bluuebunny/crossref_metadata_2025 huggingface dataset:
New Directions in Macroeceonomics
Authors: BAŞÇI Sıdıka , ZAMAN Asad
Published: June 2020

The glaring failure of modern macroeconomics to predict the Global Financial Crisis, and to provide remedies for the Great Recession which followed, has led to renewed interest in alternative approaches to Macroeconomics. There is huge amount of ongoing work aimed at creating a Macroeconomics for the 21st Century. The task is of the highest priority, as failures of economic theory have led to misery for millions. Wrong measures of GDP, and cost-benefit calculation which fail to account for environmental costs, and prioritize private profits over social welfare, have created a climate catastrophe which threatens to destroy the planet. In accordance with the importance of this task, we are expanding the scope of this journal, to cover all new approaches to economics, which fall outside of the boxes of conventional macro, micro, and econometrics of the 20th Century. This article outlines seven broad categories of research directions, and four different methodological principles which fall outside the boundaries of the conventional approach, and offer promise for building a Macroeconomics for the 21st Century. We hope to invite contributions in these areas for future issues.
Models and Reality: How Did Models Divorced from Reality Become Epistemologically Acceptable?
Authors: ZAMAN Asad
Published: June 2020

Economic models translate real problems to an artificial world, and calculate outcomes. The match between artificial worlds populated by rational robots, and the real world, is never assessed. Instead, models are judged on aesthetic grounds, involving conformity to preconceived principles of optimization and equilibrium. Despite methodological proclamations to the contrary, models are not judged by predictive performance. Economics models are formulated axiomatically, and never cross-checked against reality. Taking this (controversial) characterization of economic methodology for granted, this paper sketches trends in philosophy of science which led to a methodology which permits creation of mental models disconnected from reality. A key development was the separation of the observable phenomena from the underlying reality (noumena) which eventually allowed empiricist philosophers to jettison the underlying reality as part of what good models attempt to describe. The paper discusses contemporary methodologies for assessing models in economics and econometrics, and explains why these lead to models disconnected from reality.
Virtual welding: A didactic perspective
Authors: Karstensen Steinar , Lier Arne Roar
Published: June 2020

This research was conducted as part of a Technical and Vocational Education and Training (TVET) programme in Technical and Industrial Production and is a collaboration between Aas upper secondary school in Akershus and the Department of Vocational Teacher Education at Oslo Metropolitan University (OsloMet). Starting in autumn 2017, simulated welding has been the first step in the use of simulation teaching in order to produce qualified professionals. In TVET education, Virtual Reality technology is a new training tool for welding, and little is known about the pedagogical approaches and didactic challenges.

This article is based on interviews that were conducted with teachers and their immediate supervisors to gain insight into their prior knowledge, the approaches they intended to use, and their initial experiences of the introduction of simulation-based teaching. The research consists primarily of qualitative analyses, based on a phenomenological approach. The focus for the article is the possibilities and limitations of a virtual welding machine, as well as how it might be introduced as an educational and didactic tool in upper secondary school.

The article provides useful knowledge for those who will be using some form of simulation in teaching in general and for simulated welding in particular. This applies to both current TVET teachers and those undergoing Technical and Vocational Teacher Education.
Aplikasi e-Health Berbasis Teknologi Smartphone dalam Monitoring Klien di Komunitas: Studi Literatur
Authors: Rohayati Rohayati
Published: June 2020

The e-health is information technology in the health systems that can be used by both health workers and clients. Ehealth applications can be based on computers, the internet or smartphones. This study aims to discuss the types of e-health that can be used for health monitoring using smartphones in community setting. Data collection was carried out through electronic database, namely EBSCO, Proquest, Sciencedirect, Scopus, Springerlink and Google Scholar. The e-health that can be used to carry out health promotion and monitor the health status of clients was remote mobile health monitoring. This application was integrated with the internet and smartphone so that clients and health workers can monitor the development of the client's health status. The application that can be used to document medical history was a personal health record both internet and computer integrated so that it can be accessed by clients. Community nurses and primary care institutions are expected to be able to design and use this application to monitor and record the health status of clients in the community.

Keywords: e-health in community; smartphone; personal health records

ABSTRAK

Teknologi e-health merupakan teknologi informasi di bidang kesehatan yang dapat digunakan baik oleh petugas kesehatan maupun klien. Aplikasi e-health dapat berbasis komputer, internet maupun smartphone. Studi ini bertujuan untuk membahas jenis-jenis e-health yang dapat digunakan untuk monitoring kesehatan menggunakan smartphone. Pengumpulan data dilakukan melalui telaah literatur jurnal elektronik yaitu EBSCO, Proquest, Science direct, Scopus, Springerlink dan Google Scholar. Teknologi e-health yang dapat digunakan untuk melakukan promosi kesehatan, memonitor status kesehatan klien adalah remote mobile health monitoring. Aplikasi ini terintegrasi dengan internet dan smartphone sehingga klien dan petugas kesehatan dapat memonitor perkembangan status kesehatan klien dimanapun berada. Aplikasi yang dapat digunakan untuk melakukan dokumentasi riwayat kesehatan adalah personal health record baik terintegrasi internet maupun komputer sehingga dapat diakses oleh klien. Perawat komunitas dan institusi pelayanan primer diharapkan dapat merancang dan menggunakan aplikasi ini untuk memonitor dan mencatat status kesehatan klien di masyarakat.

