Adoptive Cellular TherapyO1 IL-15 primes an mTOR-regulated gene-expression program to prolong anti-tumor capacity of human natural killer cellsAndreas Lundqvist1, Vincent van Hoef1, Xiaonan Zhang1, Erik Wennerberg2, J...
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Adoptive Cellular TherapyO1 IL-15 primes an mTOR-regulated gene-expression program to prolong anti-tumor capacity of human natural killer cellsAndreas Lundqvist1, Vincent van Hoef1, Xiaonan Zhang1, Erik Wennerberg2, Julie Lorent1, Kristina Witt1, Laia Masvidal Sanz1, Shuo Liang1, Shannon Murray3, Ola Larsson1, Rolf Kiessling1, Yumeng Mao11Karolinska Institutet, Stockholm, Stockholms Lan, Sweden; 2Weill Cornell Medical college, New York, NY, USA; 3Nova Southeastern University, Cell Therapy Institute, Fort Lauderdale, FL, USACorrespondence: Andreas Lundqvist (***@***)
Background
NK cell-based immunotherapy is a potential therapeutic modality in patients with advanced cancers as transfer of haploidentical NK cells induces beneficial responses in patients with hematological malignancies; and leukemia clearance correlates with persistence and in vivo expansion of NK cells after infusion. Thus, sustained NK cell activity in vivo likely represents a therapy performance-limiting factor.
Methods
We performed genome-wide analysis of cytosolic and polysome-associated mRNA from interleukin (IL)-2 and IL-15 activated NK cells. Furthermore, the ability of IL-2 and IL-15 to sustain human NK cell activity following cytokine withdrawal as well as their effect on NK cells to resist tumor-induced immunosuppression was compared.
Results
After cytokine withdrawal, IL-15-treated NK cells maintained a higher level of cytotoxicity (p < 0.05) and showed lower levels of apoptosis (p < 0.05) compared with cells treated with IL-2. IL-15 augmented mTOR signaling, which correlated with increased expression of genes related to cell metabolism and respiration. Consistently, mTOR inhibition abrogated IL-15-induced cell function advantages. Moreover, mTOR-independent STAT-5 signaling contributed to improved NK cell function during cytokine activation but not following cytokine withdrawal. Upon co-culture with tumor cells or exposure to tumor cell supernatant, IL-15 activated NK cell
Heavy metals existing in the surface of sediments of the tidal river could be transferred into the surrounding natural and artificial biofilms, through physical, chemical, biological or their combination processes. Th...
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ISBN:
(纸本)9781629938141
Heavy metals existing in the surface of sediments of the tidal river could be transferred into the surrounding natural and artificial biofilms, through physical, chemical, biological or their combination processes. This paper studied on the adsorption and transfer regulation of heavy metals in biofilms grown on river rocks and inert carriers in tidal rivers. The natural and artificial biofilms, and the surrounding sediments nearby were taken, among of which the heavy metals (Mn, Zn, Cu, Pb, Ni and Cd) contents were measured using ICP-AES method. The absorption of heavy metals in the biofilms and the migration characteristics of heavy metals into the biofilms were measured and analyzed. Our results showed that the contents of heavy metal in the biofilms were similar to those in the surrounding surface sediments nearby in the tidal rivers, which was probably attributed to the dynamic equilibrium between the biofilms and its surrounding surface sediment and water. The migration of heavy metals between biofilms and surface sediment through water movement in tidal river showed certain limitations for biofilms adsorption to remove heavy metals. The contents of heavy metals in biofilms were impacted by many factors, such as the biofilms characteristics, the types and forms of existing heavy metals, the contents of heavy metals in the adjacent surface sediment, the hydrological conditions, and the formation time of biofilms. This study can provide important references for the remediation of the polluted tidal rivers by using biofilms method.
Table of contents A1 Introduction to the 8th Annual Conference on the science of dissemination and Implementation: Optimizing Personal and Population Health david Chambers, Lisa Simpson d1 discussion forum: Population...
