bluuebunny/crossref_metadata_2025 huggingface dataset:
Should Criminal Law Mirror Moral Blameworthiness or Criminal Culpability? A Reply to Husak
Authors: Sarch Alexander
Published: December 2021

In Ignorance of Law, Doug Husak defends a version of legal moralism on which ‘we should recognize a presumption that the criminal law should…be based, on conform to, or mirror critical morality’. Here I explore whether substantive criminal law rules should directly mirror not moral blameworthiness, but a distinct legal notion of criminal culpability – akin to moral blameworthiness but refined for deployment in legal systems. Contra Husak, I argue that the criminal law departing from the moral ideal embodied in the standard of moral blameworthiness is not always to be regretted. After showing how criminal culpability might come apart from moral blameworthiness, I argue that my alternative to Husak’s view has practically interesting upshots. In particular, it allows us to resist Husak’s central conclusions about the exculpatory force of normative ignorance. There are good reasons for the criminal law to make certain charitable presumptions about citizens as competent agents, which the standard of moral blameworthiness needn’t similarly embody, and this calls into question Husak’s argument for the claim that normative ignorance exculpates.
Water and soil contaminated by arsenic: the use of microorganisms and plants in bioremediation
Authors: Bertin Philippe N. , Crognale Simona , Plewniak Frédéric , Battaglia-Brunet Fabienne , Rossetti Simona , Mench Michel
Published: December 2021

Owing to their roles in the arsenic (As) biogeochemical cycle, microorganisms and plants offer significant potential for developing innovative biotechnological applications able to remediate As pollutions. This possible use in bioremediation processes and phytomanagement is based on their ability to catalyse various biotransformation reactions leading to, e.g. the precipitation, dissolution, and sequestration of As, stabilisation in the root zone and shoot As removal. On the one hand, genomic studies of microorganisms and their communities are useful in understanding their metabolic activities and their interaction with As. On the other hand, our knowledge of molecular mechanisms and fate of As in plants has been improved by laboratory and field experiments. Such studies pave new avenues for developing environmentally friendly bioprocessing options targeting As, which worldwide represents a major risk to many ecosystems and human health.
Optimal Plot Dimensions for Performance Testing of Hybrid Potato in the Field
Authors: Stockem Julia E. , Korontzis George , Wilson Stefan E. , de Vries Michiel E. , van Eeuwijk Fred A. , Struik Paul C.
Published: December 2021

Field trials to evaluate the performance of new varieties are an essential component of potato breeding. Besides the genetic differences, environmental factors can lead to variation in a trial. In variety trials, the observed differences amongst varieties should reflect genetic differences, without a large impact of the random or systematic variation in the field. One way to reduce within-field variation is to adjust the plot size and its shape in a trial. Two years of field trials in which individual plants in 90-plant plots of both diploid hybrid and tetraploid varieties were measured provided data to derive relationships between LSD% and plot size and shape. We provide a method to estimate the equations to calculate the expected variation when using different plot dimensions in a relatively homogeneous trial field for tuber yield, tuber volume, tuber count, tuber shape and the standard deviations of tuber volume and shape. Compared with the yield traits, the variation for tuber shape was relatively small. The effect of plot shape was minor. With these equations, breeders can determine what plot dimensions are needed to reach the desired precision for each trait.
Quantitative Nanostructure and Hardness Evolution in Duplex Stainless Steels: Under Real Low-Temperature Service Conditions
Authors: Das Yadunandan , Liu Jianling , Ehteshami Hossein , Odqvist Joakim , Holländer Pettersson Niklas , Wessman Sten , King Stephen , Hedström Peter
Published: December 2021

Duplex stainless steels are a group of widely used stainless steels, because of their attractive combination of strength and corrosion resistance. However, these steels embrittle because of a phase separation phenomenon in the ferrite phase when exposed to temperatures within the miscibility gap. This manuscript investigates the phase separation in two commercial stainless steels, the duplex stainless steel (DSS) 22Cr-5Ni (2205 or UNS S32205), and the super-duplex stainless steel (SDSS) 25Cr-7Ni (2507 or UNS S32750), and its subsequent effect on mechanical property evolution. Long-term isothermal aging heat treatments were carried out at industrially relevant temperatures between 250 °C and 350 °C for up to 48,000 hours, and quantitative measurements of the amplitude and wavelength of the phase separated nanostructure were obtained using Small-Angle Neutron Scattering (SANS). These quantifications were used as input parameters in hardness models to predict the hardness evolution. It is concluded that the quantitative information from SANS combined with these hardness models enables the prediction of hardness evolution in DSS at low temperatures, which in turn correlates with the embrittlement of the DSS.
18S and ITS2 rDNA sequence-structure phylogeny of Prototheca (Chlorophyta, Trebouxiophyceae)
Authors: Plieger Tanja , Wolf Matthias
Published: December 2021

