bluuebunny/crossref_metadata_2025 huggingface dataset:
Solution NMR structure of Se0862, a highly conserved cyanobacterial protein involved in biofilm formation
Authors: Zhang Ning , Chang Yong‐Gang , Tseng Roger , Ovchinnikov Sergey , Schwarz Rakefet , LiWang Andy
Published: September 2020

Biofilms are accumulations of microorganisms embedded in extracellular matrices that protect against external factors and stressful environments. Cyanobacterial biofilms are ubiquitous and have potential for treatment of wastewater and sustainable production of biofuels. But the underlying mechanisms regulating cyanobacterial biofilm formation are unclear. Here, we report the solution NMR structure of a protein, Se0862, conserved across diverse cyanobacterial species and involved in regulation of biofilm formation in the cyanobacterium Synechococcus elongatus PCC 7942. Se0862 is a class α+β protein with ααββββαα topology and roll architecture, consisting of a four‐stranded β‐sheet that is flanked by four α‐helices on one side. Conserved surface residues constitute a hydrophobic pocket and charged regions that are likely also present in Se0862 orthologs.
Solution NMR structure of Borrelia burgdorferi outer surface lipoprotein BBP28, a member of the mlp protein family
Authors: Fridmanis Jēkabs , Otikovs Mārtiņš , Brangulis Kalvis , Tārs Kaspars , Jaudzems Kristaps
Published: September 2020

Lyme disease is the most widespread vector‐transmitted disease in North America and Europe, caused by infection with Borrelia burgdorferi sensu lato complex spirochetes. We report the solution NMR structure of the B. burgdorferi outer surface lipoprotein BBP28, a member of the multicopy lipoprotein (mlp) family. The structure comprises a tether peptide, five α‐helices and an extended C‐terminal loop. The fold is similar to that of Borrelia turicatae outer surface protein BTA121, which is known to bind lipids. These results contribute to the understanding of Lyme disease pathogenesis by revealing the molecular structure of a protein from the widely found mlp family.
Insights to the Columbia Gas Explosions Lawrence and North Andover, MA September 13, 2018
Authors: Willey Ronald J.
Published: September 2020

On September 13, 2018 at approximately 4:00 pm EDT a series of emergency calls were received by 911 operators working the Lawrence and North Andover region of Massachusetts. The calls ranged from smells of “natural gas” to actual fires to actual explosions (at least five recorded). A low‐pressure natural gas supply system (0.5 psig 14 in. water column) “overpressurized” by at least one order of magnitude. Approximately 8600 customers were affected. Of these, 131 customers had some type of “extended over pressure event” such as a release of natural gas within their basement. This is a 1.5% failure rate on systems that should have been in place when over pressure occur. Unfortunately, this 1.5% failure rate translated into a multimillion dollar loss for the gas company, and the disruption of quality of life for 8600 residents, hundreds of whom were displaced for over 6 months as their homes were rebuilt. One year later, full recovery is still in progress for the area. The root cause traces back to a failed “management of change” system. With proper a hazard analysis/safety review and communication, this event could have been prevented or at least mitigated.
Effects of novaluron ingestion and topical application onGerman cockroach (Blattella germanica) development and reproduction
Authors: A Hamilton Jamora , Wada‐Katsumata Ayako , Ko Alexander , Schal Coby
Published: September 2020

BACKGROUND

Insect growth regulators disrupt insect development and reproduction. Chitin synthesis inhibitors (CSIs) allow the insect to grow normally, but because chitin is an essential component of the cuticle, formation of a new cuticle and ecdysis are prevented and the insect dies. CSIs can also kill embryos by disrupting their normal development. We evaluated the potential utility of novaluron in bait formulations against the German cockroach (Blattella germanicaL.).

RESULTS

The minimum novaluron intake that interfered with molting and reproduction was assessed by exposing nymphs and adult females to novaluron. Results showed that 1 day of feeding on 0.1% novaluron was sufficient to disrupt molting in nymphs and prevent adult females from developing viable oothecae. The long‐term effects on gravid females were investigated by feeding females 0.1% novaluron for different 5‐day intervals during successive stages of gestation. Results demonstrated that gravid females fed novaluron during any period of gestation were able to produce viable eggs. To determine if ingestion of novaluron affected mating success and fertility of adult males, males were fed novaluron and then allowed to mate with untreated virgin females. Males that fed on novaluron successfully mated, and the females produced viable oothecae. Finally, direct comparisons revealed that novaluron is equally effective by ingestion and topical application.

