bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dependence on well widths of total optical absorption coefficient of asymmetric triple GaAlAs/GaAs and GaInAs/GaAs quantum wells
Authors: Ozturk O. , Ozturk E. , Elagoz S. 
Published: July 2019

Herein, the total optical absorption coefficient (TOAC) and the electronic characteristics of asymmetric triple Ga[Formula: see text]Al[Formula: see text]As/GaAs (A model) and Ga[Formula: see text]In[Formula: see text]As/GaAs (B model) quantum wells (QWs) have been examined related to the well widths (WWs). For TOAC, we first varied all WWs equally, and then we kept a WW constant and changed the other two WWs. The wavefunctions (WFs), the subband energies and the probability densities of asymmetric triple quantum wells (ATQW) with different QW shapes under effective mass approach were determined by the solution of Schrödinger equation. According to the results obtained, the major diversities of A and B models are the effective mass and the energy gap. The potential depth and the energy levels (ELs) of A model are continuously smaller than of B model. We see that WWs have a great influence on TOAC and the electronic features of ATQW. The inter-subband absorption spectrum designates blue/red shifts, when the energy spacing varies with WWs. These characteristics draw a convenient attention for the purpose of adjustable semiconductor devices. Hence, the alteration of this absorption spectrum, which could be fit for many optical modulators and infra-red optical device applications, may be efficiently realized by changing WWs. Highlights Energy spacing varies by increasing WWs. Due to the shape of the wells, the influence of each WW is quite different from the others. TOAC varies with rising WWs. The absorption spectrum illustrates red or blue shifts depending on WWs.
Luminescence studies of Eu3+ ions in tellurite glass ceramics
Authors: Hong Tran Thi , Dung Phan Tien , Quang Vu Xuan 
Published: July 2019

The optical properties of Eu[Formula: see text] ions in tellurite glass ceramics with the chemical composition 50TeO2–29B2O3–10ZnO–10Na2O–1Eu2O3-based precursor glasses were presented. These precursor glasses have been prepared by melt quenching method in air, followed by thermal annealing at 550[Formula: see text]C for 12 h, 24 h and 36 h. After thermal annealing process, the micro–crystals appeared in host tellurite glasses. Judd–Ofelt (JO) parameters were calculated from the photoluminescence (PL) spectral measurements. The [Formula: see text], [Formula: see text] and [Formula: see text] parameters have been used to estimate the radiative properties of Eu[Formula: see text] ions in tellurite glass ceramics such as transition probabilities, branching ratio, radiative lifetimes and stimulated emission cross-section. The results of tellurite glass ceramic have been discussed and compared with the similar studies.
Thermal Performance Curve Analysis for Enhancement of an Air Conditioner in Thailand
Authors: Chaiyat Nattaporn 
Published: July 2019

This study presents a method for analysing air conditioner efficiency by using a thermal performance curve. Enhancement techniques consisting of the use of a phase change material (PCM), a vapor compression heat pump (VCHP), ultrasound, drop-in refrigerant, a commercial R-32 air conditioner using ultrasound and a double-storage tank are reported under the weather conditions in Thailand. For the PCM, Rubitherm20 (RT-20) in the forms of a paraffin ball and a plastic pack was selected to cool the return air of the evaporator, which directly caused decreases in power consumption of 7.85% and 5.78%, respectively. The R-123 VCHP was integrated with the air conditioner at the condenser to receive and boost rejected heat to the hot water temperature of 60–70∘C. Ultrasonic wave generators at 42[Formula: see text]kHz frequency were installed at the evaporator to improve heat transfer characteristics and reduce the electrical power usage of the air conditioner by 8%. The R-32 drop-in refrigerant technique was tested in an R-410a air conditioner model. The R-32 unit showed the advantages of a smaller environmental impact and a higher cooling energy efficiency ratio (EER) compared with that of the R-410a unit. Moreover, the commercial R-32 air conditioner and a 40 kHz ultrasonic generator were integrated. The combined unit revealed a higher EER of 7.69% compared with that of the conventional commercial R-32 unit. For a double-storage tank, it was shown that the maximum hot water temperature in the storage tank was approximately 49∘C. The highest effective method to enhance the cooling capacity of air-conditioner is the technique of R-32 air conditioner and ultrasonic wave for increasing the cooling efficiency of 8.54%.
Determinants of skeletal muscle oxygen consumption assessed by near-infrared diffuse correlation spectroscopy during incremental handgrip exercise
Authors: Rosenberry Ryan , Tucker Wesley J. , Haykowsky Mark J. , Trojacek Darian , Chamseddine Houda H. , Arena-Marshall Carrie A. , Zhu Ye , Wang Jing , Kellawan J. Mikhail , Tian Fenghua , Nelson Michael D. 
Published: July 2019

