bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual‐Propelled Sporopollenin‐Exine‐Capsule Micromotors for Near‐Infrared Light Triggered Degradation of Organic Pollutants
Authors: Pan Sihao , Ren Jiaoyu , Ma Enhui , Wang Ke , Yang Sicheng , Wang Hong
Published: March 2021

Towards on‐site degradation of organic pollutants, dual‐propelled sporopollenin‐exine‐capsule (SEC) micromotors loaded with horseradish peroxidase (HRP) have been developed. The magnetic propulsion of SEC micromotors enables them to follow predesignated paths to arrive the pollution site, while the chemical propulsion on the site accelerates the degradation process taking advantage of the fluid mixing effect induced by their movement and bubble generation. Near‐infrared (NIR) light is employed to trigger the rupture of the magnetic polydopamine (PDA) outer coating and release the platinum‐coated SECs loaded with HRP enzyme. The dual propulsion system combined with the biocompatible nature of the components paves the way for on‐site bioremediation of organic pollutants.
Investigating the morphological and genetic divergence of arctic char (Salvelinus alpinus)populations in lakes of arctic Alaska
Authors: Klobucar Stephen L. , Rick Jessica A. , Mandeville Elizabeth G. , Wagner Catherine E. , Budy Phaedra
Published: March 2021

Polymorphism facilitates coexistence of divergent morphs (e.g., phenotypes) of the same species by minimizing intraspecific competition, especially when resources are limiting. Arctic char (Salvelinussp.) are a Holarctic fish often forming morphologically, and sometimes genetically, divergent morphs. In this study, we assessed the morphological and genetic diversity and divergence of 263 individuals from seven populations of arctic char with varying length‐frequency distributions across two distinct groups of lakes in northern Alaska. Despite close geographic proximity, each lake group occurs on landscapes with different glacial ages and surface water connectivity, and thus was likely colonized by fishes at different times. Across lakes, a continuum of physical (e.g., lake area, maximum depth) and biological characteristics (e.g., primary productivity, fish density) exists, likely contributing to characteristics of present‐day char populations. Although some lakes exhibit bimodal size distributions, using model‐based clustering of morphometric traits corrected for allometry, we did not detect morphological differences within and across char populations. Genomic analyses using 15,934 SNPs obtained from genotyping by sequencing demonstrated differences among lake groups related to historical biogeography, but within lake groups and within individual lakes, genetic differentiation was not related to total body length. We used PERMANOVA to identify environmental and biological factors related to observed char size structure. Significant predictors included water transparency (i.e., a primary productivity proxy), char density (fish·ha‐1), and lake group. Larger char occurred in lakes with greater primary production and lower char densities, suggesting less intraspecific competition and resource limitation. Thus, char populations in more productive and connected lakes may prove more stable to environmental changes, relative to food‐limited and closed lakes, if lake productivity increases concomitantly. Our findings provide some of the first descriptions of genomic characteristics of char populations in arctic Alaska, and offer important consideration for the persistence of these populations for subsistence and conservation.
Childhood maltreatment and clinical response to mood stabilizers in patients with bipolar disorder
Authors: Cascino Giammarco , D'Agostino Giulia , Monteleone Alessio Maria , Marciello Francesca , Caivano Vito , Monteleone Palmiero , Maj Mario
Published: March 2021

Objective

The association between childhood maltreatment (CM) and clinical response to mood stabilizers has been scarcely investigated in bipolar disorder (BD). Therefore, we assessed whether CM affects the response to lithium or anticonvulsant treatments in BD patients.

Methods

A retrospective assessment of clinical response to mood stabilizers was conducted in 97 euthymic patients with BD by means of the Alda scale. History of CM was investigated through the Childhood Trauma Questionnaire.

Results

Thirty‐seven patients (24 with a history of CM and 13 without CM) were on stable lithium treatment while sixty (35 with a history of CM and 25 without CM) were on stable anticonvulsant treatment. Clinical response to drug treatment did not differ between BD with CM and those without CM in the whole sample as well as in the anticonvulsant‐treated subgroup. In the lithium‐treated subgroup, a significant negative correlation emerged between childhood physical abuse and clinical response and patients with CM showed a significantly reduced Alda score.

Conclusions

In BD patients, CM did not influence the clinical response to anticonvulsant mood stabilizers whereas it was associated with a poorer response to lithium with childhood physical abuse playing a major role in this effect.
In Memoriam: The Online Policing and Trivialization of Black Lives and Black Deaths
Authors: Symes Aliyah
Published: March 2021

The internet has proven itself an invaluable resource in providing information about the Black Lives Matter movement in real time. As people around the world make a commitment to anti‐racism and equality, social media has become a tool for meaningful engagement with the issues and, for many, a platform on which to begin their journey of anti‐racism. However, there are notable inconsistencies between people's declared commitments to social justice on social media platforms and the content they share publicly. Following posts on Twitter and Instagram, I examine the moral policing which takes place in discussions about the Black Lives Matter movement. I argue that the typical forms of virtual policing operate through similar mechanisms of whiteness that are present in respectability politics, in which only those lives deemed worthy and “good” are valued. These conditions allow for room to debate on whether an individual victim of police brutality ultimately deserved to die or not, instead of meaningfully engaging with the systems that enabled a victim's death. The conditionality of death paired with misogynoir—an intersection of racism and sexism that the BLM movement explicitly tries to disavow—has set the stage for the trivializing of Breonna Taylor's passing: some turn her untimely demise into the punch line of a joke while others comment on it in a purely performative type of activism for the sake of their social media aesthetics. I argue that these individuals' ease in piggybacking off of this movement for their own personal gain should be held up to critical scrutiny so that we can progress towards a community that benefits from meaningful solidarity and not empty performativity.
Postprandial rise of essential amino acids is impaired during critical illness and unrelated to small‐intestinal function
Authors: van Gassel Rob J. J. , van de Poll Marcel C. G. , Schaap Frank G. , Plummer Mark , Deane Adam , Olde Damink Steven W. M.
Published: March 2021

