bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inelastic Buckling of Variable-Section Columns
Authors: Young Dana 
Published: March 2021

Abstract
A method is outlined for determining the critical load for variable-section columns in the inelastic range, that is, when the column is so short that buckling takes place after the stress at any section has exceeded the proportional limit of the material. The method is based on the Engesser-Considère theory and makes use of difference equations to solve the problem. The procedure is illustrated by a numerical example. The results of calculations for three different types of pin-ended columns are given.
A Graphic Resolution of Strain
Authors: Hoff N. J. 
Published: March 2021

Abstract
A purely graphic procedure is developed for the resolution of strain data obtained from measurements by strain rosettes of any shape. The characteristic features of the procedure arc: (a) The diagram is constructed directly from the measured data, without necessitating even addition; (b) strains are represented by distances measured in the true directions; (c) the true directions of principal strain are shown; (d) the true sense of rotation of straight lines is shown. The development of the procedure affords a purely geometric proof of the representation of the state of two-dimensional strain by Mohr’s circle.
Tension Tests at Constant True Strain Rates
Authors: MacGregor C. W. , Fisher J. C. 
Published: March 2021

Abstract
Tension tests of the true stress-strain type are reported for which the true strain rate is maintained constant throughout each test. Several metals are investigated under testing temperatures ranging from −183 C to 665 C. The influence of temperature and strain velocity on the true stress-strain properties is described. A single variable called the velocity-modified temperature is used to represent the combined influences of true strain rate and testing temperature.
Electric Turret-Traversing Mechanism for Tanks
Authors: Mikina Stanley J. 
Published: March 2021

Abstract
This paper describes the development of a new electric-power drive for 360-deg traverse of tank turrets that was undertaken early in 1941. The development was brought to a successful conclusion with the satisfactory completion of Army Ordnance acceptance tests on December 6, 1941, and mass production of these traverse units was achieved shortly after Pearl Harbor Day, in time to equip the General Sherman tanks that contributed to the victories in the North African campaigns. A description of the drive and its positionally regulated system of control is given together with the mathematical analysis of system stability upon which the design criteria of the control were based.
Parallel Columns With Common Lateral Supports
Authors: Langhaar H. L. 
Published: March 2021

Abstract
Problems in the stress analyses of semimonocoque aircraft structures have suggested the investigation of the stability of a system of closely spaced, equally stressed, parallel columns with lateral bulkhead supports. The theory presented in this paper establishes a correlation between this problem and the problem of stability of a single column with lateral spring supports. Since the theory for the latter case has been developed by several authors, the correlation effects a solution of the more general problem.
Modeling Noise Radiation From Concrete Box Girder Bridges as an Infinitely Long Periodic Structure Excited by a High-Speed Train
Authors: He Yuanpeng , Cheng Gong , Han Jian , Sheng Xiaozhen 
Published: March 2021

Abstract
Concrete box girder bridges occupy over 80% of the total mileage of the Chinese high-speed railway. The box girder structure has many natural modes of low frequencies, which can be excited by a train passing at high-speed, generating low-frequency bridge noise. This paper is concerned with the prediction of such bridge noise and reports a prediction model. The model, as other existing models of the same nature, also incorporates two parts, one dealing with vehicle–track-viaduct dynamics and the other dealing with sound radiation from the girders, but takes into account more features related to high-speed. In this model, vehicle–track-viaduct dynamics is dealt with in the frequency-domain based on the theory of infinitely long periodic structure and the Fourier-series method, predicting vibration frequency spectra for each and every box girder. The predicted vibration frequency spectra of all the box girders are expressed as a sum of propagating waves at different wavenumbers, and sound radiation from each propagating wave is evaluated using the 2.5D acoustic boundary element method. This approach to sound radiation enables contributions from all the box girders to be included at a reasonable computational cost. This paper continues with a comparison in bridge vibration and noise between prediction and measurement for a typical site. And finally, based on the parameters of that site, characteristics of noise radiation from the concrete box girders are studied using the prediction model.
Protolith affiliation and tectonometamorphic evolution of the Gurla Mandhata core complex, NW Nepal Himalaya
Authors: Godin Laurent , Ahenda Mark , Grujic Djordje , Stevenson Ross , Cottle John 
Published: March 2021

