bluuebunny/crossref_metadata_2025 huggingface dataset:
In Well‐Treated Celiac Patients Low‐Level Mucosal Inflammation Predicts Response to 14‐day Gluten Challenge
Authors: Stamnaes Jorunn , Stray Daniel , Stensland Maria , Sarna Vikas K. , Nyman Tuula A. , Lundin Knut E. A. , Sollid Ludvig M.
Published: January 2021

In celiac disease (CeD), gluten activates adaptive immune cells that cause damage to the small intestinal mucosa. Histological evaluation of intestinal biopsies allows for grading of disease severity. CeD can effectively be treated with a life‐long gluten‐free diet. Gluten challenge of treated CeD patients is used to confirm diagnosis and to test drug efficacy in clinical trials, but patients respond with different magnitudes to the same gluten challenge. In this study of 19 well‐treated CeD patients, proteome analysis of total tissue or isolated epithelial cell compartment from formalin‐fixed paraffin embedded biopsies collected before and after 14‐day gluten challenge demonstrates that patients with strong mucosal response to challenge have signs of ongoing tissue inflammation already before challenge. This low‐level tissue inflammation at baseline is paralleled by increased gluten specific CD4+ T‐cell frequencies in the gut and presence of a low‐level blood inflammatory profile. Thus, apparently well‐treated CeD is frequently not entirely quiescent, with presence of low‐grade inflammation and antigluten immunity in the gut mucosa. Histology assessment alone appears insufficient to judge full recovery and gut mucosal healing of CeD patients. The findings raise a concern whether a seemingly proper gluten‐free diet is able to curb gut inflammation in all CeD patients.
Social memory and niche construction in a hypervariable environment
Authors: Douglass Kristina , Rasolondrainy Tanambelo
Published: January 2021

Background

Communities in southwest Madagascar have co‐evolved with a hypervariable environment and climate. The paleoclimate record reflects major fluctuations in climatic conditions over the course of Holocene human settlement. Archeological evidence indicates short‐term occupations of sites, suggesting that frequent residential mobility and flexible subsistence strategies have been central features of life on the southwest coast for millennia. Today, despite rapid changes linked to globalization and increasing market integration, mobility and subsistence flexibility remain key to the lives of communities of the region.

Aims

In this article, we advocate closer consideration of the social dimensions of the human niche, and their inextricable links to the biophysical world. Specifically, we explore the theoretical implications of applying a Niche Construction Theory framework to understanding the role of social memory in constructing the human niche of SW Madagascar. We look at how social memory facilitates mobility, resource use, and the creation and maintenance of social identities and ties among communities of foragers, farmers, herders, and fishers living under hypervariable climatic conditions.

Materials & Methods

We conducted an extensive oral history survey in SW Madagascar between 2017 and 2018. We interviewed over 100 elders from 32 different communities.

Results

Our analysis of the oral history archive resulted in the development of a theoretical model of human niche construction centered on the maintenance and transmission of social memory.

Discussion

We argue that social memory and the ability to transmit oral histories of exchange, reciprocity, and cooperation, as well as ecological knowledge are key adaptive mechanisms that facilitate mobility and access to resources in a hypervariable environment.

Conclusion

The preservation and transmission of oral histories and ecological knowledge are thus critical to future resilience and sustainability.
A Robust Porphyrin‐Stabilized Triplet Carbon Diradical
Authors: Wang Kaisheng , Liu Pingting , Zhang Fenni , Xu Ling , Zhou Mingbo , Nakai Akito , Kato Kenichi , Furukawa Ko , Tanaka Takayuki , Osuka Atsuhiro , Song Jianxin
Published: January 2021

The synthesis of robust high‐spin carbon radicals is an important topic in organic chemistry. Toward this end, several porphyrin‐stabilized radicals have been systematically explored. A singly naphthalene‐fused porphyrin radical was synthesized by a reaction sequence consisting of a Suzuki–Miyaura coupling of β‐borylated porphyrin with 2‐bromobenzaldehyde, addition of mesityl Grignard reagent, intramolecular Friedel–Crafts alkylation, and final oxidation with DDQ ortBuOK/O2. This strategy was also used to synthesize doubly naphthalene‐fused porphyrins andsyn‐ andanti‐fused‐anthracene‐bridged porphyrin dimers. While singly naphthalene‐fused porphyrin radical has been shown to be a stable monoradical, doubly naphthalene‐fused porphyrins andanti‐fused‐anthracene‐bridged porphyrin dimers have been shown to be closed‐shell molecules. Finally, thesyn‐dimer was characterized as a surprisingly stable radical (t1/2=28 days under ambient air and at 80 °C) that is storable for more than several months, despite its high‐spin triplet ground‐state carbon diradical.
An Enzyme‐Activatable Engineered DNAzyme Sensor for Cell‐Selective Imaging of Metal Ions
Authors: Yi Deyu , Zhao Jian , Li Lele
Published: January 2021

