bluuebunny/crossref_metadata_2025 huggingface dataset:
Bridgeless Buck-Boost PFC Rectifier with Positive Output Voltage
Authors: Hwu Kuo-Ing , Tai Yu-Kun , He Yu-Ping
Published: August 2019

A bridgeless buck-boost power-factor-correction (PFC) rectifier with positive output voltage is proposed herein. This PFC rectifier operates in the discontinuous conduction mode (DCM). Owing to the DCM, a good performance on PF is easily achieved as well as no reverse recovery currents being generated from the diodes. By means of output voltage sensing along with the traditional voltage-follower control, a proper control force is created to drive the switches. By doing so, not only the output voltage is stably controlled at a given value, but also the input current tracks the input voltage as tightly as possible. In addition, the accompanying harmonic distortion meets the requirements of the IEC6100-3-2 Class C harmonics standard, and accordingly, the proposed rectifier is suitable for the AC-DC LED driver. Finally, via mathematical deductions and experimental results, the effectiveness of the proposed bridgeless buck-boost PFC rectifier is verified.
The Self-Calibration Method for the Vertex Distance of the Elliptical Paraboloid Array
Authors: Lv Zekui , Su Zhikun , Zhang Dong , Gao Lingyu , Yang Zhiming , Fang Fengzhou , Zhang Haitao , Li Xinghua
Published: August 2019

The elliptical paraboloid array plays an important role in precision measurement, astronomical telescopes, and communication systems. The calibration of the vertex distance of elliptical paraboloids is of great significance to precise 2D displacement measurement. However, there are some difficulties in determining the vertex position with contact measurement. In this study, an elliptical paraboloid array and an optical slope sensor for displacement measurement were designed and analyzed. Meanwhile, considering the geometrical relationship and relative angle between elliptical paraboloids, a non-contact self-calibration method for the vertex distance of the elliptical paraboloid array was proposed. The proposed self-calibration method was verified by a series of experiments with a high repeatability, within 3   μ m in the X direction and within 1   μ m in the Y direction. Through calibration, the displacement measurement system error was reduced from 100   μ m to 3   μ m . The self-calibration method of the elliptical paraboloid array has great potential in the displacement measurement field, with a simple principle and high precision.
Well-Distributed Feature Extraction for Image Registration Using Histogram Matching
Authors: Mahmood Muhammad Tariq , Lee Ik Hyun
Published: August 2019

Image registration is a spatial alignment of corresponding images of the same scene acquired from different views, sensors, and time intervals. Especially, satellite image registration is a challenging task due to the high resolution of images. In addition, demands for high resolution satellite imagery are increased for more detailed and precise information in land planning, urban planning, and Earth observation. Commonly, feature-based methods are applied for image registration. In these methods, first control or key points are detected using feature detector such as scale-invariant feature transform (SIFT). The numbers and the distribution of these control points are important for the remaining steps of registration. These methods provide reasonable performance; however, they suffer from high computational cost and irregular distribution of control points. To overcome these limitations, we propose an area-based registration method using histogram matching and zero mean normalized cross-correlation (ZNCC). In multi-spectral satellite images, first, different spectral responses are adjusted by using histogram matching. Then, ZNCC is utilized to extract well-distributed control points. In addition, fast Fourier transform (FFT) and block-wise processing are applied to reduce the computational cost. The proposed method is evaluated through various input datasets. The results demonstrate its efficacy and accuracy in image registration.
Numerical Investigation of Multi-SDBD Plasma Actuators for Controlling Fluctuating Wind Load on Building Roofs
Authors: Zhang Xuewen , Li Zhengnong , Sun Fenglou , Zhao Zhefei , Wang Chequan , Hu Jiaxing
Published: August 2019

The present research aims to explore, by large-eddy simulation (LES), the potentiality and mechanism of multiple surface dielectric barrier discharge (multi-SDBD) plasma actuators to manipulate mean and fluctuating wind loads on a low-rise building. Three actuator configurations are located on the roof to induce directional wall jets in different directions. The effects of these configurations on flow structure and wind loads are studied in absence and presence of approaching flow. Results show that all subgrid-scale models can obtain accurate roof pressure, and for the diffusion and convection terms, the bounded central differencing scheme can provide more accurate predictions for the roof pressure. The control impact of active actuators gradually weakens with the increase of the approaching flow velocity. The direction of the wall jet can determine the position of the limited roof region with the reduced mean pressure coefficient. The multi-SDBD actuators continue to absorb the upstream flow and blow this flow downstream, meaning the wall jet exerts strong pressure on the local roof area at the end of the jet, which results in a significant reduction of the mean pressure coefficient. Furthermore, the counter-rotating vortices caused by the wall jet restrain the size and strength of the vortex shedding, thereby achieving the purpose of reducing the fluctuating pressure coefficient. Further analysis of the instantaneous vorticity fields indicates that the intensity and size of streamwise shedding vortices can be restrained by small-scale spanwise vortices induced by the plasma actuators. Under the action of the wall jet blowing from the trailing edge to the leading edge, the fluctuating lift and drag coefficients can be reduced by over 15% and the fluctuating pressure coefficient can be reduced by about 20% from the no actuation situation.
SEVUCAS: A Novel GIS-Based Machine Learning Software for Seismic Vulnerability Assessment
Authors: Lee Saro , Panahi Mahdi , Pourghasemi Hamid Reza , Shahabi Himan , Alizadeh Mohsen , Shirzadi Ataollah , Khosravi Khabat , Melesse Assefa M. , Yekrangnia Mohamad , Rezaie Fatemeh , Moeini Hamidreza , Pham Binh Thai , Bin Ahmad Baharin
Published: August 2019

