bluuebunny/crossref_metadata_2025 huggingface dataset:
Glioblastoma myeloid-derived suppressor cell subsets express differential macrophage migration inhibitory factor receptor profiles that can be targeted to reduce immune suppression
Authors: Alban Tyler J. , Bayik Defne , Otvos Balint , Rabljenovic Anja , Leng Lin , Jia-shiun Leu , Roversi Gustavo , Lauko Adam , Momin Arbaz , Mohammadi Alireza M. , Peereboom David M. , Ahluwalia Manmeet S. , Matsuda Kazuko , Yun Kyuson , Bucala Richard , Vogelbaum Michael A. , Lathia Justin D.
Published: December 2019

The application of tumor immunotherapy to glioblastoma (GBM) is limited by an unprecedented degree of immune suppression due to factors that include high numbers of immune suppressive myeloid cells, the blood brain barrier, and T cell sequestration to the bone marrow. We previously identified an increase in immune suppressive myeloid-derived suppressor cells (MDSCs) in GBM patients, which correlated with poor prognosis and was dependent on macrophage migration inhibitory factor (MIF). Here we examine the MIF signaling axis in detail in murine MDSC models, GBM-educated MDSCs and human GBM. We found that the monocytic subset of MDSCs (M-MDSCs), expressed high levels of the MIF cognate receptor CD74 and was localized in the tumor microenvironment. In contrast, granulocytic MDSCs (G-MDSCs) expressed high levels of the MIF non-cognate receptor CXCR2 and showed minimal accumulation in the tumor microenvironment. Furthermore, targeting M-MDSCs with ibudilast, a brain penetrant MIF-CD74 interaction inhibitor, reduced MDSC function and enhanced CD8 T cell activity in the tumor microenvironment. These findings demonstrate the MDSC subsets differentially express MIF receptors and may be leveraged for specific MDSC targeting.
Theta activity paradoxically boosts gamma and ripple frequency sensitivity in prefrontal interneurons
Authors: Merino Ricardo Martins , Leon-Pinzon Carolina , Stühmer Walter , Möck Martin , Staiger Jochen F. , Wolf Fred , Neef Andreas
Published: December 2019

Fast oscillations in cortical circuits critically depend on GABAergic interneurons. Which interneuron types and populations can drive different cortical rhythms, however, remains unresolved and may depend on brain state. Here, we measured the sensitivity of different GABAergic interneurons in prefrontal cortex under conditions mimicking distinct brain states. While fast-spiking neurons always exhibited a wide bandwidth of around 400 Hz, the response properties of spike-frequency adapting interneurons switched with the background input’s statistics. Slowly fluctuating background activity, as typical for sleep or quiet wakefulness, dramatically boosted the neurons’ sensitivity to gamma- and ripple-frequencies. A novel time-resolved dynamic gain analysis revealed rapid sensitivity modulations that enable neurons to periodically boost gamma oscillations and ripples during specific phases of ongoing low-frequency oscillations. This mechanism presumably contributes substantially to cross-frequency coupling and predicts these prefrontal interneurons to be exquisitely sensitive to high-frequency ripples, especially during brain states characterized by slow rhythms.
Inter-domain dynamics in the chaperone SurA and multi-site binding to its unfolded outer membrane protein clients
Authors: Calabrese Antonio N. , Schiffrin Bob , Watson Matthew , Karamanos Theodoros K. , Walko Martin , Humes Julia R. , Horne Jim E. , White Paul , Wilson Andrew J. , Kalli Antreas C. , Tuma Roman , Ashcroft Alison E. , Brockwell David J. , Radford Sheena E.
Published: December 2019

The periplasmic chaperone SurA plays a key role in outer membrane protein (OMP) biogenesis.E. coliSurA comprises a core domain and two peptidylprolyl isomerase domains (P1 and P2), but how it binds its OMP clients and the mechanism(s) of its chaperone action remain unclear. Here, we have used chemical cross-linking, hydrogen-deuterium exchange, single-molecule FRET and molecular dynamics simulations to map the client binding site(s) on SurA and to interrogate the role of conformational dynamics of the chaperone’s domains in OMP recognition. We demonstrate that SurA samples a broad array of conformations in solution in which P2 primarily lies closer to the core/P1 domains than suggested by its crystal structure. Multiple binding sites for OMPs are located primarily in the core domain, with binding of the unfolded OMP resulting in conformational changes between the core/P1 domains. Together, the results portray a model in which unfolded OMP substrates bind in a cradle formed between the SurA domains, with structural flexibility between its domains assisting OMP recognition, binding and release.
The R2TP chaperone assembles cellular machineries in intestinal CBC stem cells and progenitors
Authors: Maurizy Chloé , Abeza Claire , Pinet Valérie , Ferrand Marina , Paul Conception , Bremond Julie , Langa Francina , Gerbe François , Jay Philippe , Verheggen Céline , Tinari Nicola , Helmlinger Dominique , Lattanzio Rossano , Bertrand Edouard , Hahne Michael , Pradet-Balade Bérengère
Published: December 2019