CONCLUSIONS

Novaluron caused mortality in nymphs and interfered with ootheca production in adult females, but only before they formed an ootheca. It successfully reduced German cockroach populations in cages and has potential to be incorporated in cockroach baits.
Impact of Reduced Gate‐to‐Source Spacing on Indium Phosphide High Electron Mobility Transistor Performance
Authors: Calvo Ruiz Diego , Han Daxin , Bonomo Giorgio , Saranovac Tamara , Ostinelli Olivier , Bolognesi Colombo R.
Published: September 2020

Indium phosphide (InP)‐based high electron mobility transistors (HEMTs) with an offset gate enable higher maximum oscillation frequency (fMAX) values because of the resulting reduction in gate‐to‐source resistance. Following this approach, improved direct current (DC) characteristics and cutoff frequencies (fT/fMAX > 410/710 GHz with LG = 50 nm) are shown with respect to centered gate devices. However, HEMTs with an offset gate show degraded noise performances compared with centered gate devices because of a higher gate leakage current. The results show that offsetting the gate closer to the source is not desirable for ultra‐low‐noise performance.
Use of optimal mixture‐process designs and response‐surface models to study properties of calcium silicate units
Authors: Kuhnt Sonja , Becker‐Emden Eva‐Christina , Schade Tim , Eden Wolfgang , Middendorf Bernhard
Published: September 2020

Calcium silicate units are versatile and widely used construction materials for edifices. Their production process involves several factors that concern either the mixture of the raw materials or the curing process. The understanding of how raw materials and process variables interact in achieving the compressive strength of the final product enables a cost‐ and energy‐efficient layout of the production process. In this paper, we use mixture‐process experiments to derive a prediction model for compressive strength. We compare computer‐generated D‐optimal designs with different numbers of center points by various criteria and by their prediction variance throughout the design space. In contrast to traditional mixture designs, these designs take additional constraints on the mixture components into account and can include process variables. We review suitable response‐surface models, which combine mixture and process variables. Based on results from 72 experimental runs, a model for the mean compressive strength is built, combining expert knowledge with statistical model‐selection strategies. The resulting model covers not only linear effects of mixture components and process variables but also interactions and quadratic terms. For example, the influence of the lime share on compressive strength differs among the use of various sand mixtures. For desired values of predicted compressive strength, factor settings can thereby be found reducing costs and energy emission.
A novel fluoroscopy‐based robot system for pedicle screw fixation surgery
Authors: Luo Yanzhong , Li Zhuofu , Jiang Shuai , Hu Lei , Liu Wenyong , Li Weishi
Published: September 2020

Background

Robot‐assisted pedicle screw insertion has gained popularity in the spinal surgery field. Due to high cost, these spinal robots are not extensively applied in clinical surgeries. Developing an effective robot system with low cost and high clinical acceptability is one of the future trends.

Methods

We developed a novel fluoroscopy‐based robot system for pedicle screw insertion. Four live pigs were conducted with percutaneous pedicle screw insertion. Robot‐assisted surgery was performed on the left side of pedicle, while the right opposite side is placed by freehand. The respect accuracy, surgical time and fluoroscopy time were recorded.

Results

Robot‐assisted group achieved 100% (23/23) accuracy. The average times (6.4 ± 1.7) for intraoperative fluoroscopy usage per procedure were lesser than freehand group (12.5 ± 3.6), and the surgical time (6.8 ± 2.1 min) per screw was reduced compared with freehand group (12.1 ± 4.8 min).

Conclusions

Our robot system is cost‐effective and feasible for pedicle screw placement. Low economic cost makes it easier for extensive application in primary hospitals.
A unified criterion for global exponential stability of quaternion‐valued neural networks with hybrid impulses
Authors: Ji Xinrui , Lu Jianquan , Lou Jungang , Qiu Jianlong , Shi Kaibo
Published: September 2020

In this article, the stability of quaternion‐valued neural networks (QVNNs) with hybrid impulses is investigated, which contain stabilizing impulses and destabilizing impulses simultaneously. Through constructing the relationship between impulses and quaternions, this article has obtained a unified criterion for the global exponential stability of the system. First, a new form of impulsive representation is constructed, and the established systems can be decomposed into four different real parts. According to the characteristics of the impulses, the system divides the average interval of impulses (AII) into two cases, that is, and , which can process hybrid impulses simultaneously. Second, for QVNNs, by using the method of matrix p‐norm and the inequality technology, the criterion of each interval is derived. Considering the impulsive effects on the overall stability of QVNNs, the uniform criterion for the global exponential stability can be obtained. In addition, the convergence rate of QVNNs with hybrid impulses is also discussed. Finally, in order to verify the theoretical conclusions, some numerical simulations are given.
Secure sliding mode control of interval type‐2 fuzzy systems against intermittent denial‐of‐service attacks
Authors: Zhang Zhina , Niu Yugang , Zhao Haijuan
Published: September 2020

This article focuses on the sliding mode control of a class of interval type‐2 fuzzy systems with immeasurable states. During the data transmission from the sensor to the controller, the intermittent denial‐of‐service (DoS) attacks may be launched by vicious opponents. A key issue is to evaluate the tolerable region of the attacks for keeping the desired dynamic performance of the controlled interval type‐2 fuzzy systems. To this end, two weighting coefficients are first introduced to construct new membership functions. Based on this, a switched interval type‐2 fuzzy estimator is proposed to estimate the immeasurable state and compensate for the lost measurements caused by DoS attacks. And then, considering different DoS statues, a switched sliding mode controller transiting between the attack free and active cases is synthesized such that the specified sliding surface can be reached. In addition, the acceptable DoS region is quantitatively analyzed via a switched Lyapunov function. It is proven that the input‐to‐state stability of the sliding mode dynamics and the error system can be ensured within this tolerable DoS region. Finally, a simulation example is provided to illustrate the proposed control scheme.
Human induced pluripotent stem cell-derived lung organoids in an ex vivo model of the congenital diaphragmatic hernia fetal lung
Authors: Kunisaki Shaun M. , Jiang Guihua , Biancotti Juan C. , Ho Kenneth K. Y. , Dye Briana R. , Liu Allen P. , Spence Jason R.
Published: September 2020

