bluuebunny/crossref_metadata_2025 huggingface dataset:
Cartographer SLAM Method for Optimization with an Adaptive Multi-Distance Scan Scheduler
Authors: Dwijotomo Abdurahman , Abdul Rahman Mohd Azizi , Mohammed Ariff Mohd Hatta , Zamzuri Hairi , Wan Azree Wan Muhd Hafeez
Published: January 2020

This paper presents the use of Google’s simultaneous localization and mapping (SLAM) technique, namely Cartographer, and adaptive multistage distance scheduler (AMDS) to improve the processing speed. This approach optimizes the processing speed of SLAM which is known to have performance degradation as the map grows due to a larger scan matcher. In this proposed work, the adaptive method was successfully tested in an actual vehicle to map roads in real time. The AMDS performs a local pose correction by controlling the LiDAR sensor scan range and scan matcher search window with the help of scheduling algorithms. The scheduling algorithms manage the SLAM that swaps between short and long distances during map data collection. As a result, the algorithms efficiently improved performance speed similar to short distance LiDAR scans while maintaining the accuracy of the full distance of LiDAR. By swapping the scan distance of the sensor, and adaptively limiting the search size of the scan matcher to handle difference scan sizes, the pose’s generation performance time is improved by approximately 16% as compared with a fixed scan distance, while maintaining similar accuracy.
Low-Noise Multimodal Reconfigurable Sensor Readout Circuit for Voltage/Current/Resistive/Capacitive Microsensors
Authors: You Donggeun , Kim Hyungseup , Kim Jaesung , Han Kwonsang , Heo Hyunwoo , Kwon Yongsu , Kim Gyungtae , Sul Woo Suk , Lee Jong Won , Lee Boung Ju , Ko Hyoungho
Published: January 2020

This paper presents a low-noise reconfigurable sensor readout circuit with a multimodal sensing chain for voltage/current/resistive/capacitive microsensors such that it can interface with a voltage, current, resistive, or capacitive microsensor, and can be reconfigured for a specific sensor application. The multimodal sensor readout circuit consists of a reconfigurable amplifier, programmable gain amplifier (PGA), low-pass filter (LPF), and analog-to-digital converter (ADC). A chopper stabilization technique was implemented in a multi-path operational amplifier to mitigate 1/f noise and offsets. The 1/f noise and offsets were up-converted by a chopper circuit and caused an output ripple. An AC-coupled ripple rejection loop (RRL) was implemented to reduce the output ripple caused by the chopper. When the amplifier was operated in the discrete-time mode, for example, the capacitive-sensing mode, a correlated double sampling (CDS) scheme reduced the low-frequency noise. The readout circuit was designed to use the 0.18-µm complementary metal-oxide-semiconductor (CMOS) process with an active area of 9.61 mm2. The total power consumption was 2.552 mW with a 1.8-V supply voltage. The measured input referred noise in the voltage-sensing mode was 5.25 µVrms from 1 Hz to 200 Hz.
Impact Performance of a Plate Structure with Coconut-Inspired Microchannels
Authors: Shen Jie , Flores Mark , Sharits Andrew
Published: January 2020

Very few studies have been conducted in the past to reveal the underlying mechanism that causes the high-impact performance of coconuts as a natural composite material and a structure. The goal of this study is to understand the dominant microstructures of coconuts with respect to mechanical impact. In this study, we use a high-resolution X-ray computed tomography (CT) machine in scanning the microstructures and analyzing the patterns of microchannels in coconut shells. By using the established patterns, we model a novel plate structure with coconut-inspired microchannels. Numerical simulation elucidates a significant improvement in crashworthiness. The microchannel design opens a path to further developing self-healing composites and intelligent composites with sensing elements embedded in the channels.
Fractional Order PI-Based Control Applied to the Traction System of an Electric Vehicle (EV)
Authors: Munoz-Hernandez German Ardul , Mino-Aguilar Gerardo , Guerrero-Castellanos Jose Fermi , Peralta-Sanchez Edgar
Published: January 2020

This paper presents a design of a cruise control based on a fractional-order proportional and integral (PI) direct torque control applied to the traction system of an electric vehicle (EV). The paper also discusses the modeling, control design and simulation, resulting in a numerical simulator composed of detailed models of the main components: transmission system, induction motor, power electronics, control system, and vehicle dynamics. The simulation was developed in MATLAB/Simulink and will allow the estimation of the energy consumption of an EV under specific configurations. Simulation results show the efficiency of the designed control. These simulations were carried out using the velocity profiles given by the New Europe Drive Cycle (NEDC).
Diurnal Valley Winds in a Deep Alpine Valley: Observations
Authors: Schmid Fabienne , Schmidli Juerg , Hervo Maxime , Haefele Alexander
Published: January 2020

