bluuebunny/crossref_metadata_2025 huggingface dataset:
Energy Consumption Optimization Model of Multi-Type Bus Operating Organization Based on Time-Space Network
Authors: Liu Yuhuan , Yao Enjian , Liu Shasha
Published: August 2019

As a new type of green bus, the pure electric bus has obvious advantages in energy consumption and emission reduction compared with the traditional fuel bus. However, the pure electric bus has a mileage range constraint and the amount of charging infrastructure cannot meet the demand, which makes the scheduling of the electric bus driving plans more complicated. Meanwhile, many routes are operated with mixing pure electric buses and traditional fuel buses. As mentioned above, we focus on the operating organization problem with the multi-type bus (pure electric buses and traditional fuel buses), aiming to provide guidance for future application of electric buses. We take minimizing the energy consumption of vehicles, the waiting and traveling time of passengers as the objectives, while considering the constraints of vehicle full load limitation, minimal departure interval, mileage range and charging time window. The energy consumption based multi-type bus operating organization model was formulated, along with the heuristic algorithm to solve it. Then, a case study in Beijing was performed. The results showed that, the optimal mixing ratio of electric bus and fuel bus vary according to the variation of passenger flow. In general, each fuel bus could be replaced by two pure electric buses. Moreover, in the transition process of energy structure in public transport, the vehicle scale keeps increasing. The parking yard capacity and the amount of charging facilities are supposed to be further expanded.
A Novel Method for the Measurement of Geometric Errors in the Linear Motion of CNC Machine Tools
Authors: Wei Xuan , Su Zhikun , Yang Xiaohuan , Lv Zekui , Yang Zhiming , Zhang Haitao , Li Xinghua , Fang Fengzhou
Published: August 2019

In order to improve the accuracy of the linear motion of computer numerical control (CNC) machine tools, a novel method based on a new type of 1-D (1-dimensional) artifact is proposed to measure the geometric errors. Based on the properties of the displacement measurement of a revolutionary paraboloid and the angle measurement of plane mirrors, the 1-D artifact can be applied to identify position errors and angle errors. Meanwhile, the concrete 6 degrees-of-freedom error identification method is described in this paper in sufficient detail. Through measuring the 1-D artifact horizontally and vertically using the machine tool, the geometric errors can be obtained by calculating the deviation between the characteristic parameter of the 1-D artifact measured by the machine tool and that measured by a more precise method, for example, laser interferometry. Experiments were carried out on a coordinate measuring machine, and the validity and accuracy of the method were discussed by comparing the result with the identification error measured by a laser interferometer.
Anchor Design of a Ring Joint Based on Reliability in a Precast Shear Wall Structure
Authors: Zhou Jian , Zhi Xudong , Fan Feng , Jiao Anliang , Qian Hongliang
Published: August 2019

Precast buildings have been widely used owing to its outstanding features. As these buildings consist of a combination of various components, the mechanical properties of the connections play a critical role in the overall performance of the structure, particularly the vertical connections in shear wall members. A new connection called ring joint is proposed for precast buildings, and test pieces were designed to analyze the anchor performance. The damage phenomena and test data were observed and recorded. The displacement, force, and strain were analyzed, and the results indicated that the anchor length was a key factor and the connection was safe and reliable under reasonable design. Numerical analysis was conducted to explore the mechanical mechanism, and a bearing capacity model was proposed combining the bond and dowel effects simultaneously. Anchor length was determined based on reliability analysis under various conditions, and other suggestions were proposed. All these could guarantee the mechanical properties of the connection, as well as safety and reliability, and promote the popularization and application.
Multiuser Equalizer for Hybrid Massive MIMO mmWave CE-OFDM Systems
Authors: Magueta Roberto , Teodoro Sara , Castanheira Daniel , Silva Adão , Dinis Rui , Gameiro Atílio
Published: August 2019

This paper considers a multiuser broadband uplink massive multiple input multiple output (MIMO) millimeter-wave (mmWave) system. The constant envelope orthogonal frequency division multiplexing (CE-OFDM) is adopted as a modulation technique to allow an efficient power amplification, fundamental for mmWave based systems. Furthermore, a hybrid architecture is considered at the user terminals (UTs) and base station (BS) to reduce the high cost and power consumption required by a full-digital architecture, which has a radio frequency (RF) chain per antenna. Both the design of the UT’s precoder and base station equalizer are considered in this work. With the aim of maximizing the beamforming gain between each UT and the BS, the precoder analog coefficients are computed as a function of the average angles of departure (AoD), which are assumed to be known at the UTs. At the BS, the analog part is derived by assuming a system with no multi-user interference. Then, a per carrier basis nonlinear/iterative multi-user equalizer, based on the iterative block decision feedback equalization (IB-DFE) principle is designed, to explicitly remove both the multi-user and residual inter carrier interferences, not tackled in the analog part. The equalizer design metric is the sum of the mean square error (MSE) of all subcarriers, whose minimization is shown to be equivalent to the minimization of a weighted error between the hybrid and the full digital equalizer matrices. The results show that the proposed hybrid multi-user equalizer has a performance close to the fully digital counterpart.
The Optimized Production of 5-(Hydroxymethyl)furfural and Related Products from Spent Coffee Grounds
Authors: Pereira André Prates , Woodman Timothy J. , Brahmbhatt Paraj , Chuck Christopher J.
Published: August 2019

