bluuebunny/crossref_metadata_2025 huggingface dataset:
Building Energy Consumption Raw Data Forecasting Using Data Cleaning and Deep Recurrent Neural Networks
Authors: Yang Junjing , Tan Kok Keng , Santamouris Mat , Lee Siew Eang
Published: September 2019

With the rising focus on building energy big data analysis, there lacks a framework for raw data preprocessing to answer the question of how to handle the missing data in the raw data set. This study presents a methodology and framework for building energy consumption raw data forecasting. A case building is used to forecast the energy consumption by using deep recurrent neural networks. Four different methodologies to impute missing data in the raw data set are compared and implemented. The question of sensitivity of gap size and available data percentage on the imputation accuracy was tested. The cleaned data were then used for building energy forecasting. While the existing studies explored only the use of small recurrent networks of 2 layers and less, the question of whether a deep network of more than 2 layers would be performing better for building energy consumption forecasting should be explored. In addition, the problem of overfitting has been cited as a significant problem in using deep networks. In this study, the deep recurrent neural network is then used to explore the use of deeper networks and their regularization in the context of an energy load forecasting task. The results show a mean absolute error of 2.1 can be achieved through the 2*32 gated neural network model. In applying regularization methods to overcome model overfitting, the study found that weights regularization did indeed delay the onset of overfitting.
Comparative Study of the Reactivity of the Tungsten Oxides WO2 and WO3 with Beryllium at Temperatures up to 1273 K
Authors: Köppen Martin
Published: September 2019

Tungsten oxides play a pivotal role in a variety of modern technologies, e.g., switchable glasses, wastewater treatment, and modern gas sensors. Metallic tungsten is used as armor material, for example in gas turbines as well as future fusion power devices. In the first case, oxides are desired as functional materials; while in the second case, oxides can lead to catastrophic failures, so avoiding the oxidation of tungsten is desired. In both cases, it is crucial to understand the reactivity of tungsten oxides with other chemicals. In this study, the different reactivities of tungsten oxides with the highly-oxophilic beryllium are studied and compared. Tungsten-(IV)-oxide and tungsten-(VI)-oxide layers are prepared on a tungsten substrate. In the next step, a thin film of beryllium is evaporated on the samples. In consecutive steps, the sample is heated in steps of 100 K from room temperature (r. t.) to 1273 K. The chemical composition is investigated after each experimental step by high-resolution X-ray photoelectron spectroscopy (XPS) for all involved core levels as well as the valence band. A model is developed to analyze the chemical reactions after each step. In this study, we find that tungsten trioxide was already reduced by beryllium at r. t. and started to react to form the ternary compounds BeWO3 and BeWO4 at temperatures starting from 673 K. However, tungsten dioxide is resistant to reduction at temperatures of up to 1173 K. In conclusion, we find WO2 to be much more chemically resistant to the reduction agent Be than WO3.
“Not Thinking that This Means the End When You Are Seriously Ill but Doing Something Positive about It”—A Qualitative Study of Living with A Life-Changing Disease
Authors: Benkel Inger , Ljungqvist Elin , Arnby Maria , Molander Ulla
Published: September 2019

Background: Chronic diseases have an impact on and can change the lives of the persons affected by them. This study examines how a disease can influence patients’ daily lives, the strategies they adopt to cope, and their experiences of support. The study focuses on four chronic diseases: asthma-allergy, cancer, diabetes mellitus, and inflammatory rheumatic arthritis. Methods: The study has a qualitative design and includes 41 transcribed in-depth interviews and a content analysis. Results: The participants’ new life situation was changed for a very long time or forever, and this was not a voluntary choice. The new life situation comprised the following themes: life-changing—the disease could be a turning point in a negative or positive way, strategies—designed to create ways of coping with daily tasks to find a good quality of life, and support—that could be obtained from the participants’ private network or the healthcare professionals. Conclusions: The patients had to make changes in their daily life, and these could bring about different feelings and restrict activity. Healthcare professionals need more knowledge of the process of coping with such life-changing matters and what could strengthen patients and give a sense of empowerment in their lives.
ℓp-STFT: A Robust Parameter Estimator of a Frequency Hopping Signal for Impulsive Noise
Authors: Su Yang , Wang Lina , Chen Yuan , Yang Xiaolong
Published: September 2019

Impulsive noise is commonly present in many applications of actual communication networks, leading to algorithms based on the Gaussian model no longer being applicable. A robust parameter estimator of frequency-hopping (FH) signals suitable for various impulsive noise environments, referred to as ℓp-STFT, is proposed. The ℓp-STFT estimator replaces the ℓ2-norm by using the generalized version ℓp-norm where 1 < p < 2 for the derivation of the short-time Fourier transform (STFT) as an objective function. It combines impulsive noise processing with any time-frequency analysis algorithm based on STFT. Considering the accuracy of parameter estimation, the double-window spectrogram difference (DWSD) algorithm is used to illustrate the suitability of ℓp-STFT. Computer simulations are mainly conducted in α-stable noise to compare the performance of ℓp-STFT with STFT and fractional low-order STFT (FLOSTFT), Cauchy noise, and Gaussian mixture noise as supplements of different background noises to better demonstrate the robustness and accuracy of ℓp-STFT.
Microalgae Cultivation in Pilot Scale for Biomass Production Using Exhaust Gas from Thermal Power Plants
Authors: Park Sanghyun , Ahn Yongtae , Pandi Kalimuthu , Ji Min-Kyu , Yun Hyun-Shik , Choi Jae-Young
Published: September 2019

