bluuebunny/crossref_metadata_2025 huggingface dataset:
Adult-onset methylenetetrahydrofolate reductase deficiency
Authors: Vieira Daniela , Florindo Cristina , Tavares de Almeida Isabel , Macário Maria Carmo
Published: March 2020

Severe hyperhomocysteinemia (>100 µmol/L) is often associated with inborn errors of homocysteine metabolism. It manifests typically in neonatal period with developmental delay, hypotonia, feeding problems or failure to thrive. Adult-onset forms are rare and include less severe manifestations. Early diagnosis is crucial because effective treatment is available. A 23-year-old man presented with a 3-week history of speech and gait impairment, and numbness in lower limbs. Neurological examination revealed dysarthria, decreased vibratory sensation in both legs and appendicular and gait ataxia. Brain MRI revealed T2-hyperintense symmetric white matter lesions and cortical atrophy. He had folate and vitamin B12deficiency, a markedly elevated serum homocysteine and low methionine. Despite vitamin supplementation homocysteine levels remained elevated. Molecular studies of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene revealed a new pathogenic mutation (c.1003C>T (p.Arg335Cys)) and a polymorphism (C677T (p.Ala222Val)) associated with hyperhomocysteinemia, both in homozygosity. The patient started betaine with clinical and biochemical improvement.
Toxic inhalational injury
Authors: Davies Victoria , Turner Jake , Greenway Michael
Published: March 2020

A middle-aged patient presented with toxic inhalational injury, and was resuscitated prehospitally and treated in the emergency department for smoke inhalation, carbon monoxide (CO) exposure and cyanide poisoning with the use of antidotes. Due to the CO effects on spectrophotometry, an anaemia initially identified on blood gas analysis was thought to be artefactual, but was later confirmed by laboratory testing to be accurate. In addition, cyanide can confound haemoglobin testing due to its use in the analytical process and non-cyanide analysis is required when there is suspected exposure. Although no consensus exists on a first-line cyanide antidote choice, hydroxocobalamin is the only antidote without a serious side effect profile and/or deleterious cardiovascular effects. We propose prehospital enhanced care teams consider carrying hydroxocobalamin for early administration in toxic inhalational injury.
Medullary abscess: a rare clinical presentation
Authors: Muranovs Pavels , Gillon Claire , Norris John
Published: March 2020

Brain abscesses represent areas of localised infection of the brain parenchyma. Those confined to the brainstem are rare and usually fatal if untreated.Streptococcus intermediusis a common causative organism of brain abscesses and is associated with significant morbidity. We describe a case report of medullary abscess secondary to dental infection in a 68-year-old patient. The patient presented with headaches and flu-like symptoms progressing to left hemiparesis and reduced consciousness/bulbar function. The patient underwent emergency posterior fossa craniectomy and drainage with subsequent medical management with antibiotics. Prompt diagnosis, early surgical intervention and maximal therapy with antibiotics alongside extensive rehabilitation are all vital to ensure good neurological outcome. It is imperative for medical practitioners to consider the diagnosis of brain abscess in patients presenting with rapid onset neurological deterioration. Such cases require early neurological imaging with involvement of tertiary neurosurgery services.
RAP study, report 1: novel subtype of macular neovascularisation type III, cilioretinal MNV3
Authors: Haj Najeeb Bilal , Deak Gabor G , Schmidt-Erfurth Ursula Margarethe , Gerendas Bianca S
Published: March 2020

Purpose

To report on patients with macular neovascularisation type III (MNV3) arising from cilioretinal arteries (CRAs) (cilioretinal macular neovascularisation type III (cMNV3)).

Methods

We reviewed baseline examinations of patients with neovascular age-related macular degeneration using multimodal imaging. We determined the type and distribution of MNV lesions in each cMNV3 case, the range of distances from the fovea, existence of exudative maculopathy, intraretinal haemorrhage and other morphological characteristics. 50 consecutive eyes with usual MNV3 without CRA were included as a control group.

Results

102 eyes of 102 patients were identified with MNV3 lesions. Among these, we found 12 eyes (12%) with cMNV3, 84 eyes (82%) with usual MNV3 without CRA and 6 eyes (6%) with usual MNV3 with CRA. Ten cases of cMNV3 had one lesion, and two cases had two lesions. The lesions were distributed equally between the superior and inferior halves of the macula, whereas in the nasal and temporal halves, there were 8 (57%) and 6 (43%) lesions, respectively. All cMNV3 lesions were located between 500 and 1500 µm from the central fovea except one, which was located between 1500 and 3000 µm. None of the lesions had macular neovascularisation type I (MNV1) or macular neovascularisation type II (MNV2) elsewhere in both groups. Exudative maculopathy and intraretinal haemorrhage were found in seven (88%) and five (63%) of the eight pure cMNV3 cases, respectively.

