bluuebunny/crossref_metadata_2025 huggingface dataset:
Cryptotanshinone Inhibits the Growth of HCT116 Colorectal Cancer Cells Through Endoplasmic Reticulum Stress-Mediated Autophagy
Authors: Fu Xiaojing , Zhao Wenwen , Li Kangkang , Zhou Jingyi , Chen Xuehong
Published: June 2021

Among cancers, colorectal cancer (CRC) has one of the highest annual incidence and death rates. Considering severe adverse reactions associated with classical chemotherapy medications, traditional Chinese medicines have become potential drug candidates. In the current study, the effects of cryptotanshinone (CPT), a major component of Salvia miltiorrhiza Bunge (Danshen) on CRC and underlying mechanism were explored. First of all, data from in vitro experiments and in vivo zebrafish models indicated that CPT selectively inhibited the growth and proliferation of HCT116 and SW620 cells while had little effect on SW480 cells. Secondly, both ER stress and autophagy were associated with CRC viability regulation. Interestingly, ER stress inhibitor and autophagy inhibitor merely alleviated cytotoxic effects on HCT116 cells in response to CPT stimulation, while have little effect on SW620 cells. The significance of apoptosis, autophagy and ER stress were verified by clinical data from CRC patients. In summary, the current study has revealed the anti-cancer effects of CPT in CRC by activating autophagy signaling mediated by ER stress. CPT is a promising drug candidate for CRC treatment.
Semiflexible Polymer Enclosed in a 3D Compact Domain
Authors: Castro-Villarreal Pavel , Ramírez J. E.
Published: June 2021

The conformational states of a semiflexible polymer enclosed in a volume V:=ℓ3 are studied as stochastic realizations of paths using the stochastic curvature approach developed in [Rev. E 100, 012503 (2019)], in the regime whenever 3ℓ/ℓp>1, where ℓp is the persistence length. The cases of a semiflexible polymer enclosed in a cube and sphere are considered. In these cases, we explore the Spakowitz–Wang–type polymer shape transition, where the critical persistence length distinguishes between an oscillating and a monotonic phase at the level of the mean-square end-to-end distance. This shape transition provides evidence of a universal signature of the behavior of a semiflexible polymer confined in a compact domain.
Inhibition of HDAC6 Activity Protects Against Endothelial Dysfunction and Atherogenesis in vivo: A Role for HDAC6 Neddylation
Authors: Nomura Yohei , Nakano Mitsunori , Woo Sung Hyun , Han Mingming , Pandey Deepesh
Published: June 2021

We previously reported that histone deacetylase 6 (HDAC6) has an important role in endothelial cell (EC) function in vitro. However, whether HDAC6 plays a role in atherogenesis in vivo and the mechanism(s) that control HDAC6 activity/expression in response to atherogenic stimuli are unclear. The goals of this study were to determine whether HDAC6 inhibitor tubacin attenuates atherogenesis and to elucidate specific molecular mechanism(s) that regulate endothelial HDAC6 expression/activity. We evaluated whether administration of tubacin attenuated or reversed the endothelial dysfunction and atherosclerosis induced in mice by a single intraperitoneal injection of adeno-associated viruses encoding liver-target PCSK9 gain-of-function mutant followed by a high fat diet (HFD) for 18 weeks. Tubacin significantly blunted PCSK9-induced increases in pulse wave velocity (index of vascular stiffness and overall vascular health) that are also seen in atherogenic mice. Furthermore, tubacin protected vessels from defective vasorelaxation, as evaluated by acetylcholine-mediated relaxation using wire myograph. Plaque burden defined by Oil Red O staining was also found to be significantly less in mice that received tubacin than in those that received PCSK9 alone. Inhibition of the NEDDylation pathway with MLN4924, an inhibitor of NEDD8-activating enzyme 1 (NAE1), significantly increased HDAC6 activity in HAECs. Interestingly, HDAC6 expression remained unchanged. Further, HAECs exposed to the atherogenic stimulus oxidized low-density lipoprotein (OxLDL) exhibited enhanced HDAC6 activity, which was attenuated by pretreatment with MLN4924. The HDAC6 NEDDylation molecular pathway might regulate genes related to endothelial control of vasomotor tone, reactivity, and atherosclerosis. Tubacin may represent a novel pharmacologic intervention for atherogenesis and other vasculopathies.
p21-Activated Kinase 1 Is Permissive for the Skeletal Muscle Hypertrophy Induced by Myostatin Inhibition
Authors: Barbé Caroline , Loumaye Audrey , Lause Pascale , Ritvos Olli , Thissen Jean-Paul
Published: June 2021

Skeletal muscle, the most abundant tissue in the body, plays vital roles in locomotion and metabolism. Understanding the cellular processes that govern regulation of muscle mass and function represents an essential step in the development of therapeutic strategies for muscular disorders. Myostatin, a member of the TGF-β family, has been identified as a negative regulator of muscle development. Indeed, its inhibition induces an extensive skeletal muscle hypertrophy requiring the activation of Smad 1/5/8 and the Insulin/IGF-I signaling pathway, but whether other molecular mechanisms are involved in this process remains to be determined. Using transcriptomic data from various Myostatin inhibition models, we identifiedPak1as a potential mediator of Myostatin action on skeletal muscle mass. Our results show that muscle PAK1 levels are systematically increased in response to Myostatin inhibition, parallel to skeletal muscle mass, regardless of the Myostatin inhibition model. UsingPak1knockout mice, we investigated the role ofPak1in the skeletal muscle hypertrophy induced by different approaches of Myostatin inhibition. Our findings show thatPak1deletion does not impede the skeletal muscle hypertrophy magnitude in response to Myostatin inhibition. Therefore,Pak1is permissive for the skeletal muscle mass increase caused by Myostatin inhibition.
Storage Period and Different Abiotic Factors Regulate Seed Germination of Two Apocynum Species — Cash Crops in Arid Saline Regions in the Northwestern China
Authors: Jiang Li , She Chaowen , Tian Changyan , Tanveer Mohsin , Wang Lei
Published: June 2021

