bluuebunny/crossref_metadata_2025 huggingface dataset:
Weak tradeoff between xylem hydraulic efficiency and safety: climatic seasonality matters
Authors: Liu Hui , Ye Qing , Gleason Sean M. , He Pengcheng , Yin Deyi
Published: October 2020

A classic theory proposes that plant xylem cannot be both highly efficient in water transport and resistant to embolism, and therefore a hydraulic efficiency–safety trade‐off should exist. However, the trade‐off is weak, and many species exhibit both low efficiency and low safety, falling outside of the expected trade‐off space. It remains unclear under what climatic conditions these species could maintain competitive fitness.

We compiled hydraulic efficiency and safety traits for 682 observations of 499 woody species from 178 sites world‐wide and measured the position of each observation within the proposed trade‐off space.

For both angiosperms and gymnosperms, observations from sites with high climatic seasonality, especially precipitation seasonality, tended to have higher hydraulic safety and efficiency than observations from sites with low seasonality. Specifically, high vapour pressure deficit, high solar radiation, and low precipitation during the wet season were driving factors.

Strong climatic seasonality and drought in both dry and wet seasons appear to be ecological filters that select for species with co‐optimized safety and efficiency, whereas the opposite environmental conditions may allow the existence of plants with low efficiency and safety.
Trees as net sinks for methane (CH4) and nitrous oxide (N2O) in the lowland tropical rain forest on volcanic Réunion Island
Authors: Machacova Katerina , Borak Libor , Agyei Thomas , Schindler Thomas , Soosaar Kaido , Mander Ülo , Ah‐Peng Claudine
Published: October 2020

Trees are known to emit methane (CH4) and nitrous oxide (N2O), with tropical wetland trees being considerable CH4 sources. Little is known about CH4 and especially N2O exchange of trees growing in tropical rain forests under nonflooded conditions.

We determined CH4 and N2O exchange of stems of six dominant tree species, cryptogamic stem covers, soils and volcanic surfaces at the start of the rainy season in a 400‐yr‐old tropical lowland rain forest situated on a basaltic lava flow (Réunion Island). We aimed to understand the unknown role in greenhouse gas fluxes of these atypical tropical rain forests on basaltic lava flows.

The stems studied were net sinks for atmospheric CH4 and N2O, as were cryptogams, which seemed to be co‐responsible for the stem uptake. In contrast with more commonly studied rain forests, the soil and previously unexplored volcanic surfaces consumed CH4. Their N2O fluxes were negligible.

Greenhouse gas uptake potential by trees and cryptogams constitutes a novel and unique finding, thus showing that plants can serve not only as emitters, but also as consumers of CH4 and N2O. The volcanic tropical lowland rain forest appears to be an important CH4 sink, as well as a possible N2O sink.
RNA polymerase II associated proteins regulate stomatal development through direct interaction with stomatal transcription factors in Arabidopsis thaliana
Authors: Chen Liang , Zhao Mingfeng , Wu Zhongliang , Chen Sicheng , Rojo Enrique , Luo Jiangwei , Li Ping , Zhao Lulu , Chen Yan , Deng Jianming , Cheng Bo , He Kai , Gou Xiaoping , Li Jia , Hou Suiwen
Published: October 2020

RNA polymerase II (Pol II) associated proteins (RPAPs) have been ascribed diverse functions at the cellular level; however, their roles in developmental processes in yeasts, animals and plants are very poorly understood.

Through screening for interactors of NRPB3, which encodes the third largest subunit of Pol II, we identified RIMA, the orthologue of mammalian RPAP2. A combination of genetic and biochemical assays revealed the role of RIMA and other RPAPs in stomatal development in Arabidopsis thaliana.

We show that RIMA is involved in nuclear import of NRPB3 and other Pol II subunits, and is essential for restraining division and for establishing cell identity in the stomatal cell lineage. Moreover, plant RPAPs IYO/RPAP1 and QQT1/RPAP4, which interact with RIMA, are also crucial for stomatal development. Importantly, RIMA and QQT1 bind physically to stomatal transcription factors SPEECHLESS, MUTE, FAMA and SCREAMs.

The RIMA‐QQT1‐IYO complex could work together with key stomatal transcription factors and Pol II to drive cell fate transitions in the stomatal cell lineage. Direct interactions with stomatal transcription factors provide a novel mechanism by which RPAP proteins may control differentiation of cell types and tissues in eukaryotes.
Kasulis’ intimacy/integrity heuristic and epistemological pluralism in nursing
Authors: McCaffrey Graham
Published: October 2020

