The Sensitivity of Arctic Ozone Loss to Polar Stratospheric Cloud Volume and Chlorine and Bromine Loading in a Chemistry and Transport Model

Science.gov (United States)

Douglass, A. R.; Stolarski, R. S.; Strahan, S. E.; Polansky, B. C.

2006-01-01

The sensitivity of Arctic ozone loss to polar stratospheric cloud volume (V(sub PSC)) and chlorine and bromine loading is explored using chemistry and transport models (CTMs). A simulation using multi-decadal output from a general circulation model (GCM) in the Goddard Space Flight Center (GSFC) CTM complements one recycling a single year s GCM output in the Global Modeling Initiative (GMI) CTM. Winter polar ozone loss in the GSFC CTM depends on equivalent effective stratospheric chlorine (EESC) and polar vortex characteristics (temperatures, descent, isolation, polar stratospheric cloud amount). Polar ozone loss in the GMI CTM depends only on changes in EESC as the dynamics repeat annually. The GSFC CTM simulation reproduces a linear relationship between ozone loss and Vpsc derived from observations for 1992 - 2003 which holds for EESC within approx.85% of its maximum (approx.1990 - 2020). The GMI simulation shows that ozone loss varies linearly with EESC for constant, high V(sub PSC).

Temperature thresholds for chlorine activation and ozone loss in the polar stratosphere

Energy Technology Data Exchange (ETDEWEB)

Drdla, K. [NASA Ames Research Center, Moffett Field, CA (United States); Mueller, R. [Forschungszentrum Juelich (DE). Inst. of Energy and Climate Research (IEK-7)

2012-07-01

Low stratospheric temperatures are known to be responsible for heterogeneous chlorine activation that leads to polar ozone depletion. Here, we discuss the temperature threshold below which substantial chlorine activation occurs. We suggest that the onset of chlorine activation is dominated by reactions on cold binary aerosol particles, without the formation of polar stratospheric clouds (PSCs), i.e. without any significant uptake of HNO{sub 3} from the gas phase. Using reaction rates on cold binary aerosol in a model of stratospheric chemistry, a chlorine activation threshold temperature, T{sub ACL}, is derived. At typical stratospheric conditions, T{sub ACL} is similar in value to T{sub NAT} (within 1-2 K), the highest temperature at which nitric acid trihydrate (NAT) can exist. T{sub NAT} is still in use to parameterise the threshold temperature for the onset of chlorine activation. However, perturbations can cause T{sub ACL} to differ from T{sub NAT}: T{sub ACL} is dependent upon H{sub 2} O and potential temperature, but unlike T{sub NAT} is not dependent upon HNO3. Furthermore, in contrast to T{sub NAT}, T{sub ACL} is dependent upon the stratospheric sulfate aerosol loading and thus provides a means to estimate the impact on polar ozone of strong volcanic eruptions and some geo-engineering options, which are discussed. A parameterisation of T{sub ACL} is provided here, allowing it to be calculated for low solar elevation (or high solar zenith angle) over a comprehensive range of stratospheric conditions. Considering T{sub ACL} as a proxy for chlorine activation cannot replace a detailed model calculation, and polar ozone loss is influenced by other factors apart from the initial chlorine activation. However, T{sub ACL} provides a more accurate description of the temperature conditions necessary for chlorine activation and ozone loss in the polar stratosphere than T{sub NAT}. (orig.)

High-Efficiency Dielectric Metasurfaces for Polarization-Dependent Terahertz Wavefront Manipulation

KAUST Repository

Zhang, Huifang

2017-11-30

Recently, metasurfaces made up of dielectric structures have drawn enormous attentions in the optical and infrared regimes due to their high efficiency and designing freedom in manipulating light propagation. Such advantages can also be introduced to terahertz frequencies where efficient functional devices are still lacking. Here, polarization-dependent all-silicon terahertz dielectric metasurfaces are proposed and experimentally demonstrated. The metasurfaces are composed of anisotropic rectangular-shaped silicon pillars on silicon substrate. Each metasurface holds dual different functions depending on the incident polarizations. Furthermore, to suppress the reflection loss and multireflection effect in practical applications, a high-performance polarization-independent antireflection silicon pillar array is also proposed, which can be patterned at the other side of the silicon substrate. Such all-silicon dielectric metasurfaces are easy to fabricate and can be very promising in developing next-generation efficient, compact, and low-cost terahertz functional devices.

Optimized design of polarizers with low ohmic loss and any polarization state for the 28 GHz QUEST ECH/ECCD system

Energy Technology Data Exchange (ETDEWEB)

Tsujimura, Toru Ii, E-mail: tsujimura.tohru@nifs.ac.jp [National Institute for Fusion Science, National Institutes of Natural Sciences, Toki 509-5292 (Japan); Idei, Hiroshi [Research Institute for Applied Mechanics, Kyushu University, Kasuga 816-8580 (Japan); Kubo, Shin; Kobayashi, Sakuji [National Institute for Fusion Science, National Institutes of Natural Sciences, Toki 509-5292 (Japan)

2017-01-15

Highlights: • Ohmic loss was calculated on the grooved mirror surface in simulated polarizers. • Polarizers with a low ohmic loss feature were optimally designed for 28 GHz. • Smooth rounded-rectangular grooves were made by mechanical machining. • The designed polarizers can realize all polarization states. - Abstract: In a high-power long-pulse millimeter-wave transmission line for electron cyclotron heating and current drive (ECH/ECCD), the ohmic loss on the grooved mirror surface of polarizers is one of the important issues for reducing the transmission loss. In this paper, the ohmic loss on the mirror surface is evaluated in simulated real-scale polarizer miter bends for different groove parameters under a linearly-polarized incident wave excitation. The polarizers with low ohmic loss are optimally designed for a new 28 GHz transmission line on the QUEST spherical tokamak. The calculated optimum ohmic loss is restricted to only less than 1.5 times as large as the theoretical loss for a copper flat mirror at room temperature. The copper rounded-rectangular grooves of the polarizers were relatively easy to make smooth in mechanical machining and the resultant surface roughness was not more than 0.15 μm, which is only 0.38 times as large as the skin depth. The combination of the designed elliptical polarizer and the polarization rotator can also realize any polarization state of the reflected wave.

A closer look at Arctic ozone loss and polar stratospheric clouds

Directory of Open Access Journals (Sweden)

N. R. P. Harris

2010-09-01

Full Text Available The empirical relationship found between column-integrated Arctic ozone loss and the potential volume of polar stratospheric clouds inferred from meteorological analyses is recalculated in a self-consistent manner using the ERA Interim reanalyses. The relationship is found to hold at different altitudes as well as in the column. The use of a PSC formation threshold based on temperature dependent cold aerosol formation makes little difference to the original, empirical relationship. Analysis of the photochemistry leading to the ozone loss shows that activation is limited by the photolysis of nitric acid. This step produces nitrogen dioxide which is converted to chlorine nitrate which in turn reacts with hydrogen chloride on any polar stratospheric clouds to form active chlorine. The rate-limiting step is the photolysis of nitric acid: this occurs at the same rate every year and so the interannual variation in the ozone loss is caused by the extent and persistence of the polar stratospheric clouds. In early spring the ozone loss rate increases as the solar insolation increases the photolysis of the chlorine monoxide dimer in the near ultraviolet. However the length of the ozone loss period is determined by the photolysis of nitric acid which also occurs in the near ultraviolet. As a result of these compensating effects, the amount of the ozone loss is principally limited by the extent of original activation rather than its timing. In addition a number of factors, including the vertical changes in pressure and total inorganic chlorine as well as denitrification and renitrification, offset each other. As a result the extent of original activation is the most important factor influencing ozone loss. These results indicate that relatively simple parameterisations of Arctic ozone loss could be developed for use in coupled chemistry climate models.

Design and performance of a spin-polarized electron energy loss spectrometer with high momentum resolution

Energy Technology Data Exchange (ETDEWEB)

Vasilyev, D.; Kirschner, J. [Max-Planck-Institut für Mikrostrukturphysik, Weinberg 2, 06120 Halle (Germany)

2016-08-15

We describe a new “complete” spin-polarized electron energy loss spectrometer comprising a spin-polarized primary electron source, an imaging electron analyzer, and a spin analyzer of the “spin-polarizing mirror” type. Unlike previous instruments, we have a high momentum resolution of less than 0.04 Å{sup −1}, at an energy resolution of 90-130 meV. Unlike all previous studies which reported rather broad featureless data in both energy and angle dependence, we find richly structured spectra depending sensitively on small changes of the primary energy, the kinetic energy after scattering, and of the angle of incidence. The key factor is the momentum resolution.

Polarization-independent broadband meta-holograms via polarization-dependent nanoholes.

Science.gov (United States)

Zhang, Xiaohu; Li, Xiong; Jin, Jinjin; Pu, Mingbo; Ma, Xiaoliang; Luo, Jun; Guo, Yinghui; Wang, Changtao; Luo, Xiangang

2018-05-17

Composed of ultrathin metal or dielectric nanostructures, metasurfaces can manipulate the phase, amplitude and polarization of electromagnetic waves at a subwavelength scale, which is promising for flat optical devices. In general, metasurfaces composed of space-variant anisotropic units are sensitive to the incident polarization due to the inherent polarization dependent geometric phase. Here, we implement polarization-independent broadband metasurface holograms constructed by polarization-dependent anisotropic elliptical nanoholes by elaborate design of complex amplitude holograms. The fabricated meta-hologram exhibits a polarization insensitive feature with an acceptable image quality. We verify the feasibility of the design algorithm for three-dimensional (3D) meta-holograms with simulation and the feasibility for two-dimensional (2D) meta-holograms is experimentally demonstrated at a broadband wavelength range from 405 nm to 632.8 nm. The effective polarization-independent broadband complex wavefront control with anisotropic elliptical nanoholes proposed in this paper greatly promotes the practical applications of the metasurface in technologies associated with wavefront manipulation, such as flat lens, colorful holographic displays and optical storage.

Increase of cells expressing PD-L1 in bovine leukemia virus infection and enhancement of anti-viral immune responses in vitro via PD-L1 blockade

Directory of Open Access Journals (Sweden)

Ikebuchi Ryoyo

2011-09-01

Full Text Available Abstract The inhibitory receptor programmed death-1 (PD-1 and its ligand, programmed death-ligand 1 (PD-L1 are involved in immune evasion mechanisms for several pathogens causing chronic infections. Blockade of the PD-1/PD-L1 pathway restores anti-virus immune responses, with concomitant reduction in viral load. In a previous report, we showed that, in bovine leukemia virus (BLV infection, the expression of bovine PD-1 is closely associated with disease progression. However, the functions of bovine PD-L1 are still unknown. To investigate the role of PD-L1 in BLV infection, we identified the bovine PD-L1 gene, and examined PD-L1 expression in BLV-infected cattle in comparison with uninfected cattle. The deduced amino acid sequence of bovine PD-L1 shows high homology to the human and mouse PD-L1. The proportion of PD-L1 positive cells, especially among B cells, was upregulated in cattle with the late stage of the disease compared to cattle at the aleukemic infection stage or uninfected cattle. The proportion of PD-L1 positive cells correlated positively with prediction markers for the progression of the disease such as leukocyte number, virus load and virus titer whilst on the contrary, it inversely correlated with the degree of interferon-gamma expression. Blockade of the PD-1/PD-L1 pathway in vitro by PD-L1-specific antibody upregulated the production of interleukin-2 and interferon-gamma, and correspondingly, downregulated the BLV provirus load and the proportion of BLV-gp51 expressing cells. These data suggest that PD-L1 induces immunoinhibition in disease progressed cattle during chronic BLV infection. Therefore, PD-L1 would be a potential target for developing immunotherapies against BLV infection.

Malignant mesothelioma effusions are infiltrated by CD3+ T cells highly expressing PD-L1 and the PD-L1+ tumor cells within these effusions are susceptible to ADCC by the anti-PD-L1 antibody avelumab

Science.gov (United States)

Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M.; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

2016-01-01

INTRODUCTION The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. METHODS Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry and its prognostic significance. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1+ and PD-L1+ infiltrating lymphocytes and their role in inducing tumor cell PD-L1 expression. Antibody dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized IgG1 anti PD-L1 antibody towards primary mesothelioma cell lines was evaluated in presence of autologous and allogeneic NK cells. RESULTS Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1 positive, which was associated with slightly inferior overall survival compared to patients with PD-L1 negative tumors (median 23.0 vs. 33.3 months; p=0.35). The frequency of PD-L1 expression was similar in pleural and peritoneal mesothelioma patients with 62% and 64% of samples positive, respectively. Of nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12 to 83%. Of 7 patients with paired malignant effusion and peripheral blood mononuclear cells (PBMC) samples, PD-L1 expression was significantly higher on CD3+ T cells present in malignant effusions as compared with PBMC (p=0.016). In addition, CD14+PD-1+ cells were elevated in malignant effusions compared with PBMC (p=0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced IFN-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab mediated ADCC in presence of autologous NK cells. CONCLUSION The majority of pleural as well as peritoneal mesothelioma express PD-L1. Malignant effusions in this disease are characterized by presence of tumor cells and CD3+ T

Malignant Mesothelioma Effusions Are Infiltrated by CD3+ T Cells Highly Expressing PD-L1 and the PD-L1+ Tumor Cells within These Effusions Are Susceptible to ADCC by the Anti-PD-L1 Antibody Avelumab.

