Lewy bodies, health services must also address the cognitive impairments that accompany these conditions. There is growing interest in the use of nonpharmacological approaches to managing the consequences of cognitive disorder. Cognitive rehabilitation is a goal-orientated behavioural intervention which aims to enhance functional independence through the use of strategies specific to the individual’s needs and abilities. Fundamental to this therapy is a person’s capacity to set goals for rehabilitation. To date, no studies have assessed goal setting in early-stage Parkinson’s disease dementia or dementia with Lewy bodies. Semistructured interviews were carried out with 29 participants from an ongoing trial of cognitive rehabilitation for people with these conditions. Here, we examined the goal statements provided by these participants using qualitative content analysis, exploring the types and nature of the goals set. Participants’ goals reflected their motivations to learn new skills or improve performance in areas such as technology-use, self-management and orientation, medication management, and social and leisure activities. These results suggest that goal setting is achievable for these participants, provide insight into the everyday cognitive difficulties that they experience, and highlight possible domains as targets for intervention. The trial is registered withISRCTN16584442(DOI 10.1186/ISRCTN16584442 13/04/2015).
A Stereomicroscopic Evaluation of Dentinal Cracks at Different Instrumentation Lengths by Using Different Rotary Files (ProTaper Universal, ProTaper Next, and HyFlex CM): An Ex Vivo Study
Authors: Ashraf Fauzia , Shankarappa Pushpa , Misra Abhinav , Sawhney Asheesh , Sridevi Nandamuri , Singh Anu
Published: June 2016

Introduction. The aim of the present study was to evaluate the dentinal cracks after root canal preparation with rotary files: Gates Glidden, ProTaper Universal, ProTaper Next, and HyFlex CM at different instrumentation lengths.Methodology. Sixty-five mandibular premolars were mounted in the acrylic tube with simulated periodontal ligaments and the apex was exposed. The root canals were instrumented with different rotary files, namely, ProTaper Universal, ProTaper Next, and HyFlex CM, to the major apical foramen (AF), short AF, and beyond AF. The root apex was stained with 1% methylene blue dye and digital images of apical surface of every tooth were taken and development of dentinal defects was determined by using stereomicroscope. Multinomial logistic regression test was performed to identify influencing factors.Results. Instrumentation with rotary files terminated 2 mm short AF and did not cause any cracks. Significantly less cracks were seen when instrumentation with rotary files terminated 1 mm short apical foramen when compared with the instrumentation terminated at or beyond apical foramen (p<0.05).Conclusion. ProTaper Universal rotary files caused more dentinal cracks than ProTaper Next and HyFlex CM. Instrumentation short AF reduced the risk of dentinal defects.
The Verification of the Usefulness of Electronic Nose Based on Ultra-Fast Gas Chromatography and Four Different Chemometric Methods for Rapid Analysis of Spirit Beverages
Authors: Wiśniewska Paulina , Śliwińska Magdalena , Namieśnik Jacek , Wardencki Waldemar , Dymerski Tomasz
Published: June 2016

Spirit beverages are a diverse group of foodstuffs. They are very often counterfeited which cause the appearance of low quality products or wrongly labelled products on the market. It is important to find a proper quality control and botanical origin method enabling the same time preliminary check of the composition of investigated samples, which was the main goal of this work. For this purpose, the usefulness of electronic nose based on ultra-fast gas chromatography (fast GC e-nose) was verified. A set of 24 samples of raw spirits, 33 samples of vodkas, and 8 samples of whisky were analysed by fast GC e-nose. Four data analysis methods were used. The PCA was applied for the visualization of dataset, observation of the variation inside groups of samples, and selection of variables for the other three statistical methods. The SQC method was utilized to compare the quality of the samples. Both the DFA and SIMCA data analysis methods were used for discrimination of vodka, whisky, and spirits samples. The fast GC e-nose combined with four statistical methods can be used for rapid discrimination of raw spirits, vodkas, and whisky and in the same for preliminary determination of the composition of investigated samples.
Vibration Response Characteristics of the Cross Tunnel Structure
Authors: Lai Jinxing , Wang Kaiyun , Qiu Junling , Niu Fangyuan , Wang Junbao , Chen Jianxun
Published: June 2016