The R2TP chaperone cooperates with HSP90 to integrate newly synthesized proteins into multi-subunit complexes, yet its role in tissue homeostasis is unknown. Here, we generated conditional, inducible knock-out mice forRpap3to inactivate this core component of R2TP in the intestinal epithelium. In adult mice,Rpap3invalidation caused destruction of the small intestinal epithelium, and death within 10 days. Levels of R2TP substrates were decreased, with strong effects on mTOR, ATM and ATR.Rpap3-deficient CBC stem cells and progenitors also failed to import RNA polymerase II in the nucleus. This correlated with p53 activation, cell cycle arrest and apoptosis. Interestingly, post-mitotic, differentiated cells did not display any of those alterations, indicating that R2TP clients are built in actively proliferating cells. Analyses of tissues from colorectal cancer patients revealed that high RPAP3 levels correlate with bad cancer prognosis. Thus, in the intestine, the R2TP chaperone functions in physiologic and pathologic proliferation.
Estimating the quality of eukaryotic genomes recovered from metagenomic analysis
Authors: Saary Paul , Mitchell Alex L. , Finn Robert D.
Published: December 2019

Eukaryotes make up a large fraction of microbial biodiversity. However, the field of metagenomics has been heavily biased towards the study of just the prokaryotic fraction. This focus has driven the necessary methodological developments to enable the recovery of prokaryotic genomes from metagenomes, which has reliably yielded genomes from thousands of novel species. More recently, microbial eukaryotes have gained more attention, but there is yet to be a parallel explosion in the number of eukaryotic genomes recovered from metagenomic samples. One of the current deficiencies is the lack of a universally applicable and reliable tool for the estimation of eukaryote genome quality. To address this need, we have developed EukCC, a tool for estimating the quality of eukaryotic genomes based on the dynamic selection of single copy marker gene sets, with the aim of applying it to metagenomics datasets. We demonstrate that our method outperforms current genome quality estimators and have applied EukCC to datasets from two different biomes to enable the identification of novel genomes, including a eukaryote found on the human skin and aBathycoccusspecies obtained from a marine sample.
Social reprogramming in ants induces longevity-associated glia remodeling
Authors: Sheng Lihong , Shields Emily J. , Gospocic Janko , Glastad Karl M. , Ratchasanmuang Puttachai , Raj Arjun , Little Shawn , Bonasio Roberto
Published: December 2019

Healthy brain aging is of crucial societal importance; however, the mechanisms that regulate it are largely unknown. Social insects are an outstanding model to study the impact of environment and epigenetics on brain function and aging because workers and queens arise from the same genome but display profound differences in behavior and longevity. InHarpegnathos saltatorants, adult workers can transition to a queen-like phenotypic state called gamergate. This caste transition results in reprogramming of social behavior and lifespan extension. Whether these changes in brain function and physiology cause brain remodeling at the cellular level is not known. Using single-cell RNA-sequencing ofHarpegnathosbrains undergoing caste transition, we uncovered shifts in neuronal and glial populations. In particular, the conversion of workers into long-lived gamergates caused the expansion of ensheathing glia, which maintain brain health by phagocytosing damaged neuronal structures. These glia cells were lost during aging in normal workers but not in longer-lived gamergates. We observed similar caste- and age-associated differences in ensheathing glia in other Hymenoptera as well asDrosophila melanogaster. We propose that enhanced glia-based neuroprotection promotes healthy brain aging and contributes to the extended lifespan of the reproductive caste in social insects.
Coverage-dependent bias creates the appearance of binary splicing in single cells
Authors: Buen Abad Najar Carlos F. , Yosef Nir , Lareau Liana F.
Published: December 2019

Single cell RNA sequencing provides powerful insight into the factors that determine each cell’s unique identity, including variation in transcription and RNA splicing among diverse cell types. Previous studies led to the surprising observation that alternative splicing outcomes among single cells are highly variable and follow a bimodal pattern: a given cell consistently produces either one or the other isoform for a particular splicing choice, with few cells producing both isoforms. Here we show that this pattern arises almost entirely from technical limitations. We analyzed single cell alternative splicing in human and mouse single cell RNA-seq datasets, and modeled them with a probablistic simulator. Our simulations show that low gene expression and low capture efficiency distort the observed distribution of isoforms in single cells. This gives the appearance of a binary isoform distribution, even when the underlying reality is consistent with more than one isoform per cell. We show that accounting for the true amount of information recovered can produce biologically meaningful measurements of splicing in single cells.
High Gamma Cortical Processing of Continuous Speech in Younger and Older Listeners
Authors: Kulasingham Joshua P. , Brodbeck Christian , Presacco Alessandro , Kuchinsky Stefanie E. , Anderson Samira , Simon Jonathan Z.
Published: December 2019