Science.gov (United States)

Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

2016-11-01

The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry, and its prognostic significance was examined. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1-positive and PD-L1-positive infiltrating lymphocytes and their role in inducing PD-L1 expression in tumor cells. Antibody-dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized immunoglobulin G1 anti PD-L1 antibody against primary mesothelioma cell lines, was evaluated in presence of autologous and allogeneic natural killer cells. Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1-positive, which was associated with slightly inferior overall survival compared to patients with PD-L1-negative tumors (median 23.0 versus 33.3 months, p = 0.35). The frequency of PD-L1 expression was similar in patients with pleural and peritoneal mesothelioma, with 62% and 64% of samples testing positive, respectively. In nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12% to 83%. In seven patients with paired malignant effusion and peripheral blood mononuclear cell (PBMC) samples, PD-L1 expression was significantly higher on CD3-positive T cells present in malignant effusions as compared with PBMCs (p = 0.016). In addition, the numbers of CD14-positive PD-1-positive cells were increased in malignant effusions compared with PBMCs (p = 0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced interferon-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab-mediated ADCC in the presence of autologous natural killer cells. Most pleural as well as peritoneal mesotheliomas

The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors

Energy Technology Data Exchange (ETDEWEB)

Lin, David Yin-wei; Tanaka, Yoshimasa; Iwasaki, Masashi; Gittis, Apostolos G.; Su, Hua-Poo; Mikami, Bunzo; Okazaki, Taku; Honjo, Tasuku; Minato, Nagahiro; Garboczi, David N. (NIH); (Kyoto)

2008-07-29

Signaling through the programmed death 1 (PD-1) inhibitory receptor upon binding its ligand, PD-L1, suppresses immune responses against autoantigens and tumors and plays an important role in the maintenance of peripheral immune tolerance. Release from PD-1 inhibitory signaling revives 'exhausted' virus-specific T cells in chronic viral infections. Here we present the crystal structure of murine PD-1 in complex with human PD-L1. PD-1 and PD-L1 interact through the conserved front and side of their Ig variable (IgV) domains, as do the IgV domains of antibodies and T cell receptors. This places the loops at the ends of the IgV domains on the same side of the PD-1/PD-L1 complex, forming a surface that is similar to the antigen-binding surface of antibodies and T cell receptors. Mapping conserved residues allowed the identification of residues that are important in forming the PD-1/PD-L1 interface. Based on the structure, we show that some reported loss-of-binding mutations involve the PD-1/PD-L1 interaction but that others compromise protein folding. The PD-1/PD-L1 interaction described here may be blocked by antibodies or by designed small-molecule drugs to lower inhibitory signaling that results in a stronger immune response. The immune receptor-like loops offer a new surface for further study and potentially the design of molecules that would affect PD-1/PD-L1 complex formation and thereby modulate the immune response.

PDL as a multi-agent strategy logic

NARCIS (Netherlands)

D.J.N. van Eijck (Jan); B.C. Schipper

2013-01-01

textabstractPropositional Dynamic Logic or PDL was invented as a logic for reasoning about regular programming constructs. We propose a new perspective on PDL as a multi-agent strategic logic (MASL). This logic for strategic reasoning has group strategies as first class citizens, and

Tracer-tracer relations as a tool for research on polar ozone loss

Energy Technology Data Exchange (ETDEWEB)

Mueller, Rolf

2010-07-01

The report includes the following chapters: (1) Introduction: ozone in the atmosphere, anthropogenic influence on the ozone layer, polar stratospheric ozone loss; (2) Tracer-tracer relations in the stratosphere: tracer-tracer relations as a tool in atmospheric research; impact of cosmic-ray-induced heterogeneous chemistry on polar ozone; (3) quantifying polar ozone loss from ozone-tracer relations: principles of tracer-tracer correlation techniques; reference ozone-tracer relations in the early polar vortex; impact of mixing on ozone-tracer relations in the polar vortex; impact of mesospheric intrusions on ozone-tracer relations in the stratospheric polar vortex calculation of chemical ozone loss in the arctic in March 2003 based on ILAS-II measurements; (4) epilogue.

Wavelength dependence of interstellar polarization

International Nuclear Information System (INIS)

Mavko, G.E.

1974-01-01

The wavelength dependence of interstellar polarization was measured for twelve stars in three regions of the Milky Way. A 120A bandpass was used to measure the polarization at a maximum of sixteen wavelengths evenly spaced between 2.78μ -1 (3600A) and 1.28μ -1 (7800A). For such a wide wavelength range, the wavelength resolution is superior to that of any previously reported polarization measurements. The new scanning polarimeter built by W. A. Hiltner of the University of Michigan was used for the observations. Very broad structure was found in the wavelength dependence of the polarization. Extensive investigations were carried out to show that the structure was not caused by instrumental effects. The broad structure observed is shown to be in agreement with concurrent extinction measurements for the same stars. Also, the observed structure is of the type predicted when a homogeneous silicate grain model is fitted to the observed extinction. The results are in agreement with the hypothesis that the very broad band structure seen in the extinction is produced by the grains. (Diss. Abstr. Int., B)

Invariant polar bear habitat selection during a period of sea ice loss.

Science.gov (United States)

Wilson, Ryan R; Regehr, Eric V; Rode, Karyn D; St Martin, Michelle

2016-08-17

Climate change is expected to alter many species' habitat. A species' ability to adjust to these changes is partially determined by their ability to adjust habitat selection preferences to new environmental conditions. Sea ice loss has forced polar bears (Ursus maritimus) to spend longer periods annually over less productive waters, which may be a primary driver of population declines. A negative population response to greater time spent over less productive water implies, however, that prey are not also shifting their space use in response to sea ice loss. We show that polar bear habitat selection in the Chukchi Sea has not changed between periods before and after significant sea ice loss, leading to a 75% reduction of highly selected habitat in summer. Summer was the only period with loss of highly selected habitat, supporting the contention that summer will be a critical period for polar bears as sea ice loss continues. Our results indicate that bears are either unable to shift selection patterns to reflect new prey use patterns or that there has not been a shift towards polar basin waters becoming more productive for prey. Continued sea ice loss is likely to further reduce habitat with population-level consequences for polar bears. © 2016 The Author(s).

Invariant polar bear habitat selection during a period of sea ice loss

Science.gov (United States)

Wilson, Ryan R.; Regehr, Eric V.; Rode, Karyn D.; St Martin, Michelle

2016-01-01

Climate change is expected to alter many species' habitat. A species' ability to adjust to these changes is partially determined by their ability to adjust habitat selection preferences to new environmental conditions. Sea ice loss has forced polar bears (Ursus maritimus) to spend longer periods annually over less productive waters, which may be a primary driver of population declines. A negative population response to greater time spent over less productive water implies, however, that prey are not also shifting their space use in response to sea ice loss. We show that polar bear habitat selection in the Chukchi Sea has not changed between periods before and after significant sea ice loss, leading to a 75% reduction of highly selected habitat in summer. Summer was the only period with loss of highly selected habitat, supporting the contention that summer will be a critical period for polar bears as sea ice loss continues. Our results indicate that bears are either unable to shift selection patterns to reflect new prey use patterns or that there has not been a shift towards polar basin waters becoming more productive for prey. Continued sea ice loss is likely to further reduce habitat with population-level consequences for polar bears.

Small-Molecule Sigma1 Modulator Induces Autophagic Degradation of PD-L1.

Science.gov (United States)

Maher, Christina M; Thomas, Jeffrey D; Haas, Derick A; Longen, Charles G; Oyer, Halley M; Tong, Jane Y; Kim, Felix J

2018-02-01

Emerging evidence suggests that Sigma1 ( SIGMAR1 , also known as sigma-1 receptor) is a unique ligand-regulated integral membrane scaffolding protein that contributes to cellular protein and lipid homeostasis. Previously, we demonstrated that some small-molecule modulators of Sigma1 alter endoplasmic reticulum (ER)-associated protein homeostasis pathways in cancer cells, including the unfolded protein response and autophagy. Programmed death-ligand 1 (PD-L1) is a type I integral membrane glycoprotein that is cotranslationally inserted into the ER and is processed and transported through the secretory pathway. Once at the surface of cancer cells, PD-L1 acts as a T-cell inhibitory checkpoint molecule and suppresses antitumor immunity. Here, we demonstrate that in Sigma1-expressing triple-negative breast and androgen-independent prostate cancer cells, PD-L1 protein levels were suppressed by RNAi knockdown of Sigma1 and by small-molecule inhibition of Sigma1. Sigma1-mediated action was confirmed by pharmacologic competition between Sigma1-selective inhibitor and activator ligands. When administered alone, the Sigma1 inhibitor decreased cell surface PD-L1 expression and suppressed functional interaction of PD-1 and PD-L1 in a coculture of T cells and cancer cells. Conversely, the Sigma1 activator increased PD-L1 cell surface expression, demonstrating the ability to positively and negatively modulate Sigma1 associated PD-L1 processing. We discovered that the Sigma1 inhibitor induced degradation of PD-L1 via autophagy, by a mechanism distinct from bulk macroautophagy or general ER stress-associated autophagy. Finally, the Sigma1 inhibitor suppressed IFNγ-induced PD-L1. Our data demonstrate that small-molecule Sigma1 modulators can be used to regulate PD-L1 in cancer cells and trigger its degradation by selective autophagy. Implications: Sigma1 modulators sequester and eliminate PD-L1 by autophagy, thus preventing functional PD-L1 expression at the cell surface. This

PD-L1 Deficiency within Islets Reduces Allograft Survival in Mice.

Directory of Open Access Journals (Sweden)

Dongxia Ma

Full Text Available Islet transplantation may potentially cure type 1 diabetes mellitus (T1DM. However, immune rejection, especially that induced by the alloreactive T-cell response, remains a restraining factor for the long-term survival of grafted islets. Programmed death ligand-1 (PD-L1 is a negative costimulatory molecule. PD-L1 deficiency within the donor heart accelerates allograft rejection. Here, we investigate whether PD-L1 deficiency in donor islets reduces allograft survival time.Glucose Stimulation Assays were performed to evaluate whether PD-L1 deficiency has detrimental effects on islet function. Islets isolated from PDL1-deficient mice or wild- type (WT mice (C57BL/6j were implanted beneath the renal capsule of streptozotocin (STZ-induced diabetic BALB/c mice. Blood glucose levels and graft survival time after transplantation were monitored. Moreover, we analyzed the residual islets, infiltrating immune cells and alloreactive cells from the recipients.PD-L1 deficiency within islets does not affect islet function. However, islet PD-L1 deficiency increased allograft rejection and was associated with enhanced inflammatory cell infiltration and recipient T-cell alloreactivity.This is the first report to demonstrate that PD-L1 deficiency accelerated islet allograft rejection and regulated recipient alloimmune responses.

PD-L1 expression by neurons nearby tumors indicates better prognosis in glioblastoma patients

DEFF Research Database (Denmark)

Liu, Yawei; Carlsson, Robert; Ambjørn, Malene

2013-01-01

Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor. In general, tumor growth requires disruption of the tissue microenvironment, yet how this affects glioma progression is unknown. We studied program death-ligand (PD-L)1 in neurons and gliomas in tumors from GBM patients...... and associated the findings with clinical outcome. Remarkably, we found that upregulation of PD-L1 by neurons in tumor-adjacent brain tissue (TABT) associated positively with GBM patient survival, whereas lack of neuronal PD-L1 expression was associated with high PD-L1 in tumors and unfavorable prognosis...... in GBM patients, better survival in wild-type mice was associated with high neuronal PD-L1 in TABT and downregulation of PD-L1 in tumors, which was defective in Ifnb-/- mice. Our data indicated that neuronal PD-L1 signaling in brain cells was important for GBM patient survival. Reciprocal PD-L1...

PD-L1 inhibition with avelumab for metastatic Merkel cell carcinoma.

Science.gov (United States)

Gaiser, Maria Rita; Bongiorno, Michelle; Brownell, Isaac

2018-04-01

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer that lacks durable responses to traditional chemotherapy. Areas covered: After MCC was shown to be an immunogenic tumor, small trials revealed high objective response rates to PD-1/PD-L1 checkpoint inhibitors. The JAVELIN Merkel 200 (NCT02155647) trial tested the use of avelumab, a human IgG1 monoclonal antibody against PD-L1, in metastatic MCC. Avelumab recently became the first approved drug for metastatic MCC. Expert commentary: By conducting broad phase I studies assessing the safety of avelumab and a small phase II study demonstrating efficacy in this rare orphan tumor type, avelumab gained accelerated approval for the treatment of metastatic MCC. Additional studies are needed to determine how the antibody-dependent cellular cytotoxicity (ADCC) competent Fc region of avelumab contributes to disease control. Remaining questions: Longer follow-up will determine the durability of checkpoint blockade in controlling metastatic MCC. Additional studies will assess the utility and safety of adjuvant checkpoint blockade in patients with excised MCC. How to increase response rates by combining PD-1/PD-L1 blockade with other treatment approaches needs to be explored. In addition, treatment options for MCC patients who fail or do not respond to avelumab need to be identified.

[Regulatory Mechanisms of PD-L1 Expression and Its Role in Immune Evasion].

Science.gov (United States)

Kataoka, Keisuke

2017-11-01

Immune checkpoint blockade therapy using anti-PD-1 or anti-PD-L1 antibodies can unleash anti-tumor immunity and induce durable remission in a variety ofhuman cancers. However, the regulatory mechanisms of PD-L1 expression mediating immune evasion ofcancer cells have not been fully elucidated, including the genetic alterations causing PD-L1 overexpression. Recently, we have reported a novel genetic mechanism ofimmune evasion associated with structural variations(SVs)disrupting the 3'-untranslated region(UTR)ofthe PD-L1 gene in various malignancies, such as aggressive lymphomas and gastrointestinal cancers. Despite a heterogenous nature ofthese SVs, they are closely associated with a marked upregulation of PD-L1 expression, which augments tumor growth and escape from anti-tumor immunity. Here we present an overview of the regulatory mechanisms of PD-L1 expression in cancer cells, highlighting the genetic mechanisms of PD-L1 constitutive activation, with specific focus on PD-L1 3'-UTR disruption.

Viral infection of human lung macrophages increases PDL1 expression via IFNβ.

