bluuebunny/crossref_metadata_2025 huggingface dataset:
An adaptive finite element model for steerable needles
Authors: Terzano Michele , Dini Daniele , Rodriguez y Baena Ferdinando , Spagnoli Andrea , Oldfield Matthew
Published: March 2020

Penetration of a flexible and steerable needle into a soft target material is a complex problem to be modelled, involving several mechanical challenges. In the present paper, an adaptive finite element algorithm is developed to simulate the penetration of a steerable needle in brain-like gelatine material, where the penetration path is not predetermined. The geometry of the needle tip induces asymmetric tractions along the tool–substrate frictional interfaces, generating a bending action on the needle in addition to combined normal and shear loading in the region where fracture takes place during penetration. The fracture process is described by a cohesive zone model, and the direction of crack propagation is determined by the distribution of strain energy density in the tissue surrounding the tip. Simulation results of deep needle penetration for a programmable bevel-tip needle design, where steering can be controlled by changing the offset between interlocked needle segments, are mainly discussed in terms of penetration force versus displacement along with a detailed description of the needle tip trajectories. It is shown that such results are strongly dependent on the relative stiffness of needle and tissue and on the tip offset. The simulated relationship between programmable bevel offset and needle curvature is found to be approximately linear, confirming empirical results derived experimentally in a previous work. The proposed model enables a detailed analysis of the tool–tissue interactions during needle penetration, providing a reliable means to optimise the design of surgical catheters and aid pre-operative planning.
Adaptive laboratory evolution induced novel mutations in Zymomonas mobilis ATCC ZW658: a potential platform for co-utilization of glucose and xylose
Authors: Sarkar Payel , Mukherjee Mayurketan , Goswami Gargi , Das Debasish
Published: March 2020

A systematic adaptive laboratory evolution strategy was employed to develop a potential Zymomonas mobilis strain with the ability to co-utilize glucose and xylose. Z. mobilis ATCC ZW658, a recombinant xylose fermenting strain, was subjected to adaptive laboratory evolution over a period of 200 days under strict selection pressure of increasing concentration of xylose. The evolved strain exhibited 1.65 times increase in the overall specific xylose utilization rate when compared with the parent strain. Furthermore, the strain displayed significantly improved performance in terms of co-fermentation of xylose in the presence of glucose with specific glucose and xylose utilization rate of 1.24 g g−1 h−1 and 1.34 g g−1 h−1, respectively. Altered phenotypic response of the evolved strain, in terms of improved xylose utilization, co-utilization of mixed sugars, enhanced growth, ethanol production, and reduced xylitol production has been explained by novel mutations, identified using next-generation sequencing, in xylose assimilating, metabolizing, and crucial regulatory pathway genes and key enzyme activity assays.
New Times, New Crimes: Notes on the Depillarization of the Criminal Justice System
Authors: Matthews Roger
Published: March 2020

A great deal has been written about the changing nature and direction of criminology over the past two decades, including claims that we are moving into a “new penology.” Many of these claims are suggestive rather than authoritative. In contrast to most commentaries on the subject, this article provides longer historical overview and attempts to sketch out how the central structures or “pillars” of the criminal justice system have become weakened and eroded over the last 200 years and how the emergence of body of “new crimes” and their regulation is challenging what might be called the “old criminology.” The emergence of new relations between victims and offenders, criminal justice and social justice, as well as the development of innovative modes of regulation are, it is argued, changing the social and criminological landscape. This raises issues of theory and practice that challenge traditional conceptualisations of crime and punishment.
An Evolutionary Sceptical Challenge to Scientific Realism
Authors: de Ray Christophe
Published: March 2020

Evolutionary scepticism holds that the evolutionary account of the origins of the human cognitive apparatus has sceptical implications for at least some of our beliefs. A common target of evolutionary scepticism is moral realism.Scientificrealism, on the other hand, is much less frequently targeted, though the idea that evolutionary theory should make us distrustful of science is by no means absent from the literature. This line of thought has received unduly little attention. I propose to remedy this by advancing what I will call anevolutionary sceptical challenge to scientific realism. I argue that, given standard evolutionary theory, our possession of sound innate metaphysical intuitions would have taken an epistemically problematic ‘lucky accident’. This, as I will show, entails that scientific realism is a self-undermining position. I discuss objections to my argument’s two premises, including ones that appeal to the success of the sciences and to the possibility that sound innate metaphysical intuitions evolved as an evolutionary ‘by-product’. I then draw out an advantage of my argument over a similar one recently put forward by Graber and Golemon (Sophia, 2019.10.1007/s11841-018-0695-0). I finish by submitting that scientific realism, given the soundness of my argument, is faced with a new ‘Darwinian Dilemma’, and briefly address the significance of this for the debate between realists and anti-realists in the philosophy of science.
Fabrication of high thermal conductivity copper/diamond composites by electrodeposition under potentiostatic conditions
Authors: Arai Susumu , Ueda Miyoka
Published: March 2020

High thermal conductivity Cu/diamond composites were fabricated using an electrodeposition technique. The electrodes were oriented horizontally, and the cathode was located at the bottom of the plating bath. Diamond particles (10–230 μm) were first precipitated on the cathode substrate, and then copper was electrodeposited on the substrate to fill the gap between the precipitated diamond particles, which resulted in the formation of a Cu/diamond composite. The deposition behavior of the copper was electrochemically investigated, and the current densities of copper deposition under galvanostatic conditions were estimated. The current densities for the substrate with diamond particle layers were 4–10 times higher than the current density for the substrate without diamond particle layers, which led to undesired hydrogen evolution. Cu/diamond composites were formed under potentiostatic conditions without hydrogen evolution, and the resultant composites had compact morphologies. A specimen containing 49 vol% diamond particles with a mean diameter of 230 μm had the highest thermal conductivity of 600 W m−1 K−1, which is 1.5 times that of pure copper (ca. 400 W m−1 K−1).

