bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting Aldehyde Dehydrogenases to Eliminate Cancer Stem Cells in Gynecologic Malignancies
Authors: Muralikrishnan Vaishnavi , Hurley Thomas D. , Nephew Kenneth P.
Published: April 2020

Gynecologic cancers cause over 600,000 deaths annually in women worldwide. The development of chemoresistance after initial rounds of chemotherapy contributes to tumor relapse and death due to gynecologic malignancies. In this regard, cancer stem cells (CSCs), a subpopulation of stem cells with the ability to undergo self-renewal and clonal evolution, play a key role in tumor progression and drug resistance. Aldehyde dehydrogenases (ALDH) are a group of enzymes shown to be robust CSC markers in gynecologic and other malignancies. These enzymes also play functional roles in CSCs, including detoxification of aldehydes, scavenging of reactive oxygen species (ROS), and retinoic acid (RA) signaling, making ALDH an attractive therapeutic target in various clinical scenarios. In this review, we discuss the critical roles of the ALDH in driving stemness in different gynecologic malignancies. We review inhibitors of ALDH, both general and isoform-specific, which have been used to target CSCs in gynecologic cancers. Many of these inhibitors have been shown to be effective in preclinical models of gynecologic malignancies, supporting further development in the clinic. Furthermore, ALDH inhibitors, including 673A and CM037, synergize with chemotherapy to reduce tumor growth. Thus, ALDH-targeted therapies hold promise for improving patient outcomes in gynecologic malignancies.
Towards Physiologically and Tightly Regulated Vectored Antibody Therapies
Authors: Page Audrey , Fusil Floriane , Cosset François-Loïc
Published: April 2020

Cancers represent highly significant health issues and the options for their treatment are often not efficient to cure the disease. Immunotherapy strategies have been developed to modulate the patient’s immune system in order to eradicate cancerous cells. For instance, passive immunization consists in the administration at high doses of exogenously produced monoclonal antibodies directed either against tumor antigen or against immune checkpoint inhibitors. Its main advantage is that it provides immediate immunity, though during a relatively short period, which consequently requires frequent injections. To circumvent this limitation, several approaches, reviewed here, have emerged to induce in vivo antibody secretion at physiological doses. Gene delivery vectors, such as adenoviral vectors or adeno-associated vectors, have been designed to induce antibody secretion in vivo after in situ cell modification, and have driven significant improvements in several cancer models. However, anti-idiotypic antibodies and escape mutants have been detected, probably because of both the continuous expression of antibodies and their expression by unspecialized cell types. To overcome these hurdles, adoptive transfer of genetically modified B cells that secrete antibodies either constitutively or in a regulated manner have been developed by ex vivo transgene insertion with viral vectors. Recently, with the emergence of gene editing technologies, the endogenous B cell receptor loci of B cells have been modified with the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated endonuclease (Cas-9) system to change their specificity in order to target a given antigen. The expression of the modified BCR gene hence follows the endogenous regulation mechanisms, which may prevent or at least reduce side effects. Although these approaches seem promising for cancer treatments, major questions, such as the persistence and the re-activation potential of these engineered cells, remain to be addressed in clinically relevant animal models before translation to humans.
Analysis of the Circadian Regulation of Cancer Hallmarks by a Cross-Platform Study of Colorectal Cancer Time-Series Data Reveals an Association with Genes Involved in Huntington’s Disease
Authors: Yalçin Müge , El-Athman Rukeia , Ouk Koliane , Priller Josef , Relógio Angela
Published: April 2020

Accumulating evidence points to a link between circadian clock dysfunction and the molecular events that drive tumorigenesis. Here, we investigated the connection between the circadian clock and the hallmarks of cancer in an in vitro model of colorectal cancer (CRC). We used a cross-platform data normalization method to concatenate and compare available microarray and RNA-sequencing time series data of CRC cell lines derived from the same patient at different disease stages. Our data analysis suggests differential regulation of molecular pathways between the CRC cells and identifies several of the circadian and likely clock-controlled genes (CCGs) as cancer hallmarks and circadian drug targets. Notably, we found links of the CCGs to Huntington’s disease (HD) in the metastasis-derived cells. We then investigated the impact of perturbations of our candidate genes in a cohort of 439 patients with colon adenocarcinoma retrieved from the Cancer Genome Atlas (TCGA). The analysis revealed a correlation of the differential expression levels of the candidate genes with the survival of patients. Thus, our study provides a bioinformatics workflow that allows for a comprehensive analysis of circadian properties at different stages of colorectal cancer, and identifies a new association between cancer and HD.
Detection of Human CD38 Using Variable Lymphocyte Receptor (VLR) Tetramers
Authors: Khan Srijit , Liu Yanling , Ernst Laura M. , Leung Leslie Y. T. , Budylowski Patrick , Dong Shilan , Campisi Paolo , Propst Evan J. , Wolter Nikolaus E. , Grunebaum Eyal , Ostrowski Mario , Ehrhardt Götz R. A.
Published: April 2020