Protothecosis is an infectious disease caused by organisms currently classified within the green algal genus Prototheca. The disease can manifest as cutaneous lesions, olecranon bursitis or disseminated or systemic infections in both immunocompetent and immunosuppressed patients. Concerning diagnostics, taxonomic validity is important. Prototheca, closely related to the Chlorella species complex, is known to be polyphyletic, branching with Auxenochlorella and Helicosporidium. The phylogeny of Prototheca was discussed and revisited several times in the last decade; new species have been described. Phylogenetic analyses were performed using ribosomal DNA (rDNA) and partial mitochondrial cytochrome b (cytb) sequence data. In this work we use Internal Transcribed Spacer 2 (ITS2) as well as 18S rDNA data. However, for the first time, we reconstruct phylogenetic relationships of Prototheca using primary sequence and RNA secondary structure information simultaneously, a concept shown to increase robustness and accuracy of phylogenetic tree estimation. Using encoded sequence-structure data, Neighbor-Joining, Maximum-Parsimony and Maximum-Likelihood methods yielded well-supported trees in agreement with other trees calculated on rDNA; but differ in several aspects from trees using cytb as a phylogenetic marker. ITS2 secondary structures of Prototheca sequences are in agreement with the well-known common core structure of eukaryotes but show unusual differences in their helix lengths. An elongation of the fourth helix of some species seems to have occurred independently in the course of evolution.
A Study Space Analysis of Interpretation Service Needs and Optimisation
Authors: Amurun Oghene-Ovoh Tyson
Published: December 2021

The paper reports a study space analysis (SSA) of 117 published investigations of the need for interpretation services and approaches to their optimisation. The study explores literature on the adequacy and ecological validity of interpretation service and interpretation optimisation. Research on rapport building appears to be the most investigated issue. Studies on interpretation services need and planning are infrequently researched, and there exist little or no study investigating police diversity effects on interpretation service needs and the planning effects. Studies investigating cognitive load, language, and gender effects on interpreting accuracy are sparse, with most research effort concentrated in conference interpreting settings.
In vitro assessment of histamine and lactate production by a multi-strain synbiotic
Authors: Stuivenberg Gerrit , Daisley Brendan , Akouris Polycronis , Reid Gregor
Published: December 2021

Recent studies suggest histamine and d-lactate may negatively impact host health. As excess histamine is deleterious to the host, the identification of bacterial producers has contributed to concerns over the consumption of probiotics or live microorganisms in fermented food items. Some probiotic products have been suspected of inducing d-lactic-acidosis; an illness associated with neurocognitive symptoms such as ataxia. The goals of the present study were to test the in vitro production of histamine and d-lactate by a 24-strain daily synbiotic and to outline methods that others can use to test for their production. Using enzymatic based assays, no significant production of histamine was observed compared to controls (P > 0.05), while d-lactate production was comparable to a commercially available probiotic with no associated health risk. These assays provide a means to add to the safety profile of synbiotic and probiotic products.
Challenges in Using Recommended Quality of Life Measures to Assess Fluctuating Health: A Think-Aloud Study to Understand How Recall and Timing of Assessment Influence Patient Responses
Authors: Sanghera Sabina , Walther Axel , Peters Tim J. , Coast Joanna
Published: December 2021

Background

It can be challenging to measure quality of life to calculate quality-adjusted life-years in recurrent fluctuating health states, as quality of life can constantly change. It is not clear how patients who experience fluctuations complete measures and how assessment timing and recall influence responses.

Objective

We aimed to understand how patients with fluctuating health complete widely recommended and commonly used measures (EQ-5D-5L, EORTC QLQ-C30 and SF-12) and the extent to which the recall period (‘health today’, ‘past week’ and ‘past 4 weeks’) and timing of assessment influence the way that patients complete these questionnaires.

Methods

Twenty-four adult patients undergoing chemotherapy for urological, gynaecological or bowel cancers in the UK participated in think-aloud interviews, while completing the measures, completed a pictorial task illustrating how quality of life changed during the chemotherapy cycle and took part in semi-structured interviews. Transcripts were analysed using constant comparison.

Results

Patients were consistent in describing their quality of life as changing considerably throughout a chemotherapy cycle. The shorter recall period of ‘health today’ does not adequately represent patients’ quality of life because of fluctuations, patients remarked they could give a different answer depending on the timing of assessment, and many struggled to combine the “ups and downs” to answer measures with longer recall (‘past week’ and ‘past 4 weeks’). Across all measures, patients attempted to provide averages, adopt the peak-end rule or focus on the best part of their experience. Patients commonly used more than one approach when completing a given questionnaire as well as across questionnaires.

Conclusions

Patients who experience recurrent fluctuations in health are unable to provide meaningful responses about their quality of life when completing quality-of-life measures due to the recall period and timing of assessment. The use of such responses to calculate health state values in economic evaluations to inform resource allocation decisions in fluctuating conditions must be questioned.
The Future on Love and Business Organizing. An Agenda for Growth and Affirmation of People and the Environment (AGAPE)
Authors: Hummels Harry , Lee Matthew T. , Nullens Patrick , Ruffini Renato , Hancock Jennifer
Published: December 2021

Business and love appear to have little to do with each other. We hold the opposite to be true if the concept of love in business draws from two corresponding grammars. This paper contributes to the ‘agenda for growth and affirmation of people and the environment’ (agape) in business. By focusing on the grammars of love and business we operationalize the concept of love in ways that business executives, managers and employees can understand, adopt, and implement. With references to the theory and practice of management and organizations, we aim to contribute to expanding the theory and practice of responsible organizations and their leaders caring for others.
Evaluation of capabilities of the nanoindentation test in the determination of flow stress characteristics of the matrix material in porous sinters
Authors: Madej Lukasz , Legwand Adam , Setty Mohan , Mojzeszko Mateusz , Perzyński Konrad , Roskosz Stanislaw , Chrapoński Jacek
Published: December 2021