Graphic Abstract

High thermal conductivity Cu/diamond composites were fabricated by electrodeposition under a potentiostatic condition without the evolution of hydrogen gas.
Beyond the Moral Influence Theory? A Critical Examination of Vargas’s Agency Cultivation Model of Responsibility
Authors: Harland Harry
Published: March 2020

This paper repudiates Manuel Vargas’s attempt to supplant the traditional moral influence theory of responsibility (MIT) with his ‘agency cultivation model’ (ACM). By focusing on fostering responsiveness to moral considerations, ACM purports to avoid the chief pitfalls of MIT. However, I contend that ACM is far less distinctive than it initially appears and so possesses all of MIT’s defects. I also assail Vargas’s counterfactual test for assessing whether a wrongdoer can respond to moral considerations. It is argued that the counterfactual test is epistemically redundant because it can only be fleshed out once we have settled the issues it is supposed to resolve. Moreover, it tacitly inverts the relation between freedom and responsibility—we cannot attribute free will to wrongdoers unless we have already established their blameworthiness. The upshot of this is that enquiries into an agent’s freedom are irrelevant to the ethics of holding her responsible.
Kinetics of Slag Reduction in Silicomanganese Production
Authors: Canaguier Vincent , Tangstad Merete
Published: March 2020

In this study, the reduction of three silicomanganese charges prepared from industrial raw materials was investigated under isothermal conditions between 1783 K and 1933 K (1510 °C and 1660 °C). The main reactions examined are MnO and SiO2 slag reduction following the chemical equations MnO(l) + C = Mn(l) + CO(g) and SiO2(l) + 2C = Si(l) + 2CO(g). The charges containing a combination of Assmang ore, Comilog ore, high-carbon FeMn slag with quartz were pre-reduced, melted to a MnO-SiO2-Al2O3-MgO-CaO quinary slag and reduced in presence of coke using a thermogravimetric set-up. The reduced slags were further analyzed using electro-probe micro-analysis to evaluate their MnO and SiO2 contents. It is observed that the reduction pathway occurred in two stages: a first slow and stable stage was followed by a rapid rate increase during the second stage. The rate change shift between the two stages was found to depend on the initial charge’s composition and the extent of reduction, but not on the temperature. Using an established rate equation, the kinetics of MnO and SiO2 reduction were modeled over the first stage. A good fit was obtained between simulated and experimental data.
Antiplasmodial activity of Cocos nucifera leaves in Plasmodium berghei-infected mice
Authors: Tayler Nicole M. , De Jesús Rosa , Spadafora Rita , Coronado Lorena M. , Spadafora Carmenza
Published: March 2020

Plasmodium falciparum(P. falciparum) malaria presents serious public health problems worldwide. The parasite´s resistance to antimalarial drugs has proven to be a significant hurdle in the search for effective treatments against the disease. For this reason, the study of natural products to find new antimalarials remains a crucial step in the fight against malaria. In this study, we aimed to study the in vivo performance of the decoction ofC. nuciferaleaves inP. berghei-infected mice. We analyzed the effectiveness of different routes of administration and the acute toxicity of the extract. Additionally, we determined the suppressive, curative and prophylactic activity of the extract. The results showed that the decoction of leaves ofC. nuciferais most effective when administered intramuscularly to mice in comparison to intraperitoneal, subcutaneous and intragastric methods. We also found that organ signs of acute toxicity appear at 2000 mg/kg/day as evidenced by necropsy examination. Additionally, we found that the prophylactic effect of the extract is of 48% inhibition, however, there is no curative effect. Finally, in a 4-day suppressive assay, we found that the extract can inhibit the growth of the parasite by up to 54% at sub-toxic doses when administered intramuscularly.
Examination of electrodermal and cardio-vascular reactivity in virtual reality through a combined stress induction protocol
Authors: Kerous Bojan , Barteček Richard , Roman Robert , Sojka Petr , Bečev Ondřej , Liarokapis Fotis
Published: March 2020

In this study, task-related stress induction through Stroop task and social stress induction protocol based on elements of Trier Social Stress Test are examined. The aim of the paper is to find the optimal combination of social and task-related stress to be used to consistently and reliably induce a stressful reaction. In total 16 healthy subjects participated in this study that seeks to find and compare the different stressors and their relation to physiological reactivity. Our findings show that electrodermal activity measurements are suitable when using a combination of stressors while heart rate and Root Mean Square of the Successive Differences highlight a greater reactivity to task-stress.
Stent edge vascular response and in-stent geometry after aerobic exercise
Authors: Taraldsen Maria Dalen , Videm Vibeke , Hegbom Knut , Wiseth Rune , Madssen Erik
Published: March 2020