On degraded land in arid regions, cultivation of Apocynum species can provide significant environmental benefits by preventing soil erosion and desertification. Furthermore, Apocynum venetum and Apocynum pictum, which are mainly distributed in salt-barren lands in the northwestern region of China, are traditionally used to produce natural fiber and herbal tea. Direct sowing of both species may encounter various abiotic stresses such as drought and salinity. However, these effects on germination remain largely unknown, especially for seeds with different storage periods. The aim of this study was to evaluate the effects of storage period, light condition, temperature regime, drought, and salinity on germination performances of both species. Germination experiment was carried out in November 2017. There were four replicates for each treatment, and each petri dish contained 25 seeds. The results indicated that prolongation of storage period significantly decreased the germination percentage and velocity, especially under abiotic stresses. Light did not affect seed germination of A. venetum and A. pictum under any conditions. Seeds had better germination performance at 10/25 and 15/30°C than those of seeds incubated at any other temperatures. With the increase of polyethylene glycol (PEG) and salinity concentrations, seed germination for both species gradually decreased, especially for seeds stored for 2 years. Low PEG (0–20%) and salinity concentration (0–200 mM) did not significantly affect germination percentage of freshly matured seeds. However, long-time storage significantly decreased drought and salinity tolerance in A. venetum and A. pictum during germination stage. For saline soils in arid and semi-arid regions, freshly matured seeds or 1-year-stored seeds of both Apocynum species are recommended to be sown by using drip-irrigation in spring.
Removal of H3K27me3 by JMJ Proteins Controls Plant Development and Environmental Responses in Arabidopsis
Authors: Yamaguchi Nobutoshi
Published: June 2021

Trimethylation of histone H3 lysine 27 (H3K27me3) is a highly conserved repressive histone modification that signifies transcriptional repression in plants and animals. In Arabidopsis thaliana, the demethylation of H3K27 is regulated by a group of JUMONJI DOMAIN-CONTANING PROTEIN (JMJ) genes. Transcription of JMJ genes is spatiotemporally regulated during plant development and in response to the environment. Once JMJ genes are transcribed, recruitment of JMJs to target genes, followed by demethylation of H3K27, is critically important for the precise control of gene expression. JMJs function synergistically and antagonistically with transcription factors and/or other epigenetic regulators on chromatin. This review summarizes the latest advances in our understanding of Arabidopsis H3K27me3 demethylases that provide robust and flexible epigenetic regulation of gene expression to direct appropriate development and environmental responses in plants.
Sensitivity to a Break in Interaural Correlation in Frequency-Gliding Noises
Authors: Fan Langchen , Kong Lingzhi , Li Liang , Qu Tianshu
Published: June 2021

This study was to investigate whether human listeners are able to detect a binaurally uncorrelated arbitrary-noise fragment embedded in binaurally identical arbitrary-noise markers [a break in correlation, break in interaural correlation (BIAC)] in either frequency-constant (frequency-steady) or frequency-varied (unidirectionally frequency gliding) noise. Ten participants with normal hearing were tested in Experiment 1 for up-gliding, down-gliding, and frequency-steady noises. Twenty-one participants with normal hearing were tested in Experiment 2a for both up-gliding and frequency-steady noises. Another nineteen participants with normal hearing were tested in Experiment 2b for both down-gliding and frequency-steady noises. Listeners were able to detect a BIAC in the frequency-steady noise (center frequency = 400 Hz) and two types of frequency-gliding noises (center frequency: between 100 and 1,600 Hz). The duration threshold for detecting the BIAC in frequency-gliding noises was significantly longer than that in the frequency-steady noise (Experiment 1), and the longest interaural delay at which a duration-fixed BIAC (200 ms) in frequency-gliding noises could be detected was significantly shorter than that in the frequency-steady noise (Experiment 2). Although human listeners can detect a BIAC in frequency-gliding noises, their sensitivity to a BIAC in frequency-gliding noises is much lower than that in frequency-steady noise.
Research and Technology Organizations as Super Intermediaries: A Conceptual Framework for Policy and a Case Study From Tanzania
Authors: Sheikheldin Gussai H.
Published: June 2021