Exhaust gases from thermal power plants have the highest amount of carbon dioxide (CO2), presenting an environmental problem related to a severe impact on ecosystems. Extensively, the reduction of CO2 from thermal power plants has been considered with the aid of microalgae as a cost-effective, sustainable solution, and efficient biological means for recycling of CO2. Microalgae can efficiently uptake CO2 and nutrients resulting in high generation of biomass and which can be processed into different valuable products. In this study, we have taken Nephroselmis sp. KGE8, Acutodesmus obliquus KGE 17 and Acutodesmus obliquus KGE32 microalgae, which are isolated from acid mine drainage and cultivated in a photobiological incubator on a batch scale, and also confirmed that continuous culture was possible on pilot scale for biofuel production. We also evaluated the continuous culture productivity of each cultivate-harvest cycle in the pilot scale. The biomass of the cultivated microalgae was also evaluated for its availability.
Gas Turbine Cycle with External Combustion Chamber for Prosumer and Distributed Energy Systems
Authors: Mikielewicz Dariusz , Kosowski Krzysztof , Tucki Karol , Piwowarski Marian , Stępień Robert , Orynycz Olga , Włodarski Wojciech
Published: September 2019

The use of various biofuels, usually of relatively small Lower Heating Value (LHV), affects the gas turbine efficiency. The present paper shows that applying the proposed air by-pass system of the combustor at the turbine exit causes tan increase of efficiency of the turbine cycle increased by a few points. This solution appears very promising also in combined gas/steam turbine power plants. The comparison of a turbine set operating according to an open cycle with partial bypassing of external combustion chamber at the turbine exit (a new solution) and, for comparison, a turbine set operating according to an open cycle with a regenerator. The calculations were carried out for different fuels: gas from biomass gasification (LHV = 4.4 MJ/kg), biogas (LHV = 17.5 MJ/kg) and methane (LHV = 50 MJ/kg). It is demonstrated that analyzed solution enables construction of several kW power microturbines that might be used on a local scale. Such turbines, operated by prosumer’s type of organizations may change the efficiency of electricity generation on a country-wide scale evidently contributing to the sustainability of power generation, as well as the economy as a whole.
Cooling Performance Enhancement of Air-Cooled Condensers by Guiding Air Flow
Authors: Huang Xianwei , Chen Lin , Yang Lijun , Du Xiaoze , Yang Yongping
Published: September 2019

Adverse wind effects on the thermo-flow performances of air-cooled condensers (ACCs) can be effectively restrained by wind-proof devices, such as air deflectors. Based on a 2 × 300 MW coal-fired power generation unit, two types (plane and arc) of air deflectors were installed beneath the peripheral fans to improve the ACC’s cooling performance. With and without air deflectors, the air velocity, temperature, and pressure fields near the ACCs were simulated and analyzed in various windy conditions. The total air mass flow rate and unit back pressure were calculated and compared. The results show that, with the guidance of deflectors, reverse flows are obviously suppressed in the upwind condenser cells under windy conditions, which is conducive to an increased mass flow rate and heat dissipation and, subsequently, introduces a favorable thermo-flow performance of the cooling system. When the wind speed increases, the leading flow effect of the air deflectors improves, and improvements in the ACC’s performance in the wind directions of 45° and −45° are more satisfactory. However, hot plume recirculation may impede performance when the wind direction is 0°. For all cases, air deflectors in an arc shape are recommended to restrain the disadvantageous wind effects.
High-Quality All-Inorganic Perovskite CsPbBr3 Quantum Dots Emitter Prepared by a Simple Purified Method and Applications of Light-Emitting Diodes
Authors: Tien Ching-Ho , Chen Lung-Chien , Lee Kun-Yi , Tseng Zong-Liang , Dong Yu-Shen , Lin Zi-Jun
Published: September 2019

High-quality perovskite CsPbBr3 quantum dots (QDs-CsPbBr3) were prepared using the ultrasonic oscillation method, which is simple and provides variable yield according to requirements. The emission spectra over a large portion of the visible spectral region (450–650 nm) of QD-CsPbX3 (X = Cl, Br, and I) have tunable compositions that can be halide exchanged using the halide anion exchange technique and quantum size-effects. A strong peak with high intensity of (200) lattice plane of purified QDs-CsPbBr3 film is obtained, confirming the formation of an orthorhombic perovskite crystal structure of the Pnma space group. The photoluminescence of QDs-CsPbBr3 was characterized using a narrow line-width emission of 20 nm, with high quantum yields of up to 99.2%, and radioactive lifetime increasing to 26 ns. Finally, through the excellent advantages of QDs-CsPbBr3 mentioned above, purified perovskite QDs-CsPbBr3 as an active layer was utilized in perovskite quantum dot light-emitting diodes structure applications. As a result, the perovskite QDs-CsPbBr3 light-emitting diodes (LEDs) exhibits a turn-on voltage of 7 V and a maximum luminance of 5.1 cd/m2.
Financial Preparation, Disaster Experience, and Disaster Risk Perception of Rural Households in Earthquake-Stricken Areas: Evidence From the Wenchuan and Lushan Earthquakes in China’s Sichuan Province
Authors: Xu Dingde , Yong Zhuolin , Deng Xin , Liu Yi , Huang Kai , Zhou Wenfeng , Ma Zhixing
Published: September 2019

