bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and pharmacokinetics of bimagrumab in healthy older and obese adults with body composition changes in the older cohort
Authors: Rooks Daniel , Petricoul Olivier , Praestgaard Jens , Bartlett Michael , Laurent Didier , Roubenoff Ronenn
Published: December 2020

Background

Bimagrumab prevents activity of myostatin and other negative regulators of skeletal muscle mass. This randomized double‐blind, placebo‐controlled study investigated safety, pharmacokinetics (PK), and pharmacodynamics of bimagrumab in healthy older and obese adults.

Methods

A cohort of older adults (aged 70–85 years) received single intravenous infusions of bimagrumab 30 mg/kg (n = 6) or 3 mg/kg (n = 6) or placebo (n = 4) and was followed for 20 weeks. A second cohort of obese participants [body mass index (BMI) 30–45 kg/m2, aged 18–65 years] received a single intravenous infusion of bimagrumab 30 mg/kg (n = 6) or placebo (n = 2) and was followed for 12 weeks. Outcomes included the safety, tolerability, and PK of bimagrumab, in both cohorts. Measures of pharmacodynamics were performed in the older adult cohort to evaluate the effects of bimagrumab on thigh muscle volume (TMV), total lean body mass (LBM), total fat body mass, and muscle strength.

Results

All 24 randomized participants completed the study. The older adults had a mean (±SD) age of 74.5 ± 3.4 years and BMI of 26.5 ± 3.5 kg/m2. The obese participants had a mean (±SD) age of 40.4 ± 11.8 years, weight of 98.0 ± 11.3 kg, and BMI of 34.3 ± 3.9 kg/m2. Adverse events in both cohorts were mostly mild. In older adults, most commonly reported adverse events were upper respiratory tract infection, rash, and diarrhoea (each 3/16, 19%). Obese participants reported muscle spasms and rash (both 5/8, 63%) most often. Non‐linearity was observed in the PK concentration profiles of both cohorts due to target‐mediated drug disposition. Bimagrumab 3 and 30 mg/kg increased mean (±SD) TMV (Week 4: 5.3 ± 1.8% and 6.1 ± 2.2%, vs. placebo: 0.5 ± 2.1%, both P ≤ 0.02) and LBM (Week 4: 6.0 ± 3.2%, P = 0.03 and 2.4 ± 2.2%, vs. placebo: 0.1 ± 2.4%), which were maintained longer with higher dose level, while total fat body mass (Week 4: −2.7 ± 2.9% and −1.6 ± 3.0%, vs. placebo: −2.3 ± 3.2%) decreased from baseline in older adults, with no change in muscle strength.

Conclusions

Bimagrumab was safe and well tolerated and demonstrated similar PK in older and obese adults. A single dose of bimagrumab rapidly increased TMV and LBM and decreased body adiposity in older adults. Muscle hypertrophy and fat loss were sustained with extended drug exposure.
Influence of particulate alkaline biomaterial remnants in dentin on the adhesion of two resin‐based bonding systems
Authors: Ballal Nidambur Vasudev , Gandhi Poornika , Kashyap Namita N.
Published: December 2020

To study aimed to evaluate the influence of infiltrated alkaline biomaterials on the bond strength of composite obtained with etch and rinse and universal adhesive systems. Coronal dentin of extracted human molars was exposed and infiltrated with calcium hydroxide, MTA, or bioactive glass 45S5 powder. Non‐infiltrated dentin specimens served as controls. Subsequently, dentin was either acid‐etched or not, and remaining alkali content was measured by pH induction in water. Shear bond strength of an etch‐and rinse system (Adper Single Bond 2) on etched dentin was then compared to that of a universal counterpart (Single Bond [(Scotchbond) Universal] by the same manufacturer. Data was compared between groups using one‐way ANOVA and Tukey's HSD. On sound dentin, the etch‐and‐rinse system adhered stronger than the universal system (p < .05). All particles rendered the dentin alkaline. Acid etching reduced the alkali content in the infiltrated dentin. However, bond strength values were stronger with the universal system without etching than with the etch‐and rinse counterpart, which lost more than 60% of its adhesiveness. The universal adhesive system was less susceptible to alkaline contamination of the dentin than the etch‐and‐rinse counterpart. Based on the similar composition of the two systems under investigation, this is likely to the due to its 10‐MDP component.
Colorful superhydrophobic materials with durability and chemical stability based on kaolin
Authors: Qu Mengnan , Pang Yajie , Xue Menghui , Ma Lili , Peng Lei , Liu Xiangrong , Xiong Shanxin , He Jinmei
Published: December 2020