Near-infrared diffuse correlation spectroscopy (DCS) is a rapidly evolving optical imaging technique for the assessment of skeletal muscle O2 utilization (mVO2). We compared DCS-derived determinants of mVO2 with conventional measures [blood flow by brachial artery Doppler ultrasound and venous O2 saturation ([Formula: see text])] in eight volunteers at rest and during incremental handgrip exercise. Brachial artery blood flow and DCS-derived blood flow index (BFI) were linearly related (R2 = 0.57) and increased with each workload, whereas [Formula: see text] decreased from 65.3 ± 2.5% (rest) to 39.9 ± 3.0% (light exercise; P < 0.01) with no change thereafter. In contrast, DCS-derived tissue O2 saturation decreased progressively with each incremental stage ( P < 0.01), driven almost entirely by an initial steep rise in deoxyhemoglobin/myoglobin, followed by a linear increase thereafter. Whereas seemingly disparate at first glance, we believe these two approaches provide similar information. Indeed, by plotting the mean convective O2 delivery and diffusive O2 conductance, we show that the initial increase in mVO2 during the transition from rest to exercise was achieved by a greater increase in diffusive O2 conductance versus convective O2 delivery (10-fold vs. 4-fold increase, respectively), explaining the initial decline in [Formula: see text]. In contrast, the increase in mVO2 from light to heavy exercise was achieved by equal increases (1.8-fold) in convective O2 delivery and diffusive O2 conductance, explaining the plateau in [Formula: see text]. That DCS-derived BFI and deoxyhemoglobin/myoglobin (surrogate measure of O2 extraction) share the same general biphasic pattern suggests that both DCS and conventional approaches provide complementary information regarding the determinants of mVO2. NEW & NOTEWORTHY Near-infrared diffuse correlation spectroscopy (DCS) is an emerging optical imaging technique for quantifying skeletal muscle O2 delivery and utilization at the microvascular level. Here, we show that DCS provides complementary insight into the determinants of muscle O2 consumption across a wide range of exercise intensities, further establishing the utility of DCS.
Local exercise does not prevent the aortic stiffening response to acute prolonged sitting: a randomized crossover trial
Authors: Evans William S. , Stoner Lee , Willey Quentin , Kelsch Elizabeth , Credeur Daniel P. , Hanson Erik D. 
Published: July 2019

Prolonged sitting has been shown to promote endothelial dysfunction in the lower legs. Furthermore, it has been reported that simple sitting-interruption strategies, including calf raises, prevent leg endothelial dysfunction. However, it is unclear whether prolonged sitting affects central cardiovascular health, or whether simple sitting-interruption strategies prevent impaired central cardiovascular health. This study sought to answer two questions: in young, healthy adults 1) does prolonged sitting (3 h) lead to increased aortic stiffness, and 2) do intermittent calf raise exercises to prevent pooling prevent aortic stiffening. Twenty young, healthy participants (21.7 ± 2.5 yr, 70% female, 25.5 ± 6.1 kg/m2) were randomized to 3 h of sitting with (CALF) or without (CON) 10 calf raises every 10 min. Aortic stiffening [carotid-femoral pulse wave velocity (PWV)] was measured in the supine position pre- and post-sitting. Venous pooling during sitting was estimated with total hemoglobin (tHB) concentration using near-infrared spectroscopy. There were no condition × time interactions. Following 3 h of sitting, PWV significantly increased (0.30 ± 0.46 m/s, P < 0.001). There was no condition effect for PWV ( P = 0.694), indicating the intermittent calf rises did not preserve central cardiovascular health. tHb was not significantly affected by sitting ( P = 0.446) but was 1.9 μM higher for CON versus CALF ( P = 0.106). Sitting increases aortic stiffness in young, healthy individuals, a process that may be influenced by lower extremity blood pooling. Calf raises, which have been reported to preserve vascular function in the legs, do not appear to provide sufficient stimulus for maintaining central cardiovascular health. NEW & NOTEWORTHY Although simple strategies, such as fidgeting or calf raises, are sufficient for preserving vascular function in the legs, data from the current study indicate that such strategies are not sufficient for maintaining central cardiovascular health, which is linked to cardiovascular disease.
Computational analysis of airflow dynamics for predicting collapsible sites in the upper airways: machine learning approach
Authors: Yeom Seung Ho , Na Ji Sung , Jung Hwi-Dong , Cho Hyung-Ju , Choi Yoon Jeong , Lee Joon Sang 
Published: July 2019