Research and Technology Organizations (RTOs) have key roles in stories of national industrial development in many countries, and in various contexts they have transformed according to changes in their surrounding economic and policy environments. This paper proposes a conceptual framework of ‘RTOs as super intermediaries’ as they play multiple intermediary roles in the triple helix (government, research and industry), the overlap of industrial policy and research policy, and research-industry frontiers. The framework helps in understanding and advancing the role of RTOs in industrial development, particularly in developing countries. For a case study, the paper showcases research in Tanzania that explored possibilities of revamping RTOs and whether investing in them would help in spurring Tanzania's industrial development. Through key informant interviews and systemic literature review, a case study on the challenges and opportunities of RTOs was designed to examine their role and potential in industrial development and technology innovation processes. The study findings were overall in-line with two main lenses of inquiry: 1) that for RTOs to play their key roles in Tanzania, industrial policies shaped by the command economy era before the 1990s need to be reviewed and modified; and 2) that more investment in revamping RTOs will take place if policymaking processes acknowledge RTOs as super intermediaries. To organize policy lessons drawn, a multi-level policy map—micro, meso and macro—was utilized as an analytical tool.
From Conventional to Precision Fertilization: A Case Study on the Transition for a Small-Medium Farm
Authors: Brambilla Massimo , Romano Elio , Toscano Pietro , Cutini Maurizio , Biocca Marcello , Ferré Chiara , Comolli Roberto , Bisaglia Carlo
Published: June 2021

At the CREA research facility of Treviglio (Bergamo, Italy), to provide farmers with valuable hints for the transition from conventional to precision agriculture, information on crop production dynamics (Maize and Triticale) has been obtained using real-time soil mapping (resistivity technique) and production quality and quantity monitoring with a commercial yield mapping apparatus. The geostatistical processing of data resulted in the same zoning for Triticale, meaning that the characteristics of soil influenced crop behavior more than the variability resulting from other factors, which suggests that improvements in product yields can be planned and achieved acting, for instance, on variable rate distribution of fertilizers. The importance of the acquired data can help farmers to manage factors that are external to their plots of land.
Evaluation of Euthanasia Methods on Behavioral and Physiological Responses of Newly Hatched Male Layer Chicks
Authors: Wang Xi , Zhao Dan , Milby Allison C. , Archer Gregory S. , Peebles E. David , Gurung Shailesh , Farnell Morgan B.
Published: June 2021

Newly hatched male layer chicks are considered as “by-products” in the egg industry and must be humanely euthanized at the hatchery. Instantaneous mechanical destruction (maceration) is the predominant euthanasia method applied in poultry hatcheries and is approved by the American Veterinary Medical Association (AVMA). However, maceration is not perceived by the public to be a humane means of euthanasia. The effects of alternative euthanasia methods, including carbon dioxide (CO2) or nitrogen (N2) inhalation, and a commercial negative pressure stunning system on behavioral and physiological responses of day-of-hatch male layer chicks, were evaluated in a field trial. Chick behaviors, including ataxia, loss of posture, convulsions, cessation of vocalization, and cessation of movement, were monitored. Serum hormones were assessed at the end of each of the alternative euthanasia treatments, including a control group allowed to breathe normal atmospheric air. The N2 method induced unconsciousness and death later than the CO2 and negative pressure methods, and increased serum corticosterone concentrations of neonatal chicks. Carbon dioxide inhalation increased serotonin concentrations as compared to controls, as well as the N2 and the negative pressure methods. The behavioral and physical responses observed in this study suggest that both CO2 inhalation and negative pressure stunning can be employed to humanely euthanize neonatal male layer chicks.
Mitigating the Growth, Biochemical Changes, Genotoxic and Pathological Effects of Copper Toxicity in Broiler Chickens by Supplementing Vitamins C and E
Authors: Hashem Mohamed A. , Abd El Hamied Sahar S. , Ahmed Eman M. A. , Amer Shimaa A. , El-Sharnouby Mohamed E.
Published: June 2021

This experiment was carried out to explore the efficiency of an individual or combined doses of vitamin C (Vit. C) and vitamin E (Vit. E) in alleviating biochemical, genotoxicity, and pathological changes in the liver induced by copper sulfate (CuSO4) toxicity in broiler chickens. Two hundred and fifty-one-day-old broiler chicks were haphazardly allotted into five groups (five replicates/group, ten chicks/replicate). The birds were fed five experimental diets; (1) basal diet with no additives (CON), (2) basal diets supplemented with 300 mg CuSO4/kg diet (CuSO4), (3) basal diets supplemented with 300 mg CuSO4/kg diet + 250 mg Vit. C /kg diet, (4) basal diets supplemented with 300 mg CuSO4/kg diet +250 mg Vit. E /kg diet, (5) basal diets supplemented with 300 mg CuSO4/kg diet + 250 mg Vit. C /kg diet + 250 mg Vit. E /kg diet for six weeks. The results displayed that CuSO4-intoxicated birds had significantly (p < 0.05) decreased bodyweight, weight gain, and feed intake with increased feed conversion ratio from the 2nd week till the 6th week compared with the CON. However, these changes were minimized by single or combined supplementation of vitamin C and E. The FCR was insignificantly different in birds-fed diets complemented with vitamin C and E singly or in combination from the 3rd week of age compared to the CON. Serum aminotransferases (ALT, AST) and alkaline phosphatase (ALP) were elevated in CuSO4-intoxicated birds (p < 0.05). Additionally, they showed a drop in serum total protein (TP), albumin, globulins, triglycerides (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein-cholesterol (VLDL-C), and high-density lipoprotein-cholesterol (HDL-C) levels compared to the CON (p < 0.05). Concomitantly, histopathological and DNA changes were perceived in the liver of CuSO4-intoxicated birds. Co-supplementation of Vit. C and Vit. E single-handedly or combined with CuSO4-intoxicated chickens enhanced the performance traits and abovementioned changes, especially with those given combinations of vitamins. From the extant inquiry, it could be established that supplementation of vitamin C and E was beneficial for mitigating the harmful effects of CuSO4 toxicity on growth performance and liver histoarchitecture in broiler chickens.
Evolution of the Gram-Negative Antibiotic Resistance Spiral over Time: A Time-Series Analysis
Authors: Tóth Hajnalka , Buchholcz Gyula , Fésüs Adina , Balázs Bence , Nagy József Bálint , Majoros László , Szarka Krisztina , Kardos Gábor
Published: June 2021