CD38 is a multifunctional cell surface receptor expressed on multiple cell lineages of hematopoietic origin with high levels of expression on human plasma cells. Previously, we isolated the monoclonal variable lymphocyte receptor B (VLRB) MM3 antibody from the evolutionarily distant sea lamprey, which recognized the CD38 ectoenzyme exclusively on human plasma cells in a manner that correlated with CD38 enzymatic activity. The plasma cell-specific binding of VLRB MM3 contrasts with the broad pattern of expression of CD38-determined conventional antibodies specific for this antigen. In an effort to facilitate the application of this unique reagent in combination with conventional antibody panels, we explored a strategy to generate VLRB MM3 tetramers. The resulting reagent maintained the threshold-based recognition of CD38. Increased sensitivity achieved with VLRB MM3 tetramers also showed preferential recognition of germinal center centroblasts over centrocytes. VLRB MM3 tetramers thus provided a unique and versatile single-step staining reagent for the detection of human CD38 that is readily incorporated into multi-color flow cytometry panels.
Modulation of Plasma Membrane Composition and Microdomain Organization Impairs Heat Shock Protein Expression in B16-F10 Mouse Melanoma Cells
Authors: Crul Tim , Csoboz Balint , Gombos Imre , Marton Annamaria , Peter Maria , Balogh Gabor , Vizler Csaba , Szente Lajos , Vigh Laszlo
Published: April 2020

The heat shock response (HSR) regulates induction of stress/heat shock proteins (HSPs) to preserve proteostasis during cellular stress. Earlier, our group established that the plasma membrane (PM) acts as a sensor and regulator of HSR through changes in its microdomain organization. PM microdomains such as lipid rafts, dynamic nanoscale assemblies enriched in cholesterol and sphingomyelin, and caveolae, cholesterol-rich PM invaginations, constitute clustering platforms for proteins functional in signaling cascades. Here, we aimed to compare the effect of cyclodextrin (MβCD)- and nystatin-induced cholesterol modulations on stress-activated expression of the representative HSPs, HSP70, and HSP25 in mouse B16-F10 melanoma cells. Depletion of cholesterol levels with MβCD impaired the heat-inducibility of both HSP70 and HSP25. Sequestration of cholesterol with nystatin impaired the heat-inducibility of HSP25 but not of HSP70. Imaging fluorescent correlation spectroscopy marked a modulated lateral diffusion constant of fluorescently labelled cholesterol in PM during cholesterol deprived conditions. Lipidomics analysis upon MβCD treatment revealed, next to cholesterol reductions, decreased lysophosphatidylcholine and phosphatidic acid levels. These data not only highlight the involvement of PM integrity in HSR but also suggest that altered dynamics of specific cholesterol pools could represent a mechanism to fine tune HSP expression.
CCN-Based Therapeutic Peptides Modify Pancreatic Ductal Adenocarcinoma Microenvironment and Decrease Tumor Growth in Combination with Chemotherapy
Authors: Resovi Andrea , Borsotti Patrizia , Ceruti Tommaso , Passoni Alice , Zucchetti Massimo , Berndt Alexander , Riser Bruce L. , Taraboletti Giulia , Belotti Dorina
Published: April 2020

The prominent desmoplastic stroma of pancreatic ductal adenocarcinoma (PDAC) is a determinant factor in tumor progression and a major barrier to the access of chemotherapy. The PDAC microenvironment therefore appears to be a promising therapeutic target. CCN2/CTGF is a profibrotic matricellular protein, highly present in the PDAC microenvironment and associated with disease progression. Here we have investigated the therapeutic value of the CCN2-targeting BLR100 and BLR200, two modified synthetic peptides derived from active regions of CCN3, an endogenous inhibitor of CCN2. In a murine orthotopic PDAC model, the two peptides, administered as monotherapy at low doses (approximating physiological levels of CCN3), had tumor inhibitory activity that increased with the dose. The peptides affected the tumor microenvironment, inhibiting fibrosis and vessel formation and reducing necrosis. Both peptides were active in preventing ascites formation. An increased activity was obtained in combination regimens, administering BLR100 or BLR200 with the chemotherapeutic drug gemcitabine. Pharmacokinetic analysis indicated that the improved activity of the combination was not mainly determined by the substantial increase in gemcitabine delivery to tumors, suggesting other effects on the tumor microenvironment. The beneficial remodeling of the tumor stroma supports the potential value of these CCN3-derived peptides for targeting pathways regulated by CCN2 in PDAC.
The Catalytic-Dependent and -Independent Roles of Lsd1 and Lsd2 Lysine Demethylases in Heterochromatin Formation in Schizosaccharomyces pombe
Authors: Marayati Bahjat F. , Tucker James F. , De La Cerda David A. , Hou Tien-Chi , Chen Rong , Sugiyama Tomoyasu , Pease James B. , Zhang Ke
Published: April 2020