The purpose of the present study was to investigate the edge vascular response in patients treated with second-generation drug-eluting stents (DES) after 3 months of aerobic exercise intervention. Thirty-two patients with significant coronary artery disease underwent percutaneous coronary intervention with DES implantation prior to randomization to aerobic interval training (AIT, 14 patients) versus moderate continuous training (MCT, 18 patients). Plaque changes were assessed using grayscale and radiofrequency intravascular ultrasound at baseline and follow-up. The main endpoints were changes in plaque burden and necrotic core content in the 5-mm proximal and distal stent edges. Plaque burden in the distal stent edges decreased significantly in both groups (AIT: − 3.3%; MCT: − 0.4%, p = 0.01 for both), and more in the AIT group (p = 0.048). Necrotic core content decreased significantly in the distal stent edges in both groups (− 2.1 mm3 in AIT, − 0.3 mm3 in MCT, p = 0.01 for both), and more in the AIT group (p = 0.03). There were no significant changes in proximal stent edges or in in-stent geometry at follow-up. In this small study of patients treated with DES implantation, 3 months of aerobic exercise training demonstrated decreased plaque burden and necrotic core content in the distal stent edges, with larger reductions in the AIT group.
Proposed Definition of Experimental Secondary Ischemia for Mouse Subarachnoid Hemorrhage
Authors: van Lieshout Jasper Hans , Marbacher Serge , Muhammad Sajjad , Boogaarts Hieronymus D. , Bartels Ronald H. M. A. , Dibué Maxine , Steiger Hans-Jakob , Hänggi Daniel , Kamp Marcel A.
Published: March 2020

Inconsistency in outcome parameters for delayed cerebral ischemia (DCI) makes it difficult to compare results between mouse studies, in the same way inconsistency in outcome parameters in human studies has for long obstructed adequate comparison. The absence of an established definition may in part be responsible for the failed translational results. The present article proposes a standardized definition for DCI in experimental mouse models, which can be used as outcome measure in future animal studies. We used a consensus-building approach to propose a definition for “experimental secondary ischemia” (ESI) in experimental mouse subarachnoid hemorrhage that can be used as an outcome measure in preclinical studies. We propose that the outcome measure should be as follows: occurrence of focal neurological impairment or a general neurological impairment compared with a control group and that neurological impairment should occur secondarily following subarachnoid hemorrhage (SAH) induction compared with an initial assessment following SAH induction. ESI should not be used if the condition can be explained by general anesthesia or if other means of assessments sufficiently explain function impairment. If neurological impairment cannot reliably be evaluated, due to scientific setup. Verification of a significant secondary impairment of the cerebral perfusion compared with a control group is mandatory. This requires longitudinal examination in the same animal. The primary aim is that ESI should be distinguished from intervention-related ischemia or neurological deficits, in order establish a uniform definition for experimental SAH in mice that is in alignment with outcome measures in human studies.
Interactions between anxiety subtypes, personality characteristics, and emotional regulation skills as predictors of future work outcomes
Authors: Chandra Cerella M. , Szwedo David E. , Allen Joseph P. , Narr Rachel K. , Tan Joseph S.
Published: March 2020

Introduction

This study examined long‐term predictive links between different types of anxiety in late adolescence and work‐related outcomes in young adulthood. The presence of adaptive personality traits and positive emotion regulation and coping skills were hypothesized to buffer these associations, reducing the negative effects of anxiety on future work outcomes.

Methods

Hypotheses were tested using multi‐reporter data from a community sample of 184 youth in the United States followed from ages 17–30. Trait anxiety, anxious arousal, rejection sensitivity, and implicit rejection were each examined in late adolescence as predictors of work‐related ambition, work performance, job satisfaction, and career satisfaction in young adulthood. Conscientiousness, grit, emotion regulation (ER) and coping skills were examined as potential moderators.

Results

Although trait anxiety was the only anxiety variable directly predictive of work outcomes in regression analyses, personality variables and ER skills interacted with multiple types of anxiety to predict work outcomes. Interestingly, findings reflected a pattern in which a combination of greater conscientiousness and greater anxiety, and greater ER skills and greater anxiety, predicted more positive work outcomes.

Conclusions

These findings not only suggest that the development of traits such as conscientiousness and ER skills may be helpful for youth with higher levels of anxiety, but also that higher levels of anxiety, when appropriately balanced by other qualities, may be adaptive for promoting positive career development for some youth.
Birth Order and Sibling Sex Ratio in Androphilic Males and Gynephilic Females Diagnosed with Gender Dysphoria from Iran
Authors: Khorashad Behzad S. , Zucker Kenneth J. , Talaei Ali , Rajabzadeh Farzaneh , Hamed Zahra , Akbarian Pardis , Blanchard Ray
Published: March 2020

Background

This study investigated the effect of older brothers on sexual orientation in male adults diagnosed with gender dysphoria and the effect of older sisters on sexual orientation in female adults diagnosed with gender dysphoria from Iran.

Aim

To assess for the presence of a fraternal birth order effect in transgender androphilic males and a sororal birth order effect in transgender gynephilic females.

Methods

The subjects were 92 transgender males and 107 transgender females (all of whom met the DSM-5 criteria for gender dysphoria), together with 72 male and 78 female clinical controls. All the transgender males were androphilic, all the transgender females were gynephilic (preferentially attracted to members of their own biological sex), and all of the clinical controls were heterosexual (none were transgender or had a diagnosis of gender dysphoria).

Outcomes

In relation to the probands, we analyzed the sibship composition of our groups with regard to birth order and sibling sex ratio (brothers to sisters).

Results

The results for the transgender males confirmed the findings of 2 recent meta-analyses that older brothers increase the odds of androphilia in later-born males. The results for the transgender females did not clearly confirm one previous finding that older sisters increase the odds of gynephilia in later-born females—a finding obtained in a relatively large study that included gynephilic cisgender girls as well as girls diagnosed with gender dysphoria who will probably be predominantly gynephilic.

