bluuebunny/crossref_metadata_2025 huggingface dataset:
Xylem Functional Traits as Indicators of Health in Mediterranean Forests
Authors: Borghetti Marco , Gentilesca Tiziana , Colangelo Michele , Ripullone Francesco , Rita Angelo
Published: July 2020

Purpose of Review

We conducted a literature survey and meta-analysis to assess, in Mediterranean forests impacted by drought, the role of xylem functional traits as indicators of tree health, and their potential to adjust over a range of climatic conditions to support tree performance and survival. We aimed also to depict the geographic variability of xylem functional traits among Mediterranean forest trees as a tool for regional scale-oriented vulnerability assessment.

Recent Findings

Associations were investigated among xylem functional traits, hydraulic safety, and whole plant drought resistance for tree species in Mediterranean-type climates. Variable data were available from a number of study cases of Mediterranean forest communities impacted by intense drought, wherein tree growth and xylem functional traits were investigated along with tree decline and dieback episodes. Variable data were available from a number of studies that analyzed xylem trait adjustments to climatic conditions at different temporal scales.

We observed differing growth patterns and xylem conduit area responses in healthy and unhealthy trees and we sketched hydraulic strategies that may fit observed patterns. Overall, a clear role of xylem conduit size as stand-alone tree health indicator did not emerge. We showed that xylem traits may adjust along different temporal scales and may support the performance and health of Mediterranean tree species over a range of climatic conditions. We outlined substantial geographic variability in xylem traits across the Mediterranean region, suggesting patchy responses to increasing drought. Knowledge gaps and needed lines of research are highlighted.
A fuzzy mid-term capacity and production planning model for a manufacturing system with cloud-based capacity
Authors: Chen Tin-Chih Toly , Wang Yu-Cheng
Published: July 2020

Most of the past cloud manufacturing (CMfg) studies investigated the short-term production planning or job scheduling of a CMfg system, while the mid-term or long-term capacity and production planning of a CMfg system has rarely been addressed. In addition, most existing methods are suitable for CMfg systems comprising three-dimensional (3D) printers, computer numerical control (CNC) machines or robots, but ignore the coordination and transportation required for moving jobs across factories. To fill these gaps, a fuzzy mid-term capacity and production planning model for a manufacturer with cloud-based capacity is proposed in this study. The proposed methodology guides a manufacturer in choosing between non-cloud-based capacity and cloud-based capacity. It can be applied to factories utilizing machines with different degrees of automation including highly automatic equipment (such as 3D printers, CNC machines, and robots) and lowly automatic (legacy) machines, while existing methods assume that orders can be easily transferred between machines that are often highly automatic. In the proposed methodology, first, various types of capacity are unequally prioritized. Then, a fuzzy mixed-integer nonlinear programming model is formulated and optimized to make the mid-term or long-term capacity and production plan of a factory. The fuzzy capacity and production planning model is designed for factories with parallel machines. The proposed methodology has been applied to a case to illustrate its applicability. According to the experimental results, the proposed methodology successfully reduced total costs by up to 8%. The advantage of the proposed methodology over existing practices in fulfilling customers’ demand was also obvious.
Patient-level predictors of detection of depressive symptoms, referral, and uptake of depression counseling among chronic care patients in KwaZulu-Natal, South Africa
Authors: Kemp Christopher G. , Mntambo Ntokozo , Bachmann Max , Bhana Arvin , Rao Deepa , Grant Merridy , Hughes James P. , Simoni Jane M. , Weiner Bryan J. , Gigaba Sithabisile Gugulethu , Luvuno Zamasomi Prudence Busisiwe , Petersen Inge
Published: July 2020

Background

Integration of depression treatment into primary care could improve patient outcomes in low-resource settings. Losses along the depression care cascade limit integrated service effectiveness. This study identified patient-level factors that predicted detection of depressive symptoms by nurses, referral for depression treatment, and uptake of counseling, as part of integrated care in KwaZulu-Natal, South Africa.

Methods

This was an analysis of baseline data from a prospective cohort. Participants were adult patients with at least moderate depressive symptoms at primary care facilities in Amajuba, KwaZulu-Natal, South Africa. Participants were screened for depressive symptoms prior to routine assessment by a nurse. Generalized linear mixed-effects models were used to estimate associations between patient characteristics and service delivery outcomes.

Results

Data from 412 participants were analyzed. Nurses successfully detected depressive symptoms in 208 [50.5%, 95% confidence interval (CI) 38.9–62.0] participants; of these, they referred 76 (36.5%, 95% CI 20.3–56.5) for depression treatment; of these, 18 (23.7%, 95% CI 10.7–44.6) attended at least one session of depression counseling. Depressive symptom severity, alcohol use severity, and perceived stress were associated with detection. Similar factors did not drive referral or counseling uptake.