Epistemological pluralism is a recognized feature of nursing knowledge, which embraces both objective, scientific knowledge and situated knowledge that include subjective experience, values and affect, and is encountered in relationship. While there is a lively literature about describing and validating the need for pluralism in nursing's knowledge base, there has been less discussion of how to work with and across different kinds of knowing that are used in practice. In this paper, I describe Kasulis’ heuristic framework for understanding more clearly what is entailed in different kinds of knowledge, and what some of their advantages and disadvantages might be. The framework was created by Thomas Kasulis, an American scholar of Japanese philosophy who identified broad orientations in Asian and Western philosophies that he characterized as ‘intimacy’ and ‘integrity’, respectively. Kasulis emphasized that his framework is a heuristic, a tool for making distinctions more clearly between different styles of thinking, that can manifest not only between cultural traditions from different parts of the world, but also between subcultures within one of the dominant orientations. He breaks his two orientations down by five distinguishing categories of objectivity, relating, affect, embodiment and transparency. In this paper, each category is described and discussed in relation to aspects of nursing knowledge. Looking at different epistemological viewpoints in this way helps to clarify their differences, and to explain the difficulty of reading across them, when they entail basic assumptions that are not commensurable with each other. Kasulis’ framework offers a new way of reading across viewpoints commonly seen in the epistemological pluralism of nursing. It is a tool that can sharpen critical discernment about what is at stake, what can be gained, and what might get missed while operating in either the intimacy or integrity orientation.
Continued versus interrupted direct oral anticoagulation for cardiac electronic device implantation: A systematic review
Authors: Mendoza Pablo A. , Narula Sukrit , McIntyre William F. , Whitlock Richard P. , Birnie David H. , Healey Jeff S. , Belley‐Côté Emilie P.
Published: October 2020

Background

Many patients undergoing cardiac device implantation are taking direct oral anticoagulation (DOAC). Continuing DOAC during device implantation may increase periprocedural bleeding risk; however, interrupting DOACs may increase thromboembolic risk.

Objective

To compare the incidence of clinically significant pocket hematoma and thromboembolism in patients who have their DOAC continued or interrupted for cardiac device implantation.

Methods

We searched MEDLINE, EMBASE, and randomized controlled trial (CENTRAL) until December 2019 and included randomized controlled trials (RCTs) and observational studies that compared outcomes after continuing or interrupting DOAC during cardiac device implantation. Independently and in duplicate, reviewers screened titles, abstracts, and full text of potentially eligible studies. They then evaluated risk of bias and abstracted data. RCT data were pooled using a fixed‐effect model. Quality of evidence was assessed using grading of recommendations assessment, development and evaluation (GRADE).

Results

Two RCTs, representing 763 patients, and three observational studies met eligibility criteria. In RCTs, continuing DOAC for device implantation compared to interrupting DOAC resulted in no significant difference in clinically significant pocket hematoma (2.1% vs 1.8%; RR 1.15; 95% CI 0.44‐3.05) or thromboembolism (0.03% vs 0.03%; RR 1.02; 95% CI 0.06‐16.21). Quality of evidence for both outcomes was moderate due to imprecision. Observational studies showed similar results.

Conclusions

Continuing DOACs for device implantation results in little to no difference in the incidence of clinically significant pocket hematoma or thromboembolism. Given the ease of stopping and restarting DOACs, interrupting DOACs may be the preferred strategy for most patients. However, whenever continuous therapeutic anticoagulation is desired, DOAC continuation should be preferred over bridging with parenteral anticoagulation.
Seasonal and diurnal trends in progressive isotope enrichment along needles in two pine species
Authors: Kannenberg Steven A. , Fiorella Richard P. , Anderegg William R. L. , Monson Russell K. , Ehleringer James R.
Published: October 2020

The Craig–Gordon type (C–G) leaf water isotope enrichment models assume a homogeneous distribution of enriched water across the leaf surface, despite observations that Δ18O can become increasingly enriched from leaf base to tip. Datasets of this ‘progressive isotope enrichment’ are limited, precluding a comprehensive understanding of (a) the magnitude and variability of progressive isotope enrichment, and (b) how progressive enrichment impacts the accuracy of C–G leaf water model predictions. Here, we present observations of progressive enrichment in two conifer species that capture seasonal and diurnal variability in environmental conditions. We further examine which leaf water isotope models best capture the influence of progressive enrichment on bulk needle water Δ18O. Observed progressive enrichment was large and equal in magnitude across both species. The magnitude of this effect fluctuated seasonally in concert with vapour pressure deficit, but was static in the face of diurnal cycles in meteorological conditions. Despite large progressive enrichment, three variants of the C–G model reasonably successfully predicted bulk needle Δ18O. Our results thus suggest that the presence of progressive enrichment does not impact the predictive success of C–G models, and instead yields new insight regarding the physiological and anatomical mechanisms that cause progressive isotope enrichment.
The existential spatiality of rebellion: Insubordination, counter‐conduct, and places
Authors: Szaló Csaba
Published: October 2020

This article reviews the current discourse on urban struggles to bring to the surface strategies of interpretation, which deal with theoretical concerns insinuated by the situated existence of struggling subjects. The first part, concentrating on the domain of “negative places,” contrasts interpretive strategies distinguished by their orientation to the phenomena of local solidarities, alternatively, solidarities organized by collective projects. The second part turns from “negative places” to “other places” to consider the strategy of interpretation operating with the concept of affective solidarities. The article argues for a critical reinterpretation of affective solidarities in reference to Foucault's idea of “other places” to disclose how the disobedient subject's transfiguration into collective subjects of solidarity is entwined with the diversity of modes in which the corporeal existence of subjects is situated in the world.
Envisioning my mathematics classroom: Validating the Draw‐a‐Mathematics‐Teacher‐Test Rubric
Authors: Utley Juliana , Reeder Stacy , Redmond‐Sanogo Adrienne
Published: October 2020

