A handful of tumor-derived cell lines form the mainstay of cancer therapeutic development, yielding drugs with an impact typically measured as months to disease progression. To develop more effective ...breast cancer therapeutics and more readily understand their clinical impact, we constructed a functional metabolic portrait of 46 independently derived breast cell lines. Our analysis of glutamine uptake and dependence identified a subset of triple-negative samples that are glutamine auxotrophs. Ambient glutamine indirectly supports environmental cystine acquisition via the xCT antiporter, which is expressed on one-third of triple-negative tumors in vivo. xCT inhibition with the clinically approved anti-inflammatory sulfasalazine decreases tumor growth, revealing a therapeutic target in breast tumors of poorest prognosis and a lead compound for rapid, effective drug development.
•Most breast tumors survive glutamine restriction, limiting its therapeutic use•A subset of triple-negative breast tumors are true glutamine auxotrophs•Conventional biomarkers of glutamine reliance do not identify true auxotrophs•Triple-negative tumors require cystine import via the xCT transporter
Aim
To investigate the effect of simvastatin on lipopolysaccharide (LPS)‐stimulated inflammatory cytokines, cell adhesion molecules and nuclear factor‐κB (NF‐κB) transcription factors in human dental ...pulp cells (HDPCs).
Methodology
The effect of LPS and simvastatin on human dental pulp cell (HDPCs) viability was measured using a 3‐4, 5‐dimethylthiazol‐2‐yl‐2, 5 diphenyltetrazolium bromide (MTT) assay. The expression of inflammatory cytokines and cell adhesion molecules was evaluated by reverse‐transcription polymerase chain reaction (RT‐PCR), enzyme‐linked immunosorbent assay (ELISA) and Western blot analysis. NF‐κB transcription factors were evaluated by Western blot analysis. Statistical analysis was performed with analysis of variance (anova).
Results
The viability of cells exposed to different concentrations of E. coli LPS, P. gingivalis LPS and simvastatin was not significantly different compared with that of control cells (P > 0.05). LPS significantly increased interleukin (IL)‐1β (P < 0.05) and IL‐6 mRNA expression (P < 0.05) and vascular cell adhesion molecule‐1 (VCAM‐1) (P < 0.05) and intercellular adhesion molecule‐1 (ICAM‐1) protein expression (P < 0.05) in HDPCs. Treatment with simvastatin significantly attenuated LPS‐stimulated production of IL‐1β, IL‐6, VCAM‐1 and ICAM‐1 (P < 0.05). Treatment with simvastatin decreased LPS‐induced expression of p65 and phosphorylation of IκB and also significantly decreased the phosphorylation of p65 and IκB in the cytoplasm and the level of p65 in the nucleus (P < 0.05).
Conclusions
Simvastatin has a suppressing effect on LPS‐induced inflammatory cytokine, cell adhesion molecules and NF‐κB transcription factors in HDPCs. Therefore, simvastatin might be a useful candidate as a pulp‐capping agent in vital pulp therapy.
Previously, it was shown in patients with low rectal cancer that a short-axis (SA) lateral node size of 7 mm or greater on primary magnetic resonance imaging (MRI) resulted in a high lateral local ...recurrence (LLR) rate after chemoradiotherapy or radiotherapy (CRT) with total mesorectal excision (TME) and that this risk was lowered by a lateral lymph node dissection (LLND). The role of restaging MRI after (C)RT with regard to LLR risk and which specific patients might benefit from an LLND is not fully understood.
To determine the factors on primary and restaging MRI that are associated with LLR in low rectal cancer after (C)RT and to formulate specific guidelines on which patients might benefit from an LLND.
In this retrospective, multicenter, pooled cohort study, patients who underwent surgery for cT3 or cT4 low rectal cancer with a curative intent from 12 centers in 7 countries from January 2009 to December 2013 were included. All patients' MRIs were rereviewed according to a standardized protocol, with specific attention to lateral nodal features. The original cohort included 1216 patients. For this study, patients who underwent (C)RT and had a restaging MRI were selected, leaving 741 for analyses across 10 institutions, including 651 who underwent (C)RT with TME and 90 who underwent (C)RT with TME and LLND.
The main purpose was to identify the factors on primary and restaging MRI associated with LLR after (C)RT with TME. Whether high-risk patients might benefit in terms of LLR reduction from an LLND was also studied.
Of the 741 included patients, 480 (64.8%) were male, and the mean (SD) age was 60.4 (12.0) years. An SA lateral node size of 7 mm or greater on primary MRI resulted in a 5-year LLR rate of 17.9% after (C)RT with TME. At 3 years, there were no LLRs in 28 patients (29.2%) with lateral nodes that were 4 mm or less on restaging MRI. Nodes that were 7 mm or greater on primary MRI and greater than 4 mm on restaging MRI in the internal iliac compartment resulted in a 5-year LLR rate of 52.3%, significantly higher compared with nodes in the obturator compartment of that size (9.5%; hazard ratio, 5.8; 95% CI, 1.6-21.3; P = .003). Compared with (C)RT with TME alone, treatment with (C)RT with TME and LLND in these unresponsive internal nodes resulted in a significantly lower LLR rate of 8.7% (hazard ratio, 6.2; 95% CI, 1.4-28.5; P = .007).