Since it is not possible to determine the exact time of a natural disaster’s occurrence and the amount of physical and financial damage on humans or the environment resulting from their event, decision-makers need to identify areas with potential vulnerability in order to reduce future losses. In this paper, a GIS-based open source software entitled Seismic-Related Vulnerability Calculation Software (SEVUCAS), based on the Step-wise Weight Assessment Ratio Analysis (SWARA) method and geographic information system, has been developed to assess seismic vulnerability by considering four groups of criteria (i.e., geotechnical, structural, socio-economic, and physical distance to needed facilities and away from dangerous facilities). The software was developed in C# language using ArcGIS Engine functions, which provide enhanced visualization as well as user-friendly and automatic software for the seismic vulnerability assessment of buildings. Weighting of the criteria (indicators) and alternatives (sub-indicators) was done using SWARA. Also, two interpolation methods based on a radial basis function (RBF) and teaching–learning-based optimization (TLBO) were used to optimize the weights of the criteria and the classes of each alternative as well. After weighing the criteria and alternatives, the weighted overlay analysis was used to determine the final vulnerability map in the form of contours and statistical data. The difference between this software and similar ones is that people with a low level of knowledge in the area of earthquake crisis management can use it to determine and estimate the seismic vulnerabilities of their houses. This visualized operational forecasting software provides an applicable tool for both government and people to make quick and correct decisions to determine higher priority structures for seismic retrofitting implementation.
Real-Time City-Scale Time-History Analysis and Its Application in Resilience-Oriented Earthquake Emergency Responses
Authors: Lu Xinzheng , Cheng Qingle , Xu Zhen , Xu Yongjia , Sun Chujin
Published: August 2019

The resilience of cities has received worldwide attention. An accurate and rapid assessment of seismic damage, economic loss, and post-event repair time can provide an important reference for emergency rescue and post-earthquake recovery. Based on city-scale nonlinear time-history analysis (THA) and regional seismic loss prediction, a real-time city-scale time-history analysis method is proposed in this work. In this method, the actual ground motion records obtained from seismic stations are input into the building models of the earthquake-stricken area, and the nonlinear time-history analysis of these models is subsequently performed using a high-performance computing platform. The seismic damage to the buildings in the target region subjected to this earthquake is evaluated according to the analysis results. The economic loss and repair time of the earthquake-stricken areas are calculated using the engineering demand parameters obtained from the time-history analysis. A program named, “Real-time Earthquake Damage Assessment using City-scale Time-history analysis” (“RED-ACT” for short) was developed to automatically implement the above workflow. The method proposed in this work has been applied in many earthquake events, and provides a useful reference for scientific decision making for earthquake disaster relief, which is of great significance to enhancing the resilience of earthquake-stricken areas.
Random Laser Action in Dye-Doped Polymer Media with Inhomogeneously Distributed Particles and Gain
Authors: Okamoto Takashi , Mori Masaki
Published: August 2019

The properties of random lasing are investigated for bubble-structure (BS) dye-doped polymer random media in which non-scattering and no-gain regions are distributed. Experimental results demonstrate that, for BS random media, spectral narrowing and a decrease in the number of spectral spikes occur for incoherent and coherent random lasing, respectively, resulting in an increase in the spectral peak intensity in both cases. These features were observed owing to the differences in the diffusion properties of the pumping and emitted lights.
A Hybrid Inversion Scheme Combining Markov Chain Monte Carlo and Iterative Methods for Determining Optical Properties of Random Media
Authors: Jiang Yu , Hoshi Yoko , Machida Manabu , Nakamura Gen
Published: August 2019

Near-infrared spectroscopy (NIRS) including diffuse optical tomography is an imaging modality which makes use of diffuse light propagation in random media. When optical properties of a random medium are investigated from boundary measurements of reflected or transmitted light, iterative inversion schemes such as the Levenberg–Marquardt algorithm are known to fail when initial guesses are not close enough to the true value of the coefficient to be reconstructed. In this paper, we investigate how this weakness of iterative schemes is overcome using Markov chain Monte Carlo. Using time-resolved measurements performed against a polyurethane-based phantom, we present a case that the Levenberg–Marquardt algorithm fails to work but the proposed hybrid method works well. Then, with a toy model of diffuse optical tomography we illustrate that the Levenberg–Marquardt method fails when it is trapped by a local minimum but the hybrid method can escape from local minima by using the Metropolis–Hastings Markov chain Monte Carlo algorithm until it reaches the valley of the global minimum. The proposed hybrid scheme can be applied to different inverse problems in NIRS which are solved iteratively. We find that for both numerical and phantom experiments, optical properties such as the absorption and reduced scattering coefficients can be retrieved without being trapped by a local minimum when Monte Carlo simulation is run only about 100 steps before switching to an iterative method. The hybrid method is compared with simulated annealing. Although the Metropolis–Hastings MCMC arrives at the steady state at about 10,000 Monte Carlo steps, in the hybrid method the Monte Carlo simulation can be stopped way before the burn-in time.
On the Determination of Meshed Distribution Networks Operational Points after Reinforcement
Authors: Vita Vasiliki , Lazarou Stavros , Christodoulou Christos A. , Seritan George
Published: August 2019