Diurnal valley winds frequently form over complex topography, particularly under fair weather conditions, and have a significant impact on the local weather and climate. Since diurnal valley winds result from complex and multi-scale interactions, their representation in numerical weather prediction models is challenging. Better understanding of these local winds based on observations is crucial to improve the accuracy of the forecasts. This study investigates the diurnal evolution of the three-dimensional mean wind structure in a deep Alpine valley, the Rhone valley at Sion, using data from a radar wind profiler and a surface weather station operated continuously from 1 September 2016 to 17 July 2017. In particular, the wind profiler data was analyzed for a subset of days on which fair weather conditions allowed for the full development of thermally driven winds. A pronounced diurnal cycle of the wind speed, as well as a reversal of the wind direction twice per day is documented for altitudes up to about 2 km above ground level (AGL) in the warm season and less than 1 km AGL in winter. The diurnal pattern undergoes significant changes during the course of the year. Particularly during the warm-weather months of May through to September, a low-level wind maximum occurs, where mean maximum up-valley velocities of 8–10 m s−1 are found between 15–16 UTC at altitudes around 200 m AGL. In addition, during nighttime, a down-valley jet with maximum wind speeds of 4–8 m s−1 around 1 km AGL is found. A case study of a three-day period in September 2016 illustrates the occurrence of an elevated layer of cross-valley flow around 1–1.5 km AGL.
The Uncharacteristic Occurrence of the June 2013 Biomass-Burning Haze Event in Southeast Asia: Effects of the Madden-Julian Oscillation and Tropical Cyclone Activity
Authors: Oozeer Yaasiin , Chan Andy , Wang Jun , Reid Jeffrey S. , Salinas Santo V. , Ooi Maggie C. G. , Morris Kenobi I.
Published: January 2020

One of the worst haze events to ever hit Peninsular Malaysia occurred in June 2013 due to smoke from Riau, Central Sumatra. While biomass-burning in the region is common, the early occurrence of a haze episode of this magnitude was uncharacteristic of the seasonality of extreme fire events, which usually occur between August and October in the Maritime Continent (MC). This study aims to investigate the phenomenology of the June 2013 haze event and its underlying meteorological forcing agents. The aerosol and meteorological environment during the event is examined using the Moderate Resolution Imaging Spectroradiometer (MODIS) active fire hotspot detections and aerosol optical thickness retrievals, satellite-based precipitation retrievals, and meteorological indices. These datasets are then supported by a WRF-Chem simulation to provide a comprehensive picture of the event’s meteorology and aerosol transport phenomenology. While extreme fire events are more characteristic of El Nino years, the MODIS fire count over the MC in June for the years 2001–2015 was highest in 2013 when neutral El Nino/Southern Oscillation (ENSO) conditions prevailed. Although, the mean daily precipitation for June 2013 was below average for June 2003–2015. An early active tropical cyclone (TC) season occurred in 2013, and results show that the combined induced subsidence and flow enhancement due to TC Bebinca and the dry phases of a strong Madden–Julian Oscillation (MJO) event contributed to the event intensification. Results also show that Bebinca induced a decrease in surface relative humidity of at least 10% over Riau, where fire hotspots were concentrated.
Characteristics of Aerosol during a Severe Haze-Fog Episode in the Yangtze River Delta: Particle Size Distribution, Chemical Composition, and Optical Properties
Authors: Liu Ankang , Wang Honglei , Cui Yi , Shen Lijuan , Yin Yan , Wu Zhijun , Guo Song , Shi Shuangshuang , Chen Kui , Zhu Bin , Wang Jinhu , Kong Xiangchen
Published: January 2020

Particle size distribution, water soluble ions, and black carbon (BC) concentration in a long-term haze-fog episode were measured using a wide-range particle spectrometer (WPS), a monitor for aerosols and gases (MARGA), and an aethalometer (AE33) in Nanjing from 16 to 27 November, 2018. The observation included five processes of clean, mist, mix, haze, and fog. Combined with meteorological elements, the HYSPLIT model, and the IMPROVE model, we analyzed the particle size distribution, chemical composition, and optical properties of aerosols in different processes. The particle number size distribution (PNSD) in five processes differed: It was bimodal in mist and fog and unimodal in clean, mix, and haze. The particle surface area size distribution (PSSD) in different processes showed a bimodal distribution, and the second peak of the mix and fog processes shifted to a larger particle size at 480 nm. The dominant air masses in five processes differed and primarily originated in the northeast direction in the clean process and the southeast direction in the haze process. In the mist, mix, and fog processes local air masses dominated. NO3− was the primary component of water soluble ions, with the lowest proportion of 45.6% in the clean process and the highest proportion of 53.0% in the mix process. The ratio of NH4+ in the different processes was stable at approximately 23%. The ratio of SO42− in the clean process was 26.2%, and the ratio of other processes was approximately 20%. The average concentration of BC in the fog processes was 10,119 ng·m−3, which was 3.55, 1.80, 1.60, and 1.46 times that in the processes of clean, mist, mix, and haze, respectively. In the different processes, BC was primarily based on liquid fuel combustion. NO3−, SO42−, and BC were the main contributors to the atmospheric extinction coefficient and contributed more than 90% in different processes. NO3− contributed 398.43 Mm−1 in the mix process, and SO42− and BC contributed 167.90 Mm−1 and 101.19 Mm−1, respectively, during the fog process.
Sampling Errors in Observed Gravity Wave Momentum Fluxes from Vertical and Tilted Profiles
Authors: Vosper Simon B. , Ross Andrew N.
Published: January 2020