In eukaryotes, heterochromatin plays a critical role in organismal development and cell fate acquisition, through regulating gene expression. The evolutionarily conserved lysine-specific demethylases, Lsd1 and Lsd2, remove mono- and dimethylation on histone H3, serving complex roles in gene expression. In the fission yeast Schizosaccharomyces pombe, null mutations of Lsd1 and Lsd2 result in either severe growth defects or inviability, while catalytic inactivation causes minimal defects, indicating that Lsd1 and Lsd2 have essential functions beyond their known demethylase activity. Here, we show that catalytic mutants of Lsd1 or Lsd2 partially assemble functional heterochromatin at centromeres in RNAi-deficient cells, while the C-terminal truncated alleles of Lsd1 or Lsd2 exacerbate heterochromatin formation at all major heterochromatic regions, suggesting that Lsd1 and Lsd2 repress heterochromatic transcripts through mechanisms both dependent on and independent of their catalytic activities. Lsd1 and Lsd2 are also involved in the establishment and maintenance of heterochromatin. At constitutive heterochromatic regions, Lsd1 and Lsd2 regulate one another and cooperate with other histone modifiers, including the class II HDAC Clr3 and the Sirtuin family protein Sir2 for gene silencing, but not with the class I HDAC Clr6. Our findings explore the roles of lysine-specific demethylases in epigenetic gene silencing at heterochromatic regions.
Adenosine-Related Mechanisms in Non-Adenosine Receptor Drugs
Authors: Jacobson Kenneth A. , Reitman Marc L.
Published: April 2020

Many ligands directly target adenosine receptors (ARs). Here we review the effects of noncanonical AR drugs on adenosinergic signaling. Non-AR mechanisms include raising adenosine levels by inhibiting adenosine transport (e.g., ticagrelor, ethanol, and cannabidiol), affecting intracellular metabolic pathways (e.g., methotrexate, nicotinamide riboside, salicylate, and 5-aminoimidazole-4-carboxamide riboside), or undetermined means (e.g., acupuncture). However, other compounds bind ARs in addition to their canonical ‘on-target’ activity (e.g., mefloquine). The strength of experimental support for an adenosine-related role in a drug’s effects varies widely. AR knockout mice are the ‘gold standard’ method for investigating an AR role, but few drugs have been tested on these mice. Given the interest in AR modulation for treatment of cancer, CNS, immune, metabolic, cardiovascular, and musculoskeletal conditions, it is informative to consider AR and non-AR adenosinergic effects of approved drugs and conventional treatments.
Towards a Unified Theory of Learning and Information
Authors: Alabdulmohsin Ibrahim
Published: April 2020

In this paper, we introduce the notion of “learning capacity” for algorithms that learn from data, which is analogous to the Shannon channel capacity for communication systems. We show how “learning capacity” bridges the gap between statistical learning theory and information theory, and we will use it to derive generalization bounds for finite hypothesis spaces, differential privacy, and countable domains, among others. Moreover, we prove that under the Axiom of Choice, the existence of an empirical risk minimization (ERM) rule that has a vanishing learning capacity is equivalent to the assertion that the hypothesis space has a finite Vapnik–Chervonenkis (VC) dimension, thus establishing an equivalence relation between two of the most fundamental concepts in statistical learning theory and information theory. In addition, we show how the learning capacity of an algorithm provides important qualitative results, such as on the relation between generalization and algorithmic stability, information leakage, and data processing. Finally, we conclude by listing some open problems and suggesting future directions of research.
A Nonparametric Bayesian Approach to the Rare Type Match Problem
Authors: Cereda Giulia , Gill Richard D.
Published: April 2020

The “rare type match problem” is the situation in which, in a criminal case, the suspect’s DNA profile, matching the DNA profile of the crime stain, is not in the database of reference. Ideally, the evaluation of this observed match in the light of the two competing hypotheses (the crime stain has been left by the suspect or by another person) should be based on the calculation of the likelihood ratio and depends on the population proportions of the DNA profiles that are unknown. We propose a Bayesian nonparametric method that uses a two-parameter Poisson Dirichlet distribution as a prior over the ranked population proportions and discards the information about the names of the different DNA profiles. This model is validated using data coming from European Y-STR DNA profiles, and the calculation of the likelihood ratio becomes quite simple thanks to an Empirical Bayes approach for which we provided a motivation.
Association Factor for Identifying Linear and Nonlinear Correlations in Noisy Conditions
Authors: Kachouie Nezamoddin N. , Deebani Wejdan
Published: April 2020

Background: In data analysis and machine learning, we often need to identify and quantify the correlation between variables. Although Pearson’s correlation coefficient has been widely used, its value is reliable only for linear relationships and Distance correlation was introduced to address this shortcoming. Methods: Distance correlation can identify linear and nonlinear correlations. However, its performance drops in noisy conditions. In this paper, we introduce the Association Factor (AF) as a robust method for identification and quantification of linear and nonlinear associations in noisy conditions. Results: To test the performance of the proposed Association Factor, we modeled several simulations of linear and nonlinear relationships in different noise conditions and computed Pearson’s correlation, Distance correlation, and the proposed Association Factor. Conclusion: Our results show that the proposed method is robust in two ways. First, it can identify both linear and nonlinear associations. Second, the proposed Association Factor is reliable in both noiseless and noisy conditions.
Teaching Human Rights: Toward a Kingdom of Ends
Authors: Al-Daraweesh Fuad
Published: April 2020

The author argues that the current practices of human rights education produce anti-educational orthodoxies that result from a divorce between human rights and human rights education and human dignity, moral autonomy, and the right to justification.
The Effect of the Methanol–Water Interaction on the Surface Layer on Titanium in CH3OH-H2O-LiClO4 Solutions
Authors: Lelek-Borkowska Urszula , Palumbo Gaetano , Banaś Jacek
Published: April 2020