This paper proposes a calculation algorithm that creates operational points and evaluates the performance of distribution lines after reinforcement. The operational points of the line are probabilistically determined using Monte Carlo simulation for several objective functions for a given line. It is assumed that minimum voltage at all nodes has to be balanced to the maximum load served under variable distributed generation production, and to the energy produced from the intermittent renewables. The calculated maximum load, which is higher than the current load, is expected to cover the expected needs for electric vehicles charging. Following the proposed operational patterns, it is possible to have always maximum line capacity. This method is able to offer several benefits. It facilitates of network planning and the estimation of network robustness. It can be used as a tool for network planners, operators and large users. It applies to any type of network including radial and meshed.
Nonlinear Finite Element Analysis Formulation for Shear in Reinforced Concrete Beams
Authors: Kim Sang-Ho , Han Sun-Jin , Kim Kang
Published: August 2019

This study suggests a novel beam-column element formulation that utilizes an equilibrium-driven shear stress function. The beam shear is obtained from the bi-axial states of micro-planes, through matrix condensation and zero vertical traction assumptions. This properly remedies the shear stiffening of a one-dimensional beam-column element, keeping its degrees of freedom to a minimum. For verification of the proposed method, a total of seven shear test results of reinforced concrete (RC) beams were collected from the literature, in which the key variables were the reinforcement ratio, the presence of shear reinforcement, and section shape. The advantages are clearly shown in the shear stresses distributions being accurately described and the global load-displacement relations being successfully obtained and matching well with various test results. The proposed model shows satisfactory descriptions of the monotonic load-displacement response of the RC beams failing in multiple modes that vary from diagonal-tension to flexural-compression. In addition, more accurate and reliable information of sectional responses including sectional shear deformation and stresses is collected, leading to better prediction of a potential shear failure mode. Finally, the advantages of the proposed model are demonstrated by comparing the analysis results of an RCT-beam by using the different shear assumptions that include the constant and parabolic shear strains, constant shear flow, and the proposed shear stress function.
Direct Treatment of Liquids Using Low-Current Arc in Ambient Air for Biomedical Applications
Authors: Gamaleev Vladislav , Iwata Naoyuki , Hori Masaru , Hiramatsu Mineo , Ito Masafumi
Published: August 2019

In this work, we developed a portable device with low production and operation costs for generating an ambient air low-current arc (AALCA) that is transferred to the surface of a treated liquid. It was possible to generate a stable discharge, irrespective of the conductivity of the treated liquid, as a sequence of corona, repeating spark, and low-current arc discharges. The estimated concentration of reactive oxygen and nitrogen species (RONS) in plasma-treated water (PTW) produced using AALCA treatment was two orders of magnitude higher than that of PTW produced using conventional He nonequilibrium atmospheric pressure plasma jets or dielectric barrier discharges. The strong bactericidal effect of the treatment using AALCA and the water treated using AALCA was confirmed by survival tests of Escherichia coli. Further, the possibility of treating a continuous flow of liquid using AALCA was demonstrated.
A Low-Cost and Portable Smart Instrumentation for Detecting Colorectal Cancer Cells
Authors: Alam Mohammad Wajih , Wahid Khan A. , Fahmid Islam Md. , Bernhard Wendy , Geyer Clarence R. , Vizeacoumar Franco J.
Published: August 2019

Fluorescence imaging is a well-known method for monitoring fluorescence emitted from the subject of interest and provides important insights about cell dynamics and molecules in mammalian cells. Currently, many solutions exist for measuring fluorescence, but the application methods are complex and the costs are high. This paper describes the design and development of a low-cost, smart and portable fluorimeter for the detection of colorectal cancer cell expressing IRFP702. A flashlight is used as a light source, which emits light in the visible range and acts as an excitation source, while a photodiode is used as a detector. It also uses a longpass filter to only allow the wavelength of interest to pass from the cultured cell. It eliminates the need of both the dichroic mirror and excitation filter, which makes the developed device low cost, compact and portable as well as lightweight. The custom-built sample chamber is black in color to minimize interference and is printed with a 3D printer to accommodate the detector circuitry. An established colorectal cancer cell line (human colorectal carcinoma (HCT116)) was cultured in the laboratory environment. A near-infrared fluorescent protein IRFP702 was expressed in the colorectal cancer cells that were used to test the proof-of-concept. The fluorescent cancer cells were first tested with a commercial imaging system (Odyssey® CLx) and then with the developed prototype to validate the result in a preclinical setting. The developed fluorimeter is versatile as it can also be used to detect multiple types of cancer cells by simply replacing the filters based on the fluorophore.
Investigation on Residual Stress Loss during Laser Peen Texturing of 316L Stainless Steel
Authors: Li Kangmei , Wang Yifei , Cai Yu , Hu Jun
Published: August 2019