Three-dimensional lung organoids (LOs) derived from pluripotent stem cells have the potential to enhance our understanding of disease mechanisms and to enable novel therapeutic approaches in neonates with pulmonary disorders. We established a reproducible ex vivo model of lung development using transgene-free human induced pluripotent stem cells generated from fetuses and infants with Bochdalek congenital diaphragmatic hernia (CDH), a polygenic disorder associated with fetal lung compression and pulmonary hypoplasia at birth. Molecular and cellular comparisons of CDH LOs revealed impaired generation of NKX2.1+ progenitors, type II alveolar epithelial cells, and PDGFRα+ myofibroblasts. We then subjected these LOs to disease relevant mechanical cues through ex vivo compression and observed significant changes in genes associated with pulmonary progenitors, alveolar epithelial cells, and mesenchymal fibroblasts. Collectively, these data suggest both primary cell-intrinsic and secondary mechanical causes of CDH lung hypoplasia and support the use of this stem cell-based approach for disease modeling in CDH.
Modeling daily and weekly moderate and vigorous physical activity using zero‐inflated mixture Poisson distribution
Authors: Xue Xiaonan , Qi Qibin , Sotres‐Alvarez Daniela , Roesch Scott C. , Llabre Maria M. , Bainter Sierra A. , Mossavar‐Rahmani Yasmin , Kaplan Robert , Wang Tao
Published: September 2020

Recently developed accelerometer devices have been used in large epidemiological studies for continuous and objective monitoring of physical activities. Typically, physical movements are summarized as minutes in light, moderate, and vigorous physical activities in each wearing day. Because of preponderance of zeros, zero‐inflated distributions have been used for modeling the daily moderate or higher levels of physical activity. Yet, these models do not fully account for variations in daily physical activity and cannot be extended to model weekly physical activity explicitly, while the weekly physical activity is considered as an indicator for a subject's average level of physical activity. To overcome these limitations, we propose to use a zero‐inflated Poisson mixture distribution that can model daily and weekly physical activity in same family of mixture distributions. Under this method, the likelihood of an inactive day and the amount of exercise in an active day are simultaneously modeled by a joint random effects model to incorporate heterogeneity across participants. If needed, the method has the flexibility to include an additional random effect to address extra variations in daily physical activity. Maximum likelihood estimation can be obtained through Gaussian quadrature technique, which is implemented conveniently in an R package GLMMadaptive. Method performances are examined using simulation studies. The method is applied to data from the Hispanic Community Health Study/Study of Latinos to examine the relationship between physical activity and BMI groups and within a participant the difference in physical activity between weekends and weekdays.
Selenium‐Based Solar Cell with Conjugated Polymers as Both Electron and Hole Transport Layers to Realize High Water Tolerance as well as Good Long‐Term and Thermal Stability
Authors: Liu Wenbo , Yu Fei , Wang Yang , Michinobu Tsuyoshi , Fan Weijun , Zhang Qichun
Published: September 2020

Solar cells with varied absorbers, ranging from crystalline silicon to perovskite materials, are very vulnerable to water. Expensive and complicated encapsulation is needed to protect the devices. Thus, it is highly desirable to achieve encapsulation‐free solar cells with high water tolerance. Herein, encapsulation‐free selenium (Se)‐based solar cells (SSCs) with hydrophobic polymers as electron and hole transport layers are presented and can successfully tolerate the aqueous conditions. Moreover, it is found that the photocurrent–time curve under the aqueous/ambient environment can be smoothly fitted into the first‐order exponential models. The photocurrent of water‐soaking SSCs can recover to its original value after drying in the air, which proves the great water tolerance of fabricated SSCs. Furthermore, the SSCs also show good long‐term and thermal stability. The viability of encapsulation‐free SSCs under a harsh environment provides opportunities to further explore the interactions among light, water, and solar cells as well as make large‐scale industrialization applications of SSCs much easier.
A 22.3% Efficient p‐Type Back Junction Solar Cell with an Al‐Printed Front‐Side Grid and a Passivating n+‐Type Polysilicon on Oxide Contact at the Rear Side
Authors: Min Byungsul , Wehmeier Nadine , Brendemuehl Till , Merkle Agnes , Haase Felix , Larionova Yevgeniya , David Lasse , Schulte-Huxel Henning , Peibst Robby , Brendel Rolf
Published: September 2020

The fabrication of a silicon solar cell on 6 in. pseudo‐square p‐type Czochralski grown silicon wafers featuring poly‐Si‐based passivating contacts for electrons at the cell rear side and screen‐printed aluminum fingers at the front side is demonstrated. The undiffused front surface is passivated with an Al2O3/SiNx stack, and the rear surface is covered with a thin oxide/n+‐poly‐Si/Al2O3/SiNx layer system, contacted by screen‐printed silver fingers. A loss analysis shows that the recombination losses at the metal contacts on both cell sides dominate the total energy losses. A voltage of 700 mV as the highest open‐circuit voltage from a batch of seven cells is achieved, and the best cell efficiency is 22.3%, independently confirmed.
Atomic‐ and Molecular‐Level Functionalizations of Polymeric Carbon Nitride for Solar Fuel Production
Authors: Zhen Wenlong , Xue Can
Published: September 2020