The increasing consumption of coffee worldwide has led to higher amounts of spent coffee grounds (SCG) being produced which are generally disposed of in landfill or used as compost. However, the wide range of molecules present in SCG such as saccharides, lignin, lipids and proteins give this biomass source a large chemical functionality. In this work, SCG were fractionated to separate the components into three separate portions for further valorization; these were hemicellulose-enriched fractions (HEF), lignin-enriched fraction (LEF) and cellulose-enriched fraction (CEF). HEF was effectively used in the growth of the oleaginous yeast Metschnikowia pulcherrima, additionally, the C6 sugars present in this fraction suggests that it can be used in the production of 5-hydroxymethylfurfural (HMF). The LEF had a considerable high heating value (HHV) and would be suitable as a biofuel component for combustion. CEF was efficiently used in the production of HMF as 0.35 g of this product were obtained from 10 g of SCG. Such results demonstrate that SCG can be effectively used in the production of HMF within a biorefinery concept.
Holographic Mixed Reality System for Air Traffic Control and Management
Authors: Han Kyungjin , Shah Syed Hammad Hussain , Lee Jong Weon
Published: August 2019

Based on a long-term prediction by the International Civil Aviation Organization indicating steady increases in air traffic demand throughout the world, the workloads of air traffic controllers are expected to continuously increase. Air traffic control and management (ATC/M) includes the processing of various unstructured composite data along with the real-time visualization of aircraft data. To prepare for future air traffic, research and development intended to effectively present various complex navigation data to air traffic controllers is necessary. This paper presents a mixed reality-based air traffic control system for the improvement of and support for air traffic controllers’ workflow using mixed reality technology that is effective for the delivery of information such as complex navigation data. The existing control systems involve difficulties in information access and interpretation. Therefore, taking notice of the necessity for the integration of air traffic control systems, this study presents the mixed reality (MR) system, which is a new approach, that enables the control of air traffic in interactive environments. This system is provided in a form usable in actual operational environments with a head-mounted see-through display installed with a controller to enable more structured work support. In addition, since this system can be controlled first-hand by air traffic controllers, it provides a new experience through improved work efficiency and productivity.
In-Situ Approaches for the Preparation of Polythiophene-Derivative Cellulose Composites with High Flexibility and Conductivity
Authors: González Francisco , Tiemblo Pilar , Hoyos Mario
Published: August 2019

Composite materials of conjugated polymers/cellulose were fabricated by incorporating different polythiophene-derivative polymers: Poly(3,4-ethylenedioxythiophene) (PEDOT) and an alkylated derivative of poly(3,4-propylenedioxythiophene) (PProDOT). These conjugated polythiophenes were deposited by casting or spray coating methodologies onto three different cellulose substrates: Conventional filters papers as cellulose acetate, cellulose grade 40 Whatman® and cellulose membranes prepared from cellulose microfibers. The preparation of composite materials was carried out by two methodologies: (i) by employing in-situ polymerization of 3,4-ethylenedioxithiophene (EDOT) or (ii) by depositing solutions of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) or lab-synthetized PProDOT. Composite materials were studied in terms of electrical conductivity and surface morphology assessed by impedance spectroscopy, surface conductivity, SEM, and 3D optical profilometry. In-situ composite materials prepared by spray coating using iron trifluoromethane sulfonate as oxidizing agent can be handled and folded as the original cellulose membranes displaying a surface conductivity around 1 S∙cm−1. This versatile procedure to prepare conductive composite materials has the potential to be implemented in flexible electrodes for energy storage applications.
A Note on Distance-Based Entropy of Dendrimers
Authors: Ghorbani Modjtaba , Dehmer Matthias , Zangi Samaneh , Mowshowitz Abbe , Emmert-Streib Frank
Published: August 2019

This paper introduces a variant of entropy measures based on vertex eccentricity and applies it to all graphs representing the isomers of octane. Taking into account the vertex degree as well (degree-ecc-entropy), we find a good correlation with the acentric factor of octane isomers. In particular, we compute the degree-ecc-entropy for three classes of dendrimer graphs.
Heterodimerization of Mu Opioid Receptor Protomer with Dopamine D2 Receptor Modulates Agonist-Induced Internalization of Mu Opioid Receptor
Authors: Vasudevan Lakshmi , Borroto-Escuela Dasiel O. , Huysentruyt Jelle , Fuxe Kjell , Saini Deepak K. , Stove Christophe
Published: August 2019

The interplay between the dopamine (DA) and opioid systems in the brain is known to modulate the additive effects of substances of abuse. On one hand, opioids serve mankind by their analgesic properties, which are mediated via the mu opioid receptor (MOR), a Class A G protein-coupled receptor (GPCR), but on the other hand, they pose a potential threat by causing undesired side effects such as tolerance and dependence, for which the exact molecular mechanism is still unknown. Using human embryonic kidney 293T (HEK 293T) and HeLa cells transfected with MOR and the dopamine D2 receptor (D2R), we demonstrate that these receptors heterodimerize, using an array of biochemical and biophysical techniques such as coimmunoprecipitation (co-IP), bioluminescence resonance energy transfer (BRET1), Fӧrster resonance energy transfer (FRET), and functional complementation of a split luciferase. Furthermore, live cell imaging revealed that D2LR, when coexpressed with MOR, slowed down internalization of MOR, following activation with the MOR agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO).
Integrative Approaches in Structural Biology: A More Complete Picture from the Combination of Individual Techniques
Authors: Cerofolini Linda , Fragai Marco , Ravera Enrico , Diebolder Christoph A. , Renault Ludovic , Calderone Vito
Published: August 2019