The purpose of this study was to explain the mechanism of formation and to examine the composition of the anodic film formed on the surface of titanium in an anhydrous neutral methanol solution of electrolytes. In an environment deprived of water molecules, the growth of a 3D-phase titanium oxide layer is not possible. Electrochemical investigations demonstrated that the Ti surface in CH3OH-LiClO4 solutions experienced a pseudo-passivation with the formation of a methoxy layer, which resulted from the reaction of the metal surface with alcohol molecules. The presence of this methoxy surface film was confirmed through XPS and in situ FTIR measurements. The layer blocked the Ti anodic dissolution at the potential range corresponding to the stability of methanol and methoxy ions (i.e., <0.55 V). At potentials over 0.55 V, the methoxy layer was oxidised, which caused the “depassivation” of the metal surface and the etching of titanium. The addition of water changed the properties of Ti in CH3OH-LiClO4 solutions, but only with a water content above 0.2 mole fraction. Below this concentration of water, titanium behaved like it would in an anhydrous solution of methanol. In the range of water concentration of 0.2 to 0.7 mole fraction, the structure of the solution is strengthened because both components of the solvent formed separate percolating networks. The strengthening of the solution structure resulted in a strengthening of the surface layer of Ti(OH)m(OCH3)n. Such a layer had strong barrier properties similar to the properties of an organic polymer film. The formation and growth of a stable layer of TiO2 were possible only in a solvent when the water concentration was higher than ≈0.7 mole fraction.
On-Site Identification of the Material Composition of PV Modules with Mobile Spectroscopic Devices
Authors: Eder Gabriele C. , Lin Yiji , Voronko Yuliya , Spoljaric-Lukacic Lidija
Published: April 2020

With the increased development of portable and handheld molecular spectrometers within recent years, new fields of applications have opened up, such as their use (i) for material identification of samples contained in large and non-portable components and (ii) the detection of material degradation effects and failures directly in the plant. The usability and transferability of well-established analytical characterization techniques, such as attenuated total reflection (ATR) Infrared (IR)-, Raman, and Near-Infrared (NIR)-spectroscopy as mobile devices for the in-field characterization of Photovoltaic (PV) modules, are described and discussed. Material identification of the polymeric compounds incorporated in the PV modules (encapsulants, backsheets) is often an important task, especially when degradation and failures occur. Whereas the knowledge of the bill of materials is one challenge, the detection of material degradation effects is another important issue. Both tasks can be solved nondestructively by the application of mobile spectrometers. Raman spectroscopy is the best-suited method for the identification of the encapsulant within the module (measurement through 3-mm glass), while NIR measurements allowed for the nondestructive determination of the composition of the multilayer backsheet. Surface degradation effects (e.g., oxidation, hydrolysis) are best detectable with IR-spectroscopy. The application of mobile devices allows for direct material analysis in the field without dismantling PV modules, transporting them to the lab, cutting them in smaller pieces, and analyzing them in conventional bench-top spectrometers.
A Harmonic Impedance Identification Method of Traction Network Based on Data Evolution Mechanism
Authors: Yang Ruixuan , Zhou Fulin , Zhong Kai
Published: April 2020

In railway electrification systems, the harmonic impedance of the traction network is of great value for avoiding harmonic resonance and electrical matching of impedance parameters between trains and traction networks. Therefore, harmonic impedance identification is beneficial to suppress harmonics and improve the power quality of the traction network. As a result of the coupling characteristics of the traction power supply system, the identification results of harmonic impedance may be inaccurate and controversial. In this context, an identification method based on a data evolution mechanism is proposed. At first, a harmonic impedance model is established and the equivalent circuit of the traction network is established. According to the harmonic impedance model, the proposed method eliminates the outliers of the measured data from trains by the Grubbs criterion and calculates the harmonic impedance by partial least squares regression. Then, the data evolution mechanism based on the sample coefficient of determination is introduced to estimate the reliability of the identification results and to divide results into several reliability levels. Furthermore, in the data evolution mechanism through adding new harmonic data, the low-reliability results can be replaced by the new results with high reliability and, finally, the high-reliability results can cover all frequencies. Moreover, the identification results based on the simulation data show the higher reliability results are more accurate than the lower reliability results. The measured data verify that the the data evolution mechanism can improve accuracy and reliability, and their results prove the feasibility and validation of the proposed method.
A Building Life-Cycle Embodied Performance Index—The Relationship between Embodied Energy, Embodied Carbon and Environmental Impact
Authors: Hu Ming
Published: April 2020

