bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic reprogramming of inner ear cell line HEI-OC1 after dexamethasone application
Authors: Kather Michel , Koitzsch Sabine , Breit Bernhard , Plontke Stefan , Kammerer Bernd , Liebau Arne
Published: May 2021

Introduction

One approach to dampen the inflammatory reactions resulting from implantation surgery of cochlear implant hearing aids is to embed dexamethasone into the matrix of the electrode carrier. Possible side effects for sensory cells in the inner ear on the metabolomics have not yet been evaluated.

Objective

We examined changes in the metabolome of the HEI-OC1 cell line after dexamethasone incubation as a cell model of sensory cells of the inner ear.

Results and Conclusion

Untargeted GC–MS-profiling of metabolic alterations after dexamethasone treatment showed that dexamethasone had antithetical effects on the metabolic signature of the cells depending on growth conditions. The differentiated state of HEI-OC1 cells is better suited for elucidating metabolic changes induced by external factors. Dexamethasone treatment of differentiated cells led to an increase in intracellular amino acids and enhanced glucose uptake and β-oxidation in the cells. Increased availability of precursors for glycolysis and ATP production by β-oxidation stabilizes the energy supply in the cells, which could be assumed to be beneficial in coping with cellular stress. We found no negative effects of dexamethasone on the metabolic level, and changes may even prepare sensory cells to better overcome cellular stress following implantation surgery.
Quantification and distribution of 4-fluoroisobutyryl fentanyl (4-FiBF) in postmortem biological samples using UHPLC–QqQ-MS/MS
Authors: Zawadzki Marcin , Wachełko Olga , Chłopaś-Konowałek Agnieszka , Szpot Paweł
Published: May 2021

Purpose

Development of ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectrometry method for quantification of 4-fluoroisobutyryl fentanyl (4-FiBF) and its distribution in postmortem biological samples in four fatal intoxication cases, which occurred in September 2018, in Poland.

Methods

Biological fluids (blood, urine, vitreous humor, bile, gastric content) and tissues (brain, kidney, liver, stomach wall) were extracted with ethyl acetate from alkaline medium (pH 9). Fentanyl-d5 was used as internal standard.

Results

The validation parameters were as follows: lower limit of quantification: 0.1 ng/mL (biological fluids) and 0.1 ng/g (solid tissues), intra- and inter-day accuracies and precisions: not greater than 20%; recovery values: 86.9–110%; matrix effect: − 13.1–10.4%. Among all tested biological fluid, the highest concentration of 4-FiBF was found in bile (average concentration of 3390 ng/mL) while among the tissues, in liver (average concentration of 1650 ng/g). Furthermore, in collected specimens, there were also found other drugs and new psychoactive substances (NPS) e.g. N-ethylpentylon, 4-chloromethcathinone (4-CMC) and α-pyrrolidinoisohexanophenone (α-PiHP). Concentrations and distributions of these substances in postmortem samples have been also detailed. Examinations of seized drug (in case 4) revealed that it included the mix of 4-FiBF and α-PiHP.

Conclusions

The developed and fully validated method enabled for determination of 4-FiBF in postmortem biological fluids and tissues. To our knowledge, this is the first report of distribution study of 4-FiBF with other NPS (N-ethylpentylon, 4-CMC and α-PiHP) in authentic fatal intoxication cases.
An intuitive surgical handle design for robotic neurosurgery
Authors: Dimitrakakis Emmanouil , Lindenroth Lukas , Dwyer George , Aylmore Holly , Dorward Neil L. , Marcus Hani J. , Stoyanov Danail
Published: May 2021

Purpose

The expanded endoscopic endonasal approach, a representative example of keyhole brain surgery, allows access to the pituitary gland and surrounding areas through the nasal and sphenoid cavities. Manipulating rigid instruments through these constrained spaces makes this approach technically challenging, and thus, a handheld robotic instrument could expand the surgeon’s capabilities. In this study, we present an intuitive handle prototype for such a robotic instrument.

Methods

We have designed and fabricated a surgical instrument handle prototype that maps the surgeon’s wrist directly to the robot joints. To alleviate the surgeon’s wrist of any excessive strain and fatigue, the tool is mounted on the surgeon’s forearm, making it parallel with the instrument’s shaft. To evaluate the handle’s performance and limitations, we constructed a surgical task simulator and compared our novel handle with a standard neurosurgical tool, with the tasks being performed by a consultant neurosurgeon.

Results

While using the proposed handle, the surgeon’s average success rate was $$80\%$$

80
%

, compared to $$41\%$$

41
%

when using a conventional tool. Additionally, the surgeon’s body posture while using the suggested prototype was deemed acceptable by the Rapid Upper Limb Assessment ergonomic survey, while early results indicate the absence of a learning curve.

