bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling the Unsteady Dynamics of a Turbine Research Facility
Authors: Longley John P. 
Published: August 2020

Abstract
The accuracy with which experimental investigations of turbine performance need to be undertaken require either a semi- or fully automated control of the operating point as any variation can compromise the reliability of the measurements. Fundamentally, both the mass flowrate through the turbine and the applied brake torque need to be adjusted in real time so that the required operating point is maintained. This paper describes the development of a time accurate computational simulation of the unsteady dynamics of a large-scale, low-speed turbine facility when its operating point is determined by a full-authority control system. The motivation for the development of the computational simulation was to be able to safely undertake parametric studies to refine the control system and to investigate the cause of monotonic excursions of the operating point which were observed after a major rebuild. The monotonic excursions of the turbine operating point could only be reproduced by the computational simulation after an unsteady aerodynamic coupling between the turbine exit flow and the downstream centrifugal fan had been incorporated. Based on this observation, a honeycomb was installed upstream of the fan in the turbine facility. This eliminated the monotonic excursions and the fractional noise of the operating point was reduced by 37%. When combined with an earlier refinement of the control system, the fractional noise was reduced by a factor of three. This enables the number of repeated measurements to be reduced by nine and still obtain the same quality of data.
Pliocene–Pleistocene basin evolution along the Garlock fault zone, Pilot Knob Valley, California
Authors: Rittase William M. , Walker J. Douglas , Andrew Joe , Kirby Eric , Wan Elmira 
Published: August 2020

Abstract
Exposed Pliocene–Pleistocene terrestrial strata provide an archive of the spatial and temporal development of a basin astride the sinistral Garlock fault in California. In the southern Slate Range and Pilot Knob Valley, an ∼2000-m-thick package of Late Cenozoic strata has been uplifted and tilted to the northeast. We name this succession the formation of Pilot Knob Valley and provide new chronologic, stratigraphic, and provenance data for these rocks. The unit is divided into five members that record different source areas and depositional patterns: (1) the lowest exposed strata are conglomeratic rocks derived from Miocene Eagle Crags volcanic field to the south and east across the Garlock fault; (2) the second member consists mostly of fine-grained rocks with coarser material derived from both southern and northern sources; and (3) the upper three members are primarily coarse-grained conglomerates and sandstones derived from the adjacent Slate Range to the north. Tephrochronologic data from four ash samples bracket deposition of the second member to 3.6–3.3 Ma and the fourth member to between 1.1 and 0.6 Ma. A fifth tephrochronologic sample from rocks south of the Garlock fault near Christmas Canyon brackets deposition of a possible equivalent to the second member of the formation of Pilot Knob Valley at ca. 3.1 Ma. Although the age of the base of the lowest member is not directly dated, regional stratigraphic and tectonic associations suggest that the basin started forming ca. 4–5 Ma. By ca. 3.6 Ma, the northward progradation fanglomerate sourced in the Eagle Crags region waned, and subsequent deposition occurred in shallow lacustrine systems. At ca. 3.3 Ma, southward progradation of conglomerates derived from the Slate Range began. Circa 1.1 Ma, continued southward progradation of fanglomerate with Slate Range sources is characterized by a shift to coarser grain sizes, interpreted to reflect uplift of the Slate Range. Overall, basin architecture and the temporal evolution of different source regions were controlled by activity on three regionally important faults—the Garlock, the Marine Gate, and the Searles Valley faults. The timing and style of motions on these faults appear to be directly linked to patterns of basin development.
Asthma und COPD: Bronchodilatation durch nasale High-Flow-Therapie
Authors: Haidl Peter 
Published: August 2020