We followed up the interplay between antibiotic use and resistance over time in a tertiary-care hospital in Hungary. Dynamic relationships between monthly time-series of antibiotic consumption data (defined daily doses per 100 bed-days) and of incidence densities of Gram-negative bacteria (Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, and Acinetobacter baumannii) resistant to cephalosporins or carbapenems were followed using vector autoregressive models sequentially built of time-series ending in 2015, 2016, 2017, 2018, and 2019. Relationships with Gram-negative bacteria as a group were fairly stable across years. At species level, association of cephalosporin use and cephalosporin resistance of E. coli was shown in 2015–2017, leading to increased carbapenem use in these years. Association of carbapenem use and carbapenem resistance, as well as of carbapenem resistance and colistin use in case of A. baumannii, were consistent throughout; associations in case of Klebsiella spp. were rarely found; associations in case of P. aeruginosa varied highly across years. This highlights the importance of temporal variations in the interplay between changes in selection pressure and occurrence of competing resistant species.
Modeling Black Piety and Community Membership in the Virgin of Altagracia Medallions
Authors: Baez Jennifer
Published: June 2021

In the third quarter of the eighteenth century, Santo Domingo archbishop Isidoro Rodríguez Lorenzo (s. 1767–1788) issued a decree officializing the day of the cult for the Virgin of Altagracia as January 21 and made it a feast of three crosses for the villa of Salvaleón de Higüey and its jurisdiction, meaning all races (free and enslaved) were allowed to join the celebrations in church. Unrelated to the issuance of this decree and approximately during this time (c. 1760–1778), a series of painted panels depicting miracles performed by the Virgin of Altagracia was produced for her sanctuary of San Dionisio in Higüey, in all likelihood commissioned by a close succession of parish priests to the maestro painter Diego José Hilaris Holt. Painted in the coarse style of popular votive panels, they gave the cult a unifying core foundation of miracles. This essay discusses the significance of the black bodies pictured in four of the panels within the project’s implicit effort to institutionalize the regional cult and vis-à-vis the archbishop’s encouragement of non-segregated celebrations for her feast day. As January 21 was associated with a renowned Spanish creole battle against the French, this essay locates these black bodies within the cult’s newfound patriotic charisma. I examine the process by which people of color were incorporated into this community of faith as part of a two-step ritual that involved seeing images while performing difference. Through contrapuntal analysis of the archbishop’s decree, I argue the images helped model black piety and community membership within a hierarchical socioracial order.
A Study on the Life Experiences of Adolescents Who Grew up with Younger Siblings with Developmental Disabilities: Focusing on Phenomenological Analysis Methods
Authors: Park Sunwon , Ryu Wonjung , Yang Hyerin
Published: June 2021

This study aims to explore specific life experiences and what it means to “live as a sibling of a disabled person”, by focusing on the brothers and sisters of persons with disabilities; this is a cohort that has been relatively marginalized in the field of welfare for the disabled. To this end, the author conducted 1:1 in-depth interviews with four adolescents who grew up with younger siblings who have developmental disabilities, and analyzed the meaning underlying their life experiences through phenomenological research methods. As a result, a total of five core themes of those life experiences were identified: (1) the birth of a disabled younger sibling, wherein their trials began; (2) surviving differentiation within the family; (3) ambivalence toward parents; (4) adolescence, with resurfaced psychological conflicts and relieving emotions; and (5) a future to be planned around a life of coexisting with disabled siblings. This study aims to provide basic data for social welfare intervention through an illuminating and deeper understanding of the lives of siblings of the developmentally disabled who require a high level of care.
HCC in the Era of Direct-Acting Antiviral Agents (DAAs): Surgical and Other Curative or Palliative Strategies in the Elderly
Authors: Brozzetti Stefania , Tancredi Marsia , Bini Simone , De Lucia Chiara , Antimi Jessica , D’Alterio Chiara , De Sanctis Giuseppe Maria , Furlan Caterina , Malpassuti Vittoria Carolina , Lucatelli Pierleone , Di Martino Michele , Bezzi Mario , Ciardi Antonio , Pascale Rosa Maria
Published: June 2021