Conclusions

Based on these preliminary results, the proposed handle prototype could offer an improvement over current neurosurgical tools and procedural ergonomics. By redirecting forces applied during the procedure to the forearm of the surgeon, and allowing for intuitive surgeon wrist to robot-joints movement mapping without compromising the robotic end effector’s expanded workspace, we believe that this handle could prove a substantial step toward improved neurosurgical instrumentation.
On the rate of convergence of alternating minimization for non-smooth non-strongly convex optimization in Banach spaces
Authors: Both Jakub Wiktor
Published: May 2021

In this paper, the convergence of the fundamental alternating minimization is established for non-smooth non-strongly convex optimization problems in Banach spaces, and novel rates of convergence are provided. As objective function a composition of a smooth, and a block-separable, non-smooth part is considered, covering a large range of applications. For the former, three different relaxations of strong convexity are considered: (i) quasi-strong convexity; (ii) quadratic functional growth; and (iii) plain convexity. With new and improved rates benefiting from both separate steps of the scheme, linear convergence is proved for (i) and (ii), whereas sublinear convergence is showed for (iii).
A Robust Image Processing Algorithm for Optical-Based Stress–Strain Curve Corrections after Necking
Authors: Lu Feng , Mánik Tomáš , Lægreid Andersen Ida , Holmedal Bjørn
Published: May 2021

To determine the stress–strain curve of a ductile material up to the fracture from a tensile test, the necking contour is measured by an optical measurement technique. The radius of the minimal cross-sectional area and the radius of curvature are used as input for analytical necking corrections of the stress–strain curve, as well as for finite element inverse simulations. Due to the increasing surface roughness that develops during testing, a precise determination of the specimen contour is very challenging. This is crucial, since the second derivative is required for estimating the radius of curvature. A dedicated contour-tracking algorithm was developed to deal with the surface roughness and a specimen painted white with black background was found to provide enough contrast. The new algorithm was implemented in a software, which is made available as open source. Tests were made for an isotropic, commercially pure aluminum alloy and for an axisymmetric, peak aged AA6082 alloy, based on image recording by a digital camera and synchronized force measurements. Modeling by finite element simulations was performed to assess the accuracy of analytical corrections of the stress–strain curves by inverse modeling and for designing a robust contour-tracking algorithm.
Modeling of cutting forces in trochoidal milling with respect to wear-dependent topographic changes
Authors: Bergmann Jim A. , Potthoff Nils , Rickhoff Tobias , Wiederkehr Petra
Published: May 2021

The aerospace industry utilizes nickel-based super-alloys due to its high level of strength and corrosion resistance. To evaluate milling strategies regarding tool wear, the prediction of forces during these cutting operations is essential. This comprises the determination of the undeformed chip thickness. Due to the complex interdependencies of tool engagements, the determination of these thicknesses is challenging. A geometric physically-based simulation system was extended by a novel time-discrete envelope model to increase the precision of the calculated undeformed chip thicknesses. In order to take tool wear into account, digitized topographies of cutting inserts in different states of tool wear were modelled.
Echogenic Fetal Heart Without Conduction Defect in Maternal Autoimmune Disease: A Lesser Known Association
Authors: Tamhane Tejas , Baliga Pundalik , Chidambarathanu Shanthi , Suresh Indrani , Seshadri Suresh
Published: May 2021

Positive anti-Ro/SSA and anti-La/SSB antibodies in pregnant mothers are strongly associated with fetal congenital heart block (CHB). Increased echogenicity of fetal endo-myocardium is one of the lesser known manifestations of maternal autoimmune disease. In this retrospective analysis of data from the last ten years (2010–2019) at our fetal medicine unit, we identified nine fetuses presenting in the second trimester with isolated increased echogenicity of the endo-myocardium without CHB. In three cases, mothers had a pre-existing autoimmune disease. The others were diagnosed with positive autoimmune antibodies following evaluation for the echogenic fetal heart. One fetus developed a first-degree heart block at 33 weeks and another had a second-degree heart block three weeks after presentation. There was no fetal mortality. All were live-born. One fetus with tachycardia and ventricular dysfunction died within a few days of birth. Both babies with heart block are stable and on medical follow-up, while others remain asymptomatic with a normal rhythm. There seems a spectrum of fetal disease caused by maternal auto-antibodies affecting the endo-myocardium but sparing the conduction system. In fetuses with echogenic hearts, evaluation of maternal autoimmune status should be part of the protocol for optimal fetal and maternal care.
Reduced Use of Fossil Fuels can Reduce Supply of Critical Resources
Authors: Månberger André
Published: May 2021

Previous research has identified that climate change mitigation policies could increase demand for resources perceived as critical, because these are used in many renewable energy technologies. This study assesses how reducing the extraction and use of fossil fuels could affect the supply of (i) elements jointly produced with fossil fuels and (ii) elements jointly produced with a host that is currently mainly used in fossil fuel supply chains. Several critical resources are identified for which supply potential from current sources is likely to decline. Some of these, e.g. germanium and vanadium, have uses in low-carbon energy systems. Renewable energy transitions can thus simultaneously increase demand and reduce supply of critical elements. The problem is greatest for technology groups in which by-products are more difficult to recycle than the host. Photovoltaic cell technology stands out as one such group. Phasing out fossil fuels has the potential to reduce both the supply potential (i.e. primary flow) and recoverable resources (i.e. stock) of materials involved in such technology groups. Further studies could examine possibilities to increase recovery rates, extract jointly produced resources independently of hosts and how the geographical distribution of by-product supply sources might change if fossil fuel extraction is scaled back.
International Water Law Principles in Negotiations and Water Diplomacy
Authors: Schmeier Susanne
Published: May 2021