Obstructive sleep apnea (OSA) is a common sleep breathing disorder. With the use of computational fluid dynamics (CFD), this study provides a quantitative standard for accurate diagnosis and effective surgery based on the investigation of the relationship between airway geometry and aerodynamic characteristics. Based on computed tomography data from patients having normal geometry, 4 major geometric parameters were selected and a total of 160 idealized cases were modeled and simulated. We created a predictive model using Gaussian process regression (GPR) through a data set obtained through numerical method. The results demonstrated that the mean accuracy of the overall GPR model was ~72% with respect to the CFD results for the realistic upper airway model. A support vector machine model was also used to identify the degree of OSA symptoms in patients as normal-mild and moderate and severe. We achieved an accuracy of 82.5% with the training data set and an accuracy of 80% with the test data set.NEW & NOTEWORTHY There have been many studies on the analysis of obstructive sleep apnea (OSA) through computational fluid dynamics and finite element analysis. However, these methods are not useful for practical medical applications because they have limited information for OSA symptom. This study employs the machine learning algorithm to predict flow characteristics quickly and to determine the symptoms of the patient's OSA. The overall Gaussian process regression model's mean accuracy was ~72%, and the accuracy for the classification of OSA was >80%.
BRD4 Promotes Gastric Cancer Progression and Metastasis through Acetylation-Dependent Stabilization of Snail
Authors: Qin Zhong-yi , Wang Tao , Su Siyuan , Shen Li-ting , Zhu Guang-xi , Liu Qin , Zhang Liang , Liu Ke-wei , Zhang Yue , Zhou Zhi-hua , Zhang Xiao-ning , Wen Liang-zhi , Yao Yue-liang , Sun Wen-jing , Guo Yan , Liu Kai-jun , Liu Lei , Wang Xing-wei , Wei Yan-ling , Wang Jun , Xiao Hua-liang , Liu Pengda , Bian Xiu-wu , Chen Dong-feng , Wang Bin 
Published: July 2019

Abstract

Cancer metastasis, a leading cause of death in patients, is associated with aberrant expression of epigenetic modifiers, yet it remains poorly defined how epigenetic readers drive metastatic growth and whether epigenetic readers are targetable to control metastasis. Here, we report that bromodomain-containing protein 4 (BRD4), a histone acetylation reader and emerging anticancer therapeutic target, promotes progression and metastasis of gastric cancer. The abundance of BRD4 in human gastric cancer tissues correlated with shortened metastasis-free gastric cancer patient survival. Consistently, BRD4 maintained invasiveness of cancer cells in vitro and their dissemination at distal organs in vivo. Surprisingly, BRD4 function in this context was independent of its putative transcriptional targets such as MYC or BCL2, but rather through stabilization of Snail at posttranslational levels. In an acetylation-dependent manner, BRD4 recognized acetylated lysine 146 (K146) and K187 on Snail to prevent Snail recognition by its E3 ubiquitin ligases FBXL14 and β-Trcp1, thereby inhibiting Snail polyubiquitination and proteasomal degradation. Accordingly, genome-wide transcriptome analyses identified that BRD4 and Snail regulate a partially shared metastatic gene signature in gastric cancer cells. These findings reveal a noncanonical posttranscriptional regulatory function of BRD4 in maintaining cancer growth and dissemination, with immediate translational implications for treating gastric metastatic malignancies with clinically available bromodomain inhibitors.

