bluuebunny/crossref_metadata_2025 huggingface dataset:
European Green Deal: Hebel für internationale Klima- und Wirtschaftsallianzen
Authors: Bechberger Mischa , Thiele Yannick , Neumann Kirsten
Published: November 2020

Um eine Stabilisierung des Erdklimas zu erreichen, musste der Erdatmosphäre rund ein Viertel des in ihr enthaltenen Kohlendioxids, CO2, entzogen werden. Eine gigantische, aber nicht unmögliche Aufgabe, zu deren Losung es allerdings einer gemeinsamen internationalen Anstrengung aller Lander bedarf. Der European Green Deal bietet dabei eine nicht zu unterschätzende Gelegenheit für die Reaktivierung internationaler Klima-Diplomatie.
Klimafreundliche Kommunen
Authors: Frederking Angelika , Gieschen Jan-Hinrich , Lindner Maximilian , Richter Doreen
Published: November 2020

Kommunen sind die kleinste politische und administrative Einheit des Staates. Nah an der Bevölkerung haben sie auch die Aufgabe, globale Probleme auf die lokale Ebene zu übertragen und sich aufdrängende Fragen zu losen. So müssen sich Kommunen an die schon spürbar manifesten Klimaänderungen anpassen, um zukunftsfähig wirtschaften und den Bürger:innen ein lebenswertes Umfeld mit funktionierenden Infrastrukturen bieten zu können.
Introduction to Part IV: Teacher Practices
Authors: Imms Wesley , Fisher Kenn
Published: November 2020

This final section of Transitions focuses on arguably the most important element of ’successful’ ILEs—the teacher. Within educational research alone, and when looking at a hundred years or more of research into quality schooling, most arguments attract a counter-perspective. Interestingly, on one factor virtually everyone agrees; the teacher has the greatest positive impact on the quality of student learning. For this reason, we use the preceding sections to lead us into discussions about how teachers occupy and use the educational space.
Where to Now? Fourteen Characteristics of Teachers’ Transition into Innovative Learning Environments
Authors: Imms Wesley , Mahat Marian
Published: November 2020

This chapter places the preceding papers into a wider context. As part of the Innovative Learning Environment and Teacher Change (ILETC) project, seven Transitions symposia were held in five cities across Australasia, Europe and North America during 2017, 2018 and 2019. Each aimed at investigating how teachers adapt to innovative learning environments. The resulting accumulation of approximately 150 papers by graduate researchers and research groups, of which this book’s chapters are a sample, constituted a reasonable representation of international thinking on this topic. When added to three years of ILETC case studies, surveys, systematic literature reviews and teacher workshops, the project team was able to identify consistent patterns in teachers’ spatial transition actions. This chapter places the material of this book within that larger picture, specifically in terms of one project output—the development of a Spatial Transition Pathway. The Pathway emerged from these data and can be seen as an output of the material sampled in previous chapters. Certainly, the considerable work teachers had been doing to re-conceptualise their pedagogies for new spaces (done both intentionally, and at times, without realising) deserved to be mapped as a resource for others undertaking this journey. This chapter makes the case that while each teacher or school’s journey from traditional to ‘innovative’ spaces is unique, there exists some common issues that most seem to face at some time, in some way. It provides a description of fourteen ‘grand themes’ that appear commonly through the data and describes how these can be organised in a way that provides temporal and theme-based strategies and tools, developed by fellow educators to assist in this transition. This final chapter leads the reader to consider ‘where to now’? It celebrates the fact that teachers have enormous capacity to work out how to utilise innovative learning environments well and provides a framework for evidence-based actions into the future.
Porcine Model of the Arterial Switch Operation: Implications for Unique Strategies in the Management of Hypoplastic Left Ventricles
Authors: Azakie Anthony , Carney John P. , Lahti Matthew T. , Bianco Richard W. , Doyle Michelle J. , Kalra Rajat , Martin Cindy M.
Published: November 2020

There are no reports on the performance of the arterial switch operation (ASO) in a normal heart with normally related great vessels. The objective of this study was to determine whether the ASO could be performed in a healthy animal model. Cardiopulmonary bypass (CPB) and coronary translocation techniques were used to perform ASO in neonatal piglets or a staged ASO with prior main pulmonary artery (PA) banding. Primary ASO was performed in four neonatal piglets. Coronary translocation was effective with angiograms confirming patency. Piglets could not be weaned from CPB due to right ventricle (RV) dysfunction. To improve RV function for the ASO, nine piglets had PA banding. All survived the procedure. Post-banding RV pressure increased from a mean of 20.3 ± 2.2 mmHg to 36.5 ± 7.3 mmHg (p = 0.007). At 58 ± 1 days post-banding, piglets underwent cardiac MRIs revealing RV hypertrophy, and RV pressure overload with mildly reduced RV function. Catheterization confirmed RV systolic pressures of 84.0 ± 6.7 mmHg with LV systolic pressure 83.3 ± 6.7 mmHg (p = 0.43). The remaining five PA banded piglets underwent ASO at 51 ± 0 days post-banding. Three of five were weaned from bypass with patent coronary arteries and adequate RV function. We were able to successfully perform an arterial switch with documented patent coronary arteries on standard anatomy great vessels in a healthy animal model. To our knowledge this is the first time this procedure has been successfully performed. The model may have implications for studying the failing systemic RV, and may support a novel approach for management of borderline, pulsatile left ventricles.
Perceived clinical utility of a test for predicting inadequate response to TNF inhibitor therapies in rheumatoid arthritis: results from a decision impact study
Authors: Pappas Dimitrios A. , Brittle Christine , Mossell James E. , Withers Johanna B. , Lim-Harashima Jeraldine , Kremer Joel M.
Published: November 2020