International water law (IWL) principles are often called upon to address disagreements and conflict between riparian states to a shared watercourse, with various parties invoking them to guide states’ behavior towards cooperative solutions that benefit the water resources as well as broader regional cooperation and peace. This essay argues that it is particularly important to acknowledge the role IWL principles play in negotiation processes, that is, in an ex ante and non-judicial function, providing a framework for cooperation and contributing to lawmaking, which makes them important tools of international relations and water diplomacy. First, IWL principles are particularly relevant in negotiation processes. IWL principles are thus not only relevant to legal adjudication or enforcement, but are also tools of international relations and diplomacy. Additionally, in their ex ante role, in the context of negotiations or other non-judicial interactions between riparian states, IWL principles can pose an inherent dilemma, as they can both provide a framework for negotiations and be the focus of negotiations, each dimension having implications for the effectiveness of negotiations and the likelihood of negotiated compromise outcomes. Third, in spite of this inherent dilemma and its possible negative repercussions on negotiation outcomes, the use of IWL principles in negotiations has a lawmaking function, contributing to the further development and strengthening of the overall legal regime for governing shared watercourses.
L’État canadien et la reconnaissance des droits religieux autochtones
Authors: Gélinas Claude
Published: May 2021

La politique actuelle de réconciliation qui guide les rapports que l’État canadien entretient avec les peuples autochtones affiche une certaine discontinuité en matière de reconnaissance de leurs droits religieux. D’une part, les gouvernements accordent aux Autochtones certains privilèges à des fins de valorisation de leurs particularismes religieux dans l’espace public, d’une manière qui ne s’étend pas nécessairement à d’autres segments de la société. Parallèlement, par l’entremise de lois et d’ententes politiques, des nations autochtones se sont vu reconnaître des droits et privilèges en lien avec leur sphère religieuse, lesquels demeurent toutefois largement assujettis au cadre normatif établi par la majorité. Enfin, les tribunaux peinent jusqu’à présent à considérer les particularismes religieux des nations autochtones en tant que motif décisionnel. Cette reconnaissance à géométrie variable laisse transparaître un relent de colonialisme suivant lequel la dimension symbolique est valorisée, au détriment des avenues susceptibles de mener à une réelle autonomie des nations autochtones en matière d’expression religieuse.
When is illegality a defence to a tort?
Authors: Shmilovits Liron
Published: May 2021

The illegality defence is an important element of private law, but its operation has been unpredictable. In Patel v Mirza, the Supreme Court opted for a flexible approach, which does not increase predictability. This approach was recently confirmed in Henderson v Dorset Healthcare University NHS Foundation Trust and Stoffel & Co v Grondona. I propose a principle to guide the application of the illegality defence in tort: namely, the claim fails for illegality if the claimant's harm is the ordinary result of the claimant's wrongdoing. It is argued that the guiding principle: (i) substantially explains the case law; (ii) is normatively defensible; and (iii) makes the defence much more predictable.
Gender and Party Discipline: Evidence from Africa’s Emerging Party Systems
Authors: CLAYTON AMANDA , ZETTERBERG PÄR
Published: May 2021

Are men and women legislators equally loyal to their parties? We theorize that parties select candidates based on gendered criteria, leading to the (s)election of more disciplined women. Moreover, we argue that gendered expectations about proper behavior limit women legislators’ ability to act independently from their parties. Using surveys from over 800 parliamentarians across 17 African legislatures, we find that women report significantly higher levels of party discipline than do their men copartisans. From this survey data and new legislative speech data, we also find support for our proposed causal mechanisms. Further, we find that among women parliamentarians, party discipline is negatively correlated with the prioritization of womens rights. A qualitative case study of the Namibian Parliament illustrates our findings. We discuss the implications of our results for women’s legislative effectiveness, for the substantive representation of women’s interests in policy making, and for the continued democratization of emerging party systems.
NONDIVISIBILITY AMONG IRREDUCIBLE CHARACTER CO-DEGREES
Authors: AHANJIDEH NEDA
Published: May 2021

For a character$\chi $of a finite groupG, the number$\chi ^c(1)={[G:{\textrm {ker}}\chi ]}/{\chi (1)}$is called the co-degree of$\chi $. A finite groupGis an${\textrm {NDAC}} $-group (no divisibility among co-degrees) when$\chi ^c(1) \nmid \phi ^c(1)$for all irreducible characters$\chi $and$\phi $ofGwith$1< \chi ^c(1) < \phi ^c(1)$. We study finite groups admitting an irreducible character whose co-degree is a given primepand finite nonsolvable${\textrm {NDAC}} $-groups. Then we show that the finite simple groups$^2B_2(2^{2f+1})$, where$f\geq 1$,$\mbox {PSL}_3(4)$,${\textrm {Alt}}_7$and$J_1$are determined uniquely by the set of their irreducible character co-degrees.
Most permutations power to a cycle of small prime length
Authors: Glasby S. P. , Praeger Cheryl E. , Unger W. R.
Published: May 2021

We prove that most permutations of degree $n$ have some power which is a cycle of prime length approximately $\log n$. Explicitly, we show that for $n$ sufficiently large, the proportion of such elements is at least $1-5/\log \log n$ with the prime between $\log n$ and $(\log n)^{\log \log n}$. The proportion of even permutations with this property is at least $1-7/\log \log n$.
Sartre as prosecutor of occupational murder: notes from a People's Tribunal in a French mine (1970)
Authors: Marichalar Pascal , Markowitz Gerald , Rosner David
Published: May 2021

