bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative systems pharmacology model predictions for efficacy of atezolizumab and nab-paclitaxel in triple-negative breast cancer
Authors: Wang Hanwen , Ma Huilin , Sové Richard J , Emens Leisha A , Popel Aleksander S
Published: February 2021

Background

Immune checkpoint blockade therapy has clearly shown clinical activity in patients with triple-negative breast cancer, but less than half of the patients benefit from the treatments. While a number of ongoing clinical trials are investigating different combinations of checkpoint inhibitors and chemotherapeutic agents, predictive biomarkers that identify patients most likely to benefit remains one of the major challenges. Here we present a modular quantitative systems pharmacology (QSP) platform for immuno-oncology that incorporates detailed mechanisms of immune–cancer cell interactions to make efficacy predictions and identify predictive biomarkers for treatments using atezolizumab and nab-paclitaxel.

Methods

A QSP model was developed based on published data of triple-negative breast cancer. With the model, we generated a virtual patient cohort to conduct in silico virtual clinical trials and make retrospective analyses of the pivotal IMpassion130 trial that led to the accelerated approval of atezolizumab and nab-paclitaxel for patients with programmed death-ligand 1 (PD-L1) positive triple-negative breast cancer. Available data from clinical trials were used for model calibration and validation.

Results

With the calibrated virtual patient cohort based on clinical data from the placebo comparator arm of the IMpassion130 trial, we made efficacy predictions and identified potential predictive biomarkers for the experimental arm of the trial using the proposed QSP model. The model predictions are consistent with clinically reported efficacy endpoints and correlated immune biomarkers. We further performed a series of virtual clinical trials to compare different doses and schedules of the two drugs for simulated therapeutic optimization.

Conclusions

This study provides a QSP platform, which can be used to generate virtual patient cohorts and conduct virtual clinical trials. Our findings demonstrate its potential for making efficacy predictions for immunotherapies and chemotherapies, identifying predictive biomarkers, and guiding future clinical trial designs.
Foraging modes and movements of Oncorhynchus mykiss as flow and invertebrate drift recede in a California stream
Authors: Rossi Gabriel J. , Power Mary E. , Pneh Shelley , Neuswanger Jason R. , Caldwell Timothy J.
Published: February 2021

Salmonids frequently adapt their feeding and movement strategies to cope with seasonally fluctuating stream environments. Oncorhynchus mykiss tend to drift-forage in higher velocity habitat than other salmonids, yet their presence in streams with seasonally low velocity and drift suggests behavioral flexibility. We combined 3D videogrammetry with measurements of invertebrate drift and stream hydraulics to investigate the drivers of O. mykiss foraging mode and movement during the seasonal recession in a California stream. From May to July (2016), foraging movement rate increased as prey concentration and velocity declined; however, movement decreased in August as pools became low and still. In May, 80% of O. mykiss were drift-foraging, while by July, over 70% used search or benthic-foraging modes. Velocity and riffle crest depth were significant predictors of foraging mode, while drift concentration was a poor univariate predictor. However, top-ranked additive models included both hydraulic variables and drift concentration. A drift-foraging bioenergetic model was a poor predictor of foraging mode. We suggest that infall and benthic prey, as well as risk aversion, may influence late-summer foraging decisions.
Investigation on Durability Behaviour and Optimization of Concrete with Triple‐Admixtures Subjected to Freeze‐Thaw Cycles in Salt Solution
Authors: Li Xuejiao , Wang Wensheng , Zhu Zhiqing , Zheng Kunkun
Published: February 2021

In the seasonal frozen area of northeast China, cement concrete is usually in a working environment of cold climate and chlorine erosion coupling effect. In general, with a reasonable addition of air entraining agent (AEA) and multimineral admixtures such as fly ash, blast furnace slag, and silica fume, the durability of cement concrete under the effects of freeze‐thaw and salt solution can be significantly improved in cold regions. However, due to several more compositions of cement concrete with multiple mineral admixtures, it would take excessive trial mixtures to select the desired mixture proportion based on the conventional method. This means a great deal of costs of raw materials and laboratory experimental time. In this paper, the experimental scheme of mixture proportion for air‐entrained concrete with multimineral admixtures was designed based on the orthogonal experiment design method. Based on the compressive strength, rapid chloride permeability, and weight loss and relative dynamic elastic modulus after salt freeze‐thaw cycles, the influence of different mineral admixtures and their dosages on the durability of concrete subjected to freeze‐thaw in salt solution was analyzed. After that, based on genetic algorithm, an optimization of mixture proportion was proposed, which only requires less trial mixes and accessible optimization process. The test results indicated the superiority of air‐entrained concrete with multimineral admixtures when serving in salt freeze‐thaw environment. Eventually, it was also verified that the optimized concrete in this paper could achieve pleasurable durability performances under salt freeze‐thaw cycles.
The Bohras as Neo-Fāṭimids: Documentary Remains of a Fāṭimid Past in Gujarat
Authors: Akkerman Olly
Published: February 2021