Conclusions

Nurses detected patients with depressive symptoms at rates comparable to primary care providers in high-resource settings, though gaps in referral and uptake persist. Nurses were more likely to detect symptoms among patients in more severe mental distress. Implementation strategies for integrated mental health care in low-resource settings should target improved rates of detection, referral, and uptake.
Time to positivity of blood cultures among a veteran population: How long to wait before discontinuing antimicrobial therapy when suspicion of infection is low
Authors: Heintz Brett H. , DeLanoit Zach T. , Granroth Leah J. , Patterson Whitni T.
Published: July 2020

Time to positivity (TTP) of blood cultures can guide antimicrobial therapy. This single-center retrospective cohort study aimed to determine the yield of clinically significant organisms from blood cultures that were initially negative at 24 hours. Clinically significant organisms were uncommon after 24 hours (1.5%) and more common in intensive care unit settings.
GAMES AND REFLECTION IN
Authors: AGUILERA J. P.
Published: July 2020

We characterize the determinacy of
$F_\sigma $
games of length
$\omega ^2$
in terms of determinacy assertions for short games. Specifically, we show that
$F_\sigma $
games of length
$\omega ^2$
are determined if, and only if, there is a transitive model of
${\mathsf {KP}}+{\mathsf {AD}}$
containing
$\mathbb {R}$
and reflecting
$\Pi _1$
facts about the next admissible set.

As a consequence, one obtains that, over the base theory
${\mathsf {KP}} + {\mathsf {DC}} + ``\mathbb {R}$
exists,” determinacy for
$F_\sigma $
games of length
$\omega ^2$
is stronger than
${\mathsf {AD}}$
, but weaker than
${\mathsf {AD}} + \Sigma _1$
-separation.
Britain ’ s Ferns. A Field Guide to the Clubmosses, Quillworts, Horsetails and Ferns of Great Britain and Ireland . J. Merryweather.
Authors: Gibby Mary
Published: July 2020

..
Sir Robert Hart and the Writing of Modern Chinese History
Authors: Chang Chihyun
Published: July 2020

This article examines the conflicts in writing the imperial modern history of China among various stakeholders, particularly Chinese and American historians, and their dealing with a set of personal documents of Sir Robert Hart, Inspector-General of the Chinese Maritime Customs Services (CMCS) during the Qing period. This set of documents is called “Hart Industry” and contains Hart's personal papers and seventy-seven volumes of diaries, among others. Revealing the imperial Inspector-General's view on “westernization” in modern China, the Hart Industry played a key role in the development of the history of modern China throughout the twentieth century. From around 1957 until 1995, the diaries became a source of a highly politicized academic debate between Chinese Communist historians of the People's Republic of China and western historians of the Hart Industry. By providing a “study of studies” on the historiography of the colonial modern history of China, this article argues that the Hart diaries were critical to historians’ understanding of their own academic discourse.
TWO LEVEL CREDIBILITY-LIMITED REVISIONS
Authors: GARAPA MARCO
Published: July 2020

In this paper, we propose a new kind of nonprioritized operator which we call two level credibility-limited revision. When revising through a two level credibility-limited revision there are two levels of credibility and one of incredibility. When revising by a sentence at the highest level of credibility, the operator behaves as a standard revision, if the sentence is at the second level of credibility, then the outcome of the revision process coincides with a standard contraction by the negation of that sentence. If the sentence is not credible, then the original belief set remains unchanged. In this article, we axiomatically characterize several classes of two level credibility-limited revision operators.
EPISTEMIC MULTILATERAL LOGIC
Authors: INCURVATI LUCA , SCHLÖDER JULIAN J.
Published: July 2020

We presentepistemic multilateral logic, a general logical framework for reasoning involving epistemic modality. Standard bilateral systems use propositional formulae marked with signs for assertion and rejection. Epistemic multilateral logic extends standard bilateral systems with a sign for the speech act of weak assertion (Incurvati & Schlöder, 2019) and an operator for epistemic modality. We prove that epistemic multilateral logic is sound and complete with respect to the modal logic$\mathbf {S5}$modulo an appropriate translation. The logical framework developed provides the basis for a novel, proof-theoretic approach to the study of epistemic modality. To demonstrate the fruitfulness of the approach, we show how the framework allows us to reconcile classical logic with the contradictoriness of so-called Yalcin sentences and to distinguish between various inference patterns on the basis of the epistemic properties they preserve.
Survey of ground and aerial herbicide application practices in Arkansas agronomic crops
Authors: Butts Thomas R. , Barber L. Tom , Norsworthy Jason K. , Davis Jason
Published: July 2020

A thorough understanding of commonly used herbicide application practices and technologies is needed to provide recommendations and determine necessary application education efforts. An online survey to assess ground and aerial herbicide application practices in Arkansas was made available online in spring 2019. The survey was direct-emailed to 272 agricultural aviators and 831 certified commercial pesticide applicators, as well as made publicly available online through multiple media sources. A total of 124 responses were received, of which 75 responses were specific to herbicide applications in Arkansas agronomic crops, accounting for approximately 49% of Arkansas’ planted agronomic crop hectares in 2019. Ground and aerial application equipment were used for 49% and 51% of the herbicide applications on reported hectares, respectively. Rate controllers were commonly used application technologies for both ground and aerial application equipment. In contrast, global positioning system-driven automatic nozzle and boom shut-offs were much more common on ground spray equipment than aerial equipment. Applicator knowledge of nozzles and usage was limited, regardless of ground or aerial applicators, as only 28% of respondents provided a specific nozzle type used, indicating a need for educational efforts on nozzles and their importance in herbicide applications. Of the reported nozzle types, venturi nozzles and straight-stream nozzles were the most commonly used for ground and aerial spray equipment, respectively. Spray carrier volumes of 96.3 and 118.8 L ha−1 for ground spray equipment and 49.6 and 59.9 L ha−1 for aerial application equipment were the means of reported spray volumes for systemic and contact herbicides, respectively. Respondents indicated application optimization was a major benefit of utilizing newer application technologies, herbicide drift was a primary challenge, and research needs expressed by respondents included adjuvants, spray volume efficacy, and herbicide drift. Findings from this survey provided insight into current practices, technologies, and needs of Arkansas herbicide applicators. Research and education efforts can be implemented as a result to address aforementioned needs while providing applied research-based information to applicators based on current practices.
Locating Fully Locked Asperities Along the South America Subduction Megathrust: A New Physical Interseismic Inversion Approach in a Bayesian Framework
Authors: Herman M. W. , Govers R.
Published: July 2020