Clinical Implications

The fraternal (later-born) birth order effect that we found for the transgender androphilic males, similar to that found in gay men, suggests a common underlying causal mechanism.

Strengths and Limitations

Our study on Iranian patients diagnosed with gender dysphoria provides further generalizability for the study of birth order and sibling sex ratio that has, more often than not, been restricted to Western samples of adults diagnosed with gender dysphoria. It would be important to study these variables in Iranian gay men and lesbian women (without gender dysphoria) to further examine evidence for cross-cultural similarities when compared to Western samples.

Conclusions

In contrast to the well-established fraternal birth order effect for males, the possible sororal birth order effect for females needs to be examined with additional samples.
Five decades of radioglaciology
Authors: Schroeder Dustin M. , Bingham Robert G. , Blankenship Donald D. , Christianson Knut , Eisen Olaf , Flowers Gwenn E. , Karlsson Nanna B. , Koutnik Michelle R. , Paden John D. , Siegert Martin J.
Published: March 2020

Radar sounding is a powerful geophysical approach for characterizing the subsurface conditions of terrestrial and planetary ice masses at local to global scales. As a result, a wide array of orbital, airborne, ground-based, and in situ instruments, platforms and data analysis approaches for radioglaciology have been developed, applied or proposed. Terrestrially, airborne radar sounding has been used in glaciology to observe ice thickness, basal topography and englacial layers for five decades. More recently, radar sounding data have also been exploited to estimate the extent and configuration of subglacial water, the geometry of subglacial bedforms and the subglacial and englacial thermal states of ice sheets. Planetary radar sounders have observed, or are planned to observe, the subsurfaces and near-surfaces of Mars, Earth's Moon, comets and the icy moons of Jupiter. In this review paper, and the thematic issue of theAnnals of Glaciologyon ‘Five decades of radioglaciology’ to which it belongs, we present recent advances in the fields of radar systems, missions, signal processing, data analysis, modeling and scientific interpretation. Our review presents progress in these fields since the last radio-glaciologicalAnnals of Glaciologyissue of 2014, the context of their history and future prospects.
A Synergistic Approach to Data-Driven Response Planning
Authors: O’Neill Marty , Poole Michael , Mikler Armin R.
Published: March 2020

Public health practitioners face challenging, potentially high-consequence, problems that require computational support. Available computational tools may not adequately fit these problems, thus forcing practitioners to rely on qualitative estimates when making critical decisions. Scientists at the Center for Computational Epidemiology and Response Analysis and practitioners from the Texas Department of State Health Services (TXDSHS) have established a participatory development cycle where public health practitioners work closely with academia to foster the development of data-driven solutions for specific public health problems and to translate these solutions to practice. Tools developed through this cycle have been deployed at TXDSHS offices where they have been used to refine and enhance the region’s medical countermeasure distribution and dispensing capabilities. Consequently, TXDSHS practitioners planning for a 49-county region in North Texas have achieved a 29% reduction in the number of points of dispensing required to complete dispensing to the region within time limitations. Further, an entire receiving, staging, and storing site has been removed from regional plans, thus freeing limited resources (eg, personnel, security, and infrastructure) for other uses. In 2018, planners from Southeast Texas began using these tools to plan for a multi-county, full-scale exercise which was scheduled to be conducted in October 2019.
Dynamics and topological entropy of 1D Greenberg–Hastings cellular automata
Authors: KESSEBÖHMER M. , RADEMACHER J. D. M. , ULBRICH D.
Published: March 2020

In this paper we analyse the non-wandering set of one-dimensional Greenberg–Hastings cellular automaton models for excitable media with $e\geqslant 1$ excited and $r\geqslant 1$ refractory states and determine its (strictly positive) topological entropy. We show that it results from a Devaney chaotic closed invariant subset of the non-wandering set that consists of colliding and annihilating travelling waves, which is conjugate to a skew-product dynamical system of coupled shift dynamics. Moreover, we determine the remaining part of the non-wandering set explicitly as a Markov system with strictly less topological entropy that also scales differently for large $e,r$.
Reducibility of a class of nonlinear quasi-periodic systems with Liouvillean basic frequencies
Authors: ZHANG DONGFENG , XU JUNXIANG
Published: March 2020

In this paper we consider the following nonlinear quasi-periodic system:$$\begin{eqnarray}{\dot{x}}=(A+\unicode[STIX]{x1D716}P(t,\unicode[STIX]{x1D716}))x+\unicode[STIX]{x1D716}g(t,\unicode[STIX]{x1D716})+h(x,t,\unicode[STIX]{x1D716}),\quad x\in \mathbb{R}^{d},\end{eqnarray}$$ where $A$ is a $d\times d$ constant matrix of elliptic type, $\unicode[STIX]{x1D716}g(t,\unicode[STIX]{x1D716})$ is a small perturbation with $\unicode[STIX]{x1D716}$ as a small parameter, $h(x,t,\unicode[STIX]{x1D716})=O(x^{2})$ as $x\rightarrow 0$, and $P,g$ and $h$ are all analytic quasi-periodic in $t$ with basic frequencies $\unicode[STIX]{x1D714}=(1,\unicode[STIX]{x1D6FC})$, where $\unicode[STIX]{x1D6FC}$ is irrational. It is proved that for most sufficiently small $\unicode[STIX]{x1D716}$, the system is reducible to the following form: $$\begin{eqnarray}{\dot{x}}=(A+B_{\ast }(t))x+h_{\ast }(x,t,\unicode[STIX]{x1D716}),\quad x\in \mathbb{R}^{d},\end{eqnarray}$$ where $h_{\ast }(x,t,\unicode[STIX]{x1D716})=O(x^{2})~(x\rightarrow 0)$ is a high-order term. Therefore, the system has a quasi-periodic solution with basic frequencies $\unicode[STIX]{x1D714}=(1,\unicode[STIX]{x1D6FC})$, such that it goes to zero when $\unicode[STIX]{x1D716}$ does.
Predictors of client retention in a state-based tobacco quitline
Authors: Nair Uma S. , Rabe Brooke , Brady Benjamin R. , Bell Melanie L.
Published: March 2020