Background: There has been increasing interest in transnasal pulmonary aerosol administration, but the dose-response relationship has not been reported. Objectives: To determine the accumulative bronchodilator dose at which patients with stable mild-to-moderate asthma and chronic obstructive pulmonary disease (COPD) achieve similar spirometry responses before and after bronchodilator tests using albuterol via a metered dose inhaler with a valved holding chamber (MDI + VHC). Method: Adult patients who met ATS/ERS criteria for bronchodilator responses in pulmonary function laboratory were recruited and consented to participate. After a washout period, patients received escalating doubling dosages (0.5, 1, 2, and 4 mg) of albuterol in a total volume of 2 mL delivered by vibrating mesh nebulizer via a nasal cannula at 37 °C with a flow rate of 15–20 L/min using a Venturi air entrainment device. Spirometry was measured at baseline and after each dose. Titration was stopped when an additional forced expiratory volume in 1 second (FEV1) improvement was < 5%. Results: 42 patients (16 males) with stable mild-to-moderate asthma (n = 29) and COPD (n = 13) were enrolled. FEV1 increment after a cumulative dose of 1.5 mg of albuterol via nasal cannula at 15–20 L/min was similar to 4 actuations of MDI + VHC (0.34 ± 0.18 vs. 0.34 ± 0.12 L, p = 0.878). Using ATS/ERS criteria of the bronchodilator test, 33.3% (14/42) and 69% (29/42) of patients responded to 0.5 and 1.5 mg of albuterol, respectively. Conclusions: With a nasal cannula at 15–20 L/min, transnasal pulmonary delivery of 1.5 mg albuterol resulted in similar bronchodilator response as 4 actuations of MDI + VHC.
Analysis of epigenetic aging in vivo and in vitro: Factors controlling the speed and direction
Authors: Matsuyama Mieko , Søraas Arne , Yu Sarah , Kim Kyuhyeon , Stavrou Evi X , Caimi Paolo F , Wald David , deLima Marcos , Dahl John A , Horvath Steve , Matsuyama Shigemi 
Published: August 2020

The mechanism of aging is not yet fully understood. It has been recognized that there are age-dependent changes in the DNA methylation pattern of the whole genome. To date, there are several DNA methylation-based estimators of the chronological age. A majority of the estimators use the DNA methylation data from a single tissue type, such as blood. In 2013, for the first time, Steve Horvath reported the DNA methylation-based age estimator (353 CpGs were used) that could be applied to multiple tissues. A refined, more sensitive version that uses 391 CpGs was subsequently developed and validated in human cells, including fibroblasts. In this review, the age predicted by DNA methylation-based age estimator is referred to as DNAmAge, and the biological process controlling the progression of DNAmAge is referred to as the epigenetic aging in this minireview. The concepts of DNAmAge and epigenetic aging provide us opportunities to discover previously unrecognized biological events controlling aging. In this article, we discuss the frequently asked questions regarding DNAmAge and the epigenetic aging by introducing recent studies of ours and others. We focus on addressing the following questions: (1) Is there any synchronization of DNAmAge between cells in a human body?, (2) Can we use in vitro (cell culture) systems to study the epigenetic aging?, (3) Is there an age limit of DNAmAge?, and (4) Is it possible to change the speed and direction of the epigenetic aging? We describe our current understandings to these questions and outline potential future directions. Impact statement Aging is associated with DNA methylation (DNAm) changes. Recent advancement of the whole-genome DNAm analysis technology allowed scientists to develop DNAm-based age estimators. A majority of these estimators use DNAm data from a single tissue type such as blood. In 2013, a multi-tissue age estimator using DNAm pattern of 353 CpGs was developed by Steve Horvath. This estimator was named “epigenetic clock”, and the improved version using DNAm pattern of 391 CpGs was developed in 2018. The estimated age by epigenetic clock is named DNAmAge. DNAmAge can be used as a biomarker of aging predicting the risk of age-associated diseases and mortality. Although the DNAm-based age estimators were developed, the mechanism of epigenetic aging is still enigmatic. The biological significance of epigenetic aging is not well understood, either. This minireview discusses the current understanding of the mechanism of epigenetic aging and the future direction of aging research.
Effectiveness of a resistance training program on physical function, muscle strength, and body composition in community-dwelling older adults receiving home care: a cluster-randomized controlled trial
Authors: Bårdstu Hilde Bremseth , Andersen Vidar , Fimland Marius Steiro , Aasdahl Lene , Raastad Truls , Cumming Kristoffer T. , Sæterbakken Atle Hole 
Published: August 2020

Abstract
Background
Aging is associated with reduced muscle mass and strength leading to impaired physical function. Resistance training programs incorporated into older adults’ real-life settings may have the potential to counteract these changes. We evaluated the effectiveness of 8 months resistance training using easily available, low cost equipment compared to physical activity counselling on physical function, muscle strength, and body composition in community-dwelling older adults receiving home care.