Directory of Open Access Journals (Sweden)

Karl J Staples

Full Text Available Lung macrophages are an important defence against respiratory viral infection and recent work has demonstrated that influenza-induced macrophage PDL1 expression in the murine lung leads to rapid modulation of CD8+ T cell responses via the PD1 receptor. This PD1/PDL1 pathway may downregulate acute inflammatory responses to prevent tissue damage. The aim of this study was to investigate the mechanisms of PDL1 regulation by human macrophages in response to viral infection. Ex-vivo viral infection models using influenza and RSV were established in human lung explants, isolated lung macrophages and monocyte-derived macrophages (MDM and analysed by flow cytometry and RT-PCR. Incubation of lung explants, lung macrophages and MDM with X31 resulted in mean cellular infection rates of 18%, 18% and 29% respectively. Viral infection significantly increased cell surface expression of PDL1 on explant macrophages, lung macrophages and MDM but not explant epithelial cells. Infected MDM induced IFNγ release from autologous CD8+ T cells, an effect enhanced by PDL1 blockade. We observed increases in PDL1 mRNA and IFNβ mRNA and protein release by MDM in response to influenza infection. Knockdown of IFNβ by siRNA, resulted in a 37.5% reduction in IFNβ gene expression in response to infection, and a significant decrease in PDL1 mRNA. Furthermore, when MDM were incubated with IFNβ, this cytokine caused increased expression of PDL1 mRNA. These data indicate that human macrophage PDL1 expression modulates CD8+ cell IFNγ release in response to virus and that this expression is regulated by autologous IFNβ production.

Polarization-dependent optics using gauge-field metamaterials

International Nuclear Information System (INIS)

Liu, Fu; Xiao, Shiyi; Li, Jensen; Wang, Saisai; Hang, Zhi Hong

2015-01-01

We show that effective gauge field for photons with polarization-split dispersion surfaces, being realized using uniaxial metamaterials, can be used for polarization control with unique opportunities. The metamaterials with the proposed gauge field correspond to a special choice of eigenpolarizations on the Poincaré sphere as pseudo-spins, in contrary to those from either conventional birefringent crystals or optical active media. It gives rise to all-angle polarization control and a generic route to manipulate photon trajectories or polarizations in the pseudo-spin domain. As demonstrations, we show beam splitting (birefringent polarizer), all-angle polarization control, unidirectional polarization filter, and interferometer as various polarization control devices in the pseudo-spin domain. We expect that more polarization-dependent devices can be designed under the same framework

Immuno-inhibitory PD-L1 can be induced by a peptidoglycan/NOD2 mediated pathway in primary monocytic cells and is deficient in Crohn's patients with homozygous NOD2 mutations.

Science.gov (United States)

Hewitt, Rachel E; Pele, Laetitia C; Tremelling, Mark; Metz, Andrew; Parkes, Miles; Powell, Jonathan J

2012-05-01

Peptidoglycan (PGN) is a ubiquitous bacterial membrane product that, despite its well known pro-inflammatory properties, has also been invoked in immuno-tolerance of the gastrointestinal tract. PGN-induced mucosal IL-10 secretion and downregulation of Toll like receptors are potential mechanisms of action in the gut but there are few data on tolerogenic adaptive immune responses and PGN. Here, using blood-derived mononuclear cells, we showed that PGN induced marked cell surface expression of PD-L1 but not PD-L2 or CD80/CD86, and specifically in the CD14(+) monocytic fraction. This was reproduced at the gene level with rapid induction (<4 h) and, unlike for LPS stimulation, was still sustained at 24 h. Using transfected and native muramyl dipeptide (MDP), which is a cleavage product of PGN and a specific NOD2 agonist, in assays with wild type cells or those from patients with Crohn's disease carrying the Leu1007 frameshift mutation of NOD2, we showed that (i) both NOD2 dependent and independent signalling (appearing TLR2 mediated) occurred for PGN upregulation of PD-L1 (ii) upregulation is lost in response to MDP in patients with the homozygous mutation and (iii) PD-L1 upregulation was unaffected in patients with heterozygous mutations as previously reported for cytokine responses to MDP. The uptake of PGN and its cleavage products by the intestinal mucosa is well recognised and further work should consider PD-L1 upregulation as one potential mechanism of the commensal flora-driven intestinal immuno-tolerance. Indeed, recent work has shown that loss of PD-L1 signalling in the gut breaks CD8(+) T cell tolerance to self antigen and leads to severe autoimmune enteritis. Copyright © 2012 Elsevier Inc. All rights reserved.

Prognostic Value of PD-L1 in Breast Cancer: A Meta-Analysis.

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Wang, Changjun; Zhu, Hanjiang; Zhou, Yidong; Mao, Feng; Lin, Yan; Pan, Bo; Zhang, Xiaohui; Xu, Qianqian; Huang, Xin; Sun, Qiang

2017-07-01

Programmed cell death 1 ligand 1 (PD-L1) is a promising therapeutic target for cancer immunotherapy. However, the correlation between PD-L1 and breast cancer survival remains unclear. Here, we present the first meta-analysis to investigate the prognostic value of PD-L1 in breast cancer. We searched Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases for relevant studies evaluating PD-L1 expression and breast cancer survival. Fixed- and random-effect meta-analyses were conducted based on heterogeneity of included studies. Publication bias was evaluated by funnel plot and Begg's test. Overall, nine relevant studies with 8583 patients were included. PD-L1 overexpression was found in 25.8% of breast cancer patients. PD-L1 (+) associated with several high-risk prognostic indicators, such as ductal cancer (p = 0.037), high tumor grade (p = 0.000), ER negativity (p = 0.000), PR negativity (p = 0.000), HER2 positivity (p = 0.001) and aggressive molecular subtypes (HER2-rich and Basal-like p = 0.000). PD-L1 overexpression had no significant impact on metastasis-free survival (HR 0.924, 95% CI = 0.747-1.141, p = 0.462), disease-free survival (HR 1.122, 95% CI = 0.878-1.434, p = 0.357) and overall specific survival (HR 0.837, 95% CI = 0.640-1.093, p = 0.191), but significantly correlated with shortened overall survival (HR 1.573, 95% CI = 1.010-2.451, p = 0.045). PD-L1 overexpression in breast cancer associates with multiple clinicopathological parameters that indicated poor outcome, and may increase the risk for mortality. Further standardization of PD-L1 assessment assay and well-controlled clinical trials are warranted to clarify its prognostic and therapeutic value. © 2017 Wiley Periodicals, Inc.

PD-L1 expression associated with worse survival outcome in malignant pleural mesothelioma.

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Nguyen, Bella Hai; Montgomery, Renn; Fadia, Mitali; Wang, Jiali; Ali, Sayed

2018-02-01

There is currently a need to identify prognostic biomarkers to assist in a risk adopted approach in treatment of malignant pleural mesothelioma (MPM). Expression of programmed death ligand 1 (PD-L1) has been studied as a prognostic biomarker in a number of tumors given its central role in antitumoral immune response evasion. Four previously published analyses found PD-L1 positivity to be an adverse survival prognostic factor in MPM. This study aims to further investigate the relationship between PD-L1 expression in mesothelioma tissues and survival outcome. Clinical data of MPM patients from a single institution between 2006 and 2016 were reviewed. Patient's archived tissues were stained with PD-L1 (Clone Ventana SP263). PD-L1 positivity was defined as > 1% membranous staining regardless of intensity. Data from fifty eight patients were analyzed. Median age was 73, majority was male (49, 84%) and had ECOG between 0 and 2 (46, 79%). Most common histopathological subtype was epithelioid (42, 72%), 9 (16%) biphasic subtype and 7 (12%) sarcomatoid. Thirty one patients (53%) received best supportive care and twenty seven patients (47%) received chemotherapy or combination treatment. Forty-two patients had positive PD-L1 expression (72.4%). The median survival time for PD-L1 negative group is 15.5 months and 6 months for the positive group. Positive PD-L1 expression is independently correlated with worse prognosis (HR = 2.02; 95% CI, 1.005-4.057; P-value = 0.0484). Our analysis found a higher percentage of MPM patients with positive PD-L1 (> 1%) compared to other studies. Highly positive PD-L1 expression was associated with statistically significantly lower median survival time. © 2017 John Wiley & Sons Australia, Ltd.

The Expression and Biological Significance of PD-L1 on Lung Cancer Cell Lines

Directory of Open Access Journals (Sweden)

Cheng CHEN

2009-08-01

Full Text Available Background and objective Tumor-associated PD-L1 expression was recently shown to promote T-cell apoptosis and proposed as a potential mechanism of immune evasion by tumors. On the basis of the ability of tumor-associated PD-L1 to mediate activated T-cell death, it is likely that manipulation of the PD-L1 pathway at defined time points during the development of the T-cell antitumor immune response can enhance the efficacy of T-cell-based immunotherapy. Here, the levels of expression of PD-L1 on lung cancer cell lines and its role in interaction of CTL and target cells was investigated. Methods Human PBMC derived DCs were loaded with apoptotic tumor cells and stimulated by CD40 mAb (5C11. Tumor specific CTL was generated in vitro by autologous T cells co-cultured with mature DCs. Expression of PD-L1 on lung cancer cell lines H1299 and A549 were analyzed by FCM. JAM assay was used to detect the cytolytic activity of CTL with or without blocking PD-L1 by PD-L1 mAb respectively. The concentrations of IFN-γ in supernatants from distinct groups were analyzed by ELISA. Results Tumor cells-loaded mature DCs could induce the generation of the tumor specific CTL. Expression of PD-L1 was low on A549 cell, but high on H1299 cell. Blockade of PD-L1 on A549 could not improve cytolytic effect of CTL on target cells and IFN-γ production, but fragmentation of H1299 cells and IFN-γ production were significantly enhanced by the combination of PD-L1 mAb and CTL. Conclusion Expression of PD-L1 on lung cancer cell line can decrease the cytolytic effect of CTL on target cells.

PD-L1 expression and the immune microenvironment in primary invasive lobular carcinomas of the breast.

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Thompson, Elizabeth D; Taube, Janis M; Asch-Kendrick, Rebecca J; Ogurtsova, Aleksandra; Xu, Haiying; Sharma, Rajni; Meeker, Alan; Argani, Pedram; Emens, Leisha A; Cimino-Mathews, Ashley

2017-11-01

Tumor-infiltrating lymphocytes and immune checkpoint proteins such as PD-L1 are potential prognostic factors and therapeutic targets in breast cancer. Most studies characterizing the breast tumor immune microenvironment have focused on ductal carcinomas. Here we investigate the tumor microenvironment of primary invasive lobular carcinomas. Previously constructed tissue microarrays of 47 lobular carcinomas were labeled by immunohistochemistry for PD-L1, CD8, CD20, and FoxP3. The stromal immune infiltrate density was qualitatively scored as a percentage of tumor area: 1+ (50%). The average immune cell subtype per high-power field was quantitatively scored. The percentage PD-L1 labeling on tumor-infiltrating lymphocytes was scored as none, focal (lobular carcinomas contained PD-L1 + tumor-infiltrating lymphocytes with the majority showing 1+ immune infiltrates with focal-moderate PD-L1 labeling. PD-L1 was expressed by tumor cells in 17% of lobular carcinomas. In contrast to ductal carcinomas, there was no correlation between the immune infiltrate density, the PD-L1 expression by lobular carcinoma cells, tumor grade, or the expression of estrogen receptor or human epidermal growth factor receptor-2. However, both the tumor-infiltrating lymphocyte density and the average CD8 + T-cell counts correlated with immune cell PD-L1 status (P=0.004 and 0.03, respectively). Similar to breast ductal carcinomas, PD-L1 + lobular breast carcinomas had higher numbers of PD-L1 + tumor-infiltrating lymphocytes (63%) than PD-L1 - lobular carcinomas (23%; P=0.04). These data show that a subset of primary breast lobular carcinomas both express PD-L1 on tumor cells and contain PD-L1 + tumor-infiltrating lymphocytes, suggesting the possibility of both constitutive and adaptive PD-L1 expression. Together, these results support immunotherapy as a potential treatment for a subset of patients with primary invasive lobular breast carcinomas.

Structural basis of a novel PD-L1 nanobody for immune checkpoint blockade.

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Zhang, Fei; Wei, Hudie; Wang, Xiaoxiao; Bai, Yu; Wang, Pilin; Wu, Jiawei; Jiang, Xiaoyong; Wang, Yugang; Cai, Haiyan; Xu, Ting; Zhou, Aiwu

2017-01-01

The use of antibodies to target immune checkpoints, particularly PD-1/PD-L1, has made a profound impact in the field of cancer immunotherapy. Here, we identified KN035, an anti-PD-L1 nanobody that can strongly induce T-cell responses and inhibit tumor growth. The crystal structures of KN035 complexed with PD-L1 and free PD-L1, solved here at 1.7 and 2.7 Å resolution, respectively, show that KN035 competes with PD-1 (programmed death protein 1) for the same flat surface on PD-L1, mainly through a single surface loop of 21 amino acids. This loop forms two short helices and develops key hydrophobic and ionic interactions with PD-L1 residues, such as Ile54, Tyr56 and Arg113, which are also involved in PD-1 binding. The detailed mutagenesis study identified the hotspot residues of the PD-L1 surface and provides an explanation for the stronger (~1 000-fold) binding of KN035 to PD-L1 than PD-1 and its lack of binding to PD-L2. Overall, this study reveals how a single immunoglobulin-variable scaffold of KN035 or PD-1 can bind to a flat protein surface through either a single surface loop or beta-sheet strands; and provides a basis for designing new immune checkpoint blockers and generating bi-specific antibodies for combination therapy.

Energy-loss return gate via liquid dielectric polarization.

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Kim, Taehun; Yong, Hyungseok; Kim, Banseok; Kim, Dongseob; Choi, Dukhyun; Park, Yong Tae; Lee, Sangmin

2018-04-12

There has been much research on renewable energy-harvesting techniques. However, owing to increasing energy demands, significant energy-related issues remain to be solved. Efforts aimed at reducing the amount of energy loss in electric/electronic systems are essential for reducing energy consumption and protecting the environment. Here, we design an energy-loss return gate system that reduces energy loss from electric/electronic systems by utilizing the polarization of liquid dielectrics. The use of a liquid dielectric material in the energy-loss return gate generates electrostatic potential energy while reducing the dielectric loss of the electric/electronic system. Hence, an energy-loss return gate can make breakthrough impacts possible by amplifying energy-harvesting efficiency, lowering the power consumption of electronics, and storing the returned energy. Our study indicates the potential for enhancing energy-harvesting technologies for electric/electronics systems, while increasing the widespread development of these systems.

