bluuebunny/crossref_metadata_2025 huggingface dataset:
Advances in the Treatment of Cardiac Amyloidosis
Authors: Macedo Ariane Vieira Scarlatelli , Schwartzmann Pedro Vellosa , de Gusmão Breno Moreno , Melo Marcelo Dantas Tavares de , Coelho-Filho Otávio Rizzi
Published: April 2020

Opinion statement

Cardiac amyloidosis is associated with a high mortality rate, a long delay between the first signs and the diagnosis but a short interval between diagnosis and death. This scenario has changed recently due to improved disease awareness among doctors and significant progress in diagnosis thanks to multimodal imaging and a multidisciplinary approach. Therefore, during the last few years, we have had access to specific therapies for those patients. Those therapies are quite different depending on the type of amyloidosis, but there has been real progress. Systemic light chain amyloidosis (AL) with cardiac involvement is the most common form of cardiac amyloidosis. The severity of heart disease dictates the prognosis in AL amyloidosis. Advances in chemotherapy and immunotherapy that suppress light chain production have improved the outcomes. These recent improvements in survival rates have enabled therapies such as implanted cardiac defibrillators and heart transplantation that were usually not indicated for patients with advanced light chain amyloid cardiomyopathy to now be applied in selected patients. For transthyretin amyloidosis (ATTR), the second most common form of amyloidosis with cardiac involvement, there is also significant progress in treatment. Until recently, we had no specific therapy for ATTR cardiomyopathy (ATTR-CM), though now disease-modifying therapies are available. Therapies that stabilize transthyretin, such as tafamidis, have been shown to improve outcomes for patients with ATTR-CM. Modern treatments that stop the synthesis of TTR through gene silencing, such as patisiran and inotersen, have shown positive results for patients with TTR amyloidosis. Significant progress has been made in the treatment of amyloid cardiomyopathy, and hopefully, we will see even more progress with the spread of those treatments. We now can be optimistic about patients with this disease.
Ketamine as an Anesthetic for Patients with Acute Brain Injury: A Systematic Review
Authors: Gregers Mads Christian Tofte , Mikkelsen Søren , Lindvig Katrine Prier , Brøchner Anne Craveiro
Published: April 2020

For years, the use of ketamine as an anesthetic to patients suffering from acute brain injury has been debated because of its possible deleterious effects on the cerebral circulation and thus on the cerebral perfusion. Early studies suggested that ketamine could increase the intracranial pressure thus lowering the cerebral perfusion and hence reduce the oxygen supply to the injured brain. However, more recent studies are less conclusive and might even indicate that patients with acute brain injury could benefit from ketamine sedation. This systematic review summarizes the evidence regarding the use of ketamine in patients suffering from traumatic brain injury. Databases were searched for studies using ketamine in acute brain injury. Outcomes of interest were mortality, intracranial pressure, cerebral perfusion pressure, blood pressure, heart rate, spreading depolarizations, and neurological function. In total 11 studies were included. The overall level of evidence concerning the use of ketamine in brain injury is low. Only two studies found a small increase in intracranial pressure, while two small studies found decreased levels of intracranial pressure following ketamine administration. We found no evidence of harm during ketamine use in patients suffering from acute brain injury.
The composition of acid/oil interface in acid oil emulsions
Authors: Ganeeva Yulia M. , Yusupova Tatiana N. , Barskaya Ekaterina E. , Valiullova Alina Kh. , Okhotnikova Ekaterina S. , Morozov Vladimir I. , Davletshina Lucia F.
Published: April 2020

In well stimulation treatments using hydrochloric acid, undesirable water-in-oil emulsion and acid sludge may produce and then cause operational problems in oil field development. The processes intensify in the presence of Fe(III), which are from the corroded surfaces of field equipment and/or iron-bearing minerals of the oil reservoir. In order to understand the reasons of the stability of acid emulsions, acid emulsions were prepared by mixing crude oil emulsion with 15% hydrochloric acid solutions with and without Fe(III) and then separated into free and upper (water free) and intermediate (with water) layers. It is assumed that the oil phase of the free and upper layers contains the compounds which do not participate in the formation of acid emulsions, and the oil phase of the intermediate layers contains components involved in the formation of oil/acid interface. The composition of the oil phase of each layer of the emulsions was studied. It is found that the asphaltenes with a high content of sulfur, oxygen and metals as well the flocculated material of protonated non-polar oil components are concentrated at the oil/acid interface. In addition to the above, in the presence of Fe(III) the Fe(III)-based complexes with polar groups of asphaltenes are formed at the acid/oil interface, contributing to the formation of armor films which enhance the emulsion stability.
Natural Fibre Modification and Its Influence on Fibre-matrix Interfacial Properties in Biocomposite Materials
Authors: Amiandamhen S. O. , Meincken M. , Tyhoda L.
Published: April 2020

Biocomposite materials manufactured from natural fibres and polymer matrix represent a group of engineered composite products with diverse applications. These materials continue to find increasing applications due to their design flexibility, superior properties and aesthetic appeal. The applicability of these biocomposites, however, depends on the interaction in the fibre-matrix interface. This paper reviews the state of the art research in fibre-matrix interfacial interaction based on published literature. A brief background on biocomposite materials is presented. The focus of this review is the modification of natural fibres and its effect on fibre-matrix interfacial adhesion and properties. In addition, the effect of chemical treatment on fibre composition and fibre-matrix interfacial bonding mechanism are discussed.
Predicting the Past from Minimal Traces: Episodic Memory and its Distinction from Imagination and Preservation
Authors: Werning Markus
Published: April 2020