Tumor necrosis factor inhibitor (TNFi) therapies are often the first biologic therapy used to treat rheumatoid arthritis (RA) patients. However, a substantial fraction of patients do not respond adequately to TNFi therapies. A test with the ability to predict response would inform therapeutic decision-making and improve clinical and financial outcomes. A 32-question decision-impact survey was conducted with 248 rheumatologists to gauge the perceived clinical utility of a novel test that predicts inadequate response to TNFi therapies in RA patients. Participants were informed about the predictive characteristics of the test and asked to indicate prescribing decisions based on four result scenarios. Overall, rheumatologists had a favorable view of the test: 80.2% agreed that it would improve medical decision-making, 92.3% said it would increase their confidence when making prescribing decisions, and 81.5% said it would be useful when considering TNFi therapies. Rheumatologists would be more likely to prescribe a TNFi therapy when the test reported that no signal of non-response was detected (79.8%) and less likely to prescribe a TNFi therapy when a signal of non-response was detected (11.3%–25.4%). Rheumatologists (84.7%) agreed that payers should provide coverage for such a test. This study shows that rheumatologists support the clinical need for a test to predict inadequate response to TNFi therapies. Test results were perceived to lead to changes in prescribing behaviors as results instill confidence in the ordering rheumatologist.
Multiplicity results for (p, q)-Laplacian equations with critical exponent in $${\mathbb {R}}^N$$ and negative energy
Authors: Baldelli Laura , Brizi Ylenia , Filippucci Roberta
Published: November 2020

We prove existence results in all of $${\mathbb {R}}^N$$

R

N

for an elliptic problem of (p, q)-Laplacian type involving a critical term, nonnegative weights and a positive parameter $$\lambda $$
λ
. In particular, under suitable conditions on the exponents of the nonlinearity, we prove existence of infinitely many weak solutions with negative energy when $$\lambda $$
λ
belongs to a certain interval. Our proofs use variational methods and the concentration compactness principle. Towards this aim we give a detailed proof of tight convergence of a suitable sequence.
Current status of opioid epidemic in the United Kingdom and strategies for treatment optimisation in chronic pain
Authors: Alenezi Aziza , Yahyouche Asma , Paudyal Vibhu
Published: November 2020

The increase in opioid prescriptions in the United States has been accompanied by an increase in misuse as well as overdose and toxicity related morbidity and mortality. However, the extent of the increased opioid use, including misuse in the United Kingdom, currently remains less debated. Recent studies in the United Kingdom have shown a rise in opioid use and attributed deaths, particularly in areas with higher deprivation. There are also large variations amongst the devolved nations; Scotland has the highest drug-related deaths and year-on-year increase within Europe. Better clinical guidelines that can enable person-centred management of chronic pain, medicines optimisation, and early diagnosis and treatment of opioid use disorder are crucial to addressing opioid-related morbidity and mortality in the United Kingdom.
Corrigendum: Abelian n-division fields of elliptic curves and Brauer groups of product Kummer & abelian surfaces
Authors: Várilly-Alvarado Anthony , Viray Bianca
Published: November 2020

There is an error in the statement and proof of [VAV17, Proposition 5.1] that affects the statements of [VAV17, Corollaries 5.2 and 5.3]. In this note, we correct the statement of [VAV17, Proposition 5.1] and explain how to rectify subsequent statements. In brief, for a statement about abelian Galois representations of a fixed level, ‘abelian’ should be replaced with ‘liftable abelian’ (Definition 1). Statements about abelian Galois representations of arbitrarily high level, however, remain unchanged because such representations give rise to liftable abelian Galois representations of smaller, but still arbitrarily high, level. Hence the main theorems of the paper remain unchanged.
Transitions in loneliness in later life: the role of social comparisons and coping strategies
Authors: Morgan Deborah , Burholt Vanessa ,   CFAS Wales Research Team
Published: November 2020

This study explored the coping strategies and social comparisons used by older adults on different loneliness trajectories (decreased loneliness, stable loneliness and degenerating loneliness). The adaptive consequences of social comparison in later life are recognised as an important strategy for preserving life satisfaction regardless of age-related losses. Coping strategies are also important in managing loneliness. Narrative interviews were conducted with lonely older adults (N = 11) who had participated in Wave One of the Maintaining Function and Well-being in Later Life Study Wales (CFAS Wales). The study found key differences in the coping strategies employed by older adults on different loneliness trajectories. Differences in coping styles between those who reported decreased loneliness and those who were chronically lonely stemmed from perceptions as to whether loneliness was modifiable or not. Different types of social comparison were also found to modulate the loneliness experience. The findings indicate that higher-order strategies (problem, emotional and meaning focused) are not distinct entities but are part of a dynamic process. The management of loneliness in later life may be dependent on several factors, including older adults’ interpretations of the cause of loneliness. These interpretations will have implications for interventions aimed at alleviating chronic loneliness, where the focus may have to be on changing older adult's perceptions of unmodifiable loneliness.
Shanshui-thought in Experimental Music Practices: China and beyond
Authors: Wang Jing
Published: November 2020

