bluuebunny/crossref_metadata_2025_split huggingface dataset:
Late Quaternary sea-surface temperatures in the western Coral Sea: Implications for the growth of the Australian Great Barrier Reef
Authors: Lawrence K.T. , Herbert T.D. 
Published: July 2019

Abstract
Recent chronostratigraphic evidence suggests that the central Australian Great Barrier Reef formed within the past 780 k.y. Periplatform sediments of the same age recovered from the western Coral Sea record a progressive decrease in the δ18O of planktonic foraminifera to the present. Several investigators have proposed that this trend represents an appreciable late Pleistocene warming (∼4 °C) of ocean surface temperatures, which they posit catalyzed the growth of the Great Barrier Reef. Contrary to this hypothesis, we demonstrate using alkenone paleothermometry (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(U_{37}^{k{^\prime}}\) \end{document}) on sediments from Ocean Drilling Program (ODP) Site 820 that sea-surface temperatures (SSTs) in the western Coral Sea changed by ∼1.5 °C or less during the past ∼800 k.y. If the central Great Barrier Reef rose in the late Quaternary, it was therefore not due to a warming of SSTs. We explore whether a major moisture balance change and/or diagenetic alteration of calcareous microfossils can explain the higher δ18O values observed at depth in the planktonic δ18O record at ODP Site 820. Our results suggest that diagenesis provides a large isotopic overprint.
Destruction of Atlantis by a great earthquake and tsunami? A geological analysis of the Spartel Bank hypothesis
Authors: Gutscher Marc-André 
Published: July 2019

Abstract
Numerous geographical similarities exist between Plato's descriptions of Atlantis and a paleoisland (Spartel) in the western Straits of Gibraltar. The dialogues recount a catastrophic event that submerged the island ca. 11.6 ka in a single day and night, due to violent earthquakes and floods. This sudden destruction is consistent with a great earthquake (M > 8.5) and tsunami, as in the Gulf of Cadiz region in 1755 when tsunami run-up heights reached 10 m. Great earthquakes (M 8–9) and tsunamis occur in the Gulf of Cadiz with a repeat time of 1.5–2 k.y., according to the sedimentary record. An unusually thick turbidite dated as ca. 12 ka may coincide with the destructive event in Plato's account. The detailed morphology of Spartel paleoisland, as determined from recently acquired high-resolution bathymetric data, is reported here. The viability of human habitation on this paleoisland ca. 11.6 ka is discussed on the basis of a new bathymetric map.
How different are COPD-specific patient reported outcomes, health status, dyspnoea and respiratory symptoms? An observational study in a working population
Authors: Nishimura Koichi , Oga Toru , Nakayasu Kazuhito , Ogasawara Miyoko , Hasegawa Yoshinori , Mitsuma Satoshi 
Published: July 2019

ObjectivesWe hypothesised that chronic obstructive pulmonary disease (COPD)-specific health status measured by the COPD assessment test (CAT), respiratory symptoms by the evaluating respiratory symptoms in COPD (E-RS) and dyspnoea by Dyspnoea-12 (D-12) are independently based on specific conceptual frameworks and are not interchangeable. We aimed to discover whether health status, dyspnoea or respiratory symptoms could be related to smoking status and airflow limitation in a working population.DesignThis is an observational, cross-sectional study.Participants1566 healthy industrial workers were analysed.ResultsRelationships between D-12, CAT and E-RS total were statistically significant but weak (Spearman’s correlation coefficient=0.274 to 0.446). In 646 healthy non-smoking subjects, as the reference scores for healthy non-smoking subjects, that is, upper threshold, the bootstrap 95th percentile values were 1.00 for D-12, 9.88 for CAT and 4.44 for E-RS. Of the 1566 workers, 85 (5.4%) were diagnosed with COPD using the fixed ratio of the forced expiratory volume in one second/forced vital capacity <0.7, and 34 (2.2%) using the lower limit of normal. The CAT and E-RS total were significantly worse in non-COPD smokers and subjects with COPD than non-COPD never smokers, although the D-12 was not as sensitive. There were no significant differences between non-COPD smokers and subjects with COPD on any of the measures.ConclusionsAssessment of health status and respiratory symptoms would be preferable to dyspnoea in view of smoking status and airflow limitation in a working population. However, these patient-reported measures were inadequate in differentiating between smokers and subjects with COPD identified by spirometry.
Improving paediatric epilepsy management at the first level of care: a pilot education intervention for clinical officers in Zambia
Authors: Patel Archana A , Wibecan Leah , Tembo Owen , Kalyelye Prisca , Mathews Manoj , Ciccone Ornella 
Published: July 2019