On February 4, 1970, in the Fouquières-lès-Lens coal mine in northern France, sixteen miners were killed in a gas explosion (“firedamp,” grisou in French). This was an accident like many others before it, yet with a relatively high number of fatalities. The public prosecutor concluded, as usual, that there was no case against the publicly owned mine. No investigation was to be carried out. The accident had been the work of fate, of bad luck.
Gender, Race, and Migrant Labor in the “Domestic Frontier” of the Panama Canal Zone
Authors: Flores-Villalobos Joan
Published: May 2021

The cover of Maid in Panama depicts a West Indian higgler as a “mammy.” Her skin is an exaggerated ink-black, her body is large, her face round, and she wears a servant's uniform, including headscarf and apron. The higgler walks across an open field carrying a tray of tropical fruits on her head, with a background of palm trees, a placid river, and fluffy clouds.
FISCAL AFTERSHOCKS: TAXES AND CATASTROPHES IN CHILEAN HISTORY
Authors: Gil Magdalena , Atria Jorge
Published: May 2021

Socio-natural disasters remain underexplored events in economic history, even though they stress societies in several ways and are known for their relationship with institutional change. In this paper, we explore this issue showing that major earthquakes in Chile have become a window of opportunity for important fiscal reforms. Our findings indicate that there are two mechanisms to explain this relationship: first, reconstruction demands greater state expenditure and intervention; and second, the emergence of narratives that justify these reforms, such as patriotism and solidarity. However, data show that in the case of Chile, changes following disasters have had little impact on the overall tax structure of the country, and the historical preference for indirect taxes has been maintained, with limited power to impose taxes on high-income groups.
Confronting the gated community: Towards a decolonial critique of violence beyond the paradigm of war
Authors: Tavares Furtado Henrique
Published: May 2021

This article investigates the works of Dussel, Maldonado-Torres, and Mbembe as representatives of a tendency in the field of decolonial thought to assume the templates of warfare and the camp as the archetypal registers of violence in the contemporary world. Identifying this focus as the remnant of a Eurocentric vocabulary (the paradigm of war), the article proposes a shift from the language of warfare predominant in the field to a language of welfare. The article turns to the gated community (GC), instead of the camp, and the imperatives of (re)creation, instead of the logics of elimination, as new templates with which to make sense of modern/colonial violence. Moving beyond militaristic imagery, the analysis shows a form of violence that emerges as a response to the endless search for a life of convenience inside the walls of the GC. To this end, the article advances the concept of the dialect of disarrangement, the enforced but uneasy encounter between two subjectivities that inhabit the GC: the patrons (the homeowners who consume the easy life) and servants (the racialised service staff). In the GC, violence emerges in attempts to respond to this (in)convenient encounter via misrepresentations of both patrons and servants as out of their place.
Peer review of searches for studies for health technology assessments, systematic reviews, and other evidence syntheses
Authors: Lefebvre Carol , Duffy Steven
Published: May 2021

Introduction

Peer review of searches is a process whereby both the search strategies and the search process description are reviewed, ideally using an evidence-based checklist.

Rationale

As the search strategy underpins any well-conducted evidence synthesis, its quality could affect the final result. Evidence shows, however, that search strategies are prone to error.

Findings

There is increasing awareness and use of the PRESS Evidence-Based Checklist and peer review of search strategies, at the outset of evidence syntheses, prior to the searches being run, and this is now recommended by a number of evidence synthesis organizations.

Recommendations and conclusions

Searches for evidence syntheses should be peer reviewed by a suitably qualified and experienced librarian or information specialist after being designed, ideally, by another suitably qualified and experienced librarian or information specialist. Peer review of searches should take place at two important stages in the evidence synthesis process; at the outset of the project prior to the searches being run and at the prepublication stage. There is little empirical evidence, however, to support the effectiveness of peer review of searches. Further research is required to assess this. Those wishing to stay up to date with the latest developments in information retrieval, including peer review of searches, should consult the SuRe Info resource (http://www.sure-info.org), which seeks to help information specialists and others by providing easy access to the findings from current information retrieval methods research and thus support more research-based information retrieval practice.
Midazolam for conscious sedation in transcatheter device closure of atrial septal defects guided solely by transthoracic echocardiography
Authors: Wang Zeng-Chun , Liu Jian-Feng , Lei Yu-Qing , Xu Ning , Huang Shu-Ting , Chen Liang-Wan , Cao Hua , Chen Qiang
Published: May 2021

Objectives:

To investigate the safety and feasibility of midazolam for conscious sedation in transcatheter device closure of atrial septal defects guided solely by transthoracic echocardiography.

Methods:

A retrospective analysis was performed on 55 patients who underwent transcatheter device closure of atrial septal defects from October, 2019 to May, 2020. All patients received intravenous midazolam and local anesthesia with lidocaine to maintain sedation. A group of previous patients with unpublished data who underwent the same procedure with general anesthesia was set as the control group. The relevant clinical parameters, the Ramsay sedation scores, the numerical rating scale, and the post-operative satisfaction questionnaire were recorded and analyzed.

Results:

In the midazolam group, the success rate of atrial septal defect closure was 98.2%. Hemodynamic stability was observed during the procedure. None of the patients needed additional endotracheal intubation for general anesthesia. Compared with the control group, the midazolam group had no statistically significant differences in the Ramsay sedation score and numerical rating scale scores. Patients in the midazolam group experienced more post-operative satisfaction than those in the control group.

