bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary Study of the Use of Freeze-Valves for a Passive Shutdown System in Molten Salt Reactors
Authors: Li Qiming , Tang Zhongfeng , Fu Yuan , Li Zhong , Wang Naxiu 
Published: May 2019

The use of passive shutdown systems to enhance safety is one element of next-generation reactor design. The Freeze-Valve has been proposed as a key device in the passive system to stop the chain reaction of the Molten Salt Reactor (MSR), which has been chosen by Generation IV International Forum (GIF) as one of the six Generation IV reactor concepts. During reactor normal operation, the molten salt in the valve is cooled to a solid plug. In the event that the reactor overheats under accident conditions when all other active control systems fail, the plug will melt. The liquid fuel salt will be pulled out from the reactor core by gravity into dump tanks, and criticality will cease because the reaction is no longer moderated by the graphite in the reactor core. The more accurate the Freeze-Valve’s thermal design is, the more efficient the passive shutdown system becomes. In this study, an investigation of the thermal performance of the Freeze-Valve is conducted based on finite element methods verified by experimental data, and some modified designs are presented with recommendations. For further consideration, some innovative governing techniques used to control the Freeze-Valve are discussed in detail. Here, a more critical thermal design is focused on that can make the passive system shut down the nuclear reactor quickly and reliably. The Freeze-Valve can be used in the molten salt loop rather than a mechanical valve, which may become jammed by frozen salt.
Paper published with permission.
Inservice Testing Program Improvements for New Reactors: Small Modular Reactors
Authors: Lippy Ronald 
Published: May 2019

The nuclear industry is preparing for the licensing and construction of new nuclear power plants in the United States. Several new designs have been developed, including more traditional evolutionary designs, passive reactor designs, and small modular reactors (SMRs).
ASME (formerly the American Society of Mechanical Engineers) provides specific codes used to perform inspections and testing, both preservice and inservice, for many of the components used in the new reactor designs. The U.S. Nuclear Regulatory Commission (NRC) reviews information provided by applicants related to inservice testing (IST) programs for design certification (DC) and combined license (COL) applications under Part 52, “Licenses, Certifications, and Approvals for Nuclear Power Plants,” of Title 10, “Energy,” of the Code of Federal Regulations (10 CFR Part 52) (Reference 1).
The 2012 Edition of the ASME OM Code, Operation and Maintenance of Nuclear Power Plants, defines a post-2000 plant as a nuclear power plant that was issued (or will be issued) its construction permit, or combined license for construction and operation, by the applicable regulatory authority on or after January 1, 2000. The ASME New Reactors OM Code (NROMC) Task Group (TG) is assigned the task of ensuring that the preservice testing (PST) and inservice testing (IST) provisions in the ASME OM Code are adequate to provide reasonable assurance that pumps, valves, and dynamic restraints (snubbers) for post-2000 plants will operate when needed. Currently, the NROMC TG is preparing proposed guidance for the treatment of active pumps, valves, and dynamic restraints with high safety significance in nonsafety systems for passive post-2000 plants, including SMRs. (Note: For purposes of this paper, “post-2000 plant” and “new reactor” are used interchangeably throughout.)
Paper published with permission.
Implementation of Snubber Service-Life Monitoring Programs
Authors: Shutt Mark 
Published: May 2019

A well-planned and -implemented service-life program which is properly used can reduce the need for extended testing and examination activities and can result in a cost-effective overall program. Service-life monitoring is an essential part of an effective snubber program, yet it is often the least detailed and most overlooked aspect. Because of the historical emphasis on examination and testing requirements, there has been little industry-wide consistency or emphasis on the specifics of service-life monitoring activities. This paper will identify the purpose and basis for snubber service-life requirements, as well as outline key elements of an effective program to both identify service-life values and monitor them over periods of extended plant operation.
Included in the discussion will be topics such as: Identifying regulatory and code requirements, determining the scope of the program, establishing original service-life values, monitoring and evaluation, adjusting values, program documentation, and reporting. Identifying pertinent parameters for monitoring, appropriate methods for monitoring and trending, and incorporating condition monitoring and preventive-maintenance activities as alternatives to traditional programs will be discussed. Common challenges to implementing an effective program will be addressed, as well as some pitfalls to be avoided.
Paper published with permission.
Alternative Selection of Pump-Test Instrumentation and Variance of Fixed Reference Values
Authors: Gowin Mark , Robinson Tom , Kin John 
Published: May 2019