With the recent technological and computational advancements, structural biology has begun to tackle more and more difficult questions, including complex biochemical pathways and transient interactions among macromolecules. This has demonstrated that, to approach the complexity of biology, one single technique is largely insufficient and unable to yield thorough answers, whereas integrated approaches have been more and more adopted with successful results. Traditional structural techniques (X-ray crystallography and Nuclear Magnetic Resonance (NMR)) and the emerging ones (cryo-electron microscopy (cryo-EM), Small Angle X-ray Scattering (SAXS)), together with molecular modeling, have pros and cons which very nicely complement one another. In this review, three examples of synergistic approaches chosen from our previous research will be revisited. The first shows how the joint use of both solution and solid-state NMR (SSNMR), X-ray crystallography, and cryo-EM is crucial to elucidate the structure of polyethylene glycol (PEG)ylated asparaginase, which would not be obtainable through any of the techniques taken alone. The second deals with the integrated use of NMR, X-ray crystallography, and SAXS in order to elucidate the catalytic mechanism of an enzyme that is based on the flexibility of the enzyme itself. The third one shows how it is possible to put together experimental data from X-ray crystallography and NMR restraints in order to refine a protein model in order to obtain a structure which simultaneously satisfies both experimental datasets and is therefore closer to the ‘real structure’.
Adjunct Diagnostic Value of Transcranial Magnetic Stimulation in Mucopolysaccharidosis-Related Cervical Myelopathy: A Pilot Study
Authors: Cantone Mariagiovanna , Lanza Giuseppe , Le Pira Alice , Barone Rita , Pennisi Giovanni , Bella Rita , Pennisi Manuela , Fiumara Agata
Published: August 2019

Background: Cervical myelopathy (CM) is a common cause of morbidity and disability in patients with mucopolysaccharidosis (MPS) and, therefore, early detection is crucial for the best surgical intervention and follow-up. Transcranial magnetic stimulation (TMS) non-invasively evaluates the conduction through the cortico-spinal tract, also allowing preclinical diagnosis and monitoring. Methods: Motor evoked potentials (MEPs) to TMS were recorded in a group of eight patients with MPS-related CM. Responses were obtained during mild tonic muscular activation by means of a circular coil held on the “hot spot” of the first dorsal interosseous and tibialis anterior muscles, bilaterally. The motor latency by cervical or lumbar magnetic stimulation was subtracted from the MEP cortical latency to obtain the central motor conduction time. The MEP amplitude from peak to peak to cortical stimulation and the interside difference of each measure were also calculated. Results: TMS revealed abnormal findings from both upper and lower limbs compatible with axonal damage and demyelination in six of them. Notably, a subclinical cervical spinal disease was detected before the occurrence of an overt CM in two patients, whereas TMS signs compatible with a CM of variable degree persisted despite surgery in all treated subjects. Conclusions: TMS can be viewed as an adjunct diagnostic test pending further rigorous investigations.
EEG Signals Feature Extraction Based on DWT and EMD Combined with Approximate Entropy
Authors: Ji Na , Ma Liang , Dong Hui , Zhang Xuejun
Published: August 2019

The classification recognition rate of motor imagery is a key factor to improve the performance of brain–computer interface (BCI). Thus, we propose a feature extraction method based on discrete wavelet transform (DWT), empirical mode decomposition (EMD), and approximate entropy. Firstly, the electroencephalogram (EEG) signal is decomposed into a series of narrow band signals with DWT, then the sub-band signal is decomposed with EMD to get a set of stationary time series, which are called intrinsic mode functions (IMFs). Secondly, the appropriate IMFs for signal reconstruction are selected. Thus, the approximate entropy of the reconstructed signal can be obtained as the corresponding feature vector. Finally, support vector machine (SVM) is used to perform the classification. The proposed method solves the problem of wide frequency band coverage during EMD and further improves the classification accuracy of EEG signal motion imaging.
TRAIL Induces Nuclear Translocation and Chromatin Localization of TRAIL Death Receptors
Authors: Mert Ufuk , Adawy Alshaimaa , Scharff Elisabeth , Teichmann Pierre , Willms Anna , Haselmann Verena , Colmorgen Cynthia , Lemke Johannes , von Karstedt Silvia , Fritsch Jürgen , Trauzold Anna
Published: August 2019

Binding of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to the plasma membrane TRAIL-R1/-R2 selectively kills tumor cells. This discovery led to evaluation of TRAIL-R1/-R2 as targets for anti-cancer therapy, yet the corresponding clinical trials were disappointing. Meanwhile, it emerged that many cancer cells are TRAIL-resistant and that TRAIL-R1/-R2-triggering may lead to tumor-promoting effects. Intriguingly, recent studies uncovered specific functions of long ignored intracellular TRAIL-R1/-R2, with tumor-promoting functions of nuclear (n)TRAIL-R2 as the regulator of let-7-maturation. As nuclear trafficking of TRAIL-Rs is not well understood, we addressed this issue in our present study. Cell surface biotinylation and tracking of biotinylated proteins in intracellular compartments revealed that nTRAIL-Rs originate from the plasma membrane. Nuclear TRAIL-Rs-trafficking is a fast process, requiring clathrin-dependent endocytosis and it is TRAIL-dependent. Immunoprecipitation and immunofluorescence approaches revealed an interaction of nTRAIL-R2 with the nucleo-cytoplasmic shuttle protein Exportin-1/CRM-1. Mutation of a putative nuclear export sequence (NES) in TRAIL-R2 or the inhibition of CRM-1 by Leptomycin-B resulted in the nuclear accumulation of TRAIL-R2. In addition, TRAIL-R1 and TRAIL-R2 constitutively localize to chromatin, which is strongly enhanced by TRAIL-treatment. Our data highlight the novel role for surface-activated TRAIL-Rs by direct trafficking and signaling into the nucleus, a previously unknown signaling principle for cell surface receptors that belong to the TNF-superfamily.
Use of Antibiotics and Risk of Cancer: A Systematic Review and Meta-Analysis of Observational Studies
Authors: Petrelli Fausto , Ghidini Michele , Ghidini Antonio , Perego Gianluca , Cabiddu Mary , Khakoo Shelize , Oggionni Emanuela , Abeni Chiara , Hahne Jens Claus , Tomasello Gianluca , Zaniboni Alberto
Published: August 2019