The experimental music of Chinese musicians including Yan Jun, Li Jianhong, Jun-Y Chao, Shen Piji and the Tea Rockers Quintet embodies a particular mode of thinking rooted in Chineseqi-philosophy known asshanshui(山水)-thought, which considers nature and the environment as secret and nurturing.Shanshui-thought cultivates an existential gesture of following rather than obeying or conquering; it requires tacit resonance rather than object knowing.Shanshui-thought enables us to recognise the cosmic, aesthetic and moral values of music qualities ofdan(淡) (quiet and bland) andyou(幽) (inward expandedness), once described as ‘poverty’ and ‘darkness’ by the composer Christian Wolff of what he calls ascetic minimalism.
Martian Oxygen and Hydrogen Upper Atmospheres Responding to Solar and Dust Storm Drivers: Hisaki Space Telescope Observations
Authors: Masunaga K. , Yoshioka K. , Chaffin M. S. , Deighan J. , Jain S. K. , Schneider N. M. , Kimura T. , Tsuchiya F. , Murakami G. , Yamazaki A. , Terada N. , Yoshikawa I.
Published: November 2020

We present variations of oxygen 130.4 nm and hydrogen Ly‐β airglow of the Martian upper atmosphere observed by the Hisaki spacecraft in the Earth orbit. In 5‐year intermittent observations covering various Mars seasons, the 130.4 nm brightness varied from ∼700 to ∼1,200 Rayleigh, correlated with the solar 130.4 nm flux. The Ly‐β brightness, on the other hand, varied from ∼50 to ∼260 Rayleigh, correlated with the column dust optical depth rather than the solar Ly‐β flux. This suggests that the global oxygen column density in the upper atmosphere was relatively stable over the observations while the hydrogen column density was highly variable, controlled by dust storms. Although the observations were made in different Mars Years, we suggest that the hydrogen column density increased by at least 2–5 times from non‐dusty to dusty seasons. The source of the hydrogen atoms is likely water vapor transported from the lower atmosphere which subsequently photodissociate into hydrogen atoms. The amount of oxygen atoms dissociated from water vapor is small compared with those dissociated from the main CO2 atmosphere. Large brightness of both emissions was detected during the comet siding spring (CSS) approach. We suggest that a large solar 130.4 nm flux caused the large 130.4 nm brightness and an effect of the CSS approach was small. For Ly‐β, a regional dust storm during the CSS approach likely caused the large brightness. Although it is possible that the hydrogen atoms are transported from the comet, we leave the effect of CSS on the Ly‐β brightness uncertain.
Effect of the ketogenic diet on glycemic control, insulin resistance, and lipid metabolism in patients with T2DM: a systematic review and meta-analysis
Authors: Yuan Xiaojie , Wang Jiping , Yang Shuo , Gao Mei , Cao Lingxia , Li Xumei , Hong Dongxu , Tian Suyan , Sun Chenglin
Published: November 2020

Background

At present, the beneficial effect of the ketogenic diet (KD) on weight loss in obese patients is generally recognized. However, a systematic research on the role of KD in the improvement of glycemic and lipid metabolism of patients with diabetes is still found scarce.

Methods

This meta-study employed the meta-analysis model of random effects or of fixed effects to analyze the average difference before and after KD and the corresponding 95% CI, thereby evaluating the effect of KD on T2DM.

Results

After KD intervention, in terms of glycemic control, the level of fasting blood glucose decreased by 1.29 mmol/L (95% CI: −1.78 to −0.79) on average, and glycated hemoglobin A1c by 1.07 (95% CI: −1.37 to −0.78). As for lipid metabolism, triglyceride was decreased by 0.72 (95% CI: −1.01 to −0.43) on average, total cholesterol by 0.33 (95% CI: −0.66 to −0.01), and low-density lipoprotein by 0.05 (95% CI: −0.25 to −0.15); yet, high-density lipoprotein increased by 0.14 (95% CI: 0.03−0.25). In addition, patients’ weight decreased by 8.66 (95% CI: −11.40 to −5.92), waist circumference by 9.17 (95% CI: −10.67 to −7.66), and BMI by 3.13 (95% CI: −3.31 to −2.95).

Conclusion

KD not only has a therapeutic effect on glycemic and lipid control among patients with T2DM but also significantly contributes to their weight loss.
Prohibitin, STAT3 and SH2D4A physically and functionally interact in tumor cell mitochondria
Authors: Ploeger Carolin , Huth Thorben , Sugiyanto Raisatun Nisa , Pusch Stefan , Goeppert Benjamin , Singer Stephan , Tabti Redouane , Hausser Ingrid , Schirmacher Peter , Désaubry Laurent , Roessler Stephanie
Published: November 2020