Knowledge and research tying the environmental impact and embodied energy together is a largely unexplored area in the building industry. The aim of this study is to investigate the practicality of using the ratio between embodied energy and embodied carbon to measure the building’s impact. This study is based on life-cycle assessment and proposes a new measure: life-cycle embodied performance (LCEP), in order to evaluate building performance. In this project, eight buildings located in the same climate zone with similar construction types are studied to test the proposed method. For each case, the embodied energy intensities and embodied carbon coefficients are calculated, and four environmental impact categories are quantified. The following observations can be drawn from the findings: (a) the ozone depletion potential could be used as an indicator to predict the value of LCEP; (b) the use of embodied energy and embodied carbon independently from each other could lead to incomplete assessments; and (c) the exterior wall system is a common significant factor influencing embodied energy and embodied carbon. The results lead to several conclusions: firstly, the proposed LCEP ratio, between embodied energy and embodied carbon, can serve as a genuine indicator of embodied performance. Secondly, environmental impact categories are not dependent on embodied energy, nor embodied carbon. Rather, they are proportional to LCEP. Lastly, among the different building materials studied, metal and concrete express the highest contribution towards embodied energy and embodied carbon.
Space Charge Measurement and Modelling in Cross-Linked Polyethylene
Authors: Zhan Yunpeng , Chen George , Hao Miao , Pu Lu , Zhao Xuefeng , Wang Sen , Liu Jian
Published: April 2020

Cross-linked polyethylene, commercially known as XLPE, is widely used as an insulating material in high voltage cables. However, space charge accumulation under the DC field is one of the most challenging problems in the further development of XLPE insulated cable. Due to the potential electrical degradation ageing process triggered by the accumulated space charges, the IEEE standard 1732 was established for measuring space charge in HVDC extruded cables as the qualification tests. Previous research has revealed that space charge originates from either charge injection at the electrodes or ionization of impurities presenting inside the bulk. In the light of this, this paper aims to simulate the accumulation of space charge in XLPE under DC stress. Space charge measurements have been carried on the fresh and degassed XLPE samples. A modified bipolar charge transport model, by considering the dissociation of impurities, has been employed to simulate the space charge behavior in XLPE. Compared with the experimental observations, the simulation results can reveal appropriate features of hetero charge formation. Both the calculated charge dynamics and field variation are consistent with the experiment results. The restrictions and potential improvements of this preliminary model are also discussed for its future application of XLPE cables.
Effect Thresholds of Metals in Stream Sediments Based on In Situ Oligochaete Communities
Authors: Vivien Régis , Casado-Martínez Carmen , Lafont Michel , Ferrari Benoit J.D.
Published: April 2020

Aquatic oligochaetes, comprising a large number of species showing various degrees of resistance to chemical pollution, are recognized as valuable bioindicators of sediments’ quality. In the Geneva area (Switzerland), oligochaete tools were previously tested for assessing the biological quality of stream sediments, and effect thresholds of combined metals (quotients) in sediments were defined. The aims of the present study were to update this previous work with new data acquired in different cantons of Switzerland and to establish effect thresholds on oligochaete communities for individual metals and for combined metals. The oligochaete metrics “Oligochaete index of sediment bioindication (IOBS)”, “oligochaete density” and “percentage of tubificids without hair setae” proved pertinent for assessing the effects of metals and organic matter in sediments. We established a threshold effect level (TELoligo) and probable effect level (PELoligo) for eight metals in sediments (Cr, Ni, Zn, Cu, Pb, Cd, Hg and As) as well as a probable effect level for these metals combined (mPELoligo-Q). These thresholds could be used directly to screen for alteration of in situ communities restricted to sediments and/or for establishing sediment quality standards based on a combination of different biological and ecotoxicological tools.
An Untargeted Metabolomics Investigation of Jiulong Yak (Bos grunniens) Meat by 1H-NMR
Authors: Zhu Chenglin , Petracci Massimiliano , Li Cheng , Fiore Enrico , Laghi Luca
Published: April 2020

Yak represents the main meat source for Tibetan people. This work aimed to investigate the metabolome of raw meat from Jiulong yaks, focusing on specimens farmed and harvested locally through traditional procedures. Untargeted nuclear magnetic resonance spectroscopy (1H-NMR) was selected as the analytical platform. Samples from longissimus thoracis, trapezius, triceps brachii and biceps femoris muscles, with different prevalences of red and white fibers, were selected. Among the fifty-three metabolites quantified in each of them, carnitine, carnosine, creatine and taurine are known for their bioactive properties. Twelve molecules were found to be differently concentrated in relation to muscle type. Longissimus thoracis, compared to biceps femoris, had higher concentrations of carnosine and formate and lower concentrations of mannose, inosine, threonine, IMP, alanine, valine, isoleucine, tyrosine, phenylalanine and leucine. A metabolic pathway analysis suggested that the main pathways differing among the muscles were connected to the turnover of amino acids. These results contribute to a deeper understanding of yak raw meat metabolism and muscle type differences, which can be used as an initial reference for the meat industry to set up muscle-specific investigations. The possibility of simultaneously quantifying several bioactive compounds suggests that these investigations could revolve around meat’s nutritional value.
The Exact Query Complexity of Yes-No Permutation Mastermind
Authors: El Ouali Mourad , Sauerland Volkmar
Published: April 2020

Mastermind is famous two-player game. The first player (codemaker) chooses a secret code which the second player (codebreaker) is supposed to crack within a minimum number of code guesses (queries). Therefore, the codemaker’s duty is to help the codebreaker by providing a well-defined error measure between the secret code and the guessed code after each query. We consider a variant, called Yes-No AB-Mastermind, where both secret code and queries must be repetition-free and the provided information by the codemaker only indicates if a query contains any correct position at all. For this Mastermind version with n positions and k ≥ n colors and ℓ : = k + 1 − n , we prove a lower bound of ∑ j = ℓ k log 2 j and an upper bound of n log 2 n + k on the number of queries necessary to break the secret code. For the important case k = n , where both secret code and queries represent permutations, our results imply an exact asymptotic complexity of Θ ( n log n ) queries.
Comprehensive History of CSP Genes: Evolution, Phylogenetic Distribution and Functions
Authors: Liu Guoxia , Xuan Ning , Rajashekar Balaji , Arnaud Philippe , Offmann Bernard , Picimbon Jean-François
Published: April 2020