The paper develops an account of minimal traces devoid of representational content and exploits an analogy to a predictive processing framework of perception. As perception can be regarded as a prediction of the present on the basis of sparse sensory inputs without any representational content, episodic memory can be conceived of as a “prediction of the past” on the basis of a minimal trace, i.e., an informationally sparse, merely causal link to a previous experience. The resulting notion of episodic memory will be validated as a natural kind distinct from imagination. This trace minimalist view contrasts with two theory camps dominating the philosophical debate on memory. On one side, we face versions of the Causal Theory that hold on to the idea that episodic remembering requires a memory trace that causally links the event of remembering to the event of experience and carries over representational content from the content of experience to the content of remembering. The Causal Theory, however, fails to account for the epistemic generativity of episodic memory and is psychologically and information-theoretically implausible. On the other side, a new camp of simulationists is currently forming up. Motivated by empirical and conceptual deficits of the Causal Theory, they reject not only the necessity of preserving representational content, but also the necessity of a causal link between experience and memory. They argue that remembering is nothing but a peculiar form of imagination, peculiar only in that it has been reliably produced and is directed towards an episode of one’s personal past. Albeit sharing their criticism of the Causal Theory and, in particular, rejecting its demand for an intermediary carrier of representational content, the paper argues that a causal connection to experience is still necessary to fulfill even the minimal requirements of past-directedness and reliability.
Quantification of nitrate content with FT-NIR technique in lettuce (Lactuca sativa L.) variety types: a statistical approach
Authors: Boros Ildikó Fruzsina , Sipos László , Kappel Noémi , Csambalik László , Fodor Marietta
Published: April 2020

According to the Commission Regulation (EC) No. 1258/2011, the maximum allowed nitrate content of lettuce is defined within a broad range (2000–5000 mg NO3/kg), depending on harvest season and technology. This study focuses on the identification of the differences in nitrate accumulation between lettuce types and varieties, depending on production technology and on the investigation of the application of non-destructive FT-NIR spectroscopy for nitrate quantification, towards widely used UV–Vis spectroscopy.

In the present study, combinations of seasons and technologies (spring × greenhouse, autumn × open field) were employed for the production of types (batavia, butterhead, lollo and oak leaf; both red and green colored); a total of 266 lettuce heads were analyzed. It was found that with standardized technology and conditions, autumn harvested green oak leaf lettuce types accumulated significantly less nitrate, than red oak or lollo leaf types. With spring harvested lettuces, batavia types generally accumulated generally more nitrates than butterhead types. Based on the linear discriminant analysis (LDA) of FT-NIR measurements the four distinct variety types diverge; the lollo type explicitly diverges from batavia and butterhead types. The LDA further revealed, that within lollo and oak leaf variety types, red and green leaved varieties diverge as well. A model was successfully built for the FT-NIR quantification of the nitrate content of lettuce samples (R2 = 0.95; RMSEE = 74.4 mg/kg fresh weight; Q2 = 0.90; RMSECV = 99.4 mg/kg fresh weight). The developed model is capable of the execution of a fast and non-invasive measurement; the method is suitable for the routine measurement of nitrate content in lettuce.
Modeling for anthracnose development in mango in relation to weather parameters
Authors: Singh Rajender , Deepankar
Published: April 2020

Mango anthracnose severity on leaves was recorded at 14 day intervals throughout the year 2013, 2014, 2015, 2017 and 2018 on mango cultivar Dashaheri. Logistic model was best for the year 2013, 2014, 2015, 2018 and pooled data of these years had lower mean square error (MSE) 37.67, 91.29, 100.84, 65.80 and 72.32 along with high coefficient of determination (R(Dodd et al. 1991)) 0.753, 0.532, 0.534, 0.656 and 0.606, respectively. Maximum anthracnose development i.e. periodical disease progression (6.9%) was highest from 31st to 33th Standard Meteorological Weeks (SMW) because of cumulative effect of minimum temperature (27 °C) and morning relative humidity (≥ 90%) along with the rainfall (56 mm). Mango anthracnose severity was positively and significantly correlated with the minimum temperature (0.62) followed by rainfall (0.46) on all year pooled data basis, whereas the highest correlation 0.65 was observed for the years 2014 and 2015. The regression model based on pooled data has performed better an alternative regression model of each individual year with the highest adjusted R2 value i.e. 0.747, explaining the effects of minimum temperature, morning relative humidity and rainfall on the anthracnose severity.
Use of laser-induced break spectroscopy for the determination of major and trace elements in Zanthoxylum armatum
Authors: Shahida Shabnam , Khan Muhammad Imran , Azad Sadaf , Ahmed Nasar , Lashari Mushtaq Hussain , Khraisheh Majeda , Almomani Fares , Zafar Shagufta
Published: April 2020

