bluuebunny/crossref_metadata_2025 huggingface dataset:
Shift Strategy Optimization for Automatic Transmission of Heavy Trucks Based on Dynamic Programming Algorithm
Authors: Zhang Heng , Zhao Xinxin , Yang Jue , Yang Weiwei
Published: June 2021

The shift strategy of automatic transmission plays a vital role in the smoothness and economy of heavy-duty mining trucks. In this paper, an engine fuel consumption model, a 6 + 2 speed automatic transmission model, and a vehicle resistance model are built in MATLAB. Combined with the development of smart mining technology, the traditional two-parameter economic shift strategy is corrected based on vehicle load and road slope. The dynamic programming optimization algorithm is used to extract the best economical shift strategy under known working conditions to reduce the fuel consumption and the number of shifts. Finally, simulation experiments of the optimized shift strategy by dynamic programming in a typical mine work cycle are carried out. The simulation results show that the engine speed and output torque are maintained in a relatively stable and efficient working range by using the proposed shift strategy. Compared with the traditional two-parameter shift strategy, dynamic programming has advantages in reducing fuel consumption and shift numbers.
Aerodynamic Analysis of Simple Girder Bridges under Construction Phase
Authors: Sadrizadeh Sasan , Martínez-López Guillermo , Ülker-Kaustell Mahir , Karoumi Raid
Published: June 2021

Bridge designs are becoming slender and lighter, making wind dynamic effects even more important than wind static effects. Some types of bridges show especially vulnerable situations during construction stages, when the structure is lighter or does not have its final stiffness. The aim of this document is to assess the dynamic wind loading on simple girder bridges during their construction phases. The studied section is formed by two steel beams supporting a concrete slab, but the analysis was made when the concrete slab has not been built yet. Several CFD simulations were made to find the aerodynamic parameters depending on the section’s dimensions. Three construction stages were analyzed: when only one beam is placed, when both beams are in their final locations but they are not connected yet, and when both beams are joined by the bracing. The results showed that vortex shedding effects are stronger in the along-wind direction due to the low horizontal bending stiffness of the beams and their large area perpendicular to the flow. Increasing beams’ distance is a good solution to reduce wind effects. However, closing the section with light plates was more effective, decreasing the frequency of vortex shedding and its effects.
Development and Testing of a Dual-Wavelength Sensitive Photopolymer Layer for Applications in Stacking of HOE Lenses
Authors: Keshri Sanjay , Rogers Brian , Murphy Kevin , Reynolds Kevin , Naydenova Izabela , Martin Suzanne
Published: June 2021

Diffractive optical elements (DOEs) have been in development for many years and are an exciting technology with the capability to re-direct light, using diffraction rather than refraction. Holographic Optical Elements (HOEs) are a subset of diffractive optical elements for which the photonic structure is created holographically, i.e., by recording a specific interference pattern in a suitable, photosensitive optical material. Volume HOEs are of particular interest for some applications because of their very high diffraction efficiency and single diffracted order; however, high dispersion and angular wavelength selectivity still present significant challenges. This paper explores a method for producing a compound DOE useful for situations where elements designed for two separate target wavelengths can be advantageously combined to achieve a highly efficient HOE with reduced dispersion. A photopolymer material consisting of two independently sensitized laminated layers is prepared and used in sequential holographic recording at two different wavelengths. The photonic structures recorded are investigated through examination of their diffraction peaks and comparison with the structure predicted by modeling. Finally, the device is illuminated with an expanded diverging beam at both target wavelengths and with white light, and a strong diffracted beam is observed.
Fabrication of a Simultaneous Highly Transparent and Highly Hydrophobic Fibrous Films
Authors: Youn Doo-Hyeb , Lee Kyu-Sung , Jung Sun-Kyu , Kang Mangu
Published: June 2021

This paper discusses the fabrication and characterization of electrospun nanofiber scaffolds made of polystyrene (PS). The scaffolds were characterized in terms of their basis material molecular weight, fiber diameter distribution, contact angles, contact angle hysteresis, and transmittance. We propose an aligned electrospun fiber scaffold using an alignment tool (alignment jig) for the fabrication of highly hydrophobic (θW > 125°) and highly transparent (T > 80.0%) films. We fabricated the alignment jig to align the electrospun fibers parallel to each other. The correlation between the water contact angles and surface roughness of the aligned electrospun fibers was investigated. We found that the water contact angle increased as the surface roughness was increased. Therefore, the hydrophobic properties of the aligned electrospun fibers were enhanced by increasing the surface roughness. With the change in the electrospinning mode to produce aligned fibers rather than randomly distributed fibers, the transmittance of the aligned electrospun fibers increased. The increase in the porous area, leading to better light transmittance in comparison to randomly distributed light scattering through the aligned electrospun fibers increased with the fibers. Through the above investigation of electrospinning parameters, we obtained the simultaneous transparent (>80%) and hydrophobic (θW > 140°) electrospun fiber scaffold. The aligned electrospun fibers of PS had a maximum transmittance of 91.8% at the electrospinning time of 10 s. The water contact angle (WCA) of the aligned electrospun fibers increased from 77° to 141° as the deposition time increased from 10 s to 40 s. The aligned fibers deposited at 40 s showed highly hydrophobic characteristics (θW > 140°).
Coupling Denoising to Detection for SAR Imagery
Authors: Shin Sujin , Kim Youngjung , Hwang Insu , Kim Junhee , Kim Sungho
Published: June 2021