Neural processing along the ascending auditory pathway is often associated with a progressive reduction in characteristic processing rates. For instance, the well-known frequency-following response (FFR) of the auditory midbrain, as measured with electroencephalography (EEG), is dominated by frequencies from ∼100 Hz to several hundred Hz, phase-locking to the acoustic stimulus at those frequencies. In contrast, cortical responses, whether measured by EEG or magnetoencephalography (MEG), are typically characterized by frequencies of a few Hz to a few tens of Hz, time-locking to acoustic envelope features. In this study we investigated a crossover case, cortically generated responses time-locked to continuous speech features at FFR-like rates. Using MEG, we analyzed responses in the high gamma range of 70–200 Hz to continuous speech using neural source-localized reverse correlation and the corresponding temporal response functions (TRFs). Continuous speech stimuli were presented to 40 subjects (17 younger, 23 older adults) with clinically normal hearing and their MEG responses were analyzed in the 70–200 Hz band. Consistent with the relative insensitivity of MEG to many subcortical structures, the spatiotemporal profile of these response components indicated a cortical origin with ∼40 ms peak latency and a right hemisphere bias. TRF analysis was performed using two separate aspects of the speech stimuli: a) the 70–200 Hz carrier of the speech, and b) the 70–200 Hz temporal modulations in the spectral envelope of the speech stimulus. The response was dominantly driven by the envelope modulation, with a much weaker contribution from the carrier. Age-related differences were also analyzed to investigate a reversal previously seen along the ascending auditory pathway, whereby older listeners show weaker midbrain FFR responses than younger listeners, but, paradoxically, have stronger cortical low frequency responses. In contrast to both these earlier results, this study did not find clear age-related differences in high gamma cortical responses to continuous speech. Cortical responses at FFR-like frequencies shared some properties with midbrain responses at the same frequencies and with cortical responses at much lower frequencies.

Highlights

Cortical MEG responses time-lock at 80–90 Hz to continuous speech

Responses primarily driven by high gamma rate fluctuations of the speech envelope

Response strength and latency are similar for younger and older adults
Tracking dynamic adjustments to decision making and performance monitoring processes in conflict tasks
Authors: Feuerriegel Daniel , Jiwa Matthew , Turner William F , Andrejević Milan , Hester Robert , Bode Stefan
Published: December 2019

How we exert control over our decision-making has been investigated using conflict tasks, which involve stimuli containing elements that are either congruent or incongruent. In these tasks, participants adapt their decision-making strategies following exposure to incongruent stimuli. According to conflict monitoring accounts, conflicting stimulus features are detected in medial frontal cortex, and the extent of experienced conflict scales with response time (RT) and frontal theta-band activity in the electroencephalogram (EEG). However, the consequent adjustments to decision processes following response conflict are not well-specified. To characterise these adjustments and their neural implementation we recorded EEG during a modified Flanker task. We traced the time-courses of performance monitoring processes (frontal theta) and multiple processes related to perceptual decision-making. In each trial participants judged which of two overlaid gratings forming a plaid stimulus (termed the S1 target) was of higher contrast. The stimulus was divided into two sections, which each contained higher contrast gratings in either congruent or incongruent directions. Shortly after responding to the S1 target, an additional S2 target was presented, which was always congruent. Our EEG results suggest enhanced sensory evidence representations in visual cortex and reduced evidence accumulation rates for S2 targets following incongruent S1 stimuli. Results of a follow-up behavioural experiment indicated that the accumulation of sensory evidence from the incongruent (i.e. distracting) stimulus element was adjusted following response conflict. Frontal theta amplitudes positively correlated with RT following S1 targets (in line with conflict monitoring accounts). Following S2 targets there was no such correlation, and theta amplitude profiles instead resembled decision evidence accumulation trajectories. Our findings provide novel insights into how cognitive control is implemented following exposure to conflicting information, which is critical for extending conflict monitoring accounts.
An unusually short intermolecular N—H...N hydrogen bond in crystals of the hemi-hydrochloride salt of 1-exo-acetamidopyrrolizidine
Authors: Bhardwaj Minakshi , Ai Qianxiang , Parkin Sean R. , Grossman Robert B.
Published: December 2019

The title compound [systematic name: (1R*, 8S)-2-acetamidooctahydropyrrolizin-4-ium chloride–N-[(1R, 8S)-hexahydro-1H-pyrrolizin-2-yl)acetamide (1/1)], 2(C9H16N2O)·HCl or C9H17N2O+·Cl−·C9H16N2O, arose as an unexpected product when 1-exo-acetamidopyrrolizidine (AcAP; C9H16N2O) was dissolved in CHCl3. Within the AcAP pyrrolizidine group, the unsubstituted five-membered ring is disordered over two orientations in a 0.897 (5):0.103 (5) ratio. Two AcAP molecules related by a crystallographic twofold axis link to H+ and Cl− ions lying on the rotation axis, thereby forming N—H...N and N—H...Cl...H—N hydrogen bonds. The first of these has an unusually short N...N separation of 2.616 (2) Å: refinement of different models against the present data set could not distinguish between a symmetrical hydrogen bond (H atom lying on the twofold axis and equidistant from the N atoms) or static or dynamic disorder models (i.e. N—H...N + N...H—N). Computational studies suggest that the disorder model is slightly more stable, but the energy difference is very small.
Syntheses and crystal structures of 2,2,5-trimethyl-1,3-dioxane-5-carboxylic acid and 2,2,5-trimethyl-1,3-dioxane-5-carboxylic anhydride
Authors: Giesen Joseph A. , Grayson Scott M. , Mague Joel T.
Published: December 2019