The largest earthquakes in subduction zones occur where significant interseismic slip deficit has accumulated on the plate interface. Slip deficit accumulates most quickly in mechanically locked regions, and these also cause the regions around them to accumulate slip deficit; therefore, large earthquakes are typically expected to rupture in and around locked areas. The locations and dimensions of these locked zones have been difficult to resolve using standard techniques and available data sets. We develop a new statistical interseismic inversion approach that incorporates the physical interactions between nearby fault areas to directly determine the distribution of locking on the subduction plate interface (simultaneously with rigid forearc motions) from interseismic surface velocities. Because we include physical prior information in the inversion procedure, this approach reduces uncertainties in the rate of slip deficit accumulation, even in locations (such as near the trench) where kinematic inversions of onshore data have relatively low resolution. Applying the inversion to the South America subduction zone, we find that the pattern of locking and corresponding slip deficit rates correlate well with recent and historical large earthquake ruptures. Locked patch dimensions are <40 km and account for no more than 30% of the area of the plate interface. The small size of the imaged locked zones is a natural outcome of our physical assumptions and implies that mechanical locking is caused by correspondingly small geological features. Despite their small dimensions, locked zones generate substantial slip deficit on the surrounding plate interface, consistent with the slip patterns of large megathrust earthquakes.
Pevonedistat (MLN4924): mechanism of cell death induction and therapeutic potential in colorectal cancer
Authors: Ferris Jennifer , Espona-Fiedler Margarita , Hamilton Claudia , Holohan Caitriona , Crawford Nyree , McIntyre Alex J. , Roberts Jamie Z. , Wappett Mark , McDade Simon S. , Longley Daniel B. , Coyle Victoria
Published: July 2020

Pevonedistat (MLN4924), a selective inhibitor of the NEDD8-activating enzyme E1 regulatory subunit (NAE1), has demonstrated significant therapeutic potential in several malignancies. Although multiple mechanisms-of-action have been identified, how MLN4924 induces cell death and its potential as a combinatorial agent with standard-of-care (SoC) chemotherapy in colorectal cancer (CRC) remains largely undefined. In an effort to understand MLN4924-induced cell death in CRC, we identified p53 as an important mediator of the apoptotic response to MLN4924. We also identified roles for the extrinsic (TRAIL-R2/caspase-8) and intrinsic (BAX/BAK) apoptotic pathways in mediating the apoptotic effects of MLN4924 in CRC cells, as well as a role for BID, which modulates a cross-talk between these pathways. Depletion of the anti-apoptotic protein FLIP, which we identify as a novel mediator of resistance to MLN4924, enhanced apoptosis in a p53-, TRAIL-R2/DR5-, and caspase-8-dependent manner. Notably, TRAIL-R2 was involved in potentiating the apoptotic response to MLN4924 in the absence of FLIP, in a ligand-independent manner. Moreoever, when paired with SoC chemotherapies, MLN4924 demonstrated synergy with the irinotecan metabolite SN38. The cell death induced by MLN4924/SN38 combination was dependent on activation of mitochondria through BAX/BAK, but in a p53-independent manner, an important observation given the high frequency of TP53 mutation(s) in advanced CRC. These results uncover mechanisms of cell death induced by MLN4924 and suggest that this second-generation proteostasis-disrupting agent may have its most widespread activity in CRC, in combination with irinotecan-containing treatment regimens.
A global lipid map defines a network essential for Zika virus replication
Authors: Leier Hans C. , Weinstein Jules B. , Kyle Jennifer E. , Lee Joon-Yong , Bramer Lisa M. , Stratton Kelly G. , Kempthorne Douglas , Navratil Aaron R. , Tafesse Endale G. , Hornemann Thorsten , Messer William B. , Dennis Edward A. , Metz Thomas O. , Barklis Eric , Tafesse Fikadu G.
Published: July 2020

Zika virus (ZIKV), an arbovirus of global concern, remodels intracellular membranes to form replication sites. How ZIKV dysregulates lipid networks to allow this, and consequences for disease, is poorly understood. Here, we perform comprehensive lipidomics to create a lipid network map during ZIKV infection. We find that ZIKV significantly alters host lipid composition, with the most striking changes seen within subclasses of sphingolipids. Ectopic expression of ZIKV NS4B protein results in similar changes, demonstrating a role for NS4B in modulating sphingolipid pathways. Disruption of sphingolipid biosynthesis in various cell types, including human neural progenitor cells, blocks ZIKV infection. Additionally, the sphingolipid ceramide redistributes to ZIKV replication sites, and increasing ceramide levels by multiple pathways sensitizes cells to ZIKV infection. Thus, we identify a sphingolipid metabolic network with a critical role in ZIKV replication and show that ceramide flux is a key mediator of ZIKV infection.
Gate-tunable spin-galvanic effect in graphene-topological insulator van der Waals heterostructures at room temperature
Authors: Khokhriakov Dmitrii , Hoque Anamul Md. , Karpiak Bogdan , Dash Saroj P.
Published: July 2020