Hepatocellular carcinoma (HCC) accounts for 75–85% of primary liver malignancies, and elderlies have the highest incidence rates. Direct-acting antiviral agents (DAAs) have shown satisfying results in terms of HCV sustained viral response (SVR). However, data regarding HCC risk post-DAA-SVR is still conflicting. This study aims to consider HCC onset in moderate underlying liver disease. We conducted a retrospective study on 227 chronically infected patients (cHCV), treated with DAAs. Patients were divided into three groups: “de novo occurrent HCC”, “recurrent HCC”, and “without HCC”. Fifty-six patients aged <65 years (yDAA) were studied separately. HCC patients aged ≥65 years (DAA-HCC) were compared to a historical group of 100 elderly HCC patients, treated with peginterferon (Peg-IFN) ± ribavirin antiviral agents, non-SVR (hHCC). The HCC prevalence in DAA patients was 32.75%: “de novo occurrent’’ 18.13% and “recurrent’’ 14.62%, despite 42.85% of them having no fibrosis to mild or moderate fibrosis (F0-F1-F2). yDAA showed 5.36% “de novo occurrent” HCC. Curative procedure rates were compared between DAA-HCC and hHCC at the first and at recurrent presentation (22 (39.29%) vs. 72 (72%); 17 (30.36%) vs. 70 (70%), respectively (p < 0.001)). No significant difference was found in 3-year OS (p = 0.6). However, in cause-specific mortality analysis, HCC-related death was higher in the DAA-treated group, whereas cirrhosis-related death was more common in the historical group (p = 0.0288), considering together the two causes of death. A more accurate patient stratification according to multifactorial and new diagnostic investigations identifying HCC risk might allow an improvement in management and access to curative therapies.
Challenges and Opportunities in the Statistical Analysis of Multiplex Immunofluorescence Data
Authors: Wilson Christopher M. , Ospina Oscar E. , Townsend Mary K. , Nguyen Jonathan , Moran Segura Carlos , Schildkraut Joellen M. , Tworoger Shelley S. , Peres Lauren C. , Fridley Brooke L.
Published: June 2021

Immune modulation is considered a hallmark of cancer initiation and progression. The recent development of immunotherapies has ushered in a new era of cancer treatment. These therapeutics have led to revolutionary breakthroughs; however, the efficacy of immunotherapy has been modest and is often restricted to a subset of patients. Hence, identification of which cancer patients will benefit from immunotherapy is essential. Multiplex immunofluorescence (mIF) microscopy allows for the assessment and visualization of the tumor immune microenvironment (TIME). The data output following image and machine learning analyses for cell segmenting and phenotyping consists of the following information for each tumor sample: the number of positive cells for each marker and phenotype(s) of interest, number of total cells, percent of positive cells for each marker, and spatial locations for all measured cells. There are many challenges in the analysis of mIF data, including many tissue samples with zero positive cells or “zero-inflated” data, repeated measurements from multiple TMA cores or tissue slides per subject, and spatial analyses to determine the level of clustering and co-localization between the cell types in the TIME. In this review paper, we will discuss the challenges in the statistical analysis of mIF data and opportunities for further research.
A Retrospective 5-Year Single Center Study Highlighting the Risk of Cancer Predisposition in Adolescents and Young Adults
Authors: Jordan Frank , Huber Simon , Sommer Sebastian , Schenkirsch Gerhard , Frühwald Michael C. , Trepel Martin , Claus Rainer , Kuhlen Michaela
Published: June 2021

The knowledge of inherited cancer susceptibility opens a new field of cancer medicine. We conducted a retrospective single-center cohort study. Data of AYA cancer patients registered between January 2014 and December 2018 were analyzed. The median age at cancer diagnosis of 704 patients (343 males, 361 females) was 32 years (range, 15–39 years), median follow-up was 181 days (range, 1–1975 days). Solid tumors were diagnosed in 575 (81.7%) patients, hematologic malignancies in 129 (18.3%) patients. Multiple primary cancers were reported in 36 (5.1%) patients. Malignancies that may be indicators of inherited cancer susceptibility were diagnosed in 2.6% of patients with cancers of the endocrine system, in 73% of cancers of the gastrointestinal system, in 88% of tumors of the central nervous system, in 92% of cancers of the urinary tract, and in 59% of head and neck tumors. In addition, all patients with breast cancer, sarcoma, and peripheral nerve sheath tumor were in need of genetic counselling. In sum, at least 181 of 704 (25.7%) AYA cancer patients presented with malignancies suspicious of harboring pathogenic germline variants. Evaluation of AYA cancer patients for hereditary cancer predisposition needs to be integrated into daily practice.
Dynamic Evaluation of Circulating miRNA Profile in EGFR-Mutated NSCLC Patients Treated with EGFR-TKIs
Authors: Leonetti Alessandro , Capula Mjriam , Minari Roberta , Mazzaschi Giulia , Gregori Alessandro , El Hassouni Btissame , Papini Filippo , Bordi Paola , Verzè Michela , Avan Amir , Tiseo Marcello , Giovannetti Elisa
Published: June 2021

Background: Resistance to EGFR-TKIs constitutes a major challenge for the management of EGFR-mutated NSCLC, and recent evidence suggests that deregulation of specific microRNAs (miRNAs) may influence resistance to targeted agents. In this retrospective study, we explored the role of specific plasmatic miRNAs (miR-21, miR-27a and miR-181a) as a surrogate for predicting EGFR-TKI performance in EGFR-mutated NSCLC patients. Methods: Plasma samples of 39 advanced EGFR-mutated NSCLC patients treated with EGFR-TKIs were collected at different points in time and miRNA levels were assessed by RT-PCR. Results: Higher basal values of miR-21 were reported in patients who achieved a partial/complete response (PR/CR) compared to those with stability/progression of disease (SD/PD) (p = 0.011). Along the same line, patients who experienced a clinical benefit lasting at least six months displayed higher basal levels of circulating miR-21 (p = 0.039). However, dynamic evaluation of miRNA values after two months from the start of EGFR-TKI treatment showed that patients who experienced SD had an increase in miR-21 levels (Fold Change [FC] = 2.6) compared to patients achieving PR/CR (p = 0.029). The same tendency was observed for miR-27a (FC = 3.1) and miR-181a (FC = 2.0), although without reaching statistical significance. Remarkably, preclinical studies showed an increase in miR-21 levels in NSCLC cells that became resistant after exposure to EGFR-TKIs. Conclusions: Our study provides interesting insights on the role of circulating miRNAs, in particular miR-21, and their dynamic change over time in predicting EGFR-TKI response in EGFR-mutated NSCLC.
BECLIN1: Protein Structure, Function and Regulation
Authors: Tran Sharon , Fairlie W. Douglas , Lee Erinna F.
Published: June 2021