There is intense interest in imaging intracellular metal ions because of their vital roles in many cellular processes. The challenge has been to develop chemical approaches that can detect metal ions in a cell‐type‐specific manner. Herein we report the design of an enzyme‐activatable DNAzyme sensor technology that can distinguish metal‐ion signals in tumor cells from those in normal cells both in vitro and in vivo. Specifically, the sensing activity of a traditional DNAzyme sensor was inhibited by engineering with a blocking sequence containing an abasic site that can be cleaved by cancer‐specific enzymes and thus enables the selective recovery of metal‐ion sensing capability in cancer cells. We demonstrated that the DNAzyme sensor not only enables cancer‐cell‐selective sensing and imaging of metal ions through an enzymically activated pathway, but also precise control over its metal‐ion sensing activity in tumor‐bearing mice. We envision the use of this biosensing technology to probe the biological roles of diverse metal ions in specific diseases.
Constructing online concept maps in CMap Cloud collaboratively: Connecting pathways in case scenarios
Authors: Gerber Hornink Gabriel , Costa Manuel João
Published: January 2021

Learning metabolic pathways is vital for understanding biochemical processes and all of their implications for life. Their learning in the virtual environment is complex and generative learning strategies, such as the construction of online conceptual maps, can help in this process. This article presents a proposal for the collaborative construction of virtual concept maps on metabolism by students in the CMap Cloud browser application (free). A sequence of steps is suggested, which include online group brainstorming and discussions, peer assessment, and teachers feedback. This proposal is flexible and can be adapted to the didactic and technological reality of each teacher.
Human adipose‐derived stromal/stem cells are distinct from dermal fibroblasts as evaluated by biological characterization and RNA sequencing
Authors: Abreu de Melo Mariane Izabella , da Silva Cunha Pricila , Coutinho de Miranda Marcelo , Faraco Camila Cristina Fraga , Barbosa Joana Lobato , da Fonseca Ferreira Andrea , Kunrath Lima Marianna , Faria Jerusa Araújo Quintão Arantes , Rodrigues Michele Ângela , de Goes Alfredo Miranda , Gomes Dawidson Assis
Published: January 2021

Human adipose‐derived stromal/stem cells (ASC) have immunomodulatory properties and the potential to differentiate into several cell lines, important for application in regenerative medicine. However, the contamination with dermal fibroblasts (FIB) can impair the beneficial effects of ASC in cell therapy. It is then essential to develop new strategies that contribute to the distinction between these two cell types. In this study, we performed functional assays, high‐throughput RNA sequencing (RNA‐Seq) and quantitative PCR (qPCR) to find new markers that can distinguish ASC and FIB. We showed that ASC have adipogenic and osteogenic differentiation capacity and alkaline phosphatase activity, not observed in FIB. Gene expression variation analysis identified more than 2000 differentially expressed genes (DEG) between these two cell types. We validated 16 genes present in the list of DEG, including the alkaline phosphatase gene (ALPL). In conclusion, we showed that ASC and FIB have distinct biological properties as demonstrated by alkaline phosphatase activity and differentiation capacity, besides having different gene expression profiles.

Significance of the study

Although many differences between stromal stem cells derived from human adipose tissue (ASC) and human dermal fibroblasts (FIB) are described, it is still difficult to find specific markers to differentiate them. This problem can interfere with the therapeutic use of ASC. This work aimed to find new markers to differentiate these two cell populations. Our findings suggest that these cells can be distinguished by biological and molecular characteristics, such as adipogenic and osteogenic differentiation, alkaline phosphatase activity and differential gene expression profiles. The DEG were related to the regulation of the cell cycle, development process, structural organization of the cell and synthesis of the extracellular matrix. This study helps to find new cellular markers to distinguish the two populations and to better understand the properties of these cells, which can improve cell therapy.
Autologous hematopoietic transplantation following COVID‐19 infection
Authors: Brzycki Marthilde , Richard Robert , Burwick Nicholas , Graf Solomon , O'Brien Craig , Wu Daniel , Chauncey Thomas R.
Published: January 2021

Autologous hematopoietic cell transplantation following induction therapy is standard of care for most patients with newly diagnosed multiple myeloma (N Engl J Med 2017, 376; 1311). Though active COVID‐19 infection is typically a contraindication to aggressive therapy, little is known about the safety of autologous transplantation after resolution of acute symptoms and undetectable pathogen by nasopharyngeal PCR.
Necrobiosis lipoidica: A case report with dermoscopic review
Authors: Shrestha Samir , Spierings Natalia , Marahatta Suchana
Published: January 2021

The diagnosis of NL is made traditionally by Histopathological Examination (HPE). This case report will aid for alternative noninvasive modality for confirmation of the condition via dermoscopy and differentiating it from other granulomatous skin condition.
Is CSR the new competitive environment for CEOs? The association between CEO turnover, corporate social responsibility and board gender diversity: Asian evidence
Authors: Orij René P. , Rehman Saif , Khan Hashim , Khan Faisal
Published: January 2021