Unique electronic spin textures in topological states of matter are promising for emerging spin-orbit driven memory and logic technologies. However, there are several challenges related to the enhancement of their performance, electrical gate-tunability, interference from trivial bulk states, and heterostructure interfaces. We address these challenges by integrating two-dimensional graphene with a three-dimensional topological insulator (TI) in van der Waals heterostructures to take advantage of their remarkable spintronic properties and engineer proximity-induced spin-charge conversion phenomena. In these heterostructures, we experimentally demonstrate a gate-tunable spin-galvanic effect (SGE) at room temperature, allowing for efficient conversion of a non-equilibrium spin polarization into a transverse charge current. Systematic measurements of SGE in various device geometries via a spin switch, spin precession, and magnetization rotation experiments establish the robustness of spin-charge conversion in the Gr-TI heterostructures. Importantly, using a gate voltage, we reveal a strong electric field tunability of both amplitude and sign of the spin-galvanic signal. These findings provide an efficient route for realizing all-electrical and gate-tunable spin-orbit technology using TIs and graphene in heterostructures, which can enhance the performance and reduce power dissipation in spintronic circuits.
Genome-wide analysis of diamondback moth, Plutella xylostella L., from Brassica crops and wild host plants reveals no genetic structure in Australia
Authors: Perry Kym D. , Keller Michael A. , Baxter Simon W.
Published: July 2020

Molecular studies of population structure can reveal insight into the movement patterns of mobile insect pests in agricultural landscapes. The diamondback moth, Plutella xylostella L., a destructive pest of Brassica vegetable and oilseed crops worldwide, seasonally colonizes winter canola crops in southern Australia from alternative host plant sources. To investigate movement, we collected 59 P. xylostella populations from canola crops, Brassica vegetable and forage crops and brassicaceous wild host plants throughout southern Australia in 2014 and 2015 and genotyped 833 individuals using RAD-seq for genome-wide analysis. Despite a geographic sampling scale > 3,000 km and a statistically powerful set of 1,032 SNP markers, there was no genetic differentiation among P. xylostella populations irrespective of geographic location, host plant or sampling year, and no evidence for isolation-by-distance. Hierarchical STRUCTURE analysis at K = 2–5 showed nearly uniform ancestry in both years. Cluster analysis showed divergence of a small number of individuals at several locations, possibly reflecting an artefact of sampling related individuals. It is likely that genetic homogeneity within Australian P. xylostella largely reflects the recent colonization history of this species but is maintained through some level of present gene flow. Use of genome-wide neutral markers was uninformative for revealing the seasonal movements of P. xylostella within Australia, but may provide more insight in other global regions where the species has higher genetic diversity.
Cervicovaginal natural antimicrobial expression in pregnancy and association with spontaneous preterm birth
Authors: Hezelgrave Natasha L. , Seed Paul T. , Chin-Smith Evonne C. , Ridout Alexandra E. , Shennan Andrew H. , Tribe Rachel M.
Published: July 2020

There is much interest in the role of innate immune system proteins (antimicrobial peptides) in the inflammatory process associated with spontaneous preterm birth (sPTB). After promising pilot work, we aimed to validate the association between the antimicrobial peptides/proteins elafin and cathelicidin and sPTB. An observational cohort study of 405 women at high-risk, and 214 women at low-risk of sPTB. Protein concentrations of elafin and cathelicidin, and the enzyme human neutrophil elastase (HNE) were measured in over 1,000 cervicovaginal fluid (CVF) samples (10 to 24 weeks’ gestation). Adjusted CVF cathelicidin and HNE concentrations (but not elafin) were raised in high-risk women who developed cervical shortening and who delivered prematurely and were predictive of sPTB < 37 weeks, with an area under the curve (AUC) of 0.75 (95% CI 0.68 to 0.81) for cathelicidin concentration at 14 to 15+6 weeks. Elafin concentrations were affected by gestation, body mass index and smoking. CVF elafin in early pregnancy was modestly predictive of sPTB < 34 weeks (AUC 0.63, 0.56–0.70). Alterations in innate immune response proteins in early pregnancy are predictive of sPTB. Further investigation is warranted to understand the drivers for this, and their potential to contribute towards clinically useful prediction techniques.
The evolution of knowledge within and across fields in modern physics
Authors: Sun Ye , Latora Vito
Published: July 2020

The exchange of knowledge across different areas and disciplines plays a key role in the process of knowledge creation, and can stimulate innovation and the emergence of new fields. We develop here a quantitative framework to extract significant dependencies among scientific disciplines and turn them into a time-varying network whose nodes are the different fields, while the weighted links represent the flow of knowledge from one field to another at a given period of time. Drawing on a comprehensive data set on scientific production in modern physics and on the patterns of citations between articles published in the various fields in the last 30 years, we are then able to map, over time, how the ideas developed in a given field in a certain time period have influenced later discoveries in the same field or in other fields. The analysis of knowledge flows internal to each field displays a remarkable variety of temporal behaviours, with some fields of physics showing to be more self-referential than others. The temporal networks of knowledge exchanges across fields reveal cases of one field continuously absorbing knowledge from another field in the entire observed period, pairs of fields mutually influencing each other, but also cases of evolution from absorbing to mutual or even to back-nurture behaviors.
Immune lymphocytes halt replication of Francisella tularensis LVS within the cytoplasm of infected macrophages
Authors: Bradford Mary Katherine , Elkins Karen L.
Published: July 2020