This article traces the remains of Fāṭimid chancery documents, and the writing practices that surround them, among the Bohras of Gujarat. As Shiʿi Ismaʿilis, the Bohras consider themselves heirs of the Fāṭimid Imāmate (909–1171). Whereas other Ismaʿili communities, such as the Nizārīs, claim their genealogical link to the Fāṭimids through the presence of a living Imam, the Bohras legitimize their “Neo-Fāṭimid” identity through a living Arabic Ismaʿili manuscript culture. While the philological link between the Bohras and the Fāṭimids has hitherto been acknowledged through the mobility and preservation of these manuscripts, their use of documents, however, and its potential Fāṭimid influences, has remained unexplored. Based on ethnographic observations and archival research among the ʿAlawi Bohras of Baroda, I suggest that practices from the Fāṭimid chancery continued in Yemen and Gujarat in the post-Fāṭimid world, and continue to survive today in the Bohra community’s documentary culture.
Improving High School Graduation Through School Climate
Authors: Buckman David G. , Hand Nathan W. J. , Johnson Arvin
Published: February 2021

The purpose of this study was to contribute to the body of literature regarding decisions school leaders make when developing strategic plans to improve student outcomes. This study investigated whether there is a significant relationship between school climate and graduation rates for public high schools in the state of Georgia when controlling for potential covariates. Using an ordinary least squares multiple regression procedure, this study found a positive school climate increased high school graduation rates ( b = .164, p ≤ .01).
Postural sway in young female artistic and acrobatic gymnasts according to training experience and anthropometric characteristics
Authors: Opala-Berdzik Agnieszka , Głowacka Magdalena , Juras Grzegorz
Published: February 2021

Background

Gymnastics training enhances the development of postural control in children and adolescents. In competitive gymnastics, the training regimen is specific to the given gymnastic discipline and is usually followed from the early years of practicing. This study aimed to determine whether postural steadiness differed between young gymnasts practicing two distinct disciplines, and whether it was related to the duration of their training experience, age, and their anthropometric characteristics.

Methods

Thirty 10–13-year-old females ̶ ten artistic gymnasts, ten acrobatic gymnasts (training as “tops”), and ten non-athletes ̶ were examined during 60-s quiet standing trials on a force platform with the eyes open and closed. Their postural sway was represented by directional components of centre of foot pressure mean velocity. Mann-Whitney U, Wilcoxon and Spearman’s ρ tests were used for analyses.

Results

Anterior-posterior and medial-lateral centre of foot pressure mean velocities were not different between the artistic and acrobatic gymnasts (p > 0.05). In the artistic gymnasts, the duration of training experience, age, body height, body mass, and maturity offset were negatively correlated with the anterior-posterior centre of foot pressure mean velocity under eyes-open conditions. The acrobatic gymnasts’ body mass and BMI percentiles were negatively correlated with their anterior-posterior and medial-lateral centre of foot pressure mean velocities under both visual conditions (rranged from − 0.64 to − 0.93;p < 0.05). The non-athletes’ centre of foot pressure mean velocities were non-significantly correlated with their age and anthropometric measures under both visual conditions (p > 0.05).

Conclusions

The artistic gymnasts’ longer training experience, greater age, body height, body mass, and biological maturity were associated with better anterior-posterior postural steadiness when vision was available; the acrobatic gymnasts’ greater body mass and BMI percentiles were associated with better overall postural steadiness regardless of visual conditions. Relationships were observed between postural steadiness and discipline-specific training experience and anthropometric characteristics; however, causes and effects were not proven.
Local low-rank approach to nonlinear matrix completion
Authors: Sasaki Ryohei , Konishi Katsumi , Takahashi Tomohiro , Furukawa Toshihiro
Published: February 2021

This paper deals with a problem of matrix completion in which each column vector of the matrix belongs to a low-dimensional differentiable manifold (LDDM), with the target matrix being high or full rank. To solve this problem, algorithms based on polynomial mapping and matrix-rank minimization (MRM) have been proposed; such methods assume that each column vector of the target matrix is generated as a vector in a low-dimensional linear subspace (LDLS) and mapped to a pth order polynomial and that the rank of a matrix whose column vectors are dth monomial features of target column vectors is deficient. However, a large number of columns and observed values are needed to strictly solve the MRM problem using this method when p is large; therefore, this paper proposes a new method for obtaining the solution by minimizing the rank of the submatrix without transforming the target matrix, so as to obtain high estimation accuracy even when the number of columns is small. This method is based on the assumption that an LDDM can be approximated locally as an LDLS to achieve high completion accuracy without transforming the target matrix. Numerical examples show that the proposed method has a higher accuracy than other low-rank approaches.
Publisher Correction to: The gender gap and healthcare: associations between gender roles and factors affecting healthcare access in Central Malawi, June–August 2017
Authors: Azad Amee D. , Charles Anthony G. , Ding Qian , Trickey Amber W. , Wren Sherry M.
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Meteorological Drought in Northwestern Escarpment of Ethiopian Rift Valley: detection seasonal and spatial trends
Authors: Nasir Jemal , Assefa Engdawork , Zeleke Tesfaye , Gidey Eskinder
Published: February 2021

Background

The Northwestern Escarpment of the Ethiopian Rift Valley has been frequently affected by droughts for decades. The area is among the most drought-prone and chronically food-insecure parts of the country. The study areas that include the Raya Valley livelihood Zone (RVLZ), Alagie-Offla livelihood Zone (ALOFLZ), and Tsirare Catchment Livelihood Zones (TCLZ) are amongst the most vulnerable and badly affected livelihood zones in the Northwestern Escarpment of the Ethiopian Rift Valley. Hence, this study aimed to monitor the meteorological drought conditions of the three LZs from 1983 to 2016 using the Standardized Precipitation Evapotranspiration Index (SPEI) at three months’ time scale. Both monthly Climate Hazards Group InfraRed Precipitations with Station data (CHIRPS) and Enhancing National Climate Service (ENACTS) temperature data (1983–2016) at moderate spatial resolution (i.e. 4 km-by-4 km) were obtained from the National Meteorological Agency of Ethiopia.