Chromosome 8p is frequently deleted in various cancer entities and has been shown to correlate with poor patient survival. SH2D4A is located on chromosome 8p and prevents the nuclear translocation of the pro-tumorigenic transcription factor STAT3. Here, we investigated the interaction of SH2D4A and STAT3 to shed light on the non-canonical functions of STAT3 in cooperation with the tumor suppressor SH2D4A. Using an immunoprecipitation-mass spectrometry (IP-MS) approach, we identified the mitochondrial scaffold proteins prohibitin 1 (PHB1) and prohibitin 2 (PHB2) among other proteins to potentially bind to SH2D4A. Co-immunoprecipitation and proximity ligation assays confirmed direct interactions of STAT3, PHB1, and SH2D4A in situ and in vitro. In addition, cell fractionation and immunofluorescence staining revealed co-localization of these proteins with mitochondria. These interactions were selectively interrupted by the small molecule and PHB ligand FL3. Furthermore, FL3 led to a reduction of STAT3 protein levels, STAT3 transcriptional activity, and HIF1α protein stabilization upon dimethyloxalylglycine (DMOG) treatment. Besides, mitochondrial fusion and fission markers, L-OPA1, Mfn1, and FIS1, were dysregulated upon FL3 treatment. This dysregulated morphology was accompanied by significant reduction of mitochondrial respiration, thus, FL3 significantly diminished mitochondrial respirational capacity. In contrast, SH2D4A knockout increased mitochondrial respiration, whereas FL3 reversed the effect of SH2D4A knockout. The here described results indicate that the interaction of SH2D4A and PHB1 is involved in the mitochondrial function and integrity. The demonstrated interaction with STAT3, accompanied by its reduction of transcriptional activity, further suggests that SH2D4A is linking STAT3 to its mitochondrial functions, and inhibition of PHB-interaction may have therapeutic effects in tumor cells with STAT3 activation.
The armed oncolytic adenovirus ZD55-IL-24 eradicates melanoma by turning the tumor cells from the self-state into the nonself-state besides direct killing
Authors: Hu Hai-Jun , Liang Xiu , Li Hai-Lang , Du Chun-Ming , Hao Jia-Li , Wang Huai-Yuan , Gu Jin-Fa , Ni Ai-Min , Sun Lan-Ying , Xiao Jing , Hu Jin-Qing , Yuan Hao , Dai Yan-Song , Jin Xiao-Ting , Zhang Kang-Jian , Liu Xin-Yuan
Published: November 2020

ZD55-IL-24 is similar but superior to the oncolytic adenovirus ONYX-015, yet the exact mechanism underlying the observed therapeutic effect is still not well understood. Here we sought to elucidate the underlying antitumor mechanism of ZD55-IL-24 in both immunocompetent and immunocompromised mouse model. We find that ZD55-IL-24 eradicates established melanoma in B16-bearing immunocompetent mouse model not through the classic direct killing pathway, but mainly through the indirect pathway of inducing systemic antitumor immunity. Inconsistent with the current prevailing view, our further results suggest that ZD55-IL-24 can induce antitumor immunity in B16-bearing immunocompetent mouse model in fact not due to its ability to lyse tumor cells and release the essential elements, such as tumor-associated antigens (TAAs), but due to its ability to put a “nonself” label in tumor cells and then turn the tumor cells from the “self” state into the “nonself” state without tumor cell death. The observed anti-melanoma efficacy of ZD55-IL-24 in B16-bearing immunocompetent mouse model was practically caused only by the viral vector. In addition, we also notice that ZD55-IL-24 can inhibit tumor growth in B16-bearing immunocompetent mouse model through inhibiting angiogenesis, despite it plays only a minor role. In contrast to B16-bearing immunocompetent mouse model, ZD55-IL-24 eliminates established melanoma in A375-bearing immunocompromised mouse model mainly through the classic direct killing pathway, but not through the antitumor immunity pathway and anti-angiogenesis pathway. These findings let us know ZD55-IL-24 more comprehensive and profound, and provide a sounder theoretical foundation for its future modification and drug development.
Identity-by-descent detection across 487,409 British samples reveals fine scale population structure and ultra-rare variant associations
Authors: Nait Saada Juba , Kalantzis Georgios , Shyr Derek , Cooper Fergus , Robinson Martin , Gusev Alexander , Palamara Pier Francesco
Published: November 2020

Detection of Identical-By-Descent (IBD) segments provides a fundamental measure of genetic relatedness and plays a key role in a wide range of analyses. We develop FastSMC, an IBD detection algorithm that combines a fast heuristic search with accurate coalescent-based likelihood calculations. FastSMC enables biobank-scale detection and dating of IBD segments within several thousands of years in the past. We apply FastSMC to 487,409 UK Biobank samples and detect ~214 billion IBD segments transmitted by shared ancestors within the past 1500 years, obtaining a fine-grained picture of genetic relatedness in the UK. Sharing of common ancestors strongly correlates with geographic distance, enabling the use of genomic data to localize a sample’s birth coordinates with a median error of 45 km. We seek evidence of recent positive selection by identifying loci with unusually strong shared ancestry and detect 12 genome-wide significant signals. We devise an IBD-based test for association between phenotype and ultra-rare loss-of-function variation, identifying 29 association signals in 7 blood-related traits.
Quantitative estimates of average geomagnetic axial dipole dominance in deep geological time
Authors: Biggin Andrew J. , Bono Richard K. , Meduri Domenico G. , Sprain Courtney J. , Davies Christopher J. , Holme Richard , Doubrovine Pavel V.
Published: November 2020