Zanthoxylum armatum (ZA) is a medicinal plant (MP) that is widely distributed in hilly and moist areas and has a different medical effect on human curative functions. Laser-induced breakdown spectroscopy (LIBS) was employed as a simple, easy, and accurate method to analyze the elemental profile of Zanthoxylum armatum (ZA) (timur). Various elements present in different parts of ZA were identified including sodium, magnesium, calcium, potassium, titanium, iron, barium, aluminum, lithium, and silicon. The proposed method accuracy was found to be comparable with high technical complicated lab equipment The concentrations of these elements were determined and were found to be below the toxic level.
Anisotropic nonlocal diffusion equations with singular forcing
Authors: Rodríguez Ana , de Pablo Arturo , Quirós Fernando
Published: April 2020

We prove existence, uniqueness and regularity of solutions of nonlocal heat equations associated to anisotropic stable diffusion operators. The main features are that the right-hand side has very little regularity and that the spectral measure can be singular in some directions. The proofs require having good enough estimates for the corresponding heat kernels and their derivatives.
I Just Can’t Get Enough (of Experts): The Numbers of COVID-19 and the Need for a European Approach to Testing
Authors: MORVILLO Marta
Published: April 2020

This article offers a reflection on the testing strategies deployed in the generation of epidemiological data in the European Union (EU). I will argue that, while in the early days of the pandemic, Member States proceeded to testing in a rather scattered way, the shortage of resources seems to have acted as a driver of coordination, which is now increasingly being discussed at EU level. I will examine the legal and institutional framework supporting such embryonic coordination efforts and offer a preliminary assessment of their implications for a European approach to epidemiological knowledge-making.
African Solutions to African Challenges: The Role of Legitimacy in Mediating Civil Wars in Africa
Authors: Duursma Allard
Published: April 2020

The current scholarly literature on the international mediation of civil wars draws predominantly on a rationalist-materialist perspective. This perspective suggests that the ticket to mediation success is the material manipulation of the bargaining environment by third parties with a high degree of economic and military resources. I argue that legitimacy also determines outcomes of mediation because if a mediator has legitimacy, it can continue to look for a mutually satisfactory outcome and try to pull the conflict parties toward compliance. I show that legitimacy matters by systematically comparing the effectiveness of African and non-African third parties. African third parties are typically considered ineffective because of a low degree of economic and military capacity. However, they effectively mediate civil wars in Africa because of a high degree of legitimacy, which is a result of a strong conviction within the African society of states that African mediation is the most desirable type in conflicts there. Drawing on data from the Uppsala Conflict Data Program supplemented with unique data, which together cover all mediation efforts in Africa between 1960 and 2017, I find quantitative evidence supporting the effectiveness of African third parties. Compared to non-African ones, African third parties are far more likely to conclude negotiated settlements that are more likely to be durable. African third parties are especially effective if the conflict parties are highly committed to the African solutions norm. Theoretically, this study deviates from much of the literature that puts forward solely rationalist-materialist explanations of mediation success. By bringing legitimacy to the forefront, this article supplements the current mediation literature that emphasizes material sources of power and ignores social structures.
Magnetic field quantization in pulsars
Authors: Rozina Ch. , Tsintsadze N. L. , Tsintsadze L. N.
Published: April 2020

Magnetic field quantization is an important issue for degenerate environments such as neutron stars, radio pulsars and magnetars etc., due to the fact that these stars have a magnetic field higher than the quantum critical field strength of the order of

$4.4\times 10^{13}~\text{G}$

, accordingly, the cyclotron energy may be equal to or even much more than the Fermi energy of degenerate particles. We shall formulate here the exotic physics of strongly magnetized neutron stars, known as pulsars, specifically focusing on the outcomes of the quantized magnetic pressure. In this scenario, while following the modified quantum hydrodynamic model, we shall investigate both linear and nonlinear fast magnetosonic waves in a strongly magnetized, weakly ionized degenerate plasma consisting of neutrons and an electron–ion plasma in the atmosphere of a pulsar. Here, linear analysis depicts that sufficiently long, fast magnetosonic waves may exist in a weakly dispersive pulsar having finite phase speed at cutoff. To investigate one-dimensional nonlinear fast magnetosonic waves, a neutron density expression as a function of both the electron magnetic and neutron degenerate pressures, is derived with the aid of Riemann’s wave solution. Consequently, a modified Korteweg–de Vries equation is derived, having a rarefractive solitary wave solution. It is found that the basic properties such as amplitude, width and phase speed of the fast magnetoacoustic waves are significantly altered by the electron magnetic and the neutron degenerate pressures. The results of this theoretical investigation may be useful for understanding the formation and features of the solitary structures in astrophysical compact objects such as pulsars, magnetars and white dwarfs etc.
Fast collisional electron heating and relaxation in thin foils driven by a circularly polarized ultraintense short-pulse laser
Authors: Sundström Andréas , Gremillet Laurent , Siminos Evangelos , Pusztai István
Published: April 2020

The creation of well-thermalized, hot and dense plasmas is attractive for warm dense matter studies. We investigate collisionally induced energy absorption of an ultraintense and ultrashort laser pulse in a solid copper target using particle-in-cell simulations. We find that, upon irradiation by a$2\times 10^{20}~\text{W}\,\text{cm}^{-2}$intensity, 60 fs duration, circularly polarized laser pulse, the electrons in the collisional simulation rapidly reach a well-thermalized distribution with${\sim}3.5~\text{keV}$temperature, while in the collisionless simulation the absorption is several orders of magnitude weaker. Circular polarization inhibits the generation of suprathermal electrons, while ensuring efficient bulk heating through inverse bremsstrahlung, a mechanism usually overlooked at relativistic laser intensity. An additional simulation, taking account of both collisional and field ionization, yields similar results: the bulk electrons are heated to${\sim}2.5~\text{keV}$, but with a somewhat lower degree of thermalization than in the pre-set, fixed-ionization case. The collisional absorption mechanism is found to be robust against variations in the laser parameters. At fixed laser pulse energy, increasing the pulse duration rather than the intensity leads to a higher electron temperature.
Kinetic Alfvén wave generation by velocity shear in collisionless plasmas
Authors: Maiorano Teresa , Settino Adriana , Malara Francesco , Pezzi Oreste , Pucci Francesco , Valentini Francesco
Published: April 2020