Herein, we evaluate the nanoindentation test capabilities in the determination of flow stress characteristics of the matrix material in porous sinters. The Distaloy AB sample with 15% porosity after the sintering operation is selected as a case study for the investigation. 2D and 3D imaging techniques are employed first to highlight difficulties in identifying reliable nano hardness measurement zones for further properties evaluation. Then, nanoindentation test results are acquired with Berkovich tip pressed under various loads at different locations in the sample. Systematic indentations in the quartz sample are used as a cleaning procedure to minimize the effect of the possible build-up around the indenter tip. The representative indentation load range is selected based on the extracted material characteristics. With that, the stress–strain response of the sinter matrix material is identified. The reliability of the determined flow stress curve is confirmed with the use of conical nanoindentation measurement results and finite element simulations. Obtained results show that it is possible to calculate reliable flow stress characteristics of the matrix in the porous samples, with the assumption that experiments under various loading conditions and from various locations in the matrix are performed. It is also pointed out that various indentation loads should be used to eliminate the influence of the pile-up or scale effects that affect the overall material response.
Router and gateway node placement in wireless mesh networks for emergency rescue scenarios
Authors: Wzorek Mariusz , Berger Cyrille , Doherty Patrick
Published: December 2021

The focus of this paper is on base functionalities required for UAV-based rapid deployment of an ad hoc communication infrastructure in the initial phases of rescue operations. The main idea is to use heterogeneous teams of UAVs to deploy communication kits that include routers, and are used in the generation of ad hoc Wireless Mesh Networks (WMN). Several fundamental problems are considered and algorithms are proposed to solve these problems. The Router Node Placement problem (RNP) and a generalization of it that takes into account additional constraints arising in actual field usage is considered first. The RNP problem tries to determine how to optimally place routers in a WMN. A new algorithm, the RRT-WMN algorithm, is proposed to solve this problem. It is based in part on a novel use of the Rapidly Exploring Random Trees (RRT) algorithm used in motion planning. A comparative empirical evaluation between the RRT-WMN algorithm and existing techniques such as the Covariance Matrix Adaptation Evolution Strategy (CMA-ES) and Particle Swarm Optimization (PSO), shows that the RRT-WMN algorithm has far better performance both in amount of time taken and regional coverage as the generalized RNP problem scales to realistic scenarios. The Gateway Node Placement Problem (GNP) tries to determine how to locate a minimal number of gateway nodes in a WMN backbone network while satisfying a number of Quality of Service (QoS) constraints.Two alternatives are proposed for solving the combined RNP-GNP problem. The first approach combines the RRT-WMN algorithm with a preexisting graph clustering algorithm. The second approach, WMNbyAreaDecomposition, proposes a novel divide-and-conquer algorithm that recursively partitions a target deployment area into a set of disjoint regions, thus creating a number of simpler RNP problems that are then solved concurrently. Both algorithms are evaluated on real-world GIS models of different size and complexity. WMNbyAreaDecomposition is shown to outperform existing algorithms using 73% to 92% fewer router nodes while at the same time satisfying all QoS requirements.
Transonic industrial wind tunnel testing in the 2020s
Authors: Greenwell D.I.
Published: December 2021

Wind tunnels remain an essential element in the design and development of flight vehicles. However, graduates in aerospace engineering tend to have had little exposure to the demands of industrial experimental work, particularly at high speed, a situation exacerbated by a lack of up-to-date reference material. In an attempt to fill this gap, this paper presents an overview of the current and near-term status and usage of transonic industrial wind tunnels. The review is aimed at recent entrants to the field, with the aim of helping them make the step from research projects in small university facilities to commercial projects in large industrial facilities. In addition, a picture has emerged from the review that contradicts received wisdom that the wind tunnel is in decline. Globally, the industrial transonic wind tunnel is undergoing somewhat of a renaissance. Numbers are increasing, investment levels are rising, capabilities are being enhanced, and facilities are busy.
Reviewing the impacts of climate change on air transport operations
Authors: Gratton G. B. , Williams P. D. , Padhra A. , Rapsomanikis S.
Published: December 2021

Climate change is increasing global-mean tropospheric temperatures, but the localised trends are uneven, including cooling the lower stratosphere and lifting the tropopause. The wind speeds are also being modified, both at the surface and aloft. A further effect, additional to wind and temperature alone, is of increasing fluctuations and severity of extreme weather. These are impacting air transport, and this will continue. The effects are known to include increased take-off distances where excess runway lengths exist and reduced payloads where they do not, increased en-route flight times, increased frequency and severity of encounters with clear air turbulence in some regions, changed patterns of wildlife — particularly bird — activity in some regions (potentially also for other anthropogenic reasons) are shifting locations of flight safety hazards, and increased burdens upon airport and associated infrastructure. There is increasing understanding and acknowledgment by companies and authorities of these effects and the importance of mitigating them, although this is not universal and there are as yet no universally understood best practices for air transport climate change mitigation.
The Essential Role of Statistical Inference in Evaluating Electoral Systems: A Response to DeFord et al.
Authors: Katz Jonathan N. , King Gary , Rosenblatt Elizabeth
Published: December 2021