In this review we present the developmental, histological, evolutionary and functional properties of insect chemosensory proteins (CSPs) in insect species. CSPs are small globular proteins folded like a prism and notoriously known for their complex and arguably obscure function(s), particularly in pheromone olfaction. Here, we focus on direct functional consequences on protein function depending on duplication, expression and RNA editing. The result of our analysis is important for understanding the significance of RNA-editing on functionality of CSP genes, particularly in the brain tissue.
Gene Expression Profiling of Corpus luteum Reveals Important Insights about Early Pregnancy in Domestic Sheep
Authors: Pokharel Kisun , Peippo Jaana , Weldenegodguad Melak , Honkatukia Mervi , Li Meng-Hua , Kantanen Juha
Published: April 2020

The majority of pregnancy loss in ruminants occurs during the preimplantation stage, which is thus the most critical period determining reproductive success. Here, we performed a comparative transcriptome study by sequencing total mRNA from corpus luteum (CL) collected during the preimplantation stage of pregnancy in Finnsheep, Texel and F1 crosses. A total of 21,287 genes were expressed in our data. Highly expressed autosomal genes in the CL were associated with biological processes such as progesterone formation (STAR, CYP11A1, and HSD3B1) and embryo implantation (e.g., TIMP1, TIMP2 and TCTP). Among the list of differentially expressed genes, sialic acid-binding immunoglobulin (Ig)-like lectins (SIGLEC3, SIGLEC14, SIGLEC8), ribosomal proteins (RPL17, RPL34, RPS3A, MRPS33) and chemokines (CCL5, CCL24, CXCL13, CXCL9) were upregulated in Finnsheep, while four multidrug resistance-associated proteins (MRPs) were upregulated in Texel ewes. A total of 17 known genes and two uncharacterized non-coding RNAs (ncRNAs) were differentially expressed in breed-wise comparisons owing to the flushing diet effect. The significantly upregulated TXNL1 gene indicated potential for embryonic diapause in Finnsheep and F1. Moreover, we report, for the first time in any species, several genes that are active in the CL during early pregnancy (including TXNL1, SIGLEC14, SIGLEC8, MRP4, and CA5A).
Turtle Insights into the Evolution of the Reptilian Karyotype and the Genomic Architecture of Sex Determination
Authors: Bista Basanta , Valenzuela Nicole
Published: April 2020

Sex chromosome evolution remains an evolutionary puzzle despite its importance in understanding sexual development and genome evolution. The seemingly random distribution of sex-determining systems in reptiles offers a unique opportunity to study sex chromosome evolution not afforded by mammals or birds. These reptilian systems derive from multiple transitions in sex determination, some independent, some convergent, that lead to the birth and death of sex chromosomes in various lineages. Here we focus on turtles, an emerging model group with growing genomic resources. We review karyotypic changes that accompanied the evolution of chromosomal systems of genotypic sex determination (GSD) in chelonians from systems under the control of environmental temperature (TSD). These transitions gave rise to 31 GSD species identified thus far (out of 101 turtles with known sex determination), 27 with a characterized sex chromosome system (13 of those karyotypically). These sex chromosomes are varied in terms of the ancestral autosome they co-opted and thus in their homology, as well as in their size (some are macro-, some are micro-chromosomes), heterogamety (some are XX/XY, some ZZ/ZW), dimorphism (some are virtually homomorphic, some heteromorphic with larger-X, larger W, or smaller-Y), age (the oldest system could be ~195 My old and the youngest < 25 My old). Combined, all data indicate that turtles follow some tenets of classic theoretical models of sex chromosome evolution while countering others. Finally, although the study of dosage compensation and molecular divergence of turtle sex chromosomes has lagged behind research on other aspects of their evolution, this gap is rapidly decreasing with the acceleration of ongoing research and growing genomic resources in this group.
Genes Containing Long Introns Occupy Series of Bands and Interbands in Drosophila melanogaster Polytene Chromosomes
Authors: Khoroshko Varvara A. , Pokholkova Galina V. , Levitsky Victor G. , Zykova Tatyana Yu. , Antonenko Oksana V. , Belyaeva Elena S. , Zhimulev Igor F.
Published: April 2020