The evolution of a linearly polarized, long-wavelength Alfvén wave propagating in a collisionless magnetized plasma with a sheared parallel-directed velocity flow is here studied by means of two-dimensional hybrid Vlasov–Maxwell (HVM) simulations. The unperturbed sheared flow has been represented by an exact solution of the HVM set of equations of (Malara et al., Phys. Rev. E, vol. 97, 2018, 053212), thus avoiding spurious oscillations that would arise from the non-stationary initial state and inevitably affect the dynamics of the system. We have considered the evolution of both a small and a moderate amplitude Alfvén wave, in order to separate linear wave–shear flow couplings from kinetic effects, the latter being more relevant for larger wave amplitudes. The phase mixing generated by the shear flow modifies the initial perturbation, leading to the formation of small-scale transverse fluctuations at scales comparable with the proton inertial length/Larmor radius. By analysing both the polarization and group velocity of perturbations in the shear regions, we identify them as kinetic Alfvén waves (KAWs). In the moderate amplitude run, kinetic effects distort the proton distribution function in the shear region. This leads to the formation of a proton beam, at the Alfvén speed and parallel to the magnetic field. Such a feature, due to the parallel electric field associated with KAWs, positively compares with solar wind observations of suprathermal ion populations, suggesting that it may be related to the presence of ion-scale KAW-like fluctuations.
FISCAL CRISES, FORCED LOANS AND UNINTENDED INSTITUTIONAL CONSEQUENCES IN WARTIME BUENOS AIRES, 1800-1820
Authors: Moutoukias Zacarias , ’T Hart Marjolein
Published: April 2020

Between 1800 and 1820, Buenos Aires and the former colonial Viceroyalty of Rio de la Plata faced an unprecedented fiscal crisis caused by the revolutionary wars, eventually solved by levying forced loans. This paper considers the unintended institutional consequences of these loans. The novel devices allowed (1) the holders of forced-loan coupons to use these bonds to pay off debts incurred in customs duties and (2) the holders of bills of exchange involved in the provisioning of the military to use these bills to pay part of their forced loans. Starting with the conceptualisation of the institutional order as a complex system, this paper examines the interactions among the circulation of financial paper bills, the financing of war and changes in the position of the merchants' guild and the legal framework for Atlantic trade. It thereby contributes to renewing institutional change approaches in the Spanish-American context.
Direct Democracy, Constitutional Reform, and Political Inequality in Post-Colonial America
Authors: Chacón Mario , Jensen Jeffrey
Published: April 2020

The ratification of constitutional changes via referendum is an important mechanism for constraining the influence of elites, particularly when representative institutions are captured. While this electoral device is commonly employed cross-nationally, its use is far from universal. We investigate the uneven adoption of mandatory referendums by examining the divergence between Northern and Southern U.S. states in the post-independence period. We first explore why states in both regions adopted constitutional conventions as the primary mechanism for making revisions to fundamental law, but why only Northern states adopted the additional requirement of ratifying via referendum. We argue that due to distortions in state-level representation, Southern elites adopted the discretionary referendum as a mechanism to bypass the statewide electorate when issues divided voters along slave-dependency lines. We demonstrate the link between biases to apportionment and opposition to mandatory referendums using a novel data set of roll calls from various Southern state conventions, including during the secession crisis of 1861.
Marked increase in community-associated methicillin-resistant Staphylococcus aureus infections, Western Australia, 2004–2018
Authors: Bloomfield L. E. , Coombs G. W. , Tempone S. , Armstrong P. K.
Published: April 2020

This study presents enhanced surveillance data from 2004 to 2018 for all community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) specimens collected in Western Australia (WA), and describes the changing epidemiology over this period. A total of 57 557 cases were reviewed. Annual incidence rates increased from 86.2 cases per 100 000 population to 245.6 per 100 000 population (IRR = 2.9, CI95 2.7–3.0). The proportion of isolates carrying Panton–Valentine leucocidin (PVL)-associated genes increased from 3.4% to 59.8% (χ2 test for trend 7021.9, P < 0.001). The emergence of PVL-positive, ‘Queensland CA-MRSA’ (ST93-IV) and ‘WA 121’ (ST5-IV) accounted for the majority of increases in CA-MRSA across the study period. It is unclear why some clones are more prolific in certain regions. In WA, CA-MRSA rates increase as indices of temperature and humidity increase after controlling for socioeconomic disadvantage. We suggest climatic conditions may contribute to transmission, along with other socio-behavioural factors. A better understanding of the ability for certain clones to form ecological niches and cause outbreaks is required.
Evolution of the number of communicative civilizations in the Galaxy: implications on Fermi paradox
Authors: Spada Giorgio , Melini Daniele
Published: April 2020