The choice for corporate social responsibility (CSR) as a strategic tool remains a debatable issue. While past studies suggest that the financial performance of a firm is the primary driver of CEO turnover; we found that a firm's CSR performance also has a relationship with CEO turnover, a negative relationship. Consistent with the hypotheses, our findings suggest that firm's CSR performance positively moderates the firm's financial performance–CEO turnover relationship. The firm's negative CSR performance–CEO turnover relationship is more pronounced in highCSR‐ranked firms. Precisely, the findings posit that CSR appears to (a) reduce likelihood of CEO turnover in general, (b) somewhat increases the likelihood of CEO turnover in case of poor financial performance, and (c) greatly reduces the likelihood of CEO turnover in case of better financial performance is good. Therefore, a CEO who is motivated to deliver profits in a socially responsible way may face both positive and negative personal consequences. Given the importance of the board gender diversity/gender critical mass, our findings show that the presence of gender critical mass moderates the firm's negative performance (CSR and ROA)–CEO turnover relationship. Further, we split the sample into low and highCSR‐ranked firms, and the findings show that the presence of gender critical mass substitutes the firm's negative performance (CSR and ROA)–CEO turnover relation in highCSR‐ranked firms; whereas, it moderates the relation in lowCSR‐ranked firms. Therefore, the presence of gender critical mass supports the statement that “CSR—combined with board gender diversity—is the new competitive environment for CEOs.”
A collaborative strategy for detection and eviction of Sybil attacker and Sybil nodes in VANET
Authors: P. Remya Krishnan , P. Arun Raj Kumar
Published: January 2021

Vehicular ad hoc network (VANET) is a part of the intelligent transportation system (ITS) that provides safety and nonsafety applications. The high mobility of vehicles and the wireless communication environment in VANET makes it vulnerable to various attacks. One among them is the Sybil attack, where a Sybil attacker creates multiple fake identities called Sybil nodes that disrupt the functionality of VANET. Most of the existing solutions in the literature discuss identifying the Sybil nodes (virtual); very few works exist to determine the Sybil attacker (source node that generates Sybil nodes). In this paper, we propose a computation less heuristic approach that focuses on detecting the Sybil attacker and its Sybil nodes using signal strength measurements and Euclidean distance as the detection parameters. The central VANET server, Road Side Units (RSUs), and vehicles collaborate in the detection process, which improves the accuracy of our approach. The core of the approach is a reward‐based system, where the vehicle rewards are determined by collecting RSUs' feedback about the vehicle behavior. From simulation experiments, it is evident that our proposed approach achieves a maximum detection rate of 99.89% and a false positive rate of 0.012% than the existing techniques.
Modeling and delay performance analysis of wireless regional area networks under incumbent coexistence and self‐coexistence with multichannel operations
Authors: Khan Sheraz , Saengudomlert Poompat , Taparugssanagorn Attaphongse
Published: January 2021

Incumbent coexistence and self‐coexistence are common among wireless regional area networks (WRANs) using TV white space (TVWS) due to their large coverages and opportunistic spectrum access. Among incumbents of WRANs are wireless microphones (WMs) whose frequent ON–OFF activities result in intermittent availability of transmission channels. In this work, WRANs under self‐coexistence in addition to incumbent coexistence are modeled for queueing analysis using two‐dimensional (2D) Markov chains taking into account intermittent channel availability for multichannel operations. The proposed models are created based on the widely used ON–OFF Markov chain model for an individual transmission channel. The Markov chain structures depend on the number of WRANs under self‐coexistence as well as the number of transmission channels. In order to reduce the computational complexity associated with a large number of channels, truncated Markov chain models are proposed so that the scenarios with more channels than WRANs can be analyzed with the same complexity as the scenarios with the same number of channels and WRANs. The matrix geometric method is used to numerically compute steady‐state probabilities of the Markov chain, which are then used to evaluate the mean packet delay performance. These results are then used to quantify the mean packet delay obtained from channel sharing among WRANs under self‐coexistence with multichannel operations. Finally, the impact of varying the number of channels as well as varying the ON‐OFF durations of each channel on the delay performance is observed.
Phytolith‐occluded carbon sequestration potential in three major steppe types along a precipitation gradient in Northern China
Authors: Qi Limin , Sun Tingyu , Guo Xudong , Guo Ying , Li Frank Yonghong
Published: January 2021

Phytolith‐occluded carbon (PhytOC) is an important long‐term stable carbon fraction in grassland ecosystems and plays a promising role in global carbon sequestration. Determination of the PhytOC traits of different plants in major grassland types is crucial for precisely assessing their phytolith carbon sequestration potential. Precipitation is the predominant factor in controlling net primary productivity (NPP) and species composition of the semiarid steppe grasslands. We selected three representative steppe communities of the desert steppe, the dry typical steppe, and the wet typical steppe in Northern Grasslands of China along a precipitation gradient, to investigate their species composition, biomass production, and PhytOC content for quantifying its long‐term carbon sequestration potential. Our results showed that (a) the phytolith and PhytOC contents in plants differed significantly among species, with dominant grass and sedge species having relatively high contents, and the contents are significantly higher in the below‐ than the aboveground parts. (b) The phytolith contents of plant communities were 16.68, 17.94, and 15.85 g/kg in the above‐ and 86.44, 58.73, and 76.94 g/kg in the belowground biomass of the desert steppe, the dry typical steppe, and the wet typical steppe, respectively; and the PhytOC contents were 0.68, 0.48, and 0.59 g/kg in the above‐ and 1.11, 0.72, and 1.02 g/kg in the belowground biomass of the three steppe types. (c) Climatic factors affected phytolith and PhytOC production fluxes of steppe communities mainly through altering plant production, whereas their effects on phytolith and PhytOC contents were relatively small. Our study provides more evidence on the importance of incorporating belowground PhytOC production for estimating phytolith carbon sequestration potential and suggests it crucial to quantify belowground PhytOC production taking into account of plant perenniality and PhytOC deposition over multiple years.
Transfer Hydrogenation of Levulinic Acid to γ‐Valerolactone and Pyrrolidones Using a Homogeneous Nickel Catalyst
Authors: Jurado‐Vázquez Tamara , Arévalo Alma , García Juventino J.
Published: January 2021