Results

This study uncovers seasonally recurring droughts that vary in severity, frequencies, and durations within and between the livelihood zones. The results indicated that severe drought occurred in all livelihoods zone of the study area from years 1983 to 1991, while ALOFLZ and TCLZ have recorded relatively higher drought severity. From 1989 to 2016, the severity and frequency of droughts were increased during the Belg (small rain) season but decreased in Kiremt (summer). In most of the study years, there have been Belg or Kiremt or both drought seasons in the study areas. The severity and frequencies of Kiremt drought in this study were higher from 1983 to 1991, better 1993–1998, and mildly to moderate drought from 2000 to 2016. As the frequencies and persistence of mild drought have increased, the intensity and precipitation amount are too small to cultivate crops and forage growth. This problem needs special considerations on the current moisture harvesting system and afforestation practices to reduce natural and human-induced drought impacts.

Conclusions

Studying drought with long recorded meteorological data from a large number and uniformly distributed meteorological grids in small scale livelihood zones had great implications to identify the real trends of spatiotemporal meteorological drought. This enabled the researchers to investigate the real drought frequencies, severity, and durations in small scale areas. The study will support to improve the existing drought monitoring system and to build resilience to drought at the household level. The finding also will have a significant contribution to early warning systems, particularly at district levels. Ended, it needs to consider solutions for short and long drought impacts. The agricultural sector should consider the long-cycle crop growth patterns to reduce crop failures and forage problems.
Global burden of active smoking among people living with HIV on antiretroviral therapy: a systematic review and meta-analysis
Authors: Ale Boni Maxime , Amahowe Franck , Nganda Motto Malea , Danwang Célestin , Wakaba Nelly Njeri , Almuwallad Ateeq , Ale Franck Biaou Guy , Sanoussi Alamou , Abdullahi Suleiman Hudu , Bigna Jean Joel
Published: February 2021

Background

Although the high burden of both active smoking and human immunodeficiency virus (HIV) is clearly known, the relationship between them is still not well characterized. Therefore, we estimated the global prevalence of active smoking in people living with HIV (PLHIV) on antiretroviral therapy (ART) and investigated the association between exposure to active smoking and risk for suboptimal adherence to ART.

Main text: We searched PubMed, Embase, and Web of Science to identify articles published until September 19, 2019. Eligible studies reported the prevalence of active smoking in PLHIV on ART or investigated the association between active smoking and ART adherence; or enough data to compute these estimates. We used a random-effects model to pool data and quantified heterogeneity (I2). The global prevalence of active smoking was 36.1% (95% CI: 33.7–37.2; 329 prevalence data; 462 104 participants) with substantial heterogeneity. The prevalence increased with level of country income; from 10.1% (95% CI: 6.8–14.1) in low-income to 45.2% (95% CI: 42.7–47.7) in high-income countries; P < 0.0001. With regards to the Joint United Nations Programme on HIV/AIDS (UNAIDS) regions, the prevalence was higher in West and Central Europe and North America 45.4% (42.7–48.1) and lowest in the two UNAIDS regions of sub-Saharan Africa: Eastern and Southern Africa 10.7% (95% CI: 7.8–14.0) and West and Central Africa 4.4% (2.9–6.3); P < 0.0001. Globally, we estimated that there were 4 110 669 PLHIV on ART who were active smokers, among which the highest number was from Eastern and Southern Africa (35.9%) followed by Asia and the Pacific (25.9%). Active smoking was significantly associated with suboptimal ART adherence: pooled odds ratio 1.57 (95% CI: 1.37–1.80; I2 = 56.8%; 19 studies; 48 450 participants); even after considering adjusted estimates: 1.67 (95% CI: 1.39–2.01; I2 = 53.0%; 14 studies).

Conclusions

This study suggests a high prevalence of active smoking in PLHIV on ART and an association between active smoking and ART suboptimal adherence. As such, healthcare providers and policy makers should focus on adopting and implementing tobacco harm reduction strategies in HIV care, especially in sub-Saharan Africa known as epicenter of HIV pandemic with highest number of active tobacco smoking among PLHIV on ART.
Wireless logging of extracellular neuronal activity in the telencephalon of free-swimming salmonids
Authors: Takahashi Susumu , Hombe Takumi , Takahashi Riku , Ide Kaoru , Okamoto Shinichiro , Yoda Ken , Kitagawa Takashi , Makiguchi Yuya
Published: February 2021

Background

Salmonids return to the river where they were born in a phenomenon known as mother-river migration. The underpinning of migration has been extensively examined, particularly regarding the behavioral correlations of external environmental cues such as the scent of the mother-river and geomagnetic compass. However, neuronal underpinning remains elusive, as there have been no biologging techniques suited to monitor neuronal activity in the brain of large free-swimming fish. In this study, we developed a wireless biologging system to record extracellular neuronal activity in the brains of free-swimming salmonids.