Observations from radiosondes or from vertically pointing remote sensing profilers are often used to estimate the vertical flux of momentum due to gravity waves. For planar, monochromatic waves, these vertically integrated fluxes are equal to the phase averaged flux and equivalent to the horizontal averaging used to deduce momentum flux from aircraft data or in numerical models. Using a simple analytical solution for two-dimensional hydrostatic gravity waves over an isolated ridge, it is shown that this equivalence does not hold for mountain waves. For a vertical profile, the vertically integrated flux estimate is proportional to the horizontally integrated flux and decays with increasing distance of the profile location from the mountain. For tilted profiles, such as those obtained from radiosonde ascents, there is a further sampling error that increases as the trajectory extends beyond the localised wave field. The same sampling issues are seen when the effects of the Coriolis force on the gravity waves are taken into account. The conclusion of this work is that caution must be taken when using radiosondes or other vertical profiles to deduce mountain wave momentum fluxes.
Diurnal Variations of Surface and Air Temperatures on the Urban Streets in Seoul, Korea: An Observational Analysis during BBMEX Campaign
Authors: Kim Yoo-Jun , Jee Joon-Bum , Kim Geon-Tae , Nam Hyoung-Gu , Lee Jeong-Sun , Kim Baek-Jo
Published: January 2020

In this study, we used an intensive observation dataset of a mobile observation vehicle (MOVE) to investigate the characteristics of thermal environments and diurnal variations of road surface temperature (RST) and air temperature, particularly at the urban street level, during the 2019 Building Block 3-dimensional urban Meteorological Experiment (BBMEX) campaign in Seoul. For the purpose of comparing characteristics of RST and air temperature with different surrounding thermal environments, we divided the road into four sections (S1: Open Section, S2: High-Rise Buildings, S3: Low-Rise Buildings, S4: Street Trees). This study demonstrates that the greater sky view factors (SVFs) are generally coincident with the greater RSTs, with a significance at the 5% level. The diurnal variations indicated that the time lag between observed maximum air temperature and RST has about one hour, which is attributable to an increase air temperatures above artificial pavement through heat convection with some latency. The diurnal temperature ranges (DTRs) of RST in S2 and S4 were relatively smaller than those of S1 and S3, with differences ranging from 2.9 °C to 4.5 °C. The current results will assist planners and decision makers in determining policy priorities with regard to urban street design and planning.
Bulk Scaling Model of Entrainment Zone Thickness in a Convective Boundary Layer, with a Shear Effect Promoted by Velocity Difference
Authors: Li Anran , Gao Wenfeng , Liu Tao
Published: January 2020

Studying the thickness of the convective boundary layer (CBL) is helpful for understanding atmospheric structure and the diffusion of air pollutants. When there is velocity shear in CBL, the flow field structure is very different from that of shear-free CBL, which makes the thickness model of the entrainment zone deviate. A large-eddy simulation (LES) approach is carried out for a horizontally homogeneous, atmospheric CBL, with a shear effect promoted by velocity difference to explore the bulk scaling model of the entrainment zone thickness. The post-processed data indicate that the existing bulk scaling models cannot synthetically represent the effects of shear and buoyancy on entrainment, resulting in reduced accuracy or limited applicability. Based on the fraction of turbulent kinetic energy (TKE) used for entrainment, a different form of the characteristic velocity scale, which includes the shear effect, is proposed, and a modified bulk scaling model that uses a potential temperature gradient to replace the potential temperature jump across the entrainment zone is constructed with the numerical results. The new model is found to provide an improved prediction of the entrainment zone thickness in a sheared CBL.
Calculations of Resonance Parameters for the Doubly Excited 1P° States in Ps− Using Exponentially Correlated Wave Functions
Authors: Kar Sabyasachi , Ho Yew Kam
Published: January 2020

Recent observations on resonance states of the positronium negative ion (Ps−) in the laboratory created huge interest in terms of the calculation of the resonance parameters of the simple three-lepton system. We calculate the resonance parameters for the doubly excited 1P° states in Ps− using correlated exponential wave functions based on the complex-coordinate rotation method. The resonance energies and widths for the 1P° Feshbach resonance states in Ps− below the N = 2, 3, 4, 5 Ps thresholds are reported. The 1P° shape resonance above the N = 2, 4 Ps thresholds are also reported. Our predications are in agreement with the available results. Few Feshbach resonance parameters below the N = 4 and 5 Ps thresholds have been reported in the literature. Our predictions will provide useful information for future resonance experiments in Ps−.
Processing of Herbal Tea from Roselle (Hibiscus sabdariffa L.): Effects of Drying Temperature and Brewing Conditions on Total Soluble Solid, Phenolic Content, Antioxidant Capacity and Sensory Quality
Authors: Nguyen Quang Vinh , Chuyen Hoang Van
Published: January 2020

Roselle (Hibiscus sabdariffa L.) is an annual shrub popularly grown in tropical and subtropical areas. Although Roselle fruit has been used for a long time as a herbal tea due to its high content of bioactive compounds like phenolic acids and anthocyanins, the studies on the effects of the drying process and brewing conditions on the content of beneficial components and bioactivities of Roselle tea is limited. In this study, the influence of drying temperature on the retention of total phenolic content (TPC) and antioxidant capacity (AC) of the dried Roselle and the effects of brewing conditions including water temperature, liquid-solid ratio and brewing time on total soluble solid (TSS) content, total phenolic content, and antioxidant capacity of Roselle tea were investigated. The drying at 80 °C produced the dried Roselle with the highest retention of TPC (25.196 mg GAE/g) and AC (IC50 of 2.2 mg/mL for 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition) and the highest sensory quality compared to the drying at other temperatures. The brewing process using hot water at 90 °C with the solid-liquid ratio of 1:10 (g/mL) for 30 min resulted in the highest TSS content (5.4 oBx), TPC (12.7 mg GAE/g dried Roselle) and AC (73.3% DPPH inhibition) of the Roselle tea. Thus, the drying at 80 °C combined with the brewing of dried Roselle for 30 min using 90 °C hot water with the solid-liquid ratio of 1:10 (g/mL) are recommended to produce Roselle tea with the highest content of beneficial ingredients.
Current Practice in Preoperative Virtual and Physical Simulation in Neurosurgery
Authors: Mussi Elisa , Mussa Federico , Santarelli Chiara , Scagnet Mirko , Uccheddu Francesca , Furferi Rocco , Volpe Yary , Genitori Lorenzo
Published: January 2020