Detecting objects in synthetic aperture radar (SAR) imagery has received much attention in recent years since SAR can operate in all-weather and day-and-night conditions. Due to the prosperity and development of convolutional neural networks (CNNs), many previous methodologies have been proposed for SAR object detection. In spite of the advance, existing detection networks still have limitations in boosting detection performance because of inherently noisy characteristics in SAR imagery; hence, separate preprocessing step such as denoising (despeckling) is required before utilizing the SAR images for deep learning. However, inappropriate denoising techniques might cause detailed information loss and even proper denoising methods does not always guarantee performance improvement. In this paper, we therefore propose a novel object detection framework that combines unsupervised denoising network into traditional two-stage detection network and leverages a strategy for fusing region proposals extracted from both raw SAR image and synthetically denoised SAR image. Extensive experiments validate the effectiveness of our framework on our own object detection datasets constructed with remote sensing images from TerraSAR-X and COSMO-SkyMed satellites. Extensive experiments validate the effectiveness of our framework on our own object detection datasets constructed with remote sensing images from TerraSAR-X and COSMO-SkyMed satellites. The proposed framework shows better performances when we compared the model with using only noisy SAR images and only denoised SAR images after despeckling under multiple backbone networks.
Attacks and Preventive Measures on Video Surveillance Systems: A Review
Authors: Vennam Preethi , T. C. Pramod , B. M. Thippeswamy , Kim Yong-Guk , B. N. Pavan Kumar
Published: June 2021

Video surveillance systems are widely deployed with large systems for use in strategic places such as home security, public transportation, banks, ATM centers, city centers, airports, and public roads, and play a vital role in protecting critical infrastructures. As various attacks are possible in these systems, identifying attacks and considering suitable security measures are essential. In this paper, we present a detailed review of existing and possible threats in video surveillance, CCTV, and IP-camera systems. This provides insight for the better identification of the security risks associated with the design and deployment of these systems and promotes further research in this emerging field. We also present countermeasures to prevent and protect the surveillance systems from various security attacks.
Optimization of Shunted Loudspeaker for Sound Absorption by Fully Exhaustive and Backtracking Algorithm
Authors: Li Zihao , Li Xin , Liu Bilong
Published: June 2021

The shunted loudspeaker with a negative impedance converter is a physical system with multiple influencing parameters. In this paper, a fully exhaustive backtracking algorithm was used to optimize these parameters, such as moving mass, total stiffness, damping, coil inductance, force factor, circuit resistance, inductance and capacitance, in order to obtain the best sound absorption in a specific frequency range. Taking the maximum average sound absorption coefficient in the range of 100–450 Hz as the objective function, the optimized parameters of the shunted loudspeaker were analyzed. Simulation results indicated that the force factor and moving mass can be sufficiently reduced in comparison with that of a typical four-inch loudspeaker available on the market. For a given loudspeaker from the market as an example, the four optimized parameters of the shunted loudspeaker were given, and the sound absorption coefficient was measured for verification. The measured results were in good agreement with the predicted results, demonstrating the applicability of the algorithm.
EnsemblePigDet: Ensemble Deep Learning for Accurate Pig Detection
Authors: Ahn Hanse , Son Seungwook , Kim Heegon , Lee Sungju , Chung Yongwha , Park Daihee
Published: June 2021

Automated pig monitoring is important for smart pig farms; thus, several deep-learning-based pig monitoring techniques have been proposed recently. In applying automated pig monitoring techniques to real pig farms, however, practical issues such as detecting pigs from overexposed regions, caused by strong sunlight through a window, should be considered. Another practical issue in applying deep-learning-based techniques to a specific pig monitoring application is the annotation cost for pig data. In this study, we propose a method for managing these two practical issues. Using annotated data obtained from training images without overexposed regions, we first generated augmented data to reduce the effect of overexposure. Then, we trained YOLOv4 with both the annotated and augmented data and combined the test results from two YOLOv4 models in a bounding box level to further improve the detection accuracy. We propose accuracy metrics for pig detection in a closed pig pen to evaluate the accuracy of the detection without box-level annotation. Our experimental results with 216,000 “unseen” test data from overexposed regions in the same pig pen show that the proposed ensemble method can significantly improve the detection accuracy of the baseline YOLOv4, from 79.93% to 94.33%, with additional execution time.
Topology Optimization Considering Porosity Defects in Metal Additive Manufacturing
Authors: Cao Shuangyuan , Wang Hanbin , Lu Xiao , Tong Jianbin , Sheng Zhongqi
Published: June 2021