Results

Using this system, we recorded multiple neuronal activities from the telencephalon of trout swimming in a rectangular water tank. As proof of principle, we examined the activity statistics for extracellular spike waveforms and timing. We found cells firing maximally in response to a specific head direction, similar to the head direction cells found in the rodent brain. The results of our study suggest that the recorded signals originate from neurons.

Conclusions

We anticipate that our biologging system will facilitate a more detailed investigation into the neural underpinning of fish movement using internally generated information, including responses to external cues.
Three-dimensional vascular microenvironment landscape in human glioblastoma
Authors: Cribaro George P. , Saavedra-López Elena , Romarate Leire , Mitxitorena Izaskun , Díaz Laura R. , Casanova Paola V. , Roig-Martínez Meritxell , Gallego José M. , Perez-Vallés Ana , Barcia Carlos
Published: February 2021

The cellular complexity of glioblastoma microenvironments is still poorly understood. In-depth, cell-resolution tissue analyses of human material are rare but highly necessary to understand the biology of this deadly tumor. Here we present a unique 3D visualization revealing the cellular composition of human GBM in detail and considering its critical association with the neo-vascular niche. Our images show a complex vascular map of human 3D biopsies with increased vascular heterogeneity and altered spatial relationship with astrocytes or glioma-cell counterparts. High-resolution analysis of the structural layers of the blood brain barrier showed a multilayered fenestration of endothelium and basement membrane. Careful examination of T cell position and migration relative to vascular walls revealed increased infiltration corresponding with tumor proliferation. In addition, the analysis of the myeloid landscape not only showed a volumetric increase in glioma-associated microglia and macrophages relative to GBM proliferation but also revealed distinct phenotypes in tumor nest and stroma. Images and data sets are available on demand as a resource for public access.
Unclassified hepatocellular adenoma with beta-catenin mutation: a case report
Authors: Muranushi Ryo , Araki Kenichiro , Harimoto Norifumi , Yokobori Takehiko , Hoshino Kouki , Hagiwara Kei , Ishii Norihiro , Tsukagoshi Mariko , Igarashi Takamichi , Watanabe Akira , Kubo Norio , Aishima Shinichi , Shirabe Ken
Published: February 2021

Background

Hepatocellular adenoma (HCA) subtypes are considered as risk factors for malignant transformation; thus, an accurate diagnosis is important. We report a case of resected HCA previously diagnosed as unclassified HCA using immunohistochemistry, subsequently discovered to harbor a mutation in exon 3 of the beta (β)-catenin gene using deoxyribonucleic acid (DNA) sequencing.

Case presentation

The patient was a 26-year-old woman who was referred to our hospital because of a 150-mm tumor in the right lobe of the liver. Considering the possibility of malignancy, we performed right lobe hepatectomy. Based on the histopathological and immunohistochemical findings, the tumor was diagnosed as an unclassified HCA. Next, we performed sequencing of DNA isolated from the tumor and identified a mutation in exon 3 of β-catenin, suggesting that the tumor contained an activating mutation of the β-catenin gene.

Conclusion

β-Catenin mutations in HCA cannot be detected by immunohistochemistry alone, and molecular analysis is required to accurately diagnose and evaluate its prognosis.
TELETRABAJO Y AMPLIFICACIÓN DE LA DESIGUALDAD EN LA SOCIEDAD POST-PANDEMIA ESPAÑOLA.
Authors: Valenzuela-Garcia Hugo
Published: February 2021

Although teleworking existed before the pandemic, its emergence and large-scale implementation suggest a paradigm shift in the world of work. While the reception of teleworking has been optimistic in general, its sudden introduction reveals a series of underlying structural inequalities, between manual workers and cognitive workers, between European Union member countries, geographic territories, business sectors, job qualification, age, ethnicity, and class. Such structural inequality, amplified by teleworking, presents significant challenges for work and society in the future of postCovid society. The text draws on data extracted from a survey administered to 66 teleworkers during lockdown; on comparative data collected from official reports, and the theoretical literature on the evolution of cognitive capitalism and the emergence of remote work.
La calidad alimentaria en una economía cognitiva: el caso de la denominación de origen vitivinícola “León”
Authors: Macías Vázquez Alfredo
Published: February 2021

El modelo español de certificaciones geográficas de calidad alimentaria muestra signos de agotamiento. Los cambios recientes cuestionan su función como mecanismo para proteger las rentas territoriales, obligando a analizar las prácticas de los actores en la cadena de valor con nuevos enfoques. Centrados en el análisis de la Denominación de Origen Protegida “León”, el objetivo de este trabajo es interrogar los determinantes de la generación de valor en una economía posindustrial. Se constató la importancia central de ciertas mediaciones entre la producción y el consumo que sistematizan, conectan, interpretan y validan los conocimientos locales, las cuales presentan un comportamiento deficiente que incide de manera negativa en la mejora de la calidad y en la valorización de los vinos.
Continuous and interval aerobic sessions: effects on triglyceride concentrations
Authors: Santiago Eder , Costa Rochelle Rocha , Delevatti Rodrigo Sudatti , Bracht Cláudia Gomes , Preissler Artur Avelino Birk , Silveira Gustavo , Fracalossi Danielle Girolometto , Silveira Júnior Eli , Rocha Vitória de Mello Bones da , Barroso Bruna Machado , Reichert Thaís , Kruel Luiz Fernando Martins
Published: February 2021