Background

Postprandial rise of plasma essential amino acids (EAAs) determines the anabolic effect of dietary protein. Disturbed gastrointestinal function could impair the anabolic response in critically ill patients. Aim was to investigate the postprandial EAA response in critically ill patients and its relation to small‐intestinal function.

Methods

Twenty‐one mechanically ventilated patients and 9 healthy controls received a bolus containing 100 ml of a formula feed (Ensure) and 2 g of 3‐O‐Methyl‐d‐glucose (3‐OMG) via postpyloric feeding tube. Fasting and postprandial plasma concentrations of EAAs, 3‐OMG, total bile salts, and the gut‐released hormone fibroblast growth factor 19 (FGF19) were measured over a 4‐hour period. Changes over time and between groups were assessed with linear mixed‐effects analysis. Early (0–60 minutes) and total postprandial responses are summarized as the incremental area under the curve (iAUC).

Results

At baseline, fasting EAA levels were similar in both groups: 1181 (1055–1276) vs 1150 (1065–1334) μmol·L−1, P = .87. The early postprandial rise in EAA was not apparent in critically ill patients compared with healthy controls (iAUC60, −4858 [−6859 to 2886] vs 5406 [3099–16,853] µmol·L−1·60 minutes; P = .039). Impaired EAA response did not correlate with impaired 3‐OMG response (Spearman ρ 0.32, P = .09). There was a limited increase in total bile salts but no relevant FGF19 response in either group.

Conclusion

Postprandial rise of EAA is blunted in critically ill patients and unrelated to glucose absorption measured with 3‐OMG. Future studies should aim to delineate governing mechanisms of macronutrient malabsorption.
Compact triple‐mode HMSIW balanced passband filter with intrinsic common‐mode suppression
Authors: Zhu Jia‐ming , Deng Hong‐wei , Han Yang‐kun , Xing Si‐bei , Han Wei
Published: March 2021

In this article, a compact triple‐mode balanced passband filter with intrinsic common‐mode (CM) suppression is designed by using a single isosceles right triangle perturbed half‐mode substrate integrated waveguide (HMSIW) cavity. The perturbation metallic vias are introduced to tune the first three resonant modes of HMSIW cavity to form a passband. Furthermore, the planar differential microstrip‐pin feed structure is designed to excite the perturbed substrate integrated waveguide cavity. Under CM operation, when the substrate's height is less than λg/4, the space between perfect electric conductor and perfect magnetic conductor cannot transmit electromagnetic wave, so CM noise can effectively cut off at the planar differential feed structure in a wide frequency range. Finally, a prototyped prototype at 4.5 GHz is designed and fabricated, and measured results show good agreement with simulated ones.
Removal of off‐resonance xenon gas artifacts in pulmonary gas‐transfer MRI
Authors: Willmering Matthew M. , Cleveland Zackary I. , Walkup Laura L. , Woods Jason C.
Published: March 2021

Purpose

Hyperpolarized xenon (129Xe) gas‐transfer imaging allows different components of pulmonary gas transfer—alveolar air space, lung interstitium/blood plasma (barrier), and red blood cells (RBCs)—to be assessed separately in a single breath. However, quantitative analysis is challenging because dissolved‐phase 129Xe images are often contaminated by off‐resonant gas‐phase signal generated via imperfectly selective excitation. Although previous methods required additional data for gas‐phase removal, the method reported here requires no/minimal sequence modifications/data acquisitions, allowing many previously acquired images to be corrected retroactively.

Methods

129Xe imaging was implemented at 3.0T via an interleaved three‐dimensional radial acquisition of the gaseous and dissolved phases (using one‐point Dixon reconstruction for the dissolved phase) in 46 human subjects and a phantom. Gas‐phase contamination (9.5% ± 4.8%) was removed from gas‐transfer data using a modified gas‐phase image. The signal‐to‐noise ratio (SNR) and signal distributions were compared before and after contamination removal. Additionally, theoretical gaseous contaminations were simulated at different magnetic field strengths for comparison.

Results

Gas‐phase contamination at 3.0T was more diffuse and located predominantly outside the lungs, relative to simulated 1.5T contamination caused by the larger frequency offset. Phantom experiments illustrated a 91% removal efficiency. In human subjects, contamination removal produced significant changes in dissolved signal SNR (+7.8%), mean (–1.4%), and standard deviation (–2.3%) despite low contamination. Repeat measurements showed reduced variance (dissolved mean, –1.0%; standard deviation, –8.4%).

Conclusion

Off‐resonance gas‐phase contamination can be removed robustly with no/minimal sequence modifications. Contamination removal permits more accurate quantification, reduces radiofrequency stringency requirements, and increases data consistency, providing improved sensitivity needed for multicenter trials.
Consulting ‘Dr. Google’ for minimally invasive urological oncological surgeries: A contemporary web‐based trend analysis
Authors: Cacciamani Giovanni E. , Sebben Marco , Tafuri Alessandro , Nassiri Nima , Cocci Andrea , Russo Giorgio I , Hung Andrew , de Castro Abreu Andre Luis , Gill Inderbir S. , Artibani Walter
Published: March 2021

PURPOSE

To determine web‐based public interest in minimally invasive surgery (MIS) specifically for urological oncological surgical procedures and how interest in robotics and laparoscopy compares over time.