In this paper, considering the porosity defects of Additive Manufacturing (AM), a level set topology optimization method for AM with porosity constraints is proposed. The concept of topological sensitivity is used to formulate a global porosity constraint function in the proposed method, and a level set topology optimization model considering porosity defects is obtained. To improve the robustness of the algorithm, the topology optimization model is solved in two phases. At first, the classical level set method without the porosity constraint is used to initially optimize the structure. During this process, the hole nucleation method combining bi-directional evolutionary structural optimization (BESO) and the topological sensitivity is used. Secondly, the topology optimization considering the effects of porosity is implemented on the preliminary optimization results. After performing the two-step optimization, a robust structure that alleviates the harmful impact of porosity defects is obtained. Finally, the robustness and effectiveness of the proposed method are validated by several two-dimensional numerical examples.
Role of Irisin in Endocrine and Metabolic Disorders—Possible New Therapeutic Agent?
Authors: Leustean Letitia , Preda Cristina , Teodoriu Laura , Mihalache Laura , Arhire Lidia , Ungureanu Maria-Christina
Published: June 2021

Irisin is a novel hormone that provides a possible solution for the treatment of metabolic disorders. Discovered in 2012 by Boström et al., irisin very quickly became an interesting subject in medical research. Irisin has been found in cerebrospinal fluid, the cerebellum, thyroid, pineal gland, liver, pancreas, testis, spleen, adult stomach, and human fetuses. Regarding the actions of irisin, both in animals and humans, the results are contradictory but interesting. Its capability to influence adipose tissue and glycemic homeostasis may be utilized in order to treat hypothyroidism, polycystic ovary syndrome, Prader–Willi syndrome, and other endocrine and metabolic disorders. Considering its osteogenic potential, irisin might be a therapeutic choice in diseases caused by a sedentary lifestyle. New data indicate that irisin treatment may serve in the treatment of severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) infection. Furthermore, several therapeutic agents, such as insulin, metformin, fenofibrate, exenatide, and melatonin, influence the concentrations of irisin in animal models or in humans. Nutritional factors including polyunsaturated fatty acids may also have an effect on irisin concentrations. While it may be “too good to be true,” irisin offers many opportunities for future research that would aim to find its optimal therapeutical role in endocrine and metabolic diseases.
GIS-Based Evaluation Method for Accessibility of Social Infrastructure Facilities
Authors: Yhee Hayeon , Kim Sungpyo , Kang Sanghyeok
Published: June 2021

Social infrastructure is provided to improve the quality of life of residents. There are two approaches to social infrastructure planning: (1) a population-based approach and (2) an access-based approach. A plan for the social infrastructure facilities in South Korea has been developed based on the population or number of households in a region. Recently, the South Korean government presented a guideline in which accessibility is included in the criteria. This study proposes a comprehensive evaluation method for the accessibility of social infrastructure and for identifying residential areas with poor access. To obtain the travel time between the residence and the social infrastructure facility, we employed a navigation application programming interface that provides a travel time that reflects the resistances in an actual situation. The accessibility index (AI) is defined as a population-weighted average travel time. We also identified residential areas with poor access to social infrastructure by creating accessibility maps. This study includes social infrastructure facilities, such as parks, libraries, elementary schools, childcare centers, kindergartens, and sports facilities. The method proposed in this study was applied to Namdong-gu, Incheon Metropolitan City, South Korea, to evaluate its applicability. The proposed method has advantages in that (1) the AI is easy to understand because it represents an intuitive index for the overall accessibility in minutes of a region, and (2) accessibility maps effectively identify residential areas with poor access.
POL-MUX System for Noncoherent Optical Networks
Authors: Sifta Radim , Latal Michal , Munster Petr , Horvath Tomas
Published: June 2021

This paper is focused on applying a polarization multiplex to passive optical networks to double their transmission bandwidth without significant changes in the distribution network. Although polarization multiplexes are already employed for high-speed optical transport networks with digital signal processing and coherent detection, we propose a system that could be used in existing older optical networks using a dynamic polarization controller in combination with a wavelength division multiplex.
Blood–Brain Barrier Dynamic Device with Uniform Shear Stress Distribution for Microscopy and Permeability Measurements
Authors: Choublier Nina , Müller Yoann , Gomez Baisac Loris , Laedermann Jeremy , de Rham Casimir , Declèves Xavier , Roux Adrien
Published: June 2021

Neurology has always been one of the therapeutic areas with higher attrition rates. One of the main difficulties is the presence of the blood–brain barrier (BBB) that restricts access to the brain for major drugs. This low success rate has led to an increasing demand for in vitro tools. The shear stress, which positively affects endothelial cell differentiation by mimicking blood flow, is required for a more physiological in vitro BBB model. We created an innovative device specifically designed for cell culture under shear stress to investigate drug permeability. Our dynamic device encompasses two compartments communicating together via a semi-permeable membrane, on which human cerebral microvascular endothelial (hCMEC/D3) cells were seeded. The fluidic controlled environment ensures a laminar and homogenous flow to culture cells for at least seven days. Cell differentiation was characterized by immunodetection of inter-endothelial junctions directly in the device by confocal microscopy. Finally, we performed permeability assay with lucifer yellow in both static and dynamic conditions in parallel. Our dynamic device is suited to the evaluation of barrier function and the study of drug transport across the BBB, but it could also be used with other human cell types to reproduce intestinal or kidney barriers.
Classical Partition Function for Non-Relativistic Gravity
Authors: Hameeda Mir , Plastino Angelo , Rocca Mario Carlos , Zamora Javier
Published: June 2021