ObjectiveEpilepsy affects approximately 50 million people globally, with approximately 80% living in low/middle-income countries (LMIC), where access to specialist care is limited. In LMIC, primary health workers provide the majority of epilepsy care, despite limited training in this field. Recognising this knowledge gap among these providers is an essential component for closing the epilepsy treatment gap in these regions.SettingIn Zambia, the vast majority of healthcare is provided by clinical officers (COs), primary health providers with 3 years post-secondary general medical education, who predominantly work in first-level health centres around the country.ParticipantsWith cooperation from the Ministry of Health, a total of 10 COs from 4 surrounding first-level health centres around the capital city of Lusaka participated, with 9 completing the entire course.InterventionCOs were trained in a 3-week structured course on paediatric seizures and epilepsy, based on adapted evidence-based guidelines.ResultsPreassessment and postassessment were conducted to assess the intervention. Following the course, there was improved overall knowledge about epilepsy (69% vs 81%, p<0.05), specifically knowledge regarding medication management and recognition of focal seizures (p<0.05), improved seizure history taking and appropriate medication titration (p<0.05). However, knowledge regarding provoked seizures, use of diagnostic studies and general aetiologies of epilepsy remained limited.ConclusionsThis pilot project demonstrated that a focused paediatric epilepsy training programme for COs can improve knowledge and confidence in management, and as such is a promising step for improving the large epilepsy treatment gap in children in Zambia. With feasibility demonstrated, future projects are needed to expand to more rural regions for more diverse and larger sample of primary health provider participants and encompass more case-based training and repetition of key concepts as well as methods to improve and assess long-term knowledge retention.
The Tumey Giant Injection Complex, Tumey Hill, California (USA)
Authors: Zvirtes G. , Hurst A. , Philipp R. P. , Palladino G. , Grippa A. 
Published: July 2019

Abstract

The Tumey Giant Injection Complex (TGIC) is a regionally developed sandstone intrusion complex emplaced into the deep-water Kreyenhagen Shale (Eocene) in the San Joaquin Basin, Central California. Detailed geological mapping, stratigraphic reconstruction and outcrop description, supported by structural analysis, allowed the architectural characterization of the TGIC. The complex is described as two main stratigraphically constrained intervals: (1) a lower interval (250 m thick) emplaced into clay-rich mudrock, consisting dominantly of sills with stepped and multilayered geometry; and (2) an upper interval (200 m thick) characterized by injection breccia and large wing-like intrusions (
c.
600 m width × 100 m high) emplaced within predominantly biosiliceous mudrock strata. The intrusions in both intervals were derived from turbiditic channel fills intensely modified by sand fluidization. Sandstone intrusions and fractures affecting host strata are dominantly oriented sub-parallel to the basin axis striking between NW–SE and N–S, mainly dipping to NE and forming asymmetric saucer-shaped intrusions, suggesting structurally driven hydraulic fracturing and sand emplacement. The absence of a deep aquifer and potential sand sources underlying the complex suggests a lateral contribution of fluid flow. The TGIC occurs at a scale similar to injection complexes recognized in the subsurface and is a valuable reservoir analogue for hydrocarbon accumulations associated with sand injectites.
Simplifying Transactional Memory Support in C++
Authors: Zardoshti Pantea , Zhou Tingzhe , Balaji Pavithra , Scott Michael L. , Spear Michael 
Published: July 2019

C++ has supported a provisional version of Transactional Memory (TM) since 2015, via a technical specification. However, TM has not seen widespread adoption, and compiler vendors have been slow to implement the technical specification. We conjecture that the proposed TM support is too difficult for programmers to use, too complex for compiler designers to implement and verify, and not industry-proven enough to justify final standardization in its current form.
To address these problems, we present a different design for supporting TM in C++. By forbidding explicit self-abort, and by introducing an executor-based mechanism for running transactions, our approach makes it easier for developers to get code up and running with TM. Our proposal should also be appealing to compiler developers, as it allows a spectrum of levels of support for TM, with varying performance, and varying reliance on hardware TM support in order to provide scalability.
<?tight?>While our design does not enable some of the optimizations admitted by the current technical specification, we show that it enables the implementation of robust support for TM in a small, orthogonal compiler extension. Our implementation is able to handle a wide range of transactional programs, delivering low instrumentation overhead and scalability and performance on par with the current state of the art. Based on this experience, we believe our approach to be a viable means of reinvigorating the standardization of TM in C++.
Dynamic Beats Fixed
Authors: Bienkowski Marcin , Byrka Jarosław , Mucha Marcin 
Published: July 2019

