bluuebunny/crossref_metadata_2025 huggingface dataset:
Counterexamples in Measure and Integration
Authors: Schilling René L. , Kühn Franziska
Published: May 2021

Often it is more instructive to know 'what can go wrong' and to understand 'why a result fails' than to plod through yet another piece of theory. In this text, the authors gather more than 300 counterexamples - some of them both surprising and amusing - showing the limitations, hidden traps and pitfalls of measure and integration. Many examples are put into context, explaining relevant parts of the theory, and pointing out further reading. The text starts with a self-contained, non-technical overview on the fundamentals of measure and integration. A companion to the successful undergraduate textbook Measures, Integrals and Martingales, it is accessible to advanced undergraduate students, requiring only modest prerequisites. More specialized concepts are summarized at the beginning of each chapter, allowing for self-study as well as supplementary reading for any course covering measures and integrals. For researchers, it provides ample examples and warnings as to the limitations of general measure theory. This book forms a sister volume to René Schilling's other book Measures, Integrals and Martingales (www.cambridge.org/9781316620243).
Guilds, Immigration, and Immigrant Economic Organization: Alien Goldsmiths in London, 1480–1540
Authors: Berry Charlotte
Published: May 2021

Immigration was essential to trades reliant on fashion and high skill in London around the turn of the sixteenth century. This article explores the patterns of migration to the city by continental goldsmiths between 1480 and 1540 and the structure of the communities they formed. It argues that attitudes to migration within the London Goldsmiths’ Company, which governed the trade, were complex and shifted in response to evolving national legislation. A social network analysis of the relationships between alien masters and servants indicates how the alien community changed and adapted. Taking a view across the traditional late medieval and early modern period boundary allows for a deeper understanding of how attitudes to migration and to migrant communities changed as London's population began to grow.
Russia’s Night Wolves, Migrating Memory and Europe’s Eastern Frontier
Authors: Molnár Virág , Koziura Karolina , König-Paratore Franziska
Published: May 2021

The article examines the controversy triggered by the “Victory Tour” of Russia’s high-profile biker organization, the Night Wolves, to mark the 70th anniversary of the Soviet Union’s defeat of Nazi Germany. The tour provoked important questions about the relationship between European borders and the politics of World War II commemoration. The article argues that the international public discourse around the Night Wolves illuminates how state borders are being transformed both as hard, territorialized borders and as “soft,” symbolic boundaries. The analysis compares how print and online media in Russia, Poland, and Germany framed the Night Wolves’ tour across Europe. It emphasizes the construction of borders as a narrative project and maps the symbolic boundary-drawing strategies mobilized by various actors. It shows how cross-border commemorative tours can serve as a tool of transnational memory politics that shapes the very meaning and salience of state borders and regional divisions.
PROPERTIES OF THE INVERSE OF A NONCENTRAL WISHART MATRIX
Authors: Hillier Grant , Kan Raymond
Published: May 2021

The inverse of a noncentral Wishart matrix occurs in a variety of contexts in multivariate statistical work, including instrumental variable (IV) regression, but there has been very little work on its properties. In this paper, we first provide an expression for the expectation of the inverse of a noncentral Wishart matrix, and then go on to do the same for a number of scalar-valued functions of the inverse. The main result is obtained by exploiting simple but powerful group-equivariance properties of the expectation map involved. Subsequent results exploit the consequences of other invariance properties.
ENDOGENEITY IN SEMIPARAMETRIC THRESHOLD REGRESSION
Authors: Kourtellos Andros , Stengos Thanasis , Sun Yiguo
Published: May 2021

This paper estimates threshold regression models with an endogenous threshold variable using a nonparametric control function approach. Assuming diminishing threshold effects, we derive the consistency and limiting distribution of our proposed estimator constructed from the series approximation method for weakly dependent data. In addition, we propose a test for the endogeneity of the threshold variable, which is valid regardless of whether the threshold effects exist. We assess the performance of our methods using Monte Carlo simulations.
The Impact of Personal Protection Equipment on Intubation Times
Authors: Doukas Donald , Arquilla Bonnie , Halpern Pinchas , Silverberg Mark , Sinert Richard
Published: May 2021

Introduction:

Hazardous material (HAZMAT) protocols require health care providers to wear personal protective equipment (PPE) when caring for contaminated patients. Multiple levels of PPE exist (level D - level A), providing progressively more protection. Emergent endotracheal intubation (ETI) of victims can become complicated by the cumbersome nature of PPE.

Study Objective:

The null hypothesis was tested that there would be no difference in time to successful ETI between providers in different types of PPE.

Methods:

This randomized controlled trial assessed time to ETI with differing levels of PPE. Participants included 18 senior US Emergency Medicine (EM) residents and attendings, and nine US senior Anesthesiology residents. Each individual performed ETI on a mannequin (Laerdal SimMan Essential; Stavanger, Sweden) wearing the following levels of PPE: universal precautions (UP) controls (nitrile gloves and facemask with shield); partial level C (PC; rubber gloves and a passive air-purifying respirator [APR]); and complete level C (CC; passive APR with an anti-chemical suit). Primary outcome measures were the time in seconds (s) to successful intubation: Time 1 (T1) = inflation of the endotracheal tube (ETT) balloon; Time 2 (T2) = first ventilation. Data were reported as medians with Interquartile Ranges (IQR, 25%-75%) or percentages with 95% Confidence Intervals (95%, CI). Group comparisons were analyzed by Fisher’s Exact Test or Kruskal-Wallis, as appropriate (alpha = 0.017 [three groups], two-tails). Sample size analysis was based upon the power of 80% to detect a difference of 10 seconds between groups at a P = .017; 27 subjects per group would be needed.