We considered the canonical gravitational partition function Z associated to the classical Boltzmann–Gibbs (BG) distribution e−βHZ. It is popularly thought that it cannot be built up because the integral involved in constructing Z diverges at the origin. Contrariwise, it was shown in (Physica A 497 (2018) 310), by appeal to sophisticated mathematics developed in the second half of the last century, that this is not so. Z can indeed be computed by recourse to (A) the analytical extension treatments of Gradshteyn and Rizhik and Guelfand and Shilov, that permit tackling some divergent integrals and (B) the dimensional regularization approach. Only one special instance was discussed in the above reference. In this work, we obtain the classical partition function for Newton’s gravity in the four cases that immediately come to mind.
Which Way to Cope with COVID-19 Challenges? Contributions of the IoT for Smart City Projects
Authors: Fernandes Silvia
Published: June 2021

Many activities and sectors have come to a halt due to the COVID-19 crisis. People and workers’ habits and behaviors have changed dramatically, as the use of technologies and connections, virtual reality, and remote support have been enhanced. Businesses and cities have been forced to quickly adapt to the new challenges. Digital technologies have allowed people to have better access to public services due to improved use of resources. Smart cities have significant potential for linking people to work and services as never done before. Additionally, the technological convergence produces data that can enhance interactions and decisions toward the “new normal”. In this paper, the aim is to assess how Portugal is prepared to respond to the accelerated process that this context demands from cities. Portuguese SMEs have developed a good capacity for entrepreneurship and innovation; however, they are still behind in converting the knowledge acquired in sales and exports and there is still limited collaboration at the public-private level. The acceleration of smart cities through the Internet of Things (IoT) may encourage changes in these issues. A more assertive alignment between the emergent technologies and the digitization goals of companies is required. This paper opens a discussion around major needs and trends of IoT (and related technologies) since the pandemic has leveraged them. The relationship between innovation and city smartness is approached to assess main contributing and limiting variables (through the European Innovation Scoreboard), to clarify future directions toward smarter services. The tourism sector, as the largest export economic activity in the country, is addressed in this matter. An analytical framework (using, for example, Power BI and Azure IoT Hub) around this approach can choose and support the most suitable areas of development in the country.
Transdifferentiation of Human Fibroblasts into Skeletal Muscle Cells: Optimization and Assembly into Engineered Tissue Constructs through Biological Ligands
Authors: Abdel-Raouf Khaled M. A. , Rezgui Rachid , Stefanini Cesare , Teo Jeremy C. M. , Christoforou Nicolas
Published: June 2021

The development of robust skeletal muscle models has been challenging due to the partial recapitulation of human physiology and architecture. Reliable and innovative 3D skeletal muscle models recently described offer an alternative that more accurately captures the in vivo environment but require an abundant cell source. Direct reprogramming or transdifferentiation has been considered as an alternative. Recent reports have provided evidence for significant improvements in the efficiency of derivation of human skeletal myotubes from human fibroblasts. Herein we aimed at improving the transdifferentiation process of human fibroblasts (tHFs), in addition to the differentiation of murine skeletal myoblasts (C2C12), and the differentiation of primary human skeletal myoblasts (HSkM). Differentiating or transdifferentiating cells were exposed to single or combinations of biological ligands, including Follistatin, GDF8, FGF2, GDF11, GDF15, hGH, TMSB4X, BMP4, BMP7, IL6, and TNF-α. These were selected for their critical roles in myogenesis and regeneration. C2C12 and tHFs displayed significant differentiation deficits when exposed to FGF2, BMP4, BMP7, and TNF-α, while proliferation was significantly enhanced by FGF2. When exposed to combinations of ligands, we observed consistent deficit differentiation when TNF-α was included. Finally, our direct reprogramming technique allowed for the assembly of elongated, cross-striated, and aligned tHFs within tissue-engineered 3D skeletal muscle constructs. In conclusion, we describe an efficient system to transdifferentiate human fibroblasts into myogenic cells and a platform for the generation of tissue-engineered constructs. Future directions will involve the evaluation of the functional characteristics of these engineered tissues.
Low Intensity Extracorporeal Shock Wave Therapy as a Potential Treatment for Overactive Bladder Syndrome
Authors: Lu Jian-He , Chueh Kuang-Shun , Chuang Shu-Mien , Wu Yi-Hsuan , Lin Kun-Ling , Long Cheng-Yu , Lee Yung-Chin , Shen Mei-Chen , Sun Ting-Wei , Juan Yung-Shun
Published: June 2021

