bluuebunny/crossref_metadata_2025_split huggingface dataset:
Numerical Prediction to Effects of Manifolds Configuration on Flow in Swirling Flow Exhaust Pipe System
Authors: Cao L. , Liu Huimeng , Liu Yongchang , Huang Q. 
Published: March 2020

Abstract
Compared to conventional Modular Pulse Converter (MPC) system with the typical structure of symmetrical T-junction, a novel swirling flow exhaust pipe system has its advantages especially in reducing collision loss of high-speed gases near junction and having interference-free scavenging and higher energy utilization. The initial junction configuration in swirling flow exhaust system was determined with reference to T-junction in MPC. In order to analyze and compare its flow behaviors, 3D-flow fields of manifold-type junctions in swirling flow exhaust pipe system were performed with the revised KIVA II code. A non-linear algebraic Relynolds stress (ASM) model was considered in this study and comparisons were made with the standard κ–ε turbulence model. For many cases of parametric studies considered, it is found that junction’s configurations have significant influence on the velocity distribution and swirl intensity. 30° swirling flow junction is found to be unreasonable, 45° junction with oblate rectangular type contraction area is recommended in swirl flow pipe exhaust pipe system.
3D-Particle Dynamic Analyzer (PDA) measurement was introduced to measure the axial and tangential velocity components of swirling flow in main pipe. Comparisons of computed and measured velocities reveal that model predictions are in generally reasonable agreement with the measurements, indicating validity of computational code and reliability of prediction model.
The Future of Magnetic Recording
Authors: Wood Roger 
Published: March 2020

Abstract
Magnetic information storage technology has made astounding progress since its invention over a hundred years ago. For the last several years, storage packing densities in hard disk drives have doubled every year! This frantic pace is expected to soon slow because of the some very fundamental limits that are becoming increasingly evident in the technology. Conventional magnetic recording technology is expected to ultimately reach densities of several hundred Gigabits per square inch and data-rates of a few Gigabits/s (current products are ∼25 Gbit/sq.in. and over 0.5 Gbit/s). We examine the key limiting factors and then try to develop a consistent geometry and set of material properties that could support a density close to one Terabit per square inch. Finally we speculate about the external characteristics of a small hard disk drive that would store one Terabyte of information [1].
A New Finite-Element Based Suspension Model Including Displacement Limiters for Load/Unload Simulations
Authors: Weissner Stefan , Zander Uwe , Talke Frank E. 
Published: March 2020

Abstract
A new beam suspension model for load/unload simulations of magnetic hard disk drive sliders is presented. The model is applicable to the load/unload process as well as to the dynamic flying behavior of the slider on the disk. Suspension and gimbal are modeled with C1 continuous beam elements. The roll degree of freedom of the slider is decoupled from spacing and pitch. The numerical implementation of the model is described. Loading and unloading of a typical subambient pressure type slider is presented.
Self-Adjusting Flying Height Sliders for Operation in the Near-Contact Recording Regime
Authors: Hanchi J. , Serpe C. I. , Qian W. , Boutaghou Z. 
Published: March 2020

Abstract
The viability of the concept of “self-adjusting flying height” for giant magneto-resistive (GMR) recording heads designed for operation in the near-contact recording regime (flying heights below 10 nm) is demonstrated experimentally. In the present context, the realization of the latter concept relies upon the micro-texturing — production of deterministic, spatially coherent surface topography patterns — of potential contact regions on the recording heads. Through the manipulation of micro-texture pattern feature geometry and spatial distribution, the apparent area of contact, or bearing area ratio, in such regions can be varied in a controllable manner. The latter affords a means to enable the transition of head-disc interfaces (HDI) initially operating under interference contact conditions, into the fly regime without impairing the mechanical and electrical integrity of the HDI. Experimental results attesting to the feasibility of the concept self-adjusting flying height for GMR heads are presented and discussed. Practical aspects associated with the implementation of the latter concept are also discussed.
Head-Disk Interface Issues for Near Contact Recording
Authors: Wang R. H. , Raman V. , Nayak U. V. 
Published: March 2020