Results:

All 27 participants completed the study. At T1, there was no statistically significant difference (P = .27) among UP 18.0s (11.5s-19.0s), PC 21.0s (14.0s-23.5s), or CC 17.0s (13.5s-27.5s). For T2, there was also no significant (P = .25) differences among UP 24.0s (17.5s-27.0s), PC 26.0s (21.0s-32.0s), or CC 24.0s (19.5s-33.5s).

Conclusion:

There were no statistically significant differences in time to balloon inflation or ventilation. Higher levels of PPE do not appear to increase time to ETI.
Dos and Don'ts in Designing School-Based Awareness Programs for Suicide Prevention
Authors: Grosselli Luna , Herzog Kristina , Aseltine Robert H. , Balazs Judit , Carli Vladimir , Ciffone Jerry , De Leo Diego , van der Feltz-Cornelis Christina , Hawton Keith , Hegerl Ulrich , Kõlves Kairi , Kutcher Stan , Mehlum Lars , Niederkrotenthaler Thomas , Rezaeian Mohsen , Renaud Johanne , Schneider Barbara , Lewitzka Ute , Hoyer Jürgen , Knappe Susanne
Published: May 2021

Abstract. Background: Despite the promising evidence for the effectiveness of school-based awareness programs in decreasing the rates of suicidal thoughts and suicide attempts in young people, no guidelines on the targets and methods of safe and effective awareness programs exist. Aims: This study intends to distill recommendations for school-based suicide awareness and prevention programs from experts. Method: A three-stage Delphi survey was administered to an expert panel between November 2018 and March 2019. A total of 214 items obtained from open-ended questions and the literature were rated in two rounds. Consensus and stability were used as assessment criteria. Results: The panel consisted of 19 participants in the first and 13 in the third stage. Recommended targets included the reduction of suicide attempts, the enhancement of help-seeking and peer support, as well as the promotion of mental health literacy and life skills. Program evaluation, facilitating access to healthcare, and long-term action plans across multiple levels were among the best strategies for the prevention of adverse effects. Limitations: The study is based on opinions of a rather small number of experts. Conclusion: The promotion of help-seeking and peer support as well as facilitating access to mental health-care utilities appear pivotal for the success of school-based awareness programs.
Superspreading of airborne pathogens in a heterogeneous world
Authors: Kirkegaard Julius B. , Mathiesen Joachim , Sneppen Kim
Published: May 2021

Epidemics are regularly associated with reports of superspreading: single individuals infecting many others. How do we determine if such events are due to people inherently being biological superspreaders or simply due to random chance? We present an analytically solvable model for airborne diseases which reveal the spreading statistics of epidemics in socio-spatial heterogeneous spaces and provide a baseline to which data may be compared. In contrast to classical SIR models, we explicitly model social events where airborne pathogen transmission allows a single individual to infect many simultaneously, a key feature that generates distinctive output statistics. We find that diseases that have a short duration of high infectiousness can give extreme statistics such as 20% infecting more than 80%, depending on the socio-spatial heterogeneity. Quantifying this by a distribution over sizes of social gatherings, tracking data of social proximity for university students suggest that this can be a approximated by a power law. Finally, we study mitigation efforts applied to our model. We find that the effect of banning large gatherings works equally well for diseases with any duration of infectiousness, but depends strongly on socio-spatial heterogeneity.
Metabolomic analysis of skeletal muscle before and after strenuous exercise to fatigue
Authors: Ohmura Hajime , Mukai Kazutaka , Takahashi Yuji , Takahashi Toshiyuki
Published: May 2021

Thoroughbreds have high maximal oxygen consumption and show hypoxemia and hypercapnia during intense exercise, suggesting that the peripheral environment in skeletal muscle may be severe. Changes in metabolites following extreme alterations in the muscle environment in horses after exercise may provide useful evidence. We compared the muscle metabolites before and after supramaximal exercise to fatigue in horses. Six well-trained horses ran until exhaustion in incremental exercise tests. Biopsy samples were obtained from the gluteus medius muscle before and immediately after exercise for capillary electrophoresis–mass spectrometry analysis. In the incremental exercise test, the total running time and speed of the last step were 10.4 ± 1.3 (mean ± standard deviation) min and 12.7 ± 0.5 m/s, respectively. Of 73 metabolites, 18 and 11 were significantly increased and decreased after exercise, respectively. The heat map of the hierarchical cluster analysis of muscle metabolites showed that changes in metabolites were clearly distinguishable before and after exercise. Strenuous exercise increased many metabolites in the glycolytic pathway and the tricarboxylic acid cycle in skeletal muscle. Targeted metabolomic analysis of skeletal muscle may clarify the intramuscular environment caused by exercise and explain the response of working muscles to strenuous exercise that induces hypoxemia and hypercapnia in Thoroughbred horses.
Correlation between amide proton transfer-related signal intensity and diffusion and perfusion magnetic resonance imaging parameters in high-grade glioma
Authors: Nakajo Masanori , Bohara Manisha , Kamimura Kiyohisa , Higa Nayuta , Yoshiura Takashi
Published: May 2021