Abstract
Assigning correct protolith to high metamorphic-grade core zone rocks of large hot orogens is a particularly important challenge to overcome when attempting to constrain the early stages of orogenic evolution and paleogeography of lithotectonic units from these orogens. The Gurla Mandhata core complex in NW Nepal exposes the Himalayan metamorphic core (HMC), a sequence of high metamorphic-grade gneiss, migmatite, and granite, in the hinterland of the Himalayan orogen. Sm-Nd isotopic analyses indicate that the HMC comprises Greater Himalayan sequence (GHS) and Lesser Himalayan sequence (LHS) rocks. Conventional interpretation of such provenance data would require the Main Central thrust (MCT) to be also outcropping within the core complex. However, new in situ U-Th/Pb monazite petrochronology coupled with petrographic, structural, and microstructural observations reveal that the core complex is composed solely of rocks in the hanging wall of the MCT. Rocks from the core complex record Eocene and late Oligocene to early Miocene monazite (re-)crystallization periods (monazite age peaks of 40 Ma, 25–19 Ma, and 19–16 Ma) overprinting pre-Himalayan Ordovician Bhimphedian metamorphism and magmatism (ca. 470 Ma). The combination of Sm-Nd isotopic analysis and U-Th/Pb monazite petrochronology demonstrates that both GHS and LHS protolith rocks were captured in the hanging wall of the MCT and experienced Cenozoic Himalayan metamorphism during south-directed extrusion. Monazite ages do not record metamorphism coeval with late Miocene extensional core complex exhumation, suggesting that peak metamorphism and generation of anatectic melt in the core complex had ceased prior to the onset of orogen-parallel hinterland extension at ca. 15–13 Ma. The geometry of the Gurla Mandhata core complex requires significant hinterland crustal thickening prior to 16 Ma, which is attributed to ductile HMC thickening and footwall accretion of LHS protolith associated with a Main Himalayan thrust ramp below the core complex. We demonstrate that isotopic signatures such as Sm-Nd should be used to characterize rock units and structures across the Himalaya only in conjunction with supporting petrochronological and structural data.
Impact and effect mechanisms of mass campaigns in resource-constrained health systems: quasi-experimental evidence from polio eradication in Nigeria
Authors: Haenssgen Marco J , Closser Svea , Alonge Olakunle 
Published: March 2021

BackgroundMass campaigns are a key strategy for delivering life-saving interventions under Global Health Initiatives, especially in weak health system contexts. They are frequently designed parallel to the health system to rapidly achieve programme targets such as vaccination coverage, but we lack quantitative evidence demonstrating their impact and effect mechanisms on health system performance at sub-/national level. This longitudinal study responds to this gap through an analysis of polio eradication campaigns in Nigeria.MethodsUsing four rounds of Demographic and Health Surveys in Nigeria between October 2000 and December 2017, we created a longitudinal dataset containing 88 881 under-5 children/pregnancies. We estimated the relationships between individuals’ campaign exposure and health system performance indices (full RI schedule attainment, maternal healthcare services utilisation and child survival) using multilevel, mixed-effects regression models applied nationally and stratified by the six geopolitical zones in Nigeria.ResultsNationally, high-frequency mass campaigns had detrimental health systems effects that potentially left 3.6 million children deprived of full immunisation. The frequency of campaigns was most concentrated in regions with weak health systems, where the operations of RI were disrupted, alongside negative effects on child survival and institutional delivery. In contrast, regions with relatively strong health systems and few campaigns experienced beneficial effects on maternal healthcare service utilisation.ConclusionsAs we provide evidence that well-functioning health systems can benefit from mass campaigns under Global Health Initiatives, our work also challenges the established wisdom to intensify mass campaigns in weaker health systems to bypass service provision bottlenecks. Mass campaigns do not inherently benefit or damage a health system, but frequent campaigns in weak health system contexts can impede service provision. We call for an additional burden of proof and active efforts to integrate mass campaigns into routine health services by harmonising implementation plans and service delivery in weak health system contexts.
How fragile are Mediterranean diet interventions? A research-on-research study of randomised controlled trials
Authors: Grammatikopoulou Maria G , Nigdelis Meletios P , Theodoridis Xenophon , Gkiouras Konstantinos , Tranidou Antigoni , Papamitsou Theodora , Bogdanos Dimitrios P , Goulis Dimitrios G 
Published: March 2021