The association between antibiotic use and risk of cancer development is unclear, and clinical trials are lacking. We performed a systematic review and meta-analysis of observational studies to assess the association between antibiotic use and risk of cancer. PubMed, the Cochrane Library and EMBASE were searched from inception to 24 February 2019 for studies reporting antibiotic use and subsequent risk of cancer. We included observational studies of adult subjects with previous exposure to antibiotics and available information on incident cancer diagnoses. For each of the eligible studies, data were collected by three reviewers. Risk of cancer was pooled to provide an adjusted odds ratio (OR) with a 95% confidence interval (CI). The primary outcome was the risk of developing cancer in ever versus non-antibiotic users. Cancer risk’s association with antibiotic intake was evaluated among 7,947,270 participants (n = 25 studies). Overall, antibiotic use was an independent risk factor for cancer occurrence (OR 1.18, 95%CI 1.12–1.24, p < 0.001). The risk was especially increased for lung cancer (OR 1.29, 95%CI 1.03–1.61, p = 0.02), lymphomas (OR 1.31, 95%CI 1.13–1.51, p < 0.001), pancreatic cancer (OR 1.28, 95%CI 1.04–1.57, p = 0.019), renal cell carcinoma (OR 1.28, 95%CI 1.1–1.5, p = 0.001), and multiple myeloma (OR 1.36, 95%CI 1.18–1.56, p < 0.001). There is moderate evidence that excessive or prolonged use of antibiotics during a person’s life is associated with slight increased risk of various cancers. The message is potentially important for public health policies because minimizing improper antibiotic use within a program of antibiotic stewardship could also reduce cancer incidence.
Multi-Drug/Gene NASH Therapy Delivery and Selective Hyperspectral NIR Imaging Using Chirality-Sorted Single-Walled Carbon Nanotubes
Authors: Hasan Md. Tanvir , Campbell Elizabeth , Sizova Olga , Lyle Veronica , Akkaraju Giridhar , Kirkpatrick D. Lynn , Naumov Anton V.
Published: August 2019

Single-walled carbon nanotubes (SWCNTs) can serve as drug delivery/biological imaging agents, as they exhibit intrinsic fluorescence in the near-infrared, allowing for deeper tissue imaging while providing therapeutic transport. In this work, CoMoCAT (Cobalt Molybdenum Catalyst) SWCNTs, chirality-sorted by aqueous two-phase extraction, are utilized for the first time to deliver a drug/gene combination therapy and image each therapeutic component separately via chirality-specific SWCNT fluorescence. Each of (7,5) and (7,6) sorted SWCNTs were non-covalently loaded with their specific payload: the PI3 kinase inhibitor targeting liver fibrosis or CCR5 siRNA targeting inflammatory pathways with the goal of addressing these processes in nonalcoholic steatohepatitis (NASH), ultimately to prevent its progression to hepatocellular carcinoma. PX-866-(7,5) SWCNTs and siRNA-(7,6) SWCNTs were each imaged via characteristic SWCNT emission at 1024/1120 nm in HepG2 and HeLa cells by hyperspectral fluorescence microscopy. Wavelength-resolved imaging verified the intracellular transport of each SWCNT chirality and drug release. The therapeutic efficacy of each formulation was further demonstrated by the dose-dependent cytotoxicity of SWCNT-bound PX-866 and >90% knockdown of CCR5 expression with SWCNT/siRNA transfection. This study verifies the feasibility of utilizing chirality-sorted SWCNTs for the delivery and component-specific imaging of combination therapies, also suggesting a novel nanotherapeutic approach for addressing the progressions of NASH to hepatocellular carcinoma.
Hyperthermia Treatment Planning Including Convective Flow in Cerebrospinal Fluid for Brain Tumour Hyperthermia Treatment Using a Novel Dedicated Paediatric Brain Applicator
Authors: Schooneveldt Gerben , Dobšíček Trefná Hana , Persson Mikael , de Reijke Theo M. , Blomgren Klas , Kok H. Petra , Crezee Hans
Published: August 2019