Sichuan is a province in Southwest China that is famous worldwide for its earthquakes. However, few quantitative studies in China have probed the correlations between rural households’ financial preparation, disaster experience, and disaster-risk perception. Using survey data of 327 rural households from four areas stricken by the Wenchuan Earthquake and Lushan Earthquake in Sichuan, the ordinary least square (OLS) method was used to quantitatively explore the correlations between these three factors. The results show that rural households’ total family cash income, asset diversity, and whether rural households can borrow money from relatives and friends whenever there is a catastrophe such as an earthquake are significantly negatively correlated with the probability of disaster occurrence. Asset diversity and whether rural households can borrow money from banks whenever there is a catastrophe such as an earthquake are significantly positively related to the severity of disaster occurrence. The severity of residents’ disaster experience is not significantly correlated with the probability of disaster occurrence, but is significantly positively related to the severity of the disaster. The research results can provide useful enlightenment for the improvement of financial preparedness and disaster risk management for rural households in earthquake-stricken areas.
Assessment of Overheating Risk in Gynaecology Scanning Rooms during Near-Heatwave Conditions: A Case Study of the Royal Berkshire Hospital in the UK
Authors: Gough Hannah , Faulknall-Mills Samuel , King Marco-Felipe , Luo Zhiwen
Published: September 2019

Hospital buildings in the UK are at particular risk to rising summer temperatures associated with climate change. Balancing the thermal needs of patients, staff, and visitors is a challenging, complex endeavour. A case study of the ultrasound area of the Royal Berkshire Hospital’s Maternity and Gynaecology building is presented, where temperatures were measured for 35 days in waiting areas, staff offices, and ultrasound scanning rooms, aiming to assess the overheating risk posed to occupants. Local external temperature measurements were used for comparison whereby determining the indoor-outdoor environmental connection. Results show that most rooms had already breached standard overheating thresholds within the study period. Anthropogenic and waste heat from equipment has a noticeable effect on indoor temperatures. Local air-conditioning helped reduce the peaks in temperature seen between 14:00 and 17:00 for similar scanning rooms but is in contradiction to the National Health Service’s sustainability plans. Several low-level solutions such as improved signage, access to water, and the allocation of vulnerable patients to morning clinics are suggested. Barriers to solutions are also discussed and the requirement of sufficient maintenance plans for cooling equipment is empathised. These solutions are likely to be applicable to other hospital buildings experiencing similar conditions.
Characterizing Consumer Behavior in Leveraging Social Media for E-Patient and Health-Related Activities
Authors: Puspitasari Ira , Firdauzy Alia
Published: September 2019

The emergence of e-patients has encouraged consumers, people who are non-medical experts, to be more engaged in healthcare needs by utilizing online sources via social media. However, the nature of social media and regulation issues have caused concerns for the reliability and validity of the shared information. These phenomena shape consumers behavior in leveraging social media for e-patient activities. This study investigates consumer behavior using an integrated model based on the Unified Theory of Acceptance and Use of Technology (UTAUT) and the Protection Motivation Theory (PMT). The data collected from the participants (N = 312) was analyzed using partial least square structural equation modelling. The results showed that behavioral intention to use social media for e-patient activities was significantly affected by performance expectancy, effort expectancy, perceived severity, perceived susceptibility, and response efficacy; and that behavioral intention corresponded positively to usage intention. In addition, the results also indicate that the intention to use social media for health-related purposes is driven by awareness of preventing health problems and attempts to reduce the risk of developing an illness. Based on findings, this study recommends strategies and initiatives to optimize social media for promoting a healthy lifestyle and educating society about public health and healthcare management.
Effectiveness of Diabetes Community Sharp Disposal Education Module in Primary Care: An Experimental Study in North-East Peninsular Malaysia
Authors: Hasan Ummu Atiyyah , Mohd Hairon Suhaily , Yaacob Najib Majdi , Daud Aziah , Abdul Hamid Anees , Hassan Norzaihan , Ariffin Mohd Faiz , Yi Vun Lau
Published: September 2019

Background: Structured education is needed to cultivate safe sharp disposal behavior among diabetic patients. Thus, this study aimed to assess the effectiveness of the Diabetes Community Sharp Disposal Education Module in improving knowledge and sharp disposal practice among Malaysian Type 2 diabetic patients. Methods: This quasi-experimental study was conducted at primary health clinics in two districts in Kelantan, a state in the North-East Region of Peninsular Malaysia. A total of 132 Type 2 diabetic patients on insulin therapy were involved, with 68 participants in each control and intervention group. The health education intervention was based on the validated Diabetes Community Sharp Disposal Education Module. The knowledge and practices were measured using a validated questionnaire at baseline, one month, and three months after the intervention. Results: There was a significant increment in the mean knowledge score for intervention group; from baseline to one month follow up and from baseline to three months follow up [Greenhouse-Geisser; F(1.5, 199.7) = 62.38, p < 0.001; effect size (η2) = 0.318]. Intervention group had significantly higher mean knowledge score as compared to control group; at one month and three months follow up [F(1, 134) = 17.38, p < 0.001; effect size (η2) = 0.115]. There was a statistically significant increment in the proportion of participants in the intervention group who practiced the proper community sharp disposal method over time, X2(2) = 52.061, p < 0.001. Conclusions: The Diabetes Community Sharp Disposal Education Module was an effective health education tool to improve knowledge and encourage Malaysian diabetic patients to engage with proper sharp disposal practices.
Advertising Restrictions and Market Concentration in the Cigarette Industry: A Cross-Country Analysis
Authors: Mirza Maryam
Published: September 2019