We report a well‐defined homogeneous nickel‐based catalyst using the complex [dippeNi(COD)] (dippe=1,2‐bis(diisopropyl phosphino)ethane) as a catalytic precursor with high activity in the hydrogenation of levulinic acid (LVA) to yield γ‐valerolactone (GVL) under relatively mild conditions (4 h, 120 °C); formic acid (FA) is the transfer hydrogenation agent in a dehydrogenation‐hydrogenation process. Under optimized conditions, GVL was obtained with excellent yield (>99 %) and selectivity (>99 %). The Ni‐catalyst was assessed in the LVA hydrogenation with a variety of primary amines using an excess of FA (4 eq) as hydrogen donor at 15 h and 170 °C to produce 2‐pyrrolydones with excellent yield (>99 %) and fair to good selectivity (from 68 to 92 %).
Equilibrating ripple effect, disturbing information cascade effect and regional disparity – A perspective from China's tiered housing markets
Authors: Xiao Qin
Published: January 2021

The current study investigates the role of the tier‐one cities of China in affecting regional disparities within and across its five mega‐city clusters, through the lens of housing market. For that purpose, an equilibrating ripple effect is differentiated from a disturbing information cascade effect. Evidence suggests that a modest slow‐moving equilibrating force originated from Hong Kong has flowed across all tier‐one and most tier‐two cities in the mainland, indicating a narrowing of regional inequalities between Hong Kong and the mainland cities. On the other hand, a powerful disturbing force emanated from Beijing has affected all other cities, widening the inequality gap in between. The impulse response functions further suggest that this disturbing force has a permanent impact on regional disparity.
Inside Cover
Authors: Forouhesh Tehrani Kayvan , Koukourakis Nektarios , Czarske Jürgen , Mortensen Luke J.
Published: January 2021

Wavefront shaping technology can correct for wavefront distortion in turbid media and restore the diffraction‐limited imaging. However, the extent of each correction's validity, or the isoplanatic patch, in bone is unknown. In this paper, we present 1) direct measurement and 2) an in‐situ modeling method of the isoplanatic patch in the murine skull. (The authors thank Ms. Rachel Carlyle for her help with the design of the cover illustration.)

Further details can be found in the article by Kayvan Forouhesh Tehrani, Nektarios Koukourakis, Jürgen Czarske, and Luke J. Mortensen (e202000160).

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Gallic acid protects cerebral cortex, hippocampus, and striatum against oxidative damage and cholinergic dysfunction in an experimental model of manic‐like behavior: Comparison with lithium effects
Authors: Recart Vânia Machado , Spohr Luiza , Soares Mayara Sandrielly Pereira , de Mattos Bruna da Silveira , Bona Natália Pontes , Pedra Nathalia Stark , Teixeira Fernanda Cardoso , Gamaro Giovana Duzzo , Stefanello Francieli , Spanevello Roselia
Published: January 2021

Bipolar disorder is characterized by episodes of depression and mania, and oxidative stress has been associated with the observed neurochemical changes in this disease. We evaluated the effects of gallic acid on hyperlocomotion, acetylcholinesterase activity, and oxidative stress in an animal model of ketamine‐induced mania. Rats were pretreated orally with vehicle, gallic acid (50 or 100 mg/kg), or lithium (45 mg/kg twice a day) for 14 days. Between days 8 and 14, the animals also received ketamine (25 mg/kg) or saline daily. On the 15th day, hyperlocomotion was assessed, following which the animals were euthanized, and brains were collected. Results showed that ketamine‐induced hyperlocomotion and caused oxidative damage by increasing reactive oxygen species levels, lipid peroxidation, and nitrite levels, and decreasing the total thiol content and the activities of catalase, superoxide dismutase, and glutathione peroxidase in the brain. Pretreatment with gallic acid and lithium prevented hyperlocomotion and brain oxidative damage. Further, ketamine increased the acetylcholinesterase activity in the hippocampus and striatum, whereas gallic acid and lithium ameliorated this alteration. Thus, gallic acid may provide effective protection against manic‐like behavior by reducing oxidative stress and preventing cholinergic signaling dysfunction in the brain regions involved in emotion regulation.
Genetic counseling for early onset and familial dementia: Patient perspectives on exome sequencing
Authors: Rolf Bradley , Blue Elizabeth E. , Bucks Stephanie , Dorschner Michael O. , Jayadev Suman
Published: January 2021