Amide proton transfer (APT) imaging is a magnetic resonance (MR) molecular imaging technique that is sensitive to mobile proteins and peptides in living tissue. Studies have shown that APT-related signal intensity (APTSI) parallels with the malignancy grade of gliomas, allowing the preoperative assessment of tumor grades. An increased APTSI in malignant gliomas has been attributed to cytosolic proteins and peptides in proliferating tumor cells; however, the exact underlying mechanism is poorly understood. To get an insight into the mechanism of high APTSI in malignant gliomas, we investigated the correlations between APTSI and several MR imaging parameters including apparent diffusion coefficient (ADC), relative cerebral blood volume and pharmacokinetic parameters obtained in the same regions-of-interest in 22 high-grade gliomas. We found a significant positive correlation between APTSI and ADC (ρ = 0.625 and 0.490 for observers 1 and 2, respectively; p < 0.001 for both), which is known to be inversely correlated with cell density. Multiple regression analysis revealed that ADC was significantly associated with APTSI (p < 0.001 for both observers). Our results suggest possible roles of extracellular proteins and peptides in high APTSI in malignant gliomas.
Determination of selenium and copper in water and food by hierarchical dendritic nano-gold modified glassy carbon electrodes
Authors: Wang Haofan , Guo Yin , Pan Hongcheng
Published: May 2021

Hierarchical dendritic gold nanostructured films were electrodeposited on a GCE at a potential of −0.6 V and used for square-wave anodic stripping voltammetry to determine nanomolar levels of Se and Cu in water and food.
Cationic strontium hydride complexes supported by an NNNN-type macrocycle
Authors: Höllerhage Thomas , Carpentier Ambre , Spaniol Thomas P. , Maron Laurent , Englert Ulli , Okuda Jun
Published: May 2021

The NNNN-type macrocycle Me4TACD stabilized a trinuclear hydride cation with a [Sr3H4]2+ core. A labile mixed dinuclear Ca–Sr hydride cation was obtained.
Hydroxyl modified hypercrosslinked polymers: targeting high efficient adsorption separation towards aniline
Authors: Wei Zishuai , Chen Qibin , Liu Honglai
Published: May 2021

The removal of aniline from aqueous solution has a major environmental impact and attracted increasing attention in last few years.
Size dependence of CdS nanoparticles on the precursor concentration and visible light driven photocatalytic degradation of methylene blue
Authors: Thakur Smriti , Kaur Rupinder , Mandal Sanjay K.
Published: May 2021

The effect of precursor concentration on the size of the nanoparticles and their visible light driven photocatalytic degradation of methylene blue are demonstrated.
A disposable electrochemical sensor based on iron molybdate for the analysis of dopamine in biological samples
Authors: Kumar Elumalai Ashok , Chen Tse-Wei , Chen Shen-Ming , Wang Tzyy-Jiann , Anthuvan Allen Joseph , AlOmar Suliman Yousef , Ahmad Naushad , Chang Yu-Hsu
Published: May 2021

Developing cost-effective approaches for the fabrication of electrochemical devices is instantly needed for transferring from basic research to point-care technology.
Spray coagulation with snare-tip versus argon plasma coagulation: An ex vivo study evaluating tissue effects
Authors: Fetz Andrew , Farnell David , Irani Shayan , Gan S. Ian
Published: May 2021

Background and study aims Argon plasma coagulation (APC) is an effective and safe modality for many gastrointestinal conditions requiring hemostasis and/or ablation. However, it can be quite costly. A potentially more cost-effective alternative is snare-tip spray coagulation (SC). This study aimed to determine whether SC would be a safe and effective alternative to APC using an ex-vivo model.

Methods Using two resected porcine stomach, 36 randomized gastric areas were ablated for 2 seconds with either APC at 1.0 L/min 20 W (APC20) and 1.4 L/min 40 W (APC40) or SC with Effect 2 60 W (SC60) and 80 W (SC80) from 3 mm. Extent of tissue injury was then analyzed histopathologically.

Results The mean coagulation depth was 790 ± 159 µm and 825 ± 467 µm for SC60 (n = 9) and SC80 (n = 8), respectively. This was compared to 539 ± 151 µm for APC20 (n = 8) and 779 ± 267 µm for APC40 (n = 9). Mean difference (MD) in coagulation depth between SC60 and APC40 was 12 µm (95 % confidence interval [CI], –191 to 214 µm; P = 0.91) and was 47 µm (95 %CI, –162 to 255 µm; P = 0.81) between SC80 and APC40. There was a greater depth of injury with APC40 (MD, 240 µm; 95 %CI, 62 to 418 µm; P = 0.04) and with SC60 (MD, 252 µm; 95 %CI, 141 to 362 µm; P = 0.004) when compared to APC20. Mean cross-sectional area of coagulation was 2.39 ± 0.852 mm² for SC60 and 2.54 ± 1.83 mm² for SC80 compared to 1.22 ± 0.569 mm² for APC20 and 1.99 ± 0.769 mm² for APC40. Seventy-eight percent reached the muscularis mucosa (MM) and 11 % the submucosa in the SC60 group compared to 50 % and 38 % in SC80 and 56 % and 11 % in APC40, respectively. Thirty-eight percent of APC20 specimens reached the MM. The muscularis propria was unaffected.

Conclusions This small ex-vivo study suggests that SC60 and SC80 may be safe alternatives to APC40 with comparable coagulation depths and area effects.
Feasibility and safety of colonoscopy performed by nonexperts for acute lower gastrointestinal bleeding: post hoc analysis
Authors: Nishida Tsutomu , Niikura Ryota , Nagata Naoyoshi , Honda Tetsuro , Sunagozaka Hajime , Shiratori Yasutoshi , Tsuji Shigetsugu , Sumiyoshi Tetsuya , Fujita Tomoki , Kiyotoki Shu , Yada Tomoyuki , Yamamoto Katsumi , Shinozaki Tomohiro , Nakamatsu Dai , Yamada Atsuo , Fujishiro Mitsuhiro
Published: May 2021

Background and study aims It remains unclear whether the experience of endoscopists affects clinical outcomes for acute lower gastrointestinal bleeding (ALGIB). We aimed to determine the feasibility and safety of colonoscopies performed by nonexperts using secondary data from a randomized controlled trial for ALGIB.