Katz, King, and Rosenblatt (2020, American Political Science Review 114, 164–178) introduces a theoretical framework for understanding redistricting and electoral systems, built on basic statistical and social science principles of inference. DeFord et al. (2021, Political Analysis, this issue) instead focuses solely on descriptive measures, which lead to the problems identified in our article. In this article, we illustrate the essential role of these basic principles and then offer statistical, mathematical, and substantive corrections required to apply DeFord et al.’s calculations to social science questions of interest, while also showing how to easily resolve all claimed paradoxes and problems. We are grateful to the authors for their interest in our work and for this opportunity to clarify these principles and our theoretical framework.
Decay of weak solutions to Vlasov equation coupled with a shear thickening fluid
Authors: Kim Jae-Myoung
Published: December 2021

We show that the energy norm of weak solutions to Vlasov equation coupled with a shear thickening fluid on the whole space has a decay rate the energy norm $E(t) \leq {C}/{(1+t)^{\alpha }}, \forall t \geq 0$ for $\alpha \in (0,3/2)$.
Hanoi's Diplomatic Front in Sweden: Communist Propaganda Strategies in the Vietnam War
Authors: Johansson Perry
Published: December 2021

This article offers a new perspective on the Swedish protests against the Vietnam War by placing it in its broader global Cold War context. As a case study on ‘people's diplomacy’ and ‘united front strategy’, it acknowledges the importance of Chinese and Vietnamese influences on the peace campaigns in Sweden and aims, as far as possible, to reconstruct Hanoi's motives, strategies and actions to create and direct Sweden's policy and opinion on the war. With the extremely generous political freedoms granted it by official Sweden, Hanoi was able to find new international allies as well as organise political propaganda manifestations from their Stockholm base. In the end, North Vietnam's version of the war as being about national liberation fought by a people united in their resistance to a foreign, genocidal, aggressor won a large enough share of the opinion in the West to force the American political leadership to give up the fight. Hanoi's Diplomatic Front in Sweden was one of the important battlefields behind that victory
OCD, death anxiety, and attachment: what’s love got to do with it?
Authors: Verin Rachel E. , Menzies Rachel E. , Menzies Ross G.
Published: December 2021

Background:

Death anxiety has been empirically implicated in obsessive compulsive disorder (OCD). Research has shown that secure attachments appear to protect against fear of death, and are also associated with reduced risk of mental illness. However, few studies have investigated the moderating effect of attachment style in the relationship between death anxiety and OCD.

Aims:

The present study sought to explore whether attachment style moderates the relationship between death anxiety and OCD symptoms among a treatment-seeking sample of individuals diagnosed with OCD.

Method:

Following a structured diagnostic interview, a number of measures were administered to 48 participants. These included the Multidimensional Fear of Death Scale, Vancouver Obsessive Compulsive Inventory, and Experiences in Close Relationships-Revised.

Results:

As expected, death anxiety was a strong predictor of OCD severity, and other markers of psychopathology. However, contrary to hypotheses, neither anxious nor avoidant attachment style moderated the association between fear of death and OCD severity.

Conclusions:

The current findings add further support to the role of death anxiety in OCD. Given the absence of a moderating effect of attachment between death fears and OCD severity, it is possible that this proposed buffer against death anxiety may potentially be insufficient in the presence of this disorder. Further research is needed to clarify whether attachment style may moderate the relationship between death anxiety and symptom severity in other disorders.
Comparison of paracetamol and diclofenac prescribing preferences for adults in primary care
Authors: Bayram Dilara , Aydin Volkan , Sanli Abdullah , Abanoz Mustafa Naci , Sibic Busra , Pala Sedat , Atac Omer , Akici Ahmet
Published: December 2021

Introduction:

The most frequently prescribed analgesic drugs in primary care centers in Turkey are diclofenac and paracetamol, respectively. In this study, we aimed to compare paracetamol-included prescriptions (PIP) and diclofenac-included prescriptions (DIP) generated for adult patients in primary care.

Methods:

In this cross-sectional study, PIPs (n= 280 488) and DIPs (n= 337 935) created for adults by systematic sampling among primary care physicians working in Istanbul in 2016 (n= 1431) were examined. The demographic characteristics, diagnoses, and additional drugs in PIPs and DIPs were compared.

Results:

Women constituted the majority in both groups (69.8% and 67.9%, respectively;P< 0.05), and mean age at PIP (52.6 ± 18.8 years) was lower compared to DIP (56.3 ± 16.1 years), (P< 0.05). In single-diagnosis prescriptions, 11 of the 15 most common diagnoses in PIP were respiratory tract infections (47.9%); three pain-related diagnoses formed 4.6% of all these prescriptions. In DIP, the number of pain-related diagnoses, mostly of musculoskeletal origin, was eight (28.5%); four diagnoses (7.8%) were upper respiratory tract infections. While hypertension was the third most common diagnosis in PIP (6.1%), it was ranked first in DIP (8.0%). The percentage of prescriptions with additional analgesic (14.0% versus 18.3%,P< 0.001), proton-pump inhibitor (13.8% versus 18.4%;P< 0.001), and antihypertensive (22.0% versus 24.8%,P< 0.001) was lower in PIP compared to DIP. However, the percentage of prescriptions with antibiotics (31.3% versus 14.7%,P< 0.001) was higher in PIP.