Hyperthermia therapy (40–44 °C) is a promising option to increase efficacy of radiotherapy/chemotherapy for brain tumours, in particular paediatric brain tumours. The Chalmers Hyperthermia Helmet is developed for this purpose. Hyperthermia treatment planning is required for treatment optimisation, but current planning systems do not involve a physically correct model of cerebrospinal fluid (CSF). This study investigates the necessity of fluid modelling for treatment planning. We made treatments plans using the Helmet for both pre-operative and post-operative cases, comparing temperature distributions predicted with three CSF models: a convective “fluid” model, a non-convective “solid” CSF model, and CSF models with increased effective thermal conductivity (“high-k”). Treatment plans were evaluated by T90, T50 and T10 target temperatures and treatment-limiting hot spots. Adequate heating is possible with the helmet. In the pre-operative case, treatment plan quality was comparable for all three models. In the post-operative case, the high-k models were more accurate than the solid model. Predictions to within ±1 °C were obtained by a 10–20-fold increased effective thermal conductivity. Accurate modelling of the temperature in CSF requires fluid dynamics, but modelling CSF as a solid with enhanced effective thermal conductivity might be a practical alternative for a convective fluid model for many applications.
Anaplastic Thyroid Cancer: Clinical Picture of the Last Two Decades at a Single Oncology Referral Centre and Novel Therapeutic Options
Authors: Simões-Pereira Joana , Capitão Ricardo , Limbert Edward , Leite Valeriano
Published: August 2019

Anaplastic thyroid cancer (ATC) is a rare tumour but also one of the most lethal malignancies. Therapeutic modalities have usually been limited, but clinical trials with new drugs are now being implemented. The aims of this study were to analyse the clinical presentation, therapeutic modalities and independent prognostic factors for survival. We also reviewed the most recent literature on novel ATC therapies. We performed a retrospective analysis of 79 patients diagnosed between 2000 and 2018. Variables with impact on survival were identified using the Cox proportional-hazard regression model. At presentation, 6.3% had thyroid-confined disease, 30.4% evidenced extrathyroidal extension and 60.8% were already metastatic. Surgery was feasible in 41.8% and radiotherapy was applied to 35.4%, with those receiving >45 Gy having longer estimated survival (p = 0.020). Chemotherapy, either conventional or with tyrosine kinase inhibitors, was performed in 17.7% and 7.6%, respectively. Multimodality therapy with surgery, radiotherapy and chemotherapy/tyrosine kinase inhibitors (TKI) had the greatest impact on disease specific survival (DSS), providing a risk reduction of death of 96.9% (hazard ratio (HR) = 0.031, 0.005–0.210, p < 0.001). We concluded that most of these patients join reference centres at advanced stages of disease and multimodality treatment may offer the best chances for prolonging survival.
How to Deal with Second Line Dilemma in Metastatic Colorectal Cancer? A Systematic Review and Meta-Analysis
Authors: Galvano Antonio , Incorvaia Lorena , Badalamenti Giuseppe , Rizzo Sergio , Guarini Aurelia , Cusenza Stefania , Castellana Luisa , Barraco Nadia , Calò Valentina , Cutaia Sofia , Currò Giuseppe , Silvestris Nicola , Beretta Giordano Domenico , Bazan Viviana , Russo Antonio
Published: August 2019

Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy with chemotherapy (CT) as second line treatment for metastatic colorectal cancer (mCRC). The right sequence of the treatments in all RAS (KRAS/NRAS) wild type (wt) patients has not precisely defined. We evaluated the impact of aforementioned targeted therapies in second line setting, analyzing efficacy and safety data from phase III clinical trials. We performed both direct and indirect comparisons between anti-EGFR and anti-VEGF. Outcomes included disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and G3-G5 toxicities. Our results showed significantly improved OS (HR 0.83, 95% CI 0.72–0.94) and DCR (HR 1.27, 95% CI 1.04–1.54) favouring anti-VEGF combinations in overall population; no statistically significant differences in all RAS wt patients was observed (HR 0.87, 95% CI 0.70–1.09). Anti-EGFR combinations significantly increased ORR in all patients (RR 0.54, 95% CI 0.31–0.96), showing a trend also in all RAS wt patients (RR 0.63, 95% CI 0.48–0.83). No significant difference in PFS and DCR all RAS was registered. Our results provided for the first time a strong rationale to manage both targeted agents in second line setting.
Alternative Raw Materials to Produce Biodiesel through Alkaline Heterogeneous Catalysis
Authors: Sánchez Faba Edgar M. , Ferrero Gabriel O. , Dias Joana M. , Eimer Griselda A.
Published: August 2019

Recent research focuses on new biodiesel production and purification technologies that seek a carbon-neutral footprint, as well as cheap, renewable and abundant raw materials that do not compete with the demand for food. Then, many attractive alternatives arise due to their availability or low-cost, such as used cooking oil, Jatropha oil (non-edible) or byproducts of vegetable oil refineries. Due to their composition and the presence of moisture, these oils may need a pretreatment to reach the established conditions to be used in the biodiesel production process so that the final product complies with the international quality standards. In this work, a solid catalyst based on 10 wt % sodium oxide supported on mesoporous silica SBA-15, was employed in the transesterification of different feedstocks (commercial sunflower and soybean oil, used cooking oil, acid oil from soapstock and Jatropha hieronymi oil) with absolute methanol in the following reaction conditions—2–8 wt % catalyst, 14:1 methanol to oil molar ratio, 60 °C, vigorous magnetic stirring and 5 h of reaction. In this way, first- and second-generation biodiesel was obtained through heterogeneous catalysis with methyl ester yields between 52 and 97 wt %, depending on the free fatty acid content and the moisture content of the oils.
Pathogenic and Therapeutic Relevance of JAK/STAT Signaling in Systemic Lupus Erythematosus: Integration of Distinct Inflammatory Pathways and the Prospect of Their Inhibition with an Oral Agent
Authors: Alunno Alessia , Padjen Ivan , Fanouriakis Antonis , Boumpas Dimitrios T.
Published: August 2019