There has been a large increase in the adoption of tobacco advertising restrictions worldwide over the last two decades. Much of the literature studies their direct effect on cigarette demand. This paper investigates the indirect effect of advertising restrictions by evaluating the effect of the policies on the degree of concentration in the tobacco market. By using the variation between countries in timing of adoption of advertising restrictions, I estimate difference-in-difference models to examine the effect of an advertising ban on market-concentration, as measured by HHI. I find that advertising bans lead to an increase in market-concentration: HHI increased by 0.06 points for countries that adopted a ban between 2001 and 2017 conditional on trade and socio-economic characteristics, representing a 13% increase with respect to the mean (0.44). The effect is higher in developing countries (0.08 points increase). Further, I find that ‘comprehensive’ restrictions have a stronger impact on concentration, and ‘limited’ restrictions have little or no impact. These findings point to an important trade-off for policymakers: on one hand, advertising restrictions are likely to reduce consumption of cigarettes; on the other hand, due to an increase in market-concentration, they may be giving more power to tobacco companies.
Involvement of Dual Strands of miR-143 (miR-143-5p and miR-143-3p) and Their Target Oncogenes in the Molecular Pathogenesis of Lung Adenocarcinoma
Authors: Sanada Hiroki , Seki Naohiko , Mizuno Keiko , Misono Shunsuke , Uchida Akifumi , Yamada Yasutaka , Moriya Shogo , Kikkawa Naoko , Machida Kentaro , Kumamoto Tomohiro , Suetsugu Takayuki , Inoue Hiromasa
Published: September 2019

Our analyses of tumor-suppressive microRNAs (miRNAs) and their target oncogenes have identified novel molecular networks in lung adenocarcinoma (LUAD). Moreover, our recent studies revealed that some passenger strands of miRNAs contribute to cancer cell malignant transformation. Downregulation of both strands of the miR-143 duplex was observed in LUAD clinical specimens. Ectopic expression of these miRNAs suppressed malignant phenotypes in cancer cells, suggesting that these miRNAs have tumor-suppressive activities in LUAD cells. Here, we evaluated miR-143-5p molecular networks in LUAD using genome-wide gene expression and miRNA database analyses. Twenty-two genes were identified as potential miR-143-5p-controlled genes in LUAD cells. Interestingly, the expression of 11 genes (MCM4, RAD51, FAM111B, CLGN, KRT80, GPC1, MTL5, NETO2, FANCA, MTFR1, and TTLL12) was a prognostic factor for the patients with LUAD. Furthermore, knockdown assays using siRNAs showed that downregulation of MCM4 suppressed cell growth, migration, and invasion in LUAD cells. Aberrant expression of MCM4 was confirmed in the clinical specimens of LUAD. Thus, we showed that miR-143-5p and its target genes were involved in the molecular pathogenesis of LUAD. Identification of tumor-suppressive miRNAs and their target oncogenes may be an effective strategy for elucidation of the molecular oncogenic networks of this disease.
Conflicting Roles of 20-HETE in Hypertension and Stroke
Authors: Shekhar Shashank , Varghese Kevin , Li Man , Fan Letao , Booz George , Roman Richard , Fan Fan
Published: September 2019

Hypertension is the most common modifiable risk factor for stroke, and understanding the underlying mechanisms of hypertension and hypertension-related stroke is crucial. 20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid (20-HETE), which plays an important role in vasoconstriction, autoregulation, endothelial dysfunction, angiogenesis, inflammation, and blood-brain barrier integrity, has been linked to hypertension and stroke. 20-HETE can promote hypertension by potentiating the vascular response to vasoconstrictors; it also can reduce blood pressure by inhibition of sodium transport in the kidney. The production of 20-HETE is elevated after the onset of both ischemic and hemorrhagic strokes; on the other hand, subjects with genetic variants in CYP4F2 and CYP4A11 that reduce 20-HETE production are more susceptible to stroke. This review summarizes recent genetic variants in CYP4F2, and CYP4A11 influencing 20-HETE production and discusses the role of 20-HETE in hypertension and the susceptibility to the onset, progression, and prognosis of ischemic and hemorrhagic strokes.
BTLA Expression on Th1, Th2 and Th17 Effector T-Cells of Patients with Systemic Lupus Erythematosus Is Associated with Active Disease
Authors: Oster Christoph , Wilde Benjamin , Specker Christof , Sun Ming , Kribben Andreas , Witzke Oliver , Dolff Sebastian
Published: September 2019

An imbalanced T-cell homeostasis plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). Co-stimulatory and co-inhibitory molecules regulate T-cell differentiation, survival, and cytokine production. B- and T-lymphocyte attenuator (BTLA) is a co-inhibitory molecule which negatively regulates T-cell activation. The aim of this study was to investigate BTLA expression on regulatory and effector CD4+ T-cells in SLE patients with and without lupus nephritis (LN) during active and inactive disease. Therefore, peripheral blood of forty-one SLE patients and twenty-one healthy controls (HC) was phenotypically analyzed. Next, ex vivo stimulated T-cells were analyzed for the expression of BTLA on Th1-, Th2-, and Th17-effector cells by flow cytometry. Renal involvement was defined as biopsy-proven LN. Disease activity was assessed by SLE disease activity index (SLEDAI). Percentages of peripheral unstimulated BTLA+ CD4+ T-cells were significantly decreased in SLE patients with active disease. However, ex vivo stimulated Th1, Th2, and Th17 effector T-cells, expressed increased percentages of BTLA expression in active disease. In contrast, the BTLA expression on CD4+CD25++CD127− regulatory T-cells was not significantly different. BTLA seems to be an important co-inhibitory molecule in the T-cell homeostasis of patients with systemic lupus erythematosus and crucial for disease activity.
The Role of MMP8 in Cancer: A Systematic Review
Authors: Juurikka Krista , Butler Georgina S. , Salo Tuula , Nyberg Pia , Åström Pirjo
Published: September 2019