Conclusions:

Conscious sedation using midazolam is a safe and effective anesthetic technique for transcatheter device closure of atrial septal defects guided solely by transthoracic echocardiography.
Translation and Cultural Adaptation of NIH Toolbox Cognitive Tests into Swahili and Dholuo Languages for Use in Children in Western Kenya
Authors: Duffey Megan M. , Ayuku David , Ayodo George , Abuonji Emily , Nyalumbe Mark , Giella Amy K. , Hook Julie N. , Tran Tuan M. , McHenry Megan S.
Published: May 2021

Objectives:

Performing high-quality and reliable cognitive testing requires significant resources and training. As a result, large-scale studies involving cognitive testing are difficult to perform in low- and middle-income settings, limiting access to critical knowledge to improve academic achievement and economic production in these populations. The NIH Toolbox® is a collection of cognitive, motor, sensory, and emotional tests that can be administered and scored using an iPad® tablet, reducing the need for training and quality monitoring; and thus, it is a potential solution to this problem.

Methods:

We describe our process for translation and cultural adaptation of the existing NIH Toolbox tests of fluid cognition into the Swahili and Dholuo languages for use in children aged 3–14 years in western Kenya. Through serial forward and back translations, cognitive interviews, group consensus, outside feedback, and support from the NIH Toolbox team, we produced translated tests that have both face validity and linguistic validation.

Results:

During our cognitive interviews, we found that the five chosen tests (one each of attention, cognitive flexibility, working memory, episodic memory, and processing speed) were generally well understood by children aged 7–14 years in our chosen populations. The cognitive interviews informed alterations in translation as well as slight changes in some images to culturally adapt the tests.

Conclusions:

This study describes the process by which we translated five fluid cognition tests from the NIH Toolbox into the Swahili and Dholuo languages. The finished testing application will be available for future studies, including a pilot study for assessment of psychometric properties.
The Promise and Pitfalls of Online ‘Conversations’
Authors: Goldberg Sanford C.
Published: May 2021

Good conversations are one of the great joys of life. Online (social media) ‘conversations’ rarely seem to make the grade. In this paper I use some tools from philosophy in an attempt to illuminate what might be going wrong.
How Can You Spot the Experts? An Essay in Social Epistemology
Authors: Goldman Alvin I.
Published: May 2021

In the history of western philosophy, people were often encouraged to seek knowledge by starting from their own minds and proceeding in a highly individualistic spirit. In recent contemporary philosophy, by contrast, there is a movement toward Social Epistemology, which urges people to seek knowledge from what others know. However, in selected fields some people are experts while others are laypersons. It is natural for self-acknowledged laypersons to seek help from the experts. But who, exactly, are the experts? Many people claiming to be experts are not the real thing. How can laypersons identify genuine experts? This essay explores the problems that arise, pointing out some of the mistakes that can be made and how to avoid them.
Why Do Scientists Lie?
Authors: Bright Liam Kofi
Published: May 2021

It's natural to think of scientists as truth seekers, people driven by an intense curiosity to understand the natural world. Yet this picture of scientists and scientific inquiry sits uncomfortably with the reality and prevalence of scientific fraud. If one wants to get at the truth about nature, why lie? Won't that just set inquiry back, as people pursue false leads? To understand why this occurs – and what can be done about it – we need to understand the social structures scientists work within, and how some of the institutions which enable science to be such a successful endeavour all things considered, also abet and encourage fraud.
The Vulnerable Dynamics of Discourse
Authors: Giladi Paul , Petherbridge Danielle
Published: May 2021

In this paper, we offer some compelling reasons to think that issues relating to vulnerability play a significant – albeit thus far underacknowledged – role in Jürgen Habermas’s notions of communicative action and discourse. We shall argue that the basic notions of discourse and communicative action presuppose a robust conception of vulnerability and that recognising vulnerability is essential for (i) making sense of the social character of knowledge, on the epistemic side of things, and for (ii) making sense of the possibility of deliberative democracy, on the political side of things. Our paper is divided into four principal sections. In Section 1, we provide a basic outline of Habermas on communicative action and discourse. In Section 2, we develop an account of vulnerability and communication in the context of speaker/hearer relations. We specifically focus on distorted communication, vulnerability and speech. In Section 3, we focus on elaborating epistemic pathologies in the context of epistemic oppression and testimonial injustice. In Section 4, we focus on explaining how Habermasian resources contribute to vulnerability theory, and how introducing vulnerability theory to Habermas broadens or deepens his theory of communication action and his discourse ethics theory.
DATA REDUCTION BY THE HAAR FUNCTION: A CASE STUDY OF THE PHILLIPS CURVE
Authors: Gallegati Marco , Desai Meghnad , Ramsey James B.
Published: May 2021