Four Janus kinases (JAKs) (JAK1, JAK2, JAK3, TYK2) and seven signal transducers and activators of transcription (STATs) (STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6) mediate the signal transduction of more than 50 cytokines and growth factors in many different cell types. Located intracellularly and downstream of cytokine receptors, JAKs integrate and balance the actions of various signaling pathways. With distinct panels of STAT-sensitive genes in different tissues, this highly heterogeneous system has broad in vivo functions playing a crucial role in the immune system. Thus, the JAK/STAT pathway is critical for resisting infection, maintaining immune tolerance, and enforcing barrier functions and immune surveillance against cancer. Breakdowns of this system and/or increased signal transduction may lead to autoimmunity and other diseases. Accordingly, the recent development and approval of the first small synthetic molecules targeting JAK molecules have opened new therapeutic avenues of potentially broad therapeutic relevance. Extensive data are now available regarding the JAK/STAT pathway in rheumatoid arthritis. Dysregulation of the cytokines is also a hallmark of systemic lupus erythematosus (SLE), and targeting the JAK/STAT proteins allows simultaneous suppression of multiple cytokines. Evidence from in vitro studies and animal models supports a pivotal role also in the pathogenesis of cutaneous lupus and SLE. This has important therapeutic implications, given the current paucity of targeted therapies especially in the latter. Herein, we summarize the currently available literature in experimental SLE, which has led to the recent promising Phase II clinical trial of a JAK inhibitor.
Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection
Authors: Tovanabutra Sodsai , Sirijatuphat Rujipas , Pham Phuc , Bonar Lydia , Harbolick Elizabeth , Bose Meera , Song Hongshuo , Chang David , Oropeza Celina , O’Sullivan Anne , Balinang Joyce , Kroon Eugene , Colby Donn , Sacdalan Carlo , Hellmuth Joanna , Chan Phillip , Prueksakaew Peeriya , Pinyakorn Suteeraporn , Jagodzinski Linda , Sutthichom Duanghathai , Pattamaswin Suwanna , de Souza Mark , Gramzinski Robert , Kim Jerome , Michael Nelson , Robb Merlin , Phanuphak Nittaya , Ananworanich Jintanat , Valcour Victor , Kijak Gustavo , Sanders-Buell Eric , Spudich Serena ,   The MHRP Viral Sequencing Core,   the RV254/SEARCH 010 Study Team
Published: August 2019

HIV-1 disseminates to a broad range of tissue compartments during acute HIV-1 infection (AHI). The central nervous system (CNS) can serve as an early and persistent site of viral replication, which poses a potential challenge for HIV-1 remission strategies that target the HIV reservoir. CNS compartmentalization is a key feature of HIV-1 neuropathogenesis. Thus far, the timing of how early CNS compartmentalization develops after infection is unknown. We examined whether HIV-1 transmitted/founder (T/F) viruses differ between CNS and blood during AHI using single-genome sequencing of envelope gene and further examined subregions in pol and env using next-generation sequencing in paired plasma and cerebrospinal fluid (CSF) from 18 individuals. Different proportions of mostly minor variants were found in six of the eight multiple T/F-infected individuals, indicating enrichment of some variants in CSF that may lead to significant compartmentalization in the later stages of infection. This study provides evidence for the first time that HIV-1 compartmentalization in the CNS can occur within days of HIV-1 exposure in multiple T/F infections. Further understanding of factors that determine enrichment of T/F variants in the CNS, as well as potential long-term implications of these findings for persistence of HIV-1 reservoirs and neurological impairment in HIV, is needed.
Antioxidant and Pro-Oxidant Activities of Melatonin in the Presence of Copper and Polyphenols In Vitro and In Vivo
Authors: Wang Jiajia , Wang Xiaoxiao , He Yufeng , Jia Lijie , Yang Chung S. , Reiter Russel J. , Zhang Jinsong
Published: August 2019

Melatonin is a well-documented antioxidant. Physicochemical analysis using the density functional theory suggests that melatonin is a copper chelating agent; however, experimental evidence is still in demand. The present study investigated the influence of melatonin on reactive oxygen species (ROS) generated from polyphenol autoxidation in the presence of copper. Surprisingly, we found that melatonin paradoxically enhanced ROS formation in a redox system containing low concentrations of copper and quercetin (Que) or (−)-epigallocatechin-3-gallate (EGCG), due to reduction of cupric to cuprous ion by melatonin. Addition of DNA to this system inhibited ROS production, because DNA bound to copper and inhibited copper reduction by melatonin. When melatonin was added to a system containing high concentrations of copper and Que or EGCG, it diminished hydroxyl radical formation as expected. Upon addition of DNA to high concentrations of copper and Que, this pro-oxidative system generated ROS and caused DNA damage. The DNA damage was not prevented by typical scavengers of hydroxyl radical DMSO or mannitol. Under these conditions, melatonin or bathocuproine disulfonate (a copper chelator) protected the DNA from damage by chelating copper. When melatonin was administered intraperitoneally to mice, it inhibited hepatotoxicity and DNA damage evoked by EGCG plus diethyldithiocarbamate (a copper ionophore). Overall, the present study demonstrates the pro-oxidant and antioxidant activities of melatonin in the redox system of copper and polyphenols. The pro-oxidant effect is inhibited by the presence of DNA, which prevents copper reduction by melatonin. Interestingly, in-vivo melatonin protects against copper/polyphenol-induced DNA damage probably via acting as a copper-chelating agent rather than a hydroxyl radical scavenger. Melatonin with a dual function of scavenging hydroxyl radical and chelating copper is a more reliable DNA guardian than antioxidants that only have a single function of scavenging hydroxyl radical.
The Autophagy-Cilia Axis: An Intricate Relationship
Authors: Morleo Manuela , Franco Brunella
Published: August 2019