Inspired by the natural superhydrophobic surfaces with various colors such as the lotus leaves and the wings of butterflies, we report a one‐step method to fabricate superhydrophobic coatings by the combination of kaolin, acrylic color and organosiloxanes. The coatings were characterized using X‐ray photoelectron spectroscopy, scanning electron microscopy, and other analytical techniques. Different from the previously reported method, kaolin particles were introduced to generate rough hierarchical structures on the coating surface, followed by acrylic color decoration and organosiloxanes modification. The colorful superhydrophobic coatings can be constructed in various substrates, such as glass slide, filter paper, and fabric. Furthermore, the obtained coating maintained excellent mechanical durability, chemical stability, and the high‐efficiency of oil–water separation. All of the colorful coatings showed superhydrophobicity in air, and they retained water repellency even after exposed to ultraviolet or under harsh conditions. The results also indicated that the as‐prepared coatings possessed outstanding fungi‐resistance. The colorful superhydrophobic fabric can be used to separate oil/water mixtures, and the separation efficiencies are as high as 95%. We envision that the colorful superhydrophobic coatings with durability and chemical stability may be useful in various fields, such as house decoration, paint coating, antimicrobial material and oil/water separation.
Development of a dense genetic map and QTL analysis for pod borer Helicoverpa armigera (Hübner) resistance component traits in chickpea (Cicer arietinum L.)
Authors: Barmukh Rutwik , Roorkiwal Manish , Jaba Jagdish , Chitikineni Annapurna , Mishra Suraj Prasad , Sagurthi Someswar Rao , Munghate Rajendra , Sharma HC , Varshney Rajeev K.
Published: December 2020

Genetic enhancement for resistance against the pod borer, Helicoverpa armigera is crucial for enhancing production and productivity of chickpea. Here we provide some novel insights into the genetic architecture of natural variation in H. armigera resistance in chickpea, an important legume, which plays a major role in food and nutritional security. An interspecific recombinant inbred line (RIL) population developed from a cross between H. armigera susceptible accession ICC 4958 (Cicer arietinum) and resistant accession PI 489777 (Cicer reticulatum) was evaluated for H. armigera resistance component traits using detached leaf assay and under field conditions. A high‐throughput AxiomCicerSNP array was utilized to construct a dense linkage map comprising of 3,873 loci and spanning a distance of 949.27 cM. Comprehensive analyses of extensive genotyping and phenotyping data identified nine main‐effect QTLs and 955 epistatic QTLs explaining up to 42.49% and 38.05% phenotypic variance, respectively, for H. armigera resistance component traits. The main‐effect QTLs identified in this RIL population were linked with previously described genes, known to modulate resistance against lepidopteran insects in crop plants. One QTL cluster harbouring main‐effect QTLs for three H. armigera resistance component traits and explaining up to 42.49% of the phenotypic variance, was identified on CaLG03. This genomic region, after validation, may be useful to improve H. armigera resistance component traits in elite chickpea cultivars.
Large-Eddy Simulation Study of Ultra-High Fuel Injection Pressure on Gasoline Sprays
Authors: Wadekar S. , Yamaguchi A. , Oevermann M.
Published: December 2020

The development of gasoline spray at ultra-high injection pressures was analyzed using Large-Eddy simulation (LES). Two different nozzle hole geometries, divergent and convergent shape, were considered to inject the fuel at injection pressures ranging from 200 to 1500 bar inside a constant volume spray chamber maintained at atmospheric conditions. The discrete droplet phase was treated using a Lagrangian formulation together with the standard spray sub-models. The numerical results were calibrated by reproducing experimentally observed liquid penetration length and efforts were made to understand the influence of ultra-high injection pressures on the spray development. The calibrated model was then used to investigate the impact of ultra-high injection pressures on mean droplet size and droplet size distribution. In addition, the spray-induced large-scale eddies and entrainment rate were evaluated at different ultra-high injection pressures. Overall, simulation results showed a good agreement with available measurement data. At ultra-high injection pressures mean droplet sizes were significantly reduced and comprised very high velocities. Integral length scales of spray-induced turbulence and air entrainment rate into the spray were larger at higher injection pressure compared to lower ones.

Graphic abstract
Characterization of Downstream Channel Morphology of a Monsoon Dominated Dwarkeswar River in West Bengal
Authors: Malik Sadhan , Pal Subodh Chandra
Published: December 2020

Downstream changes in channel morphology and its flow were investigated over a monsoon dominated Dwarkeswar river from the western part of West Bengal. The basin has developed over the Proterozoic Granite Gneiss Complex to recent Holocene alluvium, forming three distinctive geomorphological regions of the basin e.g., dissected plateau, plate-fringe and alluvial plain area. Sixty cross-sections along the entire main stream were surveyed and bankfull channel parameters were measured. Sediment samples from each location were collected and Manning’s roughness (n) value for respective reaches were estimated and flow velocity, discharge, stream power and shear stress were calculated. The result has shown that channel width and channel capacity in the dissected plateau are increasing downstream, in the plateau-fringe area the trends are relatively constant. But in alluvial plain, width (87.3%), flow area (81.3%), discharge (84.1%), W/D ratio (91.3%) decreases downstream. Downstream decreasing channel width and channel capacity are strongly related to elevation, slope, HSI, TSI and SSI. Extremely low slope, channel switching, cohesive bank materials and vast flood plain width facilitates the river flow to spill over from the channel and spread to the surrounding area resulting diminishing discharge and thereby the channel morphology in downstream. Frequency of flow crossing bankfull limit has increased downstream resulting frequent flood diminishing channel morphology with distance down the valley.
Fenitized Basement Gneissic Xenoliths in Northern Part of Sövite Ring Dike, Amba Dongar Carbonatite Diatreme, Gujarat, India
Authors: Viladkar Shrinivas G.
Published: December 2020