Francisella tularensisis a highly infectious intracellular bacterium that causes tularemia by invading and replicating in mammalian myeloid cells.Francisellaprimarily invades host macrophages, where it escapes phagosomes within a few hours and replicates in the cytoplasm. Less is known about howFrancisellatraffics within macrophages or exits into the extracellular environment for further infection. Immune T lymphocytes control the replication ofFrancisellawithin macrophages in vitro by a variety of mechanisms, but nothing is known about intracellular bacterial trafficking in the face of such immune pressure. Here we used a murine model of infection with aFrancisellaattenuated live vaccine strain (LVS), which is under study as a human vaccine, to evaluate the hypothesis that immune T cells control intramacrophage bacterial growth by re-directing bacteria into toxic intracellular compartments of infected macrophages. We visualized the interactions of lymphocytes and LVS-infected macrophages using confocal microscopy and characterized LVS intramacrophage trafficking when co-cultured with immune lymphocytes. We focused on the late stages of infection after bacteria escape from phagosomes, through bacterial replication and the death of macrophages. We found that the majority of LVS remained cytosolic in the absence of immune pressure, eventually resulting in macrophage death. In contrast, co-culture of LVS-infected macrophages with LVS-immune lymphocytes halted LVS replication and inhibited the spread of LVS infection between macrophages, but bacteria did not return to vacuoles such as lysosomes or autophagosomes and macrophages did not die. Therefore, immune lymphocytes directly limit intracellular bacterial replication within the cytoplasm of infected macrophages.
Mechanically driven strategies to improve electromechanical behaviour of printed stretchable electronic systems
Authors: Di Vito Donato , Mosallaei Milad , Khorramdel Behnam , Kanerva Mikko , Mäntysalo Matti
Published: July 2020

Stretchable electronics promise to extend the application range of conventional electronics by enabling them to keep their electrical functionalities under system deformation. Within this framework, development of printable silver-polymer composite inks is making possible to realize several of the expected applications for stretchable electronics, which range from seamless sensors for human body measurement (e.g. health patches) to conformable injection moulded structural electronics. However, small rigid electric components are often incorporated in these devices to ensure functionality. Under mechanical loading, these rigid elements cause strain concentrations and a general deterioration of the system’s electrical performance. This work focuses on different strategies to improve electromechanical performance by investigating the deformation behaviour of soft electronic systems comprising rigid devices through Finite Element analyses. Based on the deformation behaviour of a simple stretchable device under tensile loading, three general strategies were proposed: local component encapsulation, direct component shielding, and strain dispersion. The FE behaviour achieved using these strategies was then compared with the experimental results obtained for each design, highlighting the reasons for their different resistance build-up. Furthermore, crack formation in the conductive tracks was analysed under loading to highlight its link with the evolution of the system electrical performance.
Selective protection of human cardiomyocytes from anthracycline cardiotoxicity by small molecule inhibitors of MAP4K4
Authors: Golforoush Pelin A. , Narasimhan Priyanka , Chaves-Guerrero Patricia P. , Lawrence Elsa , Newton Gary , Yan Robert , Harding Sian E. , Perrior Trevor , Chapman Kathryn L. , Schneider Michael D.
Published: July 2020

Given the poor track record to date of animal models for creating cardioprotective drugs, human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have been proposed as a therapeutically relevant human platform to guide target validation and cardiac drug development. Mitogen-Activated Protein Kinase Kinase Kinase Kinase-4 (MAP4K4) is an “upstream” member of the MAPK superfamily that is implicated in human cardiac muscle cell death from oxidative stress, based on gene silencing and pharmacological inhibition in hPSC-CMs. A further role for MAP4K4 was proposed in heart muscle cell death triggered by cardiotoxic anti-cancer drugs, given its reported activation in failing human hearts with doxorubicin (DOX) cardiomyopathy, and its activation acutely by DOX in cultured cardiomyocytes. Here, we report successful protection from DOX in two independent hPSC-CM lines, using two potent, highly selective MAP4K4 inhibitors. The MAP4K4 inhibitors enhanced viability and reduced apoptosis at otherwise lethal concentrations of DOX, and preserved cardiomyocyte function, as measured by spontaneous calcium transients, at sub-maximal ones. Notably, in contrast, no intereference was seen in tumor cell killing, caspase activation, or mitochondrial membrane dissipation by DOX, in human cancer cell lines. Thus, MAP4K4 is a plausible, tractable, selective therapeutic target in DOX-induced human heart muscle cell death.
Functional and morphological cardiovascular alterations associated with neurofibromatosis 1
Authors: Cutruzzolà Antonio , Irace Concetta , Frazzetto Marco , Sabatino Jolanda , Gullace Rosa , De Rosa Salvatore , Spaccarotella Carmen , Concolino Daniela , Indolfi Ciro , Gnasso Agostino
Published: July 2020