Teachers need the opportunity to reflect, rethink, and adapt as they continually develop their image of their role in their mathematics classrooms. Thus, the purpose of this research was to examine how the Draw‐a‐Mathematics‐Teacher‐Test (DAMTT) and rubric can be used to assess preservice elementary teachers’ images of and beliefs about their future mathematics classrooms and validate the Draw‐a‐Math‐TeacherTest‐Rubric (DAMTT‐R). Results suggest that the DAMTT‐R is a valid measure and yields consistent results. Additionally, analysis of preservice elementary teachers’ (PETs) DAMTT revealed that only slightly more than one‐third (36.9%) drew a picture and described their classroom in such a way that it reflected beliefs aligned with student‐centered pedagogic practices. While mathematics educators may aim for the majority of PETs to leave their programs having developed beliefs aligned with and supportive of student‐centered pedagogic practices, the results of this study revealed that 25% of PETs held beliefs that align with teacher‐centered pedagogic practices. Lastly, 38.1% of the PETs reflected beliefs about their pedagogic practices, as measured by the DAMTT and the DAMTT‐R, aligned with a transition between teacher‐centered and student‐centered.
Advocacy in action: Medical student reflections of an experiential curriculum
Authors: Daya Sneha , Choi Nancy , Harrison James D. , Lai Cindy J.
Published: October 2020

Introduction

Patient advocacy is a core value in medical education. Although students learn about social determinants of health (SDH) in the pre‐clinical years, applying this knowledge to patients during clerkship rotations is not prioritized. Physicians must be equipped to address social factors that affect health and recognize their roles as patient advocates to improve care and promote health equity. We created an experience‐based learning curriculum called Advocacy in Action (AiA) to promote the development and application of health advocacy knowledge and skills during an Internal Medicine (IM) clerkship rotation.

Methods

Sixty‐six students completed a mandatory curriculum, including an introductory workshop on SDH and patient advocacy using tools for communication, counselling and collaboration skills. They then actively participated in patient advocacy activities, wrote about their experience and joined a small group debriefing about it. Forty‐nine written reflections were reviewed for analysis of the impact of this curriculum on student perspectives.

Results

Written reflections had prominent themes surrounding advocacy skills development, meaningful personal experiences, interprofessional dynamics in patient advocacy and discovery of barriers to optimal patient care.

Discussion

AiA is a novel method to apply classroom knowledge of SDH to the clinical setting in order to incorporate advocacy in daily patient care. Students learned about communication with patients, working with interprofessional team members to create better health outcomes and empathy/compassion from this curriculum. It is important to utilize experiential models of individual patient‐level advocacy during clerkships so that students can continuously reflect on and integrate advocacy into their future careers.
Firm productivity and functional specialisation
Authors: de Vries Gaaitzen , Jiang Aobo , Lemmers Oscar , Wei Shang‐Jin
Published: October 2020

This paper examines the relation between productivity and specialisation of firms in business functions. We distinguish between specialisation in R&D, fabrication and marketing based on the firm's employment composition over these functions using unique survey data of Dutch firms. Our results suggest that firms specialised in R&D and marketing are significantly more productive compared to firms specialised in fabrication. We find that measures of upstreamness based on input–output tables do not significantly relate to firm productivity and are uncorrelated to measures of functional specialisation.
Atypical ocular Chelonoid herpesvirus manifestations in a captive Loggerhead turtle (Caretta caretta)
Authors: Oriá Arianne P. , Silva Danielle N. , Raposo Ana Cláudia , Estrela‐Lima Alessandra , Pires Thaís T. , Gattamorta Marco A. , Zamana Roberta R. , Matushima Eliana R. , Ofri Ron
Published: October 2020

A captive loggerhead turtle (Caretta caretta) of unknown sex, 3 years of age, presented with bilateral mucoid secretions, severe chemosis, conjunctival hyperemia, and globe retraction. The animal was evaluated ophthalmologically and systemically, and hematological, microbiological, and conjunctival cytological and biopsy samples were collected for complementary diagnosis. The histopathological examination showed amphophilic intranuclear inclusions associated with severe inflammatory infiltrate. The diagnosis of Chelonid alphaherpesvirus 5 (ChAHV 5) was confirmed with end point PCR. Following systemic treatment with L‐lysine, acyclovir and vitamin A, the ocular signs resolved. No amphophilic intranuclear inclusions were seen in a follow‐up biopsy 5 months later, and there has been no recurrence of clinical ophthalmic signs during a 4‐year follow‐up. It is suggested that ChAHV 5 be considered as a differential diagnosis in captive marine turtles that present for conjunctival disease other than fibropapillomatosis.
Efficient soluble anionic dye removal and antimicrobial properties of ZnO embedded‐ Polyphenylsulfone membrane
Authors: Shukla Arun Kumar , Alam Javed , Ali Fekri Abdulraqeb Ahmed , Alhoshan Mansour
Published: October 2020

As a result of the involvement of pollutants in water, there is the need to develop a facile and effective membrane technology that can not only treat dyes, but also kill bacteria in wastewater. In this work, a facile strategy is proposed for the preparation of a nanostructured hybrid membrane based on Polyphenylsulfone containing different ZnO nanoparticle contents. The results confirm that ZnO nanoparticle plays a key role in achieving the efficient removal of soluble anionic dyes from aqueous solution. The optimal membrane exhibits excellent dye rejection approximately 98% with impeccable water flux 19 L/m2h; and exhibits antifouling properties, presenting dye‐fouled flux recovery ratio> 90%. Moreover, an investigation of antibacterial properties of the material showed that the nanostructured hybrid membrane has good antibacterial properties (nearly 6.2 and 6.8) against both Escherichia coli and Staphylococcus aureus. Therefore, the proposed nanostructured hybrid membrane may provide an efficient for treating dye and bacteria in wastewater.
E-Learners’ Challenges and Coping Strategies in Interactive and Collaborative e-Learning in Kenya
Authors: Kibuku Rachael Njeri , Ochieng Daniel Orwa , Wausi Agnes Nduku
Published: October 2020