Conclusion:

Paracetamol appears to be preferred mostly in upper respiratory tract infections compared to the preference of diclofenac rather in painful/inflammatory musculoskeletal conditions. The presence of hypertension among the most commonly encountered diagnoses for these analgesic drugs points to challenges in establishing the diagnosing-treatment match and indicates potential irrational prescribing practice, especially for interactions.
TEMPORAL INTERPRETATION OF MONADIC INTUITIONISTIC QUANTIFIERS
Authors: BEZHANISHVILI GURAM , CARAI LUCA
Published: December 2021

We show that monadic intuitionistic quantifiers admit the following temporal interpretation: “always in the future” (for$\forall $) and “sometime in the past” (for$\exists $). It is well known that Prior’s intuitionistic modal logic${\sf MIPC}$axiomatizes the monadic fragment of the intuitionistic predicate logic, and that${\sf MIPC}$is translated fully and faithfully into the monadic fragment${\sf MS4}$of the predicate${\sf S4}$via the Gödel translation. To realize the temporal interpretation mentioned above, we introduce a new tense extension${\sf TS4}$of${\sf S4}$and provide a full and faithful translation of${\sf MIPC}$into${\sf TS4}$. We compare this new translation of${\sf MIPC}$with the Gödel translation by showing that both${\sf TS4}$and${\sf MS4}$can be translated fully and faithfully into a tense extension of${\sf MS4}$, which we denote by${\sf MS4.t}$. This is done by utilizing the relational semantics for these logics. As a result, we arrive at the diagram of full and faithful translations shown in Figure 1 which is commutative up to logical equivalence. We prove the finite model property (fmp) for${\sf MS4.t}$using algebraic semantics, and show that the fmp for the other logics involved can be derived as a consequence of the fullness and faithfulness of the translations considered.
Heat stress reduces the contribution of diazotrophs to coral holobiont nitrogen cycling
Authors: Rädecker Nils , Pogoreutz Claudia , Gegner Hagen M , Cárdenas Anny , Perna Gabriela , Geißler Laura , Roth Florian , Bougoure Jeremy , Guagliardo Paul , Struck Ulrich , Wild Christian , Pernice Mathieu , Raina Jean-Baptiste , Meibom Anders , Voolstra Christian R
Published: December 2021

Efficient nutrient cycling in the coral-algal symbiosis requires constant but limited nitrogen availability. Coral-associated diazotrophs, i.e., prokaryotes capable of fixing dinitrogen, may thus support productivity in a stable coral-algal symbiosis but could contribute to its breakdown when overstimulated. However, the effects of environmental conditions on diazotroph communities and their interaction with other members of the coral holobiont remain poorly understood. Here we assessed the effects of heat stress on diazotroph diversity and their contribution to holobiont nutrient cycling in the reef-building coral Stylophora pistillata from the central Red Sea. In a stable symbiotic state, we found that nitrogen fixation by coral-associated diazotrophs constitutes a source of nitrogen to the algal symbionts. Heat stress caused an increase in nitrogen fixation concomitant with a change in diazotroph communities. Yet, this additional fixed nitrogen was not assimilated by the coral tissue or the algal symbionts. We conclude that although diazotrophs may support coral holobiont functioning under low nitrogen availability, altered nutrient cycling during heat stress abates the dependence of the coral host and its algal symbionts on diazotroph-derived nitrogen. Consequently, the role of nitrogen fixation in the coral holobiont is strongly dependent on its nutritional status and varies dynamically with environmental conditions.
Discovery of an exosite on the SOCS2-SH2 domain that enhances SH2 binding to phosphorylated ligands
Authors: Linossi Edmond M. , Li Kunlun , Veggiani Gianluca , Tan Cyrus , Dehkhoda Farhad , Hockings Colin , Calleja Dale J. , Keating Narelle , Feltham Rebecca , Brooks Andrew J. , Li Shawn S. , Sidhu Sachdev S. , Babon Jeffrey J. , Kershaw Nadia J. , Nicholson Sandra E.
Published: December 2021

Suppressor of cytokine signaling (SOCS)2 protein is a key negative regulator of the growth hormone (GH) and Janus kinase (JAK)-Signal Transducers and Activators of Transcription (STAT) signaling cascade. The central SOCS2-Src homology 2 (SH2) domain is characteristic of the SOCS family proteins and is an important module that facilitates recognition of targets bearing phosphorylated tyrosine (pTyr) residues. Here we identify an exosite on the SOCS2-SH2 domain which, when bound to a non-phosphorylated peptide (F3), enhances SH2 affinity for canonical phosphorylated ligands. Solution of the SOCS2/F3 crystal structure reveals F3 as an α-helix which binds on the opposite side of the SH2 domain to the phosphopeptide binding site. F3:exosite binding appears to stabilise the SOCS2-SH2 domain, resulting in slower dissociation of phosphorylated ligands and consequently, enhances binding affinity. This biophysical enhancement of SH2:pTyr binding affinity translates to increase SOCS2 inhibition of GH signaling.
Conformational changes in Lassa virus L protein associated with promoter binding and RNA synthesis activity
Authors: Kouba Tomas , Vogel Dominik , Thorkelsson Sigurdur R. , Quemin Emmanuelle R. J. , Williams Harry M. , Milewski Morlin , Busch Carola , Günther Stephan , Grünewald Kay , Rosenthal Maria , Cusack Stephen
Published: December 2021