Genetic testing has become routine for many inherited conditions; however, little is known about the unique issues that arise when offering genetic testing for inherited forms of dementia. To better understand the patient perspective, we surveyed study participants about their experiences as they underwent genetic counseling and genetic testing for dementia. We recruited 50 pairs of subjects. Each pair was comprised of one person with cognitive impairment and a cognitively intact co‐participant. Study participants received pre‐ and post‐test genetic counseling and comprehensive genetic testing for dementia. During the study, participant pairs completed four surveys which asked about their experience. Testing began with a 38 gene dementia panel. Participants with negative panel results or variants of uncertain significance (VUS) were reflexed to exome sequencing (ES). Twenty‐nine participants (58%) reported that their primary motivation to join the study was for the benefit to their families. Fifty‐two percent of participants initially planned to use their test results to make health and wellness changes, but, six months after disclosure, only 31% had done so. Six months after result disclosure, approximately 90% of participant pairs accurately recalled their genetic test results. Overall satisfaction with testing was high, and decision regret was negligible. This observational study describes the experiences of study participants undergoing genetic counseling and genetic testing for dementia and found that most participant pairs accurately recalled their results up to six months following disclosure while also maintaining high levels of satisfaction without decision regret. These findings suggest that, in the context of genetic counseling, genetic testing can be effectively used in this population.
Extracellular protease production regulated by nitrogen and carbon sources in Trichoderma reesei
Authors: Sun Yu , Qian Yuanchao , Zhang Jiaxin , Wang Yifan , Li Xihai , Zhang Weican , Wang Lushan , Liu Hong , Zhong Yaohua
Published: January 2021

The filamentous fungus Trichoderma reesei is an important producer of industrial enzymes, and possesses abundant extracellular protease genes based on the genome sequence data. However, the production of extracellular proteases remains poorly understood. Here, protease production was extensively investigated on different carbon (glucose and lactose) and nitrogen sources ((NH4)2SO4, NaNO3, peptone, and corn steep liquor). It was found that protease production was dominantly regulated by nitrogen sources. Organic nitrogen sources were beneficial for protease production, while the preferred nitrogen source (NH4)2SO4 inhibited the expression of proteases. As for carbon sources, lactose was a more effective inducer than glucose for protease production. The protease activity was further examined by protease inhibitors, which suggested that protease activity was predominantly inhibited by phenylmethanesulfonyl fluoride (PMSF) and slightly suppressed by ethylenediaminetetraacetic acid (EDTA). Moreover, proteomic analysis revealed a total of 29 extracellular proteases, including 13 serine proteases, 6 aspartic proteases, and 10 metalloproteases. In addition, seven proteases were found to be present among all conditions. These results showed the regulatory profile of extracellular protease production in Trichoderma reesei grown on various carbon and nitrogen sources, which will facilitate the development of T. reesei to be an effective workhorse for enzyme or high‐value protein production in industry.
Preparation of Branch Polyethyleneimine (BPEI) Crosslinked Anion Exchange Membrane Based on Poly(styrene‐b‐(ethylene‐co‐butylene)‐b‐styrene) (SEBS)
Authors: Xiao Yafei , Zhang Minghua , Dong Dawei , Yang Zhaojie , Cao Ya , Wang Ke , Fan Minmin
Published: January 2021

Anion exchange membranes with chemical stability, high conductivity, and high mechanical properties play an important role in alkaline fuel cells. Here, a series of CPX anion exchange membranes based on poly(styrene‐b‐(ethylene‐co‐butylene)‐b‐styrene) (SEBS) and branch polyethyleneimine (BPEI) are achieved by casting, in which BPEI acts as both a crosslinking agent and an OH− conducting functional group. The introduction of BPEI facilitates the formation of good hydrophilic/hydrophobic microphase separation structure, thus improving the ion transport channel of CPX membrane. The physicochemical and electrochemical properties of the CPX membrane are significantly improved when the mass ratio of SEBS to BPEI is within an appropriate range. The OH− conductivity of the CP2 membrane (the mass ratio of SEBS to BPEI is 2) can reach 66.63 mS cm−1 at 80 °C, and more than 80% initial OH− conductivity is maintained in 1.0 m NaOH solution for 20 d at 60 °C. The strategy of using a polymer with excellent alkali resistance and oxidation resistance as the main body and introducing a conductive group that can construct microphase separation can simultaneously improve the conductivity and membrane stability. This viable strategy is a promising construction method for anion exchange membranes that can be applied to fuel cells.
Therapeutic targets and potential agents for the treatment of COVID‐19
Authors: Wu Yinuo , Li Zhe , Zhao Yun‐Song , Huang Yi‐You , Jiang Mei‐Yan , Luo Hai‐Bin
Published: January 2021

The outbreak of coronavirus disease 2019 (COVID‐19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, has become a global crisis. As of November 9, COVID‐19 has already spread to more than 190 countries with 50,000,000 infections and 1,250,000 deaths. Effective therapeutics and drugs are in high demand. The structure of SARS‐CoV‐2 is highly conserved with those of SARS‐CoV and Middle East respiratory syndrome‐CoV. Enzymes, including RdRp, Mpro/3CLpro, and PLpro, which play important roles in viral transcription and replication, have been regarded as key targets for therapies against coronaviruses, including SARS‐CoV‐2. The identification of readily available drugs for repositioning in COVID‐19 therapy is a relatively rapid approach for clinical treatment, and a series of approved or candidate drugs have been proven to be efficient against COVID‐19 in preclinical or clinical studies. This review summarizes recent progress in the development of drugs against SARS‐CoV‐2 and the targets involved.
Viscosity characterization and flow simulation and visualization of polytetrafluoroethylene paste extrusion using a green and biofriendly lubricant
Authors: Schmidt George A. , Lin Yu‐Jyun , Xu Yiyang , Wang Dongfang , Yilmaz Galip , Turng Lih‐Sheng
Published: January 2021