Laser peen texturing (LPT) is a novelty way of surface texturing based on laser shock processing. One of the most important benefits of LPT is that it can not only fabricate surface textures but also induce residual compressive stress for the target material. However, the residual stress loss leads to partial loss of residual compressive stress and even causes residual tensile stress at the laser spot center. This phenomenon is not conducive to improving the mechanical properties of materials. In this study, a numerical simulation model of LPT was developed and validated by comparison of surface deformation with experiments. In order to investigate the phenomenon of residual stress loss quantitatively, an evaluation method of residual stress field was proposed. The effects of laser power density and laser spot radius on the residual stress, especially the residual stress loss, were systematically investigated. It is found that with the increase of laser power density or laser spot radius, the thickness of residual compressive layer in depth direction becomes larger. However, both the magnitude and the affecting zone size of residual stress loss will be increased, which implies a more severe residual stress loss phenomenon.
Editorial on the Current Role of Ultrasound
Authors: Dietrich Christoph F. , Sirlin Claude B. , O’Boyle Mary , Dong Yi , Jenssen Christian
Published: August 2019

Ultrasound (US) is an important imaging tool and the most commonly used imaging modality worldwide. Although US requires expertise to be performed at the highest quality levels, basic US exams can be learned by most physicians and medical technologists with knowledge of human anatomy and with physical examination skills. The full potential of US is achieved when it is more than a pure “imaging modality”, but instead an integrated clinical, physical, and imaging assessment in which the examiner interacts directly and personally with the patient. Specific diagnostic US knowledge is strongly encouraged for specialist training in clinical disciplines.
Water Pathways for the Hindu-Kush-Himalaya and an Analysis of Three Flood Events
Authors: Boschi Robert , Lucarini Valerio
Published: August 2019

The climatology of major sources and pathways of moisture for three locales along the Hindu-Kush-Himalayan region are examined, by use of Lagrangian methods applied to the ERA-Interim dataset, over the period from 1980 to 2016 for both summer (JJA) and winter (NDJ) periods. We also investigate the major flooding events of 2010, 2013, and 2017 in Pakistan, Uttarakhand, and Kathmandu, respectively, and analyse a subset of the climatology associated with the 20 most significant rainfall events over each region of interest. A comparison is made between the climatology and extreme events, in the three regions of interest, during the summer monsoon period. For Northern Pakistan and Uttarakhand, the Indus basin plays the largest role in moisture uptake. Moisture is also gathered from Eastern Europe and Russia. Extreme events display an increased influence of sub-tropical weather systems, which manifest themselves through low-level moisture transport; predominantly from the Arabian sea and along the Gangetic plain. In the Kathmandu region, it is found that the major moisture sources come from the Gangetic plain, Arabian Sea, Red Sea, Bay of Bengal, and the Indus basin. In this case, extreme event pathways largely match those of the climatology, although an increased number of parcels originate from the western end of the Gangetic plain. These results provide insights into the rather significant influence of mid-latitudinal weather systems, even during the monsoon season, in defining the climatology of the Hindu-Kush-Himalaya region, as well as how extreme precipitation events in this region represent atypical moisture pathways. We propose a detailed investigation of how such water pathways are represented in climate models for the present climate conditions and in future climate scenarios, as this may be extremely relevant for understanding the impacts of climate change on the cryosphere and hydrosphere of the region.
Microsyntenic Clusters Reveal Conservation of lncRNAs in Chordates Despite Absence of Sequence Conservation
Authors: Herrera-Úbeda Carlos , Marín-Barba Marta , Navas-Pérez Enrique , Gravemeyer Jan , Albuixech-Crespo Beatriz , Wheeler Grant N. , Garcia-Fernàndez Jordi
Published: August 2019

Homologous long non-coding RNAs (lncRNAs) are elusive to identify by sequence similarity due to their fast-evolutionary rate. Here we develop LincOFinder, a pipeline that finds conserved intergenic lncRNAs (lincRNAs) between distant related species by means of microsynteny analyses. Using this tool, we have identified 16 bona fide homologous lincRNAs between the amphioxus and human genomes. We characterized and compared in amphioxus and Xenopus the expression domain of one of them, Hotairm1, located in the anterior part of the Hox cluster. In addition, we analyzed the function of this lincRNA in Xenopus, showing that its disruption produces a severe headless phenotype, most probably by interfering with the regulation of the Hox cluster. Our results strongly suggest that this lincRNA has probably been regulating the Hox cluster since the early origin of chordates. Our work pioneers the use of syntenic searches to identify non-coding genes over long evolutionary distances and helps to further understand lncRNA evolution.
Creatine for the Treatment of Depression
Authors: Kious Brent M. , Kondo Douglas G. , Renshaw Perry F.
Published: August 2019