Subjects with Neurofibromatosis 1 (NF1) develop vascular complications. The protein product of the gene affected in NF1, neurofibromin, physiologically modulates endothelial function and preserves vascular and myocardial structure. Our study aimed to verify whether subjects with NF1 have early, preclinical abnormalities of carotid artery structure, brachial artery function, and cardiac function. We recruited 22 NF1 subjects without previous cardiovascular events and 22 healthy control subjects. All subjects underwent measurement of carotid artery intima-media thickness (IMT), evaluation of brachial artery endothelial function after ischemia and exercise, and cardiac function. Mean IMT was 543 ± 115 μ in NF1 subjects and 487 ± 70 μ in Controls (p < 0.01). Endothelial function was significantly dumped in NF1 subjects. The dilation after ischemia and exercise was respectively 7.5(± 4.8)% and 6.7(± 3.0)% in NF1 versus 10.5(± 1.2)% and 10.5(± 2.1)% in control subjects (p < 0.02; p < 0.002). Left ventricular systolic function assessed by Global Longitudinal Strain was significantly different between NF1 subjects and Controls: − 19.3(± 1.7)% versus − 21.5(± 2.7)% (p < 0.008). These findings demonstrate that NF1 patients have early morphological and functional abnormalities of peripheral arteries and systolic cardiac impairment and suggest the need for a tight cardiovascular risk evaluation and primary prevention in subjects with NF1.
Cardanol derived P, Si and N based precursors to develop flame retardant phenolic foam
Authors: Bo Caiying , Shi Zhongyu , Hu Lihong , Pan Zheng , Hu Yun , Yang Xiaohui , Jia Puyou , Ren Xiaoli , Zhang Meng , Zhou Yonghong
Published: July 2020

A novel eco-friendly halogen-free cardanol-based flame retardant with P, Si, and N on the chain backbone (PSNCFR) was synthesized and incorporated into phenolic foams (PFs). PSNCFR was comprehensively investigated via Fourier transform infrared spectroscopy and nuclear magnetic resonance. PSNCFR endowed PFs with flame retardancy, contributed to generating a composite char defense against flames, and efficiently prevented smoking from PFs. PSNCFR introduction improved the flexural strength of the PFs to approximately 155% of that of pristine PF. PSNCFR-modified PFs displayed a high limiting oxygen index value of 41.9%. The results of cone calorimeter show that the mean heat release rate, mean effective heat of combustion, and total heat release of the PSNCFR-modified PFs reduced by 26.92%, 35.71%, and 31.25%, respectively. In particular, the total smoke production of the PSNCFR-modified PFs decreased by 64.55%, indicating excellent smoke inhibition. As for the mechanism, the condensation and gas phases during pyrolysis were responsible for the synergistic flame retardancy in the modified PFs. The findings demonstrate that PSNCFR can be used in PF preparation to overcome their drawbacks of internal brittleness and flammability.
Conservation of Cdc14 phosphatase specificity in plant fungal pathogens: implications for antifungal development
Authors: DeMarco Andrew G. , Milholland Kedric L. , Pendleton Amanda L. , Whitney John J. , Zhu Peipei , Wesenberg Daniel T. , Nambiar Monessha , Pepe Antonella , Paula Stefan , Chmielewski Jean , Wisecaver Jennifer H. , Tao W. Andy , Hall Mark C.
Published: July 2020

Cdc14 protein phosphatases play an important role in plant infection by several fungal pathogens. This and other properties of Cdc14 enzymes make them an intriguing target for development of new antifungal crop treatments. Active site architecture and substrate specificity of Cdc14 from the model fungusSaccharomyces cerevisiae(ScCdc14) are well-defined and unique among characterized phosphatases. Cdc14 appears absent from some model plants. However, the extent of conservation of Cdc14 sequence, structure, and specificity in fungal plant pathogens is unknown. We addressed this by performing a comprehensive phylogenetic analysis of the Cdc14 family and comparing the conservation of active site structure and specificity among a sampling of plant pathogen Cdc14 homologs. We show that Cdc14 was lost in the common ancestor of angiosperm plants but is ubiquitous in ascomycete and basidiomycete fungi. The unique substrate specificity of ScCdc14 was invariant in homologs from eight diverse species of dikarya, suggesting it is conserved across the lineage. A synthetic substrate mimetic inhibited diverse fungal Cdc14 homologs with similar low µMKivalues, but had little effect on related phosphatases. Our results justify future exploration of Cdc14 as a broad spectrum antifungal target for plant protection.
Structural and chemical evolution of Au-silica core–shell nanoparticles during 20 keV helium ion irradiation: a comparison between experiment and simulation
Authors: Mousley M. , Möller W. , Philipp P. , Hlawacek G. , Wirtz T. , Eswara S.
Published: July 2020

Au-silica core–shell nanoparticles have been irradiated with 20 keV He+ ions up to a maximum fluence of 4.7 × 1017 ions/cm2. The nanoscale structural and crystallographic evolution induced by He+ ion irradiation was followed at various stages using Transmission Electron Microscopy (TEM). During irradiation satellite Au clusters are formed around the main Au core, which remained crystalline even after the maximum He+ ion fluence. The spherical silica shell deformed into a hemisphere due to He+ ion irradiation. Three dimensional Monte-Carlo simulations, based on the binary collision approximation, have been performed on stacked infinite layers and an individual particle. The stacked layers results show that the He+ beam interacts with most of the nanoparticle and Au migrates in the direction of beam incidence agreeing with experimental findings. The individual particle results match the experiment in terms of the volume which is sputtered away however additional mechanisms, not included in the simulations, are present in the experiment during the satellite formation and silica shell deformation. These results show the ability for 20 keV He+ ions to be used for the modification of nanostructures. Furthermore, these results contribute to a quantitative understanding of the dynamic evolution of materials observed using microscopy techniques based on He+ ions.
Cardio-postural interactions and muscle-pump baroreflex are severely impacted by 60-day bedrest immobilization
Authors: Xu Da , Tremblay Malcom F. , Verma Ajay K. , Tavakolian Kouhyar , Goswami Nandu , Blaber Andrew P.
Published: July 2020