Abstract
As the magnetic recording density increases towards hundreds of Gb/in2, both the magnetic spacing and head-disk clearance decrease to &lt; 10 nm. By one estimate, the magnetic spacing for 1 Tb/in2 is about 6 nm and the read width is ∼ 30 nm. There are at least two different approaches to achieving this. The first one is an extension of the traditional flying interface and the second is contact recording. In the former case one needs to be concerned about maintaining adequate clearance both at sea level and at higher elevation whereas in the latter case the wear and corrosion of the heads and disks may pose major challenges.
In the flying regime, an accelerated test to assess the relative integrity of the head-disk interface is described here. This is accomplished by monitoring the acoustic emission, capacitance or friction between the head and the disk as the ambient pressure is reduced. The pressure at which an abrupt change in the above signals takes place is called take-off pressure (TOP). This is also known as altitude avalanche measurement. With this method it is possible to compare different disk and head designs at the full velocity of the slider. We present results correlating the TOP with disk roughness and the influence of disk lubricant.
An example of how head-disk interference takes place in a disk drive will be given for an experimental 10 nm flying slider. The effects of radial flying height profile, take-off height of the disk, and the disk curvature on mechanical spacing are presented. The results of changes occurring on the air bearing surface and the disks after long term flyability test are discussed.
“We Took Pictures”: Children’s Meaning-Making in Physical Education
Authors: Ní Chróinín Déirdre , Coulter Maura , Parker Melissa 
Published: March 2020

Purpose: Studying learning in primary physical education is complex and largely practical and embodied; not only involving the child, but also closely linking the lesson context. The aim of this paper is to understand teaching and learning in primary physical education through the use of photo-diaries.Method: Participants were children (n = 38) and their teachers (n = 2) from two Irish primary schools across a 6-week period. Data included children’s photo-diaries, photo-elicitation focus group interviews with the children, and interviews with their teachers.Results: Results highlight that photo-diaries supported children’s meaning-making processes about their learning, highlighting a variety of meanings grounded in the centrality of the body as performance of learning.Discussion and Conclusion: The value of photo-based approaches with primary school children to access their meaning-making and influences on their understandings is highlighted.
Decreased risk of colorectal cancer among patients with type 2 diabetes receiving Chinese herbal medicine: a population-based cohort study
Authors: Jhang Jing-Siang , Livneh Hanoch , Yang Shu-Yi , Huang Hui-Ju , Chan Michael W Y , Lu Ming-Chi , Yeh Chia-Chou , Tsai Tzung-Yi 
Published: March 2020

ObjectivesPatients with type 2 diabetes have a higher risk of colorectal cancer (CRC), but whether Chinese herbal medicines (CHMs) can reduce this risk is unknown. This study investigated the effect that CHMs have on CRC risk in patients with type 2 diabetes.Research design and methodsThis cohort study used the Taiwanese National Health Insurance Research Database to identify 54 744 patients, newly diagnosed with type 2 diabetes, aged 20–70 years, who were receiving treatment between 1998 and 2007. From this sample, we randomly selected 14 940 CHMs users and 14 940 non-CHMs users, using propensity scores matching. All were followed through 2012 to record CRC incidence. Cox proportional hazards regression was used to compute the hazard ratio (HR) of CRC by CHMs use.ResultsDuring follow-up, 235 CHMs users and 375 non-CHMs users developed CRC, incidence rates of 1.73% and 2.47% per 1000 person-years, respectively. CHM users had a significantly reduced risk of CRC compared with non-CHM users (adjusted HR=0.71; 95% CI 0.60 to 0.84). The greatest effect was in those receiving CHMs for more than 1 year. Huang-Qin, Xue-Fu-Zhu-Yu-Tang, Shu-Jing-Huo-Xue-Tang, Liu-Wei-Di-Huang-Wan, Ji-Sheng-Shen-Qi-Wan, Gan-Lu-Yin, Shao-Yao-Gan-Cao-Tang and Ban-Xia-Xie-Xin-Tang were significantly associated with lower risk of CRC.ConclusionIntegrating CHMs into the clinical management of patients with type 2 diabetes may be beneficial in reducing the risk of CRC.
Assessing the effect of closed-loop insulin delivery from onset of type 1 diabetes in youth on residual beta-cell function compared to standard insulin therapy (CLOuD study): a randomised parallel study protocol
Authors: Boughton Charlotte , Allen Janet M , Tauschmann Martin , Hartnell Sara , Wilinska Malgorzata E , Musolino Gianluca , Acerini Carlo L , Dunger Professor David , Campbell Fiona , Ghatak Atrayee , Randell Tabitha , Besser Rachel , Trevelyan Nicola , Elleri Daniela , Northam Elizabeth , Hood Korey , Scott Eleanor , Lawton Julia , Roze Stephane , Sibayan Judy , Kollman Craig , Cohen Nate , Todd John , Hovorka Roman 
Published: March 2020