Patients and methods We analyzed clinical outcomes in 159 patients with ALGIB who underwent colonoscopies performed by two groups of endoscopists: experts and nonexperts. We compared endoscopy outcomes, including identification of stigmata of recent hemorrhage (SRH), successful endoscopic treatment, adverse events (AEs), and clinical outcomes between the two groups, including 30-day rebleeding, transfusion, length of stay, thrombotic events, and 30-day mortality.

Results Expert endoscopists alone performed colonoscopies in 96 patients, and nonexperts performed colonoscopies in 63 patients. The use of antiplatelets and warfarin was significantly higher in the expert group. The SRH identification rate (24.0 and 17.5 %), successful endoscopic treatment rate (95.0 and 100 %), rate of AEs during colonoscopy (0 and 0 %), transfusion rate (6.3 and 4.8 %), length of stay (8.0 and 6.4 days), rate of thrombotic events (0 and 1.8 %), and mortality (0 and 0 %) were not different between the expert and nonexpert groups. Rebleeding within 30 days occurred more often in the expert group than in the nonexpert group (14.3 vs. 5.4 % P = 0.0914).

Conclusions The performance of colonoscopies for ALGIB by nonexperts did not result in worse clinical outcomes, suggesting that its use could be feasible for nonexperts for diagnosis and treatment of ALGIB.
Simulating energy transfer dynamics in the Fenna–Matthews–Olson complex via the modified generalized quantum master equation
Authors: Mulvihill Ellen , Lenn Kristina M. , Gao Xing , Schubert Alexander , Dunietz Barry D. , Geva Eitan
Published: May 2021

The generalized quantum master equation (GQME) provides a general and formally exact framework for simulating the reduced dynamics of open quantum systems. The recently introduced modified approach to the GQME (M-GQME) corresponds to a specific implementation of the GQME that is geared toward simulating the dynamics of the electronic reduced density matrix in systems governed by an excitonic Hamiltonian. Such a Hamiltonian, which is often used for describing energy and charge transfer dynamics in complex molecular systems, is given in terms of diabatic electronic states that are coupled to each other and correspond to different nuclear Hamiltonians. Within the M-GQME approach, the effect of the nuclear degrees of freedom on the time evolution of the electronic density matrix is fully captured by a memory kernel superoperator, which can be obtained from short-lived (compared to the time scale of energy/charge transfer) projection-free inputs. In this paper, we test the ability of the M-GQME to predict the energy transfer dynamics within a seven-state benchmark model of the Fenna–Matthews–Olson (FMO) complex, with the short-lived projection-free inputs obtained via the Ehrenfest method. The M-GQME with Ehrenfest-based inputs is shown to yield accurate results across a wide parameter range. It is also found to dramatically outperform the direct application of the Ehrenfest method and to provide better-behaved convergence with respect to memory time in comparison to an alternative implementation of the GQME approach previously applied to the same FMO model.
Spin–orbit coupling from a two-component self-consistent approach. II. Non-collinear density functional theories
Authors: Desmarais Jacques K. , Komorovsky Stanislav , Flament Jean-Pierre , Erba Alessandro
Published: May 2021

We revise formal and numerical aspects of collinear and non-collinear density functional theories in the context of a two-component self-consistent treatment of spin–orbit coupling. Theoretical and numerical analyses of the non-collinear approaches confirm their ability to yield the proper collinear limit and provide rotational invariance of the total energy for functionals in the local-density or generalized-gradient approximations (GGAs). Calculations on simple molecules corroborate the formal considerations and highlight the importance of an effective screening algorithm to provide the sufficient level of numerical stability required for a rotationally invariant implementation of non-collinear GGA functionals. The illustrative calculations provide a first numerical comparison of both previously proposed non-collinear formulations for GGA functionals. The proposed screening procedure allows us to effectively deal with points of small magnetization, which would otherwise be problematic for the evaluation of the exchange–correlation energy and/or potential for non-collinear GGA functionals. Both previously suggested formulations for the non-collinear GGA are confirmed to be adequate for total energy calculations, provided that the screening is achieved on a sufficiently fine grid. All methods are implemented in the Crystal program.
Comparison of disease severity caused by four soil-borne pathogens in winter cereal seedlings
Authors: Saad Ahmed , Macdonald Bethany , Martin Anke , Knight Noel L. , Percy Cassandra
Published: May 2021

In Australia, crown rot of cereals is predominantly caused by Fusarium pseudograminearum and Fusarium culmorum, and common root rot by Bipolaris sorokiniana. Fusarium graminearum is an important pathogen causing Fusarium head blight worldwide and has also been reported to cause crown rot of wheat. The comparative ability of F. pseudograminearum, F. culmorum, F. graminearum and B. sorokiniana to cause crown rot and common root rot across a range of winter cereal species requires investigation. In glasshouse trials, we inoculated one cultivar each of barley, bread wheat, durum wheat, oat and triticale with two strains of each of the four pathogens. At 21 days after inoculation, the sub-crown internode and leaf sheaths of each plant were visually rated for brown discoloration. Shoot length and dry weight of inoculated plants were compared with those of non-inoculated controls. Barley and bread wheat had the highest disease severity ratings on leaf sheaths and sub-crown internode (64.7–99.6%), whereas oat had the lowest disease severity ratings across all pathogens (<5%). The shoot length of all cultivars was significantly reduced (by 12.2–55%, P < 0.05) when exposed to F. pseudograminearum. This study provides a comparison of pathogenicity of crown rot and common root rot pathogens and demonstrates significant variation in visual discoloration and host response across a range of winter cereals.
Wailagilala Atoll: coral reefs, turtle nesting beaches and seabird populations
Authors: Mangubhai Sangeeta , O’Brien Mark , Aitken Jemma
Published: May 2021