It has been recently proposed DeVito [(2019) On the meaning of Fermi's paradox.Futures, 389–414] that aminimalnumber of contacts with alien radio-communicative civilizations could be justified by their logarithmically slow rate of growth in the Galaxy. Here we further develop this approach to the Fermi paradox, with the purpose of expanding the ensemble of the possible styles of growth that are consistent with the hypothesis of a minimal number of contacts. Generalizing the approach in DeVito (2019), we show that a logarithmic style of growth is still found. We also find that a style of growth following a power law would be admissible, however characterized by an exponent less than one, hence describing a sublinear increase in the number of communicative civilizations, still qualitatively in agreement with DeVito (2019). No solutions are found indicating a superlinear increase in the number of communicative civilizations, following for example an exponentially diverging law, which would cause, in the long run, an unsustainable proliferation. Although largely speculative, our findings corroborate the idea that a sublinear rate of increase in the number of communicative civilizations in the Galaxy could constitute a further resolution of Fermi paradox, implying a constant and minimal – but not zero – number of contacts.
The Pace of Fluvial Meanders on Mars and Implications for the Western Delta Deposits of Jezero Crater
Authors: Lapôtre Mathieu G. A. , Ielpi Alessandro
Published: April 2020

Although there is little doubt that rivers once flowed on Mars' surface, how sustained and frequent their flows were remains enigmatic. Understanding the hydrology of early Mars, nonetheless, is a prerequisite to resolving the planet's climate history and the astrobiological potential of various ancient putative ecosystems. In 2021, NASA's Perseverance rover will attempt to land near ancient fluviodeltaic deposits in Jezero crater. Deltas offer enhanced organic‐matter burial and preservation on Earth but translating this notion to early Martian environments remains speculative in the absence of information on flow intermittency and sedimentation rates. Here we develop a new model to infer the lateral migration rate of Martian river meanders, which, combined with orbiter‐based observations of the fluviodeltaic deposits at Jezero crater, allows us to determine a minimum timescale for the formation of its delta. We then independently constrain the total duration of delta formation, including dry spells. Our best estimates suggest that delta formation spanned ~19–37 years over a total duration of ~380,000 years, i.e., that rivers flowed for a minimum ~1 sol/15–30 Martian years and conceivably more frequently, but uncertainties on total duration are large. Despite a possibly arid climate, predicted sedimentation rates are high, suggesting a rapid burial of putative organics in distal deposits. Altogether, our results support Jezero crater's potential as a prime target to look for ancient Martian life and acquire samples to return to Earth. Any discrepancies between our predictions of the deposits' grain‐to‐bedform‐scale architecture and future rover observations will shed critical light onto Mars' early surface environments.
Stress Drop Variation of Deep‐Focus Earthquakes Based on Empirical Green's Functions
Authors: Liu Meichen , Huang Yihe , Ritsema Jeroen
Published: April 2020

We analyze source characteristics of global, deep‐focus (>350 km) earthquakes with moment magnitudes (Mw) larger than 6.0–8.2 using teleseismic P‐wave and S‐wave spectra and an empirical Green's functions approach. We estimate the corner frequency assuming Brune's source model and calculate stress drops assuming a circular crack model. Based on P‐wave and S‐wave spectra, the one standard deviation ranges are 3.5–369.8 and 8.2–328.9 MPa, respectively. Based on the P‐wave analysis, the median of our stress drop estimates is about a factor of 10 higher than the median stress drop of shallow earthquakes with the same magnitude estimated by Allmann and Shearer (2009, https://doi.org/10.1029/2008JB005821). This suggests that, on average, the shear stress of deep faults in the mantle transition zone is an order of magnitude higher than the shear stress of faults in the crust. The wide range of stress drops implies coexistence of multiple physical mechanisms.
Amagmatic Subduction Produced by Mantle Serpentinization and Oceanic Crust Delamination
Authors: Yang Jianfeng , Lu Gang , Liu Tong , Li Yang , Wang Kun , Wang Xinxin , Sun Baolu , Faccenda Manuele , Zhao Liang
Published: April 2020

Recycling of oceanic lithosphere and serpentinized peridotites into the mantle leads to dehydration melting and volcanic arcs. However, the mechanism of the occurrence of long‐term volcanic gap in subduction zones remains poorly understood. Two‐dimensional thermomechanical numerical models focusing on resisting the transport of the major hosts of hydrous minerals to mantle depths, show that thin oceanic crust together with rheologically weak and buoyant serpentinized mantle could result in hydrated lithologies piling up in the accretionary wedge and no or sparse occurrence of arc magmatism. This scenario may occur during subduction of oceanic lithosphere formed at (ultra)slow‐spreading margins characterized by thin crust and extensive mantle serpentinization, which is a plausible explanation for the “arc gaps” in the Alps and southern Tibet.
Healing Behavior of Simulated Fault Gouges From the Groningen Gas Field and Implications for Induced Fault Reactivation
Authors: Hunfeld Luuk B. , Chen Jianye , Hol Sander , Niemeijer André R. , Spiers Christopher J.
Published: April 2020