A defining characteristic of the recent geomagnetic field is its dominant axial dipole which provides its navigational utility and dictates the shape of the magnetosphere. Going back through time, much less is known about the degree of axial dipole dominance. Here we use a substantial and diverse set of 3D numerical dynamo simulations and recent observation-based field models to derive a power law relationship between the angular dispersion of virtual geomagnetic poles at the equator and the median axial dipole dominance measured at Earth’s surface. Applying this relation to published estimates of equatorial angular dispersion implies that geomagnetic axial dipole dominance averaged over 107–109 years has remained moderately high and stable through large parts of geological time. This provides an observational constraint to future studies of the geodynamo and palaeomagnetosphere. It also provides some reassurance as to the reliability of palaeogeographical reconstructions provided by palaeomagnetism.
Perceptually unidentifiable stimuli influence cortical processing and behavioral performance
Authors: Pojoga Sorin A. , Kharas Natasha , Dragoi Valentin
Published: November 2020

Our daily behavior is dynamically influenced by conscious and unconscious processes. Although the neural bases of conscious experience have been extensively investigated over the past several decades, how unconscious information impacts neural circuitry and behavior remains unknown. Here, we recorded populations of neurons in macaque primary visual cortex (V1) to find that perceptually unidentifiable stimuli repeatedly presented in the absence of awareness are encoded by neural populations in a way that facilitates their future processing in the context of a behavioral task. Such exposure increases stimulus sensitivity and information encoded in cell populations, even though animals are unaware of stimulus identity. This phenomenon is consistent with a Hebbian mechanism underlying an increase in functional connectivity specifically for the neurons activated by subthreshold stimuli. This form of unsupervised adaptation may constitute a vestigial pre-attention system using the mere frequency of stimulus occurrence to change stimulus representations even when sensory inputs are perceptually invisible.
Light-driven formation of manganese oxide by today’s photosystem II supports evolutionarily ancient manganese-oxidizing photosynthesis
Authors: Chernev Petko , Fischer Sophie , Hoffmann Jutta , Oliver Nicholas , Assunção Ricardo , Yu Boram , Burnap Robert L. , Zaharieva Ivelina , Nürnberg Dennis J. , Haumann Michael , Dau Holger
Published: November 2020

Water oxidation and concomitant dioxygen formation by the manganese-calcium cluster of oxygenic photosynthesis has shaped the biosphere, atmosphere, and geosphere. It has been hypothesized that at an early stage of evolution, before photosynthetic water oxidation became prominent, light-driven formation of manganese oxides from dissolved Mn(2+) ions may have played a key role in bioenergetics and possibly facilitated early geological manganese deposits. Here we report the biochemical evidence for the ability of photosystems to form extended manganese oxide particles. The photochemical redox processes in spinach photosystem-II particles devoid of the manganese-calcium cluster are tracked by visible-light and X-ray spectroscopy. Oxidation of dissolved manganese ions results in high-valent Mn(III,IV)-oxide nanoparticles of the birnessite type bound to photosystem II, with 50-100 manganese ions per photosystem. Having shown that even today’s photosystem II can form birnessite-type oxide particles efficiently, we propose an evolutionary scenario, which involves manganese-oxide production by ancestral photosystems, later followed by down-sizing of protein-bound manganese-oxide nanoparticles to finally yield today’s catalyst of photosynthetic water oxidation.
How to speed up ion transport in nanopores
Authors: Breitsprecher Konrad , Janssen Mathijs , Srimuk Pattarachai , Mehdi B. Layla , Presser Volker , Holm Christian , Kondrat Svyatoslav
Published: November 2020

Electrolyte-filled subnanometre pores exhibit exciting physics and play an increasingly important role in science and technology. In supercapacitors, for instance, ultranarrow pores provide excellent capacitive characteristics. However, ions experience difficulties in entering and leaving such pores, which slows down charging and discharging processes. In an earlier work we showed for a simple model that a slow voltage sweep charges ultranarrow pores quicker than an abrupt voltage step. A slowly applied voltage avoids ionic clogging and co-ion trapping—a problem known to occur when the applied potential is varied too quickly—causing sluggish dynamics. Herein, we verify this finding experimentally. Guided by theoretical considerations, we also develop a non-linear voltage sweep and demonstrate, with molecular dynamics simulations, that it can charge a nanopore even faster than the corresponding optimized linear sweep. For discharging we find, with simulations and in experiments, that if we reverse the applied potential and then sweep it to zero, the pores lose their charge much quicker than they do for a short-circuited discharge over their internal resistance. Our findings open up opportunities to greatly accelerate charging and discharging of subnanometre pores without compromising the capacitive characteristics, improving their importance for energy storage, capacitive deionization, and electrochemical heat harvesting.
Chronic neuronal activation increases dynamic microtubules to enhance functional axon regeneration after dorsal root crush injury
Authors: Wu Di , Jin Ying , Shapiro Tatiana M. , Hinduja Abhishek , Baas Peter W. , Tom Veronica J.
Published: November 2020