Background: The present study attempted to investigate the therapeutic effect and duration of low intensity extracorporeal shock wave therapy (LiESWT) on overactive bladder (OAB) symptoms, including social activity and the quality of life (QoL). Methods: In this prospective, randomized, single-blinded clinical trial, 65 participants with OAB symptom were randomly divided into receive LiESWT (0.25 mJ/mm2, 3000 pulses, 3 pulses/second) once a week for 8 weeks, or an identical sham LiESWT treatment without the energy transmission. We analyzed the difference in overactive bladder symptom score (OABSS) and 3-day urinary diary as the primary end. The secondary endpoint consisted of the change in uroflowmetry, post-voided residual (PVR) urine, and validated standardized questionnaires at the baseline (W0), 4-week (W4) and 8-week (W8) of LiESWT, and 1-month (F1), 3-month (F3) and 6-month (F6) follow-up after LiESWT. Results: 8-week LiESWT could significantly decrease urinary frequency, nocturia, urgency, and PVR volume, but meaningfully increase functional bladder capacity, average voided volume and maximal flow rate (Qmax) as compared with the W0 in the LiESWT group. In addition, the scores calculated from questionnaires were meaningfully reduced at W4, W8, F1, F3, and F6 in the LiESWT group. Conclusions: Our results revealed that the therapeutic efficacy of LiESWT could improve voided volume and ameliorate OAB symptoms, such as urgency, frequency, nocturia, and urinary incontinence, and lasted up to 6 month of follow-up. Moreover, LiESWT treatment brought statistically significant and clinically meaningful improvements in social activity and QoL of patients. These findings suggested that LiESWT could serve as an alternative non-invasive therapy for OAB patients.
Spotlight on Accessory Proteins: RTK-RAS-MAPK Modulators as New Therapeutic Targets
Authors: Pudewell Silke , Ahmadian Mohammad Reza
Published: June 2021

The RTK-RAS-MAPK axis is one of the most extensively studied signaling cascades and is related to the development of both cancers and RASopathies. In the last 30 years, many ideas and approaches have emerged for directly targeting constituent members of this cascade, predominantly in the context of cancer treatment. These approaches are still insufficient due to undesirable drug toxicity, resistance, and low efficacy. Significant advances have been made in understanding the spatiotemporal features of the constituent members of the RTK-RAS-MAPK axis, which are linked and modulated by many accessory proteins. Given that the majority of such modulators are now emerging as attractive therapeutic targets, a very small number of accessory inhibitors have yet to be discovered.
Utilizing the ABC Transporter for Growth Factor Production by fleQ Deletion Mutant of Pseudomonas fluorescens
Authors: Fabia Benedict-Uy , Bingwa Joshua , Park Jiyeon , Hieu Nguyen-Mihn , Ahn Jung-Hoon
Published: June 2021

Pseudomonas fluorescens, a gram-negative bacterium, has been proven to be a capable protein manufacturing factory (PMF). Utilizing its ATP-binding cassette (ABC) transporter, a type I secretion system, P. fluorescens has successfully produced recombinant proteins. However, besides the target proteins, P. fluorescens also secretes unnecessary background proteins that complicate protein purification and other downstream processes. One of the background proteins produced in large amounts is FliC, a flagellin protein. In this study, the master regulator of flagella gene expression, fleQ, was deleted from P. fluorescens Δtp, a lipase and protease double-deletion mutant, via targeted gene knockout. FleQ directs flagella synthesis, so the new strain, P. fluorescens ΔfleQ, does not produce flagella-related proteins. This not only simplifies purification but also makes P. fluorescens ΔfleQ an eco-friendly expression host because it will not survive outside a controlled environment. Six recombinant growth factors, namely, insulin-like growth factors I and II, beta-nerve growth factor, fibroblast growth factor 1, transforming growth factor beta, and tumor necrosis factor beta, prepared using our supercharging method, were successfully secreted by P. fluorescens ΔfleQ. Our findings demonstrate the potential of P. fluorescens ΔfleQ, combined with our supercharging process, as a PMF.
Altered Calcium Influx Pathways in Cancer-Associated Fibroblasts
Authors: Sadras Francisco , Stewart Teneale A. , Robitaille Mélanie , Peters Amelia A. , Croft Priyakshi Kalita-de , Soon Patsy S. , Saunus Jodi M. , Lakhani Sunil R. , Roberts-Thomson Sarah J. , Monteith Gregory R.
Published: June 2021

Cancer-associated fibroblasts (CAFs) represent an important component of the tumour microenvironment and are implicated in disease progression. Two outstanding questions in cancer biology are how CAFs arise and how they might be targeted therapeutically. The calcium signal also has an important role in tumorigenesis. To date, the role of calcium signalling pathways in the induction of the CAF phenotype remains unexplored. A CAF model was generated through exogenous transforming growth factor beta 1 (TGFβ1) stimulation of the normal human mammary fibroblast cell line, HMF3S (HMF3S-CAF), and changes in calcium signalling were investigated. Functional changes in HMF3S-CAF calcium signalling pathways were assessed using a fluorescent indicator, gene expression, gene-silencing and pharmacological approaches. HMF3S-CAF cells demonstrated functionally altered calcium influx pathways with reduced store-operated calcium entry. In support of a calcium signalling switch, two voltage-gated calcium channel (VGCC) family members, CaV1.2 and CaV3.2, were upregulated in HMF3S-CAFs and a subset of patient-derived breast CAFs. Both siRNA-mediated silencing and pharmacological inhibition of CaV1.2 or CaV3.2 significantly impaired CAF activation in HMF3S cells. Our findings show that VGCCs contribute to TGFβ1-mediated induction of HMF3S-CAF cells and both transcriptional interference and pharmacological antagonism of CaV1.2 and CaV3.2 inhibit CAF induction. This suggests a potential therapeutic role for targeting calcium signalling in breast CAFs.
Chronic Glaucoma Using Biodegradable Microspheres to Induce Intraocular Pressure Elevation. Six-Month Follow-Up
Authors: Rodrigo Maria Jesus , Garcia-Herranz David , Subias Manuel , Martinez-Rincón Teresa , Mendez-Martínez Silvia , Bravo-Osuna Irene , Carretero Ana , Ruberte Jesús , Garcia-Feijoo Julián , Pablo Luis Emilio , Herrero-Vanrell Rocío , Garcia-Martin Elena
Published: June 2021