BECLIN1 is a well-established regulator of autophagy, a process essential for mammalian survival. It functions in conjunction with other proteins to form Class III Phosphoinositide 3-Kinase (PI3K) complexes to generate phosphorylated phosphatidylinositol (PtdIns), lipids essential for not only autophagy but other membrane trafficking processes. Over the years, studies have elucidated the structural, biophysical, and biochemical properties of BECLIN1, which have shed light on how this protein functions to allosterically regulate these critical processes of autophagy and membrane trafficking. Here, we review these findings and how BECLIN1’s diverse protein interactome regulates it, as well as its impact on organismal physiology.
Strength and Numbers: The Role of Affinity and Avidity in the ‘Quality’ of T Cell Tolerance
Authors: This Sébastien , Valbon Stefanie F. , Lebel Marie-Ève , Melichar Heather J.
Published: June 2021

The ability of T cells to identify foreign antigens and mount an efficient immune response while limiting activation upon recognition of self and self-associated peptides is critical. Multiple tolerance mechanisms work in concert to prevent the generation and activation of self-reactive T cells. T cell tolerance is tightly regulated, as defects in these processes can lead to devastating disease; a wide variety of autoimmune diseases and, more recently, adverse immune-related events associated with checkpoint blockade immunotherapy have been linked to a breakdown in T cell tolerance. The quantity and quality of antigen receptor signaling depend on a variety of parameters that include T cell receptor affinity and avidity for peptide. Autoreactive T cell fate choices (e.g., deletion, anergy, regulatory T cell development) are highly dependent on the strength of T cell receptor interactions with self-peptide. However, less is known about how differences in the strength of T cell receptor signaling during differentiation influences the ‘function’ and persistence of anergic and regulatory T cell populations. Here, we review the literature on this subject and discuss the clinical implications of how T cell receptor signal strength influences the ‘quality’ of anergic and regulatory T cell populations.
Cattle In Vitro Induced Pluripotent Stem Cells Generated and Maintained in 5 or 20% Oxygen and Different Supplementation
Authors: Bessi Brendon Willian , Botigelli Ramon Cesar , Pieri Naira Caroline Godoy , Machado Lucas Simões , Cruz Jessica Brunhara , de Moraes Pamela , de Souza Aline Fernanda , Recchia Kaiana , Barbosa Gabriela , de Castro Raquel Vasconcelos Guimarães , Nogueira Marcelo Fábio Gouveia , Bressan Fabiana Fernandes
Published: June 2021

The event of cellular reprogramming into pluripotency is influenced by several factors, such as in vitro culture conditions (e.g., culture medium and oxygen concentration). Herein, bovine iPSCs (biPSCs) were generated in different levels of oxygen tension (5% or 20% of oxygen) and supplementation (bFGF or bFGF + LIF + 2i—bFL2i) to evaluate the efficiency of pluripotency induction and maintenance in vitro. Initial reprogramming was observed in all groups and bFL2i supplementation initially resulted in a superior number of colonies. However, bFL2i supplementation in low oxygen led to a loss of self-renewal and pluripotency maintenance. All clonal lines were positive for alkaline phosphatase; they expressed endogenous pluripotency-related genes SOX2, OCT4 and STELLA. However, expression was decreased throughout the passages without the influence of oxygen tension. GLUT1 and GLUT3 were upregulated by low oxygen. The biPSCs were immunofluorescence-positive stained for OCT4 and SOX2 and they formed embryoid bodies which differentiated in ectoderm and mesoderm (all groups), as well as endoderm (one line from bFL2i in high oxygen). Our study is the first to compare high and low oxygen environments during and after induced reprogramming in cattle. In our conditions, a low oxygen environment did not favor the pluripotency maintenance of biPSCs.
Optimal Operation of Solar Powered Electric Vehicle Parking Lots Considering Different Photovoltaic Technologies
Authors: Farahmand Mahsa Z. , Javadi Sara , Sadati Sayyed Muhammad Bagher , Laaksonen Hannu , Shafie-khah Miadreza
Published: June 2021

The performance of electric vehicles and their abilities to reduce fossil fuel consumption and air pollution on one hand and the use of photovoltaic (PV) panels in energy production, on the other hand, has encouraged parking lot operators (PLO) to participate in the energy market to gain more profit. However, there are several challenges such as different technologies of photovoltaic panels that make the problem complex in terms of installation cost, efficiency, available output power and dependency on environmental temperature. Therefore, the aim of this study is to maximize the PLO’s operational profit under the time of use energy pricing scheme by investigating the effects of different PV panel technologies on energy production and finding the best strategy for optimal operation of PVs and electric vehicle (EV) parking lots which is achieved by means of market and EV owners’ interaction. For the accurate investigation, four different PV panel technologies are considered in different seasons, with significant differences in daylight times, in Helsinki, Finland.
In Vitro Microleakage Evaluation of Bioceramic and Zinc-Eugenol Sealers with Two Obturation Techniques
Authors: De Angelis Francesco , D’Arcangelo Camillo , Buonvivere Matteo , Argentino Rachele , Vadini Mirco
Published: June 2021