Kata kunci: e-health di komunitas; smartphone; personal health records
Pre – planned surgical Obturator prosthesis followed by a definitive ones: a requisite for rehabilitation- a case report.
Authors: Naisargi Shah , Badwaik Praveen , Khanna Anshul , Patil Prashant , Deshmukh Kiran
Published: June 2020

Effective obturation of the maxillectomy defect is a challenging task for the maxillofacial prosthodontist. Multidisciplinary treatment planning is essential to achieve adequate retention and function for the prosthesis. The demand for maxillofacial prosthetic devices for the rehabilitation of patients with congenital or acquired (post-surgical, post-trauma) defects has intensified in recent years. Most of the difficulties can be overcome, to an extent, with the placement of an immediate surgical obturator. This clinical report describes the fabrication of a pre-planned surgical template (immediate surgical obturator) which uses patient’s original occlusion and tooth position, made prior to the surgical resection and inserted at the time of surgery, to provide the patient with the additional benefits of masticatory efficiency, aesthetics and psychological comfort during the healing period followed by a definitive soft liner bulb obturator to accommodate resected lesion post surgery.

Keywords: Mucormycosis, surgical template, obturator, silicone based permanent denture soft liner.
PERIPHERAL OSSIFYING FIBROMA OF MANDIBULAR ANTERIOR GINGIVA IN A YOUNG BOY – A CASE REPORT
Authors: S Jayachandran , Jeba Priya Sophia , M Archana
Published: June 2020

Peripheral ossifying fibroma is one of the common reactive oral lesions which accounts for about 9.6% of all gingival lesions. There is a predilection for females in the second to fourth decade of life. Most lesions are less than 2 cm in size, although larger ones occasionally occur. The raised lesion may appear smooth or ulcerated and most often is caused by constant irritation or trauma. The growth-like clinical presentation may lead to misclassification; however, the histologic appearance is quite diagnostic for this lesion. In this case report we are discussing the case of a young male patient with peripheral ossifying fibroma in the mandibular anterior region which was managed by complete surgical excision.

Key Words: Peripheral ossifying fibroma, reactive lesion, mandibular gingiva
Comparison between Scalpel and Laser technique for gingival depigmentation-A Split mouth study.
Authors: Tambe Lashika , Gaikwad Rajesh , Patil Chitra , Borade Shrutika B.
Published: June 2020

INTRODUCTION

An esthetic smile is a perfect balance between hard and soft tissues of the mouth. Gingiva plays an important role in the esthetic appearance of an individual. Gingival pigmentation is considered to be unaesthetic by patients, and it may have a psychological impact on them. Gingival depigmentation is a periodontal plastic surgery procedure, and variety of depigmentation techniques have been described in the literature. The aim of this study was to compare the efficacy of diode laser and scalpel in gingival depigmentation procedure.

MATERIAL AND METHOD
A total of 12 patients with age range between 20 -40 years were selected in the randamized, split mouth study. The maxillary arch was divided into two segments: 1.Segment I- right ﬁrst premolar to right central incisors. 2.Segment II- left ﬁrst premolar to left central incisors. These two segments were randomly assigned to surgical scalpel and diode laser techniques modalities. The research included the following clinical evaluation parameters at baseline and 3 months: Dummet Oral Pigmentation Index (DOPI) by Dummet and Gupta (1964)and VAS for pain.

RESULTS
There is clinically no significant difference between the Dummet Oral Pigmentation Index (DOPI)and Visual analogue scale for pain between Laser and Scalpel for gingival depigmentation.

CONCLUSION
Therefore, within the limitation of this study it can be concluded that scalpel technique is still considered the gold standard treatment for gingival depigmentation.

KEY WORDS- diode laser, Visual analogue scale (VAS), Dummet Oral Pigmentation Index (DOPI).
Rapidly Exploring Random Tree Algorithm-Based Path Planning for Worm-Like Robot
Authors: Wang Yifan , Pandit Prathamesh , Kandhari Akhil , Liu Zehao , Daltorio Kathryn A.
Published: June 2020

Inspired by earthworms, worm-like robots use peristaltic waves to locomote. While there has been research on generating and optimizing the peristalsis wave, path planning for such worm-like robots has not been well explored. In this paper, we evaluate rapidly exploring random tree (RRT) algorithms for path planning in worm-like robots. The kinematics of peristaltic locomotion constrain the potential for turning in a non-holonomic way if slip is avoided. Here we show that adding an elliptical path generating algorithm, especially a two-step enhanced algorithm that searches path both forward and backward simultaneously, can make planning such waves feasible and efficient by reducing required iterations by up around 2 orders of magnitude. With this path planner, it is possible to calculate the number of waves to get to arbitrary combinations of position and orientation in a space. This reveals boundaries in configuration space that can be used to determine whether to continue forward or back-up before maneuvering, as in the worm-like equivalent of parallel parking. The high number of waves required to shift the body laterally by even a single body width suggests that strategies for lateral motion, planning around obstacles and responsive behaviors will be important for future worm-like robots.
Combining Coordination and Hydrogen Bonds to Develop Discrete Supramolecular Metalla-Assemblies
Authors: Therrien Bruno
Published: June 2020