The Drosophila melanogaster polytene chromosomes are the best model for studying the genome organization during interphase. Despite of the long-term studies available on genetic organization of polytene chromosome bands and interbands, little is known regarding long gene location on chromosomes. To analyze it, we used bioinformatic approaches and characterized genome-wide distribution of introns in gene bodies and in different chromatin states, and using fluorescent in situ hybridization we juxtaposed them with the chromosome structures. Short introns up to 2 kb in length are located in the bodies of housekeeping genes (grey bands or lazurite chromatin). In the group of 70 longest genes in the Drosophila genome, 95% of total gene length accrues to introns. The mapping of the 15 long genes showed that they could occupy extended sections of polytene chromosomes containing band and interband series, with promoters located in the interband fragments (aquamarine chromatin). Introns (malachite and ruby chromatin) in polytene chromosomes form independent bands, which can contain either both introns and exons or intron material only. Thus, a novel type of the gene arrangement in polytene chromosomes was discovered; peculiarities of such genetic organization are discussed.
Cloning and Functional Characterization of a Flavonoid Transport-Related MATE Gene in Asiatic Hybrid Lilies (Lilium spp.)
Authors: Xu Hua , Yang Panpan , Cao Yuwei , Tang Yuchao , He Guoren , Xu Leifeng , Ming Jun
Published: April 2020

Previous studies have suggested that multidrug and toxic compound extrusion (MATE) proteins might be involved in flavonoid transportation. However, whether MATE proteins are involved in anthocyanin accumulation in Lilium is unclear. Here, a flavonoid transport-related MATE candidate gene, LhDTX35, was cloned from the Asiatic hybrid lily cultivar ‘Tiny Padhye’ by rapid amplification of 5’ and 3’ cDNA ends (RACE) and found to encode 507 amino acids. BLASTx results indicated that LhDTX35 showed high homology to the DTX35 genes of other species. Bioinformatics analysis predicted that the protein encoded by LhDTX35 possessed 12 typical transmembrane segments and had functional domains typical of the MATE-like superfamily. Phylogenetic analysis grouped LhDTX35 in the same clade as the DTX35 of other species. Notably, the expression pattern of LhDTX35 was positively correlated with floral anthocyanin accumulation in ‘Tiny Padhye’. A subcellular localization assay showed that the protein encoded by LhDTX35 was plasmalemma localized but not nuclear, indicating that the LhDTX35 gene may function as a carrier protein to transport anthocyanins in Lilium. Functional complementation of the Arabidopsis DTX35 gene demonstrated that LhDTX35 could restore silique-infertility and the anthocyaninless phenotype of an Arabidopsis DTX35 mutant. These results indicated that LhDTX35 might be involved in anthocyanin accumulation in Lilium.
Methodological Approaches to Support Process Improvement in Emergency Departments: A Systematic Review
Authors: Ortíz-Barrios Miguel Angel , Alfaro-Saíz Juan-José
Published: April 2020

The most commonly used techniques for addressing each Emergency Department (ED) problem (overcrowding, prolonged waiting time, extended length of stay, excessive patient flow time, and high left-without-being-seen (LWBS) rates) were specified to provide healthcare managers and researchers with a useful framework for effectively solving these operational deficiencies. Finally, we identified the existing research tendencies and highlighted opportunities for future work. We implemented the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology to undertake a review including scholarly articles published between April 1993 and October 2019. The selected papers were categorized considering the leading ED problems and publication year. Two hundred and three (203) papers distributed in 120 journals were found to meet the inclusion criteria. Furthermore, computer simulation and lean manufacturing were concluded to be the most prominent approaches for addressing the leading operational problems in EDs. In future interventions, ED administrators and researchers are widely advised to combine Operations Research (OR) methods, quality-based techniques, and data-driven approaches for upgrading the performance of EDs. On a different tack, more interventions are required for tackling overcrowding and high left-without-being-seen rates.
Dental Care for Asylum-Seekers in Germany: A Retrospective Hospital-Based Study
Authors: Freiberg Anna , Wienke Andreas , Bauer Lena , Niedermaier Andreas , Führer Amand
Published: April 2020

Background: The growing immigration to Germany led to more patients whose medical needs are divergent from those of the domestic population. In the field of dental health care there is a debate about how well the German health system is able to meet the resulting challenges. Data on asylum-seekers’ dental health is scarce. This work is intended to reduce this data gap. Methods: We conducted this retrospective observational study in Halle (Saale), Germany. We included all persons who were registered with the social welfare office (SWO) in 2015 and received dental treatments. From the medical records, we derived information such as complaints, diagnoses, and treatments. Results: Out of 4107 asylum-seekers, the SWO received a bill for 568 people. On average, there were 1.44 treatment cases (95%-CI: 1.34–1.55) and 2.53 contacts with the dentist per patient (95%-CI: 2.33–2.74). Among those, the majority went to the dentist because of localized (43.2%, 95%-CI: 38.7–47.7) and non-localized pain (32.0%, 95%-CI: 27.8–36.2). The most widespread diagnosis was caries (n = 469, 98.7%, 95%-CI: 97.7–99.7). Conclusion: The utilization of dental care is lower among asylum-seekers than among regularly insured patients. We assume that the low prevalence rates in our data indicate existing access barriers to the German health care system.
A New Assessment for Activities of Daily Living in Spanish Schoolchildren: A Preliminary Study of its Psychometric Properties
Authors: Barrios-Fernández Sabina , Gozalo Margarita , García-Gómez Andrés , Romero-Ayuso Dulce , Hernández-Mocholí Miguel Ángel
Published: April 2020