During blasting operations for fluorite in the mining area of the Amba Dongar, numerous xenoliths of different rock types were brought to the surface from time to time in the last several years. The present study is based on the uncovered fenitized gneissic xenoliths in sövite exposed in the mining area. With the aid of detailed petrography and BSE images it is documented that protolith gneiss has undergone extensive K-metasomatism. Details of these processes are discussed with the help of BSE images, mineral analyses and geochemistry of these rocks.
Epaology and the importance of context
Authors: Scheele F.
Published: December 2020

None
Nanolubricant additives: A review
Authors: Zhao Jun , Huang Yiyao , He Yongyong , Shi Yijun
Published: December 2020

Using nanoadditives in lubricants is one of the most effective ways to control friction and wear, which is of great significance for energy conservation, emission reduction, and environmental protection. With the scientific and technological development, great advances have been made in nanolubricant additives in the scientific research and industrial applications. This review summarizes the categories of nanolubricant additives and illustrates the tribological properties of these additives. Based on the component elements of nanomaterials, nanolubricant additives can be divided into three types: nanometal-based, nanocarbon-based, and nanocomposite-based additives. The dispersion stabilities of additives in lubricants are also discussed in the review systematically. Various affecting factors and effective dispersion methods have been investigated in detail. Moreover, the review summarizes the lubrication mechanisms of nanolubricant additives including tribofilm formation, micro-bearing effect, self-repair performance, and synergistic effect. In addition, the challenges and prospects of nanolubricant additives are proposed, which guides the design and synthesis of novel additives with significant lubrication and antiwear properties in the future.
‘It’s like Going to the Regular Class but without Being there’: A Qualitative Analysis of Older people’s Experiences of Exercise in the Home during Covid-19 Lockdown in England
Authors: Taylor Lisa , Raisborough Jayne , Harrison Katherine , Dulson Shelly
Published: December 2020

It is expected that the Covid-19 lockdown will have increased physical inactivity with negative impacts for older people, who are at greater risk of health complications from the virus. This paper draws on customer evaluation questionnaire of a Pilates class aimed at people aged over 50 years old, which transitioned from a studio setting to online classes via Zoom at the start of the lockdown in England. The paper aims to (i) evaluate the shift of exercise services to online and (ii) examine how engagement with online services has influenced people’s reaction to Covid-19 and unprecedented confinement to their homes. Our analysis shows that experiences of exercise in the home are dependent on prior exercise engagement, particularly a sense of progress and competency in exercise movements, trust in the instructor and socio-economic privileges that enable participants to love and appreciate their homes. This paper argues that online classes have had positive impact on participants’ ability to cope with lockdown: routine, structure and being seen by others all proved important well-being aspects.
State Accountability to Sovereignty of the Human Person
Authors: An-Na‘im Abdullahi Ahmed
Published: December 2020

This project seeks to develop ways of holding governments accountable for their failure to satisfy the requirements of conflict management, political stability, economic growth, and social welfare. Since offending governments tend to resist external sources of protection and assistance for an oppressed population by pleading national sovereignty, and major international actors are less likely to act unless driven by strategic or ideological reasons, the project aims at “expounding on the normative principles of responsible sovereignty, international mechanisms and strategies for their enforcement, and empirical evidence about the performance of governments as measured by the stipulates of sovereignty.” Asserting “human dignity as an overarching goal to which all peoples and societies aspire and are committed, whatever the variations of their cultural perspectives on the institutional details of the concept” the project perceives this concept as “operationally or functionally translated into a quest for recognition and respect for human beings, both as individuals and as members of identifiable groups. Human dignity demands, in the minimum, equal treatment with full rights and duties of citizenship.”
Selling Queensland
Authors: Morgan Kenneth
Published: December 2020

This article analyses the work of Richard Daintree as Agent-General for Emigration from the United Kingdom to Queensland when he held that role between 1872 and 1876. Daintree designed exhibitions in London to attract emigrants, placed advertisements in newspapers, wrote a guide to Queensland’s resources, liaised with shipping companies for passenger berths, lectured in the provinces to potential emigrants, and cooperated with emigration sub-agents provided by Queensland’s government for Scotland and Ireland. Daintree contended with two main problems during his period as Agent-General. One involved a serious case of fraud discovered in his London office, but he was not responsible for its occurrence. The other was that a change of Queensland premier from Arthur Hunter Palmer, with whom he had worked cordially, to Arthur Macalister, with whom he had fraught relations, adversely affected his work. Overall, however, the article shows that Daintree was successful in increasing net migration to Queensland during his incumbency as Agent-General.
Commentary: 'Just the tip of the iceberg'
Authors: Hodgson Patrick
Published: December 2020

This article provides a synopsis of the spread of epidemic influenza throughout Queensland in 1919–20. Statewide the story was, to a greater or lesser extent, the same – regardless of occupation or whether one was from the city or the bush, on the coast or in the far west, no one was immune; even being 300 kilometres from the nearest epicentre of the outbreak was no guarantee of safety. An examination of the state’s newspapers, particularly the Brisbane Courier, makes it evident that outbreaks of influenza erupted almost simultaneously throughout the state. Aided and abetted by Queensland’s network of railways and coastal shipping, together with the crowding of people at country shows, race meetings and celebrations of the formal conclusion of World War I, the disease was swiftly diffused throughout the state. This article hopes to give the reader a sense of how the sheer scale and urgency of the crisis at times overwhelmed authorities and communities.
Shifting gender perceptions of female Nepalese students in Brisbane, Australia
Authors: Ghimire Narayan
Published: December 2020