Wailagilala is one of two ‘true’ atolls in Fiji. Our findings confirm the presence of nesting green turtle (Chelonia mydas); continued occurrence of breeding seabird populations, including documenting the fifth site in Fiji of nesting white tern (Gygis alba); and provides data on coral genera and benthic cover.
Supersymmetric structures of Dirac oscillators in commutative and noncommutative spaces*
Authors: Wei Jing-Ying , Wang Qing , Jing Jian
Published: May 2021

The supersymmetric properties of a charged planar Dirac oscillator coupling to a uniform perpendicular magnetic field are studied. We find that there is an N = 2 supersymmetric structure in both commutative and noncommutative cases. We construct the generators of the supersymmetric algebras explicitly and show that the generators of the supersymmetric algebras can be mapped onto ones which only contain the left or right-handed chiral phonons by unitary transformations.
Anomalous anisotropic magnetoresistance in single-crystalline Co/SrTiO3(001) heterostructures*
Authors: Yang Shuang-Long , Yang De-Zheng , Miao Yu , Gao Cun-Xu , Xue De-Sheng
Published: May 2021

The anisotropic magnetoresistances (AMRs) in single crystalline Co(6 nm)/SrTiO3(001) heterostructures from 5 K to 300 K with the current direction setting along either Co[100] or Co[110] are investigated in this work. The anomalous (normal) AMR is observed below (above) 100 K. With the current along Co[100] direction, the AMR shows negative longitudinal and positive transverse magnetoresistances at T < 100 K, while the AMR is inverse with the current along Co[110]. Meanwhile, the amplitude ratio between Co[110] and Co[100] is observed to be as large as 29 at 100 K. A crystal symmetry-adapted model of AMR demonstrates that interplay between the non-crystalline component and crossed AMR component results in the anomalous AMR. Our results may reveal more intriguing magneto-transport behaviors of film on SrTiO3 or other perovskite oxides.
A terahertz on-chip InP-based power combiner designed using coupled-grounded coplanar waveguide lines*
Authors: Zhu Huali , Zhang Yong , Qu Kun , Wei Haomiao , Li Yukun , Xu Yuehang , Xu Ruimin
Published: May 2021

This article presents the design and performance of a terahertz on-chip coupled-grounded coplanar waveguide (GCPW) power combiner using a 50μm-thick InP process. The proposed topology uses two coupled-GCPW lines at the end of the input port to substitute two quarter-wavelength GCPW lines,which is different from the conventional Wilkinson power combiner and canavailably minimize the coverage area. According to the results obtained, forthe frequency range of 210–250z, the insertion losses for each two-waycombiner and four-way combiner were lower than 1.05 dB and 1.35 dB,respectively, and the in-band return losses were better than 11 dB. Moreover,the proposed on-chip GCPW-based combiners achieved a compromise in low-loss, broadband, and small-size, which can find wide applications in terahertz bands, such as power amplifiers and signal distribution networks.
Heterogeneous integration of InP HEMTs on quartz wafer using BCB bonding technology
Authors: Wang Yan-Fu , Wang Bo , Feng Rui-Ze , Tong Zhi-Hang , Liu Tong , Ding Peng , Su Yong-Bo , Zhou Jing-Tao , Yang Feng , Ding Wu-Chang , Jin Zhi
Published: May 2021

Heterogeneous integrated InP high electron mobility transistors (HEMTs) on quartz wafers are fabricated successfully by using a reverse-grown InP epitaxial structure and benzocyclobutene (BCB) bonding technology. The channel of the new device is In0.7Ga0.3As, and the gate length is 100 nm. A maximum extrinsic transconductance g
m,max of 855.5 mS/mm and a maximum drain current of 536.5 mA/mm are obtained. The current gain cutoff frequency is as high as 262 GHz and the maximum oscillation frequency reaches 288 GHz. In addition, a small signal equivalent circuit model of heterogeneous integration of InP HEMTs on quartz wafer is built to characterize device performance.
High adsorption and separation performance of CO2 over N2 in azo-based (N=N) pillar[6]arene supramolecular organic frameworks*
Authors: Jiang Yong-Chao , Li Gui-Xia , Yu Gui-Feng , Wang Juan , Huang Shu-Lai , Xu Guo-Liang
Published: May 2021