It is well known that the tunnel structure will lose its function under the long-term repeated function of the vibration effect. A prime example is the Xi’an cross tunnel structure (CTS) of Metro Line 2 and the Yongningmen tunnel, where the vibration response of the tunnel vehicle load and metro train load to the structure of shield tunnel was analyzed by applying the three-dimensional (3D) dynamic finite element model. The effect of the train running was simulated by applying the time-history curves of vibration force of the track induced by wheel axles, using the fitted formulas for vehicle and train vibration load. The characteristics and the spreading rules of vibration response of metro tunnel structure were researched from the perspectives of acceleration, velocity, displacement, and stress. It was found that vehicle load only affects the metro tunnel within 14 m from the centre, and the influence decreases gradually from vault to spandrel, haunch, and springing. The high-speed driving effect of the train can be divided into the close period, the rising period, the stable period, the declining period, and the leaving period. The stress at haunch should be carefully considered. The research results presented for this case study provide theoretical support for the safety of vibration response of Metro Line 2 structure.
Immuno-PET Imaging of Engineered Human T Cells in Tumors
Authors: Mall Sabine , Yusufi Nahid , Wagner Ricarda , Klar Richard , Bianchi Henrique , Steiger Katja , Straub Melanie , Audehm Stefan , Laitinen Iina , Aichler Michaela , Peschel Christian , Ziegler Sibylle , Mustafa Mona , Schwaiger Markus , D'Alessandria Calogero , Krackhardt Angela M.
Published: June 2016

Sensitive in vivo imaging technologies applicable to the clinical setting are still lacking for adoptive T-cell–based immunotherapies, an important gap to fill if mechanisms of tumor rejection or escape are to be understood. Here, we propose a highly sensitive imaging technology to track human TCR-transgenic T cells in vivo by directly targeting the murinized constant TCR beta domain (TCRmu) with a zirconium-89 (89Zr)-labeled anti–TCRmu-F(ab')2 fragment. Binding of the labeled or unlabeled F(ab')2 fragment did not impair functionality of transgenic T cells in vitro and in vivo. Using a murine xenograft model of human myeloid sarcoma, we monitored by Immuno-PET imaging human central memory T cells (TCM), which were transgenic for a myeloid peroxidase (MPO)–specific TCR. Diverse T-cell distribution patterns were detected by PET/CT imaging, depending on the tumor size and rejection phase. Results were confirmed by IHC and semiquantitative evaluation of T-cell infiltration within the tumor corresponding to the PET/CT images. Overall, these findings offer a preclinical proof of concept for an imaging approach that is readily tractable for clinical translation. Cancer Res; 76(14); 4113–23. ©2016 AACR.
A Strong B-cell Response Is Part of the Immune Landscape in Human High-Grade Serous Ovarian Metastases
Authors: Montfort Anne , Pearce Oliver , Maniati Eleni , Vincent Benjamin G. , Bixby Lisa , Böhm Steffen , Dowe Thomas , Wilkes Edmund H. , Chakravarty Probir , Thompson Richard , Topping Joanne , Cutillas Pedro R. , Lockley Michelle , Serody Jonathan S. , Capasso Melania , Balkwill Frances R.
Published: June 2016

Purpose: In high-grade serous ovarian cancer (HGSOC), higher densities of both B cells and the CD8+ T-cell infiltrate were associated with a better prognosis. However, the precise role of B cells in the antitumor response remains unknown. As peritoneal metastases are often responsible for relapse, our aim was to characterize the role of B cells in the antitumor immune response in HGSOC metastases.

Experimental Design: Unmatched pre and post-chemotherapy HGSOC metastases were studied. B-cell localization was assessed by immunostaining. Their cytokines and chemokines were measured by a multiplex assay, and their phenotype was assessed by flow cytometry. Further in vitro and in vivo assays highlighted the role of B cells and plasma cell IgGs in the development of cytotoxic responses and dendritic cell activation.

Results: B cells mainly infiltrated lymphoid structures in the stroma of HGSOC metastases. There was a strong B-cell memory response directed at a restricted repertoire of antigens and production of tumor-specific IgGs by plasma cells. These responses were enhanced by chemotherapy. Interestingly, transcript levels of CD20 correlated with markers of immune cytolytic responses and immune complexes with tumor-derived IgGs stimulated the expression of the costimulatory molecule CD86 on antigen-presenting cells. A positive role for B cells in the antitumor response was also supported by B-cell depletion in a syngeneic mouse model of peritoneal metastasis.