We investigated the frictional strength recovery (healing) and subsequent reactivation and slip‐weakening behavior of simulated fault gouges derived from key stratigraphic units in the seismogenic Groningen gas field (N. E. Netherlands). Direct‐shear, slide‐hold‐slide (SHS) experiments were performed at in situ conditions of 100 °C, 40 MPa effective normal stress and 10–15 MPa pore fluid pressure (synthetic formation brine). Sheared gouges were allowed to heal for periods up to 100 days before subsequent reshearing. The initial coefficient of (steady) sliding friction μ was highest in the Basal Zechstein caprock (μ = 0.65 ± 0.02) and Slochteren sandstone reservoir (μ = 0.61 ± 0.02) gouges, and the lowest in the Ten Boer claystone at the reservoir top (μ = 0.38 ± 0.01) and in the Carboniferous shale substrate (μ ≈ 0.45). Healing and subsequent reactivation led to a marked increase (∆μ) in (static) friction coefficient of up to ~0.16 in Basal Zechstein and ~0.07 in Slochteren sandstone gouges for the longest hold periods investigated, followed by a sharp strength drop (up to ~25%) and slip‐weakening trajectory. By contrast, the Ten Boer and Carboniferous gouges showed virtually no healing or strength drop. Healing rates in the Basal Zechstein and Slochteren sandstone gouges were significantly affected by the stiffness of different machines used, in line with the Ruina slip law, and with a microphysical model for gouge healing. Our results point to marked stratigraphic variation in healed frictional strength and healing rate of faults in the Groningen system, and high seismogenic potential of healed faults cutting the reservoir and Basal Zechstein caprock units, upon reactivation.
Efficient Carbon Recycling at the Central‐Northern Lesser Antilles Arc: Implications to Deep Carbon Recycling in Global Subduction Zones
Authors: Li Kan , Li Long , Aubaud Cyril , Muehlenbachs Karlis
Published: April 2020

Carbon recycling efficiency of arc (CREA) is an important parameter to assess the recycling of slab carbon into Earth's deep interior. Although previous studies observed variable degrees of recycled slab carbon at global arcs, the CREA value of any individual subduction zone has not been obtained due to the loose constraints on carbon budget in altered oceanic crust (AOC). Here, through estimates of carbon input by both sediments and AOC at DSDP Site 543 and recycled carbon output from major volcanoes in the Central‐Northern Lesser Antilles, we show an extremely efficient carbon recycling case, with the CREA value reaching 100±27%. Nearly complete slab carbon release at sub‐arc depth implies little carbon has been lost in the forearc region or subducted into the deep mantle in this subduction zone. Our results highlight strongly variable CREA on a global scale, which must be considered in the modeling of global deep carbon cycle.
Methane, Monsoons, and Modulation of Millennial‐Scale Climate
Authors: Thirumalai Kaustubh , Clemens Steven C. , Partin Judson W.
Published: April 2020

Earth's orbital geometry exerts a profound influence on climate by regulating changes in incoming solar radiation. Superimposed on orbitally paced climate change, Pleistocene records reveal substantial millennial‐scale variability characterized by abrupt changes and rapid swings. However, the extent to which orbital forcing modulates the amplitude and timing of these millennial variations is unclear. Here we isolate the magnitude of millennial‐scale variability (MMV) in two well‐dated records, both linked to precession cycles (19,000‐ and 23,000‐year periodicity): composite Chinese speleothem δ18O, commonly interpreted as a proxy for Asian monsoon intensity, and atmospheric methane. At the millennial timescale (1,000–10,000 years), we find a fundamental decoupling wherein precession directly modulates the MMV of methane but not that of speleothem δ18O, which is shown to be strikingly similar to the MMV of Antarctic ice core δ2H. One explanation is that the MMV of methane responds to changes in midlatitude to high‐latitude insolation, whereas speleothem δ18O is modulated by internal climate feedbacks.
Impaired expression of the COSMOC/MOCOS gene unit in ASD patient stem cells
Authors: Rontani Pauline , Perche Olivier , Greetham Louise , Jullien Nicolas , Gepner Bruno , Féron François , Nivet Emmanuel , Erard-Garcia Madeleine
Published: April 2020

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders with a very large number of risk loci detected in the genome. However, at best, each of them explains rare cases, the majority being idiopathic. Genomic data on ASD derive mostly from post-mortem brain analyses or cell lines derived from blood or patient-specific induced pluripotent stem cells (iPSCS). Therefore, the transcriptional and regulatory architecture of the nervous system, particularly during early developmental periods, remains highly incomplete. To access the critical disturbances that may have occurred during pregnancy or early childhood, we recently isolated stem cells from the nasal cavity of anesthetized patients diagnosed for ASD and compared them to stem cells from gender-matched control individuals without neuropsychiatric disorders. This allowed us to discover MOCOS, a non-mutated molybdenum cofactor sulfurase-coding gene that was under-expressed in the stem cells of most ASD patients of our cohort, disturbing redox homeostasis and synaptogenesis. We now report that a divergent transcription upstream of MOCOS generates an antisense long noncoding RNA, to which we coined the name COSMOC. Surprisingly, COSMOC is strongly under-expressed in all ASD patients of our cohort with the exception of a patient affected by Asperger syndrome. Knockdown studies indicate that loss of COSMOC reduces MOCOS expression, destabilizes lipid and energy metabolisms of stem cells, but also affects neuronal maturation and splicing of synaptic genes. Impaired expression of the COSMOC/MOCOS bidirectional unit might shed new lights on the origins of ASD that could be of importance for future translational studies.
Adjunctive metformin for antipsychotic-induced dyslipidemia: a meta-analysis of randomized, double-blind, placebo-controlled trials
Authors: Jiang Wen-Long , Cai Dong-Bin , Yin Fei , Zhang Ling , Zhao Xi-Wu , He Jie , Ng Chee H. , Ungvari Gabor S. , Sim Kang , Hu Mei-Ling , Zheng Wei , Xiang Yu-Tao
Published: April 2020