Some universities in Kenya have taken up e-learning to flexibly deliver learning and bridge the educational access gap. Despite the benefits that e-learning offers to the e-learners, there are challenges that they must cope with. The aim of this paper is to present the challenges that emerged from a research that was undertaken in two Institutions of Higher Learning (IHLs). It also presents the coping strategies that e-learners used to overcome the challenges. The research used the constructivist version of Grounded Theory (GT) methodology. It used in-depth interviews and participant observations to gather data from the e-learners, e-tutors, e-learning managers and e-learning platforms. Therefore, the research yielded qualitative data which was analyzed using Atlas.ti software. Data was analyzed thematically to establish the patterns of challenges and the equivalent coping strategies. The results are presented using the Gioia technique and the discussion used the vignettes technique from participants in order to preserve their voice. The challenges that emerged relate to: e-content, coursework, internet access, e-learning technology, Information and Communication Technology (ICT) skills and training, interaction and collaboration, personal issues, teaching of Science, Technology, Engineering and Mathematics (STEM) courses and the tutorials. Recommendations on how to tackle these challenges have also been suggested. An understanding of these challenges is important to the e-learning players so that they can adopt interventions to mitigate them and hence improve interaction and collaboration. The results presented in this paper are part of the larger research whose main objective was to develop an e-learning theory for interaction and collaboration.
The acute effect of resistance exercise on limb blood flow
Authors: Thomas Kate N. , Kissling Lorenz S. , Gibbons Travis D. , Akerman Ashley P. , van Rij Andre M. , Cotter James D.
Published: October 2020

New Findings

What is the central question of this study?

How does resistance exercise affect peripheral haemodynamics in the active and inactive limb?

What is the main finding and its importance?

Preliminary data indicate that resistance exercise increases flow and shear rate in the active limb transiently. The same exercise has minimal, short‐lasting influence on peripheral haemodynamics in the inactive limb, but further research is required to elaborate on resistance exercise‐mediated changes in vascular function in active and inactive limbs.

Current evidence indicates that to achieve maximum health benefits, regular resistance exercise should be a key component of structured physical activity. Several studies have revealed that regular resistance exercise may be associated with impaired vascular function, although this finding is inconsistent. Proposed explanations for impairment include substantial increases in blood pressure and increased retrograde blood flow in active limbs promoted by resistance exercise. However, few studies have examined the acute haemodynamics of resistance exercise in active – and even fewer in inactive – limbs. The purpose of this study was to characterise the haemodynamic responses in peripheral arteries in active and inactive limbs in response to resistance exercise using upper and lower limbs. Ten participants (five male, five female) familiar with resistance training performed three sets of 10 isotonic repetitions of right‐sided bicep curls or knee extensions on separate days. Blood flow, shear rate and muscle oxygenation in the active and inactive limb, and blood pressure were measured before and for 3 min after each set. Blood flow increased in response to resistance exercise in the active limb (∼8‐fold and ∼6‐fold for the upper and lower limb respectively), with concurrent significant increases in mean and antegrade shear rate. In the inactive limb, blood flow more than doubled for both upper and lower limb exercise, transiently, with no significant change in retrograde shear rate. These acute blood flow profiles following resistance exercise are not indicative of long‐term vessel impairment based on current understanding of blood flow and shear stress patterns.
The Use of Partial Stability in the Analysis of Interconnected Systems
Authors: Wang Bo , Ashrafiuon Hashem , Nersesov Sergey G.
Published: October 2020

In this paper, we develop sufficient conditions for uniform asymptotic stability of interconnected dynamical systems that are not in cascade form. We show that the stability analysis of a two-subsystem interconnection can be reduced to ensuring the stability of the first nonisolated subsystem with respect to its own state vector (partial stability) and the stability of the isolated second subsystem. In addition, based on the above results, we provide a control design framework for nonlinear systems where the control objective reduces to stabilization of only a part of the system state while guaranteeing the stability for the entire state of the system. We validate the efficacy of the proposed control framework via simulations and experiments using the wheeled mobile robot platform.
Extremum Seeking for Traffic Congestion Control With a Downstream Bottleneck
Authors: Yu Huan , Koga Shumon , Oliveira Tiago Roux , Krstic Miroslav
Published: October 2020