Conclusion

cMNV3 can be solitary or multiple, isolated or accompanied with usual MNV3 lesions, but not with concurrent MNV1 or MNV2. It is frequently associated with extensive exudative maculopathy, intraretinal haemorrhage and subretinal fluid.
Sample study protocol for adapting and translating the 5C scale to assess the psychological antecedents of vaccination
Authors: Betsch Cornelia , Bach Habersaat Katrine , Deshevoi Sergei , Heinemeier Dorothee , Briko Nikolay , Kostenko Natalia , Kocik Janusz , Böhm Robert , Zettler Ingo , Wiysonge Charles Shey , Dubé Ève , Gagneur Arnaud , Botelho-Nevers Elisabeth , Gagneux-Brunon Amandine , Sivelä Jonas
Published: March 2020

Introduction

Published in 2018, the 5C scale is psychometrically validated to assess five psychological antecedents of vaccination (confidence, complacency, constraints, calculation and collective responsibility). The original version offers a validated English and German scale to assess these determinants with a short 5-item scale (1 item per antecedent) and a long 15-item scale (3 items per antecedent). This sample study protocol provides a step-by-step guidance for the process of adapting the 5C scale to another country, language or cultural context. Data obtained from the 5C scale can support developing, implementing and evaluating an intervention and monitoring of general vaccine acceptance and demand.

Methods and analysis

Phase 1 comprises the adaptation of the 5C scale including the translation and back translation of the antecedents, an expert evaluation of the antecedents and the identification of new antecedents as well as a pretest. Phase 2 involves the validation of the translated and potentially expanded scale including the assessment of reliability, construct and concurrent validity of all items of the scale. Code for data analysis is provided.

Ethics and dissemination

The University of Erfurt’s institutional review board provided ethical clearance (EV-201900416.2). The authors suggest and encourage publicly sharing all data obtained from the translated 5C scale (eg, on publication). The materials and the code for data analysis to support the process described in this protocol are available inhttps://osf.io/2agxe/. Sharing data on vaccine acceptance and demand is in the public and the scientific interest and will facilitate gaining a global overview of its current state and development over time. The authors of the original 5C scale are currently working on an online platform to facilitate publishing the data and to visualise the psychological antecedents across different countries.
Identifying and overcoming barriers to automated external defibrillator use by GoodSAM volunteer first responders in out-of-hospital cardiac arrest using the Theoretical Domains Framework and Behaviour Change Wheel: a qualitative study
Authors: Smith Christopher M , Griffiths Frances , Fothergill Rachael T , Vlaev Ivo , Perkins Gavin D
Published: March 2020

Objectives

GoodSAM is a mobile phone app that integrates with UK ambulance services. During a 999 call, if a call handler diagnoses cardiac arrest, nearby volunteer first responders registered with the app are alerted. They can give cardiopulmonary resuscitation (CPR) and/or use a public access automated external defibrillator (AED). We aimed to identify means of increasing AED use by GoodSAM first responders.

Methods

We conducted semistructured telephone interviews, using the Theoretical Domains Framework to identify and classify barriers to AED use. We analysed findings using the Capability, Opportunity, Motivation, Behaviour (COM-B) model and subsequently used the Behaviour Change Wheel to develop potential interventions to improve AED use.

Setting

London, UK.

Participants

GoodSAM first responders alerted in the previous 7 days about a cardiac arrest.

Results

We conducted 30 telephone interviews in two batches in July and October 2018. A public access AED was taken to scene once, one had already been attached on scene another time and three participants took their own AEDs when responding. Most first responders felt capable and motivated to use public access AEDs but were concerned about delaying CPR if they retrieved one and frustrated when arriving after the ambulance service. They perceived lack of opportunities due to unavailable and inaccessible AEDs, particularly out of hours. We subsequently developed 13 potential interventions to increase AED use for future testing.

Conclusions

GoodSAM first responders used AEDs occasionally, despite a capability and motivation to do so. Those operating volunteer first responder systems should consider our proposed interventions to improve AED use. Of particular clinical importance are: highlighting AED location and providing route/time estimates to the patient via the nearest AED. This would help single responders make appropriate decisions about AED retrieval. As AED collection may extend time to reach the patient, where there is sufficient density of potential responders, systems could send one responder to initiate CPR and another to collect an AED.
Experiences and views of patients, carers and healthcare professionals on using modems in domiciliary non-invasive ventilation (NIV): a qualitative study
Authors: Mansell Stephanie K , Kilbride Cherry , Wood Martin J , Gowing Francesca , Mandal Swapna
Published: March 2020

Background

Advances in technology means that domiciliary non-invasive ventilation (NIV) devices can be remotely monitored via modems in patients’ homes. Possible benefits and challenges of modem technology have yet to be established. This study explored the perspectives and experiences of patients, their carers and healthcare professionals (HCPs) on the addition of modem technology in managing home NIV.

Methods

A qualitative study using a combination of focus groups for HCPs and interviews for carers/patients was undertaken. 12 HCPs and 22 patients/carers participated. These focus groups and interviews were audio-recorded, transcribed verbatim and analysed thematically.

Results

Five main themes were identified. ‘Surveillance: a paradox of findings’: HCPs were concerned about unduly scrutinising patients’ lives, potentially impacting on HCP patient relationships. Conversely, patients welcomed modem monitoring and did not express concerns regarding invasion of privacy. ‘Sanctions’: HCPs reported the modem increased access to care and allowed appropriate assessment of ongoing treatment. ‘Complacency and ethics’: HCPs expressed concerns patients may become complacent in seeking help due to expectations of modem monitoring, as well as being concerned regarding the ethics of modems. There was a suggestion patients and carers' expectations of monitoring were different to that of clinical practice, resulting in complacency in some cases. ‘Increased time for patient focused care’: HCPs in the focus groups described a number of ways in which using modems was more efficient. ‘Confidence: can be improved with technology’: patients and carers were positive about the impact of the modems on their health and well-being, particularly their confidence.