Introduction

Quitlines are standard care for smoking cessation; however, retaining clients in services is a problem. Little is known about factors that may predict dropout.

Aims

To examine predictors of retention while in-program and at follow-up for clients enrolling in a state quitline.

Methods

This was a retrospective analysis of quitline enrolled clients from 2011 to 2017 (N = 49,347). Client retention in-program was categorized as (a) low adherence to treatment (receiving zero coaching calls), moderate (1–2 calls), and high adherence (3+ calls). Dropout at follow-up included participants who were not reached for the 7-month follow-up.

Results

More than half the sample dropped out during treatment; 61% were not reached for follow-up. Women (odds ratio (OR) = 1.21; 95% confidence interval (CI) = [1.16, 127]) and those with high levels of nicotine dependence (OR = 1.03; 95% CI = [1.02, 1.04]) were more likely to have moderate adherence to treatment (1–2 coaching calls). Dropout at follow-up was more likely among clients who used nicotine replacement therapy (OR = 1.14; 95% CI = [1.09, 1.19]) and less likely among those who had high treatment adherence (OR = 0.41; 95% CI = [0.39, 0.42]).

Conclusion

Given the relapsing nature of tobacco use and the harms related to tobacco use, quitlines can improve their impact by offering tailored services to enhance client engagement and retention in-treatment and at follow-up.
ON THE MIX OF GOVERNMENT EXPENDITURE AND TAX REVENUES
Authors: Economides George , Park Hyun , Philippopoulos Apostolis , Sakkas Stelios
Published: March 2020

We study the implications of changes in the mix of taxes, public spending, and public finance in the Eurozone. In so doing, we build a general equilibrium OLG model that naturally incorporates all the main categories of public spending and taxes. We focus on the medium- and long-run implications of permanent reforms in the actual policy mix. When we depart from 2008, the best way out of the recession would be an increase in public spending on education and health and in turn cuts in distorting taxes including social security contributions. When we depart from the year 2017, which features a higher inherited public debt, public debt consolidation becomes the superior reform to the extent that the focus is on the medium and long run.
Laboratory Study on Fluid‐Induced Fault Slip Behavior: The Role of Fluid Pressurization Rate
Authors: Wang Lei , Kwiatek Grzegorz , Rybacki Erik , Bonnelye Audrey , Bohnhoff Marco , Dresen Georg
Published: March 2020

Understanding the physical mechanisms governing fluid‐induced fault slip is important for improved mitigation of seismic risks associated with large‐scale fluid injection. We conducted fluid‐induced fault slip experiments in the laboratory on critically stressed saw‐cut sandstone samples with high permeability using different fluid pressurization rates. Our experimental results demonstrate that fault slip behavior is governed by fluid pressurization rate rather than injection pressure. Slow stick‐slip episodes (peak slip velocity < 4 μm/s) are induced by fast fluid injection rate, whereas fault creep with slip velocity < 0.4 μm/s mainly occurs in response to slow fluid injection rate. Fluid‐induced fault slip may remain mechanically stable for loading stiffness larger than fault stiffness. Independent of fault slip mode, we observed dynamic frictional weakening of the artificial fault at elevated pore pressure. Our observations highlight that varying fluid injection rates may assist in reducing potential seismic hazards of field‐scale fluid injection projects.
MIDAS: A Miniature Device for Real‐Time Determination of the Identity and Energy of Particles in Space
Authors: Lambropoulos C. P. , Potiriadis C. , Theodoratos G. , Kazas I. , Papadimitropoulos C. , Loukas D. , Glikiotis I. , Karafasoulis K. , Paschalis P. , Kοkavesis M. , Dimopoulos S. , Delakoura A. , Pappas S. , Dimovasili E. , Dimitropoulos G.
Published: March 2020

The Miniaturized Detector for Application in Space (MIDAS) device is developed in response to the requirement of the European Space Agency for a device whose size, power consumption, and radiation data output would increase the level of space‐flight crew autonomy regarding operational decisions related to radiation hazards. It is designed as a wristwatch‐dimension cube detector for measuring track direction and energy deposition in silicon pixels, as well as energy depositions by neutrons in a plastic scintillator, which is the core of the cube. Miniaturization was achieved by using fully depleted silicon pixel detectors with the signal processing electronics residing on pixel. The device concept, simulated performance, and first measurements are presented. Simulation results indicate that it is possible to discriminate all significant ions with the aid of appropriate variables constructed using the data provided by the device. 252Cf energy spectra were reconstructed successfully using measurements obtained with the first device prototype.
A novel antifibrotic strategy utilizing conditioned media obtained from miR-150-transfected adipose-derived stem cells: validation of an animal model of liver fibrosis
Authors: Paik Kwang Yeol , Kim Kee-Hwan , Park Jung Hyun , Lee Jae Im , Kim Ok-Hee , Hong Ha-Eun , Seo Haeyeon , Choi Ho Joong , Ahn Joseph , Lee Tae Yun , Kim Say-June
Published: March 2020