In 2,2,5-trimethyl-1,3-dioxane-5-carboxylic acid, C8H14O4, the carboxyl group occupies an equatorial position on the 1,3-dioxane ring. In the crystal, O—H...O hydrogen bonds form chains of molecules, which are linked into a three-dimensional network by C—H...O hydrogen bonds. The asymmetric unit of 2,2,5-trimethyl-1,3-dioxane-5-carboxylic anhydride, C16H26O7, consists of two independent molecules, which are linked by C—H...O hydrogen bonds. In the crystal, these units are connected into corrugated layers two molecules thick and parallel to the ab plane by additional C—H...O hydrogen bonds.
Bis{4-[(2-hydroxy-5-methoxy-3-nitrobenzylidene)amino]phenyl} ether
Authors: Arafath Md. Azharul , Kwong Huey Chong , Adam Farook , Mohiuddin Md. , Sarker Md. Sohug , Salim Mohammad , Alam Md. Mahbubul
Published: December 2019

The molecule of the title compound, C28H22N4O9, exhibits crystallographically imposed twofold rotational symmetry, with a dihedral angle of 66.0 (2)° between the planes of the two central benzene rings bounded to the central oxygen atom. The dihedral angle between the planes of the central benzene ring and the terminal phenol ring is 4.9 (2)°. Each half of the molecule exhibits an imine E configuration. An intramolecular O—H...N hydrogen bond is present. In the crystal, the molecules are linked into layers parallel to the ab plane via C—H...O hydrogen bonds. The crystal studied was refined as a two-component pseudomerohedral twin.
Structural insights into the role of the N-terminus in the activation and function of extracellular serine protease fromStaphylococcus epidermidis
Authors: Manne Kartik , Narayana Sthanam V. L.
Published: December 2019

Extracellular serine protease (Esp) fromStaphylococcus epidermidisis a glutamyl endopeptidase that inhibits the growth and formation ofS. aureusbiofilms. Previously, crystal structures of the matured and active Esp have been determined. Interestingly, many of the staphylococcal glutamyl endopeptidase zymogens, including V8 fromStaphylococcus aureusand Esp fromS. epidermidis, contain unusually long pro-peptide segments; however, their function is not known. With the aim of elucidating the function of these pro-peptide segments, crystal structures of the Esp zymogen (Pro-Esp) and its variants were determined. It was observed that the N-terminus of the Pro-Esp crystal structure is flexible and is not associated with the main body of the enzyme, unlike in the known active Esp structure. In addition, the loops that border the putative substrate-binding pocket of Pro-Esp are flexible and disordered; the structural components that are responsible for enzyme specificity and efficiency in serine proteases are disordered in Pro-Esp. However, the N-terminal locked Pro-Esp variants exhibit a rigid substrate-binding pocket similar to the active Esp structure and regain activity. These structural studies highlight the role of the N-terminus in stabilizing the structural components responsible for the activity and specificity of staphylococcal glutamyl endopeptidases.
Parallel two-sided assembly line balancing with tools and tasks sharing
Authors: Yadav Ashish , Kulhary Ramawatar , Nishad Rupesh , Agrawal Sunil
Published: December 2019

Purpose

Parallel two-sided assembly lines are usually designed to produce large-sized products such as trucks and buses. In parallel two-sided assembly lines, both left and right sides of the line are used for manufacturing one or more products on two or more assembly lines located parallel to each other. The purpose of this paper is to develop a new mathematical model for the parallel two-sided assembly line balancing problem that helps to evaluate and validate the balancing operations of the machines such as removal of tools and fixtures and reallocating the operators.

Design/methodology/approach

The proposed approach is explained with the help of an example problem. In all, 22 test problems are formed using the benchmark problems P9, P12, P16 and P24. The results obtained are compared among approaches of the task(s) shared, tool(s) shared and both tool(s) and task(s) shared for effect on efficiency as the performance measure. The solution presented here follows the exact solution procedure that is solved by Lingo 16 solver.

Findings

Based on the experiments, line efficiency decreases when only tools are shared and increases when only tasks are shared. Results indicate that by sharing tasks and tools together, better line efficiency is obtained with less cost of tools and fixtures.

Practical implications

According to the industrial aspect, the result of the study can be beneficial for assembly of the products, where tools and tasks are shared between parallel workstations of two or more parallel lines.

Originality/value

According to the author’s best knowledge, this paper is the first to address the tools and tasks sharing between any pair of parallel workstations.
The latest Millennials (1995-2000): examining within-group work ethic
Authors: Hess James P.
Published: December 2019

Purpose

The purpose of this study is to examine the latest Millennials, born between 1995 and 2000, to determine any significant impact of gender, employment status and living arrangement on Meriac et al.’s (2013) dimensions of work ethic.

Design/methodology/approach

A factorial analysis of variance (ANOVA) was used to identify the main and interaction effects between variables. A one-way ANOVA then revealed any statistical significance between factor combinations to determine the meaningfulness of the interactions.

Findings

Morality/ethics, the centrality of work and hard work were not significantly impacted by any factors, whereas interaction effects between gender and employment status with self-reliance and wasted time were not attributed to any particular factor level. Yet, meaningful interaction resulted in gender and employment status with leisure and delay of gratification. Specifically, women who work 20 h or less per week have less regard for leisure than men, regardless of men’ employment status. Men who work 20 h or less per week have a higher acceptance of delay of gratification than women with the same employment status.

Practical implications

Understanding the youngest Millennials’ unique paradigms about work ethic will benefit managers as they blend them with those of other working cohorts to enhance job-to-employee fit by building and sustaining recruitment, motivation and retention efforts among all workforce members.