Background: Activities of daily living (ADL), which are divided into basic (BADL) and instrumental (IADL), allows us to survive and to live in the society. Cognitive skills are a key aspect in BADL outcomes. After reviewing existing BADL tools for Spanish schoolchildren, issues such as not covering the full age range or not having a BADL-centred vision were found. We aim to develop a new tool for BADL assessment in Spanish schoolchildren. Methods: The new tool was administered to 375 participants (47.2% boys and 52.8% girls) from 6 to 12 years of age. Analyses were carried out to find out the structure (semiconfirmatory factor analysis) and internal consistency (ordinal alpha) of BADL. Results: Four scales formed the instrument (Eating, Personal Hygiene, Getting Dressed, and General Functioning) with an interpretable solution of 12 factors (Manual Dexterity, Proprioception, Oral Sensitivity, Good Manners, Hygiene and Grooming, Toileting Needs Communication, Bladder and Bowel Control, Showering, Independent Dressing Tasks, Full Dressing, Executive Functions, and Self-Regulation) with 84 items + 6 qualitative items for girls. The reliability values obtained were acceptable (.70–.88). Conclusions: The tool seems to be a practical and reliable instrument to assess BADL and cognitive skills during BADL in Spanish schoolchildren.
Effects of Proximity between Companion Dogs and Their Caregivers on Heart Rate Variability Measures in Older Adults: A Pilot Study
Authors: Ortmeyer Heidi K. , Katzel Leslie I.
Published: April 2020

Heart rate variability (HRV) is a noninvasive tool used to evaluate autonomic nervous system function and is affected by age, stress, postural changes, and physical activity. Dog ownership has been associated with higher 24-hr HRV and increased physical activity compared to nonowners. The current pilot study was designed to evaluate the effects of proximity to a dog in real time (minute-by-minute) on older dog caregivers’ HRV measures and stress index during normal daily life over a 24-hr period. Eleven caregivers (56–83 years of age) wore ActiGraph GT9X Link accelerometers and camntech electrocardiogram monitors, and 11 dogs wore PetPace Collars and ActiGraph monitors to determine (a) proximity (absence or presence of Received Signal Strength Indicator, RSSI), (b) heart rate and HRV measures, (c) position (lying vs. sitting vs. standing), and (d) physical activity in the 11 dyads. Twenty-four hour HRV (SDNN index) and physical activity in the caregivers and dogs were related. Stress index was lower, and HRV parameters (SDNN, rMSDD, high frequency power (HF)) were higher when an RSSI signal was detected (presence of dog) compared to no RSSI signal (absence of dog) in the caregivers while inactive (lying + sitting + standing combined). HRV parameters (rMSDD and HF) were lower in the caregivers while standing and sitting compared to lying. The results from this pilot study support the hypothesis that spending time in the presence of a companion dog increases caregivers’ HRV throughout the day and suggest that proximity to a dog may contribute to overall improvements in 24-hr HRV and cardiac health in dog caregivers.
Exogenous NO Therapy for the Treatment and Prevention of Atherosclerosis
Authors: Gori Tommaso
Published: April 2020

Amyl nitrite was introduced in 1867 as the first molecule of a new class of agents for the treatment of angina pectoris. In the following 150 years, the nitric oxide pathway has been the subject of a number of pharmacological approaches, particularly since when this elusive mediator was identified as one of the most important modulators of vascular homeostasis beyond vasomotion, including platelet function, inflammation, and atherogenesis. While having potent antianginal and antiischemic properties, however, nitric oxide donors are also not devoid of side effects, including the induction of tolerance, and, as shown in the last decade, of oxidative stress and endothelial dysfunction. In turn, endothelial dysfunction is itself felt to be involved in all stages of atherogenesis, from the development of fatty streaks to plaque rupture and thrombosis. In the present review, we summarize the agents that act on the nitric oxide pathway, with a particular focus on their potentially beneficial antiatherosclerotic and unwanted pro-atherosclerotic effects.
Depth of Neuromuscular Block Is Not Associated with Abdominal Wall Distention or Surgical Conditions during Gynecologic Laparoscopic Operations. A Prospective Trial
Authors: Soltesz Stefan , Mathes Alexander , Anapolski Michael , Noé Karl Guenter
Published: April 2020

The influence of the degree of a neuromuscular block (NMB) on surgical operating conditions during laparoscopic surgery is debated controversially. The extent of abdominal distension during the time course of the NMB was assessed as a new measurement tool. In 60 patients scheduled for gynecologic laparoscopic surgery, the increase of the abdominal wall length induced by the capnoperitoneum was measured at 5 degrees of the NMB: intense NMB—post-tetanic count (PTC) = 0; deep NMB—train-of-four count (TOF) = 0 and PTC = 1–5; medium NMB—PTC > 5 and TOF = 0–1; shallow NMB—TOF > 1; full recovery—train-of-four ratio TOFR > 90%. Simultaneously, the quality of operating conditions was assessed with a standardized rating scale (SRS) reaching from 1 (extremely poor conditions) to 5 (excellent conditions). Fifty patients could be included in the analysis. The abdominal wall length increased by 10–13 mm induced by the capnoperitoneum. SRS was higher during intense NMB (4.7 ± 0.5) vs. full recovery (4.5 ± 0.5) (mean ± SD; p = 0.025). Generally, an intense NMB did not increase abdominal wall length induced by capnoperitoneum. Additionally, its influence on the quality of surgical operating conditions seems to be of minor clinical relevance.