The limitations of stem cells have led researchers to investigate the secretome, which is the secretory materials in stem cells, since the principal mechanism of action of stem cells is mediated by the secretome. In this study, we determined the antifibrotic potential of the secretome released from miR-150-transfected adipose-derived stromal cells (ASCs). The secretome released from ASCs that were transfected with antifibrotic miR-150 was obtained (referred to as the miR-150 secretome). To validate the antifibrotic effects of the miR-150 secretome, we generated in vitro and in vivo models of liver fibrosis by treating human hepatic stellate cells (LX2 cells) with thioacetamide (TAA) and subcutaneous injection of TAA into mice, respectively. In the in vitro model, more significant reductions in the expression of fibrosis-related markers, such as TGFβ, Col1A1, and α-SMA, were observed by using the miR-150 secretome than the control secretome, specifically in TAA-treated LX2 cells. In the in vivo model, infusion of the miR-150 secretome into mice with liver fibrosis abrogated the increase in serum levels of systemic inflammatory cytokines, such as IL-6 and TNF-α, and induced increased expression of antifibrotic, proliferation, and antioxidant activity markers in the liver. Our in vitro and in vivo experiments indicate that the miR-150 secretome is superior to the naive secretome in terms of ameliorating liver fibrosis, minimizing systemic inflammatory responses, and promoting antioxidant enzyme expression. Therefore, we conclude that miR-150 transfection into ASCs has the potential to induce the release of secretory materials with enhanced antifibrotic, proliferative, and antioxidant properties.
PTGES/PGE2 signaling links immunosuppression and lung metastasis in Gprc5a-knockout mouse model
Authors: Wang Tong , Jing Bo , Xu Dongliang , Liao Yueling , Song Hongyong , Sun Beibei , Guo Wenzheng , Xu Jianhua , Li Kaimi , Hu Min , Liu Shuli , Ling Jing , Kuang Yanbin , Zhang Tuo , Zhang Siwei , Yao Feng , Zhou Binhua P. , Deng Jiong
Published: March 2020

Chronic inflammation has been linked to promotion of tumorigenesis and metastasis in lung. However, due to lack of a relevant animal model for characterization, the underlying mechanism remains elusive. Lung tumor suppressor gene Gprc5a-knockout (ko) mice are susceptible to lung inflammation, tumorigenesis and metastasis, which resembles the pathological features in human patients. Here, we showed that PTGES/PGE2 signaling was highly associated with lung tumorigenesis and metastasis in Gprc5a-ko mice. Interestingly, Ptges-knockout in mouse lung tumor cells, although reduced their stemness and EMT-like features, still formed tumors and lung metastasis in immune-deficient nude mice, but not in immune-competent mice. This suggests that the major role of PTGES/PGE2 signaling in tumorigenicity and lung metastasis is through immunosuppression. Mechanistically, PTGES/PGE2 signaling intrinsically endows tumor cells resistant to T-cell cytotoxicity, and induces cytokines extrinsically for MDSC recruitment, which is crucial for suppression of T-cell immunity. Importantly, targeting PGE2 signaling in Gprc5a-ko mice by PTGES inhibitor suppressed MDSC recruitment, restored T cells, and significantly repressed lung metastasis. Thus, PTGES/PGE2 signaling links immunosuppression and metastasis in an inflammatory lung microenvironment of Gprc5a-ko mouse model.
PET imaging shows no changes in TSPO brain density after IFN-α immune challenge in healthy human volunteers
Authors: Nettis M. A. , Veronese M. , Nikkheslat N. , Mariani N. , Lombardo G. , Sforzini L. , Enache D. , Harrison N. A. , Turkheimer F. E. , Mondelli V. , Pariante C. M.
Published: March 2020

Depression is associated with peripheral inflammation, but its link with brain microglial activity remains unclear. In seven healthy males, we used repeated translocator protein-Positron Emission Tomography (TSPO-PET) dynamic scans with [11C]PBR28 to image brain microglial activation before and 24 h after the immune challenge interferon (IFN)-α. We also investigated the association between changes in peripheral inflammation, changes in microglial activity, and changes in mood. IFN-α administration decreased [11C]PBR28 PET tissue volume of distribution (Vt) across the brain (−20 ± 4%; t6 = 4.1, p = 0.01), but after correction for radioligand free-plasma fraction there were no longer any changes (+23 ± 31%; t = 0.1, p = 0.91). IFN-α increased serum IL-6 (1826 ± 513%, t6 = −7.5, p < 0.001), IL-7 (39 ± 12%, t6 = −3.6, p = 0.01), IL-10 (328 ± 48%, t6 = −12.8, p < 0.001), and IFN-γ (272 ± 64%, t6 = −7.0, p < 0.001) at 4–6 h, and increased serum TNF-α (49 ± 7.6%, t6 = −7.5, p < 0.001), IL-8 (39 ± 12%, t6 = −3.5, p = 0.013), and C-reactive protein (1320 ± 459%, t6 = −7.2, p < 0.001) at 24 h. IFN-α induced temporary mood changes and sickness symptoms after 4–6 h, measured as an increase in POMS-2 total mood score, confusion and fatigue, and a decrease in vigor and friendliness (all p ≤ 0.04). No association was found between changes in peripheral inflammation and changes in PET or mood measures. Our work suggests that brain TSPO-PET signal is highly dependent of inflammation-induced changes in ligand binding to plasma proteins. This limits its usefulness as a sensitive marker of neuroinflammation and consequently, data interpretation. Thus, our results can be interpreted as showing either that [11C]PBR28 is not sensitive enough under these conditions, or that there is simply no microglial activation in this model.
Minimal barriers to invasion during human colorectal tumor growth
Authors: Ryser Marc D. , Mallo Diego , Hall Allison , Hardman Timothy , King Lorraine M. , Tatishchev Sergei , Sorribes Inmaculada C. , Maley Carlo C. , Marks Jeffrey R. , Hwang E. Shelley , Shibata Darryl
Published: March 2020