Originality/value

This study expands existing literature by focussing on the youngest Millennials so that scholar-practitioners can closely align contemporary leadership and organisation with any unique attitudes towards work ethic and, perhaps, guide leadership transition as the next cohort emerges.
Open innovation in the semiconductor industry: analysis of Brazilian design houses
Authors: Oliveira Xênia L'amour Campos , Olave Maria Elena Leon , Moreno Edward David , Silva Glessia
Published: December 2019

Purpose

This study aims to understand how Brazilian design houses (DHs) use open innovation in joint development projects for integrated circuits.

Design/methodology/approach

As a research strategy, qualitative research using multiple case studies was made. As sources of evidence, semi-structured interviews were conducted with three DHs of Programa integrated circuit [circuito integrado(CI)]-Brasil and with four specialists in the field, as well as analysis of documents. The data were analyzed through content analysis.

Findings

The results showed the DHs use sources of external knowledge in their innovation process, to assist the development of new products, to access new knowledge and skills, to attract financial resources and to be competitive in the market of high technology.

Originality/value

The study has important implications on the semiconductor industry in Brazil, as the industry is considered strategic for the competitiveness of final goods sector. The importance of encouraging the development of partnerships in the sector, the possibility of using informal agreements to mediate the collaboration between DHs and external agents, and the improvement and long-term continuity of public policies to support the industry are among the implications. In addition to suggestions for new business approaches to assist the strengthening of this segment.
Improving employees’ intellectual capacity for cybersecurity through evidence-based malware training
Authors: He Wu , Ash Ivan , Anwar Mohd , Li Ling , Yuan Xiaohong , Xu Li , Tian Xin
Published: December 2019

Purpose

An organization’s ability to successfully manage intellectual capital is determined by the actions of its employees to prevent or minimize information security incidents. To prevent more data breaches to intellectual capital, organizations must provide regular cybersecurity awareness training for all personnel. The purpose of this paper is to investigate the effect of different evidence-based cybersecurity training methods on employees’ cybersecurity risk perception and self-reported behavior.

Design/methodology/approach

The study participants were randomly assigned into four groups (i.e. malware report, malware videos, both malware report and malware videos and no interventions) to assess the effects of cybersecurity training on their perceptions of vulnerability, severity, self-efficacy, security intention as well as their self-reported cybersecurity behaviors.

Findings

The results show that evidence-based malware report is a relatively better training method in affecting employees’ intentions of engaging in recommended cybersecurity behaviors comparing with the other training methods used in this study. A closer analysis suggests whether the training method contains self-relevant information could make a difference to the training effects.

Originality/value

This paper reports an in-depth investigation on how different evidence-based cybersecurity training methods impact employees’ perceptions of susceptibility, severity, self-efficacy, security intention as well as on their self-reported cybersecurity behaviors.
Ethical leaders manage conflict to develop trust
Authors: Wong Alfred , Wang Xiaohui , Wang Xinyan , Tjosvold Dean
Published: December 2019

Purpose

The purpose of this paper is to propose that effective ethical leaders develop high quality relationships with team members; in particular, they manage their conflicts with team members cooperatively.

Design/methodology/approach

The authors empirically tested this hypothesis with responses from 117 managers and 302 subordinates.

Findings

Through cooperative conflict management, leaders develop trusting, mutually committed relationships. Ethical leaders and their employees avoid competitive conflict where they try to impose their ideas and resolutions on each other.

Practical implications

The findings suggest that ethical leaders can have a significant impact by fostering cooperative conflict management and reducing competitive conflict management. Thus, organizations are encouraged to adopt training and selection procedures to develop more ethical leaders.

Originality/value

This study adds to leadership research that effective leaders develop high quality relationships that help them influence employees as well as to be open and influenced by them.
Fabrication and testing of PMOS current mirror-integrated MEMS pressure transducer
Authors: Kumar Shashi , Ropmay Gaddiella Diengdoh , Rathore Pradeep Kumar , Rangababu Peesapati , Akhtar Jamil
Published: December 2019

Purpose

This paper aims to describe the fabrication, packaging and testing of a resistive loadedp-channel metal-oxide-semiconductor field-effect transistor-based (MOSFET-based) current mirror-integrated pressure transducer.

Design/methodology/approach

Using the concept of piezoresistive effect in a MOSFET, three identicalp-channel MOSFETs connected in current mirror configuration have been designed and fabricated using the standard polysilicon gate process and microelectromechanical system (MEMS) techniques for pressure sensing application. The channel length and width of thep-channel MOSFETs are 100 µm and 500 µm, respectively. The MOSFET M1 of the current mirror is the reference transistor that acts as the constant current source. MOSFETs M2 and M3 are the pressure-sensing transistors embedded on the diaphragm near the mid of fixed edge and at the center of the square diaphragm, respectively, to experience both the tensile and compressive stress developed due to externally applied input pressure. A flexible square diaphragm having a length of approximately 1,000 µm and thickness of 50 µm has been realized using deep-reactive ion etching of silicon on the backside of the wafer. Then, the fabricated sensor chip has been diced and mounted on a TO8 header for the testing with pressure.