Azo-based pillar[6]arene supramolecular organic frameworks are reported for CO2 and N2 adsorption and separation by density functional theory and grand canonical Monte–Carlo simulation. Azo-based pillar[6]arene provides suitable environment for CO2 adsorption and selectivity. The adsorption and selectivity results show that introducing azo groups can effectively improve CO2 adsorption and selectivity over N2, and both CO2 adsorption and CO2 selectivity over N2 follow the sequence pillar[6]arene_N4 > pillar[6]arene_N2 > pillar[6]arene. Pillar[6]arene_N4 exhibits CO2 adsorption capacity of ∼ 1.36 mmol/g, and superior selectivity of CO2 over N2 of ∼ 116.75 with equal molar fraction at 1 bar (1 bar = 105 Pa) and 298 K. Interaction analysis confirms that both the Coulomb and van der Waals interactions between CO2 with pillar[6]arene frameworks are greater than that of N2. The stronger affinity of CO2 with pillar[6]arene_N4 than other structures and the larger isosteric heat differences between CO2 and N2 rendered pillar[6]arene_N4 to present the high CO2 adsorption capacity and high CO2 selectivity over N2. Our results highlight the potential of azo-functionalization as an excellent means to improve pillar[6]arene for CO2 capture and separation.
DOP69 Ozanimod for induction treatment of Moderate-to-Severe Ulcerative Colitis: Results from a systematic literature review and network meta-analyses
Authors: Eaton K , Duperrouzel C , Bhandari P , Craigie S , Bonner A , Cameron C , Tencer T , Kumar J
Published: May 2021

Background

Ozanimod (OZA) is an orally administered, selective sphingosine-1-phosphate receptor modulator that has been evaluated versus placebo (PBO) in the phase 3 True North trial in the treatment of adult patients with moderate-to-severe ulcerative colitis (UC). The objective of this study was to compare the relative efficacy of OZA versus other approved moderate-to-severe UC therapies via network meta-analyses (NMA).

Methods

A systematic literature review was conducted to identify randomised clinical trials published from Jan 1, 2000 to Oct 21, 2020 that evaluated biological therapies (infliximab [IFX], adalimumab [ADA], golimumab [GOL], vedolizumab [VEDO], and ustekinumab [UST]) or an oral small molecule (tofacitinib [TOF]) for adults with moderate-to-severe UC. Bayesian NMAs were performed to determine the comparative efficacy of these therapies based on clinical remission, clinical response, and endoscopic improvement in the induction phase (6 to 14 weeks). Three populations were considered: all patients (overall), first-line (biologic-naïve), or those with exposure to or failure of prior biologic therapy (biologic-experienced). All six comparator therapies were included in the overall and biologic-naive populations, whereas the biologic-experienced population included ADA, VEDO, UST, and TOF due to lack of biologic-experienced data for IFX and GOL.

Results

Twenty-two RCTs examining 10,269 patients in the induction phase were included (Figure 1). All therapies offered significant improvement over PBO across networks apart from ADA in the analysis of clinical remission and clinical response in the biologic-experienced population and ADA, VEDO, and OZA in the analysis of endoscopic improvement in the biologic-experienced population. In the overall and biologic-naïve populations, OZA offered similar efficacy to all other therapies across endpoints except for a significant improvement in endoscopic improvement over ADA (overall: OR 2.01, 95% CrI 1.14, 3.66 [Figure 2]; biologic-naïve: OR 2.13, 95% CrI 1.02, 4.50 [Figure 3]). OZA also offered similar efficacy to all other therapies across endpoints in the biologic-experienced population except for an improvement in clinical remission (OR 4.16, 95% CrI 1.55, 11.24) and clinical response (OR 3.11, 95% CrI 1.40, 7.08) over ADA (Figure 4).

Conclusion

This NMA suggests that OZA provides similar induction efficacy on clinical remission, clinical response, and endoscopic improvement versus other approved moderate-to-severe UC therapies regardless of prior biologic treatment status.
OP11 Longitudinal profiling of mucosal immune cell composition using multiplex immunohistochemistry identifies drug- and response-specific patterns in Ulcerative Colitis
Authors: Volk V , Aden K , Tran F , Mishra N , Bernardes J , Röcken C , Schreiber S , Feuerhake F , Rosenstiel P
Published: May 2021

Background

Interventions targeting key inflammatory mechanisms have expanded the therapeutic repertoire for ulcerative colitis (UC). However, exact molecular mechanisms associated with clinical response remain elusive. We conducted a multiplex-immunohistochemistry (IHC) study to monitor immune cell composition in biopsies from UC patients under 2 approved therapies targeting TNF (infliximab) and integrin (vedolizumab), and a phase IIa clinical trial with the selective IL-6 transsignalling inhibitor olamkicept, to identify spatiotemporal changes of mucosal immune cell compartments in relation to each mechanism of action.

Methods

Sigmoid biopsies from UC patients exposed to infliximab, vedolizumab or olamkicept (26 patients in total) at baseline and week 2, 6 and 14 after therapy induction were subjected to multiplex IHC for CD3, CD15, CD20, CD68, pSTAT3, and pan-cytokeratin (OPAL/Vectra Polaris, Akoya). Quantitative and spatial immune cell patterns captured by advanced image analysis (inForm, Akoya; R package PhenoptrReports) were analysed for differences between baseline and subsequent time points using Dunnett’s multiple comparisons test (GraphPad Prism 8.4.3). Accepted significance levels: *p<0.05,**p<0.01, ***p<0.001.

Results

Targeted therapies resulted in overall decrease of immune cell infiltrates (range 1.15–1.22 fold; p=0.017-0.007), irrespective of drug or specified endpoint (remission at week 14) (Fig. 1). Significant drug-specific changes of spatial immune cell distributions were discernible (Fig. 2). Anti-TNF treatment was mainly associated with decrease in CD3+ T cells (p=0.005) localized in the submucosa close to epithelium or in tertiary lymphoid organs. In contrast, integrin targeting resulted in fewer CD15+ neutrophils, mainly in the submucosal compartment (p=0.046). Olamkicept treatment resulted in unique depletion of pSTAT3+ cells in patients achieving remission at week 14 (not observed in remission after infliximab or vedolizumab). To decipher drug-independent features of clinical remission we assessed distance metrics between immune and intestinal epithelial cells in remission and non-remission patients and observed increase (endpoint compared to baseline) of the average distance to the nearest CD20 or CD15 cell in the remission (p=0.0054, p=0.0004) but not in the non-remission group (n.s.).