Polymeric carbon nitride (PCN) is a metal‐free semiconductor that has received extensive research attention due to its unique advantages such as low cost, high stability, and visible‐light response. However, pristine PCN is not an ideal photocatalyst because of fast electron–hole recombination and its inert surface for molecular adsorption. Nevertheless, benefiting from the N‐linked tri‐s‐triazine structure, PCN can be readily functionalized through chemical modifications. As such, researchers have made enormous efforts to develop various strategies for modifying PCN to achieve enhanced photocatalytic activities. Herein, recent advances in PCN functionalizations with different atomic or molecular units, including metal and nonmetal elements, small functional groups, organic functional fragments, and metal complex motifs, are summarized. Moreover, the effect of different PCN functionalization strategies on the molecular structure, optical properties, electronic behaviors, and photocatalytic activities particularly for water splitting and CO2 reduction is discussed. In the end, the remaining challenges in the structural modification of PCN and future opportunities of functional PCN‐based photocatalysts for efficient solar fuel production are elaborated on.
UV‐Selective Optically Transparent Zn(O,S)‐Based Solar Cells
Authors: Lopez-Garcia Alex J. , Bauer Andreas , Fonoll Rubio Robert , Payno David , Jehl Li-Kao Zacharie , Kazim Samrana , Hariskos Dimitrios , Izquierdo-Roca Victor , Saucedo Edgardo , Pérez-Rodríguez Alejandro
Published: September 2020

This work reports experimental evidence of a photovoltaic effect in transparent UV‐selective Zn(O,S)‐based heterojunctions. Zn(O,S) has a strong interest for the development of UV‐selective solar cells with high transparency in the visible region, required for the development of nonintrusive building‐integrated photovoltaic (BIPV) elements as transparent solar windows and glass‐based solar façades. By anion alloying, Zn(O,S) mixed crystal absorbers can be fabricated with different sulfur content across the whole compositional range. This allows adjustment of the bandgap of the absorbers in the 2.7–2.9 eV region, maximizing absorption in the UV, while keeping a high level of transparency. Zn(O,S) alloys with composition corresponding to S/(S + O) content ratios of 0.6 are successfully grown by sputtering deposition, and first glass/FTO/NiO/Zn(O,S)/ITO device prototypes are produced. The resulting devices present an average visible transmittance (AVT) of 75% and present photovoltaic effect. By introducing a thin C60 film as electron transport layer (ETL), charge extraction is enhanced, and devices show an efficiency of 0.5% and an AVT > 69%. The transparency of these devices can potentially allow for their ubiquitous installation in glazing systems as part of nonintrusive BIPV elements or to power Internet of Things (IoT) devices and sensors as an integrated transparent component.
KubCG: A dynamic Kubernetes scheduler for heterogeneous clusters
Authors: El Haj Ahmed Ghofrane , Gil‐Castiñeira Felipe , Costa‐Montenegro Enrique
Published: September 2020

Container platforms are increasingly being used to deploy cloud‐based services. Nevertheless, many cloud services are also demanding graphics processing units (GPUs) to accelerate different applications that make use of their parallel architecture, such as deep learning or just video processing. Thus, different container technologies, such as Docker and Kubernetes, are implementing GPU support. Some effort is being devoted to design algorithms to schedule applications into heterogeneous computing systems that use CPUs and GPUs together. This article is part of this effort, and we describe how to build a dynamic scheduling platform for Kubernetes that is able to manage the deployment of Docker containers in a heterogeneous cluster, which we call KubCG. This platform implements a new scheduler that optimizes the deployment of new containers by taking into account the Kubernetes Pod timeline and the historical information about the execution of the containers. We have performed different tests to validate this new algorithm, and KubCG was able to reduce the time to complete different tasks down to a 64% of the original time in our different experiments.
Nonasymptotic support recovery for high‐dimensional sparse covariance matrices
Authors: Kashlak Adam B. , Kong Linglong
Published: September 2020

For high‐dimensional data, the standard empirical estimator for the covariance matrix is very poor, and thus many methods have been proposed to more accurately estimate the covariance structure of high‐dimensional data. In this article, we consider estimation under the assumption of sparsity but regularize with respect to the individual false‐positive rate for incorrectly including a matrix entry in the support of the final estimator. The two benefits of this approach are (1) an interpretable regularization parameter removing the need for computationally expensive tuning and (2) extremely fast computation time arising from use of a binary search algorithm implemented to find the best estimator within a carefully constructed operator norm ball. We compare our approach to universal thresholding estimators and lasso‐style penalized estimators on both simulated data and data from gene expression for cancerous tumours.
Biofilms to Improve Fruit Shelf Life Using Hydrophobic and Pre‐Gel Cassava Modified Starch
Authors: Lermen Fernando Henrique , Piazza Vera Regina , Ramos Carolina Kruse , Ribeiro José Luis Duarte , Echeveste Márcia Elisa , Assad Filho Nabi , Coelho Tânia Maria
Published: September 2020