Depressed mood, which can occur in the context of major depressive disorder, bipolar disorder, and other conditions, represents a serious threat to public health and wellness. Conventional treatments are not effective for a significant proportion of patients and interventions that are often beneficial for treatment-refractory depression are not widely available. There is, therefore, an immense need to identify novel antidepressant strategies, particularly strategies that target physiological pathways that are distinct from those addressed by conventional treatments. There is growing evidence from human neuroimaging, genetics, epidemiology, and animal studies that disruptions in brain energy production, storage, and utilization are implicated in the development and maintenance of depression. Creatine, a widely available nutritional supplement, has the potential to improve these disruptions in some patients, and early clinical trials indicate that it may have efficacy as an antidepressant agent.
Antioxidative Properties of Melanins and Ommochromes from Black Soldier Fly Hermetia illucens
Authors: Ushakova Nina , Dontsov Alexander , Sakina Natalia , Bastrakov Alexander , Ostrovsky Mikhail
Published: August 2019

A comparative study of melanin and ommochrome-containing samples, isolated from the black soldier fly (BSF) by enzymatic hydrolysis, alkaline and acid alcohol extraction or by acid hydrolysis, was carried out. Melanin was isolated both as a melanin-chitin complex and as a water-soluble melanin. Acid hydrolysis followed by delipidization yielded a more concentrated melanin sample, the electron spin resonance (ESR) signal of which was 2.6 × 1018 spin/g. The ommochromes were extracted from the BSF eyes with acid methanol. The antiradical activity of BSF melanins and ommochromes was determined by the method of quenching of luminol chemiluminescence. It has been shown that delipidization of water-soluble melanin increases its antioxidant properties. A comparison of the antioxidant activity of BSF melanins and ommochromes in relation to photoinduced lipid peroxidation was carried out. The ESR characteristics of native and oxidized melanins and ommochromes were studied. It is assumed that H. illucens adult flies can be a useful source of natural pigments with antioxidant properties.
The Breakthrough of Biosimilars: A Twist in the Narrative of Biological Therapy
Authors: Kabir Eva Rahman , Moreino Shannon Sherwin , Sharif Siam Mohammad Kawsar
Published: August 2019

The coming wave of patent expiries of first generation commercialized biotherapeutical drugs has seen the global market open its doors to close copies of these products. These near perfect substitutes, which are termed as “biosimilars”, do not need to undergo intense clinical trials for their approval. However, they are mandated to produce identical similarity from their reference biologics in terms of clinical safety and efficacy. As such, these biosimilar products promise to foster unprecedented access to a wide range of life-saving biologics. However, seeing this promise be fulfilled requires the development of biosimilars to be augmented with product trust, predictable regulatory frameworks, and sustainable policies. It is vital for healthcare and marketing professionals to understand the critical challenges surrounding biosimilar use and implement informed clinical and commercial decisions. A proper framework of pharmacovigilance, education, and scientific exchange for biologics and biosimilars would ensure a dramatic rise in healthcare access and market sustainability. This paper seeks to collate and review all relevant published intelligence of the health and business potential of biosimilars. In doing so, it provides a visualization of the essential steps that are required to be taken for global biosimilar acceptance.
Synthesis and Characterization of FITC Labelled Ruthenium Dendrimer as a Prospective Anticancer Drug
Authors: Michlewska Sylwia , Kubczak Małgorzata , Maroto-Díaz Marta , Sanz del Olmo Natalia , Ortega Paula , Shcharbin Dzmitry , Gomez Ramirez Rafael , Javier de la Mata Francisco , Ionov Maksim , Bryszewska Maria
Published: August 2019

Metallodendrimers—dendrimers with included metals—are widely investigated as biocompatible equivalents to metal nanoparticles. Applications can be expected in the fields of catalysis, as chemical sensors in molecular recognition and as anticancer drugs. Metallodendrimers can also mimic certain biomolecules, for example, haemoprotein in the case of using a dendrimer with a porphyrin core. In previous papers, we showed the promising anticancer effects of carbosilane ruthenium dendrimers. The present paper is devoted to studying biocompatibility and the cytotoxic effect on normal and cancer cells of carbosilane ruthenium dendrimers labelled with fluorescent probe fluorescein isothiocyanate (FITC). The addition of fluorescent probe allowed tracking the metallodendrimer in both normal and cancer cells. It was found that carbosilane ruthenium dendrimer labelled with FITC in concentration up to 10 µmol/L was more cytotoxic for cancer cells than for normal cells. Thus, FITC labelled carbosilane ruthenium dendrimer is a good candidate for diagnostic imaging and studying anticancer effects of metallodendrimers in cancer therapy.
Overview of Optical and Electrochemical Alkaline Phosphatase (ALP) Biosensors: Recent Approaches in Cells Culture Techniques
Authors: Balbaied Thanih , Moore Eric
Published: August 2019

Alkaline phosphatase (ALP), which catalyzes the dephosphorylation process of proteins, nucleic acids, and small molecules, can be found in a variety of tissues (intestine, liver, bone, kidney, and placenta) of almost all living organisms. This enzyme has been extensively used as a biomarker in enzyme immunoassays and molecular biology. ALP is also one of the most commonly assayed enzymes in routine clinical practice. Due to its close relation to a variety of pathological processes, ALP’s abnormal level is an important diagnostic biomarker of many human diseases, such as liver dysfunction, bone diseases, kidney acute injury, and cancer. Therefore, the development of convenient and reliable assay methods for monitoring ALP activity/level is extremely important and valuable, not only for clinical diagnoses but also in the area of biomedical research. This paper comprehensively reviews the strategies of optical and electrochemical detection of ALP and discusses the electrochemical techniques that have been addressed to make them suitable for ALP analysis in cell culture.
Biomarker-Based Signature of Alzheimer’s Disease in Pre-MCI Individuals
Authors: Chipi Elena , Salvadori Nicola , Farotti Lucia , Parnetti Lucilla
Published: August 2019

