bluuebunny/crossref_metadata_2025_split huggingface dataset:
A More Accurate Definition of Mechanical and Volumetric Efficiencies for Digital Displacement® Pumps
Authors: Williamson Christopher , Manring Noah 
Published: December 2019

Abstract
The apparent volumetric displacement of digital displacement pumps and motors is reduced with increasing fluid pressure. So-called pump shrinkage has been documented in previous publications, where fluid compressibility effects were assumed to affect input and output power equally. In this paper, the authors derive the torque and flow rate of an ideal digital displacement pump. It is shown that the output power shrinks slightly more than the input. The difference between input and output shrinkage is counted as a power loss according to the accepted definition of total efficiency. New equations are presented for calculating mechanical and volumetric efficiencies which are up to 2% more accurate than the previous method (which assumes equal shrinkage) and up to 5% more accurate than conventional equations (which assume no shrinkage). Compressibility effects may be even more significant depending on pump design parameters, fluid properties, flow control algorithms and operating conditions. Calculations of partial pump efficiencies require a derived displacement volume to be known. The derived displacement volume of digital displacement pumps is considered for the first time in this paper. The contributions of this work are instructive for understanding the unique characteristics of digital displacement pumps as well as check-valve type pumps in general.
Multi-Objective Optimization of Modified Cycloidal-Toothed Gerotor Pumps by Genetic Algorithm
Authors: Robison Andrew J. , Vacca Andrea 
Published: December 2019

Abstract
Cycloidal-toothed gerotors are formed by the combination of epicycloid and a hypocyloid arcs that use the pitch circles as their base circles. They are a common profile type used in industry likely because they can be generated by simple parametric equations. One of the problems with the cycloidal-toothed profile type is that the radius of curvature of both the inner and outer gear are zero when the gears contact at the pitch point which can lead to high contact stress. A gear generation algorithm has been developed that modifies the hypocycloid tooth form to eliminate contact in regions with very low radii of curvature that is yet to be described in scientific literature. Seven performance metrics are developed to evaluate size, flow ripple, adhesive wear, contact stress, radial gap leakage, lateral gap leakage, and inlet throttling that are used as objective functions in a multi-objective optimization. The pump geometry is optimized by applying the NSGA-II algorithm with a population size of 1000 for 500 generations to produce a pareto front, and the results are compared to two cycloidal-toothed gerotors used in the automotive industry. Two designs were found that significantly reduce the contact stress in the profiles while giving the same performance in the other six objective functions in comparison to the profiles used in industry. Another two designs are found that can significantly reduce several objective functions if the size of the pump can be increased slightly.
Method for the Experimental Determination of the Bunsen Absorption Coefficient of Hydraulic Fluids
Authors: Rambaks Andris , Schmitz Katharina 
Published: December 2019

Abstract
A manometric-volumetric method to determine the Bunsen absorption coefficient of hydraulic fluids at high-pressures is presented. The virial equation of state is used to determine the amount of substance and its composition in the gaseous phase and at high-pressures. An error-analysis is presented for a best-case error estimate of the method.
Influence of Hydraulic Accumulator Performance on the Hydraulic Hybrid Powertrain
Authors: Zhang Qi , Wang Feng , Xu Bing , Stelson Kim A. 
Published: December 2019

Abstract
Owing to its high power density, hydraulic hybrid is considered as an effective approach to reducing the fuel consumption of heavy duty vehicles. A gas-charged hydraulic accumulator serves as the power buffer, storing and releasing hydraulic power through gas. An accurate hydraulic accumulator model is crucial to predict its actual performance. There are two widely used accumulator models: isothermal and adiabatic models. Neither of these models are practical to reflect its real performance in the hydraulic hybrid system. Therefore, the influence of an accumulator model considering thermal hysteresis on a hydraulic hybrid wheel loader has been studied in this paper. The difference of three accumulator models (isothermal, adiabatic and energy balance) has been identified. A dynamic simulation model of the hydraulic hybrid wheel loader has been developed. The fuel consumptions of the hydraulic hybrid wheel loader with three accumulator models has been compared. The influence of heat transfer coefficient of the accumulator housing has also been studied.
Social relations in late adolescence and incident coronary heart disease: a 38-year follow-up of the Swedish 1969–1970 Conscription Cohort
Authors: Balog Piroska , Janszky Imre , Chen Hua , Rafael Beatrix , Hemmingsson Tomas , László Krisztina D 
Published: December 2019