After a dorsal root crush injury, centrally-projecting sensory axons fail to regenerate across the dorsal root entry zone (DREZ) to extend into the spinal cord. We find that chemogenetic activation of adult dorsal root ganglion (DRG) neurons improves axon growth on an in vitro model of the inhibitory environment after injury. Moreover, repeated bouts of daily chemogenetic activation of adult DRG neurons for 12 weeks post-crush in vivo enhances axon regeneration across a chondroitinase-digested DREZ into spinal gray matter, where the regenerating axons form functional synapses and mediate behavioral recovery in a sensorimotor task. Neuronal activation-mediated axon extension is dependent upon changes in the status of tubulin post-translational modifications indicative of highly dynamic microtubules (as opposed to stable microtubules) within the distal axon, illuminating a novel mechanism underlying stimulation-mediated axon growth. We have identified an effective combinatory strategy to promote functionally-relevant axon regeneration of adult neurons into the CNS after injury.
Spatially expandable fiber-based probes as a multifunctional deep brain interface
Authors: Jiang Shan , Patel Dipan C. , Kim Jongwoon , Yang Shuo , Mills William A. , Zhang Yujing , Wang Kaiwen , Feng Ziang , Vijayan Sujith , Cai Wenjun , Wang Anbo , Guo Yuanyuan , Kimbrough Ian F. , Sontheimer Harald , Jia Xiaoting
Published: November 2020

Understanding the cytoarchitecture and wiring of the brain requires improved methods to record and stimulate large groups of neurons with cellular specificity. This requires miniaturized neural interfaces that integrate into brain tissue without altering its properties. Existing neural interface technologies have been shown to provide high-resolution electrophysiological recording with high signal-to-noise ratio. However, with single implantation, the physical properties of these devices limit their access to one, small brain region. To overcome this limitation, we developed a platform that provides three-dimensional coverage of brain tissue through multisite multifunctional fiber-based neural probes guided in a helical scaffold. Chronic recordings from the spatially expandable fiber probes demonstrate the ability of these fiber probes capturing brain activities with a single-unit resolution for long observation times. Furthermore, using Thy1-ChR2-YFP mice we demonstrate the application of our probes in simultaneous recording and optical/chemical modulation of brain activities across distant regions. Similarly, varying electrographic brain activities from different brain regions were detected by our customizable probes in a mouse model of epilepsy, suggesting the potential of using these probes for the investigation of brain disorders such as epilepsy. Ultimately, this technique enables three-dimensional manipulation and mapping of brain activities across distant regions in the deep brain with minimal tissue damage, which can bring new insights for deciphering complex brain functions and dynamics in the near future.
Genomic and transcriptomic alterations associated with drug vulnerabilities and prognosis in adenocarcinoma at the gastroesophageal junction
Authors: Lin Yuan , Luo Yingying , Sun Yanxia , Guo Wenjia , Zhao Xuan , Xi Yiyi , Ma Yuling , Shao Mingming , Tan Wen , Gao Ge , Wu Chen , Lin Dongxin
Published: November 2020

Adenocarcinoma at the gastroesophageal junction (ACGEJ) has dismal clinical outcomes, and there are currently few specific effective therapies because of limited knowledge on its genomic and transcriptomic alterations. The present study investigates genomic and transcriptomic changes in ACGEJ from Chinese patients and analyzes their drug vulnerabilities and associations with the survival time. Here we show that the major genomic changes of Chinese ACGEJ patients are chromosome instability promoted tumorigenic focal copy-number variations and COSMIC Signature 17-featured single nucleotide variations. We provide a comprehensive profile of genetic changes that are potentially vulnerable to existing therapeutic agents and identify Signature 17-correlated IFN-α response pathway as a prognostic marker that might have practical value for clinical prognosis of ACGEJ. These findings further our understanding on the molecular biology of ACGEJ and may help develop more effective therapeutic strategies.
Bedaquiline reprograms central metabolism to reveal glycolytic vulnerability in Mycobacterium tuberculosis
Authors: Mackenzie Jared S. , Lamprecht Dirk A. , Asmal Rukaya , Adamson John H. , Borah Khushboo , Beste Dany J. V. , Lee Bei Shi , Pethe Kevin , Rousseau Simon , Krieger Inna , Sacchettini James C. , Glasgow Joel N. , Steyn Adrie J. C.
Published: November 2020

The approval of bedaquiline (BDQ) for the treatment of tuberculosis has generated substantial interest in inhibiting energy metabolism as a therapeutic paradigm. However, it is not known precisely how BDQ triggers cell death in Mycobacterium tuberculosis (Mtb). Using 13C isotopomer analysis, we show that BDQ-treated Mtb redirects central carbon metabolism to induce a metabolically vulnerable state susceptible to genetic disruption of glycolysis and gluconeogenesis. Metabolic flux profiles indicate that BDQ-treated Mtb is dependent on glycolysis for ATP production, operates a bifurcated TCA cycle by increasing flux through the glyoxylate shunt, and requires enzymes of the anaplerotic node and methylcitrate cycle. Targeting oxidative phosphorylation (OXPHOS) with BDQ and simultaneously inhibiting substrate level phosphorylation via genetic disruption of glycolysis leads to rapid sterilization. Our findings provide insight into the metabolic mechanism of BDQ-induced cell death and establish a paradigm for the development of combination therapies that target OXPHOS and glycolysis.
Sound generation in zebrafish with Bio-Opto-Acoustics
Authors: Favre-Bulle Itia A. , Taylor Michael A. , Marquez-Legorreta Emmanuel , Vanwalleghem Gilles , Poulsen Rebecca E. , Rubinsztein-Dunlop Halina , Scott Ethan K.
Published: November 2020