Background: To compare two prolonged animal models of glaucoma over 24 weeks of follow-up. A novel pre-trabecular model of chronic glaucoma was achieved by injection of biodegradable poly lactic-co-glycolic acid (PLGA) microspheres (10–20 µm) (Ms20/10) into the ocular anterior chamber to progressively increase ocular hypertension (OHT). Methods: Rat right eyes were injected to induce OHT: 50% received a suspension of Ms20/10 in the anterior chamber at 0, 2, 4, 8, 12, 16 and 20 weeks, and the other 50% received a sclerosing episcleral vein injection biweekly (EPIm). Ophthalmological clinical signs, intraocular pressure (IOP), neuroretinal functionality measured by electroretinography (ERG), and structural analysis of the retina, retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) protocols using optical coherence tomography (OCT) and histological exams were performed. Results: Both models showed progressive neuroretinal degeneration (p < 0.05), and contralateral eye affectation. The Ms20/10 model showed a more progressive increase in IOP and better preservation of ocular surface. Although no statistical differences were found between models, the EPIm showed a tendency to produce thicker retinal and thinner GCL thicknesses, slower latency and smaller amplitude as measured using ERG, and more aggressive disturbances in retinal histology. In both models, while the GCL showed the greatest percentage loss of thickness, the RNFL showed the greatest and earliest rate of thickness loss. Conclusions: The intracameral model with biodegradable microspheres resulted more like the conditions observed in humans. It was obtained by a less-aggressive mechanism, which allows for adequate study of the pathology over longer periods.
Different Outcomes of Acute Encephalopathy after Status Epilepticus in Patients with Dravet Syndrome. How to Avoid Them? Comment on De Liso et al. Fatal Status Epilepticus in Dravet Syndrome. Brain Sci. 2020, 10, 889
Authors: Dravet Charlotte
Published: June 2021

Dear Editor [...]
Blockade of HVEM for Prostate Cancer Immunotherapy in Humanized Mice
Authors: Aubert Nicolas , Brunel Simon , Olive Daniel , Marodon Gilles
Published: June 2021

The herpes virus entry mediator (HVEM) delivers a negative signal to T cells mainly through the B and T lymphocyte attenuator (BTLA) molecule. Thus, HVEM/BTLA may represent a novel immune checkpoint during an anti-tumor immune response. However, a formal demonstration that HVEM can represent a target for cancer immunotherapy is still lacking. Here, we first showed that HVEM and BTLA mRNA expression levels were associated with a worse progression-free interval in patients with prostate adenocarcinomas, indicating a detrimental role for the HVEM/BTLA immune checkpoint during prostate cancer progression. We then showed that administration of a monoclonal antibody to human HVEM resulted in a twofold reduction in the growth of a prostate cancer cell line in NOD.SCID.gc-null mice reconstituted with human T cells. Using CRISPR/Cas9, we showed that the therapeutic effect of the mAb depended on HVEM expression by the tumor, with no effect on graft vs. host disease or activation of human T cells in the spleen. In contrast, the proliferation and number of tumor-infiltrating leukocytes increased following treatment, and depletion of CD8+ T cells partly alleviated treatment’s efficacy. The expression of genes belonging to various T cell activation pathways was enriched in tumor-infiltrating leukocytes, whereas genes associated with immuno-suppressive pathways were decreased, possibly resulting in modifications of leukocyte adhesion and motility. Finally, we developed a simple in vivo assay in humanized mice to directly demonstrate that HVEM expressed by the tumor is an immune checkpoint for T cell-mediated tumor control. Our results show that targeting HVEM is a promising strategy for prostate cancer immunotherapy.
Impact of Planning Method (Conventional versus Virtual) on Time to Therapy Initiation and Resection Margins: A Retrospective Analysis of 104 Immediate Jaw Reconstructions
Authors: Knitschke Michael , Bäcker Christina , Schmermund Daniel , Böttger Sebastian , Streckbein Philipp , Howaldt Hans-Peter , Attia Sameh
Published: June 2021