Methods
This open label, two-armed, parallel group, cluster randomized trial recruited older adults above 70 years (median age 86.0 (Interquartile range 80–90) years) receiving home care. Participants were randomized at cluster level to the resistance training group (RTG) or the control group (CG). The RTG trained twice a week while the CG were informed about the national recommendations for physical activity and received a motivational talk every 6th week. Outcomes were assessed at participant level at baseline, after four, and 8 months and included tests of physical function (chair rise, 8 ft-up-and-go, preferred- and maximal gait speed, and stair climb), maximal strength, rate of force development, and body composition.

Results
Twelve clusters were allocated to RTG (7 clusters, 60 participants) or CG (5 clusters, 44 participants). The number of participants analyzed was 56–64 (6–7 clusters) in RTG and 20–42 (5 clusters) in CG. After 8 months, multilevel linear mixed models showed that RTG improved in all tests of physical function and maximal leg strength (9–24%, p = 0.01–0.03) compared to CG. No effects were seen for rate of force development or body composition.

Conclusion
This study show that resistance training using easily available, low cost equipment is more effective than physical activity counselling for improving physical function and maximal strength in community-dwelling older adults receiving home care.

Trial registration
ISRCTN1067873
Spatial modes for transmission of chikungunya virus during a large chikungunya outbreak in Italy: a modeling analysis
Authors: Guzzetta Giorgio , Vairo Francesco , Mammone Alessia , Lanini Simone , Poletti Piero , Manica Mattia , Rosa Roberto , Caputo Beniamino , Solimini Angelo , Torre Alessandra Della , Scognamiglio Paola , Zumla Alimuddin , Ippolito Giuseppe , Merler Stefano 
Published: August 2020

AbstractBackgroundThe spatial spread of many mosquito-borne diseases occurs by focal spread at the scale of a few hundred meters and over longer distances due to human mobility. The relative contributions of different spatial scales for transmission of chikungunya virus require definition to improve outbreak vector control recommendations.MethodsWe analyzed data from a large chikungunya outbreak mediated by the mosquitoAedes albopictusin the Lazio region, Italy, consisting of 414 reported human cases between June and November 2017. Using dates of symptom onset, geographic coordinates of residence, and information from epidemiological questionnaires, we reconstructed transmission chains related to that outbreak.ResultsFocal spread (within 1 km) accounted for 54.9% of all cases, 15.8% were transmitted at a local scale (1–15 km) and the remaining 29.3% were exported from the main areas of chikungunya circulation in Lazio to longer distances such as Rome and other geographical areas. Seventy percent of focal infections (corresponding to 38% of the total 414 cases) were transmitted within a distance of 200 m (the buffer distance adopted by the national guidelines for insecticide spraying). Two main epidemic clusters were identified, with a radius expanding at a rate of 300–600 m per month. The majority of exported cases resulted in either sporadic or no further transmission in the region.ConclusionsEvidence suggest that human mobility contributes to seeding a relevant number of secondary cases and new foci of transmission over several kilometers. Reactive vector control based on current guidelines might allow a significant number of secondary clusters in untreated areas, especially if the outbreak is not detected early. Existing policies and guidelines for control during outbreaks should recommend the prioritization of preventive measures in neighboring territories with known mobility flows to the main areas of transmission.
The proteomics of roadside hawk (Rupornis magnirostris), broad-snouted caiman (Caiman latirostris) and loggerhead sea turtle (Caretta caretta) tears
Authors: Raposo A. C. , Lebrilla C. B. , Portela R. W. , Goonatilleke E. , Neto F. A. Dórea , Oriá A. P. 
Published: August 2020

Abstract
Background
Tears play an important role in ocular surface protection, and help wild animals maintain visual acuity in the face of air and water friction. The proteomics of tears has only been described for mammals. The knowledge of the proteomics of wild animal tears can aid not only in the setting of normal standards for ocular disease studies in these animals, but also to base the search for new molecules to be used in ophthalmology therapeutics. We therefore set out to describe the proteomic profile of roadside hawk (Rupornis magnirostris), broad-snouted caiman (Caiman latirostris) and loggerhead sea turtle (Caretta caretta) tears. Tears were collected from healthy animals, their spectral profiles were obtained with an LTQ Orbitrap XL mass spectrometer, and the dataset was analyzed against reference taxa.