Polytetrafluoroethylene (PTFE) and expanded PTFE (ePTFE) are ideal for various applications. Because PTFE does not flow, even when heated above its melting point, PTFE components are fabricated using a process called paste extrusion. This process entails blending PTFE powder particles with a lubricant to form PTFE paste, which is subsequently preformed, extruded, expanded (in the case of ePTFE), and sintered. In this study, ethanol was proposed as an alternative green lubricant for PTFE processing. Not only is ethanol benign and biofriendly, it provides excellent wettability and processing benefits. Using ethanol as a lubricant, the shear viscosity of PTFE paste and its flow behavior during paste extrusion were investigated. Frequency sweeps using a parallel‐plate rheometer were performed on PTFE paste samples and various grits of sandpaper were used to reduce wall slip of PTFE paste. A viscosity model was generated and a multiphysics software was used to simulate PTFE paste extrusion. The simulated extrusion pressure was compared to experimental data of actual paste extrusion. Flow visualization experiments using colored PTFE layers were conducted to reveal the flow profile of the PTFE paste. The morphology of the expanded ePTFE tubes was examined using scanning electron microscopy and the effect of expansion ratio on ePTFE morphology was quantified.
Kleiner Punkt – große Wirkung
Authors: Mathelitsch Leopold , Thaller Sigrid
Published: January 2021

Der Schwerpunkt spielt im Sport eine zentrale Rolle. Im Hochsprung gelingt es sogar, den Körperschwerpunkt unter der Latte durchzuschieben. Dazu wirken beim Fosbury‐Flop das Drehmoment einer Anlaufkurve und das Durchbiegen des Körpers in Rückenlage zusammen. Beim Weitsprung wiederum kann das Anheben und Senken der Arme die Sprungweite verlängern, obwohl die Flugparabel des Körperschwerpunkts nicht veränderbar ist. Genauere Analysen von Bewegungsabläufen erfordern eine genauere Kenntnis der Schwerpunkte des Körpers und seiner Segmente. Bei Frauen liegt der Gesamtschwerpunkt relativ niedriger als bei Männern. Beim Wurfspeer musste eine Reglementänderung die Lage des Schwerpunkts verschieben, um gefährliche Wurfweiten in Stadien auszuschließen.
Elektrische Raumfahrtantriebe – längst keine Science Fiction mehr
Authors: Dannenmayer Käthe
Published: January 2021

Der Raumfahrtpionier Ernst Stuhlinger prophezeite vor 50 Jahren das neue Zeitalter der Ionenantriebe, auch elektrische Antrieb genannt. Heute sind sie wirklich im Einsatz.
Experimente im Science Journal dokumentieren
Authors: Teichrew Albert , Wilhelm Thomas , Kuhn Jochen
Published: January 2021

Mit der App Science Journal kann man nicht nur die Daten der integrierten Sensoren auslesen, sondern hat darüber hinaus ein digitales Notizbuch für verschiedene Experimente an einem Ort.
Synthesis of dihydroxy telechelic oligomers of β‐butyrolactone catalyzed by titanium(IV)‐alkoxides and their use as macrodiols in polyurethane chemistry
Authors: Altmann Hagen J. , Machat Martin R. , Wolf Aurel , Gürtler Christoph , Wang Dongren , Buchmeiser Michael R.
Published: January 2021

We report on a solvent‐free approach for the synthesis of low molecular weight, α,ω‐dihydroxy telechelic poly(β‐butyrolactone). In the presence of Ti(IV) alkoxides, mixtures of β‐butyrolactone and diols, like di‐ or triethylene glycol, were reacted in ratios between 4:1 and 10:1. The oligomerization proceeds at elevated temperatures (80–100°C). Different alkoxide substituents (R = Me, iPr, tBu) of the Ti(IV)(OR)4 catalyst were investigated. The resulting oligomers were characterized by nuclear magnetic resonance (NMR), infra‐red (IR), gel‐permeation chromatography (GPC), titration, and matrix‐assisted laser desorption‐time‐of‐flight mass spectrometry (MALDI‐ToF‐MS) analysis. Aside from low molecular weight products, special effort was devoted to achieve high O‐acyl cleavage selectivity and to circumvent the formation of unsaturated end‐groups in order to form exclusively dihydroxy‐telechelic oligomers. Optimized results in terms of selectivity and reaction rates were achieved at 100°C using catalyst loadings of 0.2 mol% with respect to the monomer. The molecular weights determined by GPC were in good accordance with the ratio of monomer to diol used, confirming successful oligomer formation. Polyurethanes prepared from crude macrodiols without any additional catalyst feature molecular weights up to 50,000 g/mol. The reported work serves as concept to utilize β‐lactones for tailored polyol synthesis; the resulting products are suitable for polyurethane chemistry.
On the swelling behavior of poly(N‐Isopropylacrylamide) hydrogels exposed to perfluoroalkyl acids
Authors: Savage Dustin T. , Briot Nicolas J. , Hilt J. Zach , Dziubla Thomas D.
Published: January 2021