ObjectivesIncreasing evidence suggests that low social support is associated with an elevated risk of coronary heart disease (CHD). Earlier studies in this field were conducted in predominantly middle-aged or older samples; thus, the associations reported previously may have been confounded by subclinical manifestations of the disease. We investigated whether social relationships in late adolescence, that is, well before symptoms of subclinical disease manifest, are associated with CHD during a 38-year follow-up.SettingSweden.ParticipantsMen born 1949–1951 and conscripted for military service in Sweden during 1969–1970 (n=49 321). At conscription, participants completed questionnaires about social relationships, lifestyle and health-related factors and underwent a medical examination.Primary and secondary outcome measuresCHD, acute myocardial infarction (AMI).ResultsWe found no relationship between having no confidant and frequency of confidential discussions with friends and the risk of CHD or AMI in the first 30 years of follow-up. However, after 30 years, men with no confidant at baseline had increased CHD and AMI risks relative to those having a confidant; the childhood socioeconomic status-adjusted HR and 95% CIs (CI) were 1.25 (1.10 to 1.41) and 1.27 (1.08 to 1.49), respectively. The frequency of confidential discussions with friends had an inverse U-shaped relationship with the outcomes after 30 years; the HR (95% CI) for ‘sometimes’ versus ‘quite often’ was 1.16 (1.04 to 1.29) for CHD and 1.16 (1.01 to 1.33) for AMI. These associations persisted after adjusting for mental ill-health, lifestyle factors and systolic blood pressure. A low number of friends in late adolescence was not related to an increased CHD or AMI risk.ConclusionsNot having a confidant in late adolescence was associated positively, while the frequency of confidential discussions with friends had an inverse U-shaped relationship with CHD and AMI after 30 years of follow-up, suggesting that these associations are not due to subclinical disease manifestations.
Development and validation of a cardiovascular risk score for patients in the community after acute coronary syndrome
Authors: Poppe Katrina K , Doughty Rob N , Wells Susan , Wu Billy , Earle Nikki J , Richards A Mark , Troughton Richard W , Jackson Rod , Kerr Andrew J 
Published: December 2019

ObjectiveFollowing acute coronary syndrome (ACS), patients are managed long-term in the community, yet few tools are available to guide patient-clinician communication about risk management in that setting. We developed a score for predicting cardiovascular disease (CVD) risk among patients managed in the community after ACS.MethodsAdults aged 30–79 years with prior ACS were identified from a New Zealand primary care CVD risk management database (PREDICT) with linkage to national mortality, hospitalisation, pharmaceutical dispensing and regional laboratory data. A Cox model incorporating clinically relevant factors was developed to estimate the time to a subsequent fatal or non-fatal CVD event and transformed into a 5-year risk score. External validation was performed in patients (Coronary Disease Cohort Study) assessed 4 months post-ACS.ResultsThe PREDICT-ACS cohort included 13 703 patients with prior hospitalisation for ACS (median 1.9 years prior), 69% men, 58% European, median age 63 years, who experienced 3142 CVD events in the subsequent 5 years. Median estimated 5 year CVD risk was 24% (IQR 17%–35%). The validation cohort consisted of 2014 patients, 72% men, 92% European, median age 67 years, with 712 CVD events in the subsequent 5 years. Median estimated 5-year risk was 33% (IQR 24%–51%). The risk score was well calibrated in the derivation and validation cohorts, and Harrell’s c-statistic was 0.69 and 0.68, respectively.ConclusionsThe PREDICT-ACS risk score uses data routinely available in community care to predict the risk of recurrent clinical events. It was derived and validated in real-world contemporary populations and can inform management decisions with patients living in the community after experiencing an ACS.
Life-course socioeconomic status and lung function in adulthood: a study in the EPIPorto cohort
Authors: Rocha Vânia , Stringhini Silvia , Henriques Ana , Falcão Helena , Barros Henrique , Fraga Sílvia 
Published: December 2019