Aim of the study is to compare the quality of the apical seal offered by a zinc-eugenol and a tricalcium-silicate-based sealer, both used with the single-cone or with the continuous wave of condensation technique. Forty central incisors were divided into four groups (n = 10), according to the two sealers and the two obturation techniques under investigation, and their outer surface was isolated with nail varnish. After endodontic treatment, samples were immersed in methylene blue dye for 72 h, then included in self-curing resin and sectioned to longitudinally expose the canal apical third. The depth of dye penetration was measured in each group. Mean values were compared by two-way-ANOVA test. Multiple comparisons were performed by Tukey test. The level of significance was set at 0.05 in all tests. The continuous wave of condensation technique led to reduced microleakage. Moreover, dye penetration values were reduced for the tricalcium-silicate sealer. In terms of microleakage, the warm continuous wave of condensation technique seems promising even when combined to a bioceramic sealer.
Refinement of the Congruently Melting Composition of Nonstoichiometric Fluorite Crystals Ca1-xYxF2x (x = 0.01–0.14)
Authors: Karimov Denis N. , Sulyanova Elena A. , Sobolev Boris P.
Published: June 2021

The concentration series of nonstoichiometric crystals Ca1–xYxF2+x (x = 0.01–0.14) was obtained from a melt by directional crystallization to refine the composition of the temperature maximum on the melting curves. A precision (±9 × 10−5 Å) determination of lattice parameters of the Ca1–xYxF2+x crystals with the structure of fluorite (sp. gr. Fm-3m) was performed, and a linear equation of their concentration dependence was calculated: a(x) = 5.46385(5) + 0.1999(4) x. The distribution of yttrium along the crystals Ca1–xYxF2+x, the content of which is determined by the precision lattice parameters, is studied. The congruently melting composition x = 0.105(5) of the Ca1–xYxF2+x phase is refined by the method of directional crystallization.
Rolling Bearing Fault Diagnosis Based on VMD-MPE and PSO-SVM
Authors: Ye Maoyou , Yan Xiaoan , Jia Minping
Published: June 2021

The goal of the paper is to present a solution to improve the fault detection accuracy of rolling bearings. The method is based on variational mode decomposition (VMD), multiscale permutation entropy (MPE) and the particle swarm optimization-based support vector machine (PSO-SVM). Firstly, the original bearing vibration signal is decomposed into several intrinsic mode functions (IMF) by using the VMD method, and the feature energy ratio (FER) criterion is introduced to reconstruct the bearing vibration signal. Secondly, the multiscale permutation entropy of the reconstructed signal is calculated to construct multidimensional feature vectors. Finally, the constructed multidimensional feature vector is fed into the PSO-SVM classification model for automatic identification of different fault patterns of the rolling bearing. Two experimental cases are adopted to validate the effectiveness of the proposed method. Experimental results show that the proposed method can achieve a higher identification accuracy compared with some similar available methods (e.g., variational mode decomposition-based multiscale sample entropy (VMD-MSE), variational mode decomposition-based multiscale fuzzy entropy (VMD-MFE), empirical mode decomposition-based multiscale permutation entropy (EMD-MPE) and wavelet transform-based multiscale permutation entropy (WT-MPE)).
The Absorption Performance of Ionic Liquids–PEG200 Complex Absorbent for VOCs
Authors: Zhang Wenlin , Luo Jinping , Sun Tengfei , Yu Fengshou , Li Chunli
Published: June 2021

A novel complex absorbent composed of polyethylene glycol 200 (PEG200) and ionic liquids (ILs) was prepared for the absorption of volatile organic compounds (VOCs) such as dichloromethane (DCM) and benzene. We prepared complex absorbents composed of [EMIM][Cl], [BMIM][Cl], [HMIM][Cl], [BMIM][BF4], [BMIM][PF6], [BMIM][NTF2], and PEG200, respectively, and studied the absorption properties of these six complex absorbents for DCM and benzene. The results show that under the optimized situation, the absorptivity of [HMIM][Cl]–PEG200 complex absorbent for DCM is 85.46% in the first 5 min, and 87.15% for benzene. No obvious decay in the absorptivity of [HMIM][Cl]–PEG200 for DCM and benzene was observed in five cycles, indicating an impressive regeneration performance. Furthermore, the mechanism of ionic liquid absorption for VOC is explored by thermodynamic analysis and quantum chemical calculations. The theoretical calculation results show that the [HMIM][Cl]–DCM interaction is stronger than the [HMIM][Cl]–benzene interaction, which is consistent with the results of the absorption experiment. Moreover, the strong hydrogen bonds can be formed between both [HMIM][Cl]–DCM and [HMIM][Cl]–benzene.
A Study on the Feasibility of Anaerobic Co-Digestion of Raw Cheese Whey with Coffee Pulp Residues
Authors: Gonzalez-Piedra Sandra , Hernández-García Héctor , Perez-Morales Juan M. , Acosta-Domínguez Laura , Bastidas-Oyanedel Juan-Rodrigo , Hernandez-Martinez Eliseo
Published: June 2021