Conclusion

HCPs expressed concerns about surveillance were not corroborated by patients, suggesting acceptability of remote monitoring. Data suggests a need for increased clarity to patients/carers regarding clinical practice relating to responsiveness to modem data. The issue of complacency requires further consideration. Modem technology was acceptable and considered a useful addition by HCPs, patients and carers.

Trial registration number

NCT03905382
Clinical, pathological and genetic spectrum in 89 cases of mitochondrial progressive external ophthalmoplegia
Authors: Rodríguez-López Claudia , García-Cárdaba Luis M. , Blázquez Alberto , Serrano-Lorenzo Pablo , Gutiérrez-Gutiérrez Gerardo , San Millán-Tejado Beatriz , Muelas Nuria , Hernández-Laín Aurelio , Vílchez Juan J. , Gutiérrez-Rivas Eduardo , Arenas Joaquín , Martín Miguel A. , Domínguez-González Cristina
Published: March 2020

Background

Mitochondrial progressive external ophthalmoplegia (PEO) encompasses a broad spectrum of clinical and genetic disorders. We describe the phenotypic subtypes of PEO and its correlation with molecular defects and propose a diagnostic algorithm.

Methods

Retrospective analysis of the clinical, pathological and genetic features of 89 cases.

Results

Three main phenotypes were found: ‘pure PEO’ (42%), consisting of isolated palpebral ptosis with ophthalmoparesis; Kearns-Sayre syndrome (10%); and ‘PEO plus’, which associates extraocular symptoms, distinguishing the following subtypes: : myopathic (33%), bulbar (12%) and others (3%). Muscle biopsy was the most accurate test, showing mitochondrial changes in 95%. Genetic diagnosis was achieved in 96% of the patients. Single large-scale mitochondrial DNA (mtDNA) deletion was the most frequent finding (63%), followed by multiple mtDNA deletions (26%) due to mutations in TWNK (n=8), POLG (n=7), TK2 (n=6) or RRM2B (n=2) genes, and point mtDNA mutations (7%). Three new likely pathogenic mutations were identified in the TWNK and MT-TN genes.

Conclusions

Phenotype–genotype correlations cannot be brought in mitochondrial PEO. Muscle biopsy should be the first step in the diagnostic flow of PEO when mitochondrial aetiology is suspected since it also enables the study of mtDNA rearrangements. If no mtDNA deletions are identified, whole mtDNA sequencing should be performed.
Isotope applications to soil science at the University of Alberta — an historical perspective
Authors: Feland Brett C. , Quideau Sylvie A.
Published: March 2020

For the past 70 yr, researchers in the Soil Science/Renewable Resources Department at the University of Alberta have used isotopes to study topics of ecological importance. This review highlights the soil isotope research conducted within our department over this time, including an historical overview of studies of interest. Analytical techniques and advances in instrumentation are discussed, focusing on the measurement of light stable isotope ratios (i.e., for C, H, N, S, and O) using isotope ratio mass spectrometry (IRMS). Early soil isotope work (1950–2000s) focused on agricultural soils and soil fertility issues. These studies included the use of radioactive isotopes such as 14C and 35S, and (or) artificially enriched stable isotopes including 15N-labelled fertilizers. More recently (2000–present), the scope of research widened to include natural-abundance stable isotope ratio studies as higher-sensitivity IRMS systems became more prevalent. Current isotope research topics include N biogeochemistry in natural and managed ecosystems, land management effects on greenhouse gas emissions, carbon cycling in northern landscapes, paleo-reconstruction in peatlands, carbon sequestration in boreal forests, and biodegradation of petroleum hydrocarbons. Further technological progress also enabled new techniques such as compound-specific IRMS analysis, including δ13C and δ2H measurements of soil n-alkanes and phospholipid fatty acids. In conclusion, current IRMS instrumentation presents unparalleled opportunities for multidisciplinary research to track carbon, plant nutrients, and pollutants as they move through soils.
Measuring the effect of node aggregation on community detection
Authors: Gandica Yérali , Decuyper Adeline , Cloquet Christophe , Thomas Isabelle , Delvenne Jean-Charles
Published: March 2020

Many times the nodes of a complex network, whether deliberately or not, are aggregated for technical, ethical, legal limitations or privacy reasons. A common example is the geographic position: one may uncover communities in a network of places, or of individuals identified with their typical geographical position, and then aggregate these places into larger entities, such as municipalities, thus obtaining another network. The communities found in the networks obtained at various levels of aggregation may exhibit various degrees of similarity, from full alignment to perfect independence. This is akin to the problem of ecological and atomic fallacies in statistics, or to the Modified Areal Unit Problem in geography.