Conclusions: Our data showed that B cells infiltrating HGSOC omental metastases support the development of an antitumor response. Clin Cancer Res; 23(1); 250–62. ©2016 AACR.
Tumor-Derived CCL2 Mediates Resistance to Radiotherapy in Pancreatic Ductal Adenocarcinoma
Authors: Kalbasi Anusha , Komar Chad , Tooker Graham M. , Liu Mingen , Lee Jae W. , Gladney Whitney L. , Ben-Josef Edgar , Beatty Gregory L.
Published: June 2016

Purpose: Local tumor growth is a major cause of morbidity and mortality in nearly 30% of patients with pancreatic ductal adenocarcinoma (PDAC). Radiotherapy is commonly used for local disease control in PDAC, but its efficacy is limited. We studied the impact of selectively intervening on radiotherapy-induced inflammation as an approach to overcome resistance to radiotherapy in PDAC.

Experimental Design: PDAC cell lines derived from primary pancreatic tumors arising spontaneously in KrasLSL-G12D/+;Trp53LSL-R172H/+;Pdx-1 Cre mice were implanted into syngeneic mice and tumors were focally irradiated using the Small Animal Radiation Research Platform (SARRP). We determined the impact of depleting T cells and Ly6C+ monocytes as well as inhibiting the chemokine CCL2 on radiotherapy efficacy. Tumors were analyzed by flow cytometry and IHC to detect changes in leukocyte infiltration, tumor viability, and vascularity. Assays were performed on tumor tissues to detect cytokines and gene expression.

Results: Ablative radiotherapy alone had minimal impact on PDAC growth but led to a significant increase in CCL2 production by tumor cells and recruitment of Ly6C+CCR2+ monocytes. A neutralizing anti-CCL2 antibody selectively inhibited radiotherapy-dependent recruitment of monocytes/macrophages and delayed tumor growth but only in combination with radiotherapy (P < 0.001). This antitumor effect was associated with decreased tumor proliferation and vascularity. Genetic deletion of CCL2 in PDAC cells also improved radiotherapy efficacy.

Conclusions: PDAC responds to radiotherapy by producing CCL2, which recruits Ly6C+CCR2+ monocytes to support tumor proliferation and neovascularization after radiotherapy. Disrupting the CCL2–CCR2 axis in combination with radiotherapy holds promise for improving radiotherapy efficacy in PDAC. Clin Cancer Res; 23(1); 137–48. ©2016 AACR.
Distinct Transcriptional Changes and Epithelial–Stromal Interactions Are Altered in Early-Stage Colon Cancer Development
Authors: Mo Allen , Jackson Stephen , Varma Kamini , Carpino Alan , Giardina Charles , Devers Thomas J. , Rosenberg Daniel W.
Published: June 2016

Although the progression of mutated colonic cells is dependent upon interactions between the initiated epithelium and surrounding stroma, the nature of these interactions is poorly understood. Here, the development of an ultrasensitive laser capture microdissection (LCM)/RNA-seq approach for studying the epithelial and stromal compartments of aberrant crypt foci (ACF) is described. ACF are the earliest identifiable preneoplastic lesion found within the human colon and are detected using high-definition endoscopy with contrast dye spray. The current analysis focused on the epithelium of ACF with somatic mutations to either KRAS, BRAF, or APC, and expression patterns compared with normal mucosa from each patient. By comparing gene expression patterns among groups, an increase in a number of proinflammatory NF-κB target genes was identified that was specific to ACF epithelium, including TIMP1, RELA, and RELB. Distinct transcriptional changes associated with each somatic mutation were observed and a subset of ACF display BRAFV600E-mediated senescence-associated transcriptome characterized by increased expression of CDKN2A. Finally, LCM-captured ACF-associated stroma was found to be transcriptionally distinct from normal-appearing stroma, with an upregulation of genes related to immune cell infiltration and fibroblast activation. Immunofluorescence confirmed increased CD3+ T cells within the stromal microenvironment of ACF and an abundance of activated fibroblasts. Collectively, these results provide new insight into the cellular interplay that occurs at the earliest stages of colonic neoplasia, highlighting the important role of NF-κB, activated stromal fibroblasts, and lymphocyte infiltration.