This paper develops boundary control for freeway traffic with a downstream bottleneck. Traffic on a freeway segment with capacity drop at outlet of the segment is a common phenomenon that leads to traffic bottleneck problem. The capacity drop can be caused by lane-drop, hills, tunnel, bridge, or curvature on the road. If incoming traffic flow remains unchanged, traffic congestion forms upstream of the bottleneck since the upstream traffic demand exceeds its capacity. Therefore, it is important to regulate the incoming traffic flow of the segment to avoid overloading the bottleneck area. Traffic densities on the freeway segment are described with the Lighthill–Whitham–Richards (LWR) macroscopic partial differential equation (PDE) model. The incoming flow at the inlet of the freeway segment is controlled so that the optimal density that maximizes the outgoing flow is reached and the traffic congestion upstream of the bottleneck is mitigated. The density and traffic flow relation at the bottleneck area, usually described with fundamental diagram, is considered to be unknown. We tackle this problem using extremum seeking (ES) control with delay compensation for the LWR PDE. ES control, a nonmodel-based approach for real-time optimization, is adopted to find the optimal density for the unknown fundamental diagram. A predictor feedback control design is proposed to compensate the delay effect of traffic dynamics in the freeway segment. In the end, simulation results are obtained to validate a desired performance of the controller on the nonlinear LWR model with an unknown fundamental diagram.
Multistage Time-Optimal Control for Synchronization Process in Electric-Driven Mechanical Transmission With Angle Alignment Considering Torque Response Process
Authors: Lu Ziwang , Tian Guangyu , Onori Simona
Published: October 2020

The synchronization process takes up almost one half of the time of the gear-shifting process, and also influences the impacts between the sleeve and the gear ring. To avoid impacts and reduce time duration, a time-optimal control strategy with angle alignment is necessary for the synchronization process. Moreover, to be better accord with practice, the motor torque response process should be taken into account. The parameters in the torque response process depend on control commands, which makes the control problem a multistage one. To solve these issues, a rule-based control strategy is extracted from the dynamic programming (DP) solution of the multistage time-optimal control problem. To obtain this strategy, the dynamic model for the synchronization process with a modified Sigmoid model to precisely depict the torque response process is first solved. Then, the control problem is formulated as a multistage time-optimal control problem with three states and solved by DP. Based on the DP results, a three-stage and a four-stage rule-based control strategies are extracted for normal operation situation and startup situation, respectively. Finally, through comparative studies, the proposed rule-based control strategy can eliminate the speed difference and angle difference simultaneously with almost the same time of the bang–bang control, while the bang–bang control cannot obtain the zero terminals. Moreover, the proposed control strategy only takes 20 ms more than the pure speed synchronization control in the worst case. It would decrease when the initial speed difference increases.
Ru(0001) and SiO2/Ru(0001): XPS study
Authors: Khaniya Asim , Ezzat Sameer , Cumston Quintin , Coffey Kevin R. , Kaden William E.
Published: October 2020

X-ray photoelectron spectroscopy (XPS) is used to analyze the chemistry of the Ru(0001) film surface and the Ru/SiO2 interfacial region at different annealing conditions. The XPS spectra are collected under ultrahigh vacuum (base pressure of ∼5 × 10−10 Torr) condition using a SPECS electron spectrometer with a PHOIBOS 100 hemispherical energy analyzer and an XR 50 Al Kα x-ray source (1486.67 eV). High-resolution spectra of O 1s, Ru 3d/C 1s, and Si 2p together with survey scans are presented. The presence of 1 × 1 low energy diffraction pattern, collected from a 950 °C Ar/H2 step-annealed Ru(0001) sample, confirms the hexagonal periodicity of Ru(0001) surfaces.
Do “brassy” sounding musical instruments need increased safe distancing requirements to minimize the spread of COVID-19?
Authors: Moore Thomas R. , Cannaday Ashley E.
Published: October 2020

Brass wind instruments with long sections of cylindrical pipe, such as trumpets and trombones, sound “brassy” when played at a fortissimo level due to the generation of a shock front in the instrument. It has been suggested that these shock fronts may increase the spread of COVID-19 by propelling respiratory particles containing the SARS-CoV-2 virus several meters due to particle entrainment in the low pressure area behind the shocks. To determine the likelihood of this occurring, fluorescent particles, ranging in size from 10–50 μm, were dropped into the shock regions produced by a trombone, a trumpet, and a shock tube. Preliminary results indicate that propagation of small airborne particles by the shock fronts radiating from brass wind instruments is unlikely.
The ‘bat man’ tackles COVID-19
Authors: Kupferschmidt Kai
Published: October 2020

After a career investigating why so many viruses come from bats, Linfa Wang eyes a new challenge.
Disgraced researchers can still reap drug industry payouts
Authors: Piller Charles
Published: October 2020

After disqualification for misconduct, some doctors reap vast sums for teaching or consulting.
A high-performance solid-state electrocaloric cooling system
Authors: Wang Yunda , Zhang Ziyang , Usui Tomoyasu , Benedict Michael , Hirose Sakyo , Lee Joseph , Kalb Jamie , Schwartz David
Published: October 2020

Competitive cooling with capacitors

Current large-scale cooling devices use vapor compression refrigeration. The efficiency of air conditioners has been optimized, but they can be noisy and rely on problematic greenhouse gases. Two groups now present designs for electrocaloric cooling using lead scandium tantalate capacitors that change temperature under an electric field. Y. Wang
et al.
obtained a very large heat flux using only solid materials and a cooling fan to remove heat from their device. Torello
et al.
used fluids for heat transfer, leading to a very large temperature difference between the hot side and the cold side. The new designs demonstrate the potential for devices that might be competitive with vapor compression–based appliances with further optimization.