The regular practice of physical exercise, primarily aerobic, has been recommended as a component of the non-pharmacological treatment for dyslipidemias. However, there is a lack of studies in the literature comparing the acute effects of different aerobic exercise models (continuous and interval) on triglycerides concentrations. The purpose of the present study was to analyze the magnitude of change on triglycerides concentrations after a single session of interval and continuous exercise in persons with dyslipidemia. This study was a randomized crossover clinical trial. Fifteen volunteers performed two different aerobic sessions, a continuous and an interval session. The intensity of the continuous session was maintained between 85-90% of the heart rate at anaerobic threshold (HRAT). The interval session consisted of 9 sets of 4 minutes at 85-90%HRAT followed by one minute below 85%HRAT. Triglycerides concentrations were assessed before, immediately after and at the end of 30 minutes after all sessions. Both sessions models resulted in alterations in triglycerides concentrations immediately after exercise (p = 0.005), without difference between them (p = 0.446). Continuous session increased triglycerides concentrations by 34.9% from pre-exercise to immediately post-exercise and the interval session, by 7.9%. Thirty minutes after exercise, triglyceride concentrations showed no significant difference in relation to the pre-exercise and immediately after exercise moments in both session models. Therefore, it is concluded that aerobic exercise promotes responses in triglycerides concentrations of dyslipidemic patients, independently of the exercise method, either continuous or interval.
Bouncing back
Authors: Marsh Sian
Published: February 2021

Sian Marsh outlines why it is more important than ever for trainees on the Early Years Initial Teacher Training (EYITT) programme to critically reflect on approaches to supporting children's social and emotional development – and particularly look at ways to build their resilience.
Optically addressed spatial light modulator based on nonlinear metasurface
Authors: Gong Shengchao , Ren Mengxin , Wu Wei , Cai Wei , Xu Jingjun
Published: February 2021

Spatial light modulators (SLMs) are devices for modulating amplitude, phase, or polarization of light beams on demand. Such devices are regarded as the backbone for optical information parallel processing and future optical computers. Currently, SLMs are mainly operated in an electrical addressing manner, wherein the optical beams are modulated by electrical signals. However, future all-optical information processing systems prefer to control light directly by light (i.e., optically addressed, OA) without electro-optical conversion. Here, we present an OASLM based on a metasurface (MS-OASLM), whose operation principle relies on nonlinear polarization control of read light by another write light at the nanoscale. Its resolution is more than 10 times higher than a typical commercial SLM and achieves 500 line pairs per millimeter (corresponding to a pixel size of only 1 μm). The MS-OASLM shows unprecedented compactness and is only 400 nm in thickness. Such MS-OASLMs could provide opportunities to develop next generation all-optical information processing and high resolution display technologies.
FastTrack: An open-source software for tracking varying numbers of deformable objects
Authors: Gallois Benjamin , Candelier Raphaël
Published: February 2021

Analyzing the dynamical properties of mobile objects requires to extract trajectories from recordings, which is often done by tracking movies. We compiled a database of two-dimensional movies for very different biological and physical systems spanning a wide range of length scales and developed a general-purpose, optimized, open-source, cross-platform, easy to install and use, self-updating software called FastTrack. It can handle a changing number of deformable objects in a region of interest, and is particularly suitable for animal and cell tracking in two-dimensions. Furthermore, we introduce the probability of incursions as a new measure of a movie’s trackability that doesn’t require the knowledge of ground truth trajectories, since it is resilient to small amounts of errors and can be computed on the basis of an ad hoc tracking. We also leveraged the versatility and speed of FastTrack to implement an iterative algorithm determining a set of nearly-optimized tracking parameters—yet further reducing the amount of human intervention—and demonstrate that FastTrack can be used to explore the space of tracking parameters to optimize the number of swaps for a batch of similar movies. A benchmark shows that FastTrack is orders of magnitude faster than state-of-the-art tracking algorithms, with a comparable tracking accuracy. The source code is available under the GNU GPLv3 at https://github.com/FastTrackOrg/FastTrack and pre-compiled binaries for Windows, Mac and Linux are available at http://www.fasttrack.sh.
DEXOM: Diversity-based enumeration of optimal context-specific metabolic networks
Authors: Rodríguez-Mier Pablo , Poupin Nathalie , de Blasio Carlo , Le Cam Laurent , Jourdan Fabien
Published: February 2021

The correct identification of metabolic activity in tissues or cells under different conditions can be extremely elusive due to mechanisms such as post-transcriptional modification of enzymes or different rates in protein degradation, making difficult to perform predictions on the basis of gene expression alone. Context-specific metabolic network reconstruction can overcome some of these limitations by leveraging the integration of multi-omics data into genome-scale metabolic networks (GSMN). Using the experimental information, context-specific models are reconstructed by extracting from the generic GSMN the sub-network most consistent with the data, subject to biochemical constraints. One advantage is that these context-specific models have more predictive power since they are tailored to the specific tissue, cell or condition, containing only the reactions predicted to be active in such context. However, an important limitation is that there are usually many different sub-networks that optimally fit the experimental data. This set of optimal networks represent alternative explanations of the possible metabolic state. Ignoring the set of possible solutions reduces the ability to obtain relevant information about the metabolism and may bias the interpretation of the true metabolic states. In this work we formalize the problem of enumerating optimal metabolic networks and we introduceDEXOM, an unified approach for diversity-based enumeration of context-specific metabolic networks. We developed different strategies for this purpose and we performed an exhaustive analysis using simulated and real data. In order to analyze the extent to which these results are biologically meaningful, we used the alternative solutions obtained with the different methods to measure: 1) the improvement of in silico predictions of essential genes inSaccharomyces cerevisiaeusing ensembles of metabolic network; and 2) the detection of alternative enriched pathways in different human cancer cell lines. We also provideDEXOMas an open-source library compatible with COBRA Toolbox 3.0, available athttps://github.com/MetExplore/dexom.
Intermedilysin cytolytic activity depends on heparan sulfates and membrane composition
Authors: Drabavicius Gediminas , Daelemans Dirk
Published: February 2021