Per‐ and polyfluoroalkyl substances (PFAS) have rapidly accumulated in the environment due to their widespread use prior to commercial discussion in the early 21st century, and their slow degradation has magnified concerns of their potential toxicity. Monitoring their distribution is, therefore, necessary to evaluate and control their impact on the health of exposed populations. This investigation evaluates the capability of a simple polymeric detection scheme for PFAS based on crosslinked, thermoresponsive poly(N‐isopropylacrylamide) (PNIPAM) hydrogels. Surveying swelling perturbations induced by several hydrotropes and comparable hydrocarbon analogs, tetraethylammonium perfluorooctane sulfonate (TPFOS) showed a significantly higher swelling ratio on a mass basis (65.5 ± 8.8 at 15°C) than any of the other analytes tested. Combining swelling with the fluorimetric response of a solvachromatic dye, nile red, revealed the fluorosurfactant to initiate observable aggregation (i.e., its critical aggregation concentration) at 0.05 mM and reach saturation (i.e., its charge neutralization concentration) at 0.5 mM. The fluorosurfactant was found to homogeneously distribute throughout the polymer matrix with energy dispersive X‐ray spectroscopy, marking the swelling response as a peculiar nexus of fluorinated interfacial positioning and delocalized electrostatic repulsion. Results from the current study hold promise for exploiting the physiochemical response of PNIPAM to assess TPFOS's concentration.
Response to a case report: Idiopathic hypereosinophilic syndrome in remission with benralizumab treatment after relapse with mepolizumab
Authors: Requena Gema , Roufosse Florence , Baylis Lee D. , Steinfeld Jonathan
Published: January 2021

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Current and future approaches to wet weather flow management: A review
Authors: Peters Paige E. , Zitomer Daniel H.
Published: January 2021

Sewers can become hydraulically overburdened during high‐intensity precipitation resulting in untreated water entering receiving streams. Combined (CSOs) and sanitary sewer overflows (SSOs) cause adverse public health and environmental impacts as well as management challenges for many wastewater utilities. This novel review presents information regarding wet weather flow regulation, impacts, and current management methods, and offers ideas for future approaches in the United States. Currently, storage followed by conventional municipal water reclamation facility treatment after precipitation events is often employed. Stand‐alone alternative technologies include high‐rate solids removal, rapid disinfection, filtration, and green infrastructure. However, most current stand‐alone approaches do not address soluble BOD5 or emerging contaminants in stormwater and wastewater. As the needs for wet weather flow management change, future approaches should include a goal of zero overflows and achieve effluent quality as good as or better than conventional treatment. To help achieve zero overflows and complete treatment, the “peaker facility” concept is proposed. The peaker facility often remains idle but treats excess flow when needed. Considering the challenges of remaining idle for long periods, starting up quickly, and handling high flows, chemical oxidation may be an applicable peaker facility component. However, more research and development are needed to determine best practices.

Practitioner points

Combined (CSO) and sanitary sewer overflows (SSOs) pose both environmental and public health risks as untreated water is discharged into lakes and rivers during high‐intensity rain events.

Current stand‐alone approaches for managing or treating CSOs focus on particulate BOD/COD and solids removal, and do not typically address soluble BOD or emerging contaminants in stormwater and wastewater (including pathogens).

New wet weather policies and regulations encourage more holistic approaches by wastewater utilities, and future approaches should include a zero‐overflow goal for all CSOs and SSOs.

To help achieve zero overflows, the concept of the “peaker facility” is proposed.

Chemical oxidation may be an applicable component of peaker facilities for its short detention time and ability to remove, oxidize, or inactive water impairment‐causing contaminants.
Maximally self-interacting dark matter: models and predictions
Authors: Kamada Ayuki , Kim Hee Jung , Kuwahara Takumi
Published: January 2021

Abstract

We study self-interacting dark matter (SIDM) scenarios, where thes-wave self-scattering cross section almost saturates the Unitarity bound. Such self-scattering cross sections are singly parameterized by the dark matter mass, and are featured by strong velocity dependence in a wide range of velocities. They may be indicated by observations of dark matter halos in a wide range of masses, from Milky Way’s dwarf spheroidal galaxies to galaxy clusters. We pin down the model parameters that saturates the Unitarity bound in well-motivated SIDM models: the gaugedLμ− Lτmodel and composite asymmetric dark matter model. We discuss implications and predictions of such model parameters for cosmology like theH0tension and dark-matter direct-detection experiments, and particle phenomenology like the beam-dump experiments.
Analysis of influencing factors for the dressing process in double side face grinding
Authors: Uhlmann Eckart , Lichtschlag Linus
Published: January 2021

In grinding, the design of the dressing process is an essential part of work preparation and restoration of the grinding wheel’s profile and cutting ability. In contrast to most grinding processes, the choice of dressing parameters in double face grinding with planetary kinematics has so far only been experience-based. As a consequence, the dressing process causes a higher degree of tool wear than the machining of the workpieces. A focused design of the dressing process based on a scientific data could help to improve the ecological and the economic efficiency by reducing tool wear and the amount of dressing tools used. In this paper, methods for determining the wear condition and the result of the dressing process, including macro- and microscopic characteristic are presented. This includes a correlation analysis between parameters of wear characteristics and workpiece surface quality. Furthermore, technological investigations are carried out in order to systematically limit the main influencing factors on the dressing process. As a result, the parameters dresser grain sizedgd, rotational speed rationldand the machined dresser height ∆hdare identified as significant for dressing. The knowledge about their principal influence on the dressing result could provide the basis for further research.
Evaluation of cytokines in the tumor microenvironment of lung cancer using bronchoalveolar lavage fluid analysis
Authors: Bezel Pascal , Valaperti Alan , Steiner Urs , Scholtze Dieter , Wieser Stephan , Vonow-Eisenring Maya , Widmer Andrea , Kowalski Benedikt , Kohler Malcolm , Franzen Daniel P.
Published: January 2021

Introduction

Lung cancer is the leading cause of death by cancer. In recent years, immunotherapy with checkpoint inhibitors (ICI) emerged as a promising new therapeutic approach. However, a deeper understanding of the immunologic responses adjacent to the tumor known as tumor microenvironment (TME) is needed. Our study investigated TME of lung cancer by analyzing cytokines in bronchoalveolar lavage fluid (BALF).