Matrix metalloproteinases (MMPs) have traditionally been considered as tumor promoting enzymes as they degrade extracellular matrix components, thus increasing the invasion of cancer cells. It has become evident, however, that MMPs can also cleave and alter the function of various non-matrix bioactive molecules, leading to both tumor promoting and suppressive effects. We applied systematic review guidelines to study MMP8 in cancer including the use of MMP8 as a prognostic factor or as a target/anti-target in cancer treatment, and its molecular mechanisms. A total of 171 articles met the inclusion criteria. The collective evidence reveals that in breast, skin and oral tongue cancer, MMP8 inhibits cancer cell invasion and proliferation, and protects patients from metastasis via cleavage of non-structural substrates. Conversely, in liver and gastric cancers, high levels of MMP8 worsen the prognosis. Expression and genetic alterations of MMP8 can be used as a prognostic factor by examination of the tumor and serum/plasma. We conclude, that MMP8 has differing effects on cancers depending on their tissue of origin. The use of MMP8 as a prognostic factor alone, or with other factors, seems to have potential. The molecular mechanisms of MMP8 in cancer further emphasize its role as an important regulator of bioactive molecules.
Heat Shock Proteins Are Essential Components in Transformation and Tumor Progression: Cancer Cell Intrinsic Pathways and Beyond
Authors: Lang Benjamin J. , Guerrero-Giménez Martín Eduardo , Prince Thomas L. , Ackerman Andrew , Bonorino Cristina , Calderwood Stuart K.
Published: September 2019

Heat shock protein (HSP) synthesis is switched on in a remarkably wide range of tumor cells, in both experimental animal systems and in human cancer, in which these proteins accumulate in high levels. In each case, elevated HSP concentrations bode ill for the patient, and are associated with a poor outlook in terms of survival in most cancer types. The significance of elevated HSPs is underpinned by their essential roles in mediating tumor cell intrinsic traits such as unscheduled cell division, escape from programmed cell death and senescence, de novo angiogenesis, and increased invasion and metastasis. An increased HSP expression thus seems essential for tumorigenesis. Perhaps of equal significance is the pronounced interplay between cancer cells and the tumor milieu, with essential roles for intracellular HSPs in the properties of the stromal cells, and their roles in programming malignant cells and in the release of HSPs from cancer cells to influence the behavior of the adjacent tumor and infiltrating the normal cells. These findings of a triple role for elevated HSP expression in tumorigenesis strongly support the targeting of HSPs in cancer, especially given the role of such stress proteins in resistance to conventional therapies.
Cx43-Gap Junctions Accumulate at the Cytotoxic Immunological Synapse Enabling Cytotoxic T Lymphocyte Melanoma Cell Killing
Authors: Hofmann Francisca , Navarrete Mariela , Álvarez Javiera , Guerrero Israel , Gleisner María Alejandra , Tittarelli Andrés , Salazar-Onfray Flavio
Published: September 2019

Upon tumor antigen recognition, cytotoxic T lymphocytes (CTLs) and target cells form specialized supramolecular structures, called cytotoxic immunological synapses, which are required for polarized delivery of cytotoxic granules. In previous reports, we described the accumulation of connexin 43 (Cx43)-formed gap junctions (GJs) at natural killer (NK) cell–tumor cell cytotoxic immunological synapse. In this report, we demonstrate the functional role of Cx43-GJs at the cytotoxic immunological synapse established between CTLs and melanoma cells during cytotoxicity. Using confocal microscopy, we evaluated Cx43 polarization to the contact site between CTLs isolated from pMEL-1 mice and B16F10 melanoma cells. We knocked down Cx43 expression in B16F10 cells and evaluated its role in the formation of functional GJs and the cytotoxic activity of CTLs, by calcein transfer and granzyme B activity assays, respectively. We found that Cx43 localizes at CTL/B16F10 intercellular contact sites via an antigen-dependent process. We also found that pMEL-1 CTLs but not wild-type naïve CD8+ T cells established functional GJs with B16F10 cells. Interestingly, we observed that Cx43-GJs were required for an efficient granzyme B activity in target B16F10 cells. Using an HLA-A2-restricted/MART-1-specific CD8+ T-cell clone, we confirmed these observations in human cells. Our results suggest that Cx43-channels are relevant components of cytotoxic immunological synapses and potentiate CTL-mediated tumor cell killing.
Mechanism of Action of the Tumor Vessel Targeting Agent NGR-hTNF: Role of Both NGR Peptide and hTNF in Cell Binding and Signaling
Authors: Valentinis Barbara , Porcellini Simona , Asperti Claudia , Cota Manuela , Zhou Dan , Di Matteo Paola , Garau Gianpiero , Zucchelli Chiara , Avanzi Nilla Roberta , Rizzardi Gian Paolo , Degano Massimo , Musco Giovanna , Traversari Catia
Published: September 2019