This article explores the changes in how Nepalese female students living in Brisbane, Australia, experience shifting expectations and perceptions of gender roles. It reviews a range of literature from migration studies, geography and humanities to investigate the interrelation between gender and migration, and the ways in which transforming gender relations among the Nepalese migrants in Australia might eventuate. Specifically, the article looks at how traditional gender roles are continued or discontinued by disclosing the lived experiences of a small cohort of Nepalese female students. A summary of qualitative interviews and ethnographic observations are used to highlight how their changing perspectives on traditional gender relations result from living in the changed socio-cultural settings of the host country, and the inherent challenges of implementing the changes in conventional interpretations of gender-based roles after returning to their home country.
Lost in space
Authors: Palmer Kelly
Published: December 2020

The Gold Coast is a multiply liminal space, often represented throughout mainstream media as a holidayworld in which to escape everyday life and structured work routines. Represented as a tourist destination and space for transitions – as a space in which to get lost or lose one’s self – Gold Coast locals are misrepresented as everyday tourists, criminals and dole bludgers, essentially wanderers floating around and through the city limits. Local literary fictions capture this sense of alienation among Gold Coast locals. Georgia Savage’s The House Tibet (1992), in particular, complicates local wandering, with the text representing her runaway protagonists not as living a leisurely existence but rather experiencing the idea of homemaking as a kind of labour necessitated by socioeconomic disadvantage. In this realist narrative, Savage’s depiction of adolescent homelessness advances under-represented views of the multifaceted city while dispelling tourist myths about the Gold Coast as a youthfully unburdened site. Meanwhile, the disenfranchised boys of Amy Barker’s Omega Park (2009) see themselves as aliens in their home city and wander as a means of distancing themselves from a place in which they are trapped. This interdisciplinary investigation of narratives of wandering on the Gold Coast reveals belonging as a dynamic process of placemaking and homemaking, and a privilege of post-colonial habitation and socioeconomic comfort.
Words
Authors: Searles Colbert
Published: December 2020

THE germ of that which follows came into being many years ago in the days of my youth as a university instructor and assistant professor. It was generated by the then quite outspoken attitude of colleagues in the “exact sciences”; the sciences of which the subject-matter can be exactly weighed and measured and the force of its movements mathematically demonstrated. They assured us that the study of languages and literature had little or nothing scientific about it because: “It had no domain of concrete fact in which to work.” Ergo, the scientific spirit was theirs by a stroke of “efficacious grace” as it were. Ours was at best only a kind of “sufficient grace,” pleasant and even necessary to have, but which could, by no means ensure a reception among the elected.
Report of The Committee on Rotographs of Manuscripts and Rare Printed Books
Authors: Searles Professor Colbert
Published: December 2020

Fifty-eight Colleges, Public Libraries, and Universities have contributed to the support of the Rotograph Service of the Modern Language Association of America during the past year, 1935.
In search of a “home”: Comparing the housing challenges experienced by recently arrived Yazidi and Syrian refugees in Canada
Authors: Bhattacharyya Pallabi , Ogoe Sally , Riziki Annette , Wilkinson Lori
Published: December 2020

Housing that is affordable and appropriate is a necessity for successful integration for all newcomers. It is not uncommon for newcomers to Canada to report difficulties finding suitable, safe, and affordable housing for their families. For refugees, however, the challenges are sometimes greater. Settlement organizations and refugee sponsors experience various challenges in accommodating families with large numbers of children, but as our research shows, refugee groups have differing needs based on their culture, family composition, and experience of trauma. Using data collected from two recent studies, we identify and compare the housing needs of two newly arrived groups of refugees to Canada: Syrians and Yazidis from northern Iraq. All participants in our study have lived in Canada for 2 years or less and currently live in Alberta, Saskatchewan, Manitoba, or Ontario. Data was collected either by face-to-face surveys (with Syrian participants) or unstructured interviews (with Yazidi women) conducted in Arabic, Kurmanji, or English. We discuss their experiences of living in resettlement centers and their transition to independent housing. In addition, we discuss how family composition and previous trauma influence their housing experiences with special attention to how increasing agency increases satisfaction with housing.
Informal instruments to impose human rights obligations on foreign investors: An emerging practice of legality?
Authors: Marcoux Jean-Michel
Published: December 2020