In Nature, metal ions play critical roles at different levels, and they are often found in proteins. Therefore, metal ions are naturally incorporated in hydrogen-bonded systems. In addition, the combination of metal coordination and hydrogen bonds have been used extensively to develop supramolecular materials. However, despite this win-win combination between coordination and hydrogen bonds in many supramolecular systems, the same combination remains scarce in the field of coordination-driven self-assemblies. Indeed, as illustrated in this mini-review, only a few discrete supramolecular metalla-assemblies combining coordination and hydrogen bonds can be found in the literature, but that figure might change rapidly.
Model Based Approach to Cyber–Physical Systems Status Monitoring
Authors: Vodyaho Alexander , Abbas Saddam , Zhukova Nataly , Chervoncev Michael
Published: June 2020

The distinctive feature of new generation information systems is not only their complexity in terms of number of elements, number of connections and hierarchy levels, but also their constantly changing structure and behavior. In this situation the problem of receiving actual information about the observed complex Cyber–Physical Systems (CPS) current status becomes a rather difficult task. This information is needed by stakeholders for solving tasks concerning keeping the system operational, improving its efficiency, ensuring security, etc. Known approaches to solving the problem of the complex distributed CPS actual status definition are not enough effective. The authors propose a model based approach to solving the task of monitoring the status of complex CPS. There are a number of known model based approaches to complex distributed CPS monitoring, but their main difference in comparison with the suggested one is that known approaches by the most part use static models which are to be build manually by experts. It takes a lot of human efforts and often results in errors. Our idea is that automata models of structure and behavior of the observed system are used and both of these models are built and kept in actual state in automatic mode on the basis of log file information. The proposed approach is based, on one hand, on the results of the authors researches in the field of automatic synthesis of multi-level automata models of observed systems and, on the other hand, on well known algorithms of process mining. In the paper typical monitoring tasks are described and generalized algorithms for solving them using the proposed system of models are presented. An example of real life systems based on the suggested approach is given. The approach can be recommended to use for building CPS of medium and high complexity, characterized by high structural dynamics and cognitive behavior.
Informational Reinterpretation of the Mechanics Notions and Laws
Authors: Bormashenko Edward
Published: June 2020

The informational re-interpretation of the basic laws of the mechanics exploiting the Landauer principle is suggested. When a physical body is in rest or it moves rectilinearly with the constant speed, zero information is transferred; thus, the informational affinity of the rest state and the rectilinear motion with a constant speed is established. Inertial forces may be involved in the erasure/recording of information. The analysis of the minimal Szilard thermal engine as seen from the noninertial frame of references is carried out. The Szilard single-particle minimal thermal engine undergoes isobaric expansion relative to accelerated frame of references, enabling the erasure of 1 bit of information. The energy ΔQ spent by the inertial force for the erasure of 1 bit of information is estimated as Δ Q ≅ 5 3 k B T ¯ , which is larger than the Landauer bound but qualitatively is close to it. The informational interpretation of the equivalence principle is proposed: the informational content of the inertial and gravitational masses is the same.
Bounds on the Transmit Power of b-Modulated NFDM Systems in Anomalous Dispersion Fiber
Authors: Chimmalgi Shrinivas , Wahls Sander
Published: June 2020

The performance of various nonlinear frequency division multiplexed (NFDM) fiber-optic transmission systems has been observed to decrease with increasing signal duration. For a class of NFDM systems known as b-modulators, we show that the nonlinear bandwidth, signal duration, and power are coupled when singularities in the nonlinear spectrum are avoided. When the nonlinear bandwidth is fixed, the coupling results in an upper bound on the transmit power that decreases with increasing signal duration. Signal-to-noise ratios are consequently expected to decrease, which can help explain drops in performance observed in practice. Furthermore, we show that there is often a finite bound on the transmit power of b-modulators even if spectral singularities are allowed.
Simple Power Quality Compensation with Bidirectional Battery Charger for Electric Vehicles in Single-Phase Three-Wire Distribution Feeders
Authors: Ikeda Fuka , Nishikawa Kei , Okamoto Yuki , Yamada Hiroaki , Tanaka Toshihiko , Okamoto Masayuki
Published: June 2020

This paper deals with power quality compensation in single-phase three-wire distribution feeders using a constant DC-capacitor voltage-control (CDCVC)-based strategy of the previously proposed bidirectional battery charger (BBC) for electric vehicles under the distorted source-voltage and load-current conditions. Instantaneous active power flowing into the three-leg pulse-width-modulated (PWM) rectifier in the BBC is discussed. The instantaneous power flowing into the three-leg PWM rectifier demonstrates that the CDCVC-based strategy obtains balanced and sinusoidal source currents at a unity power factor, where the source-side active power is balanced with the load-side active power. Simulation and experimental results demonstrate that balanced and sinusoidal source currents at a unity power factor are attained in single-phase three-wire distribution feeders with both battery-charging and -discharging operations for electric vehicles even though both source voltage and load currents are distorted.
Carbazole Electroactive Amorphous Molecular Material: Molecular Design, Synthesis, Characterization and Application in Perovskite Solar Cells
Authors: Magaldi Diego , Ulfa Maria , Péralta Sébastien , Goubard Fabrice , Pauporté Thierry , Bui Thanh-Tuân
Published: June 2020

