High-definition vertically aligned liquid crystal microdisplays using a circularly polarized light

A high-definition vertically aligned liquid crystal (LC) microdisplay exhibits a excellent contrast ratio, but its fringing field effect splits the bright state unevenly and leads to a very slow response time. By utilizing a circularly polarized light instead of conventional linearly polarized light, we have overcome the long-standing problems of poor sharpness, low brightness, and slow response time. Confirming computer simulations agree with the experimental results well. This approach can be applied to both reflective and transmissive LC microdisplays

Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards

Myeloid-derived suppressor cells (MDSCs) have emerged as major regulators of immune responses in cancer and other pathological conditions. In recent years, ample evidence supports key contributions of MDSC to tumour progression through both immune-mediated mechanisms and those not directly associated with immune suppression. MDSC are the subject of intensive research with >500 papers published in 2015 alone. However, the phenotypic, morphological and functional heterogeneity of these cells generates confusion in investigation and analysis of their roles in inflammatory responses. The purpose of this communication is to suggest characterization standards in the burgeoning field of MDSC research

Antibody-Mediated LILRB2-Receptor Antagonism Induces Human Myeloid-Derived Suppressor Cells to Kill Mycobacterium tuberculosis

Tuberculosis is a leading cause of death in mankind due to infectious agents, and Mycobacterium tuberculosis (Mtb) infects and survives in macrophages (MФs). Although MФs are a major niche, myeloid-derived suppressor cells (MDSCs) are an alternative site for pathogen persistence. Both MФs and MDSCs express varying levels of leukocyte immunoglobulin-like receptor B (LILRB), which regulate the myeloid cell suppressive function. Herein, we demonstrate that antagonism of LILRB2 by a monoclonal antibody (mab) induced a switch of human MDSCs towards an M1-macrophage phenotype, increasing the killing of intracellular Mtb. Mab-mediated antagonism of LILRB2 alone and its combination with a pharmacological blockade of SHP1/2 phosphatase increased proinflammatory cytokine responses and phosphorylation of ERK1/2, p38 MAPK, and NF-kB in Mtb-infected MDSCs. LILRB2 antagonism also upregulated anti-mycobacterial iNOS gene expression and an increase in both nitric oxide and reactive oxygen species synthesis. Because genes associated with the anti-mycobacterial function of M1-MФs were enhanced in MDSCs following mab treatment, we propose that LILRB2 antagonism reprograms MDSCs from an immunosuppressive state towards a pro-inflammatory phenotype that kills Mtb. LILRB2 is therefore a novel therapeutic target for eradicating Mtb in MDSCs

Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice

Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic drainage from skin — 1 surgical and the other genetic — to quantitatively track RCT following injection of [3H]-cholesterol–loaded macrophages upstream of blocked or absent lymphatic vessels. Macrophage RCT was markedly impaired in both models, even at sites with a leaky vasculature. Inhibited RCT was downstream of cholesterol efflux from macrophages, since macrophage efflux of a fluorescent cholesterol analog (BODIPY-cholesterol) was not altered by impaired lymphatic drainage. We next addressed whether RCT was mediated by lymphatic vessels from the aortic wall by loading the aortae of donor atherosclerotic Apoe-deficient mice with [2H]6-labeled cholesterol and surgically transplanting these aortae into recipient Apoe-deficient mice that were treated with anti-VEGFR3 antibody to block lymphatic regrowth or with control antibody to allow such regrowth. [2H]-Cholesterol was retained in aortae of anti–VEGFR3-treated mice. Thus, the lymphatic vessel route is critical for RCT from multiple tissues, including the aortic wall. These results suggest that supporting lymphatic transport function may facilitate cholesterol clearance in therapies aimed at reversing atherosclerosis

5-Fluorouracil targets thymidylate synthase in the selective suppression of TH17 cell differentiation

While it is well established that treatment of cancer patients with 5-Fluorouracil (5-FU) can result in immune suppression, the exact function of 5-FU in the modulation of immune cells has not been fully established. We found that low dose 5-FU selectively suppresses TH17 and TH1 cell differentiation without apparent effect on Treg, TH2, and significantly suppresses thymidylate synthase (TS) expression in TH17 and TH1 cells but has a lesser effect in tumor cells and macrophages. Interestingly, the basal expression of TS varies significantly between T helper phenotypes and knockdown of TS significantly impairs TH17 and TH1 cell differentiation without affecting the differentiation of either Treg or TH2 cells. Finally, low dose 5-FU is effective in ameliorating colitis development by suppressing TH17 and TH1 cell development in a T cell transfer colitis model. Taken together, the results highlight the importance of the anti-inflammatory functions of low dose 5-FU by selectively suppressing TH17 and TH1 immune responses