In parallel to the negotiation of international investment agreements to protect foreign investment, intergovernmental organizations have deployed considerable efforts to adopt and implement standards of conduct for business enterprises operating abroad. Despite their informal character under international law, these instruments are increasingly mentioned in international investment agreements and investment arbitration. How can references to informal instruments elaborated by intergovernmental organizations contribute to the imposition of human rights obligations on foreign investors in international investment law? Drawing upon the interactional theory developed by Jutta Brunnée and Stephen J. Toope, this article considers these references as a practice that has the potential to strengthen the normative pull towards compliance with human rights norms. In addition to emphasizing the role of international investment law as a relevant forum to develop a practice surrounding these informal instruments, it assesses whether the use of these instruments by members of a community of practice is intended to establish a genuine sense of obligation and to impose human rights obligations on foreign investors. Even if some instances evidence a practice that strengthens such a sense of obligation, most of the references included in international investment agreements and investment arbitration do not render a practice of legality.
Cardiometabolic risk and health behaviours in adolescents with normal-weight obesity: a systematic review
Authors: Cota Bruna Clemente , Suhett Lara Gomes , Leite Nathália Nogueira , Pereira Patrícia Feliciano , Ribeiro Sarah Aparecida Vieira , Franceschini Sylvia do Carmo Castro
Published: December 2020

Objective:

To analyse the presence of cardiometabolic risk factors in adolescents with normal-weight obesity (NWO), as well as to investigate health behaviours related to the phenotype.

Design:

The study was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and the bibliographic search was carried out in the PubMed, Scielo and ScienceDirect databases.

Setting:

School, university and population.

Participants:

Adolescents between 10 and 19 years old.

Results:

A total of eight papers were included. Most studies have found a relationship between NWO and the presence of cardiometabolic risk factors, such as high waist circumference, unfavourable lipid and glycid profile. As for health behaviours, three of the eight studies included evaluated eating habits; however, the results were not conclusive. In addition, four studies analysed the practice of physical activity or physical fitness, which was lower in NWO.

Conclusions:

The available evidence indicates that NWO is related to the early development of cardiometabolic changes, physical inactivity and less physical fitness in adolescents. The results also reveal the importance of early detection of the phenotype, as well as the need for further research on the associated factors to prevent future diseases. Registration (PROSPERO: CRD42020161204).
Association of microsatellite markers with root architecture and agromorphologic traits in diverse germplasm of bread wheat
Authors: Safari Sara , Mehrabi Ali-Ashraf
Published: December 2020

Bread wheat (Triticum aestivum) is one of the most important food crops in the world. Its physiological and morphological traits are closely related to yield. Therefore, it is generally important to discover the genomic region associated with these traits. In this research, associations between 21 simple sequence repeat (SSR) markers and 10 inter-simple sequence repeat (ISSR) markers with some traits related to root structure at the embryonic and seedling stages and also some agromorphological traits at the whole plant stage were evaluated on a set of 102 wheat genotypes. A highly significant coefficient of variation among different genotypes was observed in all measured traits. A high level of polymorphism with SSR and ISSR markers was obtained. Genetic structure analysis revealed two distinct subpopulations. Significant correlations were found between genomic markers and evaluated traits. A total of nine markers, including four SSR markers in 1A, 3A, 5A and 2B chromosomal regions and five different ISSR markers were related to the studied traits. Several molecular markers were significantly associated with more than one phenotypic trait, suggesting the possible presence of pleiotropic or indirect effects. The phenotypic variation justified by these alleles ranged from 4 to 15%. Obtained genetic information can be targeted for further validation and genetic analysis in the relevant populations or other breeding sets.
Can Satellites Fill Gaps in Agricultural Water Monitoring?
Authors: Shultz David
Published: December 2020

Past studies that have estimated irrigation water usage based on satellite remote sensing have had large uncertainties that could hamper effective water management.
Analysis of Water Vapor Fluxes Over a Seasonal Snowpack Using the Maximum Entropy Production Model
Authors: Hajji Islem , Nadeau Daniel F. , Music Biljana , Anctil François , Wang Jingfeng
Published: December 2020

Snow cover plays a key role in the water and energy budgets over cold regions. Understanding and parameterizing water and heat exchange over snow surfaces in hydrologic models remains a major challenge. An innovative approach based on the theory of maximum entropy production (MEP) was developed for modeling energy budgets for snow‐covered surfaces. This study generalizes the MEP model to simulate surface water vapor (latent heat) fluxes over an entire snowpack lifecycle, including snow accumulation and melting during the early growing season. The expanded MEP model combines soil evaporation, canopy transpiration, and snow sublimation to evaluate snow water loss during the lifecycle of the snowpack. Two hypotheses are tested: (1) sublimation becomes negligible during snowmelt when snowpack is isothermal (0°C) and (2) transpiration is progressively activated as a function of the air temperature during vegetation awakening. The proposed approach is shown to be effective for modeling the total surface water vapor fluxes over the snowpack's lifecycle. Both the hypotheses are supported by field observations.
Disposable silicon-based all-in-one micro-qPCR for rapid on-site detection of pathogens
Authors: Nunez-Bajo Estefania , Silva Pinto Collins Alexander , Kasimatis Michael , Cotur Yasin , Asfour Tarek , Tanriverdi Ugur , Grell Max , Kaisti Matti , Senesi Guglielmo , Stevenson Karen , Güder Firat
Published: December 2020