NGR-hTNF is a therapeutic agent for a solid tumor that specifically targets angiogenic tumor blood vessels, through the NGR motif. Its activity has been assessed in several clinical studies encompassing tumors of different histological types. The drug’s activity is based on an improved permeabilization of newly formed tumor vasculature, which favors intratumor penetration of chemotherapeutic agents and leukocyte trafficking. This work investigated the binding and the signaling properties of the NGR-hTNF, to elucidate its mechanism of action. The crystal structure of NGR-hTNF and modeling of its interaction with TNFR suggested that the NGR region is available for binding to a specific receptor. Using 2D TR-NOESY experiments, this study confirmed that the NGR-peptides binds to a specific CD13 isoform, whose expression is restricted to tumor vasculature cells, and to some tumor cell lines. The interaction between hTNF or NGR-hTNF with immobilized TNFRs showed similar kinetic parameters, whereas the competition experiments performed on the cells expressing both TNFR and CD13 showed that NGR-hTNF had a higher binding affinity than hTNF. The analysis of the NGR-hTNF-triggered signal transduction events showed a specific impairment in the activation of pro-survival pathways (Ras, Erk and Akt), compared to hTNF. Since a signaling pattern identical to NGR-hTNF was obtained with hTNF and NGR-sequence given as distinct molecules, the inhibition observed on the survival pathways was presumably due to a direct effect of the NGR-CD13 engagement on the TNFR signaling pathway. The reduced activation of the pro survival pathways induced by NGR-hTNF correlated with the increased caspases activation and reduced cell survival. This study demonstrates that the binding of the NGR-motif to CD13 determines not only the homing of NGR-hTNF to tumor vessels, but also the increase in its antiangiogenic activity.
Synergistic Neuroprotective Effect of Schisandra chinensis and Ribes fasciculatum on Neuronal Cell Death and Scopolamine-Induced Cognitive Impairment in Rats
Authors: Park Eunkuk , Ryu Min Jeong , Kim Nam Ki , Bae Mun Hyoung , Seo Youngha , Kim Jeonghyun , Yeo Subin , Kanwal Memoona , Choi Chun Whan , Heo Jun Young , Jeong Seon-Yong
Published: September 2019

Mild cognitive impairment (MCI) is considered as a transitional stage between aging and Alzheimer’s disease. In the present study, we examined the protective effect of Schisandra chinensis (SC) and Ribes fasciculatum (RF) on neuronal cell death in vitro and scopolamine-induced cognitive impairment in Sprague Dawley® rats in vivo. A mixture of SC and RF extracts (SC+RF) significantly protected against hydrogen peroxide-induced PC12 neuronal cell death. The neuroprotective effect of SC+RF on scopolamine-induced memory impairment in rats was evaluated using the passive avoidance test and the Morris water maze test. In the passive avoidance test, SC+RF-treated rats showed an increased latency to escape, compared to the scopolamine-treated rats. Moreover, SC+RF treatment significantly reduced escape latency in water maze test, compared to treatment with scopolamine alone. To verify the long-term memory, we performed probe test of water maze test. As a result, rat treated with SC+RF spent more time in the target quadrant. Consistent with enhancement of memory function, the brain derived neurotrophic factor (BDNF) and its downstream molecules (pERK, pATK, and pCREB) are increased in SC+RF treatment in hippocampal area compared with scopolamine treated group. These results suggest that a mixture of SC and RF extracts may be a good therapeutic candidate for preventing mild cognitive impairment.
Chemical and Transcriptomic Analysis of Cuticle Lipids under Cold Stress in Thellungiella salsuginea
Authors: He Junqing , Tang Shuai , Yang Di , Chen Yue , Ling Ludi , Zou Yanli , Zhou Minqi , Xu Xiaojing
Published: September 2019

Plant cuticle lipids form outer protective layers to resist environmental stresses; however, the relationship between cuticle properties and cold tolerance is unclear. Here, the extremophyte Thellungiella salsuginea was stressed under cold conditions (4 °C) and the cuticle of rosette leaves was examined in terms of epicuticular wax crystal morphology, chemical composition, and cuticle-associated gene expression. The results show that cold induced formation of distinct lamellas within the cuticle ultrastructure. Cold stress caused 14.58% and 12.04% increases in the amount of total waxes and cutin monomer per unit of leaf area, respectively, probably associated with the increase in total fatty acids. The transcriptomic analysis was performed on rosette leaves of Thellungiella exposed to cold for 24 h. We analyzed the expression of 72 genes putatively involved in cuticle lipid metabolism, some of which were validated by qRT-PCR (quantitative reverse transcription PCR) after both 24 h and one week of cold exposure. Most cuticle-associated genes exhibited higher expression levels under cold conditions, and some key genes increased more dramatically over the one week than after just 24 h, which could be associated with increased amounts of some cuticle components. These results demonstrate that the cuticle provides some aspects of cold adaptation in T. salsuginea.
Transcription Factors AhR/ARNT Regulate the Expression of CYP6CY3 and CYP6CY4 Switch Conferring Nicotine Adaptation
Authors: Pan Yiou , Peng Tianfei , Xu Pengjun , Zeng Xiaochun , Tian Fayi , Song Jiabao , Shang Qingli
Published: September 2019