The unorthodox estimation procedure, which Phillips (1958) adopted in his original paper, is examined using the Haar wavelet filter. The application of the Haar wavelet transform to Phillips’ original data shows that Phillips’ six pairs of mean coordinates display a striking similarity with the Haar scaling coefficients that represent averages with a period greater than 16 years. This is consistent with Desai’s (1975) intuition on the interpretation of the Phillips Curve. We show that the choice of sorting observations by ascending values of the unemployment rate is crucial for reaching the goal of estimating the eye-catching nonlinear hyperbolic shape of the wage–unemployment relationship that would be otherwise linear. Interestingly, the Haar filter can account not only for the facts characterizing the Phillips’ relationship up to the early 1960s but also for two important facts mostly debated among policymakers: the downward shift of the Phillips Curve and its flattening over time.
Bioactive Trace Metals and Their Isotopes as Paleoproductivity Proxies: An Assessment Using GEOTRACES‐Era Data
Authors: Horner T. J. , Little S. H. , Conway T. M. , Farmer J. R. , Hertzberg J. E. , Janssen D. J. , Lough A. J. M. , McKay J. L. , Tessin A. , Galer S. J. G. , Jaccard S. L. , Lacan F. , Paytan A. , Wuttig K. ,   GEOTRACES–PAGES Biological Productivity Working Group Members
Published: May 2021

Phytoplankton productivity and export sequester climatically significant quantities of atmospheric carbon dioxide as particulate organic carbon through a suite of processes termed the biological pump. Constraining how the biological pump operated in the past is important for understanding past atmospheric carbon dioxide concentrations and Earth's climate history. However, reconstructing the history of the biological pump requires proxies. Due to their intimate association with biological processes, several bioactive trace metals and their isotopes are potential proxies for past phytoplankton productivity, including iron, zinc, copper, cadmium, molybdenum, barium, nickel, chromium, and silver. Here, we review the oceanic distributions, driving processes, and depositional archives for these nine metals and their isotopes based on GEOTRACES‐era datasets. We offer an assessment of the overall maturity of each isotope system to serve as a proxy for diagnosing aspects of past ocean productivity and identify priorities for future research. This assessment reveals that cadmium, barium, nickel, and chromium isotopes offer the most promise as tracers of paleoproductivity, whereas iron, zinc, copper, and molybdenum do not. Too little is known about silver to make a confident determination. Intriguingly, the trace metals that are least sensitive to productivity may be used to track other aspects of ocean chemistry, such as nutrient sources, particle scavenging, organic complexation, and ocean redox state. These complementary sensitivities suggest new opportunities for combining perspectives from multiple proxies that will ultimately enable painting a more complete picture of marine paleoproductivity, biogeochemical cycles, and Earth's climate history.
On the Rootless Nature of a Devonian Suture in SW Iberia (Ossa‐Morena Complex, Variscan Orogen): Geometry and Kinematics of the Azuaga Fault
Authors: Fernández Rubén Díez , Fernández Carlos , Arenas Ricardo , Novo‐Fernández Irene
Published: May 2021

Suture zones are key to understand collisional orogens, but not all the remains of subduction leading to collision occur in the root of the suture. The Azuaga Fault bounds a Devonian suture zone known as Central Unit. This fault is a steeply NE‐dipping, Variscan strike‐slip fault with left‐lateral and reverse oblique slip components formed during sinistral transpression in the Pennsylvanian. Motion along this fault was coeval with folding and fabric development in both its hanging wall and footwall, and also with the Matachel Fault. Tectonic flow associated with the Azuaga Fault shows high‐vorticity, explaining the exhumation of a flat‐lying Devonian suture zone via WNW‐plunging extrusion from the upper‐middle crust under inclined triclinic transpression during ENE‐WSW convergence. The exposed basal contact of the Central Unit is not the root zone of a Variscan suture zone, but instead is a NE‐dipping breaching fault that cuts across the suture zone that is contiguous to the SW under the upper section of the footwall. The peri‐Gondwanan terrane between the Central Unit and the South‐Portuguese Zone of the Iberian Massif (most of the Ossa‐Morena Zone) is underlain by a Devonian suture, implying it is a continental allochthon. Variscan suture zones in Europe are affected by strike‐slip faults. In our case, this pattern implies the location of suture zone exposures and location of its root are different. Suture zones and strike‐slip faults are common in orogens and analysis of their relationships may lead to relocation of suture zone roots and re‐thinking of upper and lower plates.
Seasonality in Intermittent Streamflow Losses Beneath a Semiarid Mediterranean Wadi
Authors: Fakir Younes , Bouimouass Houssne , Constantz Jim
Published: May 2021

Streamflow losses beneath ephemeral and intermittent streams are potentially major contributors to groundwater recharge. Compared to ephemeral streams, intermittent streams often have more than one season of streamflow and often experience shorter zero‐flow periods during the dry seasons and typically longer wet season of steady streamflow. Intermittent streams losses are lacking significant investigation on their variability over wet and dry season, and on the influence on potential groundwater recharge of flooding streamflow compared with more gradual wet seasonal baseflow. To address these issues, both streambed‐sediment water content and temperature were continuously logged over a year for an intermittent stream (wadi) under semi‐arid conditions in Central Morocco. Water content measurements uniquely distinguished between downward percolation and upward advance of the wetting front due to the rise of the water table, whereas temperature modeling was used to estimate vertical fluxes of percolated water. For the year of data, more than 90% of the estimated potential recharge occurred during winter and spring, when the alluvium typically has a higher water moisture, with most recharge generated during flooding conditions. Winter and spring baseflow generally generated low infiltration, though importantly contributes to wetting the sediment for rapid, deep percolation during flooding. Alternatively, summer flashfloods over dry sediment resulted in shallower infiltration despite higher peak streamflows. Thus, clear seasonality (seasonal variation) in relations between amounts of streamflow, streamflow loss, and depth of wetting into the streambed were distinguished over the study year. Finally, lateral recharge was detected, leading to additional seasonal water‐table fluctuation beneath the wadi.
Mapping the transcriptomics landscape of post-traumatic stress disorder symptom dimensions in World Trade Center responders
Authors: Kuan Pei-Fen , Yang Xiaohua , Ren Xu , Che Chang , Waszczuk Monika , Kotov Roman , Clouston Sean , Singh Prashant K. , Glenn Sean T. , Gomez Eduardo Cortes , Wang Jianmin , Bromet Evelyn , Luft Benjamin J.
Published: May 2021