We construct a deterministic 4-competitive algorithm for the online file migration problem, beating the currently best 20-year-old, 4.086-competitive M
ove
-T
o
-L
ocal
-M
in
(M
tlm
) algorithm by Bartal et al. (SODA 1997). Like M
tlm
, our algorithm also operates in phases, but it adapts their lengths dynamically depending on the geometry of requests seen so far. The improvement was obtained by carefully analyzing a linear model (factor-revealing linear program) of a single phase of the algorithm. We also show that if an online algorithm operates in phases of fixed length and the adversary is able to modify the graph between phases, then the competitive ratio is at least 4.086.
“Beet” the cold: beetroot juice supplementation improves peripheral blood flow, endothelial function, and anti-inflammatory status in individuals with Raynaud’s phenomenon
Authors: Shepherd Anthony I. , Costello Joseph T. , Bailey Stephen J. , Bishop Nicolette , Wadley Alex J. , Young-Min Steven , Gilchrist Mark , Mayes Harry , White Danny , Gorczynski Paul , Saynor Zoe L. , Massey Heather , Eglin Clare M. 
Published: July 2019

Raynaud’s phenomenon (RP) is characterized by recurrent transient peripheral vasospasm and lower nitric oxide (NO) bioavailability in the cold. We investigated the effect of nitrate-rich beetroot juice (BJ) supplementation on 1) NO-mediated vasodilation, 2) cutaneous vascular conductance (CVC) and skin temperature (Tsk) following local cooling, and 3) systemic anti-inflammatory status. Following baseline testing, 23 individuals with RP attended four times, in a double-blind, randomized crossover design, following acute and chronic (14 days) BJ and nitrate-depleted beetroot juice (NDBJ) supplementation. Peripheral Tskand CVC were measured during and after mild hand and foot cooling, and during transdermal delivery of acetylcholine and sodium nitroprusside. Markers of anti-inflammatory status were also measured. Plasma nitrite concentration ([nitrite]) was increased in the BJ conditions ( P < 0.001). Compared with the baseline visit, thumb CVC was greater following chronic-BJ (Δ2.0 flux/mmHg, P = 0.02) and chronic-NDBJ (Δ1.45 flux/mmHg, P = 0.01) supplementation; however, no changes in Tskwere observed ( P > 0.05). Plasma [interleukin-10] was greater, pan endothelin and systolic and diastolic blood pressure (BP) were reduced, and forearm endothelial function was improved, by both BJ and NDBJ supplementation ( P < 0.05). Acute and chronic BJ and NDBJ supplementation improved anti-inflammatory status, endothelial function and blood pressure (BP). CVC following cooling increased post chronic-BJ and chronic-NDBJ supplementation, but no effect on Tskwas observed. The key findings are that beetroot supplementation improves thumb blood flow, improves endothelial function and anti-inflammatory status, and reduces BP in people with Raynaud’s.NEW & NOTEWORTHY This is the first study to examine the effect of dietary nitrate supplementation in individuals with Raynaud’s phenomenon. The principal novel findings from this study were that both beetroot juice and nitrate-depleted beetroot juice 1) increased blood flow in the thumb following a cold challenge; 2) enhanced endothelium-dependent and -independent vasodilation in the forearm; 3) reduced systolic and diastolic blood pressure, and pan-endothelin concentration; and 4) improved inflammatory status in comparison to baseline.
Computational model of cardiovascular response to centrifugation and lower body cycling exercise
Authors: Diaz-Artiles Ana , Heldt Thomas , Young Laurence R. 
Published: July 2019