In brain tumor surgery, an appropriate and careful surgical planning process is crucial for surgeons and can determine the success or failure of the surgery. A deep comprehension of spatial relationships between tumor borders and surrounding healthy tissues enables accurate surgical planning that leads to the identification of the optimal and patient-specific surgical strategy. A physical replica of the region of interest is a valuable aid for preoperative planning and simulation, allowing the physician to directly handle the patient’s anatomy and easily study the volumes involved in the surgery. In the literature, different anatomical models, produced with 3D technologies, are reported and several methodologies were proposed. Many of them share the idea that the employment of 3D printing technologies to produce anatomical models can be introduced into standard clinical practice since 3D printing is now considered to be a mature technology. Therefore, the main aim of the paper is to take into account the literature best practices and to describe the current workflow and methodology used to standardize the pre-operative virtual and physical simulation in neurosurgery. The main aim is also to introduce these practices and standards to neurosurgeons and clinical engineers interested in learning and implementing cost-effective in-house preoperative surgical planning processes. To assess the validity of the proposed scheme, four clinical cases of preoperative planning of brain cancer surgery are reported and discussed. Our preliminary results showed that the proposed methodology can be applied effectively in the neurosurgical clinical practice both in terms of affordability and in terms of simulation realism and efficacy.
Mediator of DNA Damage Checkpoint Protein 1 Facilitates V(D)J Recombination in Cells Lacking DNA Repair Factor XLF
Authors: Beck Carole , Castañeda-Zegarra Sergio , Huse Camilla , Xing Mengtan , Oksenych Valentyn
Published: January 2020

DNA double-strand breaks (DSBs) trigger the Ataxia telangiectasia mutated (ATM)-dependent DNA damage response (DDR), which consists of histone H2AX, MDC1, RNF168, 53BP1, PTIP, RIF1, Rev7, and Shieldin. Early stages of B and T lymphocyte development are dependent on recombination activating gene (RAG)-induced DSBs that form the basis for further V(D)J recombination. Non-homologous end joining (NHEJ) pathway factors recognize, process, and ligate DSBs. Based on numerous loss-of-function studies, DDR factors were thought to be dispensable for the V(D)J recombination. In particular, mice lacking Mediator of DNA Damage Checkpoint Protein 1 (MDC1) possessed nearly wild-type levels of mature B and T lymphocytes in the spleen, thymus, and bone marrow. NHEJ factor XRCC4-like factor (XLF)/Cernunnos is functionally redundant with ATM, histone H2AX, and p53-binding protein 1 (53BP1) during the lymphocyte development in mice. Here, we genetically inactivated MDC1, XLF, or both MDC1 and XLF in murine vAbl pro-B cell lines and, using chromosomally integrated substrates, demonstrated that MDC1 stimulates the V(D)J recombination in cells lacking XLF. Moreover, combined inactivation of MDC1 and XLF in mice resulted in synthetic lethality. Together, these findings suggest that MDC1 and XLF are functionally redundant during the mouse development, in general, and the V(D)J recombination, in particular.
Lysosomal Fusion: An Efficient Mechanism Increasing Their Sequestration Capacity for Weak Base Drugs without Apparent Lysosomal Biogenesis
Authors: Skoupa Nikola , Dolezel Petr , Mlejnek Petr
Published: January 2020

Lysosomal sequestration of anticancer therapeutics lowers their cytotoxic potential, reduces drug availability at target sites, and contributes to cancer resistance. Only recently has it been shown that lysosomal sequestration of weak base drugs induces lysosomal biogenesis mediated by activation of transcription factor EB (TFEB) which, in turn, enhances their accumulation capacity, thereby increasing resistance to these drugs. Here, we addressed the question of whether lysosomal biogenesis is the only mechanism that increases lysosomal sequestration capacity. We found that lysosomal sequestration of some tyrosine kinase inhibitors (TKIs), gefitinib (GF) and imatinib (IM), induced expansion of the lysosomal compartment. However, an expression analysis of lysosomal genes, including lysosome-associated membrane proteins 1, 2 (LAMP1, LAMP2), vacuolar ATPase subunit B2 (ATP6V1B2), acid phosphatase (ACP), and galactosidase beta (GLB) controlled by TFEB, did not reveal increased expression. Instead, we found that both studied TKIs, GF and IM, induced lysosomal fusion which was dependent on nicotinic acid adenine dinucleotide phosphate (NAADP) mediated Ca2+signaling. A theoretical analysis revealed that lysosomal fusion is sufficient to explain the enlargement of lysosomal sequestration capacity. In conclusion, we demonstrated that extracellular TKIs, GF and IM, induced NAADP/Ca2+ mediated lysosomal fusion, leading to enlargement of the lysosomal compartment with significantly increased sequestration capacity for these drugs without apparent lysosomal biogenesis.
Voltage Sensing in Bacterial Protein Translocation
Authors: Knyazev Denis G. , Kuttner Roland , Bondar Ana-Nicoleta , Zimmerman Mirjam , Siligan Christine , Pohl Peter
Published: January 2020