MATERIALS AND METHODS

Worldwide search‐engine trend analysis included electronic Google queries of MIS urologic options from January 2004 to August 2019, worldwide. Join‐point regression was performed. Comparison of annual relative search volume (ARSV) and average annual percentage change (AAPC) were analysed to assess loss or gain of interest. Evaluations were made regarding 1) penetrance of interest for MIS in Urology; 2) how MIS urologic procedures compared over time; and 3) which were the top related queries to searches for urologic oncology procedures.

RESULTS

Increased interest was found for all of the MIS procedures evaluated. Mean ARSV for robotic approach was higher for the search term 'prostatectomy” (44.8 vs. 13.5; p < 0.001) and 'partial nephrectomy” (27.1 vs.11.5; p = 0.02). No statistical difference was found for the search terms 'cystectomy” or 'nephrectomy”. The analysis of mean (∆‐ARSV) of MIS procedures measured between the first and last 12 months of the study period showed an increased interest with a more pronounced ∆‐ARSV for robotic procedures. The top related searches for all surgical procedures were examined showing an increasing inquisitiveness with regards of type of urological cancers, treatment options, type of surgery and prognostic outcomes.

CONCLUSIONS

People are increasingly searching the web for MIS urological procedures. A growing appeal for robotics is demonstrated, especially for prostatectomy and partial nephrectomy where the robotic approach is gaining traction, suggesting a shift in mind‐set amongst people seeking urological healthcare information.
Spectral form factor for time-dependent matrix model
Authors: Mukherjee Arkaprava , Hikami Shinobu
Published: March 2021

Abstract

The quantum chaos is related to a Gaussian random matrix model, which shows a dip-ramp-plateau behavior in the spectral form factor for the large size N. The spectral form factor of time dependent Gaussian random matrix model shows also dip-ramp-plateau behavior with a rounding behavior instead of a kink near Heisenberg time. This model is converted to two matrix model, made of M1 and M2. The numerical evaluation for finite N and analytic expression in the large N are compared for the spectral form factor.
Cell-based treatment options facilitate regeneration of cartilage, ligaments and meniscus in demanding conditions of the knee by a whole joint approach
Authors: Angele Peter , Docheva Denitsa , Pattappa Girish , Zellner Johannes
Published: March 2021

Purpose

This article provides an update on the current therapeutic options for cell-based regenerative treatment of the knee with a critical review of the present literature including a future perspective on the use of regenerative cell-based approaches. Special emphasis has been given on the requirement of a whole joint approach with treatment of comorbidities with aim of knee cartilage restoration, particularly in demanding conditions like early osteoarthritis.

Methods

This narrative review evaluates recent clinical data and published research articles on cell-based regenerative treatment options for cartilage and other structures around the knee

Results

Cell-based regenerative therapies for cartilage repair have become standard practice for the treatment of focal, traumatic chondral defects of the knee. Specifically, matrix-assisted autologous chondrocyte transplantation (MACT) shows satisfactory long-term results regarding radiological, histological and clinical outcome for treatment of large cartilage defects. Data show that regenerative treatment of the knee requires a whole joint approach by addressing all comorbidities including axis deviation, instability or meniscus pathologies. Further development of novel biomaterials and the discovery of alternative cell sources may facilitate the process of cell-based regenerative therapies for all knee structures becoming the gold standard in the future.

Conclusion

Overall, cell-based regenerative cartilage therapy of the knee has shown tremendous development over the last years and has become the standard of care for large and isolated chondral defects. It has shown success in the treatment of traumatic, osteochondral defects but also for degenerative cartilage lesions in the demanding condition of early OA. Future developments and alternative cell sources may help to facilitate cell-based regenerative treatment for all different structures around the knee by a whole joint approach.

Level of evidence

IV.
Effect of Thermal Treatment at Inert Atmosphere on Structural and Magnetic Properties of Non-stoichiometric Zinc Ferrite Nanoparticles
Authors: Kmita Angelika , Żukrowski Jan , Kuciakowski Juliusz , Marciszko-Wiąckowska Marianna , Żywczak Antoni , Lachowicz Dorota , Gajewska Marta , Sikora Marcin
Published: March 2021

Zinc ferrite nanoparticles were obtained by chemical methods (co-precipitation and thermal decomposition of metalorganic compounds) and systematically probed with volume (XRD, VSM), microscopic (TEM) and element sensitive probes (ICP-OES, Mössbauer Spectroscopy, XPS, XAFS). Magnetic studies proved the paramagnetic response of stoichiometric ZnFe2O4 (ZF) nanoparticles, while superparamagnetic behavior was observed in as-synthesized, non-stoichiometric Zn
x
Fe3−x
O (NZF) nanoparticles. Upon annealing up to 1400 °C in an inert atmosphere, a significant change in the saturation magnetization of NZF nanoparticles was observed, which rose from approximately 50 up to 140 emu/g. We attribute this effect to the redistribution of cations in the spinel lattice and reduction of Fe3+ to Fe2+ during high-temperature treatment. Iron reduction is observed in both ZF and NZF nanoparticles, and it is related to the decomposition of zinc ferrite and associated sublimation of zinc oxide.
QTL analysis of seed germination traits in tobacco (Nicotiana tabacum L.)
Authors: Agacka-Mołdoch Monika , Rehman Arif Mian Abdur , Lohwasser Ulrike , Doroszewska Teresa , Lewis Ramsey S. , Börner Andreas
Published: March 2021