Intra-tumoral heterogeneity (ITH) could represent clonal evolution where subclones with greater fitness confer more malignant phenotypes and invasion constitutes an evolutionary bottleneck. Alternatively, ITH could represent branching evolution with invasion of multiple subclones. The two models respectively predict a hierarchy of subclones arranged by phenotype, or multiple subclones with shared phenotypes. We delineate these modes of invasion by merging ancestral, topographic, and phenotypic information from 12 human colorectal tumors (11 carcinomas, 1 adenoma) obtained through saturation microdissection of 325 small tumor regions. The majority of subclones (29/46, 60%) share superficial and invasive phenotypes. Of 11 carcinomas, 9 show evidence of multiclonal invasion, and invasive and metastatic subclones arise early along the ancestral trees. Early multiclonal invasion in the majority of these tumors indicates the expansion of co-evolving subclones with similar malignant potential in absence of late bottlenecks and suggests that barriers to invasion are minimal during colorectal cancer growth.
Global consumption and international trade in deforestation-associated commodities could influence malaria risk
Authors: Chaves Leonardo Suveges Moreira , Fry Jacob , Malik Arunima , Geschke Arne , Sallum Maria Anice Mureb , Lenzen Manfred
Published: March 2020

Deforestation can increase the transmission of malaria. Here, we build upon the existing link between malaria risk and deforestation by investigating how the global demand for commodities that increase deforestation can also increase malaria risk. We use a database of trade relationships to link the consumption of deforestation-implicated commodities in developed countries to estimates of country-level malaria risk in developing countries. We estimate that about 20% of the malaria risk in deforestation hotspots is driven by the international trade of deforestation-implicated export commodities, such as timber, wood products, tobacco, cocoa, coffee and cotton. By linking malaria risk to final consumers of commodities, we contribute information to support demand-side policy measures to complement existing malaria control interventions, with co-benefits for reducing deforestation and forest disturbance.
The X-linked trichothiodystrophy-causing gene RNF113A links the spliceosome to cell survival upon DNA damage
Authors: Shostak Kateryna , Jiang Zheshen , Charloteaux Benoit , Mayer Alice , Habraken Yvette , Tharun Lars , Klein Sebastian , Xu Xinyi , Duong Hong Quan , Vislovukh Andrii , Close Pierre , Florin Alexandra , Rambow Florian , Marine Jean-Christophe , Büttner Reinhard , Chariot Alain
Published: March 2020

Prolonged cell survival occurs through the expression of specific protein isoforms generated by alternate splicing of mRNA precursors in cancer cells. How alternate splicing regulates tumor development and resistance to targeted therapies in cancer remain poorly understood. Here we show that RNF113A, whose loss-of-function causes the X-linked trichothiodystrophy, is overexpressed in lung cancer and protects from Cisplatin-dependent cell death. RNF113A is a RNA-binding protein which regulates the splicing of multiple candidates involved in cell survival. RNF113A deficiency triggers cell death upon DNA damage through multiple mechanisms, including apoptosis via the destabilization of the prosurvival protein MCL-1, ferroptosis due to enhanced SAT1 expression, and increased production of ROS due to altered Noxa1 expression. RNF113A deficiency circumvents the resistance to Cisplatin and to BCL-2 inhibitors through the destabilization of MCL-1, which thus defines spliceosome inhibitors as a therapeutic approach to treat tumors showing acquired resistance to specific drugs due to MCL-1 stabilization.
A critical role of PRDM14 in human primordial germ cell fate revealed by inducible degrons
Authors: Sybirna Anastasiya , Tang Walfred W. C. , Pierson Smela Merrick , Dietmann Sabine , Gruhn Wolfram H. , Brosh Ran , Surani M. Azim
Published: March 2020

PRDM14 is a crucial regulator of mouse primordial germ cells (mPGCs), epigenetic reprogramming and pluripotency, but its role in the evolutionarily divergent regulatory network of human PGCs (hPGCs) remains unclear. Besides, a previous knockdown study indicated that PRDM14 might be dispensable for human germ cell fate. Here, we decided to use inducible degrons for a more rapid and comprehensive PRDM14 depletion. We show that PRDM14 loss results in significantly reduced specification efficiency and an aberrant transcriptome of hPGC-like cells (hPGCLCs) obtained in vitro from human embryonic stem cells (hESCs). Chromatin immunoprecipitation and transcriptomic analyses suggest that PRDM14 cooperates with TFAP2C and BLIMP1 to upregulate germ cell and pluripotency genes, while repressing WNT signalling and somatic markers. Notably, PRDM14 targets are not conserved between mouse and human, emphasising the divergent molecular mechanisms of PGC specification. The effectiveness of degrons for acute protein depletion is widely applicable in various developmental contexts.
Multiplexed CRISPR technologies for gene editing and transcriptional regulation
Authors: McCarty Nicholas S. , Graham Alicia E. , Studená Lucie , Ledesma-Amaro Rodrigo
Published: March 2020