The bacterial channel SecYEG efficiently translocates both hydrophobic and hydrophilic proteins across the plasma membrane. Translocating polypeptide chains may dislodge the plug, a half helix that blocks the permeation of small molecules, from its position in the middle of the aqueous translocation channel. Instead of the plug, six isoleucines in the middle of the membrane supposedly seal the channel, by forming a gasket around the translocating polypeptide. However, this hypothesis does not explain how the tightness of the gasket may depend on membrane potential. Here, we demonstrate voltage-dependent closings of the purified and reconstituted channel in the presence of ligands, suggesting that voltage sensitivity may be conferred by motor protein SecA, ribosomes, signal peptides, and/or translocating peptides. Yet, the presence of a voltage sensor intrinsic to SecYEG was indicated by voltage driven closure of pores that were forced-open either by crosslinking the plug to SecE or by plug deletion. We tested the involvement of SecY’s half-helix 2b (TM2b) in voltage sensing, since clearly identifiable gating charges are missing. The mutation L80D accelerated voltage driven closings by reversing TM2b’s dipolar orientation. In contrast, the L80K mutation decelerated voltage induced closings by increasing TM2b’s dipole moment. The observations suggest that TM2b is part of a larger voltage sensor. By partly aligning the combined dipole of this sensor with the orientation of the membrane-spanning electric field, voltage may drive channel closure.
TGF-β Promotes the Proliferation of Microglia In Vitro
Authors: Bureta Costansia , Setoguchi Takao , Saitoh Yoshinobu , Tominaga Hiroyuki , Maeda Shingo , Nagano Satoshi , Komiya Setsuro , Yamamoto Takuya , Taniguchi Noboru
Published: January 2020

The activation and proliferation of microglia is characteristic of the early stages of brain pathologies. In this study, we aimed to identify a factor that promotes microglial activation and proliferation and examined the in vitro effects on these processes. We cultured microglial cell lines, EOC 2 and SIM-A9, with various growth factors and evaluated cell proliferation, death, and viability. The results showed that only transforming growth factor beta (TGF-β) caused an increase in the in vitro proliferation of both microglial cell lines. It has been reported that colony-stimulating factor 1 promotes the proliferation of microglia, while TGF-β promotes both proliferation and inhibition of cell death of microglia. However, upon comparing the most effective doses of both (assessed from the proliferation assay), we identified no statistically significant difference between the two factors in terms of cell death; thus, both have a proliferative effect on microglial cells. In addition, a TGF-β receptor 1 inhibitor, galunisertib, caused marked inhibition of proliferation in a dose-dependent manner, indicating that inhibition of TGF-β signalling reduces the proliferation of microglia. Therefore, galunisertib may represent a promising therapeutic agent for the treatment of neurodegenerative diseases via inhibition of nerve injury-induced microglial proliferation, which may result in reduced inflammatory and neuropathic and cancer pain.
Dynamics of Existential Personality Fulfillment in the Course of Psychotherapy
Authors: Solobutina Marina M. , Miyassarova Liliya R.
Published: January 2020

The purpose of the study is to explore the clients’ perceptions of therapeutic changes due to their existential fulfillment experience and authenticity in their relationships with the world. The content of the study reveals the subjective perceptions and experiences of clients about the changes in the understanding of themselves and the world in the course of existential psychotherapy. Consideration of the qualitative changes in a person’s life as a result of psychotherapy was based on the concept of existential fulfillment and de-sedimentation of “I-structure”. An opening up of opportunities for experiencing the fullness of human existence, as well as exploring ways of avoiding existential fulfillment, present themselves as key aspects in existential psychotherapy. Research methods are Existence Scale (A. Längle and C. Orgler); semantic differential for measuring therapeutic changes of clients in the course of existential psychotherapy; and factor analysis. Going through a psychotherapeutic experience has a positive effect on the dynamics of self-distancing indices, self-transcendence, freedom, and responsibility. The experience of existential personal fulfillment in psychotherapy leads to changes in human contact with oneself and the ability to successfully interact with the external environment. Experiencing the true existential level of living helps a person to be aware of their needs and to stay in contact with their feelings.
Methods for Determining Mold Development and Condensation on the Surface of Building Barriers
Authors: Starakiewicz Aleksander , Miąsik Przemysław , Krasoń Joanna , Lichołai Lech
Published: January 2020

The article presents four equivalent methods for checking mold growth on the surface of building barriers and checking water vapor condensation on their surface. Each method applies to two parallel phenomena that may occur on a building barrier. The first method is to calculate and compare temperature factors. In the second method, the characteristic humidity in the room is calculated and compared. The third method is to calculate and compare the characteristic temperatures in the room. The fourth method is based on the calculation and comparison of characteristic water vapor pressures. Three boundary conditions are presented for each method and phenomenon: when a given phenomenon can occur, when it begins or ends, and when it does not occur. The presented methods systematize the approach to the problem of mold development and surface condensation. The presented calculation results relate to the selected building barrier functioning in specific indoor and outdoor climate conditions. The calculation results confirm the compliance of the presented methods in identifying the phenomenon of mold growth or condensation on the surface of the barrier. A graphical interpretation of the results for each method with periods of occurrence or absence of a given phenomenon is also presented.
Human Tumor–Derived Matrix Improves the Predictability of Head and Neck Cancer Drug Testing
Authors: Tuomainen Katja , Al-Samadi Ahmed , Potdar Swapnil , Turunen Laura , Turunen Minna , Karhemo Piia-Riitta , Bergman Paula , Risteli Maija , Åström Pirjo , Tiikkaja Riia , Grenman Reidar , Wennerberg Krister , Monni Outi , Salo Tuula
Published: January 2020