Implications: Fibroblasts and immune cells in the stromal microenvironment play an important role during the earliest stages of colon carcinogenesis. Mol Cancer Res; 14(9); 795–804. ©2016 AACR.
Triggering the TCR Developmental Checkpoint Activates a Therapeutically Targetable Tumor Suppressive Pathway in T-cell Leukemia
Authors: Trinquand Amélie , dos Santos Nuno R. , Tran Quang Christine , Rocchetti Francesca , Zaniboni Benedetta , Belhocine Mohamed , Da Costa de Jesus Cindy , Lhermitte Ludovic , Tesio Melania , Dussiot Michael , Cosset François-Loïc , Verhoeyen Els , Pflumio Françoise , Ifrah Norbert , Dombret Hervé , Spicuglia Salvatore , Chatenoud Lucienne , Gross David-Alexandre , Hermine Olivier , Macintyre Elizabeth , Ghysdael Jacques , Asnafi Vahid
Published: June 2016

Cancer onset and progression involves the accumulation of multiple oncogenic hits, which are thought to dominate or bypass the physiologic regulatory mechanisms in tissue development and homeostasis. We demonstrate in T-cell acute lymphoblastic leukemia (T-ALL) that, irrespective of the complex oncogenic abnormalities underlying tumor progression, experimentally induced, persistent T-cell receptor (TCR) signaling has antileukemic properties and enforces a molecular program resembling thymic negative selection, a major developmental event in normal T-cell development. Using mouse models of T-ALL, we show that induction of TCR signaling by high-affinity self-peptide/MHC or treatment with monoclonal antibodies to the CD3ϵ chain (anti-CD3) causes massive leukemic cell death. Importantly, anti-CD3 treatment hampered leukemogenesis in mice transplanted with either mouse- or patient-derived T-ALLs. These data provide a strong rationale for targeted therapy based on anti-CD3 treatment of patients with TCR-expressing T-ALL and demonstrate that endogenous developmental checkpoint pathways are amenable to therapeutic intervention in cancer cells.

Significance: T-ALLs are aggressive malignant lymphoid proliferations of T-cell precursors characterized by high relapse rates and poor prognosis, calling for the search for novel therapeutic options. Here, we report that the lineage-specific TCR/CD3 developmental checkpoint controlling cell death in normal T-cell progenitors remains switchable to induce massive tumor cell apoptosis in T-ALL and is amenable to preclinical therapeutic intervention. Cancer Discov; 6(9); 972–85. ©2016 AACR.

See related commentary by Lemonnier and Mak, p. 946.

This article is highlighted in the In This Issue feature, p. 932
Tumor- and Neoantigen-Reactive T-cell Receptors Can Be Identified Based on Their Frequency in Fresh Tumor
Authors: Pasetto Anna , Gros Alena , Robbins Paul F. , Deniger Drew C. , Prickett Todd D. , Matus-Nicodemos Rodrigo , Douek Daniel C. , Howie Bryan , Robins Harlan , Parkhurst Maria R. , Gartner Jared , Trebska-McGowan Katarzyna , Crystal Jessica S. , Rosenberg Steven A.
Published: June 2016

Adoptive transfer of T cells with engineered T-cell receptor (TCR) genes that target tumor-specific antigens can mediate cancer regression. Accumulating evidence suggests that the clinical success of many immunotherapies is mediated by T cells targeting mutated neoantigens unique to the patient. We hypothesized that the most frequent TCR clonotypes infiltrating the tumor were reactive against tumor antigens. To test this hypothesis, we developed a multistep strategy that involved TCRB deep sequencing of the CD8+PD-1+ T-cell subset, matching of TCRA–TCRB pairs by pairSEQ and single-cell RT-PCR, followed by testing of the TCRs for tumor-antigen specificity. Analysis of 12 fresh metastatic melanomas revealed that in 11 samples, up to 5 tumor-reactive TCRs were present in the 5 most frequently occurring clonotypes, which included reactivity against neoantigens. These data show the feasibility of developing a rapid, personalized TCR-gene therapy approach that targets the unique set of antigens presented by the autologous tumor without the need to identify their immunologic reactivity. Cancer Immunol Res; 4(9); 734–43. ©2016 AACR.
Plasma Mitochondrial DNA Level is a Prognostic Marker in Peritoneal Dialysis Patients
Authors: Szeto Cheuk-Chun , Lai Ka-Bik , Chow Kai-Ming , Kwan Bonnie Ching-Ha , Cheng Phyllis Mei-Shan , Kwong Vickie Wai-Ki , Choy Agnes Shin-Man , Leung Chi-Bon , Li Philip Kam-Tao
Published: June 2016