ObjectiveThis study aims to investigate the association of life-course socioeconomic status (SES) with lung function during adulthood, by exploring the influence of life-course social mobility and of cumulative exposure to low SES.MethodsParticipants were 1458 individuals from EPIPorto study, a population-based cohort of Portuguese adults. The life-course SES was computed using participants’ paternal occupation and own occupation, resulting in four patterns: stable high, upward, downward, stable low. A cumulative life-course SES index was also calculated using the participants’ paternal occupation, own education and occupation. Lung function during adulthood was assessed with forced expiratory volume in first second (FEV1) and forced vital capacity (FVC) percentages predicted (higher percentages are associated with better lung function). Linear regression models were used to estimate beta coefficients and 95% CI for the association of socioeconomic indicators and lung function.ResultsDisadvantaged SES from childhood to adulthood was associated with lower lung function (FEV1:−6.64%,−10.68;−2.60/FVC:−3.77%,−7.45;−0.08), and the greater the socioeconomic disadvantage, the lower the lung function (FEV1:−2.56%,−3.98;−1.15/FVC:−1.54%,−2.83;−0.24) among men, independently of marital status and behavioural factors. Among women, SES effects were only observed in those experiencing a stable low life-course SES at older ages (−5.15%,−10.20;−0.09). Men experiencing a downward social mobility presented the lowest lung function, but there was attenuation to the null after accounting for marital status and behavioural factors.ConclusionA life-course disadvantaged SES is an important predictor of lower lung function during adulthood. Downward social mobility was associated with the lowest lung function among men, although this association was mostly explained by behavioural factors.
Strategic Attack & Defense in Security Diffusion Games
Authors: Waniek Marcin , Michalak Tomasz P. , Alshamsi Aamena 
Published: December 2019

Security games model the confrontation between a defender protecting a set of targets and an attacker who tries to capture them. A variant of these games assumes security interdependence between targets, facilitating contagion of an attack. So far, only stochastic spread of an attack has been considered. In this work, we introduce a version of security games, where the attacker strategically drives the entire spread of attack and where interconnections between nodes affect their susceptibility to be captured.
We find that the strategies effective in the settings without contagion or with stochastic contagion are no longer feasible when spread of attack is strategic. While in the former settings it was possible to efficiently find optimal strategies of the attacker, doing so in the latter setting turns out to be an NP-complete problem for an arbitrary network. However, for some simpler network structures, such as cliques, stars, and trees, we show that it is possible to efficiently find optimal strategies of both players. For arbitrary networks, we study and compare the efficiency of various heuristic strategies. As opposed to previous works with no or stochastic contagion, we find that centrality-based defense is often effective when spread of attack is strategic, particularly for centrality measures based on the Shapley value.
First-in-Man Phase I Trial of the Selective MET Inhibitor Tepotinib in Patients with Advanced Solid Tumors
Authors: Falchook Gerald S. , Kurzrock Razelle , Amin Hesham M. , Xiong Wenyuan , Fu Siqing , Piha-Paul Sarina A. , Janku Filip , Eskandari Ghazaleh , Catenacci Daniel V. , Klevesath Manfred , Bruns Rolf , Stammberger Uz , Johne Andreas , Bladt Friedhelm , Friese-Hamim Manja , Girard Pascal , El Bawab Samer , Hong David S. 
Published: December 2019

Abstract

Purpose:
Tepotinib is an oral, potent, highly selective MET inhibitor. This first-in-man phase I trial investigated the MTD of tepotinib to determine the recommended phase II dose (RP2D).

Patients and Methods:
Patients received tepotinib orally according to one of three dose escalation regimens (R) on a 21-day cycle: R1, 30–400 mg once daily for 14 days; R2, 30–315 mg once daily 3 times/week; or R3, 300–1,400 mg once daily. After two cycles, treatment could continue in patients with stable disease until disease progression or unacceptable toxicity. The primary endpoint was incidence of dose-limiting toxicity (DLT) and treatment-emergent adverse events (TEAE). Secondary endpoints included safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor effects.

Results:
One hundred and forty-nine patients received tepotinib (R1: n = 42; R2: n = 45; R3: n = 62). Although six patients reported DLTs [one patient in R1 (115 mg), three patients in R2 (60, 100, 130 mg), two patients in R3 (1,000, 1,400 mg)], the MTD was not reached at the highest tested dose of 1,400 mg daily. The RP2D of tepotinib was established as 500 mg once daily, supported by translational modeling data as sufficient to achieve ≥95% MET inhibition in ≥90% of patients. Treatment-related TEAEs were mostly grade 1 or 2 fatigue, peripheral edema, decreased appetite, nausea, vomiting, and lipase increase. The best overall response in R3 was partial response in two patients, both with MET overexpression.