We identify the class of community detection algorithms most suitable to cope with node aggregation, and develop an index for aggregability, capturing to which extent the aggregation preserves the community structure. We illustrate its relevance on real-world examples (mobile phone and Twitter reply-to networks). Our main message is that any node-partitioning analysis performed on aggregated networks should be interpreted with caution, as the outcome may be strongly influenced by the level of the aggregation.
Silicon-based on-chip all-optical wavelength conversion for two-dimensional hybrid multiplexing signals
Authors: Chen Baobao , Chen Junfan , Zhao Yi , Gao Shiming
Published: March 2020

A silicon-based all-optical wavelength conversion (AOWC) chip is proposed and designed for two-dimensional hybrid multiplexing signals, including mode-division multiplexing (MDM) and wavelength-division multiplexing (WDM). The AOWC chip is structured by mode (de) multiplexers and highly nonlinear silicon waveguide. Tapered directional coupler-based mode (de) multiplexers are used to convert between TE[Formula: see text] and TE[Formula: see text] modes for the signal and pump. The AOWC function is realized using the four-wave mixing (FWM) effect in the multimode silicon waveguide. The on-chip conversion efficiencies are simulated to be [Formula: see text]20.66[Formula: see text]dB and [Formula: see text]20.77[Formula: see text]dB for the TE[Formula: see text] and TE[Formula: see text] mode signals, respectively. The bandwidth is 68.2[Formula: see text]nm, which can support 170 MDM-WDM (85 wavelengths [Formula: see text] 2 modes) hybrid multiplexing channels.
THE ACTUATION SPECTRUM OF SPATIOTEMPORAL NETWORKS WITH POWER-LAW TIME DEPENDENCIES
Authors: CAO QI , RAMOS GUILHERME , BOGDAN PAUL , PEQUITO SÉRGIO
Published: March 2020

The ability to steer the state of a dynamical network towards a desired state within a time horizon is intrinsically dependent on the number of driven nodes considered, as well as the network’s topology. The trade-off between time-to-control and the minimum number of driven nodes is captured by the notion of the actuation spectrum (AS). We study the actuation spectra of a variety of artificial and real-world networked systems, modeled by fractional-order dynamics that are capable of capturing non-Markovian time properties with power-law dependencies. We find evidence that, in both types of networks, the actuation spectra are similar when the time-to-control is less or equal to about 1/5 of the size of the network. Nonetheless, for a time-to-control larger than the network size, the minimum number of driven nodes required to attain controllability in networks with fractional-order dynamics may still decrease in comparison with other networks with Markovian properties. These differences suggest that the minimum number of driven nodes can be used to determine the true dynamical nature of the network. Furthermore, such differences also suggest that new generative models are required to reproduce the actuation spectra of real fractional-order dynamical networks.
Effects of rotational submarine slump dynamics on tsunami genesis: new insight from idealized models and the 1929 Grand Banks event
Authors: Zengaffinen T. , Løvholt F. , Pedersen G. K. , Harbitz C. B.
Published: March 2020

Sediment slumps are known to have generated important tsunamis such as the 1998 Papua New Guinea (PNG) and the 1929 Grand Banks events. Tsunami modellers commonly use solid blocks with short run-out distances to simulate these slumps. While such methods have the obvious advantage of being simple to use, they offer little or no insight into physical processes that drive the events. The importance of rotational slump motion to tsunamigenic potential is demonstrated in this study by employing a viscoplastic landslide model with Herschel–Bulkley rheology. A large number of simulations for different material properties and landslide configurations are carried out to link the slump's deformation, rheology, its translational and rotational kinematics, to its tsunami genesis. The yield strength of the slump is shown to be the primary material property that determines the tsunami genesis. This viscoplastic model is further employed to simulate the 1929 Grand Banks tsunami using updated geological source information. The results of this case study suggest that the viscoplastic model can be used to simulate complex slump-induced tsunami. The simulations of the 1929 Grand Banks event also indicate that a pure slump mechanism is more tsunamigenic than a corresponding translational landslide mechanism.
High-Precision 5DoF Tracking and Visualization of Catheter Placement in EVD of the Brain Using AR
Authors: Sun Xuetong , Murthi Sarah B. , Schwartzbauer Gary , Varshney Amitabh
Published: March 2020

External ventricular drainage (EVD) is a high-risk medical procedure that involves inserting a catheter inside a patient’s skull, through the brain and into a ventricle, to drain cerebrospinal fluid and thus relieve elevated intracranial pressure. Once the catheter has entered the skull, its tip cannot be seen. The neurosurgeon has to imagine its location inside the cranium and direct it toward the ventricle using only anatomic landmarks. The EVD catheter is thin and thus hard to track using infra-red depth sensors. Traditional optical tracking using fiducial or other markers inevitably changes the shape or weight of the medical instrument. We present an augmented reality system that depicts the catheter for EVD and a new technique to precisely track the catheter inside the skull. Our technique uses a new linear marker detection method that requires minimal changes to the catheter and is well suited for tracking other thin medical devices that require high-precision tracking.
Synthesis of Flexible Accelerators for Early Adoption of Ring-LWE Post-quantum Cryptography
Authors: Nejatollahi Hamid , Valencia Felipe , Banik Subhadeep , Regazzoni Francesco , Cammarota Rosario , Dutt Nikil
Published: March 2020

The advent of the quantum computer makes current public-key infrastructure insecure. Cryptography community is addressing this problem by designing, efficiently implementing, and evaluating novel public-key algorithms capable of withstanding quantum computational power. Governmental agencies, such as NIST, are promoting standardization of quantum-resistant algorithms that is expected to run for 7 years. Several modern applications must maintain permanent data secrecy; therefore, they ultimately require the use of quantum-resistant algorithms. Because algorithms are still under scrutiny for eventual standardization, the deployment of the hardware implementation of quantum-resistant algorithms is still in early stages.

In this article, we propose a methodology to design programmable hardware accelerators for lattice-based algorithms, and we use the proposed methodology to implement flexible and energy efficient post-quantum cache-based accelerators for
NewHope
,
Kyber
,
Dilithium
, Key Consensus from Lattice (
KCL
), and
R.EMBLEM
submissions to the NIST standardization contest.