Science
, this issue p.
129
, p.
125
Macroscopic somatic clonal expansion in morphologically normal human urothelium
Authors: Li Ruoyan , Du Yiqing , Chen Zhanghua , Xu Deshu , Lin Tianxin , Jin Shanzhao , Wang Gongwei , Liu Ziyang , Lu Min , Chen Xu , Xu Tao , Bai Fan
Published: October 2020

Genetic profiles of the bladder

Depending on the environment of the individual, the human bladder can be exposed to carcinogens as they are flushed through the body. Lawson
et al.
and Li
et al.
examined the genetic composition of laser-dissected microbiopsies from normal and cancer cells collected from the urothelium, a specialized epithelium lining the lower urinary tract (see the Perspective by Rozen). These complementary studies identified the mutational landscape of bladder urothelium through various sequencing strategies and identified high mutational heterogeneity within and between individuals and tumors. Both studies identified mutational profiles related to specific carcinogens such as aristolochic acid and the molecules found in tobacco. These studies present a comprehensive description of the diverse mutational landscape of the human bladder in health and disease, unraveling positive selection for cancer-causing mutations, a diversity of mutational processes, and large differences across individuals.

Science
, this issue p.
75
, p.
82
; see also p.
34
Glymphatic failure as a final common pathway to dementia
Authors: Nedergaard Maiken , Goldman Steven A.
Published: October 2020

Sleep is evolutionarily conserved across all species, and impaired sleep is a common trait of the diseased brain. Sleep quality decreases as we age, and disruption of the regular sleep architecture is a frequent antecedent to the onset of dementia in neurodegenerative diseases. The glymphatic system, which clears the brain of protein waste products, is mostly active during sleep. Yet the glymphatic system degrades with age, suggesting a causal relationship between sleep disturbance and symptomatic progression in the neurodegenerative dementias. The ties that bind sleep, aging, glymphatic clearance, and protein aggregation have shed new light on the pathogenesis of a broad range of neurodegenerative diseases, for which glymphatic failure may constitute a therapeutically targetable final common pathway.
A rival to superalloys at high temperatures
Authors: Cairney Julie
Published: October 2020

Slip-pathway activation provides plasticity in a multiprincipal element alloy with high-temperature strength
A new primary visual cortex
Authors: Beltramo Riccardo
Published: October 2020

The postrhinal cortex joins V1 as a first-order processor of visual information
The Impact of Circulating Antibody on Group B
Streptococcus
Intestinal Colonization and Invasive Disease
Authors: Vaz Michelle J. , Purrier Sheryl A. , Bonakdar Maryam , Chamby Anna B. , Ratner Adam J. , Randis Tara M.
Published: October 2020

Gastrointestinal (GI) colonization with group B
Streptococcus
(GBS) is an important precursor to late-onset (LO) disease in infants. The host-pathogen interactions that mediate progression to invasive disease remain unknown due, in part, to a paucity of robust model systems. Passively acquired maternal GBS-specific antibodies protect newborns from early-onset disease, yet their impact on GI colonization and LO disease is unexplored. Using murine models of both perinatal and postnatal GBS acquisition, we assessed the kinetics of GBS GI colonization, progression to invasive disease, and the role of GBS-specific IgG production in exposed offspring and juvenile mice at age 12 and 14 days, respectively.
HIV-2 Drug Resistance Genotyping from Dried Blood Spots
Authors: Raugi Dana N. , Nixon Robert S. , Leong Sally , Faye Khadim , Diatta Jean Phillipe , Sall Fatima , Smith Robert A. , Sall ElHadji Ibrahima , Malomar Jean Jacques , Seydi Moussa , Gottlieb Geoffrey S.
Published: October 2020

The treatment of HIV-2 in resource-limited settings (RLS) is complicated by the limited availability of HIV-2-active antiretroviral drugs and inadequate access to HIV-2 viral load and drug resistance testing. Dried blood spots (DBS)-based drug resistance testing, widely studied for HIV-1, has not been reported for HIV-2 and could present an opportunity to improve care for HIV-2-infected individuals. We selected 150 DBS specimens from ongoing studies of antiretroviral therapy (ART) for HIV-2 infection in Senegal and subjected them to genotypic drug resistance testing.
Structural and Functional Characterization of Host FHL1 Protein Interaction with Hypervariable Domain of Chikungunya Virus nsP3 Protein
Authors: Lukash Tetyana , Agback Tatiana , Dominguez Francisco , Shiliaev Nikita , Meshram Chetan , Frolova Elena I. , Agback Peter , Frolov Ilya
Published: October 2020

Replication of chikungunya virus (CHIKV) is determined by a wide range of host factors. Previously, we have demonstrated that the hypervariable domain (HVD) of CHIKV nsP3 contains linear motifs that recruit defined families of host proteins into formation of functional viral replication complexes. Now, using NMR-based structural and biological approaches, we have characterized the binding site of the cellular FHL1 protein in CHIKV HVD and defined the biological significance of this interaction. In contrast to previously described binding of G3BP to CHIKV HVD, the FHL1-HVD interaction was found to not be a prerequisite of viral replication. However, the presence of FHL1 has a stimulatory effect on CHIKV infectivity and, subsequently, the infection spread. FHL1 and CD2AP proteins were found to have overlapping binding sites in CHIKV HVD and additive proviral functions. Elimination of the FHL1-binding site in the nsP3 HVD can be used for the development of stable, attenuated vaccine candidates.
Numerical modeling of tectonic underplating in accretionary wedge systems
Authors: Ruh Jonas B.
Published: October 2020