Conclusion

Our study strongly suggests that multiplexed spatiotemporally resolved immune cell phenotyping may provide novel insights into the dynamic shifts of immune cell compartments in UC patients undergoing targeted therapy. We propose that such highly resolved digital maps of immune cells could lead to novel tools for therapeutic stratification of IBD patients.
OP29 Long-term dietary patterns are associated with pro-inflammatory and anti-inflammatory features of the gut microbiome
Authors: Bolte L , Vich Vila A , Imhann F , Collij V , Peters V , Fu J , Kurilshikov A , Campmans-Kuijpers M , Dijkstra G , Wijmenga C , Zhernakova A , Weersma R
Published: May 2021

Background

The gut microbiome directly affects the balance of pro-inflammatory and anti-inflammatory responses in the gut. As microbes thrive on dietary substrates, the question arises whether we can nourish an anti-inflammatory gut ecosystem. In this study, we investigated the relation between 173 dietary factors and the microbiome of 1425 individuals spanning four cohorts: Crohn’s disease, ulcerative colitis, irritable bowel syndrome and the general population.

Methods

Shotgun metagenomic sequencing was performed to profile gut microbial composition and function. Dietary intake was assessed through food frequency questionnaires. We performed unsupervised clustering to identify dietary patterns and microbial clusters. Next, linear models were conducted between dietary intake and microbial species and pathways, adding age, sex, caloric intake and sequencing read depth as covariates. Analyses were conducted per cohort, followed by a meta-analysis and heterogeneity estimation. Multiple testing correction was performed on the obtained p-values and a FDR <0.05 was defined as significance cut-off.

Results

We identified 38 associations between dietary patterns and microbial clusters. Moreover, 61 individual foods and nutrients were associated with 61 species and 249 metabolic pathways in the meta-analysis across healthy individuals and patients with IBS, Crohn’s disease and UC (FDR<0.05, heterogeneity p-value>0.05). Processed foods and animal-derived foods were consistently associated with higher abundances of Firmicutes, Ruminococcus species of the Blautia genus and endotoxin synthesis pathways. The opposite associations were found for clusters comprising fish, nuts, bread and legumes. Moreover, while total plant protein intake was associated with a higher Bifidobacterium abundance (FDR=0.048, coef=4.98), animal-derived protein showed a negative association (FDR=1.30x10-05, coef= -4.1). Lastly, we observed positive associations of fecal calprotectin with a fast food cluster (FDR=4.14x10-4, coef=0.24) and a cluster comprised of high-fat meat, potatoes and gravy (FDR=0.003, coef =0.22), while the opposite was seen for clusters of fish and nuts (FDR=0.038, coef= -0.1) and bread and legumes (FDR=0.005, coef= -2.48).

Conclusion

We identified dietary patterns that consistently correlate with groups of bacteria with shared functional roles in both, health and disease. Moreover, specific foods and nutrients were associated with species known to infer mucosal protection and anti-inflammatory effects. A decrease in these bacteria has already been associated with both IBS and IBD. We propose microbial mechanisms through which the diet affects inflammatory responses in the gut as a rationale for future intervention studies.
P009 Disease classifier and microbial dysbiosis index tools cross-predict various pathogenic conditions due to general microbial signal
Authors: Abbas Egbariya H , Braun T , Hadar R , Gal-Mor O , Shental N , Haberman Y , Amir A
Published: May 2021

Background

Microbial dysbiosis is widely described in inflammatory bowel disease (IBD), and has been shown to predict IBD state. However, many other diseases including neuro-psychiatric, metabolic, and malignancies, most of which do not result in gut inflammation, are also linked with gut microbial alteration. Since most studies focus on a single disease, the extent of similarity between different diseases is usually not examined.

Methods

We reanalyzed raw sequencing data from 12,838 human gut V4 16Sseq samples, spanning 59 case-controls comparisons and 28 unique diseases. Novel statistical approach was applied to reduce the effect of the different cohorts; all samples were processed uniformly, and differentially expressed amplicon sequence variants (ASVs) were identified within each cohort. The resulting behavior (direction of change and effect size) of each ASV were then combined across all studies. We used random forest as our classifier and generated non-specific dysbiosis index (NSDI).

Results

For the disease prediction, each cohort was randomly subsampled to 23 healthy and 23 disease samples. Random forest classifier was trained on one disease/control cohort, and the trained classifier was then used to predict the status of a different disease/control cohort. Disease classifiers performed well in identifying many sick vs. healthy states but failed to differentiate between different diseases. For example, a classifier trained on IBD cohort classified relatively good also disease/control in lupus, schizophrenia, or Parkinson’s from different cohorts. We show this cross-identification is due to a large number of shared disease-associated bacteria and utilize these bacteria to define a novel non-specific dysbiosis index (NSDI). After, we identified 114 non-disease specific ASVs (86 up and 28 down regulated ASVs across diseases in comparison to controls), we calculate the per-sample NSDI by rank-transforming the bacteria within the sample and computing the normalized log ratio of the sum of the ranks of the 86 down and 28 up regulated ASVs. The resulting NSDI is shown to perform better than the previously published CD dysbiosis index (Gevers et al, 2014; PMID: 24629344) indicating that NSDI can successfully differentiate between most cases and controls across a wide variety of diseases.