To the best of our knowledge, we propose the first efficient domain-specific, programmable cache-based accelerators for lattice-based algorithms. We design a single accelerator for a common kernel among various schemes with different kernel sizes, i.e., loop count, and data types. This is in contrast to the traditional approach of designing one special purpose accelerators for each scheme.

We validate our methodology by integrating our accelerators into an HLS-based SoC infrastructure based on the X86 processor and evaluate overall performance. Our experiments demonstrate the suitability of the approach and allow us to collect insightful information about the performance bottlenecks and the energy efficiency of the explored algorithms. Our results provide guidelines for hardware designers, highlighting the optimization points to address for achieving the highest energy minimization and performance increase. At the same time, our proposed design allows us to specify and execute new variants of lattice-based schemes with superior energy efficiency compared to the main application processor without changing the hardware acceleration platform. For example, we manage to reduce the energy consumption up to 2.1× and energy-delay product (EDP) up to 5.2× and improve the speedup up to 2.5×.
FFConv
Authors: Ahmad Afzal , Pasha Muhammad Adeel
Published: March 2020

Image classification is known to be one of the most challenging problems in the domain of computer vision. Significant research is being done on developing systems and algorithms improving accuracy, performance, area, and power consumption for related problems. Convolutional Neural Networks (CNNs) have shown to give outstanding accuracies for problems such as image classification, object detection, and semantic segmentation. While CNNs are pioneering the development of high accuracy systems, their excessive computational complexity presents a barrier for a more permeated deployment. Although Graphical Processing Units (GPUs), due to their massively parallel architecture, have shown to give performance orders of magnitude better than general purpose processors, the former are limited by their high power consumption and generality. Consequently, Field Programmable Gate Arrays (FPGAs) are being explored to implement CNN architectures, as they also provide massively parallel logic resources but with a relatively lower power consumption than GPUs. In this article, we present FFConv, an efficient FPGA-based fast convolutional layer accelerator for CNNs. We design a pipelined, high-throughput convolution engine based on the Winograd minimal filtering (also called Fast Convolution) algorithms for computing the convolutional layers of three popular CNN architectures: VGG16, Alexnet, and Shufflenet. We implement our accelerator on a Virtex-7 FPGA platform where we exploit the computational parallelization to the maximum while exploring optimizations aimed at improving performance. The resultant design loses only 0.43%, 0.47%, and 0.61% Top-1 classification accuracy for VGG16, Alexnet, and Shufflenet-v1, respectively, while significantly improving throughput, resource, and power efficiency compared to previous state-of-the-art designs.
Compiling for the Worst Case
Authors: Luppold Arno , Oehlert Dominic , Falk Heiko
Published: March 2020

Modern embedded hard real-time systems feature multiple tasks running on multiple processing cores. Schedulability analysis of such systems is usually performed on an abstract system level with each task being represented as a black box with fixed timing properties. If timing constraints are violated, then optimizing the system on a code-level to achieve schedulability is a tedious task.

To tackle this issue, we propose an extension to the WCET-aware C Compiler framework WCC. We integrated an optimization framework based on Integer-Linear Programming into the WCC that is able to optimize a multi-core system with multiple tasks running on each core with regards to its schedulability. We evaluate the framework by providing two approaches on a schedulability aware static Scratchpad Memory (SPM) allocation: one based on Integer-Linear Programming (ILP) and one based on a genetic algorithm.
Voltammetric Determination of Trace Zn(II) in Seawater on a Poly(sodium 4-styrenesulfonate)/Wrinkled Reduced Graphene Oxide Composite Modified Electrode
Authors: Ma Su , Wei Hong , Pan Dawei , Pan Fei , Wang Chenchen , Kang Qi
Published: March 2020

In this study, a novel poly(sodium 4-styrenesulfonate)/wrinkled reduced graphene oxide composite modified glassy carbon electrode (GCE) was prepared successfully. This electrode was used for sensitive detection of trace Zn(II) in seawater by differential pulse voltammetry (DPV). The morphology and electrochemical property of the modified electrode was characterized using scanning electron microscopy (SEM), energy dispersive spectrometry (EDS), Fourier Transform Infrared (FT-IR) spectroscopy, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Results showed that the wrinkled graphene layer formed on the electrode surface could significantly promote the electron-transfer and increase the specific surface area of the electrode. Additionally, the poly(sodium 4-styrenesulfonate) film could also effectively improve the stability of the modified electrode, absorb cations and repel anions on the electrode surface. Under the optimal conditions, the linear response to Zn(II) obtained at the modified electrode, was in the range of 5 to 720 nM with a detection limit of 1.67 nM (S/N = 3). Practical applicability of this modified electrode was successfully tested for the determination of Zn(II) in seawater samples with satisfactory results.
Hydrostatic pressure regulates CYP1A2 expression in human hepatocytes via a mechanosensitive aryl hydrocarbon receptor-dependent pathway
Authors: Burton Lewis , Scaife Paula , Paine Stuart W. , Mellor Howard R. , Abernethy Lynn , Littlewood Peter , Rauch Cyril
Published: March 2020