Expression of PD-1 and PD-L1 in poorly differentiated neuroendocrine carcinomas of the digestive system: a potential target for anti-PD-1/PD-L1 therapy.

Science.gov (United States)

Roberts, Jordan A; Gonzalez, Raul S; Das, Satya; Berlin, Jordan; Shi, Chanjuan

2017-12-01

Poorly differentiated neuroendocrine carcinoma of the digestive system has a dismal prognosis with limited treatment options. This study aimed to investigate expression of the PD-1/PD-L1 pathway in these tumors. Thirty-seven patients with a poorly differentiated neuroendocrine carcinoma of the digestive system were identified. Their electronic medical records, pathology reports, and pathology slides were reviewed for demographics, clinical history, and pathologic features. Tumor sections were immunohistochemically labeled for PD-1 and PD-L1, and expression of PD-1 and PD-L1 on tumor and tumor-associated immune cells was analyzed and compared between small cell and large cell neuroendocrine carcinomas. The mean age of patients was 61 years old with 18 men and 19 women. The colorectum (n=20) was the most common primary site; other primary sites included the pancreaticobiliary system, esophagus, stomach, duodenum, and ampulla. Expression of PD-1 was detected on tumor cells (n=6, 16%) as well as on tumor-associated immune cells (n=23, 63%). The 6 cases with PD-1 expression on tumor cells also had the expression on immune cells. Expression of PD-L1 was visualized on tumor cells in 5 cases (14%) and on tumor-associated immune cells in 10 cases (27%). There was no difference in PD-1 and PD-L1 expression between small cell and large cell neuroendocrine carcinomas. In conclusion, PD-1/PD-L1 expression is a frequent occurrence in poorly differentiated neuroendocrine carcinomas of the digestive system. Checkpoint blockade targeting the PD-1/PD-L1 pathway may have a potential role in treating patients with this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Observer-dependent sign inversions of polarization singularities.

Science.gov (United States)

Freund, Isaac

2014-10-15

We describe observer-dependent sign inversions of the topological charges of vector field polarization singularities: C points (points of circular polarization), L points (points of linear polarization), and two virtually unknown singularities we call γ(C) and α(L) points. In all cases, the sign of the charge seen by an observer can change as she changes the direction from which she views the singularity. Analytic formulas are given for all C and all L point sign inversions.

PD-L1 expression in non-small cell lung cancer : Correlations with genetic alterations

NARCIS (Netherlands)

Scheel, Andreas H.; Ansen, Sascha; Schultheis, Anne M.; Scheffler, Matthias; Fischer, Rieke N.; Michels, Sebastian; Hellmich, Martin; George, Julie; Zander, Thomas; Brockmann, Michael; Stoelben, Erich; Groen, Harry; Timens, Wim; Perner, Sven; von Bergwelt-Baildon, Michael; Buettner, Reinhard; Wolf, Juergen

2016-01-01

Inhibition of the PD-1/PD-L1 pathway may induce anticancer immune responses in non-small cell lung cancer (NSCLC). Two PD-L1 immunohistochemistry (IHC) assays have been approved as companion diagnostic tests for therapeutic anti-PD-1 antibodies. However, many aspects of PD-L1 prevalence and

Polarization-dependent aluminum metasurface operating at 450 nm

DEFF Research Database (Denmark)

Højlund-Nielsen, Emil; Zhu, Xiaolong; Carstensen, Marcus S

2015-01-01

We report on a polarization-dependent plasmonic aluminum-based high-density metasurface operating at blue wavelengths. The fabricated sub-wavelength structures, tailored in size and geometry, possess strong, localized, plasmonic resonances able to control linear polarization. Best performance...

Multiplexed Immunofluorescence Reveals Potential PD-1/PD-L1 Pathway Vulnerabilities in Craniopharyngioma.

Science.gov (United States)

Coy, Shannon; Rashid, Rumana; Lin, Jia-Ren; Du, Ziming; Donson, Andrew M; Hankinson, Todd C; Foreman, Nicholas K; Manley, Peter E; Kieran, Mark W; Reardon, David A; Sorger, Peter K; Santagata, Sandro

2018-03-02

Craniopharyngiomas are neoplasms of the sellar/parasellar region that are classified into adamantinomatous (ACP) and papillary (PCP) subtypes. Surgical resection of craniopharyngiomas is challenging, and recurrence is common, frequently leading to profound morbidity. BRAF V600E mutations render PCP susceptible to BRAF/MEK inhibitors, but effective targeted therapies are needed for ACP. We explored the feasibility of targeting the PD-1/PD-L1 immune checkpoint pathway in ACP and PCP. We mapped and quantified PD-L1 and PD-1 expression in ACP and PCP resections using immunohistochemistry, immunofluorescence, and RNA in situ hybridization. We used tissue-based cyclic immunofluorescence (t-CyCIF) to map the spatial distribution of immune cells and characterize cell cycle and signaling pathways in ACP tumor cells which intrinsically express PD-1. All ACP (15±14% of cells, n=23, average±S.D.) and PCP (35±22% of cells, n=18) resections expressed PD-L1. In ACP, PD-L1 was predominantly expressed by tumor cells comprising the cyst-lining. In PCP, PD-L1 was highly-expressed by tumor cells surrounding the stromal fibrovascular cores. ACP also exhibited tumor cell-intrinsic PD-1 expression in whorled epithelial cells with nuclear-localized beta-catenin. These cells exhibited evidence of elevated mTOR and MAPK signaling. Profiling of immune populations in ACP and PCP showed a modest density of CD8+ T-cells. ACP exhibit PD-L1 expression in the tumor cyst-lining and intrinsic PD-1 expression in cells proposed to comprise an oncogenic stem-like population. In PCP, proliferative tumor cells express PD-L1 in a continuous band at the stromal-epithelial interface. Targeting PD-L1 and/or PD-1 in both subtypes of craniopharyngioma might therefore be an effective therapeutic strategy.

Chemotherapy treatment is associated with altered PD-L1 expression in lung cancer patients

DEFF Research Database (Denmark)

Rojkó, Lívia; Reiniger, Lilla; Téglási, Vanda

2018-01-01

Objectives: While the predictive value of programmed cell death ligand-1 (PD-L1) protein expression for immune checkpoint inhibitor therapy of lung cancer has been extensively studied, the impact of standard platinum-based chemotherapy on PD-L1 or programmed cell death-1 (PD-1) expression is unkn...... expression of TC in a subset of patients, therefore, rebiopsy and re-evaluation of PD-L1 expression may be necessary for the indication of immune checkpoint inhibitor therapy.......Objectives: While the predictive value of programmed cell death ligand-1 (PD-L1) protein expression for immune checkpoint inhibitor therapy of lung cancer has been extensively studied, the impact of standard platinum-based chemotherapy on PD-L1 or programmed cell death-1 (PD-1) expression...... is unknown. The aim of this study was to determine the changes in PD-L1 expression of tumor cells (TC) and immune cells (IC), in PD-1 expression of IC, and in the amount of stromal mononuclear cell infiltration after platinum-based chemotherapy in patients with lung cancer. Materials and methods: We...

Investigation of Mach-Zehnder interferometer properties based on PLC technology

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Ren, Mei-zhen; Zhang, Jia-shun; An, Jun-ming; Wang, Yue; Wang, Liang-liang; Li, Jian-guang; Wu, Yuan-da; Yin, Xiao-jie; Hu, Xiong-wei

2018-05-01

We report investigations of three types of silica-based thermo-optic modulating Mach-Zehnder interferometers (MZIs). They are widely used in optical communication and quantum photonics. Three types of MZIs are fabricated. The waveguide structure and fabrication process are paid special attention. The power consumption is less than 250 mW for all MZIs. The polarization dependent loss (PDL) at the same attenuation using the upper heater is less than that using the lower heater for the three types of MZIs. In addition, it is found that the PDL at the same attenuation increases gradually for π, 2π and 0 phase differences. The measured response time of the three types of MZIs is less than 1.8 ms.

The wavelength dependence of polarization in NGC 2023

International Nuclear Information System (INIS)

Rolph, C. D.; Scarrott, S. M.

1989-01-01

NGC 2023 is a bright reflection nebula illuminated by the central star HD37903. At 2 microns the nebula is seen solely by reflected light from the central star but in the NIR there is excess radiation that is supposed to arise from thermal emission from a population of small grains (Sellgren, 1984). The unexpectedly high surface brightness at R and I wavelengths has led to the suggestion that even at these wavelengths there is a significant contribution from this thermal emission process (Witt, Schild, and Kraiman, 1984). If the nebula is seen by reflected starlight then this radiation will be linearly polarized. The level of polarization depends on the scattering geometry, grain size distribution, etc., and is typically 20 to 40 percent for nebulae such as NGC 1999 which is morphologically similar to NGC 2023. If, in any waveband, there is a contribution of radiation from emission processes this radiation will be unpolarized and will serve to dilute the scattered radiation to give a lower level of observed polarization. A study of the wavelength dependence of polarization in nebulae in which there may be thermal emission from grains will indicate the contribution from this process to the total luminosity. Polarization maps were produced in BVRI wavebands for the NGC 2023 nebulosity which confirm that at all wavelengths it is a reflection nebula illuminated by a central star. The wavelength dependence of polarization at representative points in the nebula and in a scatter plot of polarization in V and I wavebands at all points at which measurements are given. Results indicate that throughout the nebula there is a general trend for the level of polarization to increase with wavelength and that maximum levels of polarization occur at the longest wavelengths. No evidence is seen in the data for any significant contribution from the thermal emission from grains in the BVRI luminosity of NGC 2023

Polarized light modulates light-dependent magnetic compass orientation in birds

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Muheim, Rachel; Sjöberg, Sissel; Pinzon-Rodriguez, Atticus

2016-01-01

Magnetoreception of the light-dependent magnetic compass in birds is suggested to be mediated by a radical-pair mechanism taking place in the avian retina. Biophysical models on magnetic field effects on radical pairs generally assume that the light activating the magnetoreceptor molecules is nondirectional and unpolarized, and that light absorption is isotropic. However, natural skylight enters the avian retina unidirectionally, through the cornea and the lens, and is often partially polarized. In addition, cryptochromes, the putative magnetoreceptor molecules, absorb light anisotropically, i.e., they preferentially absorb light of a specific direction and polarization, implying that the light-dependent magnetic compass is intrinsically polarization sensitive. To test putative interactions between the avian magnetic compass and polarized light, we developed a spatial orientation assay and trained zebra finches to magnetic and/or overhead polarized light cues in a four-arm “plus” maze. The birds did not use overhead polarized light near the zenith for sky compass orientation. Instead, overhead polarized light modulated light-dependent magnetic compass orientation, i.e., how the birds perceive the magnetic field. Birds were well oriented when tested with the polarized light axis aligned parallel to the magnetic field. When the polarized light axis was aligned perpendicular to the magnetic field, the birds became disoriented. These findings are the first behavioral evidence to our knowledge for a direct interaction between polarized light and the light-dependent magnetic compass in an animal. They reveal a fundamentally new property of the radical pair-based magnetoreceptor with key implications for how birds and other animals perceive the Earth’s magnetic field. PMID:26811473

Scale dependence and small-x behaviour of polarized parton distributions

International Nuclear Information System (INIS)

Ball, R.D.; Forte, S.; Ridolfi, G.

1995-01-01

We discuss perturbative evolution of the polarized structure function g 1 in the (x, Q 2 ) plane, with special regard to the small-x region. We determine g 1 in terms of polarized quark and gluon distributions using coefficient functions to order α s . At small x g 1 then displays substantial scale dependence, which necessarily implies a corresponding scale dependence in the large-x region. This scale dependence has significant consequences for the extraction of the first moment from the experimental data, reducing its value while increasing the error. Conversely, the scale dependence may be used to constrain the size of the polarized gluon distribution. ((orig.))

Scale dependence and small x behaviour of polarized parton distributions

CERN Document Server

Ball, R D; Ridolfi, G; Forte, S; Ridolfi, G

1995-01-01

We discuss perturbative evolution of the polarized structure function g_1 in the (x,Q^2) plane, with special regard to the small-x region. We determine g_1 in terms of polarized quark and gluon distributions using coefficient functions to order alpha_s. At small x g_1 then displays substantial scale dependence, which necessarily implies a corresponding scale dependence in the large-x region. This scale dependence has significant consequences for the extraction of the first moment from the experimental data, reducing its value while increasing the error. Conversely, the scale dependence may be used to constrain the size of the polarized gluon distribution.

PD-1/PD-L1 Inhibitors for Immuno-oncology: From Antibodies to Small Molecules.