Many fossil and active accretionary wedge systems show signs of tectonic underplating, which denotes accretion of underthrust material to the base of the wedge. Underplating is a viable process for thickening of the rear part of accretionary wedges, for example as a response to horizontal growth perpendicular to strike. Here, numerical experiments with a visco-elasto-plastic rheology are applied to test the importance of backstop geometry, flexural rigidity, décollement strength, and surface erosion on the structural evolution of accretionary wedges undergoing different modes of sediment accretion, where underplating is introduced by the implementation of two, a basal and an intermediate, décollement levels. Results demonstrate that intense erosion and a strong lower plate hamper thickening of a wedge at the rear, enhancing localized underplating, antiformal stacking, and subsequent exhumation to sustain its critical taper. Furthermore, large strength contrasts between basal and intermediate décollements have an important morphological impact on wedge growth due to different resulting critical taper angles. Presented numerical experiments are compared to natural examples of accretionary wedges and are able to recreate first-order structural observations related to underplating.
Prognostic value of C-reactive protein in adults with congenital heart disease
Authors: Geenen Laurie W , Baggen Vivan J M , van den Bosch Annemien E , Eindhoven Jannet A , Kauling Robert M , Cuypers Judith A A E , Roos-Hesselink Jolien W , Boersma Eric
Published: October 2020

Background

High-sensitivity C reactive protein (hs-CRP) has been associated with outcomes in adult congenital heart disease (ACHD). However, its prognostic value beyond N-terminal pro B type natriuretic peptide (NT-proBNP) or troponin T remains unknown. We studied the temporal evolution of hs-CRP, as well as the relation between hs-CRP and adverse clinical outcomes independent of NT-proBNP and troponin T in patients with ACHD.

Methods

In this prospective cohort study, we enrolled 602 patients with ACHD (2011–2013) who underwent baseline and thereafter annual blood sampling during 4 years. Hs-CRP, hs-troponin T and NT-proBNP were measured. The primary endpoint was composed of death or heart failure (HF). Cox regression and Joint Modelling was used to relate 2log hs-CRP levels with the endpoint, with adjustment for baseline characteristics and (repeated) hs-troponin T and NT-proBNP measurements.

Results

Hs-CRP was measured at baseline in 591 patients, median age 33 years, 58% men, 90% New York Heart Association I with an average of 4.3 measurements per patient. Median follow-up was 5.9 (IQR 5.3–6.3) years (99.2% complete) and 69 patients met the endpoint. Higher baseline hs-CRP was independently associated with higher risk of death or HF (HR 1.36, 95% CI 1.19 to 1.55). Hs-CRP increased over time prior to death or HF, and repeated hs-CRP measurements were associated with the endpoint, independent of repeated NT-proBNP and hs-troponin T (HR 1.54, 95% CI 1.24 to 1.98).

Conclusions

Hs-CRP carries incremental prognostic value for the risk of death or HF, beyond NT-proBNP and hs-troponin T. Hs-CRP increased prior to the occurrence of HF or death, supporting the role of inflammation in the clinical deterioration of patients with ACHD.
PD1 blockade enhances K+channel activity, Ca2+signaling, and migratory ability in cytotoxic T lymphocytes of patients with head and neck cancer
Authors: Newton Hannah S , Gawali Vaibhavkumar S , Chimote Ameet A , Lehn Maria A , Palackdharry Sarah M , Hinrichs Benjamin H , Jandarov Roman , Hildeman David , Janssen Edith M , Wise-Draper Trisha M , Conforti Laura
Published: October 2020

Background

Immunotherapy has emerged as a promising treatment modality for head and neck squamous cell carcinoma (HNSCC). Pembrolizumab, an anti-programmed death 1 antibody, is an immunotherapy agent currently approved for metastatic HNSCC and curative intent clinical trials. Although clinical responses to pembrolizumab are promising, many patients fail to respond. However, it is well known that T cell cytotoxicity and chemotaxis are critically important in the elimination of HNSCC tumors. These functions depend on ion channel activity and downstream Ca2+fluxing abilities, which are defective in patients with HNSCC. The purpose of this study was to elucidate the effects of pembrolizumab on potassium (K+) channel (KCa3.1 and Kv1.3) activity, Ca2+fluxes, and chemotaxis in the cytotoxic T cells of patients with HNSCC and to determine their correlation with treatment response.

Methods

Functional studies were conducted in CD8+peripheral blood T cells (PBTs) and tumor infiltrating lymphocytes (TILs) from patients with HNSCC treated with pembrolizumab. Untreated patients with HNSCC were used as controls. The ion channel activity of CD8+T cells was measured by patch-clamp electrophysiology; single-cell Ca2+fluxing abilities were measured by live microscopy. Chemotaxis experiments were conducted in a three-dimensional collagen matrix. Pembrolizumab patients were stratified as responders or non-responders based on pathological response (percent of viable tumor remaining at resection; responders: ≤80% viable tumor; non-responders: >80% viable tumor).

Results

Pembrolizumab increased K+channel activity and Ca2+fluxes in TILs independently of treatment response. However, in PBTs from responder patients there was an increased KCa3.1 activity immediately after pembrolizumab treatment that was accompanied by a characteristic increase in Kv1.3 and Ca2+fluxes as compared with PBTs from non-responder patients. The effects on Kv1.3 and Ca2+were prolonged and persisted after tumor resection. Chemotaxis was also improved in responder patients’ PBTs. Unlike non-responders’ PBTs, pembrolizumab increased their ability to chemotax in a tumor-like, adenosine-rich microenvironment immediately after treatment, and additionally they maintained an efficient chemotaxis after tumor resection.