This study investigates an alternative to reduce fruit waste. Nowadays, around 40% of the fruit produced is wasted before consumption. Considering such waste and the current rate of population growth, by 2050, the world population will lack food. Due to the high content of moisture and sugar, many fruits are markedly perishable, and this characteristic contributes to the waste of food. In order to find solutions for increasing fruit durability, this study presents the development of a hydrophobic and pre‐gel modified starch, used as a protective layer to preserve post‐harvest fruits. Physicochemical analyses are carried out to monitor the rate of fruit decomposition of pears and oranges. The study concludes that protecting the fruit with the hydrophobic and pre‐gel modified starch mixture is effective in postponing the degradation process. The fruits that received regular sanitization lasted only for 22 days, while the ones that received the starch protection are suitable for consumption for up to 56 days.
A review of past changes in extratropical cyclones in the northern hemisphere and what can be learned for the future
Authors: Raible Christoph C. , Pinto Joaquim G. , Ludwig Patrick , Messmer Martina
Published: September 2020

Extratropical cyclones, a major phenomenon of the mid‐latitude atmospheric dynamics, show strong variability over a range of time scales. Future projections hint at an increase of cyclonic intensity and the associated precipitation, an important fact to be considered when developing future risk assessments. This review presents a first overview of studies which (a) puts the current variability and projected future climate changes of extratropical cyclone characteristics in a long‐term perspective, (b) shows connections to natural external forcings, and (c) deepens our understanding of cyclone intensification processes for past climate periods. We summarize the current state of knowledge for two periods in the past—the last millennium and the Last Glacial Maximum (LGM, 21,000 years ago). For these two periods, the sparse information from paleo proxy archives are compared to climate modeling results on global and regional scales. For example, strong changes of the climate mean state, induced by orbital forcing and associated feedbacks, show strong effects on different cyclone characteristics, for example, a southward shift of the storm tracks over the North Atlantic during the LGM. Other findings indicate that dynamic processes could play at least an equally important role as thermodynamic processes for the variations of cyclone‐induced precipitation. This is in contrast to the projected future changes in cyclone‐related precipitation, which are driven primarily by thermodynamic processes. The review demonstrates how a paleoclimatic view can foster an extended process understanding and be instrumental to better understand future changes in extratropical cyclones and associated characteristics.

This article is categorized under:

Paleoclimates and Current Trends > Modern Climate Change
Semiclassical quantization of the mixed-flux AdS3 giant magnon
Authors: Varga Adam
Published: September 2020

Abstract

We obtain explicit formulas for the eight bosonic and eight fermionic fluctuations around the mixed-flux generalization of the Hofman-Maldacena giant magnon on AdS3×S3×T4and AdS3×S3×S3×S1. As a check of our results, we confirm that the semiclassical quantization of these fluctuations leads to a vanishing one-loop correction to the magnon energy, as expected from symmetry based arguments.
$$ \mathcal{N} $$ = 2 Conformal SYM theories at large $$ \mathcal{N} $$
Authors: Beccaria M. , Billò M. , Galvagno F. , Hasan A. , Lerda A.
Published: September 2020

Abstract

We consider a class of $$ \mathcal{N} $$
N
= 2 conformal SU(N) SYM theories in four dimensions with matter in the fundamental, two-index symmetric and anti-symmetric representations, and study the corresponding matrix model provided by localization on a sphere S4, which also encodes information on flat-space observables involving chiral operators and circular BPS Wilson loops. We review and improve known techniques for studying the matrix model in the large-N limit, deriving explicit expressions in perturbation theory for these observables. We exploit both recursive methods in the so-called full Lie algebra approach and the more standard Cartan sub-algebra approach based on the eigenvalue distribution. The sub-class of conformal theories for which the number of fundamental hypermultiplets does not scale with N differs in the planar limit from the $$ \mathcal{N} $$
N
= 4 SYM theory only in observables involving chiral operators of odd dimension. In this case we are able to derive compact expressions which allow to push the small ’t Hooft coupling expansion to very high orders. We argue that the perturbative series have a finite radius of convergence and extrapolate them numerically to intermediate couplings. This is preliminary to an analytic investigation of the strong coupling behavior, which would be very interesting given that for such theories holographic duals have been proposed.
The herbal extract EPs® 7630 increases the antimicrobial airway defense through monocyte-dependent induction of IL-22 in T cells
Authors: Witte Katrin , Koch Egon , Volk Hans-Dieter , Wolk Kerstin , Sabat Robert
Published: September 2020

The phytotherapeutic compound EPs® 7630, an extract manufactured from Pelargonium sidoides roots, is frequently used for the treatment of airway infections. Nevertheless, the knowledge of the mode of action of EPs® 7630 is still sparse. Our study aimed at further elucidating the underlying pharmacological mechanisms by focusing on antimicrobial defense mechanisms of EPs® 7630. While investigating the influence of EPs® 7630 on lymphokine production by PBMCs, we found that EPs® 7630 is a novel inducer of IL-22 and IL-17. This cytokine-inducing effect was most pronounced for IL-22 and clearly dose-dependent starting from 1 μg/ml of the extract. Furthermore, EPs® 7630 pretreatment selectively enhanced the IL-22 and IL-17 production capacity of CD3/28-activated PBMCs while strongly limiting the IFN-γ production capacity of innate lymphoid cells. The relevance of EPs® 7630–induced IL-22 production was proven in vitro and in vivo, where IL-22 provoked a strong increase of the antimicrobial protein S100A9 in lung epithelial cells and pulmonary tissue, respectively. A detailed analysis of IL-22 induction modi revealed no direct influence of EPs® 7630 on the basal or anti-CD3/CD28 antibody-induced IL-22 production by CD4+ memory T cells. In fact, EPs® 7630–induced IL-22 production by CD4+ memory T cells was found to be essentially dependent on soluble mediators (IL-1/IL-23) as well as on direct cellular contact with monocytes. In summary, our study reveals a new immune-modulating function of EPs® 7630 that might confer IL-22 and IL-17-induced protection from bacterial airway infection.