Materials and methods

Between January 2018 and June 2019, 119 patients were prospectively enrolled in this study. For each cancer patient, levels of 16 cytokines (fractalkine, granulocyte–macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukins (IL): IL-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17A, and IL-23) were measured in BALF and serum and compared to healthy individuals and patients with other lung diseases.

Results

There were several significant differences of cytokine levels of patients with lung cancer compared to healthy individuals. However, none of them remained in the multivariate analysis compared to other lung diseases in either BALF or serum. Furthermore, there were no significant differences between the groups in cell differentiation of either BALF or serum. Cytokine levels in BALF were generally near the lower detection limit and showed almost no correlation with their respective levels measured in serum of the same individual.

Conclusions

Cytokines in BALF and serum of lung cancer patients may indicate unspecific inflammation. BAL is not recommendable as a tool to investigate TME of lung cancer. Therefore, cytokines measured in BALF are probably not appropriate as predictors in patients treated with ICIs.
MRI features of the normal prostatic peripheral zone: the relationship between age and signal heterogeneity on T2WI, DWI, and DCE sequences
Authors: Bura Vlad , Caglic Iztok , Snoj Ziga , Sushentsev Nikita , Berghe Alexandra S. , Priest Andrew N. , Barrett Tristan
Published: January 2021

Objectives

To assess the multiparametric MRI (mpMRI) appearances of normal peripheral zone (PZ) across age groups in a biopsy-naïve population, where prostate cancer (PCa) was subsequently excluded, and propose a scoring system for background PZ changes.

Methods

This retrospective study included 175 consecutive biopsy-naïve patients (40–74 years) referred with a suspicion of PCa, but with subsequent negative investigations. Patients were grouped by age into categories ≤ 54, 55–59, 60–64, and ≥ 65 years. MpMRI sequences (T2-weighted imaging [T2WI], diffusion-weighted imaging [DWI]/apparent diffusion coefficient [ADC], and dynamic contrast-enhanced imaging [DCE]) were independently evaluated by two uro-radiologists on a proposed 4-point grading scale for background change on each sequence, wherein score 1 mirrored PIRADS-1 change and score 4 represented diffuse background change. Peripheral zone T2WI signal intensity and ADC values were also analyzed for trends relating to age.

Results

There was a negative correlation between age and assigned background PZ scores for each mpMRI sequence: T2WI: r = − 0.52, DWI: r = − 0.49, DCE: r = − 0.45, p < 0.001. Patients aged ≤ 54 years had mean scores of 3.0 (T2WI), 2.7 (DWI), and 3.1 (DCE), whilst patients ≥ 65 years had significantly lower mean scores of 1.7, 1.4, and 1.9, respectively. There was moderate inter-reader agreement for all scores (range κ = 0.43–0.58). Statistically significant positive correlations were found for age versus normalized T2WI signal intensity (r = 0.2, p = 0.009) and age versus ADC values (r = 0.33, p = 0.001).

Conclusion

The normal PZ in younger patients (≤ 54 years) demonstrates significantly lower T2WI signal intensity, lower ADC values, and diffuse enhancement on DCE, which may hinder diagnostic interpretation in these patients. The proposed standardized PZ background scoring system may help convey the potential for diagnostic uncertainty to clinicians.

Key Points

• Significant, positive correlations were found between increasing age and higher normalized T2-weighted signal intensity and mean ADC values of the prostatic peripheral zone.

• Younger men exhibit lower T2-weighted imaging signal intensity, lower ADC values, and diffuse enhancement on dynamic contrast-enhanced imaging, which may hinder MRI interpretation.

• A scoring system is proposed which aims towards a standardized assessment of the normal background PZ. This may help convey the potential for diagnostic uncertainty to clinicians.
Effect of atmospheric circulation on surface air temperature trends in years 1979–2018
Authors: Räisänen Jouni
Published: January 2021

The effect of atmospheric circulation on monthly, seasonal and annual mean surface air temperature trends in the years 1979–2018 is studied by applying a trajectory-based method on the European Centre for Medium-Range Weather Forecasts ERA5 reanalysis data. To the extent that the method captures the effects of atmospheric circulation, the results suggest that circulation trends only had a minor impact on observed annual mean temperature trends in most areas. Exceptions include, for example, a decrease in annual mean warming by about 1 °C in western Siberia, and increased warming in central Europe and the Arctic Ocean. However, the effect of circulation trends on seasonal and particularly monthly temperature trends is more substantial. Subtracting the effect of circulation changes from the ERA5 temperature trends leaves residual trends with a smoother annual cycle than the original trends. The residual monthly mean temperature trends also tend to agree better with the multi-model mean temperature trends from models in the 5th Coupled Model Intercomparison Project (CMIP5) than the original ERA5 trends do, with a 42% decrease in the mean square difference over the global land area. However, the corresponding decrease in the mean square difference of the annual mean temperature trends is only 6%.