Results
For roadside hawk, 446 proteins were identified, the most abundant being albumin, transferrin, globulin and actin. For broad-snouted caiman and loggerhead sea turtle, 1358 and 163 proteins were identified, respectively. Uncharacterized proteins and transferrin were highly abundant in both species. The roadside hawk tear components and their properties were similar to those described for humans, but with a higher albumin concentration. Broad-snouted caiman tears presented a wide diversity of ontological functions, with an abundant presence of enzymatic compounds. In loggerhead sea turtle tears, the predominance of proteins with ion-transport functions was consistent with possible osmolality-maintenance mechanisms.

Conclusion
These data enhance our understanding of birds and reptiles’ tears microcomposition and may be used to base the discovery of new molecules with high biotechnological potential.
Loss of survival advantage for deficient mismatch repair in patients with advanced colorectal cancer may be caused by changes in prognostic value of CD8+T cell
Authors: Wang Bingyan , Li Fei , Guo Limei , Lu Siyi , Ma Junren , Ma Yanpeng , Meng Yan , Wang Junwei , Zhou Xin , Fu Wei 
Published: August 2020

Abstract
Background
Patients with stage II deficient mismatch repair (dMMR) show a better prognosis than patients with colorectal cancer (CRC) with proficient mismatch repair (pMMR). However, this beneficial effect is decreased in advanced stages of the disease. This study was conducted to investigate the prognostic value of dMMR in different stage and alterations in the tumor microenvironment.

Methods
This was a matched retrospective cohort study. Thirty-two patients with stage III&IV dMMR matched with 32 patients with stage I&II dMMR and 64 patients with pMMR were evaluated. Immunohistochemistry analysis was performed for the 64 patients with dMMR to explore the expression and prognostic effect of CD3, CD4, CD8, and PD-L1.

Results
Patients with stage III–IV dMMR showed no advantage in overall survival (OS) and disease-free survival (DFS) compared to patients with pMMR (P = 0.244, P = 0.667). No expression differences in CD3, CD4, CD8, and PD-L1 at the center of the tumor (CT) or invasive margin (IM) were found between patients with stage I&II and stage III&IV dMMR. High CD3 expression at the CT and high CD3 an CD4 expression at the IM improved both OS and DFS. High CD8 expression showed opposite prognostic value in patients with stage I&II and III&IV dMMR. A similar tendency was observed for PD-L1 expression.

Conclusion
Patients with stage III–IV dMMR showed no prognostic advantage over patients with pMMR. Expression of CD3, CD4, CD8, and PD-L1 was similar between stage I&II and III&IV dMMR CRC. High CD3 expression at the CT and high CD3 and CD4 expression at the IM can significantly improve patient prognosis. The opposite prognostic tendency of CD8 and PD-L1 for patients with stage I&II and III&IV dMMR may be relevant to CD8+T cell exhaustion and functional changes at inhibitory immune checkpoints.
Different surgical outcome and follow-up status between dMMR and pMMR colorectal cancer patients who fulfilled with Amsterdam-II criteria
Authors: Sun Ci-Yuan , Chiang Jy-Ming , Chen Tse-Ching , Hung Hsin-Yun , You Jeng-Fu 
Published: August 2020

Abstract
Background
Although hereditary non-polyposis colorectal cancer (HNPCC) could be subtyped into proficient or deficient mismatch repair gene expression (pMMR or dMMR), distinct clinical features between these two subgroups patients were rarely reported.

Methods
We retrospectively analyzed 175 hereditary non-polyposis colorectal cancer (HNPCC) patients between January 1995 and December 2012. Cox proportional hazards model was used to compare the differences between two subgroups.

Results
Significant differences of disease free survival (DFS) and overall survival (OS) exist between dMMR and pMMR. In addition to other factors including younger mean age of diagnosis for dMMR patients (48.6 years vs. 54.3 years), operation type (more extended colectomy for dMMR 35.8% vs. 14.5%), tumor location (right colon predominance for dMMR 61.7% vs. 27.3% and more rectum cases for pMMR 41.8% vs. 11.7%), tumor differentiation (more poor differentiation for dMMR 23.3% vs. 9.0%), N staging (more N0 cases for dMMR 70.8% vs. 50.9%), more frequently presence of extra-colonic tumors for dMMR (16.7% vs.1.8%), and lower recurrence rates (9.1% vs.35.3%). Significantly different cumulative incidences of developing metachronous colorectal cancer were observed with 6.18 for pMMR patients and 20.57 person-years for dMMR patients (p < 0.001).