Findings

The experimental result of the pressure sensor chip shows a sensitivity of approximately 0.2162 mV/psi (31.35 mV/MPa) for an input pressure of 0-100 psi. The output response shows a good linearity and very low-pressure hysteresis. In addition, the pressure-sensing structure has been simulated using the parameters of the fabricated pressure sensor and from the simulation result a pressure sensitivity of approximately 0.2283 mV/psi (33.11 mV/MPa) has been observed for input pressure ranging from 0 to 100 psi with a step size of 10 psi. The simulated and experimentally tested pressure sensitivities of the pressure sensor are in close agreement with each other.

Originality/value

This current mirror readout circuit-based MEMS pressure sensor is new and fully compatible to standard CMOS processes and has a promising application in the development CMOS-MEMS-integrated smart sensors.
Intraspecific neighbourhood effect: Population‐level consequence of aggregation of highly defended plants
Authors: Tamura Momoka , Ohgushi Takayuki , Ida Takashi Y.
Published: December 2019

There is increasing evidence that herbivore–plant interactions on a focal plant species are influenced by interspecific neighbourhood effects via neighbouring plants (i.e. an associational effect). However, intraspecific neighborhood effects imposed by plant traits have been less appreciated. Specifically, the significance of intraspecific neighbourhood effects in population‐level consequences of plants has been totally overlooked.

Using two varieties of Nicotiana tabacum (high‐ and low‐nicotine), we evaluated the neighbourhood effects based on patch‐level interactions in a split‐plot 3 × 3 factorial experiment that manipulated number of plants (4, 9 and 16 plants) and culture type (monoculture plots with high‐ and low‐nicotine plants, and polyculture plot) in an experimental garden.

We found that herbivore visits on plants varied depending on the number of plants per patch and culture type. Presence of more high‐nicotine plants decreased herbivore visits in the four plant plots, and presence of high‐nicotine plants in the nine plant plots decreased herbivore visits on both high‐ and low‐nicotine plants. In contrast, in the 16 plant plots, herbivore visits on high‐nicotine plants in polyculture plots were lower than others, including those on high‐nicotine plants in monoculture plots.

Our findings clearly demonstrated that the intraspecific neighbourhood effect could occur depending on the aggregation of highly defended plants (i.e. high density and/or plant‐spacing). This study suggests that multiple mechanisms for the neighbourhood effect simultaneously worked, depending on the patch size and composition of defensive traits of individual plants, and that intraspecific neighbourhood effects may influence population‐level consequences for plant–herbivore interaction.

A free Plain Language Summary can be found within the Supporting Information of this article.
Lost opportunity: Quantifying the dynamic economic impact of time‐area fishery closures
Authors: Smith James A. , Tommasi Desiree , Sweeney Jonathan , Brodie Stephanie , Welch Heather , Hazen Elliott L. , Muhling Barbara , Stohs Steven M. , Jacox Michael G.
Published: December 2019

Time‐area closures are an important tool for reducing fisheries bycatch, but their effectiveness and economic impact can be influenced by the changes in species distributions. For fisheries targeting highly mobile species, the economic impact of a closure may by highly dynamic, depending on the current suitability of the closed area for the target species.

We present an analysis to quantify the fine‐scale economic impact of time‐area closures: the ‘lost economic opportunity’, which is the percentage of total potential profit for an entire fishing season that occurs within and during a time‐area closure. Our analysis integrates a spatially explicit and environment‐informed catch model with a utility model that quantifies fishing revenues and costs, and thus incorporates a dynamic target species distribution in the estimated economic impact of a closure. We demonstrate this approach by evaluating the economic impact of the Loggerhead Conservation Area (LCA) on California's drift gillnet swordfish Xiphias gladius fishery.

The lost economic opportunity due to the LCA time‐area closure ranged from 0% to 6% per season, with variation due to port location and trip duration, as well as inter‐annual changes in swordfish distribution. This increased by 40%–90% when a seasonally varying swordfish price was considered.

There was a clear signal in economic impact associated with a shift from warm to cool conditions in the California Current following the 1998 El Niño, with increased lost economic opportunity from 1999. This signal was due to higher swordfish catch inside the LCA during the cool phase, associated with increased water column mixing, and due to higher catches outside the LCA in the warmer phase, associated with increased sea‐surface temperature.

Synthesis and applications. We found small economic impact from a fishery closure, but with meaningful inter‐annual variation due to environmental change and the dynamic distribution of a target species. Our approach could be used to help determine the timing of closures, simulate impacts of proposed closures and, more generally, assess some economic consequences of climate‐induced shifts in species’ ranges.
A diverse uncultivated microbial community is responsible for organic matter degradation in the Black Sea sulphidic zone
Authors: Suominen Saara , Dombrowski Nina , Sinninghe Damsté Jaap S. , Villanueva Laura
Published: December 2019