Rapid screening and low-cost diagnosis play a crucial role in choosing the correct course of intervention when dealing with highly infectious pathogens. This is especially important if the disease-causing agent has no effective treatment, such as the novel coronavirus SARS-CoV-2, and shows no or similar symptoms to other common infections. Here, we report a disposable silicon-based integrated Point-of-Need transducer (TriSilix) for real-time quantitative detection of pathogen-specific sequences of nucleic acids. TriSilix can be produced at wafer-scale in a standard laboratory (37 chips of 10 × 10 × 0.65 mm in size can be produced in 7 h, costing ~0.35 USD per device). We are able to quantitatively detect a 563 bp fragment of genomic DNA of Mycobacterium avium subspecies paratuberculosis through real-time PCR with a limit-of-detection of 20 fg, equivalent to a single bacterium, at the 35th cycle. Using TriSilix, we also detect the cDNA from SARS-CoV-2 (1 pg) with high specificity against SARS-CoV (2003).
A human tissue map of 5-hydroxymethylcytosines exhibits tissue specificity through gene and enhancer modulation
Authors: Cui Xiao-Long , Nie Ji , Ku Jeremy , Dougherty Urszula , West-Szymanski Diana C. , Collin Francois , Ellison Christopher K. , Sieh Laura , Ning Yuhong , Deng Zifeng , Zhao Carolyn W. T. , Bergamaschi Anna , Pekow Joel , Wei Jiangbo , Beadell Alana V. , Zhang Zhou , Sharma Geeta , Talwar Raman , Arensdorf Patrick , Karpus Jason , Goel Ajay , Bissonnette Marc , Zhang Wei , Levy Samuel , He Chuan
Published: December 2020

DNA 5-hydroxymethylcytosine (5hmC) modification is known to be associated with gene transcription and frequently used as a mark to investigate dynamic DNA methylation conversion during mammalian development and in human diseases. However, the lack of genome-wide 5hmC profiles in different human tissue types impedes drawing generalized conclusions about how 5hmC is implicated in transcription activity and tissue specificity. To meet this need, we describe the development of a 5hmC tissue map by characterizing the genomic distributions of 5hmC in 19 human tissues derived from ten organ systems. Subsequent sequencing results enabled the identification of genome-wide 5hmC distributions that uniquely separates samples by tissue type. Further comparison of the 5hmC profiles with transcriptomes and histone modifications revealed that 5hmC is preferentially enriched on tissue-specific gene bodies and enhancers. Taken together, the results provide an extensive 5hmC map across diverse human tissue types that suggests a potential role of 5hmC in tissue-specific development; as well as a resource to facilitate future studies of DNA demethylation in pathogenesis and the development of 5hmC as biomarkers.
Hydrogen-deuterium exchange mass spectrometry captures distinct dynamics upon substrate and inhibitor binding to a transporter
Authors: Jia Ruyu , Martens Chloe , Shekhar Mrinal , Pant Shashank , Pellowe Grant A. , Lau Andy M. , Findlay Heather E. , Harris Nicola J. , Tajkhorshid Emad , Booth Paula J. , Politis Argyris
Published: December 2020

Proton-coupled transporters use transmembrane proton gradients to power active transport of nutrients inside the cell. High-resolution structures often fail to capture the coupling between proton and ligand binding, and conformational changes associated with transport. We combine HDX-MS with mutagenesis and MD simulations to dissect the molecular mechanism of the prototypical transporter XylE. We show that protonation of a conserved aspartate triggers conformational transition from outward-facing to inward-facing state. This transition only occurs in the presence of substrate xylose, while the inhibitor glucose locks the transporter in the outward-facing state. MD simulations corroborate the experiments by showing that only the combination of protonation and xylose binding, and not glucose, sets up the transporter for conformational switch. Overall, we demonstrate the unique ability of HDX-MS to distinguish between the conformational dynamics of inhibitor and substrate binding, and show that a specific allosteric coupling between substrate binding and protonation is a key step to initiate transport.
Radiation-induced DNA damage and repair effects on 3D genome organization
Authors: Sanders Jacob T. , Freeman Trevor F. , Xu Yang , Golloshi Rosela , Stallard Mary A. , Hill Ashtyn M. , San Martin Rebeca , Balajee Adayabalam S. , McCord Rachel Patton
Published: December 2020

The three-dimensional structure of chromosomes plays an important role in gene expression regulation and also influences the repair of radiation-induced DNA damage. Genomic aberrations that disrupt chromosome spatial domains can lead to diseases including cancer, but how the 3D genome structure responds to DNA damage is poorly understood. Here, we investigate the impact of DNA damage response and repair on 3D genome folding using Hi-C experiments on wild type cells and ataxia telangiectasia mutated (ATM) patient cells. We irradiate fibroblasts, lymphoblasts, and ATM-deficient fibroblasts with 5 Gy X-rays and perform Hi-C at 30 minutes, 24 hours, or 5 days after irradiation. We observe that 3D genome changes after irradiation are cell type-specific, with lymphoblastoid cells generally showing more contact changes than irradiated fibroblasts. However, all tested repair-proficient cell types exhibit an increased segregation of topologically associating domains (TADs). This TAD boundary strengthening after irradiation is not observed in ATM deficient fibroblasts and may indicate the presence of a mechanism to protect 3D genome structure integrity during DNA damage repair.
Human blood plasma factors affect the adhesion kinetics of Staphylococcus aureus to central venous catheters
Authors: Gunaratnam Gubesh , Spengler Christian , Trautmann Simone , Jung Philipp , Mischo Johannes , Wieland Ben , Metz Carlos , Becker Sören L. , Hannig Matthias , Jacobs Karin , Bischoff Markus
Published: December 2020