Conclusions:
Tepotinib was well tolerated with clinical activity in MET-dysregulated tumors. The RP2D of tepotinib was established as 500 mg once daily. MET abnormalities can drive tumorigenesis. This first-in-man trial demonstrated that the potent, highly selective MET inhibitor tepotinib can reduce or stabilize tumor burden and is well tolerated at doses up to 1,400 mg once daily. An RP2D of 500 mg once daily, as determined from translational modeling and simulation integrating human population pharmacokinetic and pharmacodynamic data in tumor biopsies, is being used in ongoing clinical trials.
Combined Targeting of G9a and Checkpoint Kinase 1 Synergistically Inhibits Pancreatic Cancer Cell Growth by Replication Fork Collapse
Authors: Urrutia Guillermo , Salmonson Ann , Toro-Zapata Jorge , de Assuncao Thiago M. , Mathison Angela , Dusetti Nelson , Iovanna Juan , Urrutia Raul , Lomberk Gwen 
Published: December 2019

Abstract

Because of its dismal outcome, pancreatic ductal adenocarcinoma (PDAC) remains a therapeutic challenge making the testing of new pharmacologic tools a goal of paramount importance. Here, we developed a rational approach for inhibiting PDAC growth based on leveraging cell-cycle arrest of malignant cells at a phase that shows increased sensitivity to distinct epigenomic inhibitors. Specifically, we simultaneously inhibited checkpoint kinase 1 (Chk1) by prexasertib and the G9a histone methyltransferase with BRD4770, thereby targeting two key pathways for replication fork stability. Methodologically, the antitumor effects and molecular mechanisms of the combination were assessed by an extensive battery of assays, utilizing cell lines and patient-derived cells as well as 3D spheroids and xenografts. We find that the prexasertib–BRD4770 combination displays a synergistic effect on replication-associated phenomena, including cell growth, DNA synthesis, cell-cycle progression at S phase, and DNA damage signaling, ultimately leading to a highly efficient induction of cell death. Moreover, cellular and molecular data reveal that the synergistic effect of these pathways can be explained, at least in large part, by the convergence of both Chk1 and G9a functions at the level of the ATR–RPA–checkpoint pathway, which is operational during replication stress. Thus, targeting the epigenetic regulator G9a, which is necessary for replication fork stability, combined with inhibition of the DNA damage checkpoint, offers a novel approach for controlling PDAC growth through replication catastrophe.

Implications:
This study offers an improved, context-dependent, paradigm for the use of epigenomic inhibitors and provides mechanistic insight into their potential therapeutic use against PDAC.
Galectin-3 Interacts with C/EBPβ and Upregulates Hyaluronan-Mediated Motility Receptor Expression in Gastric Cancer
Authors: Kang Hyeon-Gu , Kim Won-Jin , Kang Hyeok-Gu , Chun Kyung-Hee , Kim Seok-Jun 
Published: December 2019

Abstract

The hyaluronan-mediated motility receptor (HMMR) is overexpressed in gastric cancer; however, the apparent role of HMMR has not been well defined owing to lack of detailed studies on gastric tumorigenesis. Therefore, we elucidated the functional and regulatory mechanisms of HMMR in gastric cancer. Using publicly available data, we confirmed HMMR overexpression in patients with gastric cancer. HMMR silencing decreased proliferation, migration, and invasion of gastric cancer cells, whereas HMMR overexpression reversed these effects. A gastric cancer xenograft mouse model showed statistically significant inhibition of tumor growth upon HMMR depletion. Previous data from cDNA microarray showed reduced HMMR expression upon inhibition of galectin-3. However, overexpression of galectin-3 increased HMMR expression, cell proliferation, and motility in gastric cancer cells, whereas HMMR silencing blocked these effects. Interestingly, galectin-3 interacted directly with C/EBPβ and bound to HMMR promoter to drive its transcription, and gastric cancer cell proliferation and motility. Altogether, high expression of HMMR promoted gastric cancer cell proliferation and motility and could be a prognostic factor in gastric cancer. In addition, HMMR expression was regulated by the interaction between C/EBPβ and galectin-3. Therefore, targeting HMMR along with galectin-3 and C/EBPβ complex could be a potential treatment strategy for inhibiting gastric cancer progression and metastasis.