Key messages

EPs® 7630 selectively strengthens IL-22 and IL-17 production of memory T cells.

EPs® 7630 limits the IFN-y production capacity of innate lymphoid cells.

EPs® 7630–caused IL-22 production by T cells is essentially dependent on monocytes.

IL-22 increase antimicrobial proteins (AMPs) in airway epithelium.

EPs® 7630 might protect against airway infection by induction of AMP-inducers.
An Event-B based approach for cloudcomposite services verification
Authors: Lahouij Aida , Hamel Lazhar , Graiet Mohamed , el Ayeb Béchir
Published: September 2020

The verification of the Cloud composite services’ correctness is challenging. In fact, multiple component services, derived from different Cloud providers with different service description languages and communication protocols, are involved in the composition which may raise incompatibility issues that in turn lead to a non-consistent composition. In this work, we propose a formal approach to model and verify Cloud composite services. Four verification levels are considered in this article; the structural, semantic, behavioral, and resource allocation levels. Therefore, we opted for the Event-B formal method that enables complex problems decomposition thanks to its refinement capabilities. The proposed approach has proven its efficiency for the modelling and verification of Cloud composite services. The proposed model comprises four abstract levels with respect to the four verification axes. A proof-based approach is applied to the model’s verification. We also succeeded in the validation of the model thanks to the model animation provided by the PROB tool. The use of formal methods provides a rigorous reasoning and mathematical proofs on the correction of the model which ensures the elaboration of correct-by-construction composite services.
Outpacing movement — ultrafast volume coverage in neuropediatric magnetic resonance imaging
Authors: Gräfe Daniel , Roth Christian , Weisser Margit , Krause Matthias , Frahm Jens , Voit Dirk , Hirsch Franz Wolfgang
Published: September 2020

Background

Conventional MRI sequences are often affected in neuropediatric imaging by unavoidable movements. Therefore, children younger than 6 years usually have to be examined under sedation/anesthesia. A new real-time MRI technique with automatic slice advancement allows for motion-robust T2-weighted volume coverage of the whole brain within a few seconds in adults.

Objective

To evaluate to which extent the new volume coverage method can be used to visualize cerebrospinal fluid and reduce the need for anesthesia in children.

Materials and methods

We assessed 30 children ages 6 years and younger with suspected or proven hydrocephalus, hygroma or macrocephalus using volume coverage sequences with 20 slices per second in three planes. If necessary, a parent was placed in the bore together with the child for calming and gentle immobilization. We compared visualization of cerebrospinal fluid spaces and course of the shunt catheter in volume coverage sequences vs. fast spin-echo sequences.

Results

The clinical issue could be sufficiently assessed in all children with use of volume coverage sequences, whereas conventional fast spin-echo sequences performed moderately to poorly. Visualization of the tip of a shunt failed in 16% of volume coverage scans and 27% of turbo spin-echo scans. A subsequent examination under anesthesia was never necessary. None of the examinations had to be stopped prematurely.

Conclusion

The motion-robust volume coverage sequences with T2-type contrast can be used to avoid sedation of children in the evaluation of cerebrospinal fluid spaces, even in the presence of vigorous motion. For other indications and contrasts, the technique must still be evaluated.
Chemically synthesized Gb3 glycosphingolipids: tools to access their function in lipid membranes
Authors: Sibold Jeremias , Ahadi Somayeh , Werz Daniel B. , Steinem Claudia
Published: September 2020

Gb3 glycosphingolipids are the specific receptors for bacterial Shiga toxin. Whereas the trisaccharidic head group of Gb3 defines the specificity of Shiga toxin binding, the lipophilic part composed of sphingosine and different fatty acids is suggested to determine its localization within membranes impacting membrane organisation and protein binding eventually leading to protein internalisation. While most studies use Gb3 extracts, chemical synthesis provides a unique tool to access different tailor-made Gb3 glycosphingolipids. In this review, strategies to synthesize these complex glycosphingolipids are presented. Special emphasis is put on the preparation of Gb3 molecules differing only in their fatty acid part (saturated, unsaturated, α-hydroxylated and both, unsaturated and α-hydroxylated). With these molecules in hand, it became possible to investigate the phase behaviour of liquid ordered/liquid disordered supported membranes doped with the Gb3 species by means of fluorescence and atomic force microscopy. The results clearly highlight the influence of the different fatty acids of the Gb3 sphingolipids on the phase behaviour and the binding properties of Shiga toxin B subunits, even though the membranes were only doped with 5 mol% of the receptor lipid. To obtain fluorescent Gb3 derivatives, either fatty acid labelled Gb3 molecules or head group labelled ones were synthesized. These molecules enabled us to address the question, where the Gb3 sphingolipids are localized prior protein binding by means of fluorescence microscopy on giant unilamellar vesicles. The results again demonstrate that the fatty acid of Gb3 plays a pivotal role for the overall membrane organisation.
High-level expression of aryl-alcohol oxidase 2 from Pleurotus eryngii in Pichia pastoris for production of fragrances and bioactive precursors
Authors: Jankowski Nina , Koschorreck Katja , Urlacher Vlada B.
Published: September 2020