In this paper, a study on the feasibility of the treatment of raw cheese whey by anaerobic co-digestion using coffee pulp residues as a co-substrate is presented. It considers raw whey generated in artisanal cheese markers, which is generally not treated, thus causing environmental pollution problems. An experimental design was carried out evaluating the effect of pH and the substrate ratio on methane production at 35 °C (i.e., mesophilic conditions). The interaction of the parameters on the co-substrate degradation and the methane production was analyzed using a response surface analysis. Furthermore, two kinetic models were proposed (first order and modified Gompertz models) to determine the dynamic profiles of methane yield. The results show that co-digestion of the raw whey is favored at pH = 6, reaching a maximum yield of 71.54 mLCH4 gVSrem−1 (31.5% VS removed) for raw cheese whey and coffee pulp ratio of 1 gVSwhey gVSCoffe−1. The proposed kinetic models successfully fit the experimental methane production data, the Gompertz model being the one that showed the best fit. Then, the results show that anaerobic co-digestion can be used to reduce the environmental impact of raw whey. Likewise, the methane obtained can be integrated into the cheese production process, which could contribute to reducing the cost per energy consumption.
Simulation of a CSP Solar Steam Generator, Using Machine Learning
Authors: Gonzalez Gonzalez Adrian , Alvarez Cabal Jose Valeriano , Vigil Berrocal Miguel Angel , Peón Menéndez Rogelio , Riesgo Fernández Adrian
Published: June 2021

Developing an accurate concentrated solar power (CSP) performance model requires significant effort and time. The power block (PB) is the most complex system, and its modeling is clearly the most complicated and time-demanding part. Nonetheless, PB layouts are quite similar throughout CSP plants, meaning that there are enough historical process data available from commercial plants to use machine learning techniques. These algorithms allowed the development of a very accurate black-box PB model in a very short amount of time. This PB model could be easily integrated as a block into the PM. The machine learning technique selected was SVR (support vector regression). The PB model was trained using a complete year of data from a commercial CSP plant situated in southern Spain. With a very limited set of inputs, the PB model results were very accurate, according to their validation against a new complete year of data. The model not only fit well on an aggregate basis, but also in the transients between operation modes. To validate applicability, the same model methodology is used with a data from a very different CSP Plant, located in the MENA region and with more than double nominal electric power, obtaining an excellent fitting in the validation.
Metaheuristics and Transmission Expansion Planning: A Comparative Case Study
Authors: Abdi Hamdi , Moradi Mansour , Lumbreras Sara
Published: June 2021

Transmission expansion planning (TEP), the determination of new transmission lines to be added to an existing power network, is a key element in power system planning. Using classical optimization to define the most suitable reinforcements is the most desirable alternative. However, the extent of the under-study problems is growing, because of the uncertainties introduced by renewable generation or electric vehicles (EVs) and the larger sizes under consideration given the trends for higher renewable shares and stronger market integration. This means that classical optimization, even using efficient techniques, such as stochastic decomposition, can have issues when solving large-sized problems. This is compounded by the fact that, in many cases, it is necessary to solve a large number of instances of a problem in order to incorporate further considerations. Thus, it can be interesting to resort to metaheuristics, which can offer quick solutions at the expense of an optimality guarantee. Metaheuristics can even be combined with classical optimization to try to extract the best of both worlds. There is a vast literature that tests individual metaheuristics on specific case studies, but wide comparisons are missing. In this paper, a genetic algorithm (GA), orthogonal crossover based differential evolution (OXDE), grey wolf optimizer (GWO), moth–flame optimization (MFO), exchange market algorithm (EMA), sine cosine algorithm (SCA) optimization and imperialistic competitive algorithm (ICA) are tested and compared. The algorithms are applied to the standard test systems of IEEE 24, and 118 buses. Results indicate that, although all metaheuristics are effective, they have diverging profiles in terms of computational time and finding optimal plans for TEP.
Characteristics of the Diploid, Triploid, and Tetraploid Versions of a Cannabigerol-Dominant F1 Hybrid Industrial Hemp Cultivar, Cannabis sativa ‘Stem Cell CBG’
Authors: Crawford Seth , Rojas Brendan M. , Crawford Eric , Otten Matthew , Schoenenberger Thecla A. , Garfinkel Andrea R. , Chen Hsuan
Published: June 2021

Hemp (Cannabis sativa L.) has recently become an important crop due to the growing market demands for products containing cannabinoids. Unintended cross-pollination of C. sativa crops is one of the most important threats to cannabinoid production and has been shown to reduce cannabinoid yield. Ploidy manipulation has been used in other crops to improve agronomic traits and reduce fertility; however, little is known about the performance of C. sativa polyploids. In this study, colchicine was applied to two proprietary, inbred diploid C. sativa inbred lines, ‘TS1-3’ and ‘P163’, to produce the tetraploids ‘TS1-3 (4x)’ and ‘P163 (4x)’. The diploid, triploid, and tetraploid F1 hybrids from ‘TS1-3’ × ‘P163’, ‘TS1-3 (4x)’ × ‘P163’, and ‘TS1-3 (4x)’ × ‘P163 (4x)’ were produced to test their fertilities, crossing compatibilities, and yields. The results indicated a reduction in fertility in the triploids and the tetraploids, relative to their diploid counterparts. When triploids were used as females, seed yields were less than 2% compared to when diploids were used as females; thus, triploids were determined to be female infertile. The triploids resulting from the crosses made herein displayed increases in biomass and inflorescence weight compared to the diploids created from the same parents in a field setting. Statistical increases in cannabinoid concentrations were not observed. Lastly, asymmetric crossing compatibility was observed between the diploids and the tetraploids of the genotypes tested. The results demonstrate the potential benefits of triploid C. sativa cultivars in commercial agriculture.