Nicotine is one of the most toxic secondary plant metabolites in nature and it is highly toxic to herbivorous insects. The overexpression of CYP6CY3 and its homologous isozyme CYP6CY4 in Myzus persicae nicotianae is correlated with nicotine tolerance. The expanded (AC)n repeat in promoter is the cis element for CYP6CY3 transcription. These repeat sequences are conserved in the CYP6CY3 gene from Aphis gossypii and the homologous P450 genes in Acyrthosiphon pisum. The potential transcriptional factors that may regulate CYP6CY3 were isolated by DNA pulldown and sequenced in order to investigate the underlying transcriptional regulation mechanism of CYP6CY3. These identified transcriptional factors, AhR and ARNT, whose abundance was highly correlated with an abundance of the CYP6CY3 gene, were validated. RNAi and co-transfection results further confirm that AhR and ARNT play a major role in the transcriptional regulation of the CYP6CY3 gene. When the CYP6CY3 transcript is destabilized by AhR/ARNT RNAi, the transcription of the CYP6CY4 is dramatically up-regulated, indicating a compensatory mechanism between the CYP6CY3 and CYP6CY4 genes. Our present study sheds light on the CYP6CY3 and CYP6CY4 mediated nicotine adaption of M. persicae nicotianae to tobacco. The current studies shed light on the molecular mechanisms that underlie the genotypic and phenotypic changes that are involved in insect host shifts and we conclude that AhR/ARNT regulate the expression of CYP6CY3 and CYP6CY4 cooperatively, conferring the nicotine adaption of M. persicae nicotianae to tobacco
Oxysterols in Autoimmunity
Authors: Duc Donovan , Vigne Solenne , Pot Caroline
Published: September 2019

Cholesterol is a member of the sterol family that plays essential roles in biological processes, including cell membrane stability and myelin formation. Cholesterol can be metabolized into several molecules including bile acids, hormones, and oxysterols. Studies from the last few decades have demonstrated that oxysterols are not only active metabolites but are further involved in the modulation of immune responses. Liver X Receptors (LXRs), nuclear receptors for oxysterols, are important for cholesterol homeostasis and regulation of inflammatory response but are still poorly characterized during autoimmune diseases. Here we review the current knowledge about the role of oxysterols during autoimmune conditions and focus on the implication of LXR-dependent and LXR-independent pathways. We further highlight the importance of these pathways in particular during central nervous system (CNS) autoimmunity and inflammatory bowel diseases (IBD) in both experimental models and human studies. Finally, we discuss our vision about future applications and research on oxysterols related to autoimmunity.
Calcium Mobilization in Endothelial Cell Functions
Authors: Filippini Antonio , D’Amore Antonella , D’Alessio Alessio
Published: September 2019

Endothelial cells (ECs) constitute the innermost layer that lines all blood vessels from the larger arteries and veins to the smallest capillaries, including the lymphatic vessels. Despite the histological classification of endothelium of a simple epithelium and its homogeneous morphological appearance throughout the vascular system, ECs, instead, are extremely heterogeneous both structurally and functionally. The different arrangement of cell junctions between ECs and the local organization of the basal membrane generate different type of endothelium with different permeability features and functions. Continuous, fenestrated and discontinuous endothelia are distributed based on the specific function carried out by the organs. It is thought that a large number ECs functions and their responses to extracellular cues depend on changes in intracellular concentrations of calcium ion ([Ca2+]i). The extremely complex calcium machinery includes plasma membrane bound channels as well as intracellular receptors distributed in distinct cytosolic compartments that act jointly to maintain a physiological [Ca2+]i, which is crucial for triggering many cellular mechanisms. Here, we first survey the overall notions related to intracellular Ca2+ mobilization and later highlight the involvement of this second messenger in crucial ECs functions with the aim at stimulating further investigation that link Ca2+ mobilization to ECs in health and disease.
Preparation of Gelatin and Gelatin/Hyaluronic Acid Cryogel Scaffolds for the 3D Culture of Mesothelial Cells and Mesothelium Tissue Regeneration
Authors: Kao Hao-Hsi , Kuo Chang-Yi , Chen Kuo-Su , Chen Jyh-Ping
Published: September 2019

Mesothelial cells are specific epithelial cells that are lined in the serosal cavity and internal organs. Nonetheless, few studies have explored the possibility to culture mesothelial cells in a three-dimensional (3D) scaffold for tissue engineering applications. Towards this end, we fabricated macroporous scaffolds from gelatin and gelatin/hyaluronic acid (HA) by cryogelation, and elucidated the influence of HA on cryogel properties and the cellular phenotype of mesothelial cells cultured within the 3D scaffolds. The incorporation of HA was found not to significantly change the pore size, porosity, water uptake kinetics, and swelling ratios of the cryogel scaffolds, but led to a faster scaffold degradation in the collagenase solution. Adding 5% HA in the composite cryogels also decreased the ultimate compressive stress (strain) and toughness of the scaffold, but enhanced the elastic modulus. From the in vitro cell culture, rat mesothelial cells showed quantitative cell viability in gelatin (G) and gelatin/HA (GH) cryogels. Nonetheless, mesothelial cells cultured in GH cryogels showed a change in the cell morphology and cytoskeleton arrangement, reduced cell proliferation rate, and downregulation of the mesothelium specific maker gene expression. The production of key mesothelium proteins E-cadherin and calretinin were also reduced in the GH cryogels. Choosing the best G cryogels for in vivo studies, the cell/cryogel construct was used for the transplantation of allograft mesothelial cells for mesothelium reconstruction in rats. A mesothelium layer similar to the native mesothelium tissue could be obtained 21 days post-implantation, based on hematoxylin and eosin (H&E) and immunohistochemical staining.
An Optimal Pursuit Differential Game Problem with One Evader and Many Pursuers
Authors: Ahmed Idris , Kumam Poom , Ibragimov Gafurjan , Rilwan Jewaidu , Kumam Wiyada
Published: September 2019