Restaging MRI is important in clinical decision making in lateral nodal disease. In patients with shrinkage of lateral nodes from an SA node size of 7 mm or greater on primary MRI to an SA node size of 4 mm or less on restaging MRI, which occurs in about 30% of cases, LLND can be avoided. However, persistently enlarged nodes in the internal iliac compartment indicate an extremely high risk of LLR, and an LLND lowered LLR in these cases.
Abstract Purpose The study evaluates and quantifies the potential dosimetric gains of helical tomotherapy (HT) versus step-and-shoot intensity-modulated radiotherapy (SaS-IMRT) for nasopharyngeal ...carcinoma (NPC). Materials and methods Twenty consecutive NPC patients curatively treated by HT were examined. Each case was planned by HT and SaS-IMRT (ADAC Pinnacle3 ) planning system, respectively. Dose plans were compared using dose volume histograms (DVH), conformity index ( CI ), homogeneity index ( HI ), and minimal dose to 1 cc ( Dmin_1cc ) of the planned target volume (PTV) and a comprehensive quality index ( CQI ) of ten organs at risk (OARs). The prescribed dose/fractionation was 72 Gy to the PTV, 64.8 Gy to the elective PTV, and 54 Gy to the clinically negative neck region. The plan of 54 Gy to the PTV (PTV54 ) was used to evaluate the CI and HI in the target. The cumulative doses of the three PTV plans to the OARs were calculated. Results We observed the HT plans significantly improved the CI (improvement ratio: 11.9 ± 5.5%) and HI (improvement ratio: 8.8 ± 1.5%) of the PTV54 compared with SaS-IMRT plans. In addition, the mean/maximal dose of most of the OARs except chiasm was significantly reduced in HT plans, with the CQI of 0.92 ± 0.08. A negative result of HT in chiasm was observed but only significantly revealed in cases without skull base infiltration. Conclusions A dosimetric gain in CI and HI of PTV and sparing of OARs was significantly obtained in HT versus SaS-IMRT plans in NPC patients. Whether such dosimetric superiority in HT could transfer into clinical advantages needs further investigation.
We present new data obtained with the Submillimeter Array for a sample of 14 nearby luminous and ultraluminous infrared galaxies. The galaxies were selected to have distances image Mpc and ...far-infrared luminosities image. The galaxies were observed with spatial resolutions of order 1 kpc in the CO image, CO image, super(13)CO image, and HCO super(+) image lines as well as the continuum at 880 mum and 1.3 mm. We have combined our CO and continuum data to measure an average gas-to-dust mass ratio of image (rms deviation 109) in the central regions of these galaxies, very similar to the value of 150 determined for the Milky Way. This similarity is interesting given the more intense heating from the starburst and possibly accretion activity in the luminous infrared galaxies compared to the Milky Way. We find that the peak H sub(2) surface density correlates with the far-infrared luminosity, which suggests that galaxies with higher gas surface densities inside the central kiloparsec have a higher star formation rate. The lack of a significant correlation between total H sub(2) mass and far-infrared luminosity in our sample suggests that the increased star formation rate is due to the increased availability of molecular gas as fuel for star formation in the central regions. In contrast to previous analyses by other authors, we do not find a significant correlation between central gas surface density and the star formation efficiency, as traced by the ratio of far-infrared luminosity to nuclear gas mass. Our data show that it is the star formation rate, not the star formation efficiency, that increases with increasing central gas surface density in these galaxies.
With the widespread use of sensors and small electronics in the Internet of Things (IoT) era, triboelectric nanogenerators (TENGs) have emerged as sustainable and renewable energy sources owing to ...their high efficiency, compatibility with various materials, and low cost. However, the existing TENGs exhibit a low current output and require a large mechanical input to continuously generate an enhanced current output. In this study, an inhalation‐driven vertical flutter TENG (IVF‐TENG) with an amplified current output is developed. The IVF‐TENG exhibits two types of mechanical behaviors simultaneously, generating a high‐frequency continuous electrical voltage and closed‐circuit current (ICC) output of 17 V and 1.84 μA, respectively, during inhalation, and an electrostatic discharge voltage and ICC output of 456 V and 288 mA at the beginning and end of every inspiratory cycle, respectively. As a user‐position‐indicating light, the IVF‐TENG can power 130 LEDs in series and 140 LEDs in parallel for every inhalation. The IVF‐TENG can charge a capacitor of 660 μF, with a discharge process of a few seconds, to power a commercial Bluetooth tracker and wirelessly transfer the Bluetooth signal to a smartphone. Moreover, the IVF‐TENG can detect the user's respiration state or the presence of chemical warfare agents (GB, DMMP, etc.) via output waveforms.