Approximately 75% of xenobiotics are primarily eliminated through metabolism; thus the accurate scaling of metabolic clearance is vital to successful drug development. Yet, when data is scaled from in vitro to in vivo, hepatic metabolic clearance, the primary source of metabolism, is still commonly underpredicted. Over the past decades, with biophysics used as a key component to restore aspects of the in vivo environment, several new cell culture settings have been investigated to improve hepatocyte functionalities. Most of these studies have focused on shear stress, i.e., flow mediated by a pressure gradient. One potential conclusion of these studies is that hepatocytes are naturally “mechanosensitive,” i.e., they respond to a change in their biophysical environment. We demonstrate that hepatocytes also respond to an increase in hydrostatic pressure that, we suggest, is directly linked to the lobule geometry and vessel density. Furthermore, we demonstrate that hydrostatic pressure improves albumin production and increases cytochrome P-450 (CYP) 1A2 expression levels in an aryl hydrocarbon-dependent manner in human hepatocytes. Increased albumin production and CYP function are commonly attributed to the impacts of shear stress in microfluidic experiments. Therefore, our results highlight evidence of a novel link between hydrostatic pressure and CYP metabolism and demonstrate that the spectrum of hepatocyte mechanosensitivity might be larger than previously thought.
Hypoxic activation of glucose-6-phosphate dehydrogenase controls the expression of genes involved in the pathogenesis of pulmonary hypertension through the regulation of DNA methylation
Authors: Joshi Sachindra Raj , Kitagawa Atsushi , Jacob Christina , Hashimoto Ryota , Dhagia Vidhi , Ramesh Amrit , Zheng Connie , Zhang Hui , Jordan Allan , Waddell Ian , Leopold Jane , Hu Cheng-Jun , McMurtry Ivan F. , D’Alessandro Angelo , Stenmark Kurt R. , Gupte Sachin A.
Published: March 2020

Metabolic reprogramming is considered important in the pathogenesis of the occlusive vasculopathy observed in pulmonary hypertension (PH). However, the mechanisms that link reprogrammed metabolism to aberrant expression of genes, which modulate functional phenotypes of cells in PH, remain enigmatic. Herein, we demonstrate that, in mice, hypoxia-induced PH was prevented by glucose-6-phosphate dehydrogenase deficiency (G6PDDef), and further show that established severe PH in Cyp2c44−/−mice was attenuated by knockdown with G6PD shRNA or by G6PD inhibition with an inhibitor (N-ethyl-N′-[(3β,5α)-17-oxoandrostan-3-yl]urea, NEOU). Mechanistically, G6PDDef, knockdown and inhibition in lungs: 1) reduced hypoxia-induced changes in cytoplasmic and mitochondrial metabolism, 2) increased expression of Tet methylcytosine dioxygenase 2 ( Tet2) gene, and 3) upregulated expression of the coding genes and long noncoding (lnc) RNA Pint, which inhibits cell growth, by hypomethylating the promoter flanking region downstream of the transcription start site. These results suggest functional TET2 is required for G6PD inhibition to increase gene expression and to reverse hypoxia-induced PH in mice. Furthermore, the inhibitor of G6PD activity (NEOU) decreased metabolic reprogramming, upregulated TET2 and lncPINT, and inhibited growth of control and diseased smooth muscle cells isolated from pulmonary arteries of normal individuals and idiopathic-PAH patients, respectively. Collectively, these findings demonstrate a previously unrecognized function for G6PD as a regulator of DNA methylation. These findings further suggest that G6PD acts as a link between reprogrammed metabolism and aberrant gene regulation and plays a crucial role in regulating the phenotype of cells implicated in the pathogenesis of PH, a debilitating disorder with a high mortality rate.
Neutrophil extracellular traps activate IL-8 and IL-1 expression in human bronchial epithelia
Authors: Hudock Kristin M. , Collins Margaret S. , Imbrogno Michelle , Snowball John , Kramer Elizabeth L. , Brewington John J. , Gollomp Kandace , McCarthy Cormac , Ostmann Alicia J. , Kopras Elizabeth J. , Davidson Cynthia R. , Srdiharan Anusha , Arumugam Paritha , Sengupta Shaon , Xu Yan , Worthen G. Scott , Trapnell Bruce C. , Clancy John Paul
Published: March 2020

Neutrophil extracellular traps (NETs) provide host defense but can contribute to the pathobiology of diverse human diseases. We sought to determine the extent and mechanism by which NETs contribute to human airway cell inflammation. Primary normal human bronchial epithelial cells (HBEs) grown at air-liquid interface and wild-type (wt)CFBE41o- cells (expressing wtCFTR) were exposed to cell-free NETs from unrelated healthy volunteers for 18 h in vitro. Cytokines were measured in the apical supernatant by Luminex, and the effect on the HBE transcriptome was assessed by RNA sequencing. NETs consistently stimulated IL-8, TNF-α, and IL-1α secretion by HBEs from multiple donors, with variable effects on other cytokines (IL-6, G-CSF, and GM-CSF). Expression of HBE RNAs encoding IL-1 family cytokines, particularly IL-36 subfamily members, was increased in response to NETs. NET exposure in the presence of anakinra [recombinant human IL-1 receptor antagonist (rhIL-1RA)] dampened NET-induced changes in IL-8 and TNF-α proteins as well as IL-36α RNA. rhIL-36RA limited the increase in expression of proinflammatory cytokine RNAs in HBEs exposed to NETs. NETs selectively upregulate an IL-1 family cytokine response in HBEs, which enhances IL-8 production and is limited by rhIL-1RA. The present findings describe a unique mechanism by which NETs may contribute to inflammation in human lung disease in vivo. NET-driven IL-1 signaling may represent a novel target for modulating inflammation in diseases characterized by a substantial NET burden.
Depletion of microRNA-451 in response to allergen exposure accentuates asthmatic inflammation by regulating Sirtuin2
Authors: Chung Sangwoon , Lee Yong Gyu , Karpurapu Manjula , Englert Joshua A. , Ballinger Megan N. , Davis Ian C. , Park Gye Young , Christman John W.
Published: March 2020