The fungal secretome comprises various oxidative enzymes participating in the degradation of lignocellulosic biomass as a central step in carbon recycling. Among the secreted enzymes, aryl-alcohol oxidases (AAOs) are of interest for biotechnological applications including production of bio-based precursors for plastics, bioactive compounds, and flavors and fragrances. Aryl-alcohol oxidase 2 (PeAAO2) from the fungus Pleurotus eryngii was heterologously expressed and secreted at one of the highest yields reported so far of 315 mg/l using the methylotrophic yeast Pichia pastoris (recently reclassified as Komagataella phaffii). The glycosylated PeAAO2 exhibited a high stability in a broad pH range between pH 3.0 and 9.0 and high thermal stability up to 55 °C. Substrate screening with 41 compounds revealed that PeAAO2 oxidized typical AAO substrates like p-anisyl alcohol, veratryl alcohol, and trans,trans-2,4-hexadienol with up to 8-fold higher activity than benzyl alcohol. Several compounds not yet reported as substrates for AAOs were oxidized by PeAAO2 as well. Among them, cumic alcohol and piperonyl alcohol were oxidized to cuminaldehyde and piperonal with high catalytic efficiencies of 84.1 and 600.2 mM−1 s−1, respectively. While the fragrance and flavor compound piperonal also serves as starting material for agrochemical and pharmaceutical building blocks, various positive health effects have been attributed to cuminaldehyde including anticancer, antidiabetic, and neuroprotective effects. PeAAO2 is thus a promising biocatalyst for biotechnological applications.

Key points

• Aryl-alcohol oxidase PeAAO2 from P. eryngii was produced in P. pastoris at 315 mg/l.

• Purified enzyme exhibited stability over a broad pH and temperature range.

• Oxidation products cuminaldehyde and piperonal are of biotechnological interest.

Graphical abstract
Biodistribution and dosimetry of a single dose of albumin-binding ligand [177Lu]Lu-PSMA-ALB-56 in patients with mCRPC
Authors: Kramer Vasko , Fernández René , Lehnert Wencke , Jiménez-Franco Luis David , Soza-Ried Cristian , Eppard Elisabeth , Ceballos Matias , Meckel Marian , Benešová Martina , Umbricht Christoph A. , Kluge Andreas , Schibli Roger , Zhernosekov Konstantin , Amaral Horacio , Müller Cristina
Published: September 2020

Introduction

PSMA-targeted radionuclide therapy with lutetium-177 has emerged as an effective treatment option for metastatic, castration-resistant prostate cancer (mCRPC). Recently, the concept of modifying PSMA radioligands with an albumin-binding entity was demonstrated as a promising measure to increase the tumor uptake in preclinical experiments. The aim of this study was to translate the concept to a clinical setting and evaluate the safety and dosimetry of [177Lu]Lu-PSMA-ALB-56, a novel PSMA radioligand with albumin-binding properties.

Methods

Ten patients (71.8 ± 8.2 years) with mCRPC received an activity of 3360 ± 393 MBq (120–160 μg) [177Lu]Lu-PSMA-ALB-56 followed by whole-body SPECT/CT imaging over 7 days. Volumes of interest were defined on the SPECT/CT images for dosimetric evaluation for healthy tissue and tumor lesions. General safety and therapeutic efficacy were assessed by measuring blood biomarkers.

Results

[177Lu]Lu-PSMA-ALB-56 was well tolerated, and no severe adverse events were observed. SPECT images revealed longer circulation of [177Lu]Lu-PSMA-ALB-56 in the blood with the highest uptake in tumor lesions at 48 h post injection. Compared with published data for other therapeutic PSMA radioligands (e.g. PSMA-617 and PSMA I&T), normalized absorbed doses of [177Lu]Lu-PSMA-ALB-56 were up to 2.3-fold higher in tumor lesions (6.64 ± 6.92 Gy/GBq) and similar in salivary glands (0.87 ± 0.43 Gy/GBq). Doses to the kidneys and red marrow (2.54 ± 0.94 Gy/GBq and 0.29 ± 0.07 Gy/GBq, respectively) were increased.

Conclusion

Our data demonstrated that the concept of albumin-binding PSMA-radioligands is feasible and leads to increased tumor doses. After further optimization of the ligand design, the therapeutic outcomes may be improved for patients with prostate cancer.
Response to neoadjuvant treatment among rectal cancer patients in a population-based cohort
Authors: Alwers Elizabeth , Jansen Lina , Kather Jakob , Amitay Efrat , Bläker Hendrik , Kloor Matthias , Tagscherer Katrin E. , Roth Wilfried , Herpel Esther , Chang-Claude Jenny , Brenner Hermann , Hoffmeister Michael
Published: September 2020

Background

In rectal cancer, prediction of tumor response and pathological complete response (pCR) to neoadjuvant treatment could contribute to refine selection of patients who might benefit from a delayed- or no-surgery approach. The aim of this study was to explore the association of clinical and molecular characteristics of rectal cancer with response to neoadjuvant treatment and to compare patient survival according to level of response.