Organic matter degradation in marine environments is essential for the recycling of nutrients, especially under conditions of anoxia where organic matter tends to accumulate. However, little is known about the diversity of the microbial communities responsible for the mineralization of organic matter in the absence of oxygen, as well as the factors controlling their activities. Here, we determined the active heterotrophic prokaryotic community in the sulphidic water column of the Black Sea, an ideal model system, where a tight coupling between carbon, nitrogen and sulphur cycles is expected. Active microorganisms degrading both dissolved organic matter (DOM) and protein extracts were determined using quantitative DNA stable isotope probing incubation experiments. These results were compared with the metabolic potential of metagenome‐assembled genomes obtained from the water column. Organic matter incubations showed that groups like Cloacimonetes and Marinimicrobia are generalists degrading DOM. Based on metagenomic profiles the degradation proceeds in a potential interaction with members of the Deltaproteobacteria and Chloroflexi Dehalococcoidia. On the other hand, microbes with small genomes like the bacterial phyla Parcubacteria, Omnitrophica and of the archaeal phylum Woesearchaeota, were the most active, especially in protein‐amended incubations, revealing the potential advantage of streamlined microorganisms in highly reduced conditions.
Common variable immunodeficiency presenting as sarcoidosis in a 9‐year‐old child
Authors: Maccora Ilaria , Marrani Edoardo , Ricci Silvia , Azzari Chiara , Simonini Gabriele , Cimaz Rolando , Giani Teresa
Published: December 2019

Background

Granulomatous diseases are a heterogeneous group of conditions characterized by an inflammatory infiltrate with a core of macrophages, epithelioid, giant cells and a corona of fibroblasts and lymphocytes. They are associated with a wide range of disorders such as mycobacterial and fungal infections, neoplasms, immunodeficiencies and systemic inflammatory disorders as sarcoidosis.

Case report

We report the case of a previously healthy 9‐year‐old male child who presented with persistent cough, diffuse lymphadenopathy, enlargement of liver and spleen and protracted fever. Anemia, lymphopenia and reduced platelet count was reported, with an increase of inflammatory markers. High levels of Angiotensin‐converting enzyme and chitotriosidases were noted. A PET‐CT scan showed increased uptake of 18F‐FDG glucose in multiple lymph nodes in thorax and abdomen and in the spleen. Biopsy of inguinal and bronchial nodes showed nodal granulomatous inflammation. The child was diagnosed with sarcoidosis and treated with corticosteroids with only transient efficacy. Further tests reported panhypogammaglobulinaemia and a reduced pool of B‐memory lymphocytes. Thus, the diagnosis was revised to common variable immunodeficiency (CVID).

Conclusion

Common variable immunodeficiency is a heterogeneous condition with a highly variable clinical phenotype and a strong association with autoimmune disorders. The presence of noncaseating granuloma and pulmonary lesions, along with extrapulmonary features required a step by step approach to differentiate between CVID and sarcoidosis. This enables early introduction of immunoglobulin replacement therapy and decreases the morbidity and mortality of CVID.
How City‐networks are Shaping and Failing Innovations in Urban Institutions for Sustainability and Resilience
Authors: Frantzeskaki Niki
Published: December 2019

The seminal piece of Davidson, Coenen and Gleeson gives a good overview of the role of C40 as a global intermediary for establishing networked governance and knowledge brokerage of cities. The identified benefits for cities participating and even driving city networks are well presented, however require a closer conceptual and empirical development that also considers evidence and reflection from the institutional work of other transnational networks such as ICLEI, Climate Alliance, Asian Climate Change Cities Resilience Network, 100 Resilience Cities as well as the Covenant of Mayors and UCLG. In this response article we extend the conceptualization of the benefits and risks for the roles of city‐networks as curators of institutional spaces for co‐creation and knowledge co‐production to respond to the third theme of Davidson, Coenen and Gleeson paper on the ways that city networks shape urban institutions.
Economic–Security Nexus in the AIIB: China's Quest for Security through Eurasian Connectivity
Authors: Andornino Giovanni B.
Published: December 2019

The Asian Infrastructure Investment Bank (AIIB) is mainly considered as a commercial connectivity and sustainability‐oriented infrastructure development bank, but there are also international security dimensions to the Bank. China's geostrategic and security motivations are said to be behind its spearheading of the AIIB. This essay highlights that China's national and international security calculations have evolved in the period after the Bank's opening. In the initial phase of the AIIB's formation, 2013–2017, the Bank's creation was part of Beijing's pursuit of a more outwardly ambitious and bold national/international security agenda of new institution‐building, looking to reshape the system of global governance. But since 2017, China's leadership has responded to sustained international pushback against its ambitious agenda, especially but not exclusively from the United States, and it has refocused its national security priorities onto protecting national economic growth, national sovereignty and regime preservation. Beijing has supported moves to put some distance between the AIIB and the Belt and Road Initiative (BRI), and Chinese strategists have shifted to seeing the AIIB as helpful for mitigating an economic downturn across Eurasia, and preserving China's continuing growth and regime survival in what they perceive as a period of external threat.
Constructive Engagement? The US and the AIIB
Authors: Freeman Carla P.
Published: December 2019

When the Asian Infrastructure Investment Bank (AIIB) was launched in January 2016, 57 countries signed on to its charter. The United States was not among them. It does not appear likely that the US will change its position, particularly amid deteriorating trade relations between the US and China. However, a description of the US relationship to the AIIB that is limited to opposition and non‐membership is not adequate or accurate. This analysis takes a closer look at US interactions with the AIIB, beginning with its response to the Bank when it was announced through the time of writing in 2019. The main finding of this reexamination is that relations between the United States and the AIIB have been and remain more multifaceted than the conventional narrative portrays. Since Beijing announced plans to establish the AIIB, the United States has engaged the AIIB in ways that presented opportunities for Washington to communicate its preferences with respect to the policies and operations of the Bank.
The AIIB and Sustainable Infrastructure: A Hybrid Layered Approach
Authors: Vazquez Karin Costa , Chin Gregory T.
Published: December 2019