This paper describes actions being taken by the ASME (formerly the American Society of Mechanical Engineers) Operation and Maintenance of Nuclear Power Plants (OM Code) Subgroup on Pumps (ISTB) to revise pump test requirements to be more clearly stated and provide more flexibility in performance of tests. Specifically, this paper addresses two aspects of pump test requirements that are in the process of being changed.
• Instrumentation requirements for measurement of hydraulic parameters (approved by ISTB subgroup).
• Variance around the fixed reference value for establishing pump-test conditions (approved by ASME and published in the 2012 Edition of the OM Code).
The OM Code changes discussed in this paper are currently in various stages of approval and endorsement. Therefore, the information provided in this paper is subject to change as a result of the OM Code approval and U.S. Nuclear Regulatory Commission (NRC) endorsement processes.
Paper published with permission.
Application of Phased Array Sectorial Scanning (PASS) to Determine Check-Valve Operational Readiness at the Palo Verde Nuclear Station
Authors: Cruz Domingo A. , Delgado Jesse R. 
Published: May 2019

The reliability of check valves is paramount to the safe operation of plant systems. This paper provides a description of the benefits of applying advanced phased array techniques to establish the operational readiness of swing-check valves in the static or dynamic operational modes. In addition, a utility model perspective is described explaining how the Phased Array Sectorial Scanning (PASS) data assessments can be used to support operational predictive maintenance decisions. A collaborative effort between Arizona Public Service Co., the Palo Verde plants, and IHI Southwest Technologies, Inc. (IHI), was realized when IHI personnel applied Phased Array Sequence Scanning techniques to swing-check valves operating in the closed static position, as well as to three identical valves operating in the dynamic open positions in Palo Verde Units 1, 2 and 3 respectively.
Paper published with permission.
Non-classical monocyte homing to the gut via α4β7 integrin mediates macrophage-dependent intestinal wound healing
Authors: Schleier Lena , Wiendl Maximilian , Heidbreder Karin , Binder Marie-Theres , Atreya Raja , Rath Timo , Becker Emily , Schulz-Kuhnt Anja , Stahl Annette , Schulze Lisa Lou , Ullrich Karen , Merz Simon F , Bornemann Lea , Gunzer Matthias , Watson Alastair J M , Neufert Clemens , Atreya Imke , Neurath Markus F , Zundler Sebastian 
Published: May 2019

ObjectiveTo study the role of α4β7 integrin for gut homing of monocytes and to explore the biological consequences of therapeutic α4β7 inhibition with regard to intestinal wound healing.DesignWe studied the expression of homing markers on monocyte subsets in the peripheral blood and on macrophage subsets in the gut of patients with IBD and controls with flow cytometry and immunohistochemistry. Integrin function was addressed with dynamic adhesion assays and in vivo gut homing assays. In vivo wound healing was studied in mice deficient for or depleted of α4β7 integrin.ResultsClassical and non-classical monocytes were clearly dichotomous regarding homing marker expression including relevant expression of α4β7 integrin on human and mouse non-classical monocytes but not on classical monocytes. Monocyte-expressed α4β7 integrin was functionally important for dynamic adhesion to mucosal vascular addressin cell adhesion molecule 1 and in vivo gut homing. Impaired α4β7-dependent gut homing was associated with reduced (effect size about 20%) and delayed wound healing and suppressed perilesional presence of wound healing macrophages. Non-classical monocytes in the peripheral blood were increased in patients with IBD under clinical treatment with vedolizumab.ConclusionIn addition to reported effects on lymphocytes, anti-α4β7 therapy in IBD also targets non-classical monocytes. Impaired gut homing of such monocytes might lead to a reduction of wound healing macrophages and could potentially explain increased rates of postoperative complications in vedolizumab-treated patients, which have been observed in some studies.
Mortality in adult-onset and elderly-onset IBD: a nationwide register-based cohort study 1964–2014
Authors: Olén Ola , Askling Johan , Sachs Michael C , Neovius Martin , Smedby Karin E , Ekbom Anders , Ludvigsson Jonas F 
Published: May 2019