IntroductionManagement of newly diagnosed type 1 diabetes (T1D) in children and adolescents is challenging for patients, families and healthcare professionals. The objective of this study is to determine whether continued intensive metabolic control using hybrid closed-loop (CL) insulin delivery following diagnosis of T1D can preserve C-peptide secretion, a marker of residual beta-cell function, compared with standard multiple daily injections (MDI) therapy.Methods and analysisThe study adopts an open-label, multicentre, randomised, parallel design, and aims to randomise 96 participants aged 10–16.9 years, recruited within 21 days of diagnosis with T1D. Following a baseline mixed meal tolerance test (MMTT), participants will be randomised to receive 24 months treatment with conventional MDI therapy or with CL insulin delivery. A further 24-month optional extension phase will be offered to all participants to continue with the allocated treatment. The primary outcome is the between group difference in area under the stimulated C-peptide curve (AUC) of the MMTT at 12 months post diagnosis. Analyses will be conducted on an intention-to-treat basis. Key secondary outcomes are between group differences in time spent in target glucose range (3.9–10 mmol/L), glycated haemoglobin (HbA1c) and time spent in hypoglycaemia (<3.9 mmol/L) at 12 months. Secondary efficacy outcomes include between group differences in stimulated C-peptide AUC at 24 months, time spent in target glucose range, glucose variability, hypoglycaemia and hyperglycaemia as recorded by periodically applied masked continuous glucose monitoring devices, total, basal and bolus insulin dose, and change in body weight. Cognitive, emotional and behavioural characteristics of participants and parents will be evaluated, and a cost–utility analysis performed to support adoption of CL as a standard treatment modality following diagnosis of T1D.Ethics and disseminationEthics approval has been obtained from Cambridge East Research Ethics Committee. The results will be disseminated by peer-reviewed publications and conference presentations.Trial registration numberNCT02871089; Pre-results.
The effects of sildenafil on ciliary beat frequency in patients with pulmonary non-tuberculous mycobacteria disease: phase I/II trial
Authors: Fowler Cedar , Wu Un-In , Shaffer Robyn , Smith Caroline , Barnhart Lisa , Bryant Clare , Olivier Kenneth , Holland Steven M 
Published: March 2020

RationalePulmonary non-tuberculous mycobacterial (PNTM) disease has increased over the past several decades, especially in older women. Abnormal mucociliary clearance and abnormal nasal nitric oxide (nNO) have been associated with PNTM disease in other patient cohorts. Mucociliary clearance can be affected by NO-cyclic guanosine monophosphate signalling and, therefore, modulation of the pathway may be possible with phosphodiesterase inhibitors such as sildenafil as a novel therapeutic approach.ObjectiveTo define ex vivo characteristics of PNTM disease affected by sildenafil.MethodsSubjects with PNTM infections were recruited into an open-label dose-escalation trial of sildenafil. Laboratory measurements and mucociliary measurements—ciliary beat frequency, nNO and 24-hour sputum production—were collected throughout the study period. Patients received sildenafil daily during the study period, with escalation from 20 to 40 mg three times per day.Measurements and main resultsIncreased ciliary beat frequency occurred after a single dose of 40 mg sildenafil and after extended dosing of 40 mg sildenafil. The increase ciliary beat frequency was not seen with 20 mg sildenafil dosing. There were no changes in sputum production, nNO production, Quality of Life-Bronchiectasis-NTM module (QOL-B-NTM) questionnaire or the St George’s Respiratory Questionnaire during the study period.ConclusionSildenafil, 40 mg, increased ciliary beat frequency acutely as well as with extended administration.
Cardiovascular risk factors and the risk of major adverse limb events in patients with symptomatic cardiovascular disease
Authors: Hageman Steven H J , de Borst Gert Jan , Dorresteijn Johannes A N , Bots Michiel L , Westerink Jan , Asselbergs Folkert W , Visseren Frank L J 
Published: March 2020