Staphylococcus aureus is a common cause of catheter-related blood stream infections (CRBSI). The bacterium has the ability to form multilayered biofilms on implanted material, which usually requires the removal of the implanted medical device. A first major step of this biofilm formation is the initial adhesion of the bacterium to the artificial surface. Here, we used single-cell force spectroscopy (SCFS) to study the initial adhesion of S. aureus to central venous catheters (CVCs). SCFS performed with S. aureus on the surfaces of naïve CVCs produced comparable maximum adhesion forces on three types of CVCs in the low nN range (~ 2–7 nN). These values were drastically reduced, when CVC surfaces were preincubated with human blood plasma or human serum albumin, and similar reductions were observed when S. aureus cells were probed with freshly explanted CVCs withdrawn from patients without CRBSI. These findings indicate that the initial adhesion capacity of S. aureus to CVC tubing is markedly reduced, once the CVC is inserted into the vein, and that the risk of contamination of the CVC tubing by S. aureus during the insertion process might be reduced by a preconditioning of the CVC surface with blood plasma or serum albumin.
Mortality cost of sex-specific parasitism in wild bird populations
Authors: Valdebenito José O. , Liker András , Halimubieke Naerhulan , Figuerola Jordi , Székely Tamás
Published: December 2020

Sex-specific mortality is frequent in animals although the causes of different male versus female mortalities remain poorly understood. Parasitism is ubiquitous in nature with widespread detrimental effects to hosts, making parasitism a likely cause of sex-specific mortalities. Using sex-specific blood and gastrointestinal parasite prevalence from 96 and 54 avian host species, respectively, we test the implications of parasites for annual mortality in wild bird populations using phylogenetic comparative methods. First, we show that parasite prevalence is not different between adult males and females, although Nematodes showed a statistically significant but small male-biased parasite prevalence. Second, we found no correlation between sex-biased host mortalities and sex-biased parasite prevalence. These results were consistent in both blood and gastrointestinal parasites. Taken together, our results show little evidence for sex-dependent parasite prevalence in adults in wild bird populations, and suggest that parasite prevalence is an unlikely predictor of sex difference in adult mortalities, not withstanding sampling limitations. We propose that to understand causes of sex-biased mortalities, more complex analyses are needed that incorporate various ecological and life history components of animals life that may include sex differences in exposure to predators, immune capacity and cost of reproduction.
Down-regulation of miR-let-7e attenuates LPS-induced acute lung injury in mice via inhibiting pulmonary inflammation by targeting SCOS1/NF-κB pathway
Authors: Li Wuquan , Zhang Wentao , Liu Jun , Han Yalong , Jiang He , Ji Gang , Liu Wenjun
Published: December 2020

Excessive pulmonary inflammatory response is critical in the development of acute lung injury (ALI). Previously, microRNAs (miRNAs) have been recognized as an important regulator of inflammation in various diseases. However, the effects and mechanisms of miRNAs on inflammatory response in ALI remain unclear. Herein, we tried to screen miRNAs in the processes of ALI and elucidate the potential mechanism. Using a microarray assay, microRNA let-7e (let-7e) was chose as our target for its reported suppressive roles in several inflammatory diseases. Down-regulation of let-7e by antagomiR-let-7e injection attenuated LPS-induced acute lung injury. We also found that antagomiR-let-7e could obviously improve the survival rate in ALI mice. Moreover, antagomiR-let-7e treatment reduced the production of proinflammatory cytokines (i.e., TNF-α, IL-1β and IL-6) in bronchoalveolar lavage fluid (BALF) of LPS-induced ALI mice. Luciferase reporter assays confirmed that suppressor of cytokine signaling 1 (SOCS1), a powerful attenuator of nuclear factor kappa B (NF-κB) signaling pathway, was directly targeted and suppressed by let-7e in RAW264.7 cells. In addition, it was further observed that SOCS1 was down-regulated, and inversely correlated with let-7e expression levels in lung tissues of ALI mice. Finally, down-regulation of let-7e suppressed the activation of NF-κB pathway, as evidenced by the reduction of p-IκBα, and nuclear p-p65 expressions in ALI mice. Collectively, our findings indicate that let-7e antagomir protects mice against LPS-induced lung injury via repressing the pulmonary inflammation though regulation of SOCS1/NF-κB pathway, and let-7e may act as a potential therapeutic target for ALI.
The Tinnitus Retraining Therapy Counseling Protocol as Implemented in the Tinnitus Retraining Therapy Trial
Authors: Gold Susan L. , Formby Craig , Scherer Roberta W.
Published: December 2020

Purpose

This clinical focus article is a companion to the work of Erdman et al. (2019), in which we described the rationale, development, and implementation of the standard-of-care protocol used in the Tinnitus Retraining Therapy Trial (TRTT), a multicenter, placebo-controlled, randomized, definitive efficacy trial of tinnitus retraining therapy (TRT). We now describe the historical background, development, and standardized implementation and delivery of the TRT counseling protocol (tinnitus counseling [TC]) used in the TRTT. TC is conjectured to be the key component in the TRT protocol for initiating the habituation process that reduces the response to the tinnitus signal and, ultimately, reduces its impact. In the TRTT, participants assigned to receive TC achieved > 30% reduction in the impact of tinnitus.