Alzheimer’s disease (AD) pathology begins decades before the onset of clinical symptoms. It is recognized as a clinicobiological entity, being detectable in vivo independently of the clinical stage by means of pathophysiological biomarkers. Accordingly, neuropathological studies that were carried out on healthy elderly subjects, with or without subjective experience of cognitive decline, reported evidence of AD pathology in a high proportion of cases. At present, mild cognitive impairment (MCI) represents the only clinically diagnosed pre-dementia stage. Several attempts have been carried out to detect AD as early as possible, when subtle cognitive alterations, still not fulfilling MCI criteria, appear. Importantly, pre-MCI individuals showing the positivity of pathophysiological AD biomarkers show a risk of progression similar to MCI patients. In view of successful treatment with disease modifying agents, in a clinical setting, a timely diagnosis is mandatory. In clinical routine, biomarkers assessment should be taken into consideration whenever a subject with subtle cognitive deficits (pre-MCI), who is aware of his/her decline, requests to know the cause of such disturbances. In this review, we report the available neuropsychological and biomarkers data that characterize the pre-MCI patients, thus proposing pre-MCI as the first clinical manifestation of AD.
Effects of Stathmin 1 Gene Knockout on Behaviors and Dopaminergic Markers in Mice Exposed to Social Defeat Stress
Authors: Nguyen Thong Ba , Prabhu Vishwanath Vasudev , Piao Yan Hong , Oh Young Eun , Zahra Rami Fatima , Chung Young-Chul
Published: August 2019

Stathmin (STMN), a microtubule-destabilizing factor, can regulate fear, anxiety, and learning. Social defeat stress (SDS) has detrimental effects on mental health and increases the risk of various psychiatric diseases. This study investigated the effects of STMN1 gene knockout (KO) on behavioral parameters and dopaminergic markers using an SDS mouse model. The STMN1 KO mice showed anxious hyperactivity, impaired object recognition, and decreased levels of neutral and social investigating behaviors at baseline compared to wild-type (WT) mice. The impact of SDS on neutral, social investigating and dominant behaviors differed markedly between the STMN1 WT and KO mice. In addition, different levels of total DARPP-32 and pDARPP-32 Thr75 expression were observed among the control, unsusceptible, and susceptible groups of STMN1 KO mice. Our results show that STMN1 has specific roles in locomotion, object recognition, and social interactions. Moreover, SDS had differential impacts on social interactions and dopaminergic markers between STMN1 WT and KO mice.
Metabolic Abnormalities in Glioblastoma and Metabolic Strategies to Overcome Treatment Resistance
Authors: Zhou Weihua , Wahl Daniel R.
Published: August 2019

Glioblastoma (GBM) is the most common and aggressive primary brain tumor and is nearly universally fatal. Targeted therapy and immunotherapy have had limited success in GBM, leaving surgery, alkylating chemotherapy and ionizing radiation as the standards of care. Like most cancers, GBMs rewire metabolism to fuel survival, proliferation, and invasion. Emerging evidence suggests that this metabolic reprogramming also mediates resistance to the standard-of-care therapies used to treat GBM. In this review, we discuss the noteworthy metabolic features of GBM, the key pathways that reshape tumor metabolism, and how inhibiting abnormal metabolism may be able to overcome the inherent resistance of GBM to radiation and chemotherapy.
L19-IL2 Immunocytokine in Combination with the Anti-Syndecan-1 46F2SIP Antibody Format: A New Targeted Treatment Approach in an Ovarian Carcinoma Model
Authors: Orecchia Paola , Balza Enrica , Pietra Gabriella , Conte Romana , Bizzarri Nicolò , Ferrero Simone , Mingari Maria Cristina , Carnemolla Barbara
Published: August 2019

Epithelial ovarian cancer (EOC) is the fifth most common cancer affecting the female population. At present, different targeted treatment approaches may improve currently employed therapies leading either to the delay of tumor recurrence or to disease stabilization. In this study we show that syndecan-1 (SDC1) and tumor angiogenic-associated B-fibronectin isoform (B-FN) are involved in EOC progression and we describe the prominent role of SDC1 in the vasculogenic mimicry (VM) process. We also investigate a possible employment of L19-IL2, an immunocytokine specific for B-FN, and anti-SDC1 46F2SIP (small immuno protein) antibody in combination therapy in a human ovarian carcinoma model. A tumor growth reduction of 78% was obtained in the 46F2SIP/L19-IL2-treated group compared to the control group. We observed that combined treatment was effective in modulation of epithelial-mesenchymal transition (EMT) markers, loss of stemness properties of tumor cells, and in alleviating hypoxia. These effects correlated with reduction of VM structures in tumors from treated mice. Interestingly, the improved pericyte coverage in vascular structures suggested that combined therapy could be efficacious in induction of vessel normalization. These data could pave the way for a possible use of L19-IL2 combined with 46F2SIP antibody as a novel therapeutic strategy in EOC.
Enrichment of Aldolase C Correlates with Low Non-Mutated IDH1 Expression and Predicts a Favorable Prognosis in Glioblastomas
Authors: Chang Yu-Chan , Tsai Hsing-Fang , Huang Shang-Pen , Chen Chi-Long , Hsiao Michael , Tsai Wen-Chiuan
Published: August 2019