Multiplexed CRISPR technologies, in which numerous gRNAs or Cas enzymes are expressed at once, have facilitated powerful biological engineering applications, vastly enhancing the scope and efficiencies of genetic editing and transcriptional regulation. In this review, we discuss multiplexed CRISPR technologies and describe methods for the assembly, expression and processing of synthetic guide RNA arrays in vivo. Applications that benefit from multiplexed CRISPR technologies, including cellular recorders, genetic circuits, biosensors, combinatorial genetic perturbations, large-scale genome engineering and the rewiring of metabolic pathways, are highlighted. We also offer a glimpse of emerging challenges and emphasize experimental considerations for future studies.
Ruthenium anchored on carbon nanotube electrocatalyst for hydrogen production with enhanced Faradaic efficiency
Authors: Kweon Do Hyung , Okyay Mahmut Sait , Kim Seok-Jin , Jeon Jong-Pil , Noh Hyuk-Jun , Park Noejung , Mahmood Javeed , Baek Jong-Beom
Published: March 2020

Developing efficient and stable electrocatalysts is crucial for the electrochemical production of pure and clean hydrogen. For practical applications, an economical and facile method of producing catalysts for the hydrogen evolution reaction (HER) is essential. Here, we report ruthenium (Ru) nanoparticles uniformly deposited on multi-walled carbon nanotubes (MWCNTs) as an efficient HER catalyst. The catalyst exhibits the small overpotentials of 13 and 17 mV at a current density of 10 mA cm–2 in 0.5 M aq. H2SO4 and 1.0 M aq. KOH, respectively, surpassing the commercial Pt/C (16 mV and 33 mV). Moreover, the catalyst has excellent stability in both media, showing almost “zeroloss” during cycling. In a real device, the catalyst produces 15.4% more hydrogen per power consumed, and shows a higher Faradaic efficiency (92.28%) than the benchmark Pt/C (85.97%). Density functional theory calculations suggest that Ru–C bonding is the most plausible active site for the HER.
Design of AIEgens for near-infrared IIb imaging through structural modulation at molecular and morphological levels
Authors: Li Yuanyuan , Cai Zhaochong , Liu Shunjie , Zhang Haoke , Wong Sherman T. H. , Lam Jacky W. Y. , Kwok Ryan T. K. , Qian Jun , Tang Ben Zhong
Published: March 2020

Fluorescence imaging in near-infrared IIb (NIR-IIb, 1500–1700 nm) spectrum holds a great promise for tissue imaging. While few inorganic NIR-IIb fluorescent probes have been reported, their organic counterparts are still rarely developed, possibly due to the shortage of efficient materials with long emission wavelength. Herein, we propose a molecular design philosophy to explore pure organic NIR-IIb fluorophores by manipulation of the effects of twisted intramolecular charge transfer and aggregation-induced emission at the molecular and morphological levels. An organic fluorescent dye emitting up to 1600 nm with a quantum yield of 11.5% in the NIR-II region is developed. NIR-IIb fluorescence imaging of blood vessels and deeply-located intestinal tract of live mice based on organic dyes is achieved with high clarity and enhanced signal-to-background ratio. We hope this study will inspire further development on the evolution of pure organic NIR-IIb dyes for bio-imaging.
Author Correction: Caspase-11 signaling enhances graft-versus-host disease
Authors: Lu Yanyan , Meng Ran , Wang Xiangyu , Xu Yajing , Tang Yiting , Wu Jianfeng , Xue Qianqian , Yu Songlin , Duan Mingwu , Shan Dongyong , Wang Qingde , Wang Haichao , Billiar Timothy R. , Xiao Xianzhong , Chen Fangping , Lu Ben
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Partitioning of diet between species and life history stages of sympatric and cryptic snappers (Lutjanidae) based on DNA metabarcoding
Authors: Takahashi Miwa , DiBattista Joseph D. , Jarman Simon , Newman Stephen J. , Wakefield Corey B. , Harvey Euan S. , Bunce Michael
Published: March 2020

Lutjanus erythropterusandL. malabaricusare sympatric, sister taxa that are important to fisheries throughout the Indo-Pacific. Their juveniles are morphologically indistinguishable (i.e. cryptic). A DNA metabarcoding dietary study was undertaken to assess the diet composition and partitioning between the juvenile and adult life history stages of these two lutjanids. Major prey taxa were comprised of teleosts and crustaceans for all groups except adultL. erythropterus, which instead consumed soft bodied invertebrates (e.g. tunicates, comb jellies and medusae) as well as teleosts, with crustaceans being notably absent. Diet composition was significantly different among life history stages and species, which may be associated with niche habitat partitioning or differences in mouth morphology within adult life stages. This study provides the first evidence of diet partitioning between cryptic juveniles of overlapping lutjanid species, thus providing new insights into the ecological interactions, habitat associations, and the specialised adaptations required for the coexistence of closely related species. This study has improved our understanding of the differential contributions of the juvenile and adult diets of these sympatric species within food webs. The diet partitioning reported in this study was only revealed by the taxonomic resolution provided by the DNA metabarcoding approach and highlights the potential utility of this method to refine the dietary components of reef fishes more generally.