Primary cilia are microtubule-based organelles protruding from the surface of almost all vertebrate cells. This organelle represents the cell’s antenna which acts as a communication hub to transfer extracellular signals into intracellular responses during development and in tissue homeostasis. Recently, it has been shown that loss of cilia negatively regulates autophagy, the main catabolic route of the cell, probably utilizing the autophagic machinery localized at the peri-ciliary compartment. On the other side, autophagy influences ciliogenesis in a context-dependent manner, possibly to ensure that the sensing organelle is properly formed in a feedback loop model. In this review we discuss the recent literature and propose that the autophagic machinery and the ciliary proteins are functionally strictly related to control both autophagy and ciliogenesis. Moreover, we report examples of diseases associated with autophagic defects which cause cilia abnormalities, and propose and discuss the hypothesis that, at least some of the clinical manifestations observed in human diseases associated to ciliary disfunction may be the result of a perturbed autophagy.
Theoretical Study of the Electronic and Magnetic Properties and Phase Stability of the Full Heusler Compound Pd2CoAl
Authors: Hao Liyu , You Jiaxue , Khenata Rabah , Wang Yanfeng , Wang Xiaotian , Yang Tie
Published: August 2019

Based on first principles calculation, a systematical investigation has been performed to study the electronic, magnetic, dynamic, and mechanical properties of the full Heusler compound Pd2CoAl. It is found that the L21-type structure is energetically more stable than the XA-type due to the lower total energy. The obtained lattice constant in cubic ground state is 6.057 Å, which matches well with previous study. The calculated electronic band structure reveals the metallic nature of Pd2CoAl and its total magnetic moment of 1.78 μB is mainly contributed by Co atom from strong spin splitting effect, as indicated with the distinctive distributions of the density of states in two spin directions. Under uniform strains from −5% to +5%, the variation of total magnetic moment has been obtained and it is still caused by the much larger change from Co atom, compared with Pd and Al atoms. The tetragonal structure has further been analyzed and we found that there is possible martensitic phase transformation because the total energy can be further reduced when the cubic structure is varied into the tetragonal one. The large energy difference of 0.165 eV between the tetragonal and cubic phases is found at the c/a ratio of 1.30. The total density of states has been compared between the cubic and tetragonal phases for Pd2CoAl and results show tetragonal phase transformation could reduce the states at the Fermi energy level in both directions. In addition, the dynamic and mechanical stabilities have also been evaluated for Pd2CoAl in both cubic and tetragonal structures and results confirm that the tetragonal phase shows good stability against the cubic phase, which further verifies that the tetragonal phase transformation is highly expected. In the end, the strong elastic anisotropy in the tetragonal structure has been clearly shown with the calculated directional dependence of the Young’s modulus and shear modulus.
Phytoplankton Blooms, Red Tides and Mucilaginous Aggregates in the Urban Thessaloniki Bay, Eastern Mediterranean
Authors: Genitsaris Savvas , Stefanidou Natassa , Sommer Ulrich , Moustaka-Gouni Maria
Published: August 2019

We investigated the plankton community composition and abundance in the urban marine environment of Thessaloniki Bay. We collected water samples weekly from March 2017 to February 2018 at the coastal front of Thessaloniki city center and monthly samples from three other inshore sites along the urban front of the bay. During the study period, conspicuous and successive phytoplankton blooms, dominated by known mucilage-producing diatoms alternated with red tide events formed by the dinoflagellates Noctiluca scintillans and Spatulodinium pseudonoctiluca, and an extensive mucilage aggregate phenomenon, which appeared in late June 2017. At least 11 known harmful algae were identified throughout the study, with the increase in the abundance of the known harmful dinoflagellate Dinophysis cf. acuminata occurring in October and November 2017. Finally, a red tide caused by the photosynthetic ciliate Mesodinium rubrum on December 2017 was conspicuous throughout the sampling sites. The above-mentioned harmful blooms and red tides were linked to high nutrient concentrations and eutrophication. This paper provides an overview of eutrophication impacts on the response of the unicellular eukaryotic plankton organisms and their impact on water quality and ecosystem services.
Biotic and Abiotic Factors Affecting the Population Dynamics of Ceratium hirundinella, Peridinium cinctum, and Peridiniopsis elpatiewskyi
Authors: Zarei Darki Behrouz , Krakhmalnyi Alexandr F.
Published: August 2019

The present research was conducted to assess the impact of abiotic and biotic factors on the growth of freshwater dinoflagellates such as Ceratium hirundinella, Peridinium cinctum, and Peridiniopsis elpatiewskyi, which reduce the quality of drinking water in the Zayandeh Rud Reservoir. To this end, 152 algal and zoological samples were collected from the reservoir located in the Central part of Iran in January, April, July, and October 2011. Abiotic factors such as pH, temperature, conductivity, transparency, dissolved oxygen, and nutrient concentration of the water were measured in all study stations. The results showed that the population dynamics of dinoflagellates in the Zayandeh Rud Reservoir was different depending on season, station, and depth. The findings proved that C. hirundinella was one of the dominant autumn planktons in the highest biovolume in the Zayandeh Rud Reservoir. While P. elpatiewskyi was present in the reservoir throughout a year with biovolume peak in summer. Accompanying bloom of P. elpatiewskyi and C. hirundinella, P. cinctum also grew in well-heated summer and autumn waters. It was further found that Ceratium density was positively correlated with sulfate ion concentrations, while the growth of P. cinctum and P. elpatiewskyi were associated, first and foremost, with NO2− and Mn.
Triple Test Plus Rapid Cognitive Screening Test: A Combination of Clinical Signs and A Tool for Cognitive Assessment in Older Adults
Authors: Koc Okudur Saadet , Dokuzlar Ozge , Kaya Derya , Soysal Pinar , Isik Ahmet Turan
Published: August 2019