Antipsychotic-induced dyslipidemia could increase the risk of cardiovascular diseases. This is a meta-analysis of randomized double-blind placebo-controlled trials to examine the efficacy and safety of adjunctive metformin for dyslipidemia induced by antipsychotics in schizophrenia. The standardized mean differences (SMDs) and risk ratios (RRs) with their 95% confidence intervals (CIs) were calculated using the random-effects model with the RevMan 5.3 version software. The primary outcome was the change of serum lipid level. Twelve studies with 1215 schizophrenia patients (592 in metformin group and 623 in placebo group) were included and analyzed. Adjunctive metformin was significantly superior to placebo with regards to low density lipoprotein cholesterol (LDL-C) [SMD: −0.37 (95%CI:−0.69, −0.05),P = 0.02;I2 = 78%], total cholesterol [SMD: −0.47 (95%CI:−0.66, −0.29),P < 0.00001;I2 = 49%], triglyceride [SMD: −0.33 (95%CI:−0.45, −0.20),P < 0.00001;I2 = 0%], and high density lipoprotein cholesterol [SMD: 0.29 (95%CI:0.02, 0.57),P = 0.03;I2 = 69%]. The superiority of metformin in improving LDL-C level disappeared in a sensitivity analysis and 80% (8/10) of subgroup analyses. Metformin was significantly superior to placebo with regards to decrease in body weight, body mass index, glycated hemoglobin A1c, fasting insulin, and homeostasis model assessment-insulin resistance (P = 0.002–0.01), but not regarding changes in waist circumference, waist-to-hip rate, leptin, fasting glucose, and blood pressure (P = 0.07–0.33). The rates of discontinuation due to any reason [RR: 0.97 (95%CI: 0.66, 1.43),P = 0.89;I2 = 0%] was similar between the two groups. Adjunctive metformin could be useful to improve total cholesterol and triglyceride levels, but it was not effective in improving LDL-C level in schizophrenia.
Altered anterior cingulate glutamatergic metabolism in depressed adolescents with current suicidal ideation
Authors: Lewis Charles P. , Port John D. , Blacker Caren J. , Sonmez A. Irem , Seewoo Bhedita J. , Leffler Jarrod M. , Frye Mark A. , Croarkin Paul E.
Published: April 2020

The anterior cingulate cortex (ACC) is involved in emotion regulation and salience processing. Prior research has implicated ACC dysfunction in suicidal ideation (SI) and suicidal behavior. This study aimed to quantify ACC glutamatergic concentrations and to examine relationships with SI in a sample of healthy and depressed adolescents. Forty adolescents underwent clinical evaluation and proton magnetic resonance spectroscopy (1H-MRS) at 3 T, utilizing a 2-dimensionalJ-averaged PRESS sequence sampling a medial pregenual ACC voxel. Cerebrospinal fluid-corrected ACC metabolite concentrations were compared between healthy control (HC,n = 16), depressed without SI (Dep/SI−,n = 13), and depressed with SI (Dep/SI+,n = 11) youth using general linear models covarying for age, sex, and psychotropic medication use. Relationships between ACC metabolites and continuous measures of SI were examined using multiple linear regressions. ROC analysis was used to determine the ability of glutamate+glutamine (Glx) and theN-acetylaspartate (NAA)/Glx ratio to discriminate Dep/SI− and Dep/SI+ adolescents. Dep/SI+ adolescents had higher Glx than Dep/SI− participants (padj = 0.012) and had lower NAA/Glx than both Dep/SI− (padj = 0.002) and HC adolescents (padj = 0.039). There were significant relationships between SI intensity and Glx (pFDR = 0.026), SI severity and NAA/Glx (pFDR = 0.012), and SI intensity and NAA/Glx (pFDR = 0.004). ACC Glx and NAA/Glx discriminated Dep/SI− from Dep/SI+ participants. Uncoupled NAA−glutamatergic metabolism in the ACC may play a role in suicidal ideation and behavior. Longitudinal studies are needed to establish whether aberrant glutamatergic metabolism corresponds to acute or chronic suicide risk. Glutamatergic biomarkers may be promising targets for novel risk assessment and interventional strategies for suicidal ideation and behavior.
On the diagnostic and neurobiological origins of bipolar disorder
Authors: Charney Alexander W. , Mullins Niamh , Park You Jeong , Xu Jonathan
Published: April 2020

Psychiatry is constructed around a taxonomy of several hundred diagnoses differentiated by nuances in the timing, co-occurrence, and severity of symptoms. Bipolar disorder (BD) is notable among these diagnoses for manic, depressive, and psychotic symptoms all being core features. Here, we trace current understanding of the neurobiological origins of BD and related diagnoses. To provide context, we begin by exploring the historical origins of psychiatric taxonomy. We then illustrate how key discoveries in pharmacology and neuroscience gave rise to a generation of neurobiological hypotheses about the origins of these disorders that facilitated therapeutic innovation but failed to explain disease pathogenesis. Lastly, we examine the extent to which genetics has succeeded in filling this void and contributing to the construction of an objective classification of psychiatric disturbance.
Emerging role of PTEN loss in evasion of the immune response to tumours
Authors: Vidotto Thiago , Melo Camila Morais , Castelli Erick , Koti Madhuri , dos Reis Rodolfo Borges , Squire Jeremy A.
Published: April 2020