Gene expression has provided promising insights into the pathophysiology of post-traumatic stress disorder (PTSD); however, specific regulatory transcriptomic mechanisms remain unknown. The present study addressed this limitation by performing transcriptome-wide RNA-Seq of whole-blood samples from 226 World Trade Center responders. The investigation focused on differential expression (DE) at the gene, isoform, and for the first time, alternative splicing (AS) levels associated with the symptoms of PTSD: total burden, re-experiencing, avoidance, numbing, and hyperarousal subdimensions. These symptoms were associated with 76, 1, 48, 15, and 49 DE genes, respectively (FDR < 0.05). Moreover, they were associated with 103, 11, 0, 43, and 32 AS events. Avoidance differed the most from other dimensions with respect to DE genes and AS events. Gene set enrichment analysis (GSEA) identified pathways involved in inflammatory and metabolic processes, which may have implications in the treatment of PTSD. Overall, the findings shed a novel light on the wide range of transcriptomic alterations associated with PTSD at the gene and AS levels. The results of DE analysis associated with PTSD subdimensions highlights the importance of studying PTSD symptom heterogeneity.
Mechanical tibial loading remotely suppresses brain tumors by dopamine-mediated downregulation of CCN4
Authors: Fan Yao , Zha Rongrong , Sano Tomohiko , Zhao Xinyu , Liu Shengzhi , Woollam Mark D. , Wu Di , Sun Xun , Li Kexin , Egi Motoki , Li Fangjia , Minami Kazumasa , Siegel Amanda P. , Horiuchi Takashi , Liu Jing , Agarwal Mangilal , Sudo Akihiro , Nakshatri Harikrishna , Li Bai-Yan , Yokota Hiroki
Published: May 2021

Mechanical loading to the bone is known to be beneficial for bone homeostasis and for suppressing tumor-induced osteolysis in the loaded bone. However, whether loading to a weight-bearing hind limb can inhibit distant tumor growth in the brain is unknown. We examined the possibility of bone-to-brain mechanotransduction using a mouse model of a brain tumor by focusing on the response to Lrp5-mediated Wnt signaling and dopamine in tumor cells. The results revealed that loading the tibia with elevated levels of tyrosine hydroxylase, a rate-limiting enzyme in dopamine synthesis, markedly reduced the progression of the brain tumors. The simultaneous application of fluphenazine (FP), an antipsychotic dopamine modulator, enhanced tumor suppression. Dopamine and FP exerted antitumor effects through the dopamine receptors DRD1 and DRD2, respectively. Notably, dopamine downregulated Lrp5 via DRD1 in tumor cells. A cytokine array analysis revealed that the reduction in CCN4 was critical for loading-driven, dopamine-mediated tumor suppression. The silencing of Lrp5 reduced CCN4, and the administration of CCN4 elevated oncogenic genes such as MMP9, Runx2, and Snail. In summary, this study demonstrates that mechanical loading regulates dopaminergic signaling and remotely suppresses brain tumors by inhibiting the Lrp5-CCN4 axis via DRD1, indicating the possibility of developing an adjuvant bone-mediated loading therapy.
Targeting novel LSD1-dependent ACE2 demethylation domains inhibits SARS-CoV-2 replication
Authors: Tu Wen Juan , McCuaig Robert D. , Melino Michelle , Rawle Daniel J. , Le Thuy T. , Yan Kexin , Suhrbier Andreas , Johnston Rebecca L. , Koufariotis Lambros T. , Waddell Nicola , Cross Emily M. , Tsimbalyuk Sofiya , Bain Amanda , Ahern Elizabeth , Collinson Natasha , Phipps Simon , Forwood Jade K. , Seddiki Nabila , Rao Sudha
Published: May 2021

Treatment options for COVID-19 remain limited, especially during the early or asymptomatic phase. Here, we report a novel SARS-CoV-2 viral replication mechanism mediated by interactions between ACE2 and the epigenetic eraser enzyme LSD1, and its interplay with the nuclear shuttling importin pathway. Recent studies have shown a critical role for the importin pathway in SARS-CoV-2 infection, and many RNA viruses hijack this axis to re-direct host cell transcription. LSD1 colocalized with ACE2 at the cell surface to maintain demethylated SARS-CoV-2 spike receptor-binding domain lysine 31 to promote virus–ACE2 interactions. Two newly developed peptide inhibitors competitively inhibited virus–ACE2 interactions, and demethylase access to significantly inhibit viral replication. Similar to some other predominantly plasma membrane proteins, ACE2 had a novel nuclear function: its cytoplasmic domain harbors a nuclear shuttling domain, which when demethylated by LSD1 promoted importin-α-dependent nuclear ACE2 entry following infection to regulate active transcription. A novel, cell permeable ACE2 peptide inhibitor prevented ACE2 nuclear entry, significantly inhibiting viral replication in SARS-CoV-2-infected cell lines, outperforming other LSD1 inhibitors. These data raise the prospect of post-exposure prophylaxis for SARS-CoV-2, either through repurposed LSD1 inhibitors or new, nuclear-specific ACE2 inhibitors.
CRISPECTOR provides accurate estimation of genome editing translocation and off-target activity from comparative NGS data
Authors: Amit Ido , Iancu Ortal , Levy-Jurgenson Alona , Kurgan Gavin , McNeill Matthew S. , Rettig Garrett R. , Allen Daniel , Breier Dor , Ben Haim Nimrod , Wang Yu , Anavy Leon , Hendel Ayal , Yakhini Zohar
Published: May 2021