Short-radius centrifugation combined with exercise has been suggested as a potential countermeasure against spaceflight deconditioning. Both the long-term and acute physiological responses to such a combination are incompletely understood. We developed and validated a computational model to study the acute cardiovascular response to centrifugation combined with lower body ergometer exercise. The model consisted of 21 compartments, including the upper body, renal, splanchnic, and leg circulation, as well as a four-chamber heart and pulmonary circulation. It also included the effects of gravity gradient and ergometer exercise. Centrifugation and exercise profiles were simulated and compared with experimental data gathered on 12 subjects exposed to a range of gravitational levels (1 and 1.4G measured at the feet) and workload intensities (25–100 W). The model was capable of reproducing cardiovascular changes (within ± 1 SD from the group-averaged behavior) due to both centrifugation and exercise, including dynamic responses during transitions between the different phases of the protocol. The model was then used to simulate the hemodynamic response of hypovolemic subjects (blood volume reduced by 5–15%) subjected to similar gravitational stress and exercise profiles, providing insights into the physiological responses of experimental conditions not tested before. Hypovolemic results are in agreement with the limited available data and the expected responses based on physiological principles, although additional experimental data are warranted to further validate our predictions, especially during the exercise phases. The model captures the cardiovascular response for a range of centrifugation and exercise profiles, and it shows promise in simulating additional conditions where data collection is difficult, expensive, or infeasible.NEW & NOTEWORTHY Artificial gravity combined with exercise is a potential countermeasure for spaceflight deconditioning, but the long-term and acute cardiovascular response to such gravitational stress is still largely unknown. We provide a novel mathematical model of the cardiovascular system that incorporates gravitational stress generated by centrifugation and lower body cycling exercise, and we validate it with experimental measurements from human subjects. Simulations of experimental conditions not used for model development corroborate the model’s predictive capabilities.
Suppression of Prostate Cancer Pathogenesis Using an MDA-9/Syntenin (SDCBP) PDZ1 Small-Molecule Inhibitor
Authors: Das Swadesh K. , Kegelman Timothy P. , Pradhan Anjan K. , Shen Xue-Ning , Bhoopathi Praveen , Talukdar Sarmistha , Maji Santanu , Sarkar Devanand , Emdad Luni , Fisher Paul B. 
Published: July 2019

Abstract
Metastasis is the primary determinant of death in patients with diverse solid tumors and MDA-9/Syntenin (SDCBP), a pro-metastatic and pro-angiogenic gene, contributes to this process. Recently, we documented that by physically interacting with IGF-1R, MDA-9/Syntenin activates STAT3 and regulates prostate cancer pathogenesis. These observations firmly established MDA-9/Syntenin as a potential molecular target in prostate cancer. MDA-9/Syntenin contains two highly homologous PDZ domains predicted to interact with a plethora of proteins, many of which are central to the cancerous process. An MDA-9/Syntenin PDZ1 domain-targeted small molecule (PDZ1i) was previously developed using fragment-based drug discovery (FBDD) guided by NMR spectroscopy and was found to be well-tolerated in vivo, had significant half-life (t1/2 = 9 hours) and displayed substantial anti-prostate cancer preclinical in vivo activity. PDZ1i blocked tumor cell invasion and migration in vitro, and metastasis in vivo. Hence, we demonstrate that PDZ1i an MDA-9/Syntenin PDZ1 target-specific small-molecule inhibitor displays therapeutic potential for prostate and potentially other cancers expressing elevated levels of MDA-9/Syntenin.
ПРОЦЕДУРА ВИВЧЕННЯ ВАЛІДАЦІЙНОГО ПАРАМЕТРА “СТАБІЛЬНІСТЬ ПРИ РОЗВЕДЕННІ” АНАЛІТИЧНОЇ МЕТОДИКИ КІЛЬКІСНОГО ВИЗНАЧЕННЯ ДЕЯКИХ АНТИГІПЕРТЕНЗИВНИХ АНАЛІТІВ У БІОЛОГІЧНИХ РІДИНАХ ДЛЯ ПРОВЕДЕННЯ ФАРМАКОКІНЕТИЧНИХ ДОСЛІДЖЕНЬ
Authors: Logoyda L. S. 
Published: July 2019