Standard and Embedded Solitons in Nematic Optical Fibers

A model for a non-Kerr cylindrical nematic fiber is presented. We use the multiple scales method to show the possibility of constructing different kinds of wavepackets of transverse magnetic (TM) modes propagating through the fiber. This procedure allows us to generate different hierarchies of nonlinear partial differential equations (PDEs) which describe the propagation of optical pulses along the fiber. We go beyond the usual weakly nonlinear limit of a Kerr medium and derive an extended Nonlinear Schrodinger equation (eNLS) with a third order derivative nonlinearity, governing the dynamics for the amplitude of the wavepacket. In this derivation the dispersion, self-focussing and diffraction in the nematic are taken into account. Although the resulting nonlinear $PDE$ may be reduced to the modified Korteweg de Vries equation (mKdV), it also has additional complex solutions which include two-parameter families of bright and dark complex solitons. We show analytically that under certain conditions, the bright solitons are actually double embedded solitons. We explain why these solitons do not radiate at all, even though their wavenumbers are contained in the linear spectrum of the system. Finally, we close the paper by making comments on the advantages as well as the limitations of our approach, and on further generalizations of the model and method presented.Comment: "Physical Review E, in press

Early prediction of clinical response to checkpoint inhibitor therapy in human solid tumors through mathematical modeling

Background:: Checkpoint inhibitor therapy of cancer has led to markedly improved survival of a subset of patients in multiple solid malignant tumor types, yet the factors driving these clinical responses or lack thereof are not known. We have developed a mechanistic mathematical model for better understanding these factors and their relations in order to predict treatment outcome and optimize personal treatment strategies. Methods:: Here, we present a translational mathematical model dependent on three key parameters for describing efficacy of checkpoint inhibitors in human cancer: tumor growth rate (α), tumor-immune infiltration (Λ), and immunotherapy-mediated amplification of anti-tumor response (µ). The model was calibrated by fitting it to a compiled clinical tumor response dataset (n = 189 patients) obtained from published anti-PD-1 and anti-PD-L1 clinical trials, and then validated on an additional validation cohort (n = 64 patients) obtained from our in-house clinical trials. Results:: The derived parameters Λ and µ were both significantly different between responding versus nonresponding patients. Of note, our model appropriately classified response in 81.4% of patients by using only tumor volume measurements and within 2 months of treatment initiation in a retrospective analysis. The model reliably predicted clinical response to the PD-1/PD-L1 class of checkpoint inhibitors across multiple solid malignant tumor types. Comparison of model parameters to immunohistochemical measurement of PD-L1 and CD8+ T cells confirmed robust relationships between model parameters and their underlying biology. Conclusions:: These results have demonstrated reliable methods to inform model parameters directly from biopsy samples, which are conveniently obtainable as early as the start of treatment. Together, these suggest that the model parameters may serve as early and robust biomarkers of the efficacy of checkpoint inhibitor therapy on an individualized per-patient basis. Funding:: We gratefully acknowledge support from the Andrew Sabin Family Fellowship, Center for Radiation Oncology Research, Sheikh Ahmed Center for Pancreatic Cancer Research, GE Healthcare, Philips Healthcare, and institutional funds from the University of Texas M.D. Anderson Cancer Center. We have also received Cancer Center Support Grants from the National Cancer Institute (P30CA016672 to the University of Texas M.D. Anderson Cancer Center and P30CA072720 the Rutgers Cancer Institute of New Jersey). This research has also been supported in part by grants from the National Science Foundation Grant DMS-1930583 (ZW, VC), the National Institutes of Health (NIH) 1R01CA253865 (ZW, VC), 1U01CA196403 (ZW, VC), 1U01CA213759 (ZW, VC), 1R01CA226537 (ZW, RP, WA, VC), 1R01CA222007 (ZW, VC), U54CA210181 (ZW, VC), and the University of Texas System STARS Award (VC). BC acknowledges support through the SER Cymru II Programme, funded by the European Commission through the Horizon 2020 Marie Skłodowska-Curie Actions (MSCA) COFUND scheme and the Welsh European Funding Office (WEFO) under the European Regional Development Fund (ERDF). EK has also received support from the Project Purple, NIH (U54CA210181, U01CA200468, and U01CA196403), and the Pancreatic Cancer Action Network (16-65-SING). MF was supported through NIH/NCI center grant U54CA210181, R01CA222959, DoD Breast Cancer Research Breakthrough Level IV Award W81XWH-17-1-0389, and the Ernest Cockrell Jr. Presidential Distinguished Chair at Houston Methodist Research Institute. RP and WA received serial research awards from AngelWorks, the Gillson-Longenbaugh Foundation, and the Marcus Foundation. This work was also supported in part by grants from the National Cancer Institute to SHC (R01CA109322, R01CA127483, R01CA208703, and U54CA210181 CITO pilot grant) and to PYP (R01CA140243, R01CA188610, and U54CA210181 CITO pilot grant). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Phase II Trial of Concurrent Sunitinib and Image-Guided Radiotherapy for Oligometastases