In vitro cancer drug testing carries a low predictive value. We developed the human leiomyoma–derived matrix “Myogel” to better mimic the human tumor microenvironment (TME). We hypothesized that Myogel could provide an appropriate microenvironment for cancer cells, thereby allowing more in vivo–relevant drug testing. We screened 19 anticancer compounds, targeting the epidermal growth factor receptor (EGFR), MEK, and PI3K/mTOR on 12 head and neck squamous cell carcinoma (HNSCC) cell lines cultured on plastic, mouse sarcoma–derived Matrigel (MSDM), and Myogel. We applied a high-throughput drug screening assay under five different culturing conditions: cells in two-dimensional (2D) plastic wells and on top or embedded in Matrigel or Myogel. We then compared the efficacy of the anticancer compounds to the response rates of 19 HNSCC monotherapy clinical trials. Cancer cells on top of Myogel responded less to EGFR and MEK inhibitors compared to cells cultured on plastic or Matrigel. However, we found a similar response to the PI3K/mTOR inhibitors under all culturing conditions. Cells grown on Myogel more closely resembled the response rates reported in EGFR-inhibitor monotherapy clinical trials. Our findings suggest that a human tumor matrix improves the predictability of in vitro anticancer drug testing compared to current 2D and MSDM methods.
PML/RARa Interferes with NRF2 Transcriptional Activity Increasing the Sensitivity to Ascorbate of Acute Promyelocytic Leukemia Cells
Authors: Banella Cristina , Catalano Gianfranco , Travaglini Serena , Divona Mariadomenica , Masciarelli Silvia , Guerrera Gisella , Fazi Francesco , Lo-Coco Francesco , Voso Maria Teresa , Noguera Nelida Ines
Published: January 2020

NRF2 (NF-E2 p45-related factor 2) orchestrates cellular adaptive responses to stress. Its quantity and subcellular location is controlled through a complex network and its activity increases during redox perturbation, inflammation, growth factor stimulation, and energy fluxes. Even before all-trans retinoic acid (ATRA) treatment era it was a common experience that acute promyelocytic leukemia (APL) cells are highly sensitive to first line chemotherapy. Since we demonstrated how high doses of ascorbate (ASC) preferentially kill leukemic blast cells from APL patients, we aimed to define the underlying mechanism and found that promyelocytic leukemia/retinoic acid receptor α (PML/RARa) inhibits NRF2 function, impedes its transfer to the nucleus and enhances its degradation in the cytoplasm. Such loss of NRF2 function alters cell metabolism, demarcating APL tissue from both normal promyelocytes and other acute myeloide leukemia (AML) blast cells. Resistance to ATRA/arsenic trioxide (ATO) treatment is rare but grave and the metabolically-oriented treatment with high doses of ASC, which is highly effective on APL cells and harmless on normal hematopoietic stem cells (HSCs), could be of use in preventing clonal evolution and in rescuing APL-resistant patients.
Autophagy in the Immunosuppressive Perivascular Microenvironment of Glioblastoma
Authors: Molina Maria L. , García-Bernal David , Martinez Salvador , Valdor Rut
Published: January 2020

Glioblastoma (GB) has been shown to up-regulate autophagy with anti- or pro-oncogenic effects. Recently, our group has shown how GB cells aberrantly up-regulate chaperone-mediated autophagy (CMA) in pericytes of peritumoral areas to modulate their immune function through cell-cell interaction and in the tumor’s own benefit. Thus, to understand GB progression, the effect that GB cells could have on autophagy of immune cells that surround the tumor needs to be deeply explored. In this review, we summarize all the latest evidence of several molecular and cellular immunosuppressive mechanisms in the perivascular tumor microenvironment. This immunosuppression has been reported to facilitate GB progression and may be differently modulated by several types of autophagy as a critical point to be considered for therapeutic interventions.
An Update on Neurofibromatosis Type 1-Associated Gliomas
Authors: Lobbous Mina , Bernstock Joshua D. , Coffee Elizabeth , Friedman Gregory K. , Metrock Laura K , Chagoya Gustavo , Elsayed Galal , Nakano Ichiro , Hackney James R. , Korf Bruce R. , Nabors Louis B.
Published: January 2020

Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome that affects children and adults. Individuals with NF1 are at high risk for central nervous system neoplasms including gliomas. The purpose of this review is to discuss the spectrum of intracranial gliomas arising in individuals with NF1 with a focus on recent preclinical and clinical data. In this review, possible mechanisms of gliomagenesis are discussed, including the contribution of different signaling pathways and tumor microenvironment. Furthermore, we discuss the recent notable advances in the developing therapeutic landscape for NF1-associated gliomas including clinical trials and collaborative efforts.
The Meniscus Tear: A Review of Stem Cell Therapies
Authors: Jacob George , Shimomura Kazunori , Krych Aaron J. , Nakamura Norimasa
Published: January 2020