Mutations inPTENactivate the phosphoinositide 3-kinase (PI3K) signalling network, leading to many of the characteristic phenotypic changes of cancer. However, the primary effects of this gene on oncogenesis through control of the PI3K–AKT–mammalian target of rapamycin (mTOR) pathway might not be the only avenue by which PTEN affects tumour progression. PTEN has been shown to regulate the antiviral interferon network and thus alter how cancer cells communicate with and are targeted by immune cells. An active, T cell-infiltrated microenvironment is critical for immunotherapy success, which is also influenced by mutations in DNA damage repair pathways and the overall mutational burden of the tumour. As PTEN has a role in the maintenance of genomic integrity, it is likely that a loss of PTEN affects the immune response at two different levels and might therefore be instrumental in mediating failed responses to immunotherapy. In this review, we summarise findings that demonstrate how the loss of PTEN function elicits specific changes in the immune response in several types of cancer. We also discuss ongoing clinical trials that illustrate the potential utility of PTEN as a predictive biomarker for immune checkpoint blockade therapies.
The deubiquitylase USP2 maintains ErbB2 abundance via counteracting endocytic degradation and represents a therapeutic target in ErbB2-positive breast cancer
Authors: Zhang Jinrui , Liu Shuyan , Li Qiong , Shi Yulin , Wu Yueguang , Liu Fang , Wang Shanshan , Zaky Mohamed Y. , Yousuf Waleed , Sun Qianhui , Guo Dong , Wang Taishu , Zhang Yingqiu , Wang Yang , Li Man , Liu Han
Published: April 2020

ErbB2 overexpression identifies a subclass of breast cancer as ErbB2-positive that is frequently associated with poor prognosis. Current ErbB2-targeted therapies have profoundly improved patient outcomes, but mutations occurring in ErbB2 have been shown to confer drug resistance. Induction of ErbB2 degradation was proposed as an intriguing strategy to battle with ErbB2-positive breast cancer and reduced mutation-incurred drug resistance. Although multiple HSP90 inhibitors have been demonstrated to effectively trigger ErbB2 degradation, none succeeded in the clinical evaluations. To develop novel ErbB2-targeting strategies, we investigated the endocytic degradation and reversible ubiquitylation of ErbB2 in breast cancer. In this study, we reveal that HSP90 inhibition leads to efficient ubiquitylation and endocytic degradation of ErbB2 through the canonical endo-lysosomal route. USP2 associates with internalized ErbB2 and prevents its lysosomal sorting and degradation via exerting deubiquitylase activity. Accordingly, the USP2 inhibitor ML364 is capable of inducing ErbB2 ubiquitylation and accelerating its turnover. ML364 potentiates the pro-degradation effects of HSP90 inhibitors on ErbB2 and hence sensitizes ErbB2-positive breast cancer cells to HSP90 inhibition. The combination of USP2 and HSP90 inhibitors effectively restrains ErbB2-positive breast cancer xenograft growth in vivo. Based on these observations, we conclude that USP2 safeguards ErbB2 surface levels by antagonizing its ubiquitylation-mediated endocytic degradation, which can be exploited to design novel therapeutic strategies against ErbB2-driven malignancies as combinatorial treatment with HSP90 inhibitors.
Interplay of Calcium and Nitric Oxide in improvement of Growth and Arsenic-induced Toxicity in Mustard Seedlings
Authors: Singh Rachana , Parihar Parul , Prasad Sheo Mohan
Published: April 2020

In this study, Ca2+ mediated NO signalling was studied in response to metalloid (As) stress in Brassica seedlings. Arsenic toxicity strongly suppressed the growth (fresh weight, root and shoot length), photosynthetic pigments, Chl a fluorescence indices (Kinetic traits: Fv, Fm, Fv/Fo, Fm/Fo, ФPo or Fv/Fm, Ψo, ФEo, PIABS, Area and N and redox status (AsA/DHA and GSH/GSSG ratios) of the cell; whereas energy flux traits: ABS/RC, TRo/RC, ETo/RC and DIo/RC along with Fo, Fo/Fv, Fo/Fm, ФDo and Sm) were enhanced. Further, addition of EGTA (Ca2+ scavenger) and LaCl3 (plasma membrane Ca2+ channel blocker) to As + Ca; while c‒PTIO (NO scavenger) and l‒NAME (NO synthase inhibitor) to As + SNP treated seedlings, siezed recovery on above parameters caused due to Ca2+ and NO supplementation, respectively to As stressed seedlings thereby indicating their signalling behaviour. Further, to investigate the link between Ca2+ and NO, when c‒PTIO and l‒NAME individually as well as in combination were supplemented to As + Ca treated seedlings; a sharp inhibition in above mentioned traits was observed even in presence of Ca2+, thereby signifying that NO plays crucial role in Ca2+ mediated signalling. In addition, As accumulation, ROS and their indices, antioxidant system, NO accumulation and thiol compounds were also studied that showed varied results.