Science.gov (United States)

Geng, Qiaohong; Jiao, Peifu; Jin, Peng; Su, Gaoxing; Dong, Jinlong; Yan, Bing

2018-02-12

The recent regulatory approvals of immune checkpoint protein inhibitors, such as ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab ushered a new era in cancer therapy. These inhibitors do not attack tumor cells directly but instead mobilize the immune system to re-recognize and eradicate tumors, which endows them with unique advantages including durable clinical responses and substantial clinical benefits. PD-1/PD-L1 inhibitors, a pillar of immune checkpoint protein inhibitors, have demonstrated unprecedented clinical efficacy in more than 20 cancer types. Besides monoclonal antibodies, diverse PD- 1/PD-L1 inhibiting candidates, such as peptides, small molecules have formed a powerful collection of weapons to fight cancer. The goal of this review is to summarize and discuss the current PD-1/PD-L1 inhibitors including candidates under clinical development, their molecular interactions with PD-1 or PD-L1, the disclosed structureactivity relationships of peptides and small molecules as inhibitors. Current PD-1/PD-L1 inhibitors under clinical development are exclusively dominated by antibodies. The molecular interactions of therapeutic antibodies with PD-1 or PD-L1 have been gradually elucidated for the design of novel inhibitors. Various peptides and traditional small molecules have been investigated in preclinical model to discover novel PD-1/PD-L1 inhibitors. Peptides and small molecules may play an important role in immuno-oncology because they may bind to multiple immune checkpoint proteins via rational design, opening opportunity for a new generation of novel PD-1/PD-L1 inhibitors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Paired Comparison of PD-L1 Expression on Cytologic and Histologic Specimens from Malignancies in the Lung Assessed with PD-L1 IHC 28-8pharmDx and PD-L1 IHC 22C3pharmDx

DEFF Research Database (Denmark)

Skov, Birgit G.; Skov, Torsten

2017-01-01

of the patients are diagnosed on cytology alone. We hypothesized that cytologic cell block material is suitable for PD-L1 analysis. Materials and Methods: Eighty-six paired samples of malignancies from the lung where cytologic cell block and histologic material were available from the same lesion were stained...... with PD-L1 IHC 28-8pharmDx and PD-L1 IHC 22C3pharmDx. Scorings of like material (cytology or histology) stained with different assays were analyzed in order to evaluate the analytical agreement between assays. Scoring of different materials stained with like assays were analyzed in order to evaluate...... the agreement between cytology and histology. Results: A high degree of agreement was found between 28- 8pharmDx and 22C3pharmDx, whether applied to histologic or cytologic cell blocks, with Pearson R2 of 0.95. The Pearson R2 between 2 rounds of assessment of the same assay on the same type of material was also...

Greenhouse gas mitigation can reduce sea-ice loss and increase polar bear persistence

Science.gov (United States)

Amstrup, Steven C.; Deweaver, E.T.; Douglas, David C.; Marcot, B.G.; Durner, George M.; Bitz, C.M.; Bailey, D.A.

2010-01-01

On the basis of projected losses of their essential sea-ice habitats, a United States Geological Survey research team concluded in 2007 that two-thirds of the worlds polar bears (Ursus maritimus) could disappear by mid-century if business-as-usual greenhouse gas emissions continue. That projection, however, did not consider the possible benefits of greenhouse gas mitigation. A key question is whether temperature increases lead to proportional losses of sea-ice habitat, or whether sea-ice cover crosses a tipping point and irreversibly collapses when temperature reaches a critical threshold. Such a tipping point would mean future greenhouse gas mitigation would confer no conservation benefits to polar bears. Here we show, using a general circulation model, that substantially more sea-ice habitat would be retained if greenhouse gas rise is mitigated. We also show, with Bayesian network model outcomes, that increased habitat retention under greenhouse gas mitigation means that polar bears could persist throughout the century in greater numbers and more areas than in the business-as-usual case. Our general circulation model outcomes did not reveal thresholds leading to irreversible loss of ice; instead, a linear relationship between global mean surface air temperature and sea-ice habitat substantiated the hypothesis that sea-ice thermodynamics can overcome albedo feedbacks proposed to cause sea-ice tipping points. Our outcomes indicate that rapid summer ice losses in models and observations represent increased volatility of a thinning sea-ice cover, rather than tipping-point behaviour. Mitigation-driven Bayesian network outcomes show that previously predicted declines in polar bear distribution and numbers are not unavoidable. Because polar bears are sentinels of the Arctic marine ecosystem and trends in their sea-ice habitats foreshadow future global changes, mitigating greenhouse gas emissions to improve polar bear status would have conservation benefits throughout

Greenhouse gas mitigation can reduce sea-ice loss and increase polar bear persistence.

Science.gov (United States)

Amstrup, Steven C; Deweaver, Eric T; Douglas, David C; Marcot, Bruce G; Durner, George M; Bitz, Cecilia M; Bailey, David A

2010-12-16

On the basis of projected losses of their essential sea-ice habitats, a United States Geological Survey research team concluded in 2007 that two-thirds of the world's polar bears (Ursus maritimus) could disappear by mid-century if business-as-usual greenhouse gas emissions continue. That projection, however, did not consider the possible benefits of greenhouse gas mitigation. A key question is whether temperature increases lead to proportional losses of sea-ice habitat, or whether sea-ice cover crosses a tipping point and irreversibly collapses when temperature reaches a critical threshold. Such a tipping point would mean future greenhouse gas mitigation would confer no conservation benefits to polar bears. Here we show, using a general circulation model, that substantially more sea-ice habitat would be retained if greenhouse gas rise is mitigated. We also show, with Bayesian network model outcomes, that increased habitat retention under greenhouse gas mitigation means that polar bears could persist throughout the century in greater numbers and more areas than in the business-as-usual case. Our general circulation model outcomes did not reveal thresholds leading to irreversible loss of ice; instead, a linear relationship between global mean surface air temperature and sea-ice habitat substantiated the hypothesis that sea-ice thermodynamics can overcome albedo feedbacks proposed to cause sea-ice tipping points. Our outcomes indicate that rapid summer ice losses in models and observations represent increased volatility of a thinning sea-ice cover, rather than tipping-point behaviour. Mitigation-driven Bayesian network outcomes show that previously predicted declines in polar bear distribution and numbers are not unavoidable. Because polar bears are sentinels of the Arctic marine ecosystem and trends in their sea-ice habitats foreshadow future global changes, mitigating greenhouse gas emissions to improve polar bear status would have conservation benefits throughout

PD-1/PD-L blockade in gastrointestinal cancers: lessons learned and the road toward precision immunotherapy

Directory of Open Access Journals (Sweden)

Junyu Long

2017-08-01

Full Text Available Abstract Gastrointestinal (GI malignancies are the most prevalent tumors worldwide, with increasing incidence and mortality. Although surgical resection, chemotherapy, radiotherapy, and molecular targeted therapy have led to significant advances in the treatment of GI cancer patients, overall survival is still low. Therefore, alternative strategies must be identified to improve patient outcomes. In the tumor microenvironment, tumor cells can escape the host immune response through the interaction of PD-1 and PD-L, which inhibits the function of T cells and tumor-infiltrating lymphocytes while increasing the function of immunosuppressive T regulatory cells. The use of an anti-PD-1/PD-L blockade enables reprogramming of the immune system to efficiently identify and kill tumor cells. In recent years, the efficacy of PD-1/PD-L blockade has been demonstrated in many tumors, and this treatment is expected to be a pan-immunotherapy for tumors. Here, we review the signaling pathway underlying the dysregulation of PD-1/PD-L in tumors, summarize the current clinical data for PD-1/PD-L inhibitors in GI malignancies, and discuss road toward precision immunotherapy in relation to PD-1/PD-L blockade. The preliminary data for PD-1/PD-L inhibitors are encouraging, and the precision immunotherapy of PD-1/PD-L inhibitors will be a viable and pivotal clinical strategy for GI cancer therapy.

PD-1/PD-L blockade in gastrointestinal cancers: lessons learned and the road toward precision immunotherapy.

Science.gov (United States)

Long, Junyu; Lin, Jianzhen; Wang, Anqiang; Wu, Liangcai; Zheng, Yongchang; Yang, Xiaobo; Wan, Xueshuai; Xu, Haifeng; Chen, Shuguang; Zhao, Haitao

2017-08-03

Gastrointestinal (GI) malignancies are the most prevalent tumors worldwide, with increasing incidence and mortality. Although surgical resection, chemotherapy, radiotherapy, and molecular targeted therapy have led to significant advances in the treatment of GI cancer patients, overall survival is still low. Therefore, alternative strategies must be identified to improve patient outcomes. In the tumor microenvironment, tumor cells can escape the host immune response through the interaction of PD-1 and PD-L, which inhibits the function of T cells and tumor-infiltrating lymphocytes while increasing the function of immunosuppressive T regulatory cells. The use of an anti-PD-1/PD-L blockade enables reprogramming of the immune system to efficiently identify and kill tumor cells. In recent years, the efficacy of PD-1/PD-L blockade has been demonstrated in many tumors, and this treatment is expected to be a pan-immunotherapy for tumors. Here, we review the signaling pathway underlying the dysregulation of PD-1/PD-L in tumors, summarize the current clinical data for PD-1/PD-L inhibitors in GI malignancies, and discuss road toward precision immunotherapy in relation to PD-1/PD-L blockade. The preliminary data for PD-1/PD-L inhibitors are encouraging, and the precision immunotherapy of PD-1/PD-L inhibitors will be a viable and pivotal clinical strategy for GI cancer therapy.

A comparative study of PD-L1 immunohistochemical assays with four reliable antibodies in thymic carcinoma.

Science.gov (United States)

Sakane, Tadashi; Murase, Takayuki; Okuda, Katsuhiro; Takino, Hisashi; Masaki, Ayako; Oda, Risa; Watanabe, Takuya; Kawano, Osamu; Haneda, Hiroshi; Moriyama, Satoru; Saito, Yushi; Yamada, Takeshi; Nakanishi, Ryoichi; Inagaki, Hiroshi

2018-01-23

Currently, four immunohistochemical assays are registered with the US Food and Drug Administration to detect the expression of PD-L1. We investigated the PD-L1 expression in thymic carcinomas using these four diagnostic assays. The cases of 53 patients were reviewed and their specimens were subjected to four PD-L1 assays with different antibodies (SP142, SP263, 22C3, and 28-8). The PD-L1 expression in tumor cells (TCs) and immune cells (ICs) was evaluated. In TCs, the four assays showed similar scores in each case. Histopathologically, high TC scores were observed in squamous cell carcinomas (SqCCs). Meanwhile, there were no significant relationships among the IC scores in the four assays. In SqCCs, the high expression of PD-L1 (defined as ≥50% TC score) in TCs tended to be associated with early stage cancer. The patients with high expression levels of PD-L1 tended to show longer overall survival in the 22C3 assays (p=0.0200). In thymic carcinomas, the staining pattern showed high concordance among the four assays when TCs - rather than ICs - were stained. High PD-L1 positivity in TCs, especially in SqCCs, indicated that PD-1/PD-L1 targeted therapy may be a promising therapeutic approach.

Polarization-dependent diffraction in all-dielectric, twisted-band structures

Energy Technology Data Exchange (ETDEWEB)

Kardaś, Tomasz M.; Jagodnicka, Anna; Wasylczyk, Piotr, E-mail: pwasylcz@fuw.edu.pl [Photonic Nanostructure Facility, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Pasteura 5, 02-093 Warszawa (Poland)

2015-11-23

We propose a concept for light polarization management: polarization-dependent diffraction in all-dielectric microstructures. Numerical simulations of light propagation show that with an appropriately configured array of twisted bands, such structures may exhibit zero birefringence and at the same time diffract two circular polarizations with different efficiencies. Non-birefringent structures as thin as 3 μm have a significant difference in diffraction efficiency for left- and right-hand circular polarizations. We identify the structural parameters of such twisted-band matrices for optimum performance as circular polarizers.

Targeting the upstream transcriptional activator of PD-L1 as an alternative strategy in melanoma therapy.

Science.gov (United States)

Zhu, Bo; Tang, Liming; Chen, Shuyang; Yin, Chengqian; Peng, Shiguang; Li, Xin; Liu, Tongzheng; Liu, Wei; Han, Changpeng; Stawski, Lukasz; Xu, Zhi-Xiang; Zhou, Guangbiao; Chen, Xiang; Gao, Xiumei; Goding, Colin R; Xu, Nan; Cui, Rutao; Cao, Peng

2018-05-22

Programmed cell death ligand 1 (PD-L1) interacts with programmed cell death protein-1 (PD-1) as an immune checkpoint. Reactivating the immune response by inhibiting PD-L1 using therapeutic antibodies provides substantial clinical benefits in many, though not all, melanoma patients. However, transcriptional suppression of PD-L1 expression as an alternative therapeutic anti-melanoma strategy has not been exploited. Here we provide biochemical evidence demonstrating that ultraviolet radiation (UVR) induction of PD-L1 in skin is directly controlled by nuclear factor E2-related transcription factor 2 (NRF2). Depletion of NRF2 significantly induces tumor infiltration by both CD8 + and CD4 + T cells to suppress melanoma progression, and combining NRF2 inhibition with anti-PD-1 treatment enhanced its anti-tumor function. Our studies identify a critical and targetable PD-L1 upstream regulator and provide an alternative strategy to inhibit the PD-1/PD-L1 signaling in melanoma treatment.

Climate impact of idealized winter polar mesospheric and stratospheric ozone losses as caused by energetic particle precipitation

Science.gov (United States)

Meraner, Katharina; Schmidt, Hauke

2018-01-01

Energetic particles enter the polar atmosphere and enhance the production of nitrogen oxides and hydrogen oxides in the winter stratosphere and mesosphere. Both components are powerful ozone destroyers. Recently, it has been inferred from observations that the direct effect of energetic particle precipitation (EPP) causes significant long-term mesospheric ozone variability. Satellites observe a decrease in mesospheric ozone up to 34 % between EPP maximum and EPP minimum. Stratospheric ozone decreases due to the indirect effect of EPP by about 10-15 % observed by satellite instruments. Here, we analyze the climate impact of winter boreal idealized polar mesospheric and polar stratospheric ozone losses as caused by EPP in the coupled Max Planck Institute Earth System Model (MPI-ESM). Using radiative transfer modeling, we find that the radiative forcing of mesospheric ozone loss during polar night is small. Hence, climate effects of mesospheric ozone loss due to energetic particles seem unlikely. Stratospheric ozone loss due to energetic particles warms the winter polar stratosphere and subsequently weakens the polar vortex. However, those changes are small, and few statistically significant changes in surface climate are found.

Energy and polarization dependence of resonant inelastic X-ray scattering in Nd2CuO4

International Nuclear Information System (INIS)

Hill, J.P.; Kao, C.C.; Haemaelaeinen, K.