Meniscal injuries have posed a challenging problem for many years, especially considering that historically the meniscus was considered to be a structure with no important role in the knee joint. This led to earlier treatments aiming at the removal of the entire structure in a procedure known as a meniscectomy. However, with the current understanding of the function and roles of the meniscus, meniscectomy has been identified to accelerate joint degradation significantly and is no longer a preferred treatment option in meniscal tears. Current therapies are now focused to regenerate, repair, or replace the injured meniscus to restore its native function. Repairs have improved in technique and materials over time, with various implant devices being utilized and developed. More recently, strategies have applied stem cells, tissue engineering, and their combination to potentiate healing to achieve superior quality repair tissue and retard the joint degeneration associated with an injured or inadequately functioning meniscus. Accordingly, the purpose of this current review is to summarize the current available pre-clinical and clinical literature using stem cells and tissue engineering for meniscal repair and regeneration.
Host Calcium Channels and Pumps in Viral Infections
Authors: Chen Xingjuan , Cao Ruiyuan , Zhong Wu
Published: January 2020

Ca2+ is essential for virus entry, viral gene replication, virion maturation, and release. The alteration of host cells Ca2+ homeostasis is one of the strategies that viruses use to modulate host cells signal transduction mechanisms in their favor. Host calcium-permeable channels and pumps (including voltage-gated calcium channels, store-operated channels, receptor-operated channels, transient receptor potential ion channels, and Ca2+-ATPase) mediate Ca2+ across the plasma membrane or subcellular organelles, modulating intracellular free Ca2+. Therefore, these Ca2+ channels or pumps present important aspects of viral pathogenesis and virus–host interaction. It has been reported that viruses hijack host calcium channels or pumps, disturbing the cellular homeostatic balance of Ca2+. Such a disturbance benefits virus lifecycles while inducing host cells’ morbidity. Evidence has emerged that pharmacologically targeting the calcium channel or calcium release from the endoplasmic reticulum (ER) can obstruct virus lifecycles. Impeding virus-induced abnormal intracellular Ca2+ homeostasis is becoming a useful strategy in the development of potent antiviral drugs. In this present review, the recent identified cellular calcium channels and pumps as targets for virus attack are emphasized.
Expression of Adenoviral E1A in Transformed Cells as an Additional Factor of HDACi-Dependent FoxO Regulation
Authors: Morshneva Alisa , Gnedina Olga , Marusova Tamara , Igotti Maria
Published: January 2020

The adenoviral early region 1A (E1A) protein has proapoptotic and angiogenic activity, along with its chemosensitizing effect, making it the focus of increased interest in the context of cancer therapy. It was previously shown that E1A-induced chemosensitization to different drugs, including histone deacetylases inhibitors (HDACi), appears to be mediated by Forkhead box O (FoxO) transcription factors. In this study, we explore the relationship between E1A expression and the modulation of FoxO activity with HDACi sodium butyrate (NaBut). We show here that the basal FoxO level is elevated in E1A-expressing cells. Prolonged NaBut treatment leads to the inhibition of the FoxO expression and activity in E1A-expressing cells. However, in E1A-negative cells, NaBut promotes the transactivation ability of FoxO over time. A more detailed investigation revealed that the NaBut-induced decrease of FoxO activity in E1A-expressing cells is due to the NaBut-dependent decrease in E1A expression. Therefore, NaBut-induced inhibition of FoxO in E1A-positive cells can be overcome under unregulated overexpression of E1A. Remarkably, the CBP/p300-binding domain of E1Aad5 is responsible for stabilization of the FoxO protein. Collectively, these data show that the expression of E1A increases the FoxO stability but makes the FoxO level more sensitive to HDACi treatment.
Is Autophagy Involved in Pepper Fruit Ripening?
Authors: López-Vidal Omar , Olmedilla Adela , Sandalio Luisa María , Sevilla Francisca , Jiménez Ana
Published: January 2020

Autophagy is a universal self-degradation process involved in the removal and recycling of cellular constituents and organelles; however, little is known about its possible role in fruit ripening, in which the oxidation of lipids and proteins and changes in the metabolism of different cellular organelles occur. In this work, we analyzed several markers of autophagy in two critical maturation stages of pepper (Capsicum annuum L.) fruits where variations due to ripening become clearly visible. Using two commercial varieties that ripen to yellow and red fruits respectively, we studied changes in the gene expression and protein content of several autophagy (ATG) components, ATG4 activity, as well as the autophagy receptor NBR1 and the proteases LON1 and LON2. Additionally, the presence of intravacuolar vesicles was analyzed by electron microscopy. Altogether, our data reveal that autophagy plays a role in the metabolic changes which occur during ripening in the two studied varieties, suggesting that this process may be critical to acquiring final optimal quality of pepper fruits.
The Role of Notch Signaling in Macrophages during Inflammation and Infection: Implication in Rheumatoid Arthritis?
Authors: Keewan Esra’a , Naser Saleh A.
Published: January 2020

Notch signaling coordinates numerous cellular processes and has been implicated in many pathological conditions, including rheumatoid arthritis (RA). Although the role of Notch signaling in development, maturation, differentiation, and activation of lymphocytes has been comprehensively reported, less is known about its role in myeloid cells. Certainly, limited data are available about the role of Notch signaling in macrophages during inflammation and infection. In this review, we discuss the recent advances pertaining to the role of Notch signaling in differentiation, activation, and metabolism of macrophages during inflammation and infection. We also highlight the reciprocal interplay between Notch signaling and other signaling pathways in macrophages under different inflammatory and infectious conditions including pathogenesis of RA. Finally, we discuss approaches that could consider Notch signaling as a potential therapeutic target against infection- and inflammation-driven diseases.
Dissimilar Appearances Are Deceptive–Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma
Authors: Linck-Paulus Lisa , Hellerbrand Claus , Bosserhoff Anja K. , Dietrich Peter
Published: January 2020