Significance:
These findings reveal a novel posttranscriptional regulatory function of the epigenetic reader BRD4 in cancer metastasis via stabilizing Snail, with immediate translational implication for treating metastatic malignancies with clinically available bromodomain inhibitors.
Dose Optimization for Anticancer Drug Combinations: Maximizing Therapeutic Index via Clinical Exposure-Toxicity/Preclinical Exposure-Efficacy Modeling
Authors: Bottino Dean C. , Patel Mayankbhai , Kadakia Ekta , Zhou Jilai , Patel Chirag , Neuwirth Rachel , Iartchouk Natasha , Brake Rachael , Venkatakrishnan Karthik , Chakravarty Arijit 
Published: July 2019

Abstract

Purpose:
Recommended phase II dose (RP2D) determination for combination therapy regimens is a constrained optimization problem of maximizing antitumor activity within the constraint of clinical tolerability to provide a wide therapeutic index. A methodology for addressing this problem was developed and tested using clinical and preclinical data from combinations of the investigational drugs TAK-117, a PI3Kα inhibitor, and TAK-228, a TORC1/2 dual inhibitor.

Experimental Design:
Utilizing free fraction-corrected average concentrations, C_{117}^{avg}\ and C_{228}^{avg}, which are the primary pharmacokinetic predictors of single-agent preclinical antitumor activity, a preclinical exposure-efficacy surface was characterized, allowing for nonlinear interactions between growth rate inhibition of the agents on a MDA-MB-361 cell line xenograft model. Logistic regression was used to generate an exposure-effect surface for C_{117}^{avg}\ and C_{228}^{avg} versus clinical toxicity outcomes [experiencing a dose-limiting toxicity (DLT)] in single-agent and combination dose-escalation studies. A maximum tolerated exposure curve was defined at which DLT probability was 25%; predicted antitumor activity along this curve was used to determine optimal RP2D.

Results:
The toxicity constraint curve determined from early clinical data predicted that any clinically tolerable combination was unlikely to result in greater antitumor activity than either single-agent TAK-117 or TAK-228 administered at their respective MTDs. Similar results were obtained with 10 other cell lines, with one agent or the other predicted to outperform the combination.

Conclusions:
This methodology represents a general, principled way of evaluating and selecting optimal RP2D combinations in oncology. The methodology will be retested upon availability of clinical data from TAK-117/TAK-228 combination phase II studies.
See related commentary by Mayawala et al., p. 6564
Inhibition of Bcl-2 Synergistically Enhances the Antileukemic Activity of Midostaurin and Gilteritinib in Preclinical Models of FLT3-Mutated Acute Myeloid Leukemia
Authors: Ma Jun , Zhao Shoujing , Qiao Xinan , Knight Tristan , Edwards Holly , Polin Lisa , Kushner Juiwanna , Dzinic Sijana H. , White Kathryn , Wang Guan , Zhao Lijing , Lin Hai , Wang Yue , Taub Jeffrey W. , Ge Yubin 
Published: July 2019

Abstract

Purpose:
To investigate the efficacy of the combination of the FLT3 inhibitors midostaurin or gilteritinib with the Bcl-2 inhibitor venetoclax in FLT3-internal tandem duplication (ITD) acute myeloid leukemia (AML) and the underlying molecular mechanism.

Experimental Design:
Using both FLT3-ITD cell lines and primary patient samples, Annexin V-FITC/propidium iodide staining and flow cytometry analysis were used to quantify cell death induced by midostaurin or gilteritinib, alone or in combination with venetoclax. Western blot analysis was performed to assess changes in protein expression levels of members of the JAK/STAT, MAPK/ERK, and PI3K/AKT pathways, and members of the Bcl-2 family of proteins. The MV4-11–derived xenograft mouse model was used to assess in vivo efficacy of the combination of gilteritinib and venetoclax. Lentiviral overexpression of Mcl-1 was used to confirm its role in cell death induced by midostaurin or gilteritinib with venetoclax. Changes of Mcl-1 transcript levels were assessed by RT-PCR.

Results:
The combination of midostaurin or gilteritinib with venetoclax potently and synergistically induces apoptosis in FLT3-ITD AML cell lines and primary patient samples. The FLT3 inhibitors induced downregulation of Mcl-1, enhancing venetoclax activity. Phosphorylated-ERK expression is induced by venetoclax but abolished by the combination of venetoclax with midostaurin or gilteritinib. Simultaneous downregulation of Mcl-1 by midostaurin or gilteritinib and inhibition of Bcl-2 by venetoclax results in “free” Bim, leading to synergistic induction of apoptosis. In vivo results show that gilteritinib in combination with venetoclax has therapeutic potential.