Hearing is a crucial sense in underwater environments for communication, hunting, attracting mates, and detecting predators. However, the tools currently used to study hearing are limited, as they cannot controllably stimulate specific parts of the auditory system. To date, the contributions of hearing organs have been identified through lesion experiments that inactivate an organ, making it difficult to gauge the specific stimuli to which each organ is sensitive, or the ways in which inputs from multiple organs are combined during perception. Here, we introduce Bio-Opto-Acoustic (BOA) stimulation, using optical forces to generate localized vibrations in vivo, and demonstrate stimulation of the auditory system of zebrafish larvae with precise control. We use a rapidly oscillated optical trap to generate vibrations in individual otolith organs that are perceived as sound, while adjacent otoliths are either left unstimulated or similarly stimulated with a second optical laser trap. The resulting brain-wide neural activity is characterized using fluorescent calcium indicators, thus linking each otolith organ to its individual neuronal network in a way that would be impossible using traditional sound delivery methods. The results reveal integration and cooperation of the utricular and saccular otoliths, which were previously described as having separate biological functions, during hearing.
ELISA detection of SARS-CoV-2 antibodies in saliva
Authors: MacMullan Melanie A. , Ibrayeva Albina , Trettner Kylie , Deming Laura , Das Sudipta , Tran Frances , Moreno Jose Ricardo , Casian Joseph G. , Chellamuthu Prithivi , Kraft Jeffrey , Kozak Kenneth , Turner Fred E. , Slepnev Vladimir I. , Le Page Lydia M.
Published: November 2020

To facilitate containment of the COVID-19 pandemic currently active in the United States and across the world, options for easy, non-invasive antibody testing are required. Here we have adapted a commercially available, serum-based enzyme-linked immunosorbent assay (ELISA) for use with saliva samples, achieving 84.2% sensitivity and 100% specificity in a set of 149 clinical samples. This strategy will enable widespread, affordable testing for patients who experienced this disease, whilst minimizing exposure risk for healthcare workers.
Human proximity seeking in family pigs and dogs
Authors: Pérez Fraga Paula , Gerencsér Linda , Andics Attila
Published: November 2020

Family dogs (Canis familiaris) seek human contact from an early age, can discriminate and prefer their caregivers over other humans. To investigate if being kept as a family animal is sufficient to induce similar early human proximity-seeking in another domestic mammal, here we directly compared such behaviours in dogs and similarly raised domestic pigs (Sus scrofa domesticus). We used a preference test to measure proximity-seeking behaviours of 4-month-old family pigs and dogs in the presence of their caregiver and either a stranger or a familiar object, in a novel environment. We found that both pigs and dogs preferred their caregivers over the familiar object but not over the stranger. However, when the caregiver and the stranger were present, only dogs showed an overall preference for human proximity, and pigs spent more time away from both humans. These results suggest that both dogs and pigs seek the proximity of their caregiver, but there is a difference in how each species generalizes their experience to other humans. Species-specific predispositions, including that dogs have a longer socialization period and that humans are more salient as a social stimulus for them, may be important for the early development of an overall preference for humans.
Control of the surface plasmon dispersion and Purcell effect at the metamaterial-dielectric interface
Authors: Ivanov Konstantin A. , Morozov Konstantin M. , Pozina Galia , Gubaydullin Azat R. , Girshova Elizaveta I. , Kaliteevski Mikhail A.
Published: November 2020

The use of metamaterial as a way to mitigate the negative effects of absorption in metals on the Purcell effect in metal-dielectric structures is investigated. A layered metal-dielectric structure is considered as an anisotropic medium in the long-wavelength limit. The dispersion of the surface plasmon appearing at the boundary between such a structure and a different dielectric material, as well as the position of the peak in the local density of states are studied for various combinations of materials and filling factors of the periodic structure. The calculated frequency dependence of the Purcell factor demonstrates an increase in peak value compared to the conventional plasmonic structure. The results obtained using effective media approach are compared to the results of numerical modelling.
Competing for congestible goods: experimental evidence on parking choice
Authors: Pereda María , Ozaita Juan , Stavrakakis Ioannis , Sánchez Angel
Published: November 2020

Congestible goods describe situations in which a group of people share or use a public good that becomes congested or overexploited when demand is low. We study experimentally a congestible goods problem of relevance for parking design, namely how people choose between a convenient parking lot with few spots and a less convenient one with unlimited space. We find that the Nash equilibrium predicts reasonably well the competition for the convenient parking when it has few spots, but not when it has more availability. We then show that the Rosenthal equilibrium, a bounded-rational approach, is a better description of the experimental results accounting for the randomness in the decision process. We introduce a dynamical model that shows how Rosenthal equilibria can be approached in a few rounds of the game. Our results give insights on how to deal with parking problems such as the design of parking lots in central locations in cities and open the way to better understand similar congestible goods problems in other contexts.
Scalable method for micro-CT analysis enables large scale quantitative characterization of brain lesions and implants
Authors: Kastner David B. , Kharazia Viktor , Nevers Rhino , Smyth Clay , Astudillo-Maya Daniela A. , Williams Greer M. , Yang Zhounan , Holobetz Cristofer M. , Santina Luca Della , Parkinson Dilworth Y. , Frank Loren M.
Published: November 2020