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Table of contents A1 Introduction to the 8th Annual Conference on the science of dissemination and Implementation: Optimizing Personal and Population Health david Chambers, Lisa Simpson d1 discussion forum: Population health d&I research Felicia Hill-Briggs d2 discussion forum: Global health d&I research Gila Neta, Cynthia Vinson d3 discussion forum: Precision medicine andd&I research david Chambers S1 Predictors of community therapists’ use of therapy techniques in a large public mental health system Rinad Beidas, Steven Marcus, Gregory Aarons, Kimberly Hoagwood, Sonja Schoenwald, Arthur Evans, Matthew Hurford, Ronnie Rubin, Trevor Hadley, Frances Barg, Lucia Walsh, danielle Adams, david Mandell S2 Implementing brief cognitive behavioral therapy (CBT) in primary care: Clinicians’ experiences from the field Lindsey Martin, Joseph Mignogna, Juliette Mott, Natalie Hundt, Michael Kauth, Mark Kunik, Aanand Naik, Jeffrey Cully S3 Clinician competence: Natural variation, factors affecting, and effect on patient outcomes Alan McGuire, dominique White, Tom Bartholomew, John McGrew, Lauren Luther, Angie Rollins, Michelle Salyers S4 Exploring the multifaceted nature of sustainability in community-based prevention: A mixed-method approach Brittany Cooper, Angie Funaiole S5 Theory informed behavioral health integration in primary care: Mixed methods evaluation of the implementation of routine depression and alcohol screening and assessment Julie Richards, Amy Lee, Gwen Lapham, Ryan Caldeiro, Paula Lozano, Tory Gildred, Carol Achtmeyer, Evette Ludman, Megan Addis, Larry Marx, Katharine Bradley S6 Enhancing the evidence for specialty mental health probation through a hybrid efficacy and implementation study Tonya Vandeinse, Amy Blank Wilson, Burgin Stacey, Byron Powell, Alicia Bunger, Gary Cuddeback S7 Personalizing evidence-based child mental health care within a fiscally mandated policy reform Miya Barnett, Nicole Stadnick, Lauren Brookman-Frazee, Anna Lau S8 Levera
Four novel ideas are proposed in this paper to integrate an active RFId tag with thermal convection angular accelerometer on an engineering plastic substrate,thus the device is a wireless *** first innovative idea is ...
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Four novel ideas are proposed in this paper to integrate an active RFId tag with thermal convection angular accelerometer on an engineering plastic substrate,thus the device is a wireless *** first innovative idea is that this device is without any movable parts,so it is very *** second new idea is that it is made on an engineering plastic substrate,such as polyimide,the thermal conductivity is much lower than silicon,so it can save more power and very useful for mobile *** third new idea is that the xenon gas is applied in the chamber for heat convection instead of CO used in the traditional thermal convection *** dioxide can produce oxidation effect to the heater and thermal sensors,while the inert gas xenon will *** fourth new idea is the most powerful one to integrate with an active RFId tag on the same substrate,thus it is very useful for mobile operation,and is very easy for usage and *** one considers sensitivity as the first priority,then choose the floating structure(233°C/(rad/s)).On the other hand,if the response speed is the requirement,then the non-floating structure is better(70μs).
Background: Climate-smart agriculture (CSA) addresses the challenge of meeting the growing demand for food, fibre and fuel, despite the changing climate and fewer opportunities for agricultural expansion on additional...