In this review, we summarize the current knowledge on miRNAs as therapeutic targets in two cancer types that were frequently described to be driven by miRNAs—melanoma and hepatocellular carcinoma (HCC). By focusing on common microRNAs and associated pathways in these—at first sight—dissimilar cancer types, we aim at revealing similar molecular mechanisms that are evolved in microRNA-biology to drive cancer progression. Thereby, we also want to outlay potential novel therapeutic strategies. After providing a brief introduction to general miRNA biology and basic information about HCC and melanoma, this review depicts prominent examples of potent oncomiRs and tumor-suppressor miRNAs, which have been proven to drive diverse cancer types including melanoma and HCC. To develop and apply miRNA-based therapeutics for cancer treatment in the future, it is essential to understand how miRNA dysregulation evolves during malignant transformation. Therefore, we highlight important aspects such as genetic alterations, miRNA editing and transcriptional regulation based on concrete examples. Furthermore, we expand our illustration by focusing on miRNA-associated proteins as well as other regulators of miRNAs which could also provide therapeutic targets. Finally, design and delivery strategies of miRNA-associated therapeutic agents as well as potential drawbacks are discussed to address the question of how miRNAs might contribute to cancer therapy in the future.
Hedgehog and Gpr161: Regulating cAMP Signaling in the Primary Cilium
Authors: Tschaikner Philipp , Enzler Florian , Torres-Quesada Omar , Aanstad Pia , Stefan Eduard
Published: January 2020

Compartmentalization of diverse types of signaling molecules contributes to the precise coordination of signal propagation. The primary cilium fulfills this function by acting as a spatiotemporally confined sensory signaling platform. For the integrity of ciliary signaling, it is mandatory that the ciliary signaling pathways are constantly attuned by alterations in both oscillating small molecules and the presence or absence of their sensor/effector proteins. In this context, ciliary G protein-coupled receptor (GPCR) pathways participate in coordinating the mobilization of the diffusible second messenger molecule 3′,5′-cyclic adenosine monophosphate (cAMP). cAMP fluxes in the cilium are primarily sensed by protein kinase A (PKA) complexes, which are essential for the basal repression of Hedgehog (Hh) signaling. Here, we describe the dynamic properties of underlying signaling circuits, as well as strategies for second messenger compartmentalization. As an example, we summarize how receptor-guided cAMP-effector pathways control the off state of Hh signaling. We discuss the evidence that a macromolecular, ciliary-localized signaling complex, composed of the orphan GPCR Gpr161 and type I PKA holoenzymes, is involved in antagonizing Hh functions. Finally, we outline how ciliary cAMP-linked receptor pathways and cAMP-sensing signalosomes may become targets for more efficient combinatory therapy approaches to counteract dysregulation of Hh signaling.
Facile Route of Fabricating Long-Term Microbicidal Silver Nanoparticle Clusters against Shiga Toxin-Producing Escherichia coli O157:H7 and Candida auris
Authors: Gangadoo Sheeana , Elbourne Aaron , Medvedev Alexander E. , Cozzolino Daniel , Truong Yen B. , Crawford Russell J. , Wang Peng-Yuan , Truong Vi Khanh , Chapman James
Published: January 2020

Microbial contamination remains a significant issue for many industrial, commercial, and medical applications. For instance, microbial surface contamination is detrimental to numerous aspects of food production, infection transfer, and even marine applications. As such, intense scientific interest has focused on improving the antimicrobial properties of surface coatings via both chemical and physical routes. However, there is a lack of synthetic coatings that possess long-term microbiocidal performance. In this study, silver nanoparticle cluster coatings were developed on copper surfaces via an ion-exchange and reduction reaction, followed by a silanization step. The durability of the microbiocidal activity for these develped surfaces was tested against pathogenic bacterial and fungal species, specifically Escherichia coli O157:H7 and Candida auris, over periods of 1- and 7-days. It was observed that more than 90% of E. coli and C. auris were found to be non-viable following the extended exposure times. This facile material fabrication presents as a new surface design for the production of durable microbicidal coatings which can be applied to numerous applications.
Lossy Mode Resonance Sensors Fabricated by RF Magnetron Sputtering GZO Thin Film and D-Shaped Fibers
Authors: Tien Chuen-Lin , Mao Tzu-Chi , Li Chi-Yuan
Published: January 2020

We demonstrate a new refractive index (RI) and salinity sensor based on a lossy mode resonance (LMR) effect which combines fiber-optic side-polishing and radio-frequency (RF) sputtering techniques. The side-polished fiber can enhance optical fibers to generate an evanescent field in sensing applications. Gallium-doped zinc oxide (GZO) thin films produce a high attenuation lossy mode resonance effect that permits a highly sensitive refractive index and salinity fiber sensor. GZO thin film was prepared by an RF magnetron sputtering method. The thickness of the D-shaped fiber sensing device was 74.7 μm, and a GZO film thickness of 67 nm was deposited on the polished surface of the D-shaped fiber to fabricate LMR type liquid salinity sensors. The sensitivity of 3637.8 nm/RIU was achieved in the RI range of 1.333 to 1.392. To investigate the sensitivities of LMR salinity sensors, the NaCl solution salinities of 0%, 50%, 100%, 150%, 200%, and 250% were measured in this work. The experimental result shows that the sensitivity of the salinity sensor is 0.964 nm per salinity unit (SU).