Method and Results

The design and implementation of standardized treatments in multisite randomized controlled trials presents many challenges for investigators. Here, subsequent to presenting the background, rationale, and the TRT protocol model, we describe the development, refinement, and training/certification for standardized delivery of TC in the TRTT. The primary challenges encountered while distilling and streamlining TC for standardized delivery across multiple clinicians and their replacements at six participating military treatment centers in the TRTT are considered, and the resulting counseling protocol is detailed.

Conclusions

The standardized and streamlined TC used in the TRTT was successful for treating debilitating tinnitus among persons with functionally adequate unaided hearing sensitivity. The structured TC protocol described here appears to be the main determinant of the significant and sizable TRT treatment effects measured in the TRTT, thus bolstering the merits of this standardized counseling approach as one model for the clinical implementation of TRT for the treatment of primary tinnitus.
Progress Review on Topological Properties of Heusler Materials
Authors: Lin Zhi
Published: December 2020

Starting from crystal, electronic and magnetic structures of Heusler compounds, this paper studies the new topological materials related to Heusler compounds and their topological properties, such as anomalous Hall effect, skyrmions, chiral anomaly, Dirac fermion, Weyl fermion, transverse Nernst thermoelectric effect, thermal spintronics and topological surface states. It can be discovered that the topological state of Heusler compound can be well protected due to its high symmetry, thus producing rich topological properties. Heusler materials belonged to Weyl semimetals usually have strong anomalous Hall effect, and the Heusler materials with doping or Anomalous Nernst Effect (ANE) usually have higher thermoelectric figure of merit. These anomalous effects are closely related to the strong spin–orbit interaction. In application, people can use the non-dissipative edge state of quantum anomalous Hall effect to develop a new generation of low-energy transistors and electronic devices. The conversion efficiency of thermoelectric materials can be improved by ANE, and topological superconductivity can be used to promote the progress of quantum computation.
Water quality management in the coastal zone of the sea
Authors: Dreizis Yuriy
Published: December 2020

Sea resort areas are currently one of the most successful developing regions. At the same time, the ecological condition of such regions is important, especially those that specialize in the provision of recreational and tourist services. The quality of coastal water resources played an important role in the sustainable development of those coastal tourist areas. Analysis of physical factors of water exchange was carried out and assessment of water resources quality of the coastal zone of the sea was made, including in closed and semi-enclosed water areas. It has been shown that water exchange is the most important factor in the management of the quality of marine waters of partially enclosed coastal areas. The results of the studies made it possible to assess the circulation of coastal marine waters and the change in certain indicators of water quality, including in the presence of various coastal protection facilities, based on 0-dimensional and system-dynamic models. The results obtained can be used to predict the state of water resources in coastal territories.
Immunotropic effect of oyster mushroom beta-glucans, in combination with birch tree triterpene betulin, and beastim, dipeptide of gamma-D-glutamyl-tryptophan
Authors: Konusova Valentina , Frioui Mohamed , Shamtsyan Mark , Vorobeychikov Eugene , Simbirtsev Andrey
Published: December 2020

Immunotropic effect of oyster mushroom beta-glucans, birch tree triterpenes and dipeptide of gamma-D-glutamyl-tryptophan were studied on white male mice. The study demonstrated that bestim, beta-glucan, as well as a combined preparation consisting of bestim, betulin and beta-glucan administered in a single dose) have an immunotropic effect, which is confirmed by reliable increase in the mass of the thymus, as well as the “mass ratio of the thymus”. The reaction of the spleen of animals to the studied preparations was less obvious. Stimulation of humoral immunity of animals by these preparations was also detected.
Motivation of infection control in nurses' viewpoint
Authors: Platace Diana , Puzirevska Kristine , Kreile Amanda , Millere Inga
Published: December 2020

The spread of hospital infections in high-risk units remains even though infection control and prevention measures are being improved annually. It is associated with factors such as age, severity of the underlying disease, duration of hospitalization, antibacterial therapy, resistance to microorganisms, and the number of invasive procedures. The human resources and the financial distribution in medicine play the key role in controlling infections. Intensive care nurses supervising and taking care of the patients 24 hours a day have an invaluable role in controlling infections and reducing hospital infections. The aim of the study is to find out the nurses' opinions about the factors motivating infection control in the intensive care units and in the department of internal medicine. The study used a quantitative study method-survey (n = 160). The questionnaire included questions about the factors influencing infection control and the factors motivating the nurse. Questionnaires involved nurses in the intensive care units and in the department of internal medicine, who care for patients in Latvian multifunctional regional hospitals. The study suggests that nurses are motivated by both material and non-material motivating factors. The material motivating factors in nurses' viewpoint are maintenance of workplace, the premium of work quality, the premium for night work and overtime, premium for work on holidays, possibility to attend courses and training, vacation pay, as well as environment of work. The non-material motivating factors in nurses' viewpoint are the attitude of the supervisor, being respectful of their workplace, the relations with colleagues, acknowledgment for the work done, the responsibility at work, the pride and respect for the work to be done, the challenges, interesting job and variety in work tasks, as well as the growth and development in the workplace.