To understand fundamental mechanisms associated with post-flight orthostatic intolerance we investigated the interaction between the cardiovascular and postural functions before and after 60 days of head down bedrest (HDBR). Twenty healthy young males (35.0 ± 1.7 years) were subjected to 60-day HDBR at 6˚ to simulate spaceflight-induced fluid shifts. A supine-to-stand (STS) test was conducted to evaluate cardio-postural control before and after (R) HDBR while an assessment of cardiovascular function was performed during HDBR. Beat-to-beat heart period, systolic blood pressure, and electromyography impulses were derived for wavelet transform coherence and causality analyses of the cardio-postural control and used to assess changes in the muscle-pump baroreflex. During quiet stand of the STS test, compared to baseline, heart rate was 50% higher on the day of exit from bedrest (R0) and 20% higher eight days later (R8). There was a 50% increase in deoxygenated hemoglobin on R0 and R8. Leg muscle activity reduced, and postural sway increased after HDBR. Causality of the muscle-pump baroreflex was reduced on R0 (0.73 ± 0.2) compared to baseline (0.87 ± 0.2) with complete recovery by R8. The muscle-pump baroreflex also had decreased gain and fraction time active following HDBR. Overall, our data show a significantly impaired muscle-pump baroreflex following bedrest.
Clinical and imaging features of intraosseous arteriovenous malformations in jaws: a 15-year experience of single centre
Authors: Li Xiao , Su Lixin , Wang Deming , Gui Zhipeng , Jiang Mengda , Yang Xitao , Han Yifeng , Zhang Liming , Zheng Lianzhou , Fan Xindong
Published: July 2020

Intraosseous arteriovenous malformations in jaws (j-AVMs) are rare congenital high-flow vascular anomalies with a high tendency of life-threatening haemorrhage and are regarded as one of the most dangerous haemorrhagic diseases in maxillofacial region. Pre-treatment clinical and imaging evaluations serve as the most important diagnostic modalities. A retrospective study involved 211 patients with j-AVMs from November 2003 to November 2017 was performed. The male-to-female ratio of j-AVMs was approximately 4:3. The mean age of the patients with j-AVMs is 21.86. Bleeding was the main complaint associated with j-AVMs. J-AVMs occurred in the mandible more often than in the maxilla (64.93% and 32.23%, respectively). Most j-AVMs (95.26%) occurred in the posterior teeth region. Classical imaging features of j-AVMs included: an unclear maxillary sinus with a mild ground-glass appearance (maxillary j-AVMs) and a clear oval or irregular lucency that is mostly centred on the root of the first molar (mandibular j-AVMs) on OPGs, enhancement in the cancellous bone on contrast-enhanced CTs. Other atypical features of j-AVMs were also concluded. A comprehensive diagnose system based on clinical and imaging features of j-AVMs could provide valuable reference data for clinical management of j-AVMs and help avoid improper iatrogenic trauma or delayed treatment.
Differences in the insect fauna associated to a monocultural pasture and a silvopasture in Southeastern Brazil
Authors: Paiva Iris Guedes , Auad Alexander Machado , Veríssimo Bruno Antonio , Silveira Luís Cláudio Paterno
Published: July 2020

A major challenge for global agriculture is the reduction of the environmental impacts caused by meat and dairy production, and the conversion of monocultural pastures to silvopastoral systems has emerged as an important ally in this process. In order to understand the effects of this conversion we analysed 4 years of sampling of the insect fauna from a conventional monocultural pasture and a silvopastoral system in Minas Gerais, Brazil. We aimed to determine whether the changes caused by the conversion affected the abundance, richness and diversity of the insect orders found in the two systems. Total abundance, richness and diversity did not differ between the two systems, but we detected a significant difference in community composition. Several insect orders showed differences in either abundance, richness or diversity between the two systems, and several families of Hymenoptera, which contains pollinators and natural enemies, showed important increases in the silvopasture. Conversion of monocultural pastures to silvopastures can have important consequences on insect fauna involved in essential ecosystem functions, and the implementation of silvopastures at larger scales has the potential to benefit biodiversity conservation and ecosystem service provision at the landscape scale.
TIMP-3 facilitates binding of target metalloproteinases to the endocytic receptor LRP-1 and promotes scavenging of MMP-1
Authors: Carreca Anna P. , Pravatà Veronica M. , Markham Matthew , Bonelli Simone , Murphy Gillian , Nagase Hideaki , Troeberg Linda , Scilabra Simone D.
Published: July 2020