Cholesterol-dependent cytolysins (CDCs), of which intermedilysin (ILY) is an archetypal member, are a group of pore-forming toxins secreted by a large variety of pathogenic bacteria. These toxins, secreted as soluble monomers, oligomerize upon interaction with cholesterol in the target membrane and transect it as pores of diameters of up to 100 to 300 Å. These pores disrupt cell membranes and result in cell lysis. The immune receptor CD59 is a well-established cellular factor required for intermedilysin pore formation. In this study, we applied genome-wide CRISPR-Cas9 knock-out screening to reveal additional cellular co-factors essential for ILY-mediated cell lysis. We discovered a plethora of genes previously not associated with ILY, many of which are important for membrane constitution. We show that heparan sulfates facilitate ILY activity, which can be inhibited by heparin. Furthermore, we identified hits in both protein and lipid glycosylation pathways and show a role for glucosylceramide, demonstrating that membrane organization is important for ILY activity. We also cross-validated identified genes with vaginolysin and pneumolysin and found that pneumolysin’s cytolytic activity strongly depends on the asymmetric distribution of membrane phospholipids. This study shows that membrane-targeting toxins combined with genetic screening can identify genes involved in biological membrane composition and metabolism.
Effects of glyphosate residues and different concentrate feed proportions in dairy cow rations on hepatic gene expression, liver histology and biochemical blood parameters
Authors: Heymann Ann-Katrin , Schnabel Karina , Billenkamp Fabian , Bühler Susanne , Frahm Jana , Kersten Susanne , Hüther Liane , Meyer Ulrich , von Soosten Dirk , Trakooljul Nares , Teifke Jens Peter , Dänicke Sven
Published: February 2021

Glyphosate (GLY) is worldwide one of the most used active substances in non-selective herbicides. Although livestock might be orally exposed via GLY-contaminated feedstuffs, not much is known about possible hepatotoxic effects of GLY. As hepatic xenobiotic and nutrient metabolism are interlinked, toxic effects of GLY residues might be influenced by hepatic nutrient supply. Therefore, a feeding trial with lactating dairy cows was conducted to investigate effects of GLY-contaminated feedstuffs and different concentrate feed proportions (CFP) in the diets as tool for varying nutrient supply to the liver. For this, 61 German Holstein cows (207 ± 49 days in milk; mean ± standard deviation) were either fed a GLY-contaminated total mixed ration (TMR, GLY groups, mean GLY intake 122.7 μg/kg body weight/day) or control TMR (CON groups, mean GLY intake 1.2 μg/kg body weight/day) for 16 weeks. Additionally, both groups were further split into subgroups fed a lower (LC, 30% on dry matter basis) or higher (HC, 60% on dry matter basis) CFP resulting in groups CONHC (n = 16), CONLC (n = 16), GLYHC (n = 15), GLYLC (n = 14). Blood parameters aspartate aminotransferase, γ-glutamyltransferase, glutamate dehydrogenase, cholesterol, triglyceride, total protein, calcium, phosphorus, acetic acid and urea and histopathological evaluation were not influenced by GLY, whereas all mentioned parameters were at least affected by time, CFP or an interactive manner between time and CFP. Total bilirubin blood concentration was significantly influenced by an interaction between GLY and CFP with temporarily elevated concentrations in GLYHC, whereas the biological relevance remained unclear. Gene expression analysis indicated 167 CFP-responsive genes, while seven genes showed altered expression in GLY groups compared to CON groups. Since expression changes of GLY-responsive genes were low and liver-related blood parameters changed either not at all or only slightly, the tested GLY formulation was considered to have no toxic effects on the liver of dairy cows.
Bizonytalanság, stratégia és teljesítmény – Kvalitatív kutatás innovatív kis- és középvállalatok vezetői körében (Uncertainty, strategy and performance – Qualitative research in innovative SMEs)
Authors: Szabó Zsolt Roland
Published: February 2021