Conclusions:
Inhibition of Bcl-2 via venetoclax synergistically enhances the efficacy of midostaurin and gilteritinib in FLT3-mutated AML.
See related commentary by Perl, p. 6567
Genomic Profiling of Blood-Derived Circulating Tumor DNA from Patients with Colorectal Cancer: Implications for Response and Resistance to Targeted Therapeutics
Authors: Choi In Sil , Kato Shumei , Fanta Paul T. , Leichman Lawrence , Okamura Ryosuke , Raymond Victoria M. , Lanman Richard B. , Lippman Scott M. , Kurzrock Razelle 
Published: July 2019

Abstract
Molecular profiling of circulating tumor DNA (ctDNA) is a promising noninvasive tool. Here, next-generation sequencing (NGS) of blood-derived ctDNA was performed in patients with advanced colorectal cancer. We investigated ctDNA-derived genomic alterations, including potential actionability, concordance with tissue NGS, and serial dynamics in 78 patients with colorectal cancer using a clinical-grade NGS assay that detects single nucleotide variants (54–73 genes) and selected copy-number variants, fusions, and indels. Overall, 63 patients [80.8% (63/78)] harbored ctDNA alterations; 59 [75.6% (59/78)], ≥1 characterized alteration (variants of unknown significance excluded). All 59 patients had actionable alterations potentially targetable with FDA-approved drugs [on-label and/or off-label (N = 54) or with experimental drugs in clinical trials (additional five patients); University of California San Diego Molecular Tumor Board assessment]: 45, by OncoKB (http://oncokb.org/#/). The tissue and blood concordance rates for common specific alterations ranged from 62.3% to 86.9% (median = 5 months between tests). In serial samples from patients on anti-EGFR therapy, multiple emerging alterations in genes known to be involved in therapeutic resistance, including KRAS, NRAS, BRAF, EGFR, ERBB2, and MET were detected. In conclusion, over 80% of patients with stage IV colorectal cancer had detectable ctDNA, and the majority had potentially actionable alterations. Concordance between tissue and blood was between 62% and 87%, despite a median of 5 months between tests. Resistance alterations emerged on anti-EGFR therapy. Therefore, biopsy-free, noninvasive ctDNA analysis provides data relevant to the clinical setting. Importantly, sequential ctDNA analysis detects patterns of emerging resistance allowing for precision planning of future therapy.
HDL (High-Density Lipoprotein) Cholesterol Efflux Capacity Is Associated With Incident Cardiovascular Disease in the General Population
Authors: Ebtehaj Sanam , Gruppen Eke G. , Bakker Stephan J.L. , Dullaart Robin P.F. , Tietge Uwe J.F. 
Published: July 2019

Objective:
Focus is shifting from HDL-C (high-density lipoprotein cholesterol) as predictive biomarker for cardiovascular disease (CVD) towards antiatherogenic HDL functionalities. Still, limited data exist on the prospective association of HDL function metrics with CVD events. The current work aimed to determine, if baseline HDL-C efflux capacity (CEC) is associated with future CVD events in the general population.

Approach and Results:

We performed a prospective study among participants of the PREVEND (Prevention of Renal and Vascular End-stage Disease) cohort (follow-up, 12 years). From the overall n=8592 subjects 325 with previous CVD events were excluded; of the remaining 8267 eligible participants all subjects with new CVD events during follow-up were selected and individually matched to controls for age, sex, smoking status, and HDL-C levels. CEC at baseline was quantified using human THP-1-derived macrophage foam cells and apolipoprotein B-depleted plasma. Despite identical HDL-C and apoA (apolipoprotein)-I levels between cases (n=351) and controls (n=354) CEC was significantly lower in cases (0.93±0.29 versus 1.01±0.24 arbitrary units;
P
<0.001). In all subjects combined, CEC correlated positively with HDL-C and apoA-I and negatively with body mass index, hsCRP (high-sensitivity C-reactive protein), and urinary albumin excretion. CEC was inversely associated with incident CVD events, both expressed per quartile and per 1 SD change (odds ratio, 0.73; 95% CI, 0.62–0.86;
P
<0.001); this association remained significant after adjustments for HDL-C, hsCRP, kidney function, and several other clinical covariates.

Conclusions:
Combined these data demonstrate that in the general population baseline CEC is significantly associated with the future development of CVD events independent of HDL-C and apoA-I plasma levels.