AimTo determine the relationship between non-high-density lipoprotein cholesterol (non-HDL-c), systolic blood pressure (SBP) and smoking and the risk of major adverse limb events (MALE) and the combination with major adverse cardiovascular events (MALE/MACE) in patients with symptomatic vascular disease.MethodsPatients with symptomatic vascular disease from the Utrecht Cardiovascular Cohort - Secondary Manifestations of ARTerial disease (1996–2017) study were included. The effects of non-HDL-c, SBP and smoking on the risk of MALE were analysed with Cox proportional hazard models stratified for presence of peripheral artery disease (PAD). MALE was defined as major amputation, peripheral revascularisation or thrombolysis in the lower limb.ResultsIn 8139 patients (median follow-up 7.8 years, IQR 4.0–11.8), 577 MALE (8.7 per 1000 person-years) and 1933 MALE/MACE were observed (29.1 per 1000 person-years). In patients with PAD there was no relation between non-HDL-c and MALE, and in patients with coronary artery disease (CAD), cerebrovascular disease (CVD) or abdominal aortic aneurysm (AAA) the risk of MALE was higher per 1 mmol/L non-HDL-c (HR 1.14, 95% CI 1.01 to 1.29). Per 10 mm Hg SBP, the risk of MALE was higher in patients with PAD (HR 1.06, 95% CI 1.01 to 1.12) and in patients with CVD/CAD/AAA (HR 1.15, 95% CI 1.08 to 1.22). The risk of MALE was higher in smokers with PAD (HR 1.45, 95% CI 0.97 to 2.14) and CAD/CVD/AAA (HR 7.08, 95% CI 3.99 to 12.57).ConclusionsThe risk of MALE and MALE/MACE in patients with symptomatic vascular disease differs according to vascular disease location and is associated with non-HDL-c, SBP and smoking. These findings confirm the importance of MALE as an outcome and underline the importance of risk factor management in patients with vascular disease.
Potent STING activation stimulates immunogenic cell death to enhance antitumor immunity in neuroblastoma
Authors: Wang-Bishop Lihong , Wehbe Mohamed , Shae Daniel , James Jamaal , Hacker Benjamin C. , Garland Kyle , Chistov Plamen P. , Rafat Marjan , Balko Justin M. , Wilson John T. 
Published: March 2020

BackgroundNeuroblastoma (NB) is a childhood cancer for which new treatment options are needed. The success of immune checkpoint blockade in the treatment of adult solid tumors has prompted the exploration of immunotherapy in NB; however, clinical evidence indicates that the vast majority of NB patients do not respond to single-agent checkpoint inhibitors. This motivates a need for therapeutic strategies to increase NB tumor immunogenicity. The goal of this study was to evaluate a new immunotherapeutic strategy for NB based on potent activation of the stimulator of interferon genes (STING) pathway.MethodsTo promote STING activation in NB cells and tumors, we utilized STING-activating nanoparticles (STING-NPs) that are designed to mediate efficient cytosolic delivery of the endogenous STING ligand, 2’3’-cGAMP. We investigated tumor-intrinsic responses to STING activation in both MYCN-amplified and non-amplified NB cell lines, evaluating effects on STING signaling, apoptosis, and the induction of immunogenic cell death. The effects of intratumoral administration of STING-NPs on CD8+T cell infiltration, tumor growth, and response to response to PD-L1 checkpoint blockade were evaluated in syngeneic models of MYCN-amplified and non-amplified NB.ResultsThe efficient cytosolic delivery of 2’3’-cGAMP enabled by STING-NPs triggered tumor-intrinsic STING signaling effects in both MYCN-amplified and non-amplified NB cell lines, resulting in increased expression of interferon-stimulated genes and pro-inflammatory cytokines as well as NB cell death at concentrations 2000-fold to 10000-fold lower than free 2’3’-cGAMP. STING-mediated cell death in NB was associated with release or expression of several danger associated molecular patterns that are hallmarks of immunogenic cell death, which was further validated via cell-based vaccination and tumor challenge studies. Intratumoral administration of STING-NPs enhanced STING activation relative to free 2’3’-cGAMP in NB tumor models, converting poorly immunogenic tumors into tumoricidal and T cell-inflamed microenvironments and resulting in inhibition of tumor growth, increased survival, and induction of immunological memory that protected against tumor re-challenge. In a model of MYCN-amplified NB, STING-NPs generated an abscopal response that inhibited distal tumor growth and improved response to PD-L1 immune checkpoint blockade.ConclusionsWe have demonstrated that activation of the STING pathway, here enabled by a nanomedicine approach, stimulates immunogenic cell death and remodels the tumor immune microenvironment to inhibit NB tumor growth and improve responses to immune checkpoint blockade, providing a multifaceted immunotherapeutic approach with potential to enhance immunotherapy outcomes in NB.
Pre-existing antitherapeutic antibodies against the Fc region of the hu14.18K322A mAb are associated with outcome in patients with relapsed neuroblastoma
Authors: Goldberg Jacob L , Navid Fariba , Hank Jacquelyn A , Erbe Amy K , Santana Victor , Gan Jacek , de Bie Fenna , Javaid Amal M , Hoefges Anna , Merdler Michael , Carmichael Lakeesha , Kim KyungMann , Bishop Michael W , Meager Michael M , Gillies Stephen D , Pandey Janardan P , Sondel Paul M 
Published: March 2020