A szerző kvalitatív kutatási módszerekkel vizsgálja a kis- és középvállalatok (kkv-k) innovatív tevékenységeinek korlátait és lehetőségeit. A vizsgálat tárgyai (legalább) Magyarország szintjén új terméket vagy szolgáltatást nyújtó kkv-k, melyek határozott növekedési szándékkal rendelkeznek. Az eredmények egységes vizsgálati keretben, 41 vezető véleménye alapján születtek meg, három területre fókuszálva: (1) a környezeti bizonytalanság megítélése, (2) a szervezet követett stratégiája, kettős képessége, kiaknázó és felderítő tevékenysége, és (3) a versenyképes teljesítménycélok, konfigurációk. A cikk a kutatás lépéseit részletesen bemutatja, fontos eredményének tekinthető, hogy rámutat arra, hogy a kutatási és fejlesztési, valamint az innovatív tevékenységek legfontosabb gátja leginkább a vezetési és szervezési képességek és a stratégiai gondolkodás hiányára vezethető vissza a kis- és középvállalkozásokban. ______ The author conducted a qualitative research on the innovation potential of small and medium size enterprises (SMEs). SMEs with new products and services and with growth orientation are in the focus of the research. The standardized research design is based on 41 owner managers’ responses. It is focusing on 3 main areas: (1) environmental uncertainty, (2) the strategy followed by the organization, its ambidextrous capability, exploitative and explorative behavior, and (3) competitive performance and configurations. The paper describes a qualitative research design in detail. The main finding of the research is that the lack of managerial skills and strategic thinking inhibit SMEs to conduct innovation as well as to engage in research and development activities.
MAKROEKONOMİK DEĞİŞKENLERİN DÖVİZ KURU DEĞİŞMELERİNE ETKİSİ: BİR PANEL VERİ ANALİZİ
Authors: KUBAR Yeşim , ÇOBAN Hatem
Published: February 2021

Türkiye’de döviz kurları 2002-2013 yılları arasında yavaş artış gösterirken, 2014-2016 yılları arasında daha hızlı artış göstermiştir. Döviz kurlarındaki söz konusu bu durum bir taraftan belirsizliğe neden olurken diğer taraftan dövizle iş yapan kesimleri olumsuz etkilemektedir. Bu nedenle döviz kurlarının etkin bir şekilde yönlendirilebilmesi için döviz kurlarını etkileyen faktörler belirlenmelidir.

Bu çalışmada son zamanların en çok konuşulan ekonomik konularından, döviz kuru olgusu ele alınmakta, 1995-2016 dönemini kapsayan yıllık verilerle reel döviz kuru, dış ticaret haddi, faiz oranı, ödemeler dengesi, ticaret hacmi (GSYH %), büyüme oranı, GSYH deflatörü, yatırım harcamaları değişkenlerinin, döviz kuru ilişkisini tespit etmek, Dünya ekonomileri için önemli ticaret ortakları, üretim merkezleri ve ileri teknoloji ihracatçısı olan Brezilya, Avro Bölgesi, İsrail, Japonya, İngiltere Çin, Rusya, İran, Singapur ülkeleri ile Türkiye’nin etkilenme boyutu ile etkileyen değişkenleri ortaya koymak amaçlanmaktadır.
Effect of laser inclination angle on mechanical properties of Hastelloy X processed by selective laser melting
Authors: Xuewen Zong , Jian Zhang , Hanguang Fu
Published: February 2021

Selective laser melting at various laser inclination angles was used to prepare Hastelloy X alloy specimens. The morphology, fracture, tensile strength, stress, and strain of Hastelloy X alloy specimens were studied using optical microscopy, scanning electron microscopy, and a tensile tester. The temperature field of the manufacturing process was analyzed based on finite element analysis, and the internal relationship between the temperature field and the process was constructed in terms of cooling speed. The results show that the temperature field is a dynamic process with a high cooling rate; the average cooling rate reaches 3.23 × 106 °C × s−1. The greater the inclination angle, the greater the thermal gradient, resulting in higher cooling rates. Due to the cross-influence of grain refinement at high cooling rates and residual stress, the tensile strength and yield strength of Hastelloy X alloy showed first increasing and then decreasing trends with respect to inclination angle. However, at an inclination angle of 30°, the voids and crack defects of Hastelloy X alloy fractures were reduced, and the tensile strength and yield strength reached 881.38 and 701.60 MPa, respectively. At this angle, the mechanical properties were excellent and met the requirements of the aviation industry.
Effect of Lanthanum on mechanical and wear properties of high-pressure die-cast Mg-3Al-3Sn-3Sb alloy
Authors: Yarkadaş Güven , Kumruoğlu Levent Cenk , Özarslan Selma , Şevik Hüseyin
Published: February 2021

In the present study, the effect of an La alloying element with different quantities (1, 3 and 5 wt.-%) on the microstructure, mechanical and dry sliding wear properties of Mg- 3Al-3Sn-3Sb alloy was investigated. The wear tests were done on the alloys using pin on-disk equipment against a 4140 steel disc as counterpart under three different sliding velocities of 0.3, 0.6 and 1.2 ms-1 and four different loads of 5, 10, 20 and 40 N. The microstructural results showed that the new intermetallic phases (La5Sn3 and LaSnSb2) were formed with addition of La to the main alloy. Also, it was observed that the hardness of the Mg-3Al-3Sn-3Sb alloy was raised with increasing La addition. Furthermore, the tensile properties of the Mg-3Al-3Sn-3Sb alloy improved with rising La content at room and elevated temperature. The wear rates of the alloys increase with increasing of the sliding speed and load. In addition to this, the wear rate of the Mg-3Al-3Sn-3Sb alloy was found to be higher than that of the La content alloys for all test conditions.
The crystal structure of benzeneseleninic acid anhydride, C12H10O3Se2
Authors: Hosten Eric C. , Betz Richard
Published: February 2021