This essay examines the AIIB’s approach to investing in sustainable infrastructure (SI). The main argument is that the AIIB is taking a hybrid layered approach to SI investment. On the one hand, the Bank is following the ‘do no harm’ pathway of the traditional MDBs, of using safeguards to avoid and compensate adverse social and environmental impacts. On the other hand, it is pursuing innovation, and a more transformative agenda, that encourages investment in SI projects that generate broader, positive developmental spillovers. In pursuing its hybrid agenda, the AIIB is developing its own multi‐layered safeguards regime to ensure smooth and strong SI investment, and alignment between the Bank’s overarching strategic policy, its ESF, sector and thematic strategies, and projects. The analysis also details three ways in which the AIIB stands out from other MDBs for how it is ‘trying new things’ with its approach to SI investment: first, is how ‘economic sustainability’ is one of the main considerations for project selection alongside environmental, social and governance sustainability; second, how the Bank has integrated social and indigenous and oversight safeguards into its ‘environmental and social framework’ (ESF); third, its creation of large‐scale public‐private Funds for green finance and climate finance.
Perceptions of extended‐release buprenorphine injections for opioid use disorder among people who regularly use opioids in Australia
Authors: Larance Briony , Degenhardt Louisa , Grebely Jason , Nielsen Suzanne , Bruno Raimondo , Dietze Paul , Lancaster Kari , Larney Sarah , Santo Thomas , Shanahan Marian , Memedovic Sonja , Ali Robert , Farrell Michael
Published: December 2019

Aims

To examine perceptions of extended‐release (XR) buprenorphine injections among people who regularly use opioids in Australia.

Design

Cross‐sectional survey prior to implementation. XR‐buprenorphine was registered in Australia in November 2018.

Setting

Sydney, Melbourne and Hobart.

Participants

A total of 402 people who regularly use opioids interviewed December 2017 to March 2018.

Measurements

Primary outcome concerned the proportion of participants who believed XR‐buprenorphine would be a good treatment option for them, preferred weekly versus monthly injections and perceived advantages/disadvantages of XR‐buprenorphine. Independent variables concerned the demographic characteristics and features of current opioid agonist treatment (OAT; medication‐type, dose, prescriber/dosing setting, unsupervised doses, out‐of‐pocket expenses and travel distance).

Findings

Sixty‐eight per cent [95% confidence interval (CI) = 63–73%] believed XR‐buprenorphine was a good treatment option for them. They were more likely to report being younger [26–35 versus > 55 years; odds ratio (OR) = 3.16, 95% CI = 1.12–8.89; P = 0.029], being female (OR = 1.67, 95% CI = 1.04–2.69; P = 0.034), < 10 years school education (OR = 1.87, 95% CI = 1.12–3.12; P = 0.016) and past‐month heroin (OR = 1.81, 95% CI = 1.15–2.85; P = 0.006) and methamphetamine use (OR = 1.90, 95% CI = 1.20–3.01; P = 0.006). Fifty‐four per cent reported no preference for weekly versus monthly injections, 7% preferred weekly and 39% preferred monthly. Among OAT recipients (n = 255), believing XR‐buprenorphine was a good treatment option was associated with shorter treatment episodes (1–2 versus ≥ 2 years; OR = 3.93, 95% CI = 1.26–12.22; P = 0.018), fewer unsupervised doses (≤ 8 doses past‐month versus no take‐aways; OR = 0.50; 95% CI = 0.27–0.93; P = 0.028) and longer travel distance (≥ 5 versus < 5 km; OR = 2.10, 95% CI = 1.20–3.65; P = 0.009). Sixty‐nine per cent reported ‘no problems or concerns’ with potential differences in availability, flexibility and location of XR‐buprenorphine.

Conclusions

Among regular opioid users in Australia, perceptions of extended‐release buprenorphine as a good treatment option are associated with being female, recent illicit drug use and factors relating to the (in)convenience of current opioid agonist treatment.
Optimal sampling design and the accuracy of occupancy models
Authors: Reich Henry T.
Published: December 2019

We present general theoretical limits on the possible accuracy (mean squared error or MSE) of occupancy estimates for a large range of occupancy study designs with imperfect detection and confirm our theoretical results via a simulation study. In particular, we show that for a given total survey effort, the best possible MSE is driven by two design‐related factors: the fraction of visits made at occupied sites (regardless of whether that occupancy status is known or not) and the number of visits made to each site with unknown occupancy status (ie, sites with no detections). The limits reveal that there is very little room for improvement over optimal implementations of the three existing occupancy design paradigms: standard design (visit S sites K times each), removal design (visit S sites up to K times each, halting visits to each site following a positive detection), and conditional design (visit S sites once, then resurvey sites with a positive detection an additional times). For the small portion of the occupancy‐detection parameter space where improvement can be achieved, we introduce a new hybrid survey design with accuracy closer to the theoretical limit, which we illustrate by reanalyzing an existing coyote (Canis latrans) camera trap dataset. Our results provide new clarity and intuition regarding key factors of occupancy study design.