Genetic mapping of seed germination traits has been performed with many plant species. In tobacco, however, investigations are rare. In the present study, a bi-parental mapping population consisting of 118 doubled haploid lines and derived from a cross between ‘Beinhart-1000’ and ‘Hicks’ was investigated. Four germination-related traits, total germination (TG), normal germination (NG), time to reach 50% of total germination (T50), and the area under the curve after 200 h of germination (AUC) were considered by examining seeds either untreated or after a moderate controlled deterioration (CD). Quantitative trait loci were found for all traits distributed on 11 out of the 24 linkage groups. It was demonstrated that, as in many other species, germination-related traits are very complex and under polygenic control.
Resource Controllability of Business Processes Under Conditional Uncertainty
Authors: Zavatteri Matteo , Combi Carlo , Viganò Luca
Published: March 2021

A current research problem in the area of business process management deals with the specification and checking of constraints on resources (e.g., users, agents, autonomous systems, etc.) allowed to be committed for the execution of specific tasks. Indeed, in many real-world situations, role assignments are not enough to assign tasks to the suitable resources. It could be the case that further requirements need to be specified and satisfied. As an example, one would like to avoid that employees that are relatives are assigned to a set of critical tasks in the same process in order to prevent fraud. The formal specification of a business process and its related access control constraints is obtained through a decoration of a classic business process with roles, users, and constraints on their commitment. As a result, such a process specifies a set of tasks that need to be executed by authorized users with respect to some partial order in a way that all authorization constraints are satisfied. Controllability refers in this case to the capability of executing the process satisfying all these constraints, even when some process components, e.g., gateway conditions, can only be observed, but not decided, by the process engine responsible of the execution. In this paper, we proposeconditional constraint networks with decisions (CCNDs)as a model to encode business processes that involve access control and conditional branches that may be both controllable and uncontrollable. We define weak, strong, and dynamic controllability of CCNDs as two-player games, classify their computational complexity, and discuss strategy synthesis algorithms. We provide an encoding from the business processes we consider here into CCNDs to exploit off-the-shelf their strategy synthesis algorithms. We introduce$$\textsc {Zeta}$$ZETA, a tool for checking controllability of CCNDs, synthesizing execution strategies, and executing controllable CCNDs, by also supporting user interactivity. We use$$\textsc {Zeta}$$ZETAto compare with the previous research, provide a new experimental evaluation for CCNDs, and discuss limitations.
Six fragments of a theory of translation as understanding
Authors: Kubin Wolfgang
Published: March 2021

Against the common view of translation as the translation of a text or an author the article argues there is not such a thing. Any translation has its basis in the (subjective) understanding of the translator who only translates according to one’s own comprehension. So there is no loyal translation in the sense of “word-for-word” (Wortwörtlichkeit). It is also an error to think editions are reliable and dictionaries offer a kind of complete vocabulary. So what a translation can do is to open up a wide range of possibilities. The only norm is the logic of understanding an author and a text. Thus individual understanding and individual translating are the two sides of one coin.
Hyper-oncotic vs. Hypo-oncotic Albumin Solutions: a Systematic Review of Clinical Efficacy and Safety
Authors: Haynes Gary R. , Bassiri Kayleigh
Published: March 2021

Several albumin solutions are available for volume expansion. Hyper-oncotic solutions (≥ 20%) are more effective than hypo-oncotic (≤ 5%) as they recruit endogenous extracellular fluid into blood vessels rather than adding volume. The latter may cause volume overload, with several associated complications. This systematic review aimed to evaluate evidence on the efficacy and safety of hyper-oncotic vs. hypo-oncotic albumin solutions across different clinical settings. The review was conducted according to PRISMA guidelines. Ninety articles were retained (58 randomized controlled trials). Four studies directly compared albumin solutions. SWIPE showed that cumulative fluid balance at 48 h was significantly lower with 20% vs. 5% albumin (mean − 576 mL;P = 0.01). Twenty percent albumin was also associated with decreased chloride load vs. 4% albumin in critically ill patients. All 10 pre-/intraoperative studies evaluated 4–5% solutions; 14 studies evaluated 4–5% albumin in postoperative patients. Renal injury was reported in some studies; however, hydroxyethyl starch was associated with higher incidence vs. albumin. Importantly, 20% albumin preserved cumulative organ function in liver transplantation, and 25% albumin was more beneficial than saline in cardiac surgery patients. Thirty-two studies were performed in critically ill patients. Several studies reported increased risk of positive fluid balance and chloride load with hypo-oncotic albumin, whereas multiple benefits were associated with 20% albumin, including improved endothelial function and perfusion. Of 18 pediatric studies that evaluated ≤ 10% albumin, benefits such as correction of hypotension and improved cardiac output were noted. In conclusion, hyper-oncotic albumin solutions should be more routinely used to avoid potential risks associated with hypo-oncotic solutions.
Mathematical Foundations of Infinite-Dimensional Statistical Models
Authors: Giné Evarist , Nickl Richard
Published: March 2021