Conclusions

Pembrolizumab enhanced K+channel activity, Ca2+fluxes and chemotaxis of CD8+T cells in patients with HNSCC, with a unique pattern of response in responder patients that is conducive to the heightened functionality of their cytotoxic T cells.
HX008, an anti-PD1 antibody, plus irinotecan as second-line treatment for advanced gastric or gastroesophageal junction cancer: a multicenter, single-arm phase II trial
Authors: Song Yan , Li Ning , Li Qun , Liang Xinjun , Zhang Shu , Fan Qingxia , Yin Xianli , Zhuang Zhixiang , Liu Yunpeng , Zhang Jingdong , Kou Xiaoge , Zhong Haijun , Wang Xiaofei , Dou Yiwei , Huang Jing
Published: October 2020

Background

Irinotecan is used as second-line treatment in advanced gastric or gastroesophageal junction (G/GEJ) cancer. The role of anti-programmed death-1 (PD-1) antibody plus irinotecan, in this setting and population is unclear.

Methods

This multicenter, open-label, single-arm, phase II trial was conducted in 11 Chinese hospitals. Eligible patients had histologically confirmed advanced G/GEJ cancer that refractory to, or intolerant of, first-line chemotherapy with a platinum and/or fluoropyrimidine. Subjects received HX008 200 mg intravenously every 3 weeks plus irinotecan 160 mg/m2 intravenously every 2 weeks until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) as assessed according to Response Evaluation Criteria In Solid Tumors V.1.1.

Results

Between October 2018 and September 2019, a total of 58 patients with advanced G/GEJ cancer were enrolled in this study. Median follow-up was 10.5 months (range 7.4–18.9) months. Confirmed ORR was observed in 16 patients, for an ORR of 27.6% (95% CI 16.1% to 39.1%); 19 patients experienced stable disease, leading to a disease control rate of 60.3% (95% CI 46.4% to 73.0%). ORR in patients with PD-ligand 1 (L1) positive (Combined Positive Score (CPS) ≥1) and negative (CPS＜1) tumors was 38.5% (5/13) and 37.5% (3/8), respectively. Median duration of response was 8.0 months (range 1.5–12.5), 6 of 16 (37.5%) responses were ongoing. Median progression-free survival (PFS) was 4.2 months (95% CI 2.2 to 5.5). Median overall survival (OS) was not reached (NR) (95% CI 8.7 to NR). Patients with PD-L1 positive tumors tended to have longer OS than those with PD-L1 negative tumors, but the difference was not statistically significant (NR vs 8.7 months, p=0.1858).

The most common treatment-related adverse events of grade 3 or 4 included neutropenia (32.8%), leukopenia (31.0%), anemia (17.2%), decreased appetite (8.6%), vomit (6.9%), nausea (6.9%) and fatigue (5.2%). There were no treatment-related deaths.

Conclusion

The combination of HX008 and irinotecan demonstrated promising activity and manageable safety as second-line treatment in patients with advanced G/GEJ cancer, which warrants further study.

Trial registration number

NCT03704246
Equity in access to facial transplantation
Authors: Kimberly Laura L , Ramly Elie P , Alfonso Allyson R , Diep Gustave K , Berman Zoe P , Rodriguez Eduardo D
Published: October 2020

We examine ethical considerations in access to facial transplantation (FT), with implications for promoting health equity. As a form of vascularised composite allotransplantation, FT is still considered innovative with a relatively low volume of procedures performed to date by a small number of active FT programmes worldwide. However, as numbers continue to increase and institutions look to establish new FT programmes, we anticipate that attention will shift from feasibility towards ensuring the benefits of FT are equitably available to those in need. This manuscript assesses barriers to care and their ethical implications across a number of considerations, with the intent of mapping various factors relating to health equity and fair access to FT. Evidence is drawn from an evolving clinical experience as well as published scholarship addressing several dimensions of access to FT. We also explore novel concerns that have yet to be mentioned in the literature.
Republished: First clinical report of aspiration through a novel 0.088-inch catheter positioned in the M1 middle cerebral artery for ELVO thrombectomy
Authors: Gershon Blake S , Bageac Devin V , Shigematsu Tomoyoshi , Majidi Shahram , De Leacy Reade
Published: October 2020

Two patients, separated by 1 year, underwent mechanical thrombectomy using next generation, highly navigable 0.088-inch large bore catheters, which were navigated to and aspirated within the M1 middle cerebral artery segment. Case 1 demonstrates the first reported clinical application of this technique used in conjunction with stent retriever and direct aspiration through an intermediate catheter, resulting in modified thrombolysis in cerebral infarction (mTICI) score 3 recanalisation, and a 90-day modified Rankin Score of 1. In case 2, direct on-clot aspiration was applied through a 0.088-inch guide catheter in the left M1 segment, resulting in mTICI score 3 recanalisation and a National Institutes of Health Stroke Scale score of 1 at discharge. There was no evidence of untoward events in either case. Advancement of a 0.088-inch catheter into the M1 segment offers potential benefits to thrombectomy by improving device-thrombus interaction, inducing local flow arrest and protecting proximal vessels from embolus to new territories.