1998-01-01

The authors report the energy and polarization dependence of resonant inelastic x-ray scattering from Nd 2 CuO 4 . An energy loss feature at ∼6 eV is observed in the vicinity of the Cu K-edge. Numerical calculations based on the Anderson impurity model identify this as a charge transfer excitation to the anti-bonding state. The incident polarization is shown to select the intermediate states participating in the resonance process. Resonances are observed at 8,990 eV and 9,000 eV with the incident polarization perpendicular and parallel to the CuO planes, respectively. In contrast to the single-site model calculations, no resonances are observed associated with the 1s3d 10 L intermediate states, suggesting non-local effects play a role

Retrospective Molecular Epidemiology Study of PD-L1 Expression in Patients with EGFR-Mutant Non-small Cell Lung Cancer.

Science.gov (United States)

Cho, Jong Ho; Zhou, Wei; Choi, Yoon-La; Sun, Jong-Mu; Choi, Hyejoo; Kim, Tae-Eun; Dolled-Filhart, Marisa; Emancipator, Kenneth; Rutkowski, Mary Anne; Kim, Jhingook

2018-01-01

Data are limited on programmed death ligand 1 (PD-L1) expression in epidermal growth factor receptor ( EGFR )-mutant non-small cell lung cancer (NSCLC). We retrospectively evaluated the relationship between PD-L1 expression and recurrence-free survival (RFS) and overall survival in 319 patients with EGFR -mutant NSCLC who were treated at Samsung Medical Center from 2006 to 2014. Membranous PD-L1 expression on tumor cells was measured using the PD-L1 IHC 22C3 pharmDx antibody and reported as tumor proportion score (TPS). Kaplan-Meier methods, log-rank test, and Cox proportional hazards models were used for survival analysis. All patients had ≥1 EGFR mutation-54% in exon 19 and 39% in exon 21. Overall, 51% of patients had PD-L1-positive tumors. The prevalence of PD-L1 positivity was higher among patients with stages II-IV versus stage I disease (64% vs. 44%) and among patients with other EGFR mutations (75%) than with L858R mutation (39%) or exon 19 deletion (52%). PD-L1 positivity was associated with shorter RFS, with an adjusted hazard ratio of 1.52 (95% confidence interval [CI], 0.81 to 2.84; median, 18 months) for the PD-L1 TPS ≥ 50% group, 1.51 (95% CI, 1.02 to 2.21; median, 31 months) for the PD-L1 TPS 1%-49% group, and 1.51 (95% CI, 1.05 to 2.18) for the combined PD-L1-positive groups (TPS ≥ 1%) compared with the PD-L1-negative group (median, 35 months). PD-L1 expression is associated with disease stage and type of EGFR mutation. PD-L1 positivity might be associated with worse RFS among patients with surgically treated EGFR -mutant NSCLC.

Polarization diversity DPSK demodulator on the silicon-on-insulator platform with simple fabrication

DEFF Research Database (Denmark)

Ding, Yunhong; Huang, Bo; Ou, Haiyan

2013-01-01

of a tapered waveguide followed by a 2 × 2 multimode interferometer. A lowest insertion loss of 0.5 dB with low polarization dependent loss of 1.6 dB and low polarization dependent extinction ratio smaller than 3 dB are measured for the polarization diversity circuit. Clear eye-diagrams and a finite power...

The immune checkpoint regulator PD-L1 is a specific target for naturally occurring CD4(+) T cells

DEFF Research Database (Denmark)

Munir, Shamaila; Andersen, Gitte Holmen; Svane, Inge Marie

2013-01-01

Programmed cell death 1 ligand 1 (PD-L1) is an important regulator of T-cell responses and may consequently limit anticancer immunity. We have recently identified PD-L1-specific, cytotoxic CD8(+) T cells. In the present study, we develop these findings and report that CD4(+) helper T cells...... spontaneously recognize PD-L1. We examined the locality of a previously identified HLA-A*0201-restricted PD-L1-epitope for the presence of possible CD4(+) T-cell epitopes. Thus, we identified naturally occurring PD-L1-specific CD4(+) T cells among the peripheral blood lymphocytes of cancer patients...... and - to lesser extents - healthy donors, by means of ELISPOT assays. PD-L1-specific CD4(+) T cells appeared to be TH17 cells exhibiting an effector T-cell cytokine profile. Hence, PD-L1-specific CD4(+) T cells released interferon γ (IFNγ), tumor necrosis factor α (TNFα) and interleukin-17 (IL-17) in response...

Prognostic and predictive values of PD-L1 expression in patients with digestive system cancer: a meta-analysis.

Science.gov (United States)

Dai, Cong; Wang, Meng; Lu, Jun; Dai, Zhiming; Lin, Shuai; Yang, Pengtao; Tian, Tian; Liu, Xinghan; Min, Weili; Dai, Zhijun

2017-01-01

PD-L1 has been reported to be expressed in diverse human malignancies. However, the prognostic value of PD-L1 in digestive system cancers remains inconclusive. Therefore, we conducted this meta-analysis to evaluate the prognostic impact of PD-L1 expression in digestive system cancers. We searched the PubMed, Embase, and the Chinese National Knowledge Infrastructure for publications concerning PD-L1 expression in digestive system cancers. Correlations of PD-L1 expression level with overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) were analyzed. Finally, 32 studies with 7,308 patients were included. Our results show that PD-L1 expression was significantly associated with poorer OS (hazard ratio [HR] =1.44, 95% confidence interval [CI] =1.18-1.76, P digestive system cancers, especially in gastric cancer and pancreatic cancer. In addition, PD-L1 may act as a new parameter for predicting poor prognosis and a promising target for anticancer therapy in digestive system cancers.

Intrinsic and Extrinsic Regulation of PD-L2 Expression in Oncogene-Driven Non-Small Cell Lung Cancer.

Science.gov (United States)

Shibahara, Daisuke; Tanaka, Kentaro; Iwama, Eiji; Kubo, Naoki; Ota, Keiichi; Azuma, Koichi; Harada, Taishi; Fujita, Jiro; Nakanishi, Yoichi; Okamoto, Isamu

2018-03-27

The interaction of programmed cell death ligand 2 (PD-L2) with programmed cell death 1 is implicated in tumor immune escape. The regulation of PD-L2 expression in tumor cells has remained unclear, however. We here examined intrinsic and extrinsic regulation of PD-L2 expression in NSCLC. PD-L2 expression was evaluated by reverse transcription and real-time polymerase chain reaction analysis and by flow cytometry. BEAS-2B cells stably expressing an activated mutant form of EGFR or the echinoderm microtubule associated protein like 4 (EML4)-ALK receptor tyrosine kinase fusion oncoprotein manifested increased expression of PD-L2 at both the mRNA and protein levels. Furthermore, treatment of NSCLC cell lines that harbor such driver oncogenes with corresponding EGFR or ALK tyrosine kinase inhibitors or depletion of EGFR or ALK by small interfering RNA transfection suppressed expression of PD-L2, demonstrating that activating EGFR mutations or echinoderm microtubule associated protein like 4 gene (EML4)-ALK receptor tyrosine kinase gene (ALK) fusion intrinsically induce PD-L2 expression. We also found that interferon gamma (IFN-γ) extrinsically induced expression of PD-L2 through signal transducer and activator of transcription 1 signaling in NSCLC cells. Oncogene-driven expression of PD-L2 in NSCLC cells was inhibited by knockdown of the transcription factors signal transducer and activator of transcription 3 (STAT3) or c-FOS. IFN-γ also activated STAT3 and c-FOS, suggesting that these proteins may also contribute to the extrinsic induction of PD-L2 expression. Expression of PD-L2 is induced intrinsically by activating EGFR mutations or EML4-ALK fusion and extrinsically by IFN-γ, with STAT3 and c-FOS possibly contributing to both intrinsic and extrinsic pathways. Our results thus provide insight into the complexity of tumor immune escape in NSCLC. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

New model for assessing dose and dose rate sensitivity of Gamma ray radiation loss in polarization maintaining optical fibers

International Nuclear Information System (INIS)

Zhang Hongchen; Liu Hai; Qiao Wenqiang; Xue Huijie; He Shiyu

2012-01-01

Highlights: ► Building a new phenomenological theory model to investigate the relation about the irradiation induced loss with irradiation dose and dose rate. ► The Gamma ray irradiation induced loss of the “Capsule” type and “Panda” type polarization maintaining optical fibers at 1310 nm wavelength are investigated. ► The anti irradiation performance of the “Panda” type polarization maintaining optical fiber is better than that of the “Capsule” type polarization maintaining optical fiber, the reason is that the stress region doped by GeO 2 . - Abstract: The Gamma ray irradiation induced loss of the “Capsule” type and “Panda” type polarization maintaining optical fibers at 1310 nm wavelength are investigated. A phenomenological theory model is introduced and the influence of irradiation dose and dose rate on the irradiation induced loss is discussed. The phenomenological theoretical results are consistent with the experimental results of the irradiation induced loss for the two types of polarization maintaining optical fibers. The anti irradiation performance of the “Panda” type polarization maintaining optical fiber is better than that of the “Capsule” type polarization maintaining optical fiber, the reason is that the stress region dope with GeO 2 . Meanwhile, both of the polarization maintaining optical fiber irradiation induced loss increase with increasing the irradiation dose. In the case of same dose, the high dose rate Gamma ray irradiation induced optical fiber losses are higher than that of the low dose rate.

Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab.

Science.gov (United States)

Lee, Hyun Tae; Lee, Ju Yeon; Lim, Heejin; Lee, Sang Hyung; Moon, Yu Jeong; Pyo, Hyo Jeong; Ryu, Seong Eon; Shin, Woori; Heo, Yong-Seok

2017-07-17

In 2016 and 2017, monoclonal antibodies targeting PD-L1, including atezolizumab, durvalumab, and avelumab, were approved by the FDA for the treatment of multiple advanced cancers. And many other anti-PD-L1 antibodies are under clinical trials. Recently, the crystal structures of PD-L1 in complex with BMS-936559 and avelumab have been determined, revealing details of the antigen-antibody interactions. However, it is still unknown how atezolizumab and durvalumab specifically recognize PD-L1, although this is important for investigating novel binding sites on PD-L1 targeted by other therapeutic antibodies for the design and improvement of anti-PD-L1 agents. Here, we report the crystal structures of PD-L1 in complex with atezolizumab and durvalumab to elucidate the precise epitopes involved and the structural basis for PD-1/PD-L1 blockade by these antibodies. A comprehensive comparison of PD-L1 interactions with anti-PD-L1 antibodies provides a better understanding of the mechanism of PD-L1 blockade as well as new insights into the rational design of improved anti-PD-L1 therapeutics.

Frequency dependence of polarization phase difference

International Nuclear Information System (INIS)

Rao, K.S.; Rao, Y.S.; Wang, J.R.

1993-09-01

Polarimetric AIRSAR data of July 13, 1990 acquired over Mahatango watershed area was processed for the identification of corn fields an forested areas. Polarization Phase Difference (PPD) values were computed for the corn fields at P-, L- and C- bands and studied as a function of frequency. The results compare well with the model calculations at 24 deg. incidence angle where as the locations of corn fields were computed to be at 35 deg. incidence angle. The discrepancy is attributed to lack of accurate ground truth and the undulating topography of the corn fields. Another study reported here deals with the usefulness of Polarization Index (PI) for the study of vegetation. PI was found to be dependent on frequency for corn fields where as for forest trees no such dependence was noticed. PI HH,HV is more useful parameter compared to PI HH,VV even for the study of corn fields. (author). 19 refs, 7 figs

Immuno-Oncology Biomarkers for Gastric and Gastroesophageal Junction Adenocarcinoma: Why PD-L1 Testing May Not Be Enough.

Science.gov (United States)

Weinberg, Benjamin A; Xiu, Joanne; Hwang, Jimmy J; Shields, Anthony F; Salem, Mohamed E; Marshall, John L

2018-04-27

The treatment of patients with advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinomas has been transformed by the U.S. Food and Drug Administration approval of pembrolizumab. Tumor and adjacent tissue must stain positively for the programmed cell death ligand 1 (PD-L1) protein by companion diagnostic testing. However, some patients with PD-L1-negative tumors also benefit from pembrolizumab. High microsatellite instability (MSI) and tumor mutational load (TML) are positive predictive biomarkers for immune checkpoint inhibition (ICI) in other tumors. We sought to identify more patients who could benefit from ICI using alternative PD-L1 thresholds, MSI, and TML. Tumor specimens underwent next-generation sequencing (NGS) and PD-L1 testing using immunohistochemistry. NGS was used to determine TML and MSI. We profiled 581 G/GEJ adenocarcinoma specimens. PD-L1 staining was scored for intensity (0, none; 1+, weak; 2+, moderate; 3+, strong). Using 2+ staining at a 5% threshold, 9.3% of tumors were PD-L1 positive, and using 1+ staining at 1%, 16.2% were PD-L1 positive. 6.9% of tumors had high MSI. High TML (≥17 mutations per megabase) was seen in 6.9%, and medium TML (≥7) was seen in 56.5% of tumors. Thirty (5.2%) PD-L1-negative tumors at the 1+, 1% threshold had high TML or high MSI. Primary tumors had higher rates of high TML (8.8% vs. 3.9%; p  = .0377) and high MSI (8.5% vs. 3.9%; p  = .0471) than metastases. PD-L1 testing alone fails to detect patients who may benefit from ICI. Lower PD-L1 thresholds and TML testing should be considered in future clinical trials. Pembrolizumab is approved by the U.S. Food and Drug Administration for patients with refractory gastric and gastroesophageal cancers if the tumor and adjacent tissue stain positively for the programmed cell death ligand 1 (PD-L1) protein by companion diagnostic testing. Tumor mutational load, microsatellite instability (MSI), and alternative PD-L1 testing thresholds may serve as

Climate impact of idealized winter polar mesospheric and stratospheric ozone losses as caused by energetic particle precipitation

Directory of Open Access Journals (Sweden)

K. Meraner

2018-01-01

Full Text Available Energetic particles enter the polar atmosphere and enhance the production of nitrogen oxides and hydrogen oxides in the winter stratosphere and mesosphere. Both components are powerful ozone destroyers. Recently, it has been inferred from observations that the direct effect of energetic particle precipitation (EPP causes significant long-term mesospheric ozone variability. Satellites observe a decrease in mesospheric ozone up to 34 % between EPP maximum and EPP minimum. Stratospheric ozone decreases due to the indirect effect of EPP by about 10–15 % observed by satellite instruments. Here, we analyze the climate impact of winter boreal idealized polar mesospheric and polar stratospheric ozone losses as caused by EPP in the coupled Max Planck Institute Earth System Model (MPI-ESM. Using radiative transfer modeling, we find that the radiative forcing of mesospheric ozone loss during polar night is small. Hence, climate effects of mesospheric ozone loss due to energetic particles seem unlikely. Stratospheric ozone loss due to energetic particles warms the winter polar stratosphere and subsequently weakens the polar vortex. However, those changes are small, and few statistically significant changes in surface climate are found.