Methods

Resected rectal cancer patients were selected from a population-based cohort study. Molecular tumor markers were determined from the surgical specimen. Tumor response and pCR were defined as downstaging in T or N stage and absence of tumor cells upon pathological examination, respectively. The associations of patient and tumor characteristics with tumor response and pCR were explored, and patient survival was determined by degree of response to neoadjuvant treatment.

Results

Among 1536 patients with rectal cancer, 602 (39%) received neoadjuvant treatment. Fifty-five (9%) patients presented pCR, and 239 (49%) and 250 (53%) patients showed downstaging of the T and N stages, respectively. No statistically significant associations were observed between patient or tumor characteristics and tumor response or pCR. Patients who presented any type of response to neoadjuvant treatment had significantly better cancer-specific and overall survival compared with non-responders.

Conclusion

In this study, patient characteristics were not associated with response to neoadjuvant treatment, and molecular characteristics determined after surgical resection of the tumor were not predictive of pCR or tumor downstaging. Future studies should include molecular biomarkers from biopsy samples before neoadjuvant treatment.
Non-statin lipid-lowering therapy over time in very-high-risk patients: effectiveness of fixed-dose statin/ezetimibe compared to separate pill combination on LDL-C
Authors: Katzmann Julius L. , Sorio-Vilela Francesc , Dornstauder Eugen , Fraas Uwe , Smieszek Timo , Zappacosta Sofia , Laufs Ulrich
Published: September 2020

Background

Many patients at very-high atherosclerotic cardiovascular disease risk do not reach guideline-recommended targets for LDL-C. There is a lack of data on real-world use of non-statin lipid-lowering therapies (LLT) and little is known on the effectiveness of fixed-dose combinations (FDC). We therefore studied prescription trends in oral non-statin LLT and their effects on LDL-C.

Methods

A retrospective analysis was conducted of electronic medical records of outpatients at very-high cardiovascular risk treated by general practitioners (GPs) and cardiologists, and prescribed LLT in Germany between 2013 and 2018.

Results

Data from 311,242 patients were analysed. Prescriptions for high-potency statins (atorvastatin and rosuvastatin) increased from 10.4% and 25.8% of patients treated by GPs and cardiologists, respectively, in 2013, to 34.7% and 58.3% in 2018. Prescription for non-statin LLT remained stable throughout the period and low especially for GPs. Ezetimibe was the most prescribed non-statin LLT in 2018 (GPs, 76.1%; cardiologists, 92.8%). Addition of ezetimibe in patients already prescribed a statin reduced LDL-C by an additional 23.8% (32.3 ± 38.4 mg/dL), with a greater reduction with FDC [reduction 28.4% (40.0 ± 39.1 mg/dL)] as compared to separate pills [19.4% (27.5 ± 33.8 mg/dL)]; p < 0.0001. However, only a small proportion of patients reached the recommended LDL-C level of < 70 mg/dL (31.5% with FDC and 21.0% with separate pills).

Conclusions

Prescription for high-potency statins increased over time. Non-statin LLT were infrequently prescribed by GPs. The reduction in LDL-C when statin and ezetimibe were prescribed in combination was considerably larger for FDC; however, a large proportion of patients still remained with uncontrolled LDL-C levels.

Graphic abstract
High risk of hip dislocation following polyethylene liner exchange in total hip arthroplasty—is cup revision necessary?
Authors: Dammerer D. , Schneider F. , Renkawitz T. , Putzer D. , Bogensperger M. , Biedermann R.
Published: September 2020

Purpose

Polyethylene (PE) wear remains a common reason for revision surgery following total hip arthroplasty (THA). An established treatment method is isolated liner exchange in a well-fixed acetabular cup and entails a known high risk of hip dislocation after revision surgery. The purpose of this retrospective study was to determine the rate of hip dislocation after liner exchange.

Methods

Patients were included if (1) the PE liner was removable, (2) the acetabular shell was stable with acceptable orientation, (3) no osteolysis around the acetabular cup was found and (4) no dislocation of the THA occurred before revision surgery. We reviewed medical histories and performed radiological measurements using Einzel-Bild-Röntgen-Analyse (EBRA) software. EBRA measurements and statistical investigations were performed by two independent investigators.

Results

A total of 82 patients were included in our study. Mean follow-up was six (range: 3.6–9.9) years. In 13 (15.8%) patients THA dislocations occurred at a mean postoperative period of 20.2 (range: 1–44) weeks after revising the PE liner. This is equivalent to an absolute risk increase of 16% after revision surgery, which results in a number needed to harm of 6. This means that every sixth patient with isolated liner exchange can expect to experience dislocation due to wear.

Conclusion

In conclusion, isolated exchange of the polyethylene liner because of wear showed a high risk of dislocation and further cup revision. Our results suggest that the threshold for revising well-fixed components in the case of liner wear should be lowered.

Trial Registration number and date of registration

Number: 20140710-1012 and Date: 2016-03-09.