IntroductionThe Mediterranean diet (MD) is a traditional regional dietary pattern and a healthy diet recommended for the primary and secondary prevention of various diseases and health conditions. Results from the higher level of primary evidence, namely randomised controlled trials (RCTs), are often used to produce dietary recommendations; however, the robustness of RCTs with MD interventions is unknown.MethodsA systematic search was conducted and all MD RCTs with dichotomous primary outcomes were extracted from PubMed. The fragility (FI) and the reverse fragility index (RFI) were calculated for the trials with significant and non-significant comparisons, respectively.ResultsOut of 27 RCTs of parallel design, the majority failed to present a significant primary outcome, exhibiting an FI equal to 0. The median FI of the significant comparisons was 5, ranging between 1 and 39. More than half of the comparisons had an FI <5, indicating that the addition of 1–4 events to the treatment arm eliminated the statistical significance. For the comparisons with an FI=0, the RFI ranged between 1 and 29 (Median RFI: 7). When the included RCTs were stratified according to masking, the use of a composite primary endpoint, sample size, outcome category, or dietary adherence assessment method, no differences were exhibited in the FI and RFI between groups, except for the RFI among different compliance assessment methods.ConclusionsIn essence, the present study shows that even in the top tiers of evidence hierarchy, research on the MD may lack robustness, setting concerns for the formulation of nutrition recommendations.
Knowledge and attitudes of university health students in the Pacific Islands towards childhood hearing loss and hearing services: a Samoan survey study protocol
Authors: Kaspar Annette , Pifeleti Sione , Driscoll Carlie 
Published: March 2021

IntroductionThe Pacific Islands have among the highest rates of ear disease and hearing loss in the world, especially among children. Given that Ear, Nose and Throat (ENT)/audiology specialists are limited in the region, the successful implementation of ear and hearing health services will depend on the participation and support of the wider community of health professionals. There are currently no studies from the Pacific Islands investigating the knowledge and attitudes of either health students or health professionals towards childhood hearing loss and hearing services.Methods and analysisSurvey of medical and nursing students (n=370) currently enrolled at the National University of Samoa. Students will independently and anonymously complete a 10-item questionnaire. The questions assess attitudes to childhood hearing loss (two questions), knowledge of aetiology of childhood hearing loss (three questions), and knowledge of identification and interventions for children with hearing loss (five questions). Responses are based on a 5-point Likert scale (Strongly agree/Agree/Neutral/Disagree/Strongly disagree).Discussion/conclusionWe publish these protocols to facilitate similar studies in other low-income and middle-income countries, and especially among our Pacific Island neighbours.
Exploring activity levels in physical education lessons in the UK: a cross-sectional examination of activity types and fitness levels
Authors: Beale Nick , Eldridge Emma , Delextrat Anne , Esser Patrick , Bushnell Oliver , Curtis Emily , Wassenaar Thomas , Wheatley Catherine , Johansen-Berg Heidi , Dawes Helen 
Published: March 2021