ObjectivesTo examine all-cause and cause-specific mortality in adult-onset and elderly-onset IBD and to describe time trends in mortality over the past 50 years.DesignSwedish nationwide register-based cohort study 1964–2014, comparing mortality in 82 718 incident IBD cases (inpatient and non-primary outpatient care) with 10 times as many matched general population reference individuals (n=801 180) using multivariable Cox regression to estimate HRs. Among patients with IBD, the number of participants with elderly-onset (≥60 years) IBD was 17 873.ResultsDuring 984 330 person-years of follow-up, 15 698/82 718 (19%) of all patients with IBD died (15.9/1000 person-years) compared with 121 095/801 180 (15.1%) of reference individuals, corresponding to an HR of 1.5 for IBD (95% CI=1.5 to 1.5 (HR=1.5; 95% CI=1.5 to 1.5 in elderly-onset IBD)) or one extra death each year per 263 patients. Mortality was increased specifically for UC (HR=1.4; 95% CI=1.4 to 1.5), Crohn’s disease (HR=1.6; 95% CI=1.6 to 1.7) and IBD-unclasssified (HR=1.6; 95% CI=1.5 to 1.8). IBD was linked to increased rates of multiple causes of death, including cardiovascular disease (HR=1.3; 1.3 to 1.3), malignancy (HR=1.4; 1.4 to 1.5) and digestive disease (HR=5.2; 95% CI=4.9 to 5.5). Relative mortality during the first 5 years of follow-up decreased significantly over time. Incident cases of 2002–2014 had 2.3 years shorter mean estimated life span than matched comparators.ConclusionsAdult-onset and elderly-onset patients with UC, Crohn’s disease and IBD-unclassified were all at increased risk of death. The increased mortality remained also after the introduction of biological therapies but has decreased over time.
Balloon-mounted stents for acute intracranial large vessel occlusion secondary to presumed atherosclerotic disease: evolution in an era of supple intermediate catheters
Authors: Gross Bradley A , Desai Shashvat M , Walker Gregory , Jankowitz Brian Thomas , Jadhav Ashutosh , Jovin Tudor G 
Published: May 2019

IntroductionTreatment of acute large vessel occlusion (LVO) stroke secondary to intracranial atherosclerotic disease (ICAD) is more nuanced with disparate and infrequently reported outcomes. The deployment of balloon-mounted stents presents an expedient approach with renewed feasibility in the modern era of supple intermediate catheters.MethodsA prospectively maintained endovascular stroke database was searched for patients undergoing intracranial stenting with balloon-mounted stents for acute LVO. Demographic, angiographic, and clinical data were extracted to determine procedural technique and success, measured both angiographically and clinically.ResultsSixty patients underwent stenting for acute LVO secondary to ICAD. Mean presenting National Institutes of Health Stroke Scale (NIHSS) score was 18 and 62% of treated sites were in the posterior circulation. Cases were performed under IV conscious sedation unless the patient was already intubated. Successful recanalization was achieved in 93% of cases (Thrombolysis in Cerebral Infarction (TICI) grade 2b in 48% and TICI grade 3 in 45%). Mean improvement in NIHSS score on post-procedure day 1 was 3.4. Good outcome (modified Rankin Scale score 0–2) at 3 months was 34% and the mortality rate was 34%. The rate of peri-procedural symptomatic hemorrhage was 8% and the rate of acute/subacute stent thrombosis was 7%. In this small cohort, patient age, sex, presenting NIHSS, comorbidities, smoking, tissue plasminogen activator administration, and stent location were not significant predictors of recanalization or good outcome.ConclusionTreatment of acute LVO stroke with balloon-mounted stents for ICAD has reperfusion rates and clinical outcomes comparable to thrombectomy, with higher rates of hemorrhage and mortality. Because stent placement was performed after attempted thrombectomy, a trial of primary stenting versus thrombectomy should be considered in patients suspected of underlying ICAD.
Quantified fracture (joint) clustering in Archean basement, Wyoming: application of the normalized correlation count method
Authors: Wang Qiqi , Laubach S. E. , Gale J. F. W. , Ramos M. J. 
Published: May 2019

We demonstrate statistically significant self-organized clustering over a length scale range from 10
−2
to 10
1
m for north-striking opening-mode fractures (joints) in Late Archean Mount Owen Quartz Monzonite. Spatial arrangement is a critical fracture network attribute that until recently has only been assessed qualitatively. We use normalized fracture intensity plots and the normalized correlation count (NCC) method of Marrett
et al.
to discriminate clustered from randomly placed or evenly spaced patterns quantitatively over a wide range of length scales and to test the statistical significance of the resulting patterns. We propose a procedure for interpreting cluster patterns on NCC diagrams generated by the freely available spatial analysis software CorrCount. Results illustrate the efficacy of NCC to measure fracture clustering patterns in texturally homogeneous Archean granitic rock in a setting distant (>2 km) from folds or faults. In their current geological setting, these regional fractures are conduits for water flow and their patterns – and the NCC approach to defining clusters – may be useful guides to the spatial arrangement style and clustering magnitude of conductive fractures in other, less accessible fractured basement rocks.