Virtual surgical planning (VSP) and patient-specific implants are currently increasing for immediate jaw reconstruction after ablative oncologic surgery. This technique contributes to more accurate and efficient preoperative planning and shorter operation time. The present retrospective, single-center study analyzes the influence of time delay caused by VSP vs. conventional (non-VSP) reconstruction planning on the soft and hard tissue resection margins for necessary oncologic safety. A total number of 104 cases of immediate jaw reconstruction with free fibula flap are included in the present study. The selected method of reconstruction (conventionally, non-VSP: n = 63; digitally, VSP: n = 41) are analyzed in detail. The study reveals a statistically significant (p = 0.008) prolonged time to therapy initiation with a median of 42 days when the VSP method compared with non-VSP (31.0 days) is used. VSP did not significantly affect bony or soft tissue resection margin status. Apart from this observation, no significant differences concerning local tumor recurrence, lymph node, and distant metastases rates are found according to the reconstruction method, and affect soft or bone tissue resection margins. Thus, we conclude that VSP for immediate jaw reconstruction is safe for oncological purposes.
Prognostic Significance of KIF11 and KIF14 Expression in Pancreatic Adenocarcinoma
Authors: Klimaszewska-Wiśniewska Anna , Neska-Długosz Izabela , Buchholz Karolina , Durślewicz Justyna , Grzanka Dariusz , Kasperska Anna , Antosik Paulina , Zabrzyński Jan , Grzanka Alina , Gagat Maciej
Published: June 2021

Available biomarkers for pancreatic adenocarcinoma (PAC) are inadequate to guide individual patient prognosis or therapy. Therefore, herein we aimed to verify the hypothesis that differences in the expression of KIF11 and KIF14, i.e., molecular motor proteins being primarily implicated in cell division events could account for the differences in the clinical outcome of PAC patients. In-house immunohistochemistry was used to evaluate the protein expressions of KIF11 and KIF14 in PAC, whereas RNA-seq datasets providing transcript expression data were obtained from public sources. IHC and mRNA results were correlated with clinicopathological features and overall survival (OS). Furthermore, the genes co-expressed with KIF11 or KIF14 were predicted and functionally annotated. In our series, malignant ducts displayed more intense but less abundant KIF11 staining than normal-appearing ducts. The former was also true for KIF14, whereas the prevalence of positive staining was similar in tumor and normal adjacent tissues. Based on categorical immunoreactive scores, we found KIF11 and KIF14 to be frequently downregulated or upregulated in PAC cases, respectively, and those with elevated levels of either protein, or both together, were associated with better prognosis. Specifically, we provide the first evidence that KIF11 or KIF14 proteins can robustly discriminate between patients with better and worse OS, independently of other relevant clinical risk factors. In turn, mRNA levels of KIF11 and KIF14 were markedly elevated in tumor tissues compared to normal tissues, and this coincided with adverse prognosis, even after adjusting for multiple confounders. Tumors with low predicted KIF11 or KIF14 expression were seen to have enrichment for circadian clock, whereas those with high levels were enriched for the genomic instability-related gene set. KIF11 and KIF14 were strongly correlated with one another, and CEP55, ASPM, and GAMT were identified as the main hub genes. Importantly, the combined expression of these five genes emerged as the most powerful independent prognostic indicator associated with poor survival outcome compared to classical clinicopathological factors and any marker alone. In conclusion, our study identifies novel prognostic biomarkers for PAC, which await validation.
Pitfalls in the Diagnosis of Nodular Lymphocyte Predominant Hodgkin Lymphoma: Variant Patterns, Borderlines and Mimics
Authors: Younes Sheren , Rojansky Rebecca B. , Menke Joshua R. , Gratzinger Dita , Natkunam Yasodha
Published: June 2021

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) represents approximately 5% of Hodgkin lymphoma and typically affects children and young adults. Although the overall prognosis is favorable, variant growth patterns in NLPHL correlate with disease recurrence and progression to T-cell/histiocyte-rich large B-cell lymphoma or frank diffuse large B-cell lymphoma (DLBCL). The diagnostic boundary between NLPHL and DLBCL can be difficult to discern, especially in the presence of variant histologies. Both diagnoses are established using morphology and immunophenotype and share similarities, including the infrequent large tumor B-cells and the lymphocyte and histiocyte-rich microenvironment. NLPHL also shows overlap with other lymphomas, particularly, classic Hodgkin lymphoma and T-cell lymphomas. Similarly, there is overlap with non-neoplastic conditions, such as the progressive transformation of germinal centers. Given the significant clinical differences among these entities, it is imperative that NLPHL and its variants are carefully separated from other lymphomas and their mimics. In this article, the characteristic features of NLPHL and its diagnostic boundaries and pitfalls are discussed. The current understanding of genetic features and immune microenvironment will be addressed, such that a framework to better understand biological behavior and customize patient care is provided.
Energy-Dependent Time-Resolved Photoluminescence of Self-Catalyzed InN Nanocolumns
Authors: Lai Fang-I , Yang Jui-Fu , Chen Wei-Chun , Hsieh Dan-Hua , Lin Woei-Tyng , Hsu Yu-Chao , Kuo Shou-Yi
Published: June 2021

In this study, we report the optical properties and carrier dynamics of different surface dimensionality n-type wurtzite InN with various carrier concentrations using photoluminescence (PL) and an energy-dependent, time-resolved photoluminescence (ED-TRPL) analysis. Experimental results indicated that the InN morphology can be controlled by the growth temperature, from one-dimensional (1D) nanorods to two-dimensional (2D) films. Moreover, donor-like nitrogen vacancy (VN) is responsible for the increase in carrier concentration due to the lowest formation energies in the n-type InN samples. The PL results also reveal that the energies of emission peaks are higher in the InN samples with 2D features than that with 1D features. These anomalous transitions are explained as the recombination of Mahan excitons and localized holes, and further proved by a theoretical model, activation energy and photon energy-dependent lifetime analysis.
High Catalytic Performance and Sustainability of Zr Modified Aluminophosphate for Vapor-Phase Selective O-Methylation of Catechol with Methanol
Authors: Ren Xinfeng , Xu Dongfei , Yin Yuchen , Zou Xiujing , Wang Yankai , Shang Xingfu , Wang Xueguang
Published: June 2021