PurposePatients with cancer receiving tumor-reactive humanized monoclonal antibody (mAb) therapy can develop a human antihuman antibody (HAHA) response against the therapeutic mAb. We evaluated for HAHA in patients with neuroblastoma treated in a phase I study of humanized anti-GD2 mAb (immunoglobulin (Ig)G1 isotype), hu14.18K322A (NCT00743496). The pretreatment sera (collected prior to mAb treatment) from 9 of 38 patients contained antitherapeutic antibodies, even though they had no prior mAb exposure. We sought to characterize these pre-existing antitherapeutic antibodies (PATA).Experimental designThe PATA+ pretreatment samples were characterized via ELISA; clinical associations with PATA status were evaluated.ResultsPretreatment sera from eight of nine PATA+ patients also bound rituximab and demonstrated preferential ELISA reactivity against the Fc portions of hu14.18K322A and rituximab as compared with the Fab portions of these mAbs. These PATA+ sera also recognized dinutuximab (human IgG1 isotype) and mouse IgG2a isotype mAbs, but not a mouse IgG1 isotype or the fully human panitumumab (IgG2 isotype) mAb. Of the 38 treated patients, only 4 patients (all in the PATA+ cohort) demonstrated no disease progression for>2.5 years without receiving further therapy (p=0.002).ConclusionsThis study demonstrates an association between clinical outcome and the presence of PATA against determinant(s) on the Fc component of the therapeutic mAb, suggesting that the PATA may be playing a role in augmenting mAb-based antitumor effects. Further analyses for the presence of PATA in a larger cohort of patients with relapsed neuroblastoma, analyses of their clinical correlates, identification of their immunological targets, and potential antitumor mechanisms are warranted.
Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab
Authors: Minchom Anna , Yuan Wei , Crespo Mateus , Gurel Bora , Figueiredo Ines , Wotherspoon Andrew , Miranda Susana , Riisnaes Ruth , Ferreira Ana , Bertan Claudia , Pereira Rita , Clarke Matt , Baker Chloe , Ang Joo Ern , Fotiadis Nicos , Tunariu Nina , Carreira Suzanne , Popat Sanjay , O'Brien Mary , Banerji Udai , de Bono Johann , Lopez Juanita 
Published: March 2020

BackgroundThis case represents an exceptional response to pembrolizumab in a patient with epithelioid mesothelioma with a further response on rechallenge.Case presentationA 77-year-old woman with advanced epithelioid mesothelioma extensively pretreated with chemotherapy demonstrated a prolonged response of 45 months to 52 cycles of pembrolizumab. On rechallenge with pembrolizumab, further disease stability was achieved. Serial biopsies and analysis by immunohistochemistry and immunofluorescence demonstrated marked immune infiltration and documented the emergency of markers of immune exhaustion. Whole exome sequencing demonstrated a reduction in tumor mutational burden consistent with subclone elimination by immune checkpoint inhibitor (CPI) therapy. The relapse biopsy had missense mutation in BTN2A1.ConclusionThis case supports rechallenge of programme death receptor 1 inhibitor in cases of previous CPI sensitivity and gives molecular insights.