In nonparametric and high-dimensional statistical models, the classical Gauss–Fisher–Le Cam theory of the optimality of maximum likelihood estimators and Bayesian posterior inference does not apply, and new foundations and ideas have been developed in the past several decades. This book gives a coherent account of the statistical theory in infinite-dimensional parameter spaces. The mathematical foundations include self-contained 'mini-courses' on the theory of Gaussian and empirical processes, approximation and wavelet theory, and the basic theory of function spaces. The theory of statistical inference in such models - hypothesis testing, estimation and confidence sets - is presented within the minimax paradigm of decision theory. This includes the basic theory of convolution kernel and projection estimation, but also Bayesian nonparametrics and nonparametric maximum likelihood estimation. In a final chapter the theory of adaptive inference in nonparametric models is developed, including Lepski's method, wavelet thresholding, and adaptive inference for self-similar functions. Winner of the 2017 PROSE Award for Mathematics.
Evidence from the Dayao Paleolithic site, Inner Mongolia for human migration into arid northwest China during mid-Pleistocene interglacials
Authors: Ge Junyi , Wang Yinghua , Shan Mingchao , Feng Xingwu , Chen Fuyou , Wu Haibin , Li Qin , Zhou Xinying , Li Yan , Tang Ruiping , Olsen John W. , Deng Chenglong , Gao Xing
Published: March 2021

The Dayao Paleolithic site, located in Inner Mongolia on the eastern margin of China's vast northwestern drylands, was a lithic quarry-workshop utilized by Pleistocene human migrants through the region. Determining the age of this activity has previously yielded controversial results. Our magnetostratigraphic and OSL dating results suggest the two artifact-bearing paleosols are correlated with MIS 5 and 7, respectively. Correlating paleoclimatic data with marine δ18O records leads us to conclude that two sandy gravel layers containing many artifacts in the lower part of the Dayao sequence were formed during MIS 9 and 11, if not earlier. Our results reveal that the earliest human occupation at the Dayao site occurred before ca. 400 ka during a relatively warm and moist interglacial period, similar to several subsequent occupations, documenting the earliest and northernmost archaeological assemblage yet reported in China's arid northwest. We conclude that the northward and southward displacements of the East Asian summer monsoon rain belt during past interglacial-glacial cycles were responsible for the discontinuous human occupation detected at the Dayao site. The penetration of this precipitation regime into dryland ecologies via the Huanghe (Yellow River) Valley effectively created a corridor for hominin migration into China's arid northwest.
How to Understand What Passes All Understanding: Using the Documentary Papyri to Understand εἰρήνη in Paul
Authors: Dormandy Michael
Published: March 2021

In popular culture, the Pauline texts referring to ‘peace’ are illustrated by serene and tranquil scenes. I shall argue that to Paul's first readers, ‘peace’ evoked rather different images – military victories, arrests of criminals and the unloading of corn. I argue this because of how εἰρήνη is normally used in documentary papyri, that is personal letters, administrative documents and other non-literary written material. I explain my method and then present the papyrological evidence, including references to the various ‘peace-officials’. I argue that εἰρήνη meant something like ‘good order’. I use this insight to interpret Rom 5.1 and Phil 4.7.
Paul's Temporal Thinking: 2 Cor 2.14–7.4 as Paraenetic Autobiography
Authors: Engberg-Pedersen Troels
Published: March 2021

A precise temporal (and sometimes topographical) scheme is found behind Second Corinthians at three levels: (i) 1–7 (past: Ephesus → Macedonia), 8–9 (present: Macedonia), 10–13 (future: Macedonia → Corinth); (ii) 2.12–7.16 (Troas (2.12–13) → the Hellespont (2.14–7.4) → Macedonia (7.5–16)); (iii) 2.14–7.4. For (i)-(ii), see 1 Thess 1–3 and 2.17–3.10. For (iii), I detail this temporal structure: (a) 3.1–18 → 4.1–6; (b) 4.7–5.10 → 5.11–13; (c) 5.14–6.10 → 6.11–7.4, viz. (a) Paul's initial call and (b) his life in the present and future → his general missionary practice, including to ‘you’, and (c) his now directly addressing ‘you’ with strong paraenesis.
Fashioning Mark: Early Christian Discussions about the Scribe and Status of the Second Gospel
Authors: Moss Candida
Published: March 2021

This article examines early Christian theories about the identity and role of Mark as transmitter of Petrine tradition. Building upon recent work in classics, it argues that the identification of Mark as Peter's interpreter, the description of his composition as lacking order and his reported excellent memory would have led ancient readers of Papias to conclude that Mark was performing literate servile work. The positioning of Mark in this way strengthened claims about the accuracy of Mark's text.
Impact of Hydrostratigraphic Continuity on Brine‐to‐Freshwater Interface Dynamics: Implications From a Two‐Dimensional Parametric Study in an Arid and Endorheic Basin
Authors: McKnight S. V. , Boutt D. F. , Munk L. A.
Published: March 2021