Conclusion

A robust non-specific general response of the gut microbiome is detected across different diseases, some of which is shared with IBD. Classifiers trained on a single disease may identify the general non-specific signal and therefore care should be taken when interpreting the classifier predictions. Finally, our NSDI can be used to prioritize the per-sample degree of dysbiosis.
P020 Mapping the changing intercellular communication and its downstream effect in Ulcerative Colitis
Authors: Potari-gul L , Modos D , Turei D , Valdeolivas A , Madgwick M , Saez-Rodriguez J , Korcsmaros T
Published: May 2021

Background

Intercellular communication is essential for growing and differentiating in multicellular organisms by transducing the signal from cell to cell. Despite its importance, the molecular background is less discovered due to the lack of data. This gap has started to be addressed with the appearance of single-cell omics approaches providing an insight among others into the gene expression of individual cells.

Methods

We have developed a method to predict and compare cell-cell signalling interactions using single-cell RNAseq data from colon biopsies. Transcriptomic data alone is not capable of connecting the cells, a reliable network resource is needed to mediate the signal via protein-protein interactions between the source and target cells. Here we used OmniPath - a resource providing not only intra- and intercellular interactions but also annotations of proteins involved in the interplay of cells - to reconstruct signalling networks. We examined intercellular communication among five cell-types (regulatory T cell, macrophage, dendritic cell, goblet cell and myofibroblast) in healthy colon and during Ulcerative Colitis.

Results

Our analysis shows that there are significant differences in the type of cell-cell communication (ligand-receptor connections, adherens junctions, etc.) between the healthy and Ulcerative Colitis (UC) conditions, and these differences lead to altered downstream effects in the signal receiving cell. In both conditions, the ligand-receptor and adhesion connections were overrepresented, however cell junctions were less abundant in UC. Regarding the communication among the five cell-types, in healthy condition, cells are tightly connected to dendritic cells while in diseased condition to regulatory T cells. Focusing on ligand-receptor interactions between myofibroblasts and regulatory T cells, our pipeline identified the MAPK, Toll-like receptor (TLR) 2/6 and TLR 7/8 pathways enriched downstream in healthy conditions. In contrast, TLR3 and TLR4 pathways were affected by the myofibroblast in Ulcerative Colitis.

Conclusion

We found key intercellular mechanisms leading to well-defined differential pathway activation profiles. We showed that in uninflamed UC condition myofibroblasts disrupt the anti-inflammatory effect of regulatory T cells. Our pipeline is able to predict and analyse cell-cell interactions and their downstream effects and to highlight the differences in healthy and diseased states.
P051 Macrophages as a source of Notch Ligands in Crohn’s disease: implications in fibrosis
Authors: Jorge M A , Barrachina M D , Bauset C , Gisbert-Ferrándiz L , Cosin-Roger J , Coll S , Calatayud S , López-Serrano A , Ortiz-Masiá D
Published: May 2021

Background

Fibrosis constitute the main complications associated to Crohn’s disease (CD). Notch signalling has been implicated in lung, kidney, liver and cardiac fibrosis. Macrophages contribute to fibrosis through the release of different mediators and the pattern of secretion may vary according to their microenvironment. The aim of the present study is to analyze the role of Notch ligands derived from macrophages in the complications of CD.

Methods

We have analyzed: the mRNA expression of cytokines and Notch ligands in CD patients with fistulizing and stenting pattern, the mRNA and protein expression of macrophage markers and Notch ligands in macrophages treated with the main cytokines present in CD patients (IFNγ-, IL10-, IL4, TNFα-U937 treated cells), the mRNA expression of fibrosis markers of DLL4-HT29 treated cells. Results are expressed as fold induction (mean±SEM, n≥4). Statistical analysis was performed with one-way ANOVA followed by Newman-Keuls test. Correlations were analyzed with the Spearman coefficient.

Results

The mRNA expression of IFNγ, TNFα, IL4, IL6 and IL10 was significantly higher in intestinal samples from B2- and B3-CD patients (11.4±1.6, 6.9±1.3, 16.4±3.9, 4.1±0.4, and 5.0±1.0 respectively for B2, and 14.2±1.8, 9.6±2.6, 21.5±4.1, 6.3±1.0 and 9.2±1.7 respectively for B3) than in controls (1.0±0.09, 1.1±0.2, 1.2±0.1, 1.1±0.1 and 1.0±0.1 respectively). The mRNA expression of DLL3 and DLL4 was significantly higher in intestinal samples from B2 (6.1±1.3 and 9.3±2.4, respectively) than in B3 CD patients (4.4±1.0 and 1.8±0.7, respectively) and in controls (0.9±0.2 and 0.7±1.2 respectively). IFNγ-U937 treated cells increased significantly the mRNA expression of DLL3 and DLL4 (2,9±0,6 N=5 N=4 and 3,7±1,1 N=4, respectively) respect vehicle; IL1β increased significantly the expression of DLL4 (1,8±0,01 N=4) and TNFα increased significantly the expression of DLL3 (7,1±2,2 N=4), respect vehicle. DLL4-HT29 treated cells increased significantly fibrosis markers (VIMENTIN (4,6±0,6 N=6), α-SMA (20,9±8,2 N=6), SNAIL1 (1,8±0,4 N=6), SNAIL2 (8,3±1,3 N=6), ZEB1 (8,2±4,3 N=6) and ZEB2 (4,3±0,2 N=6), respect vehicle.

Conclusion

Macrophages may act as a source of Notch ligands who could act as fibrosis mediators in CD patients with a stenting (B2) behavior. The microenvironment rich in IFNγ could activate the fibrosis process in epithelial cells by favoring the expression of DLL4 in macrophages.