In perovskite photovoltaics (PSCs), the role of the hole transporting material (HTM) is highly important as it significantly influents to the global device’s performance and stability. Hole transporter ensures the extraction of hole at the perovskite/HTM interface and transport it towards the cathode. Thus, accurate molecular design affording to efficient and cost-effective HTM is of major interest. Small molecules having glass forming property is an attractive class as it can form morphologically stable thin film. Herein, a carbazole molecular glass bearing a polymerizable function was designed and synthetized. Its characteristics are suitable for application as HTM in PSCs. The preliminary photovoltaic application lead to device efficiency of 14–15% depending on the chemical composition of the perovskite employed. These promising results open the way to design new alternative molecular and polymeric HTMs suitable for solution processed hybrid solar cells.
Phytoremediation—From Environment Cleaning to Energy Generation—Current Status and Future Perspectives
Authors: Grzegórska Anna , Rybarczyk Piotr , Rogala Andrzej , Zabrocki Dawid
Published: June 2020

Phytoremediation is a technology based on the use of green plants to remove, relocate, deactivate, or destroy harmful environmental pollutants such as heavy metals, radionuclides, hydrocarbons, and pharmaceuticals. Under the general term of phytoremediation, several processes with distinctively different mechanisms of action are hidden. In this paper, the most popular modes of phytoremediation are described and discussed. A broad but concise review of available literature research with respect to the dominant process mechanism is provided. Moreover, methods of plant biomass utilization after harvesting, with particular regard to possibilities of “bio-ore” processing for metal recovery, or using energy crops as a valuable source for bio-energy production (bio-gas, bio-ethanol, bio-oil) are analyzed. Additionally, obstacles hindering the commercialization of phytoremediation are presented and discussed together with an indication of future research trends.
Efficiency Analysis and Integrated Design of Rocket-Augmented Turbine-Based Combined Cycle Engines with Trajectory Optimization
Authors: Guo Feng , Luo Wenguo , Gui Feng , Zhu Jianfeng , You Yancheng , Xing Fei
Published: June 2020

An integrated analysis method for a rocket-augmented turbine-based combined cycle (TBCC) engine is proposed based on the trajectory optimization method of the Gauss pseudospectral. The efficiency and energy of the vehicles with and without the rocket are analyzed. Introducing an appropriate rocket to assist the TBCC-powered vehicle will reduce the total energy consumption of drag, and increase the vehicle efficiency in the transonic and the mode transition. It results in an increase in the total efficiency despite a reduction in engine efficiency. Therefore, introducing a rocket as the auxiliary power is not only a practical solution to enable flight over a wide-speed range when the TBCC is incapable but also probably an economical scheme when the the TBCC meets the requirements of thrust. When the vehicle drag is low, the rocket works for a short time and its optimal relative thrust is small. Thus, the TBCC combined with a booster rocket will be a more simple and suitable scheme. When the vehicle drag is high, the operating time of the rocket is long and the optimal relative thrust is large. The specific impulse has a significant impact on the flight time and the total fuel consumption. Accordingly, the combination form for the rocket-based combined cycle (RBCC) engines and the turbine will be more appropriate to obtain higher economic performance.
A Novel Sparse Attack Vector Construction Method for False Data Injection in Smart Grids
Authors: Xia Meng , Du Dajun , Fei Minrui , Li Xue , Yang Taicheng
Published: June 2020

To improve the security of smart grids (SGs) by finding the system vulnerability, this paper investigates the sparse attack vectors’ construction method for malicious false data injection attack (FDIA). The drawbacks of the existing attack vector construction methods include avoiding discussing the feasible region and validity of the attack vector. For the above drawbacks, this paper has three main contributions: (1) To construct the appropriate attack evading bad data detection (BDD), the feasible region of the attack vector is proved by projection transformation theory. The acquisition of the feasible region can help the defender to formulate the defense strategy; (2) an effective attack is proposed and the constraint of effectiveness is obtained using norm theory; (3) the domain of the state variations caused by the attack vector in the feasible region is calculated, while the singular value decomposition method is adopted. Finally, an attack vector is constructed based on l 0 -norm using OMP algorithms in the feasible domain. Simulation results confirm the feasibility and effectiveness of the proposed technique.
Seasonal Energy Flexibility Through Integration of Liquid Sorption Storage in Buildings
Authors: Baldini Luca , Fumey Benjamin
Published: June 2020