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Background: Climate-smart agriculture (CSA) addresses the challenge of meeting the growing demand for food, fibre and fuel, despite the changing climate and fewer opportunities for agricultural expansion on additional lands. CSA focuses on contributing to economic development, poverty reduction and food security;maintaining and enhancing the productivity and resilience of natural and agricultural ecosystem functions, thus building natural capital;and reducing trade-offs involved in meeting these goals. Current gaps in knowledge, work within CSA, and agendas for interdisciplinary research andscience-based actions identified at the 2013 Global science Conference on Climate-Smart Agriculture (davis, CA, USA) are described here within three themes: (1) farm and food systems, (2) landscape and regional issues and (3) institutional and policy aspects. The first two themes comprise crop physiology and genetics, mitigation and adaptation for livestock and agriculture, barriers to adoption of CSA practices, climate risk management and energy and biofuels (theme 1);and modelling adaptation and uncertainty, achieving multifunctionality, food and fishery systems, forest biodiversity and ecosystem services, rural migration from climate change and metrics (theme 2). Theme 3 comprises designing research that bridges disciplines, integrating stakeholder input to directly link science, action and governance. Outcomes: In addition to interdisciplinary research among these themes, imperatives include developing (1) models that include adaptation and transformation at either the farm or landscape level;(2) capacity approaches to examine multifunctional solutions for agronomic, ecological and socioeconomic challenges;(3) scenarios that are validated by direct evidence and metrics to support behaviours that foster resilience and natural capital;(4) reductions in the risk that can present formidable barriers for farmers during adoption of new technology and practices;and (5) an understan
Being a “gracious professional” is the key to leadership, whether you’re an engineer, a scientist, or an MIT professor. As managing director of Stanford University's ***, this Renaissance woman spends her time ...
Being a “gracious professional” is the key to leadership, whether you’re an engineer, a scientist, or an MIT professor. As managing director of Stanford University's ***, this Renaissance woman spends her time developing “adaptive learners.” Olin college's first president (and first employee) has plenty to say about engineering—and education. Rethinking the MBA at Harvard Business School.
In this research, we proposed a guidance law by refining the fuzzy membership functions and applying neural optimization algorithms alternatively in each step, such as Gradient descent (Gd) and Levenberg-Marquardt (LM...
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In this research, we proposed a guidance law by refining the fuzzy membership functions and applying neural optimization algorithms alternatively in each step, such as Gradient descent (Gd) and Levenberg-Marquardt (LM) methods. The boundaries of fuzzy error membership functions are lowered to increase the system performance. Besides, the error rate and output are divided into six types of models for trade-off. Both missile turning rate time constant and radome aberration error slope are taken into consideration. Comparisons with the proportion navigation (PN), fuzzy and the proposed methods are also made; we note the performances obtained by the proposed method are better. Besides, the acceleration commands are lower than the previous research and without oscillation or diverging effects at the final stage of interception. Thus even there are system parameter variation effects; the guidance loops can always track the target, and yields better guidance performances.
Previous studies have demonstrated that melatonin combined with exercise can alleviate secondary damage after spinal cord injury in rats. Therefore, it is hypothesized that melatonin combined with exercise can also al...
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Previous studies have demonstrated that melatonin combined with exercise can alleviate secondary damage after spinal cord injury in rats. Therefore, it is hypothesized that melatonin combined with exercise can also alleviate ischemic brain damage. In this study, adult rats were subjected to right middle cerebral artery occlusion after receiving 10 mg/kg melatonin or vehicle subcutaneously twice daily for 14 days. Forced exercise using an animal treadmill was performed at 20 m/min for 30 minutes per day for 6 days prior to middle cerebral artery occlusion. After middle cerebral artery occlusion, each rat received melatonin combined with exercise, melatonin or exercise alone equally for 7 days until sacrifice. Interestingly, rats receiving melatonin combined with exercise exhibited more severe neurological deficits than those receiving melatonin or exercise alone. Hypoxia-inducible factor la mRNA in the brain tissue was upregulated in rats receiving melatonin combined with exercise. Similarly, microtubule associated protein-2 mRNA expression was significantly upregulated in rats receiving melatonin alone. Chondroitin sulfate proteoglycan 4 (NG2) mRNA expression was significantly decreased in rats receiving melatonin combined with exercise as well as in rats receiving exercise alone. Furthermore, neural cell loss in the primary motor cortex was significantly reduced in rats receiving melatonin or exercise alone, but the change was not observed in rats receiving melatonin combined with exercise. These findings suggest that excessive intervention with melatonin, exercise or their combination may lead to negative effects on ischemia/reperfusion-induced brain damage.
This research applied both the traditional and the fuzzy control methods for mobile satellite antenna tracking system design. Firstly, the antenna tracking and the stabilization loops were designed according to the tr...
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