Controlling off-target editing activity is one of the central challenges in making CRISPR technology accurate and applicable in medical practice. Current algorithms for analyzing off-target activity do not provide statistical quantification, are not sufficiently sensitive in separating signal from noise in experiments with low editing rates, and do not address the detection of translocations. Here we present CRISPECTOR, a software tool that supports the detection and quantification of on- and off-target genome-editing activity from NGS data using paired treatment/control CRISPR experiments. In particular, CRISPECTOR facilitates the statistical analysis of NGS data from multiplex-PCR comparative experiments to detect and quantify adverse translocation events. We validate the observed results and show independent evidence of the occurrence of translocations in human cell lines, after genome editing. Our methodology is based on a statistical model comparison approach leading to better false-negative rates in sites with weak yet significant off-target activity.
Offspring survival changes over generations of captive breeding
Authors: Farquharson Katherine A. , Hogg Carolyn J. , Grueber Catherine E.
Published: May 2021

Conservation breeding programs such as zoos play a major role in preventing extinction, but their sustainability may be impeded by neutral and adaptive population genetic change. These changes are difficult to detect for a single species or context, and impact global conservation efforts. We analyse pedigree data from 15 vertebrate species – over 30,000 individuals – to examine offspring survival over generations of captive breeding. Even accounting for inbreeding, we find that the impacts of increasing generations in captivity are highly variable across species, with some showing substantial increases or decreases in offspring survival over generations. We find further differences between dam and sire effects in first- versus multi-generational analysis. Crucially, our multispecies analysis reveals that responses to captivity could not be predicted from species’ evolutionary (phylogenetic) relationships. Even under best-practice captive management, generational fitness changes that cannot be explained by known processes (such as inbreeding depression), are occurring.
Immunotranscriptomic profiling the acute and clearance phases of a human challenge dengue virus serotype 2 infection model
Authors: Hanley John P. , Tu Huy A. , Dragon Julie A. , Dickson Dorothy M. , Rio-Guerra Roxana del , Tighe Scott W. , Eckstrom Korin M. , Selig Nicholas , Scarpino Samuel V. , Whitehead Stephen S. , Durbin Anna P. , Pierce Kristen K. , Kirkpatrick Beth D. , Rizzo Donna M. , Frietze Seth , Diehl Sean A.
Published: May 2021

About 20–25% of dengue virus (DENV) infections become symptomatic ranging from self-limiting fever to shock. Immune gene expression changes during progression to severe dengue have been documented in hospitalized patients; however, baseline or kinetic information is difficult to standardize in natural infection. Here we profile the host immunotranscriptome response in humans before, during, and after infection with a partially attenuated rDEN2Δ30 challenge virus (ClinicalTrials.gov NCT02021968). Inflammatory genes including type I interferon and viral restriction pathways are induced during DENV2 viremia and return to baseline after viral clearance, while others including myeloid, migratory, humoral, and growth factor immune regulation factors pathways are found at non-baseline levels post-viremia. Furthermore, pre-infection baseline gene expression is useful to predict rDEN2Δ30-induced immune responses and the development of rash. Our results suggest a distinct immunological profile for mild rDEN2Δ30 infection and offer new potential biomarkers for characterizing primary DENV infection.
High-efficiency CO2 separation using hybrid LDH-polymer membranes
Authors: Xu Xiaozhi , Wang Jiajie , Zhou Awu , Dong Siyuan , Shi Kaiqiang , Li Biao , Han Jingbin , O’Hare Dermot
Published: May 2021

Membrane-based gas separation exhibits many advantages over other conventional techniques; however, the construction of membranes with simultaneous high selectivity and permeability remains a major challenge. Herein, (LDH/FAS)n-PDMS hybrid membranes, containing two-dimensional sub-nanometre channels were fabricated via self-assembly of unilamellar layered double hydroxide (LDH) nanosheets and formamidine sulfinic acid (FAS), followed by spray-coating with a poly(dimethylsiloxane) (PDMS) layer. A CO2transmission rate for (LDH/FAS)25-PDMS of 7748 GPU together with CO2selectivity factors (SF) for SF(CO2/H2), SF(CO2/N2) and SF(CO2/CH4) mixtures as high as 43, 86 and 62 respectively are observed. The CO2permselectivity outperforms most reported systems and is higher than the Robeson or Freeman upper bound limits. These (LDH/FAS)n-PDMS membranes are both thermally and mechanically robust maintaining their highly selective CO2separation performance during long-term operational testing. We believe this highly-efficient CO2separation performance is based on the synergy of enhanced solubility, diffusivity and chemical affinity for CO2in the sub-nanometre channels.