The article estimates energy flexibility provided to the electricity grid by integration of long-term thermal energy storage in buildings. To this end, a liquid sorption storage combined with a compression heat pump is studied for a single-family home. This combination acts as a double-stage heat pump comprised of a thermal and an electrical stage. It lowers the temperature lift to be overcome by the electrical heat pump and thus increases its coefficient of performance. A simplified model is used to quantify seasonal energy flexibility by means of electric load shifting evaluated with a monthly resolution. Results are presented for unlimited and limited storage capacity leading to a total seasonal electric load shift of 631.8 kWh/a and 181.7 kWh/a, respectively. This shift, referred to as virtual battery effect, provided through long-term thermal energy storage is large compared to typical electric battery capacities installed in buildings. This highlights the significance of building-integrated long-term thermal energy storage for provision of energy flexibility to the electricity grid and hence for the integration of renewables in our energy system.
Smart Energy Management for Series Hybrid Electric Vehicles Based on Driver Habits Recognition and Prediction
Authors: Joud Loïc , Da Silva Rui , Chrenko Daniela , Kéromnès Alan , Le Moyne Luis
Published: June 2020

The objective of this work is to develop an optimal management strategy to improve the energetic efficiency of a hybrid electric vehicle. The strategy is built based on an extensive experimental study of mobility in order to allow trips recognition and prediction. For this experimental study, a dedicated autonomous acquisition system was developed. On working days, most trips are constrained and can be predicted with a high level of confidence. The database was built to assess the energy and power needed based on a static model for three types of cars. It was found that most trips could be covered by a 10 kWh battery. Regarding the optimization strategy, a novel real time capable energy management approach based on dynamic vehicle model was created using Energetic Macroscopic Representation. This real time capable energy management strategy is done by a combination of cycle prediction based on results obtained during the experimental study. The optimal control strategy for common cycles based on dynamic programming is available in the database. When a common cycle is detected, the pre-determined optimum strategy is applied to the similar upcoming cycle. If the real cycle differs from the reference cycle, the control strategy is adapted using quadratic programming. To assess the performance of the strategy, its resulting fuel consumption is compared to the global optimum calculated using dynamic programming and used as a reference; its optimality factor is above 98%.
Innovation Dynamics of Socio-Technical Alignment in Community Energy Storage: The Cases of DrTen and Ecovat
Authors: Koirala Binod Prasad , van Oost Ellen , van der Windt Henny
Published: June 2020

With energy transition gaining momentum, energy storage technologies are increasingly spotlighted as they can effectively handle mismatches in supply and demand. The decreasing cost of distributed energy generation technologies and energy storage technologies as well as increasing demand for local flexibility is opening up new possibilities for the deployment of energy storage technologies in local energy communities. In this context, community energy storage has potential to better integrate energy supply and demand at the local level and can contribute towards accommodating the needs and expectations of citizens and local communities as well as future ecological needs. However, there are techno-economical and socio-institutional challenges of integrating energy storage technologies in the largely centralized present energy system, which demand socio-technical innovation. To gain insight into these challenges, this article studies the technical, demand and political articulations of new innovative local energy storage technologies based on an embedded case study approach. The innovation dynamics of two local energy storage innovations, the seasalt battery of DrTen® and the seasonal thermal storage Ecovat®, are analysed. We adopt a co-shaping perspective for understanding innovation dynamics as a result of the socio-institutional dynamics of alignment of various actors, their articulations and the evolving network interactions. Community energy storage necessitates thus not only technical innovation but, simultaneously, social innovation for its successful adoption. We will assess these dynamics also from the responsible innovation framework that articulates various forms of social, environmental and public values. The socio-technical alignment of various actors, human as well as material, is central in building new socio-technical configurations in which the new storage technology, the community and embedded values are being developed.
Nebulization Criteria and Quantification
Authors: Hailu Nardos , Postema Michiel , Krejcar Ondrej , Assefa Dawit
Published: June 2020

The application of atomization technology is common in fields such as agriculture, cosmetics, environmental sciences, and medicine. Aerosolized drugs are administered using nebulizers to treat both pulmonary and nonpulmonary diseases. The characterization and measurement of nebulizers are of great significance in analyzing the performance and accuracy of the nebulizing system and the advancement of the technology. Nevertheless, the characterization of aerosols has been a long-standing challenge in scientific disciplines ranging from atmospheric physics to health sciences. The study of factors that influence nebulization has not been undertaken systematically using experimental techniques. Numerical modeling (NM) and computational fluid dynamics (CFD) can address such issues. This article provides a concise overview of the literature on the application of computational fluid dynamics to medical nebulizers and aerosol measurements.
A Pre-Existing Myogenic Temporomandibular Disorder Increases Trigeminal Calcitonin Gene-Related Peptide and Enhances Nitroglycerin-Induced Hypersensitivity in Mice
Authors: Shu Hui , Liu Sufang , Tang Yuanyuan , Schmidt Brian L. , Dolan John C. , Bellinger Larry L. , Kramer Phillip R. , Bender Steven D. , Tao Feng
Published: June 2020