Despite the prevalence of density‐dependent flow systems in the brine‐rich aquifers of arid climates and coastal aquifers, the impact of realistic geologic conditions on interface geometry and density‐dependent time‐sensitive dynamics remains poorly constrained. Salar de Atacama provides an analog for exploring interface dynamics in arid regions. A site‐specific two‐dimensional hydrostratigraphic interpretation is used to examine the dynamics of the brine‐to‐freshwater interface. With the same simulation framework and core data, a separate parametric series of hydraulic conductivity distributions with varying horizontal continuity provides a mechanistic explanation for observed dynamics. Comparing modeled interfaces and their sensitivity to perturbations in recharge in each realization yields insight into interface dynamics coupled with horizontal continuity in subsurface heterogeneity. Recharge fluctuation is introduced to each distribution following the interface reaching a dynamic steady state. Metrics for results evaluation include interface slope geometry, interface width, migration length, and response rate. Analyses suggest that the average slope of the modeled interface shallows by 0.01 and 0.05 m ⋅ m−1for an increase in continuity of highly permeable pathways by a factor of two and three, respectively. Increasing continuity also increases the overall response times and the variability in response. Results indicate that accurate representations of transient dynamics in modeling density‐dependent brine‐to‐freshwater interface dynamics requires the consideration of heterogeneity, as saline intrusion in the highest continuity group extends over twice as far on average and the modeled interface takes over 43% more time on average to reach a new dynamic steady state when compared to their homogeneous counterparts.
Mean Flow Direction Modulates Non‐Fickian Transport in a Heterogeneous Alluvial Aquifer‐Aquitard System
Authors: Pauloo Richard A. , Fogg Graham E. , Guo Zhilin , Henri Christopher V.
Published: March 2021

Regional‐scale groundwater quality degradation from nonpoint source pollution threatens the long‐term sustainability of major alluvial aquifer‐aquitard systems worldwide. Models are needed to simulate regionally upscaled transport processes in heterogeneous geology that produces non‐Fickian (anomalous) transport. In this investigation, we show the impact of nonhorizontal and nonvertical mean flow direction on non‐Fickian transport within a 3D, kilometer‐scale, typical alluvial aquifer‐aquitard system. Notably, vertical anisotropy in K and seasonal pumping and recharge can fundamentally change hydraulic gradients and shift the mean flow direction between mostly horizontal and mostly vertical flow. Detailed 3D flow and transport simulations under varying mean flow directions indicate that alterations to hydraulic gradients which control the mean flow direction can lead to increasingly non‐Fickian transport. Under mostly horizontal flow, diffusion and slow advection dominant low‐K facies slow mass transfer rates from low‐K material, and preferential flow along connected high‐K networks causes increased spatial spreading along the mean flow direction. Conversely, predominantly vertical flow caused by spatially distributed pumping and recharge shifts mass transfer processes in low‐K material from diffusion and slow advection dominant to advection dominant, resulting in vertically oriented particle trajectories that compactly migrate through high‐K and low‐K facies alike, and increasingly Fickian transport. Thus, mean flow direction transience driven by vertical anisotropy in K and seasonal pumping and recharge can create oscillating transport patterns, that range from persistently non‐Fickian to more Fickian. Results illustrate the regional‐scale hydrogeologic factors that explain why upscaled transport models fail to capture non‐Fickian effects resulting from mean flow direction transience
Characteristics of Meiyu Seen From Multiple Observational Analyses and Reanalyses
Authors: Tong Mingjun , Zheng Zhihai , Fu Qiang
Published: March 2021

This study examines characteristics of Meiyu during the Meiyu season from June 1 to July 31 for 1998–2017 using two observational analyses (i.e., Tropical Rainfall Measuring Mission [TRMM] and Global Precipitation Climatology Project [GPCP]) and four reanalysis data sets (i.e., Modern‐Era Retrospective Analysis for Research and Applications, Version 2 [MERRA2], ERA5, JRA55, and NCEP/DOE). The Meiyu mean precipitation from GPCP is slightly larger than TRMM but GPCP has smaller precipitation variance as compared with TRMM. MERRA2 and ERA5 are consistent with TRMM precipitation in terms of both mean and variance patterns, while JRA55 (NCEP/DOE) has smaller mean precipitation and variance in the middle and lower reaches of the Yangtze River in China (near southern Japan). For the interannual variability of the precipitation averaged over the Meiyu region, the correlation with TRMM from high to low is ranked by MERRA2, GPCP, JRA55, ERA5, and NCEP/DOE. For the Meiyu evolution, GPCP, MERRA2, ERA5, and JRA55 capture the gradual northward movement of the Meiyu belt from June 2 to July 10, as shown in TRMM, but NCEP/DOE does not. For the large‐scale meteorology conditions for the strong and weak Meiyu years, the relative humidity vertical profiles from the four reanalyses are analyzed. All reanalyses except NCEP/DOE show that the relative humidity is larger in the strong Meiyu years than that in the weak Meiyu years and relative humidity over Japan and South Korea is larger than that over the lower reaches of the Yangtze River. It is recommended that TRMM and MERRA2 reanalysis be used for the investigations of the Meiyu precipitation and variability and large‐scale conditions.
A monolithic single-chip point-of-care platform for metabolomic prostate cancer detection
Authors: Annese Valerio F. , Patil Samadhan B. , Hu Chunxiao , Giagkoulovits Christos , Al-Rawhani Mohammed A. , Grant James , Macleod Martin , Clayton David J. , Heaney Liam M. , Daly Ronan , Accarino Claudio , Shah Yash D. , Cheah Boon C. , Beeley James , Evans Thomas R. Jeffry , Jones Robert , Barrett Michael P. , Cumming David R. S.
Published: March 2021