Lassa virus is endemic in West Africa and can cause severe hemorrhagic fever. The viral L protein transcribes and replicates the RNA genome via its RNA-dependent RNA polymerase activity. Here, we present nine cryo-EM structures of the L protein in the apo-, promoter-bound pre-initiation and active RNA synthesis states. We characterize distinct binding pockets for the conserved 3’ and 5’ promoter RNAs and show how full-promoter binding induces a distinct pre-initiation conformation. In the apo- and early elongation states, the endonuclease is inhibited by two distinct L protein peptides, whereas in the pre-initiation state it is uninhibited. In the early elongation state, a template-product duplex is bound in the active site cavity together with an incoming non-hydrolysable nucleotide and the full C-terminal region of the L protein, including the putative cap-binding domain, is well-ordered. These data advance our mechanistic understanding of how this flexible and multifunctional molecular machine is activated.
Assessing costs of Indonesian fires and the benefits of restoring peatland
Authors: Kiely L. , Spracklen D. V. , Arnold S. R. , Papargyropoulou E. , Conibear L. , Wiedinmyer C. , Knote C. , Adrianto H. A.
Published: December 2021

Deforestation and drainage has made Indonesian peatlands susceptible to burning. Large fires occur regularly, destroying agricultural crops and forest, emitting large amounts of CO2and air pollutants, resulting in adverse health effects. In order to reduce fire, the Indonesian government has committed to restore 2.49 Mha of degraded peatland, with an estimated cost of US$3.2-7 billion. Here we combine fire emissions and land cover data to estimate the 2015 fires, the largest in recent years, resulted in economic losses totalling US$28 billion, whilst the six largest fire events between 2004 and 2015 caused a total of US$93.9 billion in economic losses. We estimate that if restoration had already been completed, the area burned in 2015 would have been reduced by 6%, reducing CO2emissions by 18%, and PM2.5emissions by 24%, preventing 12,000 premature mortalities. Peatland restoration could have resulted in economic savings of US$8.4 billion for 2004–2015, making it a cost-effective strategy for reducing the impacts of peatland fires to the environment, climate and human health.
Fluorinated rhamnosides inhibit cellular fucosylation
Authors: Pijnenborg Johan F. A. , Rossing Emiel , Merx Jona , Noga Marek J. , Titulaer Willem H. C. , Eerden Nienke , Veizaj Raisa , White Paul B. , Lefeber Dirk J. , Boltje Thomas J.
Published: December 2021

The sugar fucose is expressed on mammalian cell membranes as part of glycoconjugates and mediates essential physiological processes. The aberrant expression of fucosylated glycans has been linked to pathologies such as cancer, inflammation, infection, and genetic disorders. Tools to modulate fucose expression on living cells are needed to elucidate the biological role of fucose sugars and the development of potential therapeutics. Herein, we report a class of fucosylation inhibitors directly targeting de novo GDP-fucose biosynthesis via competitive GMDS inhibition. We demonstrate that cell permeable fluorinated rhamnose 1-phosphate derivatives (Fucotrim I & II) are metabolic prodrugs that are metabolized to their respective GDP-mannose derivatives and efficiently inhibit cellular fucosylation.
Wafer-scale integration of stretchable semiconducting polymer microstructures via capillary gradient
Authors: Qiu Yuchen , Zhang Bo , Yang Junchuan , Gao Hanfei , Li Shuang , Wang Le , Wu Penghua , Su Yewang , Zhao Yan , Feng Jiangang , Jiang Lei , Wu Yuchen
Published: December 2021

Organic semiconducting polymers have opened a new paradigm for soft electronics due to their intrinsic flexibility and solution processibility. However, the contradiction between the mechanical stretchability and electronic performances restricts the implementation of high-mobility polymers with rigid molecular backbone in deformable devices. Here, we report the realization of high mobility and stretchability on curvilinear polymer microstructures fabricated by capillary-gradient assembly method. Curvilinear polymer microstructure arrays are fabricated with highly ordered molecular packing, controllable pattern, and wafer-scale homogeneity, leading to hole mobilities of 4.3 and 2.6 cm2 V−1 s−1 under zero and 100% strain, respectively. Fully stretchable field-effect transistors and logic circuits can be integrated in solution process. Long-range homogeneity is demonstrated with the narrow distribution of height, width, mobility, on-off ratio and threshold voltage across a four-inch wafer. This solution-assembly method provides a platform for wafer-scale and reproducible integration of high-performance soft electronic devices and circuits based on organic semiconductors.
Temporal and spatial earthquake clustering revealed through comparison of millennial strain-rates from 36Cl cosmogenic exposure dating and decadal GPS strain-rate
Authors: Iezzi Francesco , Roberts Gerald , Faure Walker Joanna , Papanikolaou Ioannis , Ganas Athanassios , Deligiannakis Georgios , Beck Joakim , Wolfers Soeren , Gheorghiu Delia
Published: December 2021