Migraine is commonly reported among patients with temporomandibular disorders (TMDs), especially myogenic TMD. The pathophysiologic mechanisms related to the comorbidity of the two conditions remain elusive. In the present study, we combined masseter muscle tendon ligation (MMTL)-produced myogenic TMD with systemic injection of nitroglycerin (NTG)-induced migraine-like hypersensitivity in mice. Facial mechanical allodynia, functional allodynia, and light-aversive behavior were evaluated. Sumatriptan, an FDA-approved medication for migraine, was used to validate migraine-like hypersensitivity. Additionally, we examined the protein level of calcitonin gene-related peptide (CGRP) in the spinal trigeminal nucleus caudalis using immunohistochemistry. We observed that mice with MMTL pretreatment have a prolonged NTG-induced migraine-like hypersensitivity, and MMTL also enabled a non-sensitizing dose of NTG to trigger migraine-like hypersensitivity. Systemic injection of sumatriptan inhibited the MMTL-enhanced migraine-like hypersensitivity. MMTL pretreatment significantly upregulated the protein level of CGRP in the spinal trigeminal nucleus caudalis after NTG injection. Our results indicate that a pre-existing myogenic TMD can upregulate NTG-induced trigeminal CGRP and enhance migraine-like hypersensitivity.
Cell Type- and Sex-Specific Dysregulation of Thyroid Hormone Receptors in Placentas in Gestational Diabetes Mellitus
Authors: Knabl Julia , de Maiziere Lena , Hüttenbrenner Rebecca , Hutter Stefan , Jückstock Julia , Mahner Sven , Kainer Franz , Desoye Gernot , Jeschke Udo
Published: June 2020

Thyroid hormones are essential for development of trophoblasts and the fetus. They also regulate a wide range of metabolic processes. We investigated the influence of maternal gestational diabetes mellitus (GDM) on thyroid hormone receptor (THR) isoforms THRα1, THRα2, THRβ1 and THRβ2 of the human placenta in a sex- and cell-type specific manner. Term placental tissue was obtained from women with (n = 40) or without GDM (control; n = 40). THRs levels were measured by semi-quantitative immunohistochemistry and real-time qRT-PCR. We localized THR immunostaining in syncytiotrophoblast (SCT), which was the tissue with the strongest signal. Double immunofluorescence identified THR in decidual cells in the stroma and in extravillous cytotrophoblasts. GDM did not change THRα1 immunolabelling intensity in decidua, but was associated with a stronger immunolabelling in SCT compared to GDM (p < 0.05). The SCT difference of GDM vs. control was strongest (p < 0.01) in female placentas. THRα2 was only weakly present and immunolabelling was weaker (p < 0.05) in SCT of only male GDM placentas in comparison to male controls. THRβ1/β2 immunostaining was weak in all cell types without changes in GDM. However, more THRβ1/2 protein was present (p < 0.001) in male than female placentas. All these protein changes were paralleled by changes of THR transcript levels. The data show that THR are expressed in term trophoblast in relation to fetal sex. Maternal GDM influences predominantly THRα1 in SCT, with the strongest GDM effect in SCT of female placentas.
An Atomic Force Microscopy Study on the Effect of β-Galactosidase, α-l-Rhamnosidase and α-l-Arabinofuranosidase on the Structure of Pectin Extracted from Apple Fruit Using Sodium Carbonate
Authors: Pieczywek Piotr Mariusz , Cybulska Justyna , Zdunek Artur
Published: June 2020

The enzyme driven changes in plant cell wall structure during fruit ripening result in debranching, depolymerization and solubilization of pectin polysaccharides, which has an effect in terms of the postharvest quality losses in fruit. Atomic force microscopy (AFM) has revealed that diluted alkali soluble pectins (DASP) from fruit and vegetables have an interesting tendency to self-assemble into regular structures. However, the mechanism is not yet fully understood. The current study is aimed at investigating the role of neutral sugars, namely galactose, rhamnose and arabinose in the formation of the branched structure of DASP. β-galactosidase, α-l-rhamnosidase and α-l-arabinofuranosidase enzymes were used for the treatment of DASP extracted from Golden Delicious apple flesh (Malus domestica cv. Golden Delicious). The effects of the selective degradation of pectic polysaccharides after 15, 30, 60, 90 and 120 min of incubation were observed using AFM. The α-l-rhamnosidase enzyme activity on pectin extracted with Na2CO3 did not cause any visible or measurable degradation of the molecular structure. The moderate effects of β-galactosidase enzymatic treatment suggested the possible role of galactose in the branching of DASP molecules deposited on mica. Data obtained for α-l-arabinofuranosidase indicated the crucial role of arabinose in the formation and preservation of the highly branched structure of the DASP fraction.
Global View of Candidate Therapeutic Target Genes in Hormone-Responsive Breast Cancer
Authors: Salvati Annamaria , Gigantino Valerio , Nassa Giovanni , Mirici Cappa Valeria , Ventola Giovanna Maria , Cracas Daniela Georgia Cristina , Mastrocinque Raffaella , Rizzo Francesca , Tarallo Roberta , Weisz Alessandro , Giurato Giorgio
Published: June 2020