Thematic collection:
This article is part of the Naturally Fractured Reservoirs collection available at:
https://www.lyellcollection.org/cc/naturally-fractured-reservoirs
Polo-like Kinase 1 Inhibition as a Therapeutic Approach to Selectively Target BRCA1-Deficient Cancer Cells by Synthetic Lethality Induction
Authors: Carbajosa Sofía , Pansa María Florencia , Paviolo Natalia S. , Castellaro Andrés M. , Andino Diego L. , Nigra Ayelén D. , García Iris Alejandra , Racca Ana C. , Rodriguez-Berdini Lucía , Angiolini Virginia , Guantay Laura , Villafañez Florencia , Federico María Belén , Rodríguez-Baili María Celeste , Caputto Beatriz L. , Drewes Gerard , Madauss Kevin P. , Gloger Israel , Fernandez Elmer , Gil Germán A. , Bocco José Luis , Gottifredi Vanesa , Soria Gastón 
Published: May 2019

Abstract

Purpose:
BRCA1 and BRCA2 deficiencies are widespread drivers of human cancers that await the development of targeted therapies. We aimed to identify novel synthetic lethal relationships with therapeutic potential using BRCA-deficient isogenic backgrounds.

Experimental Design:
We developed a phenotypic screening technology to simultaneously search for synthetic lethal (SL) interactions in BRCA1- and BRCA2-deficient contexts. For validation, we developed chimeric spheroids and a dual-tumor xenograft model that allowed the confirmation of SL induction with the concomitant evaluation of undesired cytotoxicity on BRCA-proficient cells. To extend our results using clinical data, we performed retrospective analysis on The Cancer Genome Atlas (TCGA) breast cancer database.

Results:
The screening of a kinase inhibitors library revealed that Polo-like kinase 1 (PLK1) inhibition triggers strong SL induction in BRCA1-deficient cells. Mechanistically, we found no connection between the SL induced by PLK1 inhibition and PARP inhibitors. Instead, we uncovered that BRCA1 downregulation and PLK1 inhibition lead to aberrant mitotic phenotypes with altered centrosomal duplication and cytokinesis, which severely reduced the clonogenic potential of these cells. The penetrance of PLK1/BRCA1 SL interaction was validated using several isogenic and nonisogenic cellular models, chimeric spheroids, and mice xenografts. Moreover, bioinformatic analysis revealed high-PLK1 expression in BRCA1-deficient tumors, a phenotype that was consistently recapitulated by inducing BRCA1 deficiency in multiple cell lines as well as in BRCA1-mutant cells.

Conclusions:
We uncovered an unforeseen addiction of BRCA1-deficient cancer cells to PLK1 expression, which provides a new means to exploit the therapeutic potential of PLK1 inhibitors in clinical trials, by generating stratification schemes that consider this molecular trait in patient cohorts.
Mutant-Selective Irreversible EGFR Inhibitor, Naquotinib, Inhibits Tumor Growth in NSCLC Models with EGFR-Activating Mutations, T790M Mutation, and AXL Overexpression
Authors: Tanaka Hiroaki , Sakagami Hideki , Kaneko Naoki , Konagai Satoshi , Yamamoto Hiroko , Matsuya Takahiro , Yuri Masatoshi , Yamanaka Yosuke , Mori Masamichi , Takeuchi Masahiro , Koshio Hiroyuki , Hirano Masaaki , Kuromitsu Sadao 
Published: May 2019