Background/Aims: Circulating bacterial DNA fragment is related to systemic inflammatory state in peritoneal dialysis (PD) patients. We hypothesize that circulating mitochondrial DNA, which has a similar structure with bacterial DNA, correlates with systemic inflammatory state and predicts cardiovascular event in new PD patients. Methods: We measured plasma mitochondrial DNA level by quantitative polymerase chain reaction (PCR) in 197 new PD patients and 150 patients with chronic kidney disease. PD patients were followed for 24 months for the development of cardiovascular event, hospitalization, and patient survival. Results: There was a stepwise increase in plasma mitochondrial DNA level with worsening renal function. The average plasma mitochondrial DNA level was 18.0 ± 1.2 PCR cycles. Plasma mitochondrial DNA level correlated with serum CRP level (r = -0.538, p < 0.0001). At 24 months, the event-free survival was 67.4%, 66.4%, 63.4% and 44.2% for plasma mitochondrial DNA level quartiles I, II, III and IV, respectively (p = 0.049). After adjusting for confounders, plasma mitochondrial DNA level, malnutrition-inflammation score, and baseline arterial pulse wave velocity were independent predictors of composite cardiovascular end-point; each doubling in plasma mitochondrial DNA level confers 16.0% (95% confidence interval, 2.5 - 31.3%, p = 0.001) excess in risk. Plasma mitochondrial DNA also correlated with the number of hospital admission (r = -0.218, p = 0.002) and duration of hospitalization for cardiovascular reasons (r = -0.232, p = 0.001). Conclusion: Plasma mitochondrial DNA level significantly correlates with systemic inflammatory state, and is a strong predictor of cardiovascular event as well as the need of hospitalization in new PD patients.
Combined Association of Serum Uric Acid and Metabolic Syndrome with Chronic Kidney Disease in Hypertensive Patients
Authors: Dai Haijiang , Lu Shijuan , Tang Xiaohong , Lu Minggen , Chen Ruifang , Chen Zhiheng , Yang Pingting , Liu Chang , Zhou Honghao , Lu Yao , Yuan Hong
Published: June 2016

Background/Aims: Chronic kidney disease (CKD) is one of the major complications of hypertension. It is not only associated with the future burden of end-stage renal disease but also affects mortality and cardiovascular outcomes caused by hypertension. To help understand the pathogenesis and early prevention of progressive CKD, this large-scale study is designed to determine the complex association between serum uric acid (SUA), metabolic syndrome and the prevalence of CKD in hypertensive patients. Methods: A total of 19,848 hypertensive subjects were enrolled in this cross-sectional study. Patients with proteinuria and/or an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 were considered CKD cases. Results: Hypertensive subjects with CKD had a higher prevalence of hyperuricemia and metabolic syndrome, as well as higher levels of SUA, BMI, waist circumference (WC), SBP, DBP, TG, fasting blood glucose and lower levels of HDL-C. Compared to patients without CKD, the multivariate-adjusted odds ratios [ORs, 95% confidence interval (CI)] for CKD patients were 2.30 (2.02-2.63) for hyperuricemia, 1.21 (1.04-1.41) for abdominal obesity, 1.21 (1.06-1.38) for elevated TG, 1.29 (1.06-1.56) for low HDL-C, 1.54 (1.36-1.75) for elevated fasting glucose, and 1.49 (1.30-1.71) for metabolic syndrome. Increasing SUA levels and number of individual metabolic syndrome components were associated with an increased prevalence of CKD. Compared with patients classified in the lowest SUA categories and with ≤1 metabolic syndrome components, subjects with HUA and 4 metabolic syndrome components had a 5.77-fold increased OR for CKD based on the multivariate-adjusted analysis. Conclusion: Both elevated SUA and metabolic syndrome are associated with an increased prevalence of CKD in hypertensive subjects. Subjects with higher SUA and sum of individual metabolic syndrome components simultaneously have a higher prevalence of CKD.
Optical Coherence Tomographic Analysis of Retina in Retinitis Pigmentosa Patients
Authors: Liu Guodong , Liu Xiaoqiang , Li Hui , Du Qing , Wang Fang
Published: June 2016

Retinitis pigmentosa (RP) is a progressive inherited retinal disease characterized by nyctalopia, visual field constriction, and reduced full-field electroretinograms. The progressive loss of photoreceptors leads to vision loss at the end stage of RP. The prevalence of RP is approximately 1/4,000. Since it is one of the major causes of visual impairment worldwide, morphological and functional assessments are useful for estimating the retinal structure and function in RP. Optical coherence tomography (OCT) is a well-established method of examining retinal structure in situ, and the obtained images by OCT help to analyze morphological abnormalities. Changes revealed by OCT have provided insights into the pathology of RP as well as for predicting the prognosis of RP. In this review, we present the typical morphological changes in RP and their relationships with visual function in eyes with RP.