The aldolases family is one of the main enzymes involved in the process of glycolysis. Aldolase C (ALDOC), which belongs to the aldolase family, is found in normal brain tissue and is responsible for the repair of injured tissue. However, the role of ALDOC in glioblastoma remains unclear. In this study, we data-mined in silico databases to evaluate aldolase family members’ mRNA expression in glioblastoma patient cohorts for determining its prognostic values. After that, we also performed immunohistochemical stain (IHC) analysis to evaluate protein expression levels of ALDOC in glioblastoma tissues. From The Cancer Genome Atlas (TCGA) database analyses, higher mRNA expression levels in normal brain tissue compared to glioblastoma was observed. In addition, compared to low-grade glioma, ALDOC expression was significantly downregulated in high-grade glioblastoma. Besides, the expression level of ALDOC was associated with molecular subtypes of glioblastomas and recurrent status in several data sets. In contrast, aldolase A (ALDOA) and aldolase B (ALDOB) revealed no significant prognostic impacts in the glioblastoma cohorts. Furthermore, we also proved that ALDOC mRNA and protein expression inversely correlated with non-mutated IDH1 expressions in glioblastoma patient cohorts. Additionally, the concordance of low ALDOC and high non-mutated IDH1 expressions predicted a stronger poor prognosis in glioblastoma patients compared to each of above tests presented alone. The plausible ALDOC and IDH1 regulatory mechanism was further elucidated. Our results support high ALDOC expression in glioblastomas that might imply the mutated status of IDH1, less possibility of mesenchymal subtype, and predict a favorable prognosis.
Trends in Overall Survival and Treatment Patterns in Two Large Population-Based Cohorts of Patients with Breast and Colorectal Cancer
Authors: van Abbema Doris , Vissers Pauline , de Vos-Geelen Judith , Lemmens Valery , Janssen-Heijnen Maryska , Tjan-Heijnen Vivianne
Published: August 2019

Previous studies showed substantial improvement of survival rates in patients with cancer in the last two decades. However, lower survival rates have been reported for older patients compared to younger patients. In this population-based study, we analyzed treatment patterns and the survival of patients with breast cancer (BC) and colorectal cancer (CRC). Patients with stages I–III BC and CRC and diagnosed between 2003 and 2012 were selected from the Netherlands Cancer Registry (NCR). Trends in treatment modalities were evaluated with the Cochran-Armitage trend test. Trends in five-year overall survival were calculated with the Cox hazard regression model. The Ederer II method was used to calculate the five-year relative survival. The relative excess risk of death (RER) was estimated using a multivariate generalized linear model. During the study period, 98% of BC patients aged <75 years underwent surgery, whereas for patients ≥75 years, rates were 79.3% in 2003 and 66.7% in 2012 (p < 0.001). Most CRC patients underwent surgery irrespective of age or time period, although patients with rectal cancer aged ≥75 years received less surgery or radiotherapy over the entire study period than younger patients. The administration of adjuvant chemotherapy increased over time for CRC and BC patients, except for BC patients aged ≥75 years. The five-year relative survival improved only in younger BC patients (adjusted RER 0.95–0.96 per year), and was lower for older BC patients (adjusted RER 1.00, 95% Confidence Interval (CI) 0.98–1.02, and RER 1.00; 95% CI 0.98–1.01 per year for 65–74 years and ≥75 years, respectively). For CRC patients, the five-year relative survival improved over time for all ages (adjusted RER on average was 0.95 per year). In conclusion, the observed survival trends in BC and CRC patients suggest advances in cancer treatment, but with striking differences in survival between older and younger patients, particularly for BC patients.
Role of the Microenvironment in Regulating Normal and Cancer Stem Cell Activity: Implications for Breast Cancer Progression and Therapy Response
Authors: Bhat Vasudeva , Allan Alison L. , Raouf Afshin
Published: August 2019

The epithelial cells in an adult woman’s breast tissue are continuously replaced throughout their reproductive life during pregnancy and estrus cycles. Such extensive epithelial cell turnover is governed by the primitive mammary stem cells (MaSCs) that proliferate and differentiate into bipotential and lineage-restricted progenitors that ultimately generate the mature breast epithelial cells. These cellular processes are orchestrated by tightly-regulated paracrine signals and crosstalk between breast epithelial cells and their tissue microenvironment. However, current evidence suggests that alterations to the communication between MaSCs, epithelial progenitors and their microenvironment plays an important role in breast carcinogenesis. In this article, we review the current knowledge regarding the role of the breast tissue microenvironment in regulating the special functions of normal and cancer stem cells. Understanding the crosstalk between MaSCs and their microenvironment will provide new insights into how an altered breast tissue microenvironment could contribute to breast cancer development, progression and therapy response and the implications of this for the development of novel therapeutic strategies to target cancer stem cells.
The PI3K/AKT/mTOR and CDK4/6 Pathways in Endocrine Resistant HR+/HER2− Metastatic Breast Cancer: Biological Mechanisms and New Treatments
Authors: Presti Daniele , Quaquarini Erica
Published: August 2019