ObjectivesTo establish pupil fitness levels, and the relationship to global norms and physical education (PE) enjoyment. To measure and describe physical activity (PA) levels during secondary school PE lessons, in the context of recommended levels, and how levels vary with activity and lesson type.MethodsA cross-sectional design; 10 697 pupils aged 12.5 (SD 0.30) years; pupils who completed a multistage fitness test and wore accelerometers to measure PA during PE lessons. Multilevel models estimated fitness and PE activity levels, accounting for school and class-level clustering.ResultsCardiorespiratory fitness was higher in boys than girls (ß=−0.48; 95% CI −0.56 to −0.39, p<0.001), within absolute terms 51% of boys and 54% of girls above the 50th percentile of global norms. On average, pupils spent 23.8% of PE lessons in moderate-to-vigorous PA (MVPA), and 7.1% in vigorous PA (VPA). Fitness-focused lessons recorded most VPA in co-educational (ß=1.09; 95% CI 0.43 to 1.74) and boys-only lessons (ß=0.32; 95% CI −0.21 to 0.85). In girls-only lessons, track athletics recorded most VPA (ß=0.13; 95% CI −0.50 to 0.75) and net/wall/racket games (ß=0.97; 95% CI 0.12 to 1.82) the most MVPA. For all lesson types, field athletics was least active (ß=−0.85; 95% CI −1.33 to −0.36). There was a relationship of enjoyment of PE to fitness (ß=1.03; 95% CI 0.83 to 1.23), and this relationship did not vary with sex (ß=−0.14 to 0.23; 95% CI −0.16 to 0.60).ConclusionsPE lessons were inactive compared with current guidelines. We propose that if we are to continue to develop a range of sporting skills in schools at the same time as increasing levels of fitness and PA, there is a need to introduce additional sessions of PE activity focused on increasing physical activity.Trial registration numberNCT03286725.
Safety and activity of the TGFβ receptor I kinase inhibitor galunisertib plus the anti-PD-L1 antibody durvalumab in metastatic pancreatic cancer
Authors: Melisi Davide , Oh Do-Youn , Hollebecque Antoine , Calvo Emiliano , Varghese Anna , Borazanci Erkut , Macarulla Teresa , Merz Valeria , Zecchetto Camilla , Zhao Yumin , Gueorguieva Ivelina , Man Michael , Gandhi Leena , Estrem Shawn T , Benhadji Karim A , Lanasa Mark C , Avsar Emin , Guba Susan C , Garcia-Carbonero Rocio 
Published: March 2021

BackgroundWe assessed the safety, efficacy, and pharmacokinetics of the transforming growth factor beta (TGFβ) receptor inhibitor galunisertib co-administered with the anti-programmed death-ligand 1 (PD-L1) antibody durvalumab in recurrent/refractory metastatic pancreatic cancer previously treated with ≤2 systemic regimens.MethodsThis was a two-part, single-arm, multinational, phase Ib study. In a dose-finding phase, escalating oral doses of galunisertib were co-administered on days 1–14 with fixed-dose intravenous durvalumab 1500 mg on day 1 every 4 weeks (Q4W), followed by an expansion cohort phase.ResultsThe galunisertib recommended phase II dose (RP2D) when co-administered with durvalumab 1500 mg Q4W was 150 mg two times per day. No dose-limiting toxicities were recorded. Among 32 patients treated with galunisertib RP2D, 1 patient had partial response, 7 had stable disease, 15 had objective progressive disease, and 9 were not evaluable. Disease control rate was 25.0%. Median overall survival and progression-free survival were 5.72 months (95% CI: 4.01 to 8.38) and 1.87 months (95% CI: 1.58 to 3.09), respectively. Pharmacokinetic profiles for combination therapy were comparable to those published for each drug. There was no association between potential biomarkers and treatment outcomes.ConclusionGalunisertib 150 mg two times per day co-administered with durvalumab 1500 mg Q4W was tolerable. Clinical activity was limited. Studying this combination in patients in an earlier line of treatment or selected for predictive biomarkers of TGFβ inhibition might be a more suitable approach.Trial registration numberClinicalTrials.gov identifier:NCT02734160.
Androgen Receptor Regulates CD44 Expression in Bladder Cancer
Authors: Sottnik Joseph L. , Vanderlinden Lauren , Joshi Molishree , Chauca-Diaz Ana , Owens Charles , Hansel Donna E. , Sempeck Colin , Ghosh Debashis , Theodorescu Dan 
Published: March 2021