Implications:
This study provides evidence that galectin-3 interacts with C/EBPβ in gastric cancer, and galectin-3 and C/EBPβ complex promotes gastric cancer cell progression and motility through upregulating HMMR expression.
B Lymphocytes and Macrophages in the Perivascular Adipose Tissue Are Associated With Coronary Atherosclerosis: An Autopsy Study
Authors: Farias‐Itao Daniela Souza , Pasqualucci Carlos Augusto , Nishizawa Aline , da Silva Luiz Fernando Ferraz , Campos Fernanda Marinho , Bittencourt Márcio Sommer , da Silva Karen Cristina Souza , Leite Renata Elaine Paraízo , Grinberg Lea Tenenholz , Ferretti‐Rebustini Renata Eloah de Lucena , Jacob‐Filho Wilson , Suemoto Claudia Kimie 
Published: December 2019

Background

Macrophages and T lymphocytes in the perivascular adipose tissue (Pv
AT
) were previously linked to coronary artery disease. However, the role of these cells and B lymphocytes in the human Pv
AT
adjacent to unstable atherosclerotic plaques has not been investigated. Moreover, previous studies were inconclusive on whether Pv
AT
inflammation was restricted to the surroundings of the atheroma plaque.

Methods and Results

Coronary arteries were freshly dissected with the surrounding Pv
AT
. Atherosclerotic plaques were classified according to the internationally accepted anatomopathological criteria. Immune cells in the Pv
AT
were detected using immunohistochemistry and then quantified. We used linear and logistic regressions with robust standard errors, adjusted for possible confounding factors. In 246 atherosclerotic plaques (205 stable and 41 unstable plaques) from 82 participants (mean age=69.0±14.4 years; 50% men), the percentage of arterial obstruction was positively correlated with the densities of
CD
68
+
macrophages (
P
=0.003) and
CD
20
+
B lymphocytes (
P
=0.03) in the periplaque Pv
AT
. The number of cells was greater in the periplaque Pv
AT
than in the distal Pv
AT
(macrophages,
P
<0.001; B lymphocytes,
P
=0.04). In addition, the density of macrophages in the periplaque Pv
AT
was greater in the presence of unstable plaques (
P
=0.03) and was also greater near unstable plaques than in the distal Pv
AT
(
P
=0.001).
CD
3
+
T lymphocytes were not associated with percentage of obstruction and stable/unstable plaque composition.

Conclusions

The density of
CD
20
+
B lymphocytes and
CD
68
+
macrophages in periplaque Pv
AT
was increased with plaque size, and the
CD
68
+
macrophages were greater near unstable atherosclerotic plaques than near stable lesions. This inflammation was more intense in the periplaque Pv
AT
than in the Pv
AT
distal to the atherosclerotic plaques.
Associations Between Features of Nonstenosing Carotid Plaque on Computed Tomographic Angiography and Ischemic Stroke Subtypes
Authors: Knight‐Greenfield Ashley , Quitlong Nario Joel Jose , Vora Amar , Baradaran Hediyeh , Merkler Alex , Navi Babak B. , Kamel Hooman , Gupta Ajay 
Published: December 2019

Background

Thromboembolism from nonstenosing carotid plaques may be an underrecognized cause of embolic strokes of undetermined source (
ESUS
). We evaluated the association between features of nonstenosing atherosclerotic plaque on computed tomographic angiography and
ESUS
.

Methods and Results

We identified consecutive acute ischemic stroke patients from 2011 to 2015 who had unilateral anterior territory infarction on brain magnetic resonance imaging and a neck computed tomographic angiography. We included
ESUS
cases and as controls, cardioembolic strokes. Patients with ≥50% internal carotid artery atherosclerotic stenosis ipsilateral to the stroke were excluded from this analysis. Reviewers blinded to infarct location and stroke cause retrospectively evaluated computed tomographic angiography studies for specific plaque features including thickness of the total, soft, and calcified plaque; presence of ulceration; and perivascular fat attenuation. Paired
t
tests and McNemar's test for paired data were used to compare plaque features ipsilateral versus contralateral to the side of infarction. Ninety‐one patients with
ESUS
or cardioembolic stroke were included in this study. Total plaque thickness was greater on the infarcted side (2.1±2.0 mm) than the contralateral side (1.2±1.5 mm) (
P
=0.006) among
ESUS
cases, but not among cardioembolic cases (1.9±1.6 mm versus 1.8±1.6 mm) (
P
=0.32).

Conclusions

Among
ESUS
cases, total plaque thickness was greater ipsilateral to the side of infarction than on the contralateral, stroke‐free side. No such side‐to‐side differences were apparent in cardioembolic strokes. Our findings suggest that nonstenosing large‐artery atherosclerotic plaques represent one underlying mechanism of
ESUS
.