To assess whether continental extension and seismic hazard are spatially-localized on single faults or spread over wide regions containing multiple active faults, we investigated temporal and spatial slip-rate variability over many millennia using in-situ 36Cl cosmogenic exposure dating for active normal faults near Athens, Greece. We study a ~ NNE-SSW transect, sub-parallel to the extensional strain direction, constrained by two permanent GPS stations located at each end of the transect and arranged normal to the fault strikes. We sampled 3 of the 7 seven normal faults that exist between the GPS sites for 36Cl analyses. Results from Bayesian inference of the measured 36Cl data implies that some faults slip relatively-rapidly for a few millennia accompanied by relative quiescence on faults across strike, defining out-of-phase fault activity. Assuming that the decadal strain-rate derived from GPS applies over many millennia, slip on a single fault can accommodate ~ 30–75% of the regional strain-rate for a few millennia. Our results imply that only a fraction of the total number of Holocene active faults slip over timescales of a few millennia, so continental deformation and seismic hazard are localized on specific faults and over a length-scale shorter than the spacing of the present GPS network over this time-scale. Thus, (1) the identification of clustered fault activity is vital for probabilistic seismic hazard assessments, and (2) a combination of dense geodetic observations and palaeoseismology is needed to identify the precise location and width of actively deforming zones over specific time periods.
A large-scale population-based epidemiological study on the prevalence of central sensitization syndromes in Japan
Authors: Haruyama Yasuo , Sairenchi Toshimi , Uchiyama Koji , Suzuki Keisuke , Hirata Koichi , Kobashi Gen
Published: December 2021

A cross-sectional study of 21,665 Japanese residents was performed to investigate the prevalence of central sensitization syndromes (CSS). CSS were assessed using the Central Sensitization Inventory (CSI-A). CSS were defined as a CSI-A score of 40 or higher. Age, sex, district, 10 CSS-related diseases (CSI-B), lifestyle, and mental factors were rated in a self-reported survey. The prevalence of CSS and its relationship with potential factors were examined by sex using descriptive and logistic regression models. The prevalence of CSS was 4.2% in all participants and was significantly higher in women (4.9%) than in men (2.7%). Adjusted odds ratios correlated with CSS for an age of 80–97 years versus 60–79 years (2.07 and 2.89), one or more CSI-B diseases (3.58 and 3.51), few sleeping hours (2.18 and 1.98), high perceived stress (5.00 and 4.91), low (2.94 and 2.71) and high (0.45 and 0.66) resilience versus moderate resilience, and exercise habits (0.68 and 0.55) in men and women (all P < 0.05). The relationship between CSS and age 20 and 59 years, ex-smokers, coffee intake, and alcohol intake differed by sex. The prevalence of CSS was estimated to be low in the healthy population. CSS correlated with CSS-related diseases and some positive and negative factors.
Efficacy of AAV serotypes to target Schwann cells after intrathecal and intravenous delivery
Authors: Kagiava A. , Richter J. , Tryfonos C. , Leal-Julià M. , Sargiannidou I. , Christodoulou C. , Bosch A. , Kleopa K. A.
Published: December 2021

To optimize gene delivery to myelinating Schwann cells we compared clinically relevant AAV serotypes and injection routes. AAV9 and AAVrh10 vectors expressing either EGFP or the neuropathy-associated gene GJB1/Connexin32 (Cx32) under a myelin specific promoter were injected intrathecally or intravenously in wild type and Gjb1-null mice, respectively. Vector biodistribution in lumbar roots and sciatic nerves was higher in AAVrh10 injected mice while EGFP and Cx32 expression rates and levels were similar between the two serotypes. A gradient of biodistribution away from the injection site was seen with both intrathecal and intravenous delivery, while similar expression rates were achieved despite higher vector amounts injected intravenously. Quantified immune cells in relevant tissues were similar to non-injected littermates. Overall, AAV9 and AAVrh10 efficiently transduce Schwann cells throughout the peripheral nervous system with both clinically relevant routes of administration, although AAV9 and intrathecal injection may offer a more efficient approach for treating demyelinating neuropathies.
Lifestyle and mental health 1 year into COVID-19
Authors: Barbieri Paolo Nicola , Giuntella Osea , Saccardo Silvia , Sadoff Sally
Published: December 2021

In previous work, Giuntella et al. (Proc Natl Acad Sci 118:e2016632118, 2021), we documented large disruptions to physical activity, sleep, time use and mental health among young adults at the onset of the COVID-19 pandemic in Spring 2020. This study explores the trends 1 year into COVID-19, as vaccines began to roll out, COVID-19 deaths declined, and social distancing measures eased in the United States. We combine biometric and survey data from multiple cohorts of college students spanning Spring 2019 through Spring 2021 (N = 1179). Our results show persistent impacts of the pandemic on physical activity and mental health. One year into the pandemic, daily steps averaged about 6300 per day compared to about 9800 per day prior to the pandemic, a 35% decline. Almost half of participants were at risk of clinical depression compared to a little over one-third prior to the pandemic, a 36% increase. The impacts on screen time, social interactions and sleep duration at the onset of COVID-19 largely dissipated over the course of the pandemic, though screen time remained significantly higher than pre-pandemic levels. In contrast to the sharp changes in lifestyle and mental health documented as the pandemic emerged in March 2020, we do not find evidence of behavioral changes or improvements in mental well-being over the course of Spring 2021 as the pandemic eased.
Elastic Correlation Adjusted Regression (ECAR) scores for high dimensional variable importance measuring
Authors: Zhou Yuan , Fa Botao , Wei Ting , Sun Jianle , Yu Zhangsheng , Zhang Yue
Published: December 2021