The incidence of asthma has increased from 5.5% to near 8% of the population, which is a major health concern. The hallmarks of asthma include eosinophilic airway inflammation that is associated with chronic airway remodeling. Allergic airway inflammation is characterized by a complex interplay of resident and inflammatory cells. MicroRNAs (miRNAs) are small noncoding RNAs that function as posttranscriptional modulators of gene expression. However, the role of miRNAs, specifically miR-451, in the regulation of allergic airway inflammation is unexplored. Our previous findings showed that oxidant stress regulates miR-451 gene expression in macrophages during an inflammatory process. In this paper, we examined the role of miR-451 in regulating macrophage phenotype using an experimental poly-allergenic murine model of allergic airway inflammation. We found that miR-451 contributes to the allergic induction of CCL17 in the lung and plays a key role in proasthmatic macrophage activation. Remarkably, administration of a Sirtuin 2 (Sirt2) inhibitor diminished alternate macrophage activation and markedly abrogated triple-allergen [dust mite, ragweed, Aspergillus fumigatus (DRA)]-induced lung inflammation. These data demonstrate a role for miR-451 in modulating allergic inflammation by influencing allergen-mediated macrophages phenotype.
Olfaction contributes to the learned avidity for glucose relative to fructose in mice
Authors: Glendinning John I. , Maleh Jennifer , Ortiz Gabriella , Touzani Khalid , Sclafani Anthony
Published: March 2020

When offered glucose and fructose solutions, rodents consume more glucose solution because it produces stronger postoral reinforcement. Intake of these sugars also conditions a higher avidity for glucose relative to fructose. We asked which chemosensory cue mediates the learned avidity for glucose. We subjected mice to 18 days of sugar training, offering them 0.3, 0.6, and 1 M glucose and fructose solutions. Before and after training, we measured avidity for 0.3 and 0.6 M glucose and fructose in brief-access lick tests. First, we replicated prior work in C57BL/6 mice. Before training, the mice licked at a slightly higher rate for 0.6 M fructose; after training, they licked at a higher rate for 0.6 M glucose. Second, we assessed the necessity of the glucose-specific ATP-sensitive K+(KATP) taste pathway for the learned avidity for glucose, using mice with a nonfunctional KATPchannel [regulatory sulfonylurea receptor (SUR1) knockout (KO) mice]. Before training, SUR1 KO and wild-type mice licked at similar rates for 0.6 M glucose and fructose; after training, both strains licked at a higher rate for 0.6 M glucose, indicating that the KATPpathway is not necessary for the learned discrimination. Third, we investigated the necessity of olfaction by comparing sham-treated and anosmic mice. The mice were made anosmic by olfactory bulbectomy or ZnSO4treatment. Before training, sham-treated and anosmic mice licked at similar rates for 0.6 M glucose and fructose; after training, sham-treated mice licked at a higher rate for 0.6 M glucose, whereas anosmic mice licked at similar rates for both sugars. This demonstrates that olfaction contributes significantly to the learned avidity for glucose.
Phenolic Profile, Antioxidant Activity, and Enzyme Inhibitory Properties ofLimonium delicatulum(Girard) Kuntze andLimonium quesadenseErben
Authors: Ruiz-Riaguas A. , Zengin G. , Sinan K.I. , Salazar-Mendías C. , Llorent-Martínez E.J.
Published: March 2020

In this work, we report the phytochemical composition and bioactive potential of methanolic and aqueous extracts of leaves fromLimonium delicatulum(Girard) Kuntze andLimonium quesadenseErben. The characterization and quantitation of individual phytochemicals were performed with liquid chromatography with diode array and electrospray-tandem mass spectrometry detection. Myricetin glycosides were abundant inL. delicatulum, whereasL. quesadensewas rich in gallo(epi)catechin-O-gallate. Total phenolics, flavonols, and flavonoids were assayed with conventional methods. Antioxidant and radical scavenging assays (phosphomolybdenum, DPPH, ABTS, CUPRAC, FRAP, and metal chelating activity), as well as enzyme inhibitory assays (acetylcholinesterase, butyrylcholinesterase, tyrosinase, amylase, glucosidase, and lipase), were performed to evaluate the potential bioactivity. The methanolic extracts of both species presented higher phenolic content and bioactivity than the aqueous extracts. Overall,L. quesadenseextracts exhibited the most potent activity for most assays, representing a potential source of bioactive compounds for the pharmaceutical and food industries.
Experimental-Based Optimization of Injection Molding Process Parameters for Short Product Cycle Time
Authors: Mukras Saad M. S.
Published: March 2020