Breast cancer (BC) is a heterogeneous disease characterized by different biopathological features, differential response to therapy and substantial variability in long-term-survival. BC heterogeneity recapitulates genetic and epigenetic alterations affecting transformed cell behavior. The estrogen receptor alpha positive (ERα+) is the most common BC subtype, generally associated with a better prognosis and improved long-term survival, when compared to ERα-tumors. This is mainly due to the efficacy of endocrine therapy, that interfering with estrogen biosynthesis and actions blocks ER-mediated cell proliferation and tumor spread. Acquired resistance to endocrine therapy, however, represents a great challenge in the clinical management of ERα+ BC, causing tumor growth and recurrence irrespective of estrogen blockade. Improving overall survival in such cases requires new and effective anticancer drugs, allowing adjuvant treatments able to overcome resistance to first-line endocrine therapy. To date, several studies focus on the application of loss-of-function genome-wide screenings to identify key (hub) “fitness” genes essential for BC progression and representing candidate drug targets to overcome lack of response, or acquired resistance, to current therapies. Here, we review the biological significance of essential genes and relative functional pathways affected in ERα+ BC, most of which are strictly interconnected with each other and represent potential effective targets for novel molecular therapies.
Molecular Modeling of Chemosensory Protein 3 from Spodoptera litura and Its Binding Property with Plant Defensive Metabolites
Authors: Singh Sujata , Tyagi Chetna , Rather Irfan A. , Sabir Jamal S.M. , Hassan Md. Imtaiyaz , Singh Archana , Singh Indrakant Kumar
Published: June 2020

Chemosensory perception in insects involves a broad set of chemosensory proteins (CSPs) that identify the bouquet of chemical compounds present in the external environment and regulate specific behaviors. The current study is focused on the Spodoptera litura (Fabricius) chemosensory-related protein, SlitCSP3, a midgut-expressed CSP, which demonstrates differential gene expression upon different diet intake. There is an intriguing possibility that SlitCSP3 can perceive food-derived chemical signals and modulate insect feeding behavior. We predicted the three-dimensional structure of SlitCSP3 and subsequently performed an accelerated molecular dynamics (aMD) simulation of the best-modeled structure. SlitCSP3 structure has six α-helices arranged as a prism and a hydrophobic binding pocket predominated by leucine and isoleucine. We analyzed the interaction of selected host plant metabolites with the modeled structure of SlitCSP3. Out of two predicted binding pockets in SlitCSP3, the plant-derived defensive metabolites 2-b-D-glucopyranosyloxy-4-hydroxy-7-methoxy-1, 4-benzoxazin-3-one (DIMBOA), 6-Methoxy-2–benzoxazolinone (MBOA), and nicotine were found to interact preferably to the hydrophobic site 1, compared to site 2. The current study provides the potential role of CSPs in recognizing food-derived chemical signals, host-plant specialization, and adaptation to the varied ecosystem. Our work opens new perspectives in designing novel pest-management strategies. It can be further used in the development of CSP-based advanced biosensors.
Quantitative Phosphoproteomics Reveals Cell Alignment and Mitochondrial Length Change under Cyclic Stretching in Lung Cells
Authors: Wang Wei-Hsuan , Hsu Chia-Lang , Huang Hsuan-Cheng , Juan Hsueh-Fen
Published: June 2020

Lung cancer is a leading cause of death. Most previous studies have been based on traditional cell-culturing methods. However, lung cells are periodically subjected to mechanical forces during breathing. Understanding the mechanisms underlying the cyclic stretching induced in lung cells may be important for lung cancer therapy. Here, we applied cyclic stretching to stimulate the continual contraction that is present under physiological conditions in lung cells. We first uncovered the stretching-induced phosphoproteome in lung cancer cell line A549 and fibroblast cell line IMR-90. We identified 2048 and 2604 phosphosites corresponding to 837 and 1008 phosphoproteins in A549 and IMR-90, respectively. Furthermore, we combined our phosphoproteomics and public gene expression data to identify the biological functions in response to cyclic stretching. Interestingly, cytoskeletal and mitochondrial reorganization were enriched. We further used cell imaging analysis to validate the profiling results and found that this physical force changed cell alignment and mitochondrial length. This study not only reveals the molecular mechanism of cyclic stretching but also provides evidence that cell stretching causes cellular rearrangement and mitochondrial length change.
GABAA Receptor/STEP61 Signaling Pathway May Be Involved in Emulsified Isoflurane Anesthesia in Rats
Authors: Zhao Xingkai , Chang Guangjun , Cheng Yan , Zhou Zhenlei
Published: June 2020

(1) Background: Emulsified isoflurane (EISO) is a type of intravenous anesthetic. How emulsified isoflurane works in the brain is still unclear. The aim of this study was to explore whether epigenetic mechanisms affect anesthesia and to evaluate the anesthetic effects of emulsified isoflurane in rats. (2) Methods: Rats were randomly divided into four groups (n = 8/group): The tail vein was injected with normal saline 0.1 mL·kg−1·min−1 for the control (Con) group, with intralipid for the fat emulsion (FE) group, with EISO at 60 mg·kg−1·min−1 for the high-concentration (HD) group, and 45 mg·kg−1·min−1 for the low-concentration (LD) group. The consciousness state, motor function of limbs, and response to nociceptive stimulus were observed after drug administration. (3) Results: Using real-time polymerase chain reaction (PCR) to assess the promoter methylation of ion channel proteins in the cerebral cortex of rats anesthetized by EISO, we demonstrated that the change in the promoters’ methylation of the coding genes for gamma-aminobutyric acid A receptor α1 subunit (GABAAα1), N-methyl-D-aspartate receptor subunit 1 (NMDAR1), and mu opioid receptor 1 (OPRM1) was accompanied by the change in messenger ribonucleic acid (mRNA) and protein expression by these genes. (4) Conclusion: These data suggest that the epigenetic factors’ modulation might offer a novel approach to explore the anesthetic mechanism of EISO.
Maternal Immune Activation Induces Neuroinflammation and Cortical Synaptic Deficits in the Adolescent Rat Offspring
Authors: Cieślik Magdalena , Gąssowska-Dobrowolska Magdalena , Jęśko Henryk , Czapski Grzegorz A. , Wilkaniec Anna , Zawadzka Aleksandra , Dominiak Agnieszka , Polowy Rafał , Filipkowski Robert K. , Boguszewski Paweł M. , Gewartowska Magdalena , Frontczak-Baniewicz Małgorzata , Sun Grace Y. , Beversdorf David Q. , Adamczyk Agata
Published: June 2020