There is a global unmet need for rapid and cost-effective prognostic and diagnostic tools that can be used at the bedside or in the doctor’s office to reduce the impact of serious disease. Many cancers are diagnosed late, leading to costly treatment and reduced life expectancy. With prostate cancer, the absence of a reliable test has inhibited the adoption of screening programs. We report a microelectronic point-of-care metabolite biomarker measurement platform and use it for prostate cancer detection. The platform, using an array of photodetectors configured to operate with targeted, multiplexed, colorimetric assays confined in monolithically integrated passive microfluidic channels, completes a combined assay of 4 metabolites in a drop of human plasma in under 2 min. A preliminary clinical study using l-amino acids, glutamate, choline, and sarcosine was used to train a cross-validated random forest algorithm. The system demonstrated sensitivity to prostate cancer of 94% with a specificity of 70% and an area under the curve of 0.78. The technology can implement many similar assay panels and hence has the potential to revolutionize low-cost, rapid, point-of-care testing.
SRSF1 inhibits autophagy through regulating Bcl-x splicing and interacting with PIK3C3 in lung cancer
Authors: Lv Yuesheng , Zhang Wenjing , Zhao Jinyao , Sun Bing , Qi Yangfan , Ji Haoyu , Chen Chaoqun , Zhang Jinrui , Sheng Junxiu , Wang Taishu , Dominguez Daniel , Liu Han , Liu Quentin , Meng Songshu , Li Xiaoling , Wang Yang
Published: March 2021

Alternative splicing is a critical process to generate protein diversity. However, whether and how alternative splicing regulates autophagy remains largely elusive. Here we systematically identify the splicing factor SRSF1 as an autophagy suppressor. Specifically, SRSF1 inhibits autophagosome formation by reducing the accumulation of LC3-II and numbers of autophagosomes in different cell lines. Mechanistically, SRSF1 promotes the splicing of the long isoform of Bcl-x that interacts with Beclin1, thereby dissociating the Beclin1-PIK3C3 complex. In addition, SRSF1 also directly interacts with PIK3C3 to disrupt the interaction between Beclin1 and PIK3C3. Consequently, the decrease of SRSF1 stabilizes the Beclin1 and PIK3C3 complex and activates autophagy. Interestingly, SRSF1 can be degraded by starvation- and oxidative stresses-induced autophagy through interacting with LC3-II, whereas reduced SRSF1 further promotes autophagy. This positive feedback is critical to inhibiting Gefitinib-resistant cancer cell progression both in vitro and in vivo. Consistently, the expression level of SRSF1 is inversely correlated to LC3 level in clinical cancer samples. Our study not only provides mechanistic insights of alternative splicing in autophagy regulation but also discovers a new regulatory role of SRSF1 in tumorigenesis, thereby offering a novel avenue for potential cancer therapeutics.
Epigenetic regulation of p62/SQSTM1 overcomes the radioresistance of head and neck cancer cells via autophagy-dependent senescence induction
Authors: Lee Myungjin , Nam Hae Yun , Kang Hee-Bum , Lee Won Hyeok , Lee Geun-Hee , Sung Gi-Jun , Han Myung Woul , Cho Kyung-Ja , Chang Eun-Ju , Choi Kyung-Chul , Kim Seong Who , Kim Sang Yoon
Published: March 2021

Tumors are composed of subpopulations of cancer cells with functionally distinct features. Intratumoral heterogeneity limits the therapeutic effectiveness of cancer drugs. To address this issue, it is important to understand the regulatory mechanisms driving a subclonal variety within a therapy-resistant tumor. We identified tumor subclones of HN9 head and neck cancer cells showing distinct responses to radiation with different levels of p62 expression. Genetically identical grounds but epigenetic heterogeneity of the p62 promoter regions revealed that radioresistant HN9-R clones displayed low p62 expression via the creation of repressive chromatin architecture, in which cooperation between DNMT1 (DNA methyltransferases 1) and HDAC1 (histone deacetylases 1) resulted in DNA methylation and repressive H3K9me3 and H3K27me3 marks in the p62 promoter. Combined inhibition of DNMT1 and HDAC1 by genetic depletion or inhibitors enhanced the suppressive effects on proliferative capacity and in vivo tumorigenesis following irradiation. Importantly, ectopically p62-overexpressed HN9-R clones increased the induction of senescence along with p62-dependent autophagy activation. These results demonstrate the heterogeneous expression of p62 as the key component of clonal variation within a tumor against irradiation. Understanding the epigenetic diversity of p62 heterogeneity among subclones allows for improved identification of the functional state of subclones and provides a novel treatment option to resolve resistance to current therapies.
A neural m6A/Ythdf pathway is required for learning and memory in Drosophila
Authors: Kan Lijuan , Ott Stanislav , Joseph Brian , Park Eun Sil , Dai Wei , Kleiner Ralph E. , Claridge-Chang Adam , Lai Eric C.
Published: March 2021

Epitranscriptomic modifications can impact behavior. Here, we used Drosophila melanogaster to study N6-methyladenosine (m6A), the most abundant modification of mRNA. Proteomic and functional analyses confirm its nuclear (Ythdc1) and cytoplasmic (Ythdf) YTH domain proteins as major m6A binders. Assays of short term memory in m6A mutants reveal neural-autonomous requirements of m6A writers working via Ythdf, but not Ythdc1. Furthermore, m6A/Ythdf operate specifically via the mushroom body, the center for associative learning. We map m6A from wild-type and Mettl3 mutant heads, allowing robust discrimination of Mettl3-dependent m6A sites that are highly enriched in 5’ UTRs. Genomic analyses indicate that Drosophila m6A is preferentially deposited on genes with low translational efficiency and that m6A does not affect RNA stability. Nevertheless, functional tests indicate a role for m6A/Ythdf in translational activation. Altogether, our molecular genetic analyses and tissue-specific m6A maps reveal selective behavioral and regulatory defects for the Drosophila Mettl3/Ythdf pathway.
Kinesin-1 activity recorded in living cells with a precipitating dye
Authors: Angerani Simona , Lindberg Eric , Klena Nikolai , Bleck Christopher K. E. , Aumeier Charlotte , Winssinger Nicolas
Published: March 2021