Investigation of the genetic basis of traits or clinical outcomes heavily relies on identifying relevant variables in molecular data. However, characteristics such as high dimensionality and complex correlation structures of these data hinder the development of related methods, resulting in the inclusion of false positives and negatives. We developed a variable importance measure method, termed the ECAR scores, that evaluates the importance of variables in the dataset. Based on this score, ranking and selection of variables can be achieved simultaneously. Unlike most current approaches, the ECAR scores aim to rank the influential variables as high as possible while maintaining the grouping property, instead of selecting the ones that are merely predictive. The ECAR scores’ performance is tested and compared to other methods on simulated, semi-synthetic, and real datasets. Results showed that the ECAR scores improve the CAR scores in terms of accuracy of variable selection and high-rank variables’ predictive power. It also outperforms other classic methods such as lasso and stability selection when there is a high degree of correlation among influential variables. As an application, we used the ECAR scores to analyze genes associated with forced expiratory volume in the first second in patients with lung cancer and reported six associated genes.
Tracking deep-sea internal wave propagation with a differential pressure gauge array
Authors: Yang Chu-Fang , Chi Wu-Cheng , van Haren Hans , Lin Ching-Ren , Kuo Ban-Yuan
Published: December 2021

Temperature is used to trace ocean density variations, and reveals internal waves and turbulent motions in the deep ocean, called ‘internal motions.’ Ambient temperature detected by geophysical differential pressure gauges (DPGs) may provide year-long, complementary observations. Here, we use data from four DPGs fixed on the ocean bottom and a high-resolution temperature sensor (T-sensor) 13 m above the seafloor as a square-kilometer array deployed offshore ~ 50 km east of Taiwan facing the open Pacific Ocean to examine the impact of temperature on DPG signals related to internal motions. The DPG signals correlate with T-sensor temperature variations between 0.002 and 0.1 mHz, but have time shifts partially caused by slow thermal conduction from the ambient seafloor to the DPG chamber and partially by internal motion propagation time across the array. Applying beamforming-frequency-wavenumber analysis and linear regression to the arrayed T-sensor and DPG data, we estimate the propagating slowness of the internal motions to be between 0.5 and 7.4 s m−1 from the northwest and northeast quadrants of the array. The thermal relaxation time of the DPGs is within 103–104 s. This work shows that a systematic scan of DPG data at frequencies < 0.1 mHz may help shed light on patterns of internal wave propagation in the deep ocean, especially in multi-scale arrays.
A brain extraction algorithm for infant T2 weighted magnetic resonance images based on fuzzy c-means thresholding
Authors: Bae Inyoung , Chae Jong-Hee , Han Yeji
Published: December 2021

It is challenging to extract the brain region from T2-weighted magnetic resonance infant brain images because conventional brain segmentation algorithms are generally optimized for adult brain images, which have different spatial resolution, dynamic changes of imaging intensity, brain size and shape from infant brain images. In this study, we propose a brain extraction algorithm for infant T2-weighted images. The proposed method utilizes histogram partitioning to separate brain regions from the background image. Then, fuzzy c-means thresholding is performed to obtain a rough brain mask for each image slice, followed by refinement steps. For slices that contain eye regions, an additional eye removal algorithm is proposed to eliminate eyes from the brain mask. By using the proposed method, accurate masks for infant T2-weighted brain images can be generated. For validation, we applied the proposed algorithm and conventional methods to T2 infant images (0–24 months of age) acquired with 2D and 3D sequences at 3T MRI. The Dice coefficients and Precision scores, which were calculated as quantitative measures, showed the highest values for the proposed method as follows: For images acquired with a 2D imaging sequence, the average Dice coefficients were 0.9650 ± 0.006 for the proposed method, 0.9262 ± 0.006 for iBEAT, and 0.9490 ± 0.006 for BET. For the data acquired with a 3D imaging sequence, the average Dice coefficient was 0.9746 ± 0.008 for the proposed method, 0.9448 ± 0.004 for iBEAT, and 0.9622 ± 0.01 for BET. The average Precision was 0.9638 ± 0.009 and 0.9565 ± 0.016 for the proposed method, 0.8981 ± 0.01 and 0.8968 ± 0.008 for iBEAT, and 0.9346 ± 0.014 and 0.9282 ± 0.019 for BET for images acquired with 2D and 3D imaging sequences, respectively, demonstrating that the proposed method could be efficiently used for brain extraction in T2-weighted infant images.
Placozoan fiber cells: mediators of innate immunity and participants in wound healing
Authors: Mayorova Tatiana D. , Hammar Katherine , Jung Jae H. , Aronova Maria A. , Zhang Guofeng , Winters Christine A. , Reese Thomas S. , Smith Carolyn L.
Published: December 2021

Placozoa is a phylum of non-bilaterian marine animals. These small, flat organisms adhere to the substrate via their densely ciliated ventral epithelium, which mediates mucociliary locomotion and nutrient uptake. They have only six morphological cell types, including one, fiber cells, for which functional data is lacking. Fiber cells are non-epithelial cells with multiple processes. We used electron and light microscopic approaches to unravel the roles of fiber cells in Trichoplax adhaerens, a representative member of the phylum. Three-dimensional reconstructions of serial sections of Trichoplax showed that each fiber cell is in contact with several other cells. Examination of fiber cells in thin sections and observations of live dissociated fiber cells demonstrated that they phagocytose cell debris and bacteria. In situ hybridization confirmed that fiber cells express genes involved in phagocytic activity. Fiber cells also are involved in wound healing as evidenced from microsurgery experiments. Based on these observations we conclude that fiber cells are multi-purpose macrophage-like cells. Macrophage-like cells have been described in Porifera, Ctenophora, and Cnidaria and are widespread among Bilateria, but our study is the first to show that Placozoa possesses this cell type. The phylogenetic distribution of macrophage-like cells suggests that they appeared early in metazoan evolution.