Endocrine-based treatments are the normal standard-of-care in women with hormone receptor-positive/Human Epidermal growth factor Receptor 2-negative metastatic breast cancer. Despite the well-known efficacy of these drugs as first-line therapies, about 50% of women develop endocrine resistance and disease progression. The treatment of these patients has represented one of the most important research fields in the last few years, with several multicenter phase II/III trials published or still ongoing. Novel therapies, such as cyclin-dependent kinase (CDK)4/6 and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) inhibitors, have significantly changed the prognosis of patients progressing to a previous endocrine treatment, allowing a great benefit in terms of progression-free survival and, in some cases, of overall survival. However, identifying response predictors is essential for the rational use of these drugs to avoid unnecessary toxicity and costs, and to ensure the optimal therapeutic sequence is used. In this review, we analyze the PI3K/AKT/mTOR and CDK4/6 pathways and their roles in endocrine resistant metastatic breast cancer. We then focus on the new treatments developed and the roles of these drugs in overcoming endocrine resistance, describing the latest clinical trials that led to the approval of the drugs in clinical practice.
Novel Carbazole-Piperazine Hybrid Small Molecule Induces Apoptosis by Targeting BCL-2 and Inhibits Tumor Progression in Lung Adenocarcinoma In Vitro and Xenograft Mice Model
Authors: Mongre Raj Kumar , Mishra Chandra Bhushan , Prakash Amresh , Jung Samil , Lee Beom Suk , Kumari Shikha , Hong Jin Tae , Lee Myeong-Sok
Published: August 2019

Lung cancer is a type of deadly cancer and a leading cause of cancer associated death worldwide. BCL-2 protein is considered as an imperative target for the treatment of cancer due to their significant involvement in cell survival and death. A carbazole-piperazine hybrid molecule ECPU-0001 was designed and synthesized as a potent BCL-2 targeting agent with effective anticancer cancer activity. Interaction of ECPU-001 has been assessed by docking, molecular dynamics (MD) simulation, and thermal shift assay. Further, in vitro and in vivo anticancer activity was executed by cytotoxicity assay, FACS, colony formation and migration assay, western blotting, immunocyto/histochemistry and xenograft nude mice model. Molecular docking and MD simulation study confirmed that ECPU-0001 nicely interacts with the active site of BCL-2 by displaying a Ki value of 5.72 µM and binding energy (ΔG) of –8.35 kcal/mol. Thermal shift assay also validated strong interaction of this compound with BCL-2. ECPU-0001 effectively exerted a cytotoxic effect against lung adenocarnoma cells A459 with an IC50 value of 1.779 µM. Molecular mechanism of action have also been investigated and found that ECPU-0001 induced apoptosis in A459 cell by targeting BCL-2 to induce intrinsic pathway of apoptosis. Administration of ECPU-0001 significantly inhibited progression of tumor in a xenograft model without exerting severe toxicity and remarkably reduced tumor volume as well as tumor burden in treated animals. Our investigation bestowed ECPU-0001 as an effective tumoricidal agent which exhibited impressive anticancer activity in vitro as well as in vivo by targeting BCL-2 associated intrinsic pathway of apoptosis. Thus, ECPU-0001 may provide a valuable input for therapy of lung adenosarcoma in future, however, further extensive investigation of this compound will be needed.
Gastric Normal Adjacent Mucosa Versus Healthy and Cancer Tissues: Distinctive Transcriptomic Profiles and Biological Features
Authors: Russi Sabino , Calice Giovanni , Ruggieri Vitalba , Laurino Simona , La Rocca Francesco , Amendola Elena , Lapadula Cinzia , Compare Debora , Nardone Gerardo , Musto Pellegrino , De Felice Mario , Falco Geppino , Zoppoli Pietro
Published: August 2019

Gastric cancer (GC) is a leading cause of cancer-related deaths in the world. Molecular heterogeneity is a major determinant for the clinical outcomes and an exhaustive tumor classification is currently missing. Histologically normal tissue adjacent to the tumor (NAT) is commonly used as a control in cancer studies, nevertheless a recently published paper described the unique characteristics of the NAT in several tumor types. Little is known about the global gene expression profile of gastric NAT (gNAT) which could be an effective tool for a more realistic definition of GC molecular signature. Here, we integrated data of 512 samples from the Genotype-Tissue Expression project (GETx) and The Cancer Genome Atlas (TCGA) to analyze the transcriptome of healthy gastric tissues, gNAT, and GC samples. We validated TCGA-GETx data mining through inHouse gNAT and GC expression dataset. Differential gene expression together with pathway enrichment analyses, indeed, led to different results when using the gNAT or the healthy tissue as control. Based on our analyses, gNAT showed a peculiar gene signature and biological features, like the estrogen receptor pathways activation, suggesting a molecular behavior partially different from both healthy and GC tissues. Therefore, using gNAT as healthy control tissue in the characterization of tumor associated biological processes and pathways could lead to suboptimal results.