Anatomic evaluation is an important aspect of many studies in neuroscience; however, it often lacks information about the three-dimensional structure of the brain. Micro-CT imaging provides an excellent, nondestructive, method for the evaluation of brain structure, but current applications to neurophysiological or lesion studies require removal of the skull as well as hazardous chemicals, dehydration, or embedding, limiting their scalability and utility. Here we present a protocol using eosin in combination with bone decalcification to enhance contrast in the tissue and then employ monochromatic and propagation phase-contrast micro-CT imaging to enable the imaging of brain structure with the preservation of the surrounding skull. Instead of relying on descriptive, time-consuming, or subjective methods, we develop simple quantitative analyses to map the locations of recording electrodes and to characterize the presence and extent of hippocampal brain lesions.
New solar energy-storage resource of plasmon-activated water solution with higher chemical potential
Authors: Yang Chih-Ping , Yu Shih-Hao , Mai Fu-Der , Kuo Tai-Chih , Liu Yu-Chuan
Published: November 2020

Nowadays, solar energy is the most environmentally friendly energy source to drive many chemical reactions and physical processes. However, the corresponding fabrication procedures for obtaining excellent energy-storage devices are relatively complicated and expensive. In this work, we report an innovative strategy on plasmon-activated water (PAW) serving as energy-storage medium from solar energy. The lifetime of the created energetic PAW solution from hot electron transfer (HET) on Au nanoparticles (AuNPs) illuminated with sunshine can last for 2 days, making the energy-storage system is practically available. Encouragingly, the energy-conversion efficiency from the solar energy in the PAW solution is ca. 6.7%. Compared to conventional deionized (DI) water solution, the prepared metastable PAW solution exhibited distinctly higher chemical potential at room temperature. It demonstrates abilities in faster evaporation and enhancing chemical reactions, including hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Our proposed strategy on the simple and cheap energy-storage system based on prepared PAW utilizing solar energy is the first time shown in the literature.
Antidermatophytic activity of some newly synthesized arylhydrazonothiazoles conjugated with monoclonal antibody
Authors: Ouf Salama A. , Gomha Sobhi M. , Eweis Mohamed , Ouf Ahmed S. , Sharawy Ihab A. A. , Alharbi Sulaiman A.
Published: November 2020

A new series of 5-arylhydrazonothiazole derivatives 5a–d has been synthesized, elucidated, and evaluated for their antidermatophytic activity. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of the newly synthesized products were investigated against 18 dermatophyte fungal isolates related to Epidermophyton floccosum, Microsporum canis, and Trichophyton rubrum. The morphological alterations induced by the synthesized derivatives singly or conjugated with the monoclonal antibody were examined on spores of T. rubrum using a scanning electron microscope. The efficacy of synthesized derivative 5a applied at its respective MFC alone or conjugated with anti-dermatophyte monoclonal antibody 0014 in skin infection treatment of guinea pigs due to inoculation with one of the examined dermatophytes, in comparison with fluconazole as standard reference drug was evaluated. In an in vivo experiment, the efficiency of 5a derivative conjugated with the antibody induced 100% healing after 45 days in the case of T. rubrum and M. canis-infected guinea pigs.
Fractional SIR epidemiological models
Authors: Taghvaei Amirhossein , Georgiou Tryphon T. , Norton Larry , Tannenbaum Allen
Published: November 2020

The purpose of this work is to make a case for epidemiological models with fractional exponent in the contribution of sub-populations to the incidence rate. More specifically, we question the standard assumption in the literature on epidemiological models, where the incidence rate dictating propagation of infections is taken to be proportional to the product between the infected and susceptible sub-populations; a model that relies on strong mixing between the two groups and widespread contact between members of the groups. We contend, that contact between infected and susceptible individuals, especially during the early phases of an epidemic, takes place over a (possibly diffused) boundary between the respective sub-populations. As a result, the rate of transmission depends on the product of fractional powers instead. The intuition relies on the fact that infection grows in geographically concentrated cells, in contrast to the standard product model that relies on complete mixing of the susceptible to infected sub-populations. We validate the hypothesis of fractional exponents (1) by numerical simulation for disease propagation in graphs imposing a local structure to allowed disease transmissions and (2) by fitting the model to the JHU CSSE COVID-19 Data for the period Jan-22-20 to April-30-20, for the countries of Italy, Germany, France, and Spain.
Understanding contagion dynamics through microscopic processes in active Brownian particles
Authors: Norambuena Ariel , Valencia Felipe J. , Guzmán-Lastra Francisca
Published: November 2020

Together with the universally recognized SIR model, several approaches have been employed to understand the contagion dynamics of interacting particles. Here, Active Brownian particles (ABP) are introduced to model the contagion dynamics of living agents that perform a horizontal transmission of an infectious disease in space and time. By performing an ensemble average description of the ABP simulations, we statistically describe susceptible, infected, and recovered groups in terms of particle densities, activity, contagious rates, and random recovery times. Our results show that ABP reproduces the time dependence observed in traditional compartmental models such as the Susceptible-Infected-Recovery (SIR) models and allows us to explore the critical densities and the contagious radius that facilitates the virus spread. Furthermore, we derive a first-principles analytical expression for the contagion rate in terms of microscopic parameters, without considering free parameters as the classical SIR-based models. This approach offers a novel alternative to incorporate microscopic processes into analyzing SIR-based models with applications in a wide range of biological systems.