Less time-consuming, easy-to-apply and more reliable cognitive screening tests are essential for use in primary care. The aim of this study was to investigate the diagnostic value of the Turkish version of the Rapid Cognitive Screen (RCS-T) and Triple Test individually and the combination of RCS-T with each sign and Triple Test to screen elderly patients for cognitive impairment (CI). A total of 357 outpatients aged 60 or older, who underwent comprehensive geriatric assessment, were included in the study. Presence or absence of attended alone sign (AAS), head-turning sign, and applause sign was investigated. The mean age of the patients was 74.29 ± 7.46. Of those, 61 patients (28 men, 33 women) had Alzheimer’s disease (AD), 59 patients had mild cognitive impairment (MCI) (29 men, 30 women), and 237 (80 men, 157 women) were cognitively robust. The sensitivity of the combination of RCS-T and negative for AAS for CI, AD and MCI is 0.79, 0.86 and 0.61, respectively; the specificity was 0.92, 0.93 and 0.92, respectively; and the positive and negative predictive values revealed good diagnostic accuracy. The combination of RCS-T and negative for AAS is a simple, effective and rapid way to identify possible CI in older adults.
A Comparative Study of Multiscale Sample Entropy and Hierarchical Entropy and Its Application in Feature Extraction for Ship-Radiated Noise
Authors: Li Weijia , Shen Xiaohong , Li Yaan
Published: August 2019

The presence of marine ambient noise makes it difficult to extract effective features from ship-radiated noise. Traditional feature extraction methods based on the Fourier transform or wavelets are limited in such a complex ocean environment. Recently, entropy-based methods have been proven to have many advantages compared with traditional methods. In this paper, we propose a novel feature extraction method for ship-radiated noise based on hierarchical entropy (HE). Compared with the traditional entropy, namely multiscale sample entropy (MSE), which only considers information carried in the lower frequency components, HE takes into account both lower and higher frequency components of signals. We illustrate the different properties of HE and MSE by testing them on simulation signals. The results show that HE has better performance than MSE, especially when the difference in signals is mainly focused on higher frequency components. Furthermore, experiments on real-world data of five types of ship-radiated noise are conducted. A probabilistic neural network is employed to evaluate the performance of the obtained features. Results show that HE has a higher classification accuracy for the five types of ship-radiated noise compared with MSE. This indicates that the HE-based feature extraction method could be used to identify ships in the field of underwater acoustic signal processing.
Optimization and Evaluation of Ventilation Mode in Marine Data Center Based on AHP-Entropy Weight
Authors: Feng Guozeng , Lei Shuya , Guo Yuejiao , Meng Bo , Jiang Qingfeng
Published: August 2019

The ventilation mode affects the cooling efficiency of the air conditioners significantly in marine data centers. Three different ventilation modes, namely, underfloor ventilation, overhead ventilation, side ventilation, are numerically investigated for a typical marine data center. Four independent parameters, including temperature, velocity, air age, and uniformity index, are applied to evaluate the performances of the three ventilation modes. Further, the analytic hierarchy process (AHP) entropy weight model is established and further analysis is conducted to find the optimal ventilation mode of the marine data center. The results indicate that the underfloor ventilation mode has the best performance in the airflow patterns and temperature distribution evaluation projects, with the highest scores of 91.84 and 90.60. If low energy consumption is required, it is recommended to select the overhead ventilation mode with a maximum score of 93.50. The current evaluation results agree fairly well with the three dimensional simulation results, which further proves that the AHP entropy weight method is reasonable and has a high adaptability for the evaluation of air conditioning ventilation modes.
Sex Differences in the Complexity of Healthy Older Adults’ Magnetoencephalograms
Authors: Shumbayawonda Elizabeth , Abásolo Daniel , López-Sanz David , Bruña Ricardo , Maestu Fernando , Fernández Alberto
Published: August 2019

The analysis of resting-state brain activity recording in magnetoencephalograms (MEGs) with new algorithms of symbolic dynamics analysis could help obtain a deeper insight into the functioning of the brain and identify potential differences between males and females. Permutation Lempel-Ziv complexity (PLZC), a recently introduced non-linear signal processing algorithm based on symbolic dynamics, was used to evaluate the complexity of MEG signals in source space. PLZC was estimated in a broad band of frequencies (2–45 Hz), as well as in narrow bands (i.e., theta (4–8 Hz), alpha (8–12 Hz), low beta (12–20 Hz), high beta (20–30 Hz), and gamma (30–45 Hz)) in a sample of 98 healthy elderly subjects (49 males, 49 female) aged 65–80 (average age of 72.71 ± 4.22 for males and 72.67 ± 4.21 for females). PLZC was significantly higher for females than males in the high beta band at posterior brain regions including the precuneus, and the parietal and occipital cortices. Further statistical analyses showed that higher complexity values over highly overlapping regions than the ones mentioned above were associated with larger hippocampal volumes only in females. These results suggest that sex differences in healthy aging can be identified from the analysis of magnetoencephalograms with novel signal processing methods.