Вступ. Біоаналітична методологія є основоположником досліджень з вивчення біоеквівалентності й терапевтичного моніторингу лікарських засобів, тому основну увагу при вивченні фармакокінетики та біоеквівалентності потрібно приділяти розробці й валідації біоаналітичних методик аналізу.
Мета дослідження – провести експериментальне вивчення валідаційного параметра “стабільність при розведенні” аналітичної методики кількісного визначення амлодипіну, бісопрололу та еналаприлу в плазмі крові для виконання фармакокінетичних досліджень.
Методи дослідження. Біоаналітична методика визначення амлодипіну, бісопрололу та еналаприлу ґрунтується на ВЕРХ/МС/МС аналізі аналітів у досліджуваних розчинах, отриманих із зразків плазми після попереднього осадження білків.
Результати й обговорення. У цій роботі описано валідаційний параметр “стабільність при розведенні”. Розроблено електронні протоколи з використанням Microsoft Exсel, в яких передбачено поля для введення даних. Для розробки процедури визначення та оцінки dilution integrity виконано модельний експеримент. Бланкові зразки плазми розбавляли 2- і 4-кратні розведення при шести визначеннях. Розведення зразків не вплинуло на правильність та прецизійність розробленої методики. Валідаційний параметр “стабільність при розведенні” (dilution integrity) незаслужено обділено увагою в керівництвах з валідації біоаналітичних методик – можливість розведення зразків дозволяє звужувати діапазон застосування методики і використовувати для калібрування більш просту модель, отримувати кращі показники лінійності, правильності та прецизійності; розробляти методику для низьких концентрацій і використовувати її як універсальну.
Висновки. Проведено експериментальне вивчення валідаційного параметра “стабільність при розведенні” аналітичної методики кількісного визначення амлодипіну, бісопрололу та еналаприлу в плазмі крові для виконання фармакокінетичних досліджень. Висновок щодо розробленої методики по валідаційному параметру “стабільність при розведенні” – коректна.
ВИВЧЕННЯ ВАЛІДАЦІЙНОГО ПАРАМЕТРА “ЛІНІЙНІСТЬ/КАЛІБРУВАЛЬНА МОДЕЛЬ” АНАЛІТИЧНОЇ МЕТОДИКИ КІЛЬКІСНОГО ВИЗНАЧЕННЯ УРОКАРБУ В ПЛАЗМІ КРОВІ ДЛЯ ПРОВЕДЕННЯ ФАРМАКОКІНЕТИЧНИХ ДОСЛІДЖЕНЬ
Authors: Drapak L. V. 
Published: July 2019

Вступ. Аналіз публікацій у провідних світових хіміко-аналітичних та фармацевтичних журналах дозволяє зробити висновок про пріоритетний інтерес дослідників до валідації біоаналітичних методик, на що вказує постійне вивчення валідаційних параметрів, у тому числі параметра “лінійність/калібрувальна модель”. Таким чином, набувають актуальності питання, пов’язані з визначенням валідаційного параметра “лінійність/калібрувальна модель”, який використовують під час доклінічних фармакологічних досліджень лікарських засобів та розробки стандартизованих підходів до проведення таких валідаційних робіт для оригінальних субстанцій.
Мета дослідження – провести експериментальне вивчення валідаційного параметра “лінійність/калібрувальна модель” аналітичної методики кількісного визначення урокарбу в плазмі крові для виконання фармакокінетичних досліджень.
Методи дослідження. Біоаналітична методика визначення урокарбу ґрунтується на ВЕРХ/МС/МС аналізі аналітів у досліджуваних розчинах, отриманих із зразків плазми після попереднього осадження білків. Проби хроматографують із використанням хроматографічної колонки Discovery C18, 50×2,1 мм, з розміром часток 5 мкм та градієнтного елюювання.
Результати й обговорення. Придатність біоаналітичної методики була підтверджена валідаційними характеристиками, які висувають до біоаналітичних методик. У цій роботі описано валідаційний параметр “лінійність/калібрувальна модель”. Розроблено електронні протоколи з використанням Microsoft Exсel, в яких передбачено поля для введення даних. При побудові калібрувальної кривої необхідно виконати такі умови: для нижньої межі кількісного визначення відхилення від номінальної концентрації повинно бути не більшим ±20 %, для калібрувальних розчинів з концентраціями, вищими, ніж нижня межа кількісного визначення, – не більшим ±15 %. Доведено лінійну залежність між концентрацією та площею хроматографічних піків урокарбу в діапазоні концентрацій 1–100 нг/мл. Рівняння регресії – y=0,00365x+0,000177, коефіцієнт кореляції – r2 0,9993.
Висновки. Проведено експериментальне вивчення валідаційного параметра “лінійність/калібрувальна модель” аналітичної методики кількісного визначення урокарбу в плазмі крові для виконання фармакокінетичних досліджень. Висновок щодо розробленої методики стосовно валідаційного параметра “лінійність/калібрувальна модель” – коректна.