Maternal immune activation (MIA), induced by infection during pregnancy, is an important risk factor for neuro-developmental disorders, such as autism. Abnormal maternal cytokine signaling may affect fetal brain development and contribute to neurobiological and behavioral changes in the offspring. Here, we examined the effect of lipopolysaccharide-induced MIA on neuro-inflammatory changes, as well as synaptic morphology and key synaptic protein level in cerebral cortex of adolescent male rat offspring. Adolescent MIA offspring showed elevated blood cytokine levels, microglial activation, increased pro-inflammatory cytokines expression and increased oxidative stress in the cerebral cortex. Moreover, pathological changes in synaptic ultrastructure of MIA offspring was detected, along with presynaptic protein deficits and down-regulation of postsynaptic scaffolding proteins. Consequently, ability to unveil MIA-induced long-term alterations in synapses structure and protein level may have consequences on postnatal behavioral changes, associated with, and predisposed to, the development of neuropsychiatric disorders.
Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury
Authors: Sang Yizhen , Tsuji Kenji , Inoue-Torii Akiko , Fukushima Kazuhiko , Kitamura Shinji , Wada Jun
Published: June 2020

Podocyte injury is an independent risk factor for the progression of renal diseases. Semaphorin3A (SEMA3A), expressed in podocytes and tubular cells in the mammalian adult kidneys, has been reported to regulate diverse biological functions and be associated with renal diseases. Here, we investigated pathological roles of SEMA3A signaling on podocyte injury using a doxorubicin (Dox)-induced mouse model and examined the therapeutic effect of SEMA3A-inhibitor (SEMA3A-I). We demonstrated that Dox caused massive albuminuria and podocyte apoptosis as well as an increase of SEMA3A expression in podocytes, all of which were ameliorated with SEMA3A-I treatment. In addition, c-Jun N-terminal kinase (JNK), known as a downstream of SEMA3A signaling, was activated in Dox-injected mouse podocytes while SEMA3A-I treatment partially blocked the activation. In vitro, SEMA3A-I protected against Dox-induced podocyte apoptosis and recombinant SEMA3A caused podocyte apoptosis with activation of JNK signaling. JNK inhibitor, SP600125, attenuated SEMA3A-induced podocyte apoptosis, indicating that the JNK pathway would be involved in SEMA3A-induced podocyte apoptosis. Furthermore, the analysis of human data revealed a positive correlation between levels of urinary SEMA3A and protein, suggesting that SEMA3A is associated with podocyte injury. In conclusion, SEMA3A has essential roles in podocyte injury and it would be the therapeutic target for protecting from podocyte injury.
Molecular and Translational Research on Colorectal Cancer
Authors: Passardi Alessandro , Scarpi Emanuela , Ulivi Paola
Published: June 2020

Colorectal cancer (CRC) is the third most frequently diagnosed cancer in the world [...]
Stable Fibroblast Growth Factor 2 Dimers with High Pro-Survival and Mitogenic Potential
Authors: Nawrocka Daria , Krzyscik Mateusz Adam , Opaliński Łukasz , Zakrzewska Malgorzata , Otlewski Jacek
Published: June 2020

Fibroblast growth factor 2 (FGF2) is a heparin-binding growth factor with broad mitogenic and cell survival activities. Its effector functions are induced upon the formation of 2:2 FGF2:FGFR1 tetrameric complex. To facilitate receptor activation, and therefore, to improve the FGF2 biological properties, we preorganized dimeric ligand by a covalent linkage of two FGF2 molecules. Mutations of the FGF2 WT protein were designed to obtain variants with a single surface-exposed reactive cysteine for the chemical conjugation via maleimide-thiol reaction with bis-functionalized linear PEG linkers. We developed eight FGF2 dimers of defined topology, differing in mutual orientation of individual FGF2 molecules. The engineered proteins remained functional in terms of FGFR downstream signaling activation and were characterized by the increased stability, mitogenic potential and anti-apoptotic activity, as well as induced greater migration responses in normal fibroblasts, as compared to FGF2 monomer. Importantly, biological activity of the dimers was much less dependent on the external heparin administration. Moreover, some dimeric FGF2 variants internalized more efficiently into FGFR overexpressing cancer cells. In summary, in the current work, we showed that preorganization of dimeric FGF2 ligand increased the stability of the growth factor, and therefore, enhanced its biological activity.