C12H10O3Se2, triclinic, P

1
‾

$‾{1}$

(no. 2), a = 9.1794(3) Å, b = 11.5706(5) Å, c = 12.3976(5) Å, α = 85.291(2)°, β = 72.198(2)°, γ = 74.084(2)°, V = 1205.65(8) Å3, Z = 4, R

gt
(F) = 0.0275, wR

ref
(F
2) = 0.0698, T = 200 K.
The first casting mould for a ‘Syrian Bottle’ from Lipnik, Bulgaria
Authors: Leschtakov Lyuben , Zimmermann Thomas
Published: February 2021

The following article presents the first mould ever discovered for casting a so-called “Syrian Bottle”, a distinctive vessel type that originated in Mesopotamia around the mid 3rd millennium BC and soon after spread to Anatolia, the Aegean and Southeast Europe, as imports and local derivatives. A few examples were made from precious metals and lead, the most notable one being a golden globular bottle, part of “Priam’s” Treasure A” from Early Bronze Age Troy. The mould from Lipnik seems to have been intended for the production of small metal bottles of ‘Syrian’ shape, and supportive agents like a green sand core applied for the production of such a complex item. The mould, however, was obviously never used. A review of associated manufacturing details like pegholes, riser and vent show that although these features were particularly prominent in the 2nd millennium BC, moulds from earlier (Anatolian) contexts do possess such characteristics as well. This currently unique, locally produced example is therefore dated to the latest 3rd or earliest second millennium BC, coinciding with ever-growing interaction between distant cultural entities stretching from Mesopotamia to Southeast Europe and beyond, and allowing for the exchange of ideas, fashions and technologies.
Appropriate abdominal imaging for the emergency department patient
Authors: Knott Danielle R.
Published: February 2021

Abdominal x-ray series (AXR) and abdominal CT scans (ACT) are commonly performed to aid in the diagnosis for patients who present to the emergency room with abdominal pain. Patients commonly receive both an AXR and ACT, due to a lack of knowledge regarding imaging appropriateness among healthcare professionals who order these exams. A primary simple retrospective data-analysis was performed to understand the prevalence of how often both exams were ordered in three Nova Scotia emergency departments. A literature review was also conducted to compare the diagnostic accuracy of each diagnostic imaging modality. Several articles showed that patients who have an AXR also have an ACT that demonstrates an abnormal finding. Emergency department physicians are not reassured when abdominal x-rays are negative and do not show abnormal findings, and as a result, a CT scan is also performed. Radiation dose must be considered when ordering multiple diagnostic imaging exams. A low-dose CT (LDCT) can be used to reduce the radiation exposure to the patient, while maintaining high diagnostic quality images. Image quality can be enhanced at a reduced radiation dose by using an image reconstruction technique such as adaptive statistical iterative reconstruction (ASIR). Understanding the most appropriate abdominal imaging modality for emergency department patients allows for fewer examinations being ordered and a reduction of radiation dose to the patient. When the most appropriate imaging is performed, a definitive diagnosis can be made and the best treatment can be provided to patients. This information can help to create an imaging appropriateness protocol for emergency departments.Additional research can help determine the cost differences between the two exams and the influence a protocol change could have on the emergency and diagnostic imaging departments.Keywords: AXR – Abdominal x-ray series, ACT – Abdominal computed tomography scan, CT – Computed tomography, SDCT – Standard-dose CT, LDCT – Low-dose CT, ASIR – Adaptative statistical iterative reconstruction FBP – Filtered back projection, CTDIvol – Volume computed tomography dose index
Science communication: understanding its challenges and opportunities – review of three books
Authors: MacDonald Bertrum H.
Published: February 2021

N/A
Education in Doctoral School and Fees
Authors: Brzuszczak Przemysław
Published: February 2021

This article discusses the issue of fees that may be charged to doctoral students at doctoral schools. In compliance with Article 198 par. 8 of the Act – the Law on Higher Education and Science: “Doctoral education shall not be subject to fees.” This regulation may be prima facie interpreted as excluding the possibility of charging any fees to doctoral students at doctoral schools. However, this is an oversimplification. Whereas, indeed, any activities directly related to the education of doctoral students should be free of charge, doubts arise with regard to other types of fees enumerated in Article 79 of the referred Act. And so, in literature there is a consensus that three admissible types of fees potentially paid by doctoral students are those referred to in Article 79 par. 2 points 1–2 and 6 that is those charged for conducting the recruitment process (point 1), carrying out the verification of learning outcomes (point 2), using student dormitories and canteens (point 6). The interpretation of the regulations concerning fees in the entities running doctoral schools should not have an extensive or implicit character. Thus, in this context the objective scope of these regulations seems to be relatively narrow. In the practice of doctoral schools’ functioning, a certain problem, although potentially probably small, may prove to be the legislator’s waiver as of 1 October 2019 (as opposed to the fees charged at the hitherto doctoral studies) of fees due to repeating by a doctoral student of classes due to unsatisfactory academic performance and while issuing copies of certain documents. A lack of relevant provisions at a statutory level excludes charging fees in a situation when a doctoral student achieves unsatisfactory grades from taken classes or repeatedly loses such documents as, for instance, a doctoral student’s ID card, a student book, diplomas and copies thereof, supplements to diplomas. Therefore, the author postulates de lege ferenda relevant legislative amendments.