BACKGROUND: Preclinical data suggest that sunitinib enhances the efficacy of radiotherapy. We tested the combination of sunitinib and hypofractionated image-guided radiotherapy (IGRT) in a cohort of patients with historically incurable distant metastases. METHODS: Twenty five patients with oligometastases, defined as 1-5 sites of active disease on whole body imaging, were enrolled in a phase II trial from 2/08 to 9/10. The most common tumor types treated were head and neck, liver, lung, kidney and prostate cancers. Patients were treated with the recommended phase II dose of 37.5 mg daily sunitinib (days 1-28) and IGRT 50 Gy (days 8-12 and 15-19). Maintenance sunitinib was used in 33% of patients. Median follow up was 17.5 months (range, 0.7 to 37.4 months). RESULTS: The 18-month local control, distant control, progression-free survival (PFS) and overall survival (OS) were 75%, 52%, 56% and 71%, respectively. At last follow-up, 11 (44%) patients were alive without evidence of disease, 7 (28%) were alive with distant metastases, 3 (12%) were dead from distant metastases, 3 (12%) were dead from comorbid illness, and 1 (4%) was dead from treatment-related toxicities. The incidence of acute grade ≥ 3 toxicities was 28%, most commonly myelosuppression, bleeding and abnormal liver function tests. CONCLUSIONS: Concurrent sunitinib and IGRT achieves major clinical responses in a subset of patients with oligometastases. TRIAL REGISTRATION: ClinicalTrials.gov NCT00463060

[[alternative]]A Qualitative Study on the Death Concept and Emotion Response of Kindergarten's Students

[[abstract]]本研究旨在探討幼兒的死亡概念、影響幼兒死亡概念的可能因素、以及幼兒面對死亡的情緒反應。以作為幼稚園老師、家長實施幼兒生死教育與輔導之參考。 本研究採用質性研究，以嘉義市某幼稚園十六位四歲至六歲幼兒為研究對象，搜集資料的方式包括繪畫、訪談、家長問卷，經現象學資料分析後，獲得以下的研究結果： 一、幼兒的死亡概念 幼兒的死亡概念內涵可歸類為：所有生物都會死（人、動物、植物）、不能復活、死亡原因（自然因素致死、外力因素致死、其他：自殺）、身體功能停止（動也不動、沒呼吸沒心跳）、死後世界（靈魂和鬼神、天堂與地獄）、與死後處理（死亡判斷、屍體處理、死亡符號）等六項次概念。 二、影響幼兒死亡概念的可能因素 對幼兒死亡概念產生影響的可能因素包括：年齡、性別、家庭宗教信仰、接觸死亡的經驗、以及各種不同的訊息來源（學校老師、家人談論、宗教人員、傳播媒體、童書）。其中性別因素只侷限於幼兒繪畫上的差異，而本研究中幼兒的死亡概念則未受家庭宗教信仰之不同而有不同的影響。 三、幼兒面對死亡的情緒 接觸不同的死亡經驗，會引發幼兒不同面向與程度的情緒反應。其一，幼兒面對親人死亡時可能會有：好奇、害怕、沒感覺、傷心與難過等情緒反應出現；其二，寵物死亡時幼兒可能產生的反應為：沒感覺、可憐、害怕、傷心與難過等情緒；其三，對與自己無關他人、動物死亡的情緒有：沒感覺、可憐、恐怖與害怕、生氣、傷心與難過等反應；其四，面對將來自己和親人的死亡所觸動的情緒是：擔心自己會死、害怕自己死後會下地獄、害怕分離，擔心父母死後自己會失去依靠，沒人照顧。但這些情緒並不必然有時間的先後順序關係，也未必是具有相關死亡經驗的幼兒都一定會完全出現的反應。 最後研究者根據研究結果，分別就對實施幼兒生死教育與輔導、以及未來研究兩方面提出具體建議。[[abstract]]The purposes of this thesis are to investigate kindergarten’s students concept of death, to discuss the possible factors which influence children’s concepts of death; and furthermore, to explore their emotion response and coping tactics toward death. All the research data is collected from 16 young children aged 4-6 in the kindergarten. Based on the framework of qualitative research and the methodology of phenomenalism, the research design includes interviewing these kids in person, analyzing their drawings, and visiting their parents with structured questionnaire. The research results are as follows: 1. The death concepts of kindergarten’s students include: universality（all beings have to die, including human beings, animals and plants）; irrevocability; causality (interior, exterior, suicide, etc); dysfunctionality (not move anymore , or no-breathing, no-heartbeating); a world after death (soul and ghost, Heaven and Hades); management after death (judgment of death, funeral affairs & symbols of death). 2. The factors which may affect young children’s concept of death include age, sex, family religion, previous experiences with death, and various resources of message (school, family, media, Children books). However, there are no significant effects between different religious families in this study, and sex difference exists only in drawing. 3. Different experiences with death will lead to different facets and levels of emotion response. On the one hand, when their intimate families or pets die, the young children may be curious, afraid, sad and even feelingless; on the other hand, the young children may be feelingless, feel pity, afraid and sad when they encounter death experiences which are not so close to them. Nevertheless, when they have to face the death of their intimate families in the future, they feel afraid and anxious: they worry about death of themselves, and the possibility of going to hell after death; and also they are afraid of parting, and losing care and dependence if their parents die. This research did not find any chronological relationship between these emotion reactions, and the relationship between death experiences and emotion reactions is not significant. Finally, based on the findings of this study, suggestions of life-and-death education to educational organizations, parents and related academic institutions are provided