The inhalation‐driven vertical flutter triboelectric nanogenerator (IVF‐TENG) generates two types of electrical outputs (continuous output and electrostatic discharge output) for every inhalation cycle owing to vertical flutter motion. The IVF‐TENG can function as a gas mask‐integrated self‐powered multifunctional system (self‐powered user‐position‐indicating light, auxiliary power source, user's respiration state detector, and chemical warfare agents sensor).
A
bstract
Recasting phenomenological Lagrangians in terms of SM effective field theory (SMEFT) provides a valuable means of connecting potential BSM physics at momenta well above the electroweak ...scale to experimental signatures at lower energies. In this work we jointly fit the Wilson coefficients of SMEFT operators as well as the PDFs in an extension of the CT18 global analysis framework, obtaining self-consistent constraints to possible BSM physics effects. Global fits are boosted with machine-learning techniques in the form of neural networks to ensure efficient scans of the full PDF+SMEFT parameter space. We focus on several operators relevant for top-quark pair and jet production at hadron colliders and obtain constraints on the Wilson coefficients with Lagrange Multiplier scans. We find mild correlations between the extracted Wilson coefficients, PDFs, and other QCD parameters, and see indications that these correlations may become more prominent in future analyses based on data of higher precision. This work serves as a new platform for joint analyses of SM and BSM physics based on the CTEQ-TEA framework.
The hematopoietic SCT (HSCT) activity in nine Asian countries/regions was surveyed to overview the current situation. Data of 58 113 HSCTs (allogeneic: 63% vs autologous: 37%) performed between 1986 ...and 2006 by 432 transplant teams were collected. The number of HSCTs has been increasing in the past two decades in most countries/regions. The increase in allogeneic HSCTs is greater than in autologous HSCTs. The proportion of unrelated donors among allogeneic HSCTs in 2006 varied widely from <1% (Iran and Vietnam) to 62% (Japan). The use of each stem cell source, that is, BM, PBSC, cord blood and others (including co-infusion of BM and PBSC), also varied widely (36, 58, 0.1 and 6% in HSCT from related donors, respectively, and 53, 11, 35 and 1% in HSCT from unrelated donors, respectively). HSCTs have been continuously increasing for all indications except for chronic myelogenous leukemia and solid tumors. Hemoglobinopathy is a common indication among non-malignant diseases in many Asian countries/regions except for China, Japan and Korea. This survey clearly shows the recent progress of HSCTs in Asia and also some differences in donor and stem cell selection and disease application among countries/regions.
As a valuable tool for harvesting energy, triboelectric nanogenerators (TENGs) exhibit notable advantages over other energy‐harvesting methods in terms of their low weight, low cost and high‐power ...density. Despite their application potential in the domain of portable electronics, TENGs exhibit a limited maximum output owing to the high surface charge density during operation. Furthermore, TENGs inherently produce alternative current (AC); thus, an additional electrical circuit such as a rectifying circuit must be used as a portable power source. To overcome these problems, a triboelectric generation mechanism that can produce both AC and direct current outputs with amplified electrical current through the addition of a simple mechanical component is established. The proposed pillar‐type TENG (P‐TENG) can minimize the electrical loss during operation that occurs due to the contact between electrodes, allowing electrons to flow directly. Moreover, a miniaturized and portable variant of the P‐TENG is designed to harvest mechanical energy in daily‐life activities.
This paper reports an alternative current/direct current (AC/DC) convertible pillar‐type triboelectric nanogenerator that produces amplified current output and has an AC/DC selective mechanism by using high charge density air breakdown and movement of a ring electrode. It can be also designed as a miniature device to improve portability for everyday use.
We present a detailed comparison of the CO (3-2) emitting molecular gas between a local sample of luminous infrared galaxies (U/LIRGs) and a high-redshift sample that comprises submm selected ...galaxies (SMGs), quasars, and Lyman Break Galaxies (LBGs). The U/LIRG sample consists of our recent CO (3-2) survey using the Submillimeter Array while the CO (3-2) data for the high-redshift population are obtained from the literature. We find that the and L FIR relation is correlated over five orders of magnitude, which suggests that the molecular gas traced in CO (3-2) emission is a robust tracer of dusty star formation activity. The near unity slope of 0.93 ± 0.03 obtained from a fit to this relation suggests that the star formation efficiency is constant to within a factor of 2 across different types of galaxies residing in vastly different epochs. The CO (3-2) size measurements suggest that the molecular gas disks in local U/LIRGs (0.3-3.1 kpc) are much more compact than the SMGs (3-16 kpc), and that the size scales of SMGs are comparable to the nuclear separation (5-40 kpc) of the widely separated nuclei of U/LIRGs in our sample. We argue from these results that the SMGs studied here are predominantly intermediate stage mergers, and that the wider line widths arise from the violent merger of two massive gas-rich galaxies taking place deep in a massive halo potential.
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