The objective of this paper is to study a pursuit differential game with finite or countably number of pursuers and one evader. The game is described by differential equations in l 2 -space, and integral constraints are imposed on the control function of the players. The duration of the game is fixed and the payoff functional is the greatest lower bound of distances between the pursuers and evader when the game is terminated. However, we discuss the condition for finding the value of the game and construct the optimal strategies of the players which ensure the completion of the game. An important fact to note is that we relaxed the usual conditions on the energy resources of the players. Finally, some examples are provided to illustrate our result.
New 1,4-Dienonesteroids from the Octocoral Dendronephthya sp.
Authors: Huynh Thanh-Hao , Chen Pei-Chin , Yang San-Nan , Lin Feng-Yu , Su Tung-Pin , Chen Lo-Yun , Peng Bo-Rong , Hu Chiung-Chin , Chen You-Ying , Wen Zhi-Hong , Wu Tung-Ying , Sung Ping-Jyun
Published: September 2019

Two new steroids, dendronesterones D (1) and E (2), featuring with 1,4-dienone moiety, along with three known steroids, methyl 3-oxochola-4,22-diene-24-oate (3), 5α,8α-epidioxy-24(S)- methylcholesta-6,22-dien-3β-ol (4), and 5α,8α-epidioxy-24(S)-methylcholesta-6,9(11),22-trien-3β-ol (5), were isolated from an octocoral Dendronephthya sp. The structures of steroids 1 and 2 were elucidated by using spectroscopic methods and steroid 1 was found to exhibit significant in vitro anti-inflammatory activity in lipopolysaccharides (LPS)-induced RAW264.7 macrophage cells by inhibiting the expression of the iNOS protein.
Production of Indole-3-Lactic Acid by Bifidobacterium Strains Isolated fromHuman Infants
Authors: Sakurai Takuma , Odamaki Toshitaka , Xiao Jin-zhong
Published: September 2019

Recent studies have shown that metabolites produced by microbes can be considered as mediators of host-microbial interactions. In this study, we examined the production of tryptophan metabolites by Bifidobacterium strains found in the gastrointestinal tracts of humans and other animals. Indole-3-lactic acid (ILA) was the only tryptophan metabolite produced in bifidobacteria culture supernatants. No others, including indole-3-propionic acid, indole-3-acetic acid, and indole-3-aldehyde, were produced. Strains of bifidobacterial species commonly isolated from the intestines of human infants, such as Bifidobacterium longum subsp. longum, Bifidobacterium longum subsp. infantis, Bifidobacterium breve, and Bifidobacterium bifidum, produced higher levels of ILA than did strains of other species. These results imply that infant-type bifidobacteria might play a specific role in host–microbial cross-talk by producing ILA in human infants.
Design, Synthesis, and Activity Evaluation of Novel N-benzyl Deoxynojirimycin Derivatives for Use as α-Glucosidase Inhibitors
Authors: Zeng Fanxin , Yin Zhongping , Chen Jiguang , Nie Xuliang , Lin Ping , Lu Tao , Wang Meng , Peng Dayong
Published: September 2019

To obtain α-glucosidase inhibitors with high activity, 19 NB-DNJDs (N-benzyl-deoxynojirimycin derivatives) were designed and synthesized. The results indicated that the 19 NB-DNJDs displayed different inhibitory activities towards α-glucosidase in vitro. Compound 18a (1-(4-hydroxy-3-methoxybenzyl)-2-(hydroxymethyl) piperidine-3,4,5-triol) showed the highest activity, with an IC50 value of 0.207 ± 0.11 mM, followed by 18b (1-(3-bromo-4-hydroxy-5-methoxybenzyl)-2-(hydroxymethyl) piperidine-3,4,5-triol, IC50: 0.276 ± 0.13 mM). Both IC50 values of 18a and 18b were significantly lower than that of acarbose (IC50: 0.353 ± 0.09 mM). According to the structure-activity analysis, substitution of the benzyl and bromine groups on the benzene ring decreased the inhibition activity, while methoxy and hydroxyl group substitution increased the activity, especially with the hydroxyl group substitution. Molecular docking results showed that three hydrogen bonds were formed between compound 18a and amino acids in the active site of α-glucosidase. Additionally, an arene–arene interaction was also modelled between the phenyl ring of compound 18a and Arg 315. The three hydrogen bonds and the arene–arene interaction resulted in a low binding energy (−5.8 kcal/mol) and gave 18a a higher inhibition activity. Consequently, compound 18a is a promising candidate as a new α-glucosidase inhibitor for the treatment of type Ⅱ diabetes.
Calculation of the Global and Local Conceptual DFT Indices for the Prediction of the Chemical Reactivity Properties of Papuamides A–F Marine Drugs
Authors: Flores-Holguín Norma , Frau Juan , Glossman-Mitnik Daniel
Published: September 2019

A well-behaved model chemistry previously validated for the study of the chemical reactivity of peptides was considered for the calculation of the molecular properties and structures of the Papuamide family of marine peptides. A methodology based on Conceptual Density Functional Theory (CDFT) was chosen for the determination of the reactivity descriptors. The molecular active sites were associated with the active regions of the molecules related to the nucleophilic and electrophilic Parr functions. Finally, the drug-likenesses and the bioactivity scores for the Papuamide peptides were predicted through a homology methodology relating them with the calculated reactivity descriptors, while other properties such as the pKas were determined following a methodology developed by our group.