Abstract
First- and second-generation EGFR tyrosine kinase inhibitors (TKI) are effective clinical therapies for patients with non–small cell lung cancer (NSCLC) harboring EGFR-activating mutations. However, almost all patients develop resistance to these drugs. The EGFR T790M mutation of EGFR is the most predominant mechanism for resistance. In addition, activation of AXL signaling is one of the suggested alternative bypassing pathways for resistance to EGFR-TKIs. Here, we report that naquotinib, a pyrazine carboxamide–based EGFR-TKI, inhibited EGFR with activating mutations, as well as T790M resistance mutation while sparing wild-type (WT) EGFR. In in vivo murine xenograft models using cell lines and a patient-derived xenograft model, naquotinib induced tumor regression of NSCLC with EGFR-activating mutations with or without T790M resistance mutation, whereas it did not significantly inhibit WT EGFR signaling in skin. Furthermore, naquotinib suppressed tumor recurrence during the treatment period of 90 days. In addition, unlike erlotinib and osimertinib, naquotinib inhibited the phosphorylation of AXL and showed antitumor activity against PC-9 cells overexpressing AXL in vitro and in vivo. Our findings suggest that naquotinib has therapeutic potential in patients with NSCLC with EGFR-activating mutations, T790M resistance mutation, and AXL overexpression.
СТРАТЕГІЧНЕ ПЛАНУВАННЯ БІЗНЕС-ДІЯЛЬНОСТІ СТОМАТОЛОГІЧНОГО ЦЕНТРУ, ОСНОВАНОГО НА ЗАСАДАХ ДЕРЖАВНО-ПРИВАТНОГО ПАРТНЕРСТВА
Authors: Chopchik V. D. , Orlova N. M. 
Published: May 2019

Мета: науково обґрунтувати методику здійснення стратегічного планування у стоматологічному медичному центрі, основаному на принципах державно-приватного партнерства.
Матеріали і методи. Методику стратегічного планування у стоматологічному центрі обґрунтовано на основі системного підходу і системного аналізу із використанням інформаційно-аналітичного методу. Інформаційною базою для її формування є наукові праці фахівців із організації та управління охороною здоров’я, а також результати власних досліджень.
Результати. У статті представлено методику стратегічного планування бізнес-діяльності стоматологічного центру на принципах державно-приватного партнерства, яка включає послідовність етапів планування, графік і моніторинг їх проведення. Запропонована методика створює організаційно-методичні умови для проведення стратегічного менеджменту та сприяє забезпеченню економічної ефективності діяльності центру. Методика є особливо важливою для центрів, основаних на принципах державно-приватного партнерства, оскільки їх діяльність націлена насамперед на задоволення потреб населення у широкому спектрі послуг, необхідних для збереження і зміцнення стоматологічного здоров’я.
Висновки. Запропоновану методику проведення стратегічного планування бізнес-процесів буде використано при розробці оптимізованої функціонально-організаційної моделі стоматологічного центру, який працює на принципах державно-приватного партнерства.
ГОЛОВНІ АСПЕКТИ ПІДГОТОВКИ СІМЕЙНОГО ЛІКАРЯ В УКРАЇНІ
Authors: Sichkoriz O. Y. 
Published: May 2019

Мета: аналіз проблеми та перспективи підготовки сімейних лікарів на післядипломному етапі.
Матеріали і методи. Чинні законодавчі акти проаналізовані за принципом структурно-логічного аналізу.
Результати. Основною метою інтернатури за спеціальністю «Загальна практика – сімейна медицина» є формування професійної компетентності для забезпечення готовності лікарів-інтернів до самостійної роботи як лікаря-спеціаліста. Інтернатура проводиться у формі очно-заочного навчання на кафедрах вищих медичних навчальних закладів і закладів післядипломної освіти та практичного стажування в базових установах охорони здоров’я. Заочне стажування для лікарів-інтернів за спеціальністю «Загальна практика – сімейна медицина» повинно здійснюватись на базі первинної медико-санітарної допомоги та амбулаторій сімейного лікаря.
Навчальний план та програма інтернатури розраховані на 2 роки. Протягом першого року – 6 місяців навчання на відповідних кафедрах вищих медичних навчальних закладів, 5 місяців – робота на базі первинної медико-санітарної допомоги та амбулаторій сімейного лікаря, один місяць – відпустка. Протягом другого року – 4 місяці – навчання на відповідних кафедрах вищих медичних навчальних закладів, 7 місяців – робота на базі первинної медико-санітарної допомоги та амбулаторій сімейного лікаря, один місяць – відпустка.
Підготовку сімейного лікаря необхідно починати з додипломної освіти з викладанням основ пропедевтики за синдромологічним підходом та специфічного клінічного мислення з орієнтацією на загальну практику – сімейну медицину.
Висновки. Тривалість навчання в інтернатурі з сімейної медицини повинна відповідати рекомендованим термінам міжнародних професійних організацій: WONCA, EURACT, UEMO тощо і тривати не менше 3 років. Заочне навчання має передбачати обов’язкове стажування тривалістю 1–3 місяці в тому закладі, куди скеровані майбутні спеціалісти відповідно до державного розподілу.