Guaiacol produced by O-methylation of catechol with methanol over solid catalysts is a green environmental synthesis route. In order to achieve high catalytic efficiency, it is quite necessary to employ low-cost catalysts with high activity and stability. Herein, series of aluminophosphate catalysts were synthesized by a simple precipitation route modified by Zr. The characterization results indicated that the prepared Al-P-Zr catalysts possessed appropriate weak acid and weak base sites, which were beneficial for the O-methylation of catechol with methanol. Different Zr amount and calcined temperature exerted a significant influence on physicochemical properties of the catalysts and catalytic performance. The Al-P-Zr catalysts containing Zr/Al molar ratio of 0.012 calcined under 400 °C showed the optimal catalytic activity and long-term stability for vapor-phase selective O-methylation of catechol with methanol.
A Potentiometric Electronic Tongue as a Discrimination Tool of Water-Food Indicator/Contamination Bacteria
Authors: Ghrissi Hiba , Veloso Ana C. A. , Marx Ítala M. G. , Dias Teresa , Peres António M.
Published: June 2021

Microorganism assessment plays a key role in food quality and safety control but conventional techniques are costly and/or time consuming. Alternatively, electronic tongues (E-tongues) can fulfill this critical task. Thus, a potentiometric lab-made E-tongue (40 lipid sensor membranes) was used to differentiate four common food contamination bacteria, including two Gram positive (Enterococcus faecalis, Staphylococcus aureus) and two Gram negative (Escherichia coli, Pseudomonas aeruginosa). Principal component analysis and a linear discriminant analysis-simulated annealing algorithm (LDA-SA) showed that the potentiometric signal profiles acquired during the analysis of aqueous solutions containing known amounts of each studied bacteria allowed a satisfactory differentiation of the four bacterial strains. An E-tongue-LDA-SA model (12 non-redundant sensors) correctly classified 98 ± 5% of the samples (repeated K-fold-CV), the satisfactory performance of which can be attributed to the capability of the lipid membranes to establish electrostatic interactions/hydrogen bonds with hydroxyl, amine and/or carbonyl groups, which are comprised in the bacteria outer membranes. Furthermore, multiple linear regression models, based on selected subsets of E-tongue sensors (12–15 sensors), also allowed quantifying the bacteria contents in aqueous solutions (0.993 ± 0.011 ≤ R2 ≤ 0.998 ± 0.005, for repeated K-fold-CV). In conclusion, the E-tongue could be of great value as a preliminary food quality and safety diagnosis tool.
A Boost Converter Employing Quadratic Sawtooth Waveform Generator for SiPM-Based Radiation Sensors
Authors: Jeon Hyuntak
Published: June 2021

This paper proposes an optimized step-up power converter using a quadratic sawtooth waveform generator for a silicon photomultiplier (SiPM) used as a radiation sensor for mobile radiation dosimeters. Although our step-up converter uses the topology of a switched inductor boost converter in voltage mode, it achieves a fast transient performance thanks to the proposed quadratic sawtooth waveform generator, which can increase the loop bandwidth. As a result, the proposed boost converter can stably regulate the bias voltage of an SiPM, even in a situation where the radiation particles are injected. In addition, since the proposed quadratic sawtooth waveform generator can be designed with low power, it was able to achieve 86% peak efficiency even under the light load conditions.
Nitrogen and Sulfur Co-Doped Graphene as Efficient Electrode Material for L-Cysteine Detection
Authors: Varodi Codruța , Pogăcean Florina , Cioriță Alexandra , Pană Ovidiu , Leoștean Cristian , Cozar Bogdan , Radu Teodora , Coroș Maria , Ștefan-van Staden Raluca Ioana , Pruneanu Stela-Maria
Published: June 2021

Two graphene samples co-doped with nitrogen and sulfur were synthesized by the hydrothermal method using thiourea as doping and reducing agent for graphene oxide (GO). An appropriate amount of thiourea was added to the aqueous dispersion of GO, previously sonicated for 30 min. The mixture was poured into an autoclave and placed in the oven for 3 h, at 120 and 200 °C. The samples were denoted NSGr-120 and NSGr-200, respectively, in agreement with the reaction temperatures. They were next morphologically and structurally characterized by advanced techniques, such as SEM/TEM, XPS, XRD, and FTIR. According to XPS analysis, the NSGr-120 sample has higher amounts of heteroatoms in comparison with NSGr-200, indicating that the reaction temperature is a crucial factor that affects the doping degree. In order to reveal the influence of the doping degree on the electrochemical performances of graphene-modified electrodes, they were tested in solutions containing L-cysteine molecules. The electrode with the best electrocatalytic performances, GC/NSGr-120, was tested to detect L-cysteine in a pharmaceutical drug, proving its applicability in real sample analysis.