Matrix metalloproteinases (MMPs) and the related families of disintegrin metalloproteinases (ADAMs) and ADAMs with thrombospondin repeats (ADAMTSs) play a crucial role in extracellular matrix (ECM) turnover and shedding of cell-surface molecules. The proteolytic activity of metalloproteinases is post-translationally regulated by their endogenous inhibitors, known as tissue inhibitors of metalloproteinases (TIMPs). Several MMPs, ADAMTSs and TIMPs have been reported to be endocytosed by the low-density lipoprotein receptor-related protein-1 (LRP-1). Different binding affinities of these proteins for the endocytic receptor correlate with different turnover rates which, together with differences in their mRNA expression, determines their nett extracellular levels. In this study, we used surface plasmon resonance to evaluate the affinity between LRP-1 and a number of MMPs, ADAMs, ADAMTSs, TIMPs and metalloproteinase/TIMP complexes. This identified MMP-1 as a new LRP-1 ligand. Among the proteins analyzed, TIMP-3 bound to LRP-1 with highest affinity (KD = 1.68 nM). Additionally, we found that TIMP-3 can facilitate the clearance of its target metalloproteinases by bridging their binding to LRP-1. For example, the free form of MMP-1 was found to have a KD of 34.6 nM for LRP-1, while the MMP-1/TIMP-3 complex had a sevenfold higher affinity (KD = 4.96 nM) for the receptor. TIMP-3 similarly bridged binding of MMP-13 and MMP-14 to LRP-1. TIMP-1 and TIMP-2 were also found to increase the affinity of target metalloproteinases for LRP-1, albeit to a lesser extent. This suggests that LRP-1 scavenging of TIMP/metalloproteinase complexes may be a general mechanism by which inhibited metalloproteinases are removed from the extracellular environment.
Climatological influences on major storm events during the last millennium along the Atlantic coast of France
Authors: Pouzet Pierre , Maanan Mohamed
Published: July 2020

This paper reviews the climatological influences on major past storm events in the North-east Atlantic. Analyses are based on a millenary record of sedimentological and historical impacts affecting coastal societies. The effects of 20 past storms have been found from sedimentary deposits from the last 1,000 years. Historical archives confirmed these events. This paper highlights five major storms that have markedly impacted coastal populations. They date back to 1351–1352, 1469, 1645, 1711 and 1751 AD. The 1351–1352 AD event is defined as a millennium storm that was “likely apocalyptical”, provoking serious damage and long lasting floods on much of the European coast. Major storm impacts have mostly been recorded during positive North Atlantic Oscillation phases. Four decreasing temperature phases are concomitant with 1300–1355, 1420–1470, 1560–1590 and 1690–1715 AD periods, during which much of the northern Atlantic coast of France underwent severe storm damages.
Harmonizing hybridization dissonance in conservation
Authors: Quilodrán Claudio S. , Montoya-Burgos Juan I. , Currat Mathias
Published: July 2020

A dramatic increase in the hybridization between historically allopatric species has been induced by human activities. However, the notion of hybridization seems to lack consistency in two respects. On the one hand, it is inconsistent with the biological species concept, which does not allow for interbreeding between species, and on the other hand, it is considered either as an evolutionary process leading to the emergence of new biodiversity or as a cause of biodiversity loss, with conservation implications. In the first case, we argue that conservation biology should avoid the discussion around the species concept and delimit priorities of conservation units based on the impact on biodiversity if taxa are lost. In the second case, we show that this is not a paradox but an intrinsic property of hybridization, which should be considered in conservation programmes. We propose a novel view of conservation guidelines, in which human-induced hybridization may also be a tool to enhance the likelihood of adaptation to changing environmental conditions or to increase the genetic diversity of taxa affected by inbreeding depression. The conservation guidelines presented here represent a guide for the development of programmes aimed at protecting biodiversity as a dynamic evolutionary system.
Organophosphorus zwitterions engaged in a conjugated macrocycle on fullerene
Authors: Hashikawa Yoshifumi , Okamoto Shu , Murata Yasujiro
Published: July 2020

Organophosphorus zwitterions are one of the most important but elusive intermediates for carbon–carbon bond formation in synthetic chemistry and biology. However, a lack of isolated examples due to their lability has hampered in-depth understanding of structures and their reaction mechanisms. In this study, we crystallographically reveal the solid-state structure of a phosha-Michael adduct engaged in a cage-opened C60 skeleton, which is formed as a kinetic product. This compound exhibits dark brown colour in solution with an intense absorption band that extends to 1000 nm, reflecting intramolecular charge transfer transitions. From the 1,2-dicarbonyl moiety on the conjugated orifice, β-oxo-phosphorus ylide is formed as a thermodynamic product. The reaction mechanism that has long been disputed is examined by experimental and theoretical studies, showing a pathway which includes an SN2 reaction as a key step instead of the hitherto considered carbene pathway.
Time-reversal of an unknown quantum state
Authors: Lebedev A. V. , Vinokur V. M.
Published: July 2020

For decades, researchers have sought to understand how the irreversibility of the surrounding world emerges from the seemingly time-symmetric, fundamental laws of physics. Quantum mechanics conjectured a clue that final irreversibility is set by the measurement procedure and that the time-reversal requires complex conjugation of the wave function, which is overly complex to spontaneously appear in nature. Building on this Landau-Wigner conjecture, it became possible to demonstrate that time-reversal is exponentially improbable in a virgin nature and to design an algorithm artificially reversing a time arrow for a given quantum state on the IBM quantum computer. However, the implemented arrow-of-time reversal embraced only the known states initially disentangled from the thermodynamic reservoir. Here we develop a procedure for reversing the temporal evolution of an arbitrary unknown quantum state. This opens the route for general universal algorithms sending temporal evolution of an arbitrary system backward in time.