PD-L1 expression in EBV-negative diffuse large B-cell lymphoma: clinicopathologic features and prognostic implications.

Science.gov (United States)

Xing, Wei; Dresser, Karen; Zhang, Rui; Evens, Andrew M; Yu, Hongbo; Woda, Bruce A; Chen, Benjamin J

2016-09-13

Programmed cell death ligand 1 (PD-L1) is a cell surface glycoprotein that regulates the cellular immune response and serves as a targetable immune checkpoint molecule. PD-L1 is expressed on tumor cells and the immune microenvironment of several human malignancies, including a subset of aggressive lymphomas. We sought to investigate further the clinical and pathologic features of EBV-negative diffuse large B-cell lymphoma (DLBCL) cases that express PD-L1. Immunohistochemical staining using an anti-PD-L1 monoclonal antibody was performed on DLBCL cases from 86 patients. These patients received standard chemotherapy treatment and were followed for up to 175 months. Overall, 14 cases (16%) were considered positive for PD-L1 in tumor cells. In comparison with PD-L1 negative cases, PD-L1 positive cases had a higher rate of non-GCB type (71% vs. 30%, P=0.0060), and higher Ann Arbor stage (II-IV) (100% vs. 73%, P=0.0327). No significant differences were seen in the immunohistochemical expression of BCL2, MYC, or Ki67. Patients with tumors expressing PD-L1 demonstrated inferior overall survival (OS) upon long term follow up (P=0.0447). Both age/sex-adjusted and multivariate analyses identified PD-L1 as an independent predictor for OS (P=0.0101 and P=0.0424). There was no significant difference, however, in terms of remission rates after first treatment, relapse rates, and progression free survival between the groups. Identification of DLBCL cases that express PD-L1 may serve to select a subset of patients that could further benefit from targeted immunotherapy.

Progress of PD-1/PD-L1 Inhibitors in Non-small Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Zhansheng JIANG

2017-02-01

Full Text Available Pembrolizumab, an inhibitor target programmed death 1 (PD-1, was approved into the first line therapy in advanced non-small cell lung cancer (NSCLC. It was a milestone that immune checkpoints drugs have played an important role in the treatment system of NSCLC. The results of clinical trials revealed the superiority of PD-1/programmed death ligand 1 (PD-L1 inhibitors compared with chemotherapy in first-line, second-line and multidrug resistance phase therapy. Objective response rate (ORR was up to 80% with pembrolizumab plus chemotherapy, and progression-free survival (PFS with single pembrolizumab in first line was nearly 1 year (10.3 months, the hazard ratio for death fell by 40%. Overall survival (OS was more or less 1 year with single drug pembrolizumab, nivolumab and atezolizumab for second line therapy. PD-L1 expression was a predictor of PD-1/PD-L1 inhibitors. The positive rate of PD-L1 (more than 1% in advanced NSCLC was about 60% with little difference between the tissue types. However, there was no gold standard test of PD-L1 expression.

Structural Biology of the Immune Checkpoint Receptor PD-1 and Its Ligands PD-L1/PD-L2

NARCIS (Netherlands)

Zak, Krzysztof M.; Grudnik, Przemyslaw; Magiera, Katarzyna; Dömling, Alexander; Dubin, Grzegorz; Holak, Tad A.

2017-01-01

Cancer cells can avoid and suppress immune responses through activation of inhibitory immune checkpoint proteins, such as PD-1, PD-L1, and CTLA-4. Blocking the activities of these proteins with monoclonal antibodies, and thus restoring T cell function, has delivered breakthrough therapies against

Tasmanian tigers and polar bears: The documentary moving image and (species loss

Directory of Open Access Journals (Sweden)

Belinda Smaill

2015-04-01

Full Text Available In this essay I explore how two divergent examples of the nonfiction moving image can be understood in relation to the problem of representing species loss. The species that provide the platform for this consideration are the thylacine, better known as the Tasmanian tiger, and the polar bear. They represent the two contingencies of species loss: endangerment and extinction. My analysis is structured around moving images from the 1930s of the last known thylacine and the very different example of Arctic Tale (Adam Ravetch, Sarah Robertson, 2007, a ‘Disneyfied’ film that dramatises climate change and its impact on the polar bear. Species loss is frequently perceived in a humanist sense, reflecting how we ‘imagine ourselves’ or anthropocentric charactersations of non-human others. I offer a close analysis of the two films, examining the problem of representing extinction through a consideration of the play of absence and presence, vitality and extinguishment, that characterises both the ontology of cinema and narratives about species loss.

RAC1 P29S regulates PD-L1 expression in melanoma

Science.gov (United States)

Vu, Ha Linh; Rosenbaum, Sheera; Purwin, Timothy J.; Davies, Michael A.; Aplin, Andrew E.

2015-01-01

Summary Whole exome sequencing of cutaneous melanoma has led to the detection of P29 mutations in RAC1 in 5–9% of samples, but the role of RAC1 P29 mutations in melanoma biology remains unclear. Using reverse phase protein array analysis to examine the changes in protein/phospho-protein expression, we identified cyclin B1, PD-L1, Ets-1, and Syk as being selectively upregulated with RAC1 P29S expression and downregulated with RAC1 P29S depletion. Using the melanoma patient samples in TCGA, we found PD-L1 expression to be significantly increased in RAC1 P29S patients compared to RAC1 WT as well as other RAC1 mutants. The finding that PD-L1 is upregulated suggests that oncogenic RAC1 P29S may promote suppression of the antitumor immune response. This is a new insight into the biological function of RAC1 P29S mutations with potential clinical implications as PD-L1 is a candidate biomarker for increased benefit from treatment with anti-PD1 or anti-PD-L1 antibodies. PMID:26176707

Low-loss 3D-laser-written mid-infrared LiNbO3 depressed-index cladding waveguides for both TE and TM polarizations.

Science.gov (United States)

Nguyen, Huu-Dat; Ródenas, Airán; Vázquez de Aldana, Javier R; Martín, Guillermo; Martínez, Javier; Aguiló, Magdalena; Pujol, Maria Cinta; Díaz, Francesc

2017-02-20

We report mid-infrared LiNbO3 depressed-index microstructured cladding waveguides fabricated by three-dimensional laser writing showing low propagation losses (~1.5 dB/cm) at 3.68 µm wavelength for both the transverse electric and magnetic polarized modes, a feature previously unachieved due to the strong anisotropic properties of this type of laser microstructured waveguides and which is of fundamental importance for many photonic applications. Using a heuristic modeling-testing iteration design approach which takes into account cladding induced stress-optic index changes, the fabricated cladding microstructure provides low-loss single mode operation for the mid-IR for both orthogonal polarizations. The dependence of the localized refractive index changes within the cladding microstructure with post-fabrication thermal annealing processes was also investigated, revealing its complex dependence of the laser induced refractive index changes on laser fabrication conditions and thermal post-processing steps. The waveguide modes properties and their dependence on thermal post-processing were numerically modeled and fitted to the experimental values by systematically varying three fundamental parameters of this type of waveguides: depressed refractive index values at sub-micron laser-written tracks, track size changes, and piezo-optic induced refractive index changes.

Dual inhibition of STAT1 and STAT3 activation downregulates expression of PD-L1 in human breast cancer cells.

Science.gov (United States)

Sasidharan Nair, Varun; Toor, Salman M; Ali, Bassam R; Elkord, Eyad

2018-05-02

Breast cancer is the most commonly diagnosed cancer, and it is a leading cause of cancer-related deaths in females worldwide. Triple-negative breast cancer (TNBC) constitutes 15% of breast cancer and shows distinct metastasis profiles with poor prognosis. Strong PD-L1 expression has been observed in some tumors, supporting their escape from immune surveillance. Targeting PD-L1 could be a promising therapeutic approach in breast cancer patients. We investigated potential molecular mechanisms for constitutive expression of PD-L1 by inhibiting upstream STAT1 and STAT3 signals. PD-L1 expression in three breast cancer cell lines was measured using quantitative PCR and western blotting. Activation of STAT1 and STAT3 was blocked using pharmacological inhibitors and siRNA. The mechanism underlying the constitutive expression of PD-L1 was investigated using ChIP and co-immunoprecipitation assays. We found that individual inhibition of STAT1 and STAT3 activation partially downregulated PD-L1, while combined inhibition completely downregulated PD-L1 expression. Moreover, our results suggest that pSTAT1-pSTAT3 dimerize in cytosol and translocate to the nucleus, where they bind to PD-L1 promoter and induce PD-L1 expression. These findings provide a rationale for combined targeting of STAT1 and STAT3 for the development of immune-based cancer therapies for down regulation of PD-L1 expression.

Nonlinear polarization effects in a birefringent single mode optical fiber

International Nuclear Information System (INIS)

Ishiekwene, G.C.; Mensah, S.Y.; Brown, C.S.

2001-04-01

The nonlinear polarization effects in a birefringent single mode optical fiber is studied using Jacobi elliptic functions. We find that the polarization state of the propagating beam depends on the initial polarization as well as the intensity of the input light in a complicated way. The Stokes polarization parameters are either periodic or aperiodic depending on the value of the Jacobian modulus. Our calculations suggest that the effective beat length of the fiber can become infinite at a higher critical value of the input power when polarization dependent losses are considered. (author)

Measuring polarization dependent dispersion of non-polarizing beam splitter cubes with spectrally resolved white light interferometry

Science.gov (United States)

Csonti, K.; Hanyecz, V.; Mészáros, G.; Kovács, A. P.

2017-06-01

In this work we have measured the group-delay dispersion of an empty Michelson interferometer for s- and p-polarized light beams applying two different non-polarizing beam splitter cubes. The interference pattern appearing at the output of the interferometer was resolved with two different spectrometers. It was found that the group-delay dispersion of the empty interferometer depended on the polarization directions in case of both beam splitter cubes. The results were checked by inserting a glass plate in the sample arm of the interferometer and similar difference was obtained for the two polarization directions. These results show that to reach high precision, linearly polarized white light beam should be used and the residual dispersion of the empty interferometer should be measured at both polarization directions.

Plasmonic vortex generator without polarization dependence

Science.gov (United States)

Wang, Han; Liu, Lixia; Liu, Chunxiang; Li, Xing; Wang, Shuyun; Xu, Qing; Teng, Shuyun

2018-03-01

In view of the limitations of vortex generators with polarization dependence at present, we propose a plasmonic vortex generator composed of rectangular holes etched in silver film, in which the optical vortex can be generated under arbitrary linearly polarized light illumination. Two sets of rectangular holes are arranged equidistantly on a circle and rotate in postulate directions. Theoretical analysis provides the design principle for the vortex generator, and numerical simulations give guidance on designating the vortex generator parameters. Experimental measurements verify the performance of the proposed vortex generator. Moreover, two alternative structures for the generation of a plasmonic vortex are also provided in this paper. The resulting perfect vortex, compact structure and flexible illumination conditions will lead to wide applications of this plasmonic vortex generator.

Lactoferricin B reverses cisplatin resistance in head and neck squamous cell carcinoma cells through targeting PD-L1.

Science.gov (United States)

Zhang, Pei; Liu, Jinzhong; Li, Wenlu; Li, Shanshan; Han, Xinguang

2018-05-15

Head and neck squamous cell carcinoma (HNSCC) ranks among the top most common cancers with a poor prognosis. The mechanism of chemoresistance is still not well known. This study is to investigate the programmed death-ligand 1 (PD-L1) expression in HNSCC, and test the effect of lactoferricin B (LfcinB) on chemoresistance and its mechanism. We analyzed 510 HNSCC patients in TCGA database and investigated how CD274 expression was related to patient prognosis. PD-L1 was verified from HNSCC samples at local hospital with immunohistochemistry. PD-L1 expression in the acquired cisplatin-resistant HNSCC cells was examined by PCR and WB in order to test PD-L1-induced chemoresistance. LfcinB inoculation in cisplatin-resistant HNSCC cells and in the nude mice was introduced to test the effect of LfcinB on targeting cisplatin resistance and its mechanism. High CD274 mRNA (>125 FPKM) from TCGA database had a significantly reduced 5-year survival rate, and a lower 5-year survival rate in the chemotherapy and radiotherapy-treated patients (P < .05). PD-L1 overexpression was further supported from analysis of 40 HNSCC specimens. PD-L1 and IL-6 in the established cisplatin-resistant HNSCC cells were shown significantly higher (P < .05). IL-6 and PD-L1 expression were partially inhibited by the anti-IL-6/STAT3 antibody. LfcinB displayed a direct cytotoxic effect on cisplatin-resistant HNSCC cells and HNSCC xenografts of cisplatin-resistant cells in the nude mice displayed significant reduction in tumor volume after LfcinB injection (P < .05). Besides, the increase of IL-6 and PD-L1 in cisplatin-resistant HNSCC cells was abolished in vitro by LfcinB (P < .05). PD-L1 expression in HNSCC cells correlates with poor prognosis and chemoresistance, and LfcinB might provide therapeutic potential in HNSCC patients through modulating IL-6 and PD-L1. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Polarization Dependence of Surface Enhanced Raman Scattering on a Single Dielectric Nanowire

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Hua Qi

2012-01-01

Full Text Available Our measurements of surface enhanced Raman scattering (SERS on Ga2O3 dielectric nanowires (NWs core/silver composites indicate that the SERS enhancement is highly dependent on the polarization direction of the incident laser light. The polarization dependence of the SERS signal with respect to the direction of a single NW was studied by changing the incident light angle. Further investigations demonstrate that the SERS intensity is not only dependent on the direction and wavelength of the incident light, but also on the species of the SERS active molecule. The largest signals were observed on an NW when the incident 514.5 nm light was polarized perpendicular to the length of the NW, while the opposite phenomenon was observed at the wavelength of 785 nm. Our theoretical simulations of the polarization dependence at 514.5 nm and 785 nm are in good agreement with the experimental results.