Conclusions
Distinct clinicopathological features significantly exist between dMMR and pMMR subtypes patient, MMR status should be consider to tailor operation types and follow up surveillance between these two subgroups patients who all fulfilled with Amsterdam-II criteria.
An EGFR T790M-mutated lung adenocarcinoma undergoing large-cell neuroendocrine carcinoma transformation after osimertinib therapy: a case report
Authors: Miyazaki Shinichi , Kuno Yasumasa , Hayai Shunsaku , Teramachi Ryo , Yamashita Ryo , Saito Yusuke , Higuchi Kosuke , Nara Yoshiharu , Ikeda Takuya 
Published: August 2020

Abstract
Background
Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, is selective for both epidermal growth factor receptor tyrosine kinase inhibitor–sensitizing and T790M resistance mutations. Almost all patients who initially respond to an epidermal growth factor receptor tyrosine kinase inhibitor subsequently report disease progression. Epidermal growth factor receptor–dependent resistance mechanisms, bypass pathway activation, and histological transformation have been reported with osimertinib therapy.

Case presentation
We report a case of a 64-year-old Asian man with epidermal growth factor receptor T790M-positive adenocarcinoma that transformed to epidermal growth factor receptor T790M-negative large-cell neuroendocrine carcinoma after osimertinib therapy. A prompt rebiopsy revealed a rare mechanism of resistance to epidermal growth factor receptor tyrosine kinase inhibitor, and subsequently treatment with carboplatin and etoposide was effective.

Conclusions
Despite the promising emergence of circulating tumoral DNA testing, this case report emphasizes the importance of rebiopsy of a progressive epidermal growth factor receptor–mutant tumor.
Different dietary starch sources alter the carcass traits, meat quality, and the profile of muscle amino acid and fatty acid in finishing pigs
Authors: Yu Miao , Li Zhenming , Rong Ting , Wang Gang , Liu Zhichang , Chen Weidong , Li Jiazhou , Li Jianhao , Ma Xianyong 
Published: August 2020

Abstract
Background
With increasing health awareness among consumers, the demand for healthier, tastier, higher quality and nutritional value pork is increasing. It has been shown that different dietary starch sources can alter the carcass traits and meat quality. However, research on the effects of different starch sources with clear different amylose/amylopectin ratio on the amino acid and fatty acid composition in Longissimus thoracis (L. thoracis) muscle of pigs is limited. This study aimed to investigate the effects of different dietary starch sources on carcass traits, meat quality, muscle amino acid and fatty acid composition, and the mRNA expression levels of genes involved in lipid metabolism and muscle fiber characteristics in finishing pigs. A total of 72 Duroc × Landrace × Large White barrows were randomly allocated to 3 different dietary treatment groups with 8 replicate pens/group and 3 pigs per pen. Tapioca starch (TS), corn starch (CS), and pea starch (PS), with amylose/amylopectin ratio of 0.11, 0.25, and 0.44, respectively, were used as their dietary starch sources for 40 days.

Results
Results showed that the PS diet significantly increased (P < 0.05) the final body weight, average daily gain, loin-eye area, and fat-free lean index compared with the TS diet, but significantly decreased (P < 0.05) the feed to gain ratio and backfat thickness. Compared with the TS diet, PS diet also increased (P < 0.05) the pH45 min, marbling scores, the content of intramuscular fat and inosine monophosphate in the L. thoracis, and decreased (P < 0.05) the drip loss and shear force. In addition, compared with the TS diet, PS diet increased (P < 0.05) the proportions of flavor amino acids, DHA, EPA, and n-3 polyunsaturated fatty acid (PUFA) in the L. thoracis compared with TS diet, but decreased (P < 0.05) the ratio of n-6/n-3 PUFA. Furthermore, compared with the TS diet, PS diet also upregulated (P < 0.05) the lipogenic genes (FAS, LPL, SCD, ACCα) and myosin heavy-chain (MyHC)-IIa mRNA expression levels compared with the TS diet, but downregulated (P < 0.05) the CPT1B and MyHC-IIb mRNA levels.

Conclusions
In conclusion, these results provided compelling evidence that the different dietary starch source altered the carcass traits, meat flavor and quality in finishing pigs, and consumption of a diet with higher amylose/amylopectin ratio results in the production of a healthy, higher quality, and nutritional value pork.