This paper presents a framework for optimizing injection molding process parameters for minimum product cycle time subjected to constraints on the product defects. Two product defects, namely, volumetric shrinkage and warpage, as well as seven process parameters including injection speed, injection pressure, cooling time, packing pressure, mold temperature, packing time, and melt temperature, were considered. Injection molding experiments were conducted on specifically chosen test points and results were used to compute the volumetric shrinkage and warpage (at each test point). Thereafter, three relationships between the product cycle time (one relationship), the two product defects (two relationships), and the injection molding parameters were constructed using the kriging technique. An optimization problem to minimize the product cycle time (described by the first relationship) subject to constraints on the product defects (described by the latter two relationships) was then formulated. A combination set of points between the lower and upper extreme values of acceptable product defect was generated to serve as constraints for the two product defects. The optimization problem was then solved using the Fmincon function, available in the Matlab optimization toolbox. A plot of the optimization results revealed an appreciable tradeoff between the cycle time and the two product defects. To validate the optimization, an additional injection molding experiment was conducted for one of the optimization results. Results from the additional experiment showed reasonably close agreement with simulation optimization results differing in the cycle time, the warpage and volumetric shrinkage by 6.7%, 3.2%, and 8%, respectively.
Earthquake Response Analysis of Tall Reinforced Concrete Chimneys considering Eccentricity
Authors: Jiang Yingchun , Liu Tielin , Bai Yikui
Published: March 2020

A numerical algorithm is presented to analyze earthquake response of tall reinforced concrete (RC) chimneys based on stick multidegree-of-freedom models. The algorithm considers the eccentricity phenomena between spatial discrete nodes and corresponding centroids of investigated lumps. The spatial discrete segments of the chimney are used to construct the investigated lumps. The equations of dynamic equilibrium of the investigated lumps are derived, and the numerical calculation procedure is implemented. Phenomena of eccentricity are studied for 150 m and 210 m RC chimneys. Seismic stresses and effects of vertical ground motion for the two chimneys are also studied. Numerical results show that the tensile and compressive stresses of the seismic control cross sections of the chimneys may increase under the actions of several specific earthquake waves by considering existing eccentricities. The effect of eccentricity on the earthquake responses of tall RC chimney should be considered, and stresses caused by vertical ground motion should not be neglected to obtain accurate earthquake response of chimneys.
Cross‐Cultural Adaptation and Validation of the Simplified Chinese Version of the Lower Extremity Functional Scale
Authors: Zhang Chuanxin , Liu Yaqun , Yuan Shuai , Yang Tianbo , Gao Yuan , Zhu Chao , Ding Zheru
Published: March 2020

Purpose. The purpose of this study was to cross‐culturally adapt and validate the Simplified Chinese version of the Lower Extremity Functional Scale (SC‐LEFS). Methods. The original English version of the Lower Extremity Functional Scale was translated and cross‐culturally adapted into Simplified Chinese according to international guidelines. The SC‐LEFS and 36‐Item Short‐Form Health Survey were administered to 213 patients with lower extremity musculoskeletal disorders. Psychometric properties including internal consistency, test‐retest reliability, content validity, and construct validity were tested. Results. There were no floor or ceiling effects for the SC‐LEFS. The scale had high values for internal consistency (Cronbach α = 0.97) and test‐retest reliability (intraclass correlation coefficient = 0.97). Corrected item‐total correlations for every item ranged from 0.67 to 0.89. And the item‐level content validity index (I‐CVI) for each item ranged from 0.78 to 1.00. Principal component analysis revealed a one‐factor structure. Nine of ten prior hypotheses were confirmed, which further supports good construct validity within the SC‐LEFS. Conclusion. The SC‐LEFS has high internal consistency, good test‐retest reliability and content validity, convergent construct validity, and a one‐factor structure. Thus, it could be regarded as a reliable and valid tool to assess activity limitations in Chinese patients with lower extremity musculoskeletal disorders.
Research on Multi-Time-Delay Gene Regulation Network Based on Fuzzy Label Propagation
Authors: Li Haigang , Zhang Qian , Li Ming
Published: March 2020

In view of time delay existing in gene regulation, by using the analysis idea and methods of complex network, this paper proposes a multi-time-delay gene regulation network analysis method based on the fuzzy label propagation. The algorithm takes the relative change trend coefficient, the correlation coefficient, and the mutual information as the similarity measurement indexes for the gene pair, fully reflecting the correlation of gene pairs and simultaneously obtaining the gene regulation relationship and the time delay through the fuzzy label propagation algorithm of the semisupervised learning. Experimental results of the cell cycle-regulated genes of yeast show that the proposed construction method of GRN can not only correctly select potential regulation genes but also provide details about the gene regulator model, thereby more accurately constructing gene regulation network.
Channel Compression Optimization Oriented Bus Passenger Object Detection
Authors: Zhang Shuo , Wu Yanxia , Men Chaoguang , Ren Ning , Li Xiaosong
Published: March 2020

Bus passenger flow information can facilitate scientific dispatching plans, which is essential to decision making and operation performance evaluation. Real-time acquisition of bus passenger flow information is an indispensable part for bus intellectualization. The method of passenger flow statistics in bus video monitoring scene based on deep convolution neural network can provide rich information for passenger flow statistics. In order to adapt to the real scenario of mobile and embedded devices on buses, and to consider the bandwidth limitation, this paper uses a lightweight network model M7, which is suitable for the vehicle system. Based on the classic network model tiny YOLO, the model is optimized by a depthwise separable convolution method. The optimized network model M7 reduces the number of parameters and improves the detection speed, while maintaining a low loss in detection accuracy. As such, the network model M7 is compressed and further optimized by removing redundant channels. The experimental results show that the detection speed of the network model target recognition after channel compression is 40%, which is faster than the precious channel compression on the premise of ensuring detection.