Abstract

The androgen receptor (AR) is important in the development of both experimental and human bladder cancer. However, the role of AR in bladder cancer growth and progression is less clear, with literature indicating that more advanced stage and grade disease are associated with reduced AR expression. To determine the mechanisms underlying these relationships, we profiled AR-expressing human bladder cancer cells by AR chromatin immunoprecipitation sequencing and complementary transcriptomic approaches in response to in vitro stimulation by the synthetic androgen R1881. In vivo functional genomics consisting of pooled shRNA or pooled open reading frame libraries was employed to evaluate 97 genes that recapitulate the direction of expression associated with androgen stimulation. Interestingly, we identified CD44, the receptor for hyaluronic acid, a potent biomarker and driver of progressive disease in multiple tumor types, as significantly associated with androgen stimulation. CRISPR-based mutagenesis of androgen response elements associated with CD44 identified a novel silencer element leading to the direct transcriptional repression of CD44 expression. In human patients with bladder cancer, tumor AR and CD44 mRNA and protein expression were inversely correlated, suggesting a clinically relevant AR–CD44 axis. Collectively, our work describes a novel mechanism partly explaining the inverse relationship between AR and bladder cancer tumor progression and suggests that AR and CD44 expression may be useful for prognostication and therapeutic selection in primary bladder cancer.

Significance:
This study describes novel AREs that suppress CD44 and an expected inverse correlation of AR-CD44 expression observed in human bladder tumors.
Simultaneous Inhibition of LSD1 and TGFβ Enables Eradication of Poorly Immunogenic Tumors with Anti–PD-1 Treatment
Authors: Sheng Wanqiang , Liu Yi , Chakraborty Damayanti , Debo Brian , Shi Yang 
Published: March 2021

Abstract

Epigenetic regulators are a class of promising targets in combination with immune checkpoint inhibitors for cancer treatment, but the impact of the broad effects of perturbing epigenetic regulators on tumor immunotherapy remains to be fully explored. Here we show that ablation of the histone demethylase LSD1 in multiple tumor cells induces TGFβ expression, which exerts an inhibitory effect on T-cell immunity through suppressing the cytotoxicity of intratumoral CD8+ T cells and consequently dampens the antitumor effect of LSD1 ablation–induced T-cell infiltration. Importantly, concurrent depletion of LSD1 and TGFβ in combination with PD-1 blockade significantly increases both CD8+ T-cell infiltration and cytotoxicity, leading to eradication of poorly immunogenic tumors and a long-term protection from tumor rechallenge. Thus, combining LSD1 inhibition with blockade of TGFβ and PD-1 may represent a promising triple combination therapy for treating certain refractory tumors.

SignIficance:
Cotargeting LSD1 and TGFβ cooperatively elevates intratumoral CD8+ T-cell infiltration and unleashes their cytotoxicity, leading to tumor eradication upon anti–PD-1 treatment. Our findings illustrate a duality of epigenetic perturbations in immunotherapy and implicate the combination of LSD1 inhibition with dual PD-1/TGFβ blockade in treating certain poorly immunogenic tumors.
This article is highlighted in the In This Issue feature, p. 1861
Therapeutic Targeting of Checkpoint Receptors within the DNAM1 Axis
Authors: Alteber Zoya , Kotturi Maya F. , Whelan Sarah , Ganguly Sudipto , Weyl Emmanuel , Pardoll Drew M. , Hunter John , Ophir Eran 
Published: March 2021

AbstractTherapeutic antibodies targeting the CTLA4/PD-1 pathways have revolutionized cancer immunotherapy by eliciting durable remission in patients with cancer. However, relapse following early response, attributable to primary and adaptive resistance, is frequently observed. Additional immunomodulatory pathways are being studied in patients with primary or acquired resistance to CTLA4 or PD-1 blockade. The DNAM1 axis is a potent coregulator of innate and adaptive immunity whose other components include the immunoglobulin receptors TIGIT, PVRIG, and CD96, and their nectin and nectin-like ligands. We review the basic biology and therapeutic relevance of this family, which has begun to show promise in cancer clinical trials.Significance:Recent studies have outlined the immuno-oncologic ascendancy of coinhibitory receptors in the DNAM1 axis such as TIGIT and PVRIG and, to a lesser extent, CD96. Biological elucidation backed by ongoing clinical trials of single-agent therapy directed against TIGIT or PVRIG is beginning to provide the rationale for testing combination regimens of DNAM1 axis blockers in conjunction with anti–PD-1/PD-L1 agents.