Kinesin-1 is a processive motor protein that uses ATP-derived energy to transport a variety of intracellular cargoes toward the cell periphery. The ability to visualize and monitor kinesin transport in live cells is critical to study the myriad of functions associated with cargo trafficking. Herein we report the discovery of a fluorogenic small molecule substrate (QPD-OTf) for kinesin-1 that yields a precipitating dye along its walking path on microtubules (MTs). QPD-OTf enables to monitor native kinesin-1 transport activity in cellulo without external modifications. In vitro assays show that kinesin-1 and MTs are sufficient to yield fluorescent crystals; in cells, kinesin-1 specific transport of cargo from the Golgi appears as trails of fluorescence over time. These findings are further supported by docking studies, which suggest the binding of the activity-based substrate in the nucleotide binding site of kinesin-1.
Point-of-care bulk testing for SARS-CoV-2 by combining hybridization capture with improved colorimetric LAMP
Authors: Bokelmann Lukas , Nickel Olaf , Maricic Tomislav , Pääbo Svante , Meyer Matthias , Borte Stephan , Riesenberg Stephan
Published: March 2021

Efforts to contain the spread of SARS-CoV-2 have spurred the need for reliable, rapid, and cost-effective diagnostic methods which can be applied to large numbers of people. However, current standard protocols for the detection of viral nucleic acids while sensitive, require a high level of automation and sophisticated laboratory equipment to achieve throughputs that allow whole communities to be tested on a regular basis. Here we present Cap-iLAMP (capture and improved loop-mediated isothermal amplification) which combines a hybridization capture-based RNA extraction of gargle lavage samples with an improved colorimetric RT-LAMP assay and smartphone-based color scoring. Cap-iLAMP is compatible with point-of-care testing and enables the detection of SARS-CoV-2 positive samples in less than one hour. In contrast to direct addition of the sample to improved LAMP (iLAMP), Cap-iLAMP prevents false positives and allows single positive samples to be detected in pools of 25 negative samples, reducing the reagent cost per test to ~1 Euro per individual.
Drebrin controls scar formation and astrocyte reactivity upon traumatic brain injury by regulating membrane trafficking
Authors: Schiweck Juliane , Murk Kai , Ledderose Julia , Münster-Wandowski Agnieszka , Ornaghi Marta , Vida Imre , Eickholt Britta J.
Published: March 2021

The brain of mammals lacks a significant ability to regenerate neurons and is thus particularly vulnerable. To protect the brain from injury and disease, damage control by astrocytes through astrogliosis and scar formation is vital. Here, we show that brain injury in mice triggers an immediate upregulation of the actin-binding protein Drebrin (DBN) in astrocytes, which is essential for scar formation and maintenance of astrocyte reactivity. In turn, DBN loss leads to defective astrocyte scar formation and excessive neurodegeneration following brain injuries. At the cellular level, we show that DBN switches actin homeostasis from ARP2/3-dependent arrays to microtubule-compatible scaffolds, facilitating the formation of RAB8-positive membrane tubules. This injury-specific RAB8 membrane compartment serves as hub for the trafficking of surface proteins involved in astrogliosis and adhesion mediators, such as β1-integrin. Our work shows that DBN-mediated membrane trafficking in astrocytes is an important neuroprotective mechanism following traumatic brain injury in mice.
A single inverse-designed photonic structure that performs parallel computing
Authors: Camacho Miguel , Edwards Brian , Engheta Nader
Published: March 2021

In the search for improved computational capabilities, conventional microelectronic computers are facing various problems arising from the miniaturization and concentration of active electronics. Therefore, researchers have explored wave systems, such as photonic or quantum devices, for solving mathematical problems at higher speeds and larger capacities. However, previous devices have not fully exploited the linearity of the wave equation, which as we show here, allows for the simultaneous parallel solution of several independent mathematical problems within the same device. Here we demonstrate that a transmissive cavity filled with a judiciously tailored dielectric distribution and embedded in a multi-frequency feedback loop can calculate the solutions of a number of mathematical problems simultaneously. We design, build, and test a computing structure at microwave frequencies that solves two independent integral equations with any two arbitrary inputs and also provide numerical results for the calculation of the inverse of four 5 x 5 matrices.
Improving gene function predictions using independent transcriptional components
Authors: Urzúa-Traslaviña Carlos G. , Leeuwenburgh Vincent C. , Bhattacharya Arkajyoti , Loipfinger Stefan , van Vugt Marcel A. T. M. , de Vries Elisabeth G. E. , Fehrmann Rudolf S. N.
Published: March 2021

The interpretation of high throughput sequencing data is limited by our incomplete functional understanding of coding and non-coding transcripts. Reliably predicting the function of such transcripts can overcome this limitation. Here we report the use of a consensus independent component analysis and guilt-by-association approach to predict over 23,000 functional groups comprised of over 55,000 coding and non-coding transcripts using publicly available transcriptomic profiles. We show that, compared to using Principal Component Analysis, Independent Component Analysis-derived transcriptional components enable more confident functionality predictions, improve predictions when new members are added to the gene sets, and are less affected by gene multi-functionality. Predictions generated using human or mouse transcriptomic data are made available for exploration in a publicly available web portal.