PD-L1 Expression and Survival among Patients with Advanced Non-Small Cell Lung Cancer Treated with Chemotherapy

DEFF Research Database (Denmark)

Sørensen, Steffen Filskov; Zhou, Wei; Dolled-Filhart, Marisa

2016-01-01

with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy are inconsistent. MATERIAL AND METHODS: We evaluated the relationship between PD-L1 expression and overall survival (OS) among 204 patients with advanced NSCLC treated at Aarhus University Hospital, Aarhus, Denmark, from 2007 to 2012. PD......-positive tumors, and 50% had PD-L1 weak-positive tumors. No statistically significant association was found between PD-L1 expression and survival; adjusted hazard ratio of 1.34 (95% confidence interval, 0.88-2.03; median OS, 9.0 months) for the PD-L1 strong-positive group and 1.07 (0.74-1.55; median OS, 9...... by immunohistochemistry to be frequently expressed in patients with advanced NSCLC. However, PD-L1 expression is not a strong prognostic marker in patients with advanced NSCLC treated with chemotherapy....

The relationship between the PD-1/PD-L1 pathway and DNA mismatch repair in cervical cancer and its clinical significance

Directory of Open Access Journals (Sweden)

Feng YC

2018-01-01

Full Text Available Yang-chun Feng,1,2 Wen-li Ji,3 Na Yue,3 Yan-chun Huang,2 Xiu-min Ma1 1Clinical Laboratory Center, The First Affiliated Hospital of Xinjiang Medical University, 2Clinical Laboratory Center, 3Clinical Pathology Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, People’s Republic of China Background: According to recent clinical observations, deficient DNA mismatch repair (dMMR is capable of improving antitumor effects of the PD-1/PD-L1 pathway, suggesting that dMMR may act as a prognostic indicator of PD-1/PD-L1 antibody drugs. In this study, we examined the dMMR and PD-1/PD-L1 expression, as well as explored the correlation of dMMR status with PD-1/PD-L1 expression in cervical cancer patients, in order to optimize cervical cancer patient selection for PD-1/PD-L1 antibody drug treatment, which is helpful to avoid adverse effects and keep costs manageable. Methods: Sixty-six tissue samples from patients with squamous cell carcinoma were collected, and data of their clinical characteristics were also gathered. Based on these samples, the expression levels of MLH1, MSH2, and PD-L1 in cancer cells were tested by immunohistochemical assay (IHC. Moreover, PD-1/PD-L1 expression in tumor-invading lymphocytes (TILs was detected by IHC as well. Six single-nucleotide-repeat markers of microsatellite instability (MSI, including NR-27, MONO-27, BAT-25, NR-24, NR-21, and BAT-26, were tested by capillary electrophoresis sequencer analysis. According to expression of MLH1, MSH2 and the MSI test, all 66 cases were divided into dMMR or proficient DNA mismatch repair (pMMR groups. The comparisons of dMMR and PD-L1 in cancer cells and of PD-1/PD-L1 in TILs were conducted categorized by age, childbearing history, history of abortion, ethnicity, and cancer cell differentiation subgroup. Furthermore, PD-L1 levels in cancer cells and PD-1/PD-L1 in TILs were analyzed and compared in both dMMR and pMMR subgroups. Results: Of the patient samples, 25

Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade.

Science.gov (United States)

Lipson, Evan J; Lilo, Mohammed T; Ogurtsova, Aleksandra; Esandrio, Jessica; Xu, Haiying; Brothers, Patricia; Schollenberger, Megan; Sharfman, William H; Taube, Janis M

2017-01-01

Monoclonal antibodies that block immune regulatory proteins such as programmed death-1 (PD-1) have demonstrated remarkable efficacy in controlling the growth of multiple tumor types. Unresectable or metastatic basal cell carcinoma, however, has largely gone untested. Because PD-Ligand-1 (PD-L1) expression in other tumor types has been associated with response to anti-PD-1, we investigated the expression of PD-L1 and its association with PD-1 expression in the basal cell carcinoma tumor microenvironment. Among 40 basal cell carcinoma specimens, 9/40 (22%) demonstrated PD-L1 expression on tumor cells, and 33/40 (82%) demonstrated PD-L1 expression on tumor-infiltrating lymphocytes and associated macrophages. PD-L1 was observed in close geographic association to PD-1+ tumor infiltrating lymphocytes. Additionally, we present, here, the first report of an objective anti-tumor response to pembrolizumab (anti-PD-1) in a patient with metastatic PD-L1 (+) basal cell carcinoma, whose disease had previously progressed through hedgehog pathway-directed therapy. The patient remains in a partial response 14 months after initiation of therapy. Taken together, our findings provide a rationale for testing anti-PD-1 therapy in patients with advanced basal cell carcinoma, either as initial treatment or after acquired resistance to hedgehog pathway inhibition.

Understanding the structural and energetic basis of PD-1 and monoclonal antibodies bound to PD-L1: A molecular modeling perspective.

Science.gov (United States)

Shi, Danfeng; Zhou, Shuangyan; Liu, Xuewei; Zhao, Chenxi; Liu, Huanxiang; Yao, Xiaojun

2018-03-01

The inhibitors blocking the interaction between programmed cell death protein 1(PD-1) and programmed death-ligand 1(PD-L1) can activate the immune response of T cell and eliminate cancer cells. The crystallographic studies have provided structural insights of the interactive interfaces between PD-L1 and its protein ligands. However, the hotspot residues on PD-L1 as well as structural and energetic basis for different protein ligands still need to be further investigated. Molecular modeling methods including molecular dynamics simulation, per-residue free energy decomposition, virtual alanine scanning mutagenesis and residue-residue contact analysis were used to qualitatively and quantitatively analyze the interactions between PD-L1 and different protein ligands. The results of virtual alanine scanning mutagenesis suggest that Y56, Q66, M115, D122, Y123, R125 are the hotspot residues on PD-L1. The residue-residue contact analysis further shows that PD-1 interacts with PD-L1 mainly by F and G strands while monoclonal antibodies like avelumab and BMS-936559 mainly interact with PD-L1 by CDR2 and CDR3 loops of the heavy chain. A structurally similar β-hairpin peptide with 13 or 14 residues was extracted from each protein ligand and these β-hairpin peptides were found tightly binding to the putative hotspot residues on PD-L1. This study recognizes the hotspot residues on PD-L1 and uncovers the common structural and energetic basis of different protein ligands binding to PD-L1. These results will be valuable for the design of small molecule or peptide inhibitors targeting on PD-L1. Copyright © 2017 Elsevier B.V. All rights reserved.

Variability in Immunohistochemical Detection of Programmed Death Ligand 1 (PD-L1) in Cancer Tissue Types

Science.gov (United States)

Scognamiglio, Giosuè; De Chiara, Anna; Di Bonito, Maurizio; Tatangelo, Fabiana; Losito, Nunzia Simona; Anniciello, Annamaria; De Cecio, Rossella; D’Alterio, Crescenzo; Scala, Stefania; Cantile, Monica; Botti, Gerardo

2016-01-01

In normal cell physiology, programmed death 1 (PD-1) and its ligand, PD-L1, play an immunoregulatory role in T-cell activation, tolerance, and immune-mediated tissue damage. The PD-1/PD-L1 pathway also plays a critical role in immune escape of tumor cells and has been demonstrated to correlate with a poor prognosis of patients with several types of cancer. However, recent reports have revealed that the immunohistochemical (IHC) expression of the PD-L1 in tumor cells is not uniform for the use of different antibodies clones, with variable specificity, often doubtful topographical localization, and with a score not uniquely defined. The purpose of this study was to analyze the IHC expression of PD-L1 on a large series of several human tumors to correctly define its staining in different tumor tissues. PMID:27213372

Passive technologies for future large-scale photonic integrated circuits on silicon: polarization handling, light non-reciprocity and loss reduction

Directory of Open Access Journals (Sweden)

Daoxin Dai

2012-03-01

Full Text Available Silicon-based large-scale photonic integrated circuits are becoming important, due to the need for higher complexity and lower cost for optical transmitters, receivers and optical buffers. In this paper, passive technologies for large-scale photonic integrated circuits are described, including polarization handling, light non-reciprocity and loss reduction. The design rule for polarization beam splitters based on asymmetrical directional couplers is summarized and several novel designs for ultra-short polarization beam splitters are reviewed. A novel concept for realizing a polarization splitter–rotator is presented with a very simple fabrication process. Realization of silicon-based light non-reciprocity devices (e.g., optical isolator, which is very important for transmitters to avoid sensitivity to reflections, is also demonstrated with the help of magneto-optical material by the bonding technology. Low-loss waveguides are another important technology for large-scale photonic integrated circuits. Ultra-low loss optical waveguides are achieved by designing a Si3N4 core with a very high aspect ratio. The loss is reduced further to <0.1 dB m−1 with an improved fabrication process incorporating a high-quality thermal oxide upper cladding by means of wafer bonding. With the developed ultra-low loss Si3N4 optical waveguides, some devices are also demonstrated, including ultra-high-Q ring resonators, low-loss arrayed-waveguide grating (demultiplexers, and high-extinction-ratio polarizers.

The Emerging Role of PD-1/PD-L1-Targeting Immunotherapy in the Treatment of Metastatic Urothelial Carcinoma.

Science.gov (United States)

Gwynn, Morgan E; DeRemer, David L

2018-01-01

To summarize and evaluate immunotherapy agents targeting programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) recently approved for the treatment of metastatic urothelial carcinomas (UC). A literature review was performed using PubMed (2012 to June 2017), the American Society of Clinical Oncology abstract databases (2012 to June 2017 Annual Meetings/symposia), and the America Association for Cancer Research symposia (2012 to June 2017). A search using clinicaltrials.gov was conducted to identify studies for atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab. English language phase I to III studies assessing PD-1 and PD-L1 in UC were incorporated. Atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab have demonstrated clinical efficacy with tolerable toxicities in patients with metastatic UC with disease progression following platinum-based chemotherapy. Anti-PD-1/PD-L1 therapies may provide overall survival advantage; these are currently being evaluated in ongoing phase 3 studies. Greater objective response rates seem to be observed in PD-L1-positive patients versus PD-L1-negative patients, but methodologies in this assessment differ among clinical trials. The identification of biomarkers that provide greater insight into patients who positively respond to PD-1/PD-L1 therapies are needed. Treatment options for metastatic UC have expanded to include PD-1/PD-L1 therapies. These agents should be strongly considered as second-line therapy over single-agent chemotherapy for patients who fail or progress after platinum-based treatment.

Ultra-high tunable liquid crystal-plasmonic photonic crystal fiber polarization filter.

Science.gov (United States)

Hameed, Mohamed Farhat O; Heikal, A M; Younis, B M; Abdelrazzak, Maher; Obayya, S S A

2015-03-23

A novel ultra-high tunable photonic crystal fiber (PCF) polarization filter is proposed and analyzed using finite element method. The suggested design has a central hole infiltrated with a nematic liquid crystal (NLC) that offers high tunability with temperature and external electric field. Moreover, the PCF is selectively filled with metal wires into cladding air holes. Results show that the resonance losses and wavelengths are different in x and y polarized directions depending on the rotation angle φ of the NLC. The reported filter of compact device length 0.5 mm can achieve 600 dB / cm resonance losses at φ = 90° for x-polarized mode at communication wavelength of 1300 mm with low losses of 0.00751 dB / cm for y-polarized mode. However, resonance losses of 157.71 dB / cm at φ = 0° can be achieved for y-polarized mode at the same wavelength with low losses of 0.092 dB / cm for x-polarized mode.

Magnetization-dependent viscosity in brute-force-polarized liquid 3He

DEFF Research Database (Denmark)

Vermeulen, G.A.; Schuhl, A.; Joffrin, J.

1988-01-01

A new method to measure the magnetization dependence of the viscosity in polarized liquid He3 is presented. The magnetization is obtained by "brute-force polarization" at 45 mK in magnetic fields up to 11 T; it is subsequently destroyed by saturation of the NMR signal. Our result, a relative...... increase of the viscosity of (31.5)×10-3 at 3.9% polarization and a pressure of 30 bars, disagrees with a prediction based on the "nearly metamagnetic" model....

THE EFFICIENCY AND WAVELENGTH DEPENDENCE OF NEAR-INFRARED INTERSTELLAR POLARIZATION TOWARD THE GALACTIC CENTER

Energy Technology Data Exchange (ETDEWEB)

Hatano, Hirofumi; Kurita, Mikio; Kanai, Saori; Sato, Shuji [Department of Astrophysics, Nagoya University, Chikusa-ku, Nagoya 464-8602 (Japan); Nishiyama, Shogo; Nakajima, Yasushi; Tamura, Motohide; Kandori, Ryo [National Astronomical Observatory of Japan, Mitaka, Tokyo 181-8858 (Japan); Nagata, Tetsuya; Yoshikawa, Tatsuhito [Department of Astronomy, Kyoto University, Sakyo-ku, Kyoto 606-8502 (Japan); Kato, Daisuke [Department of Astronomy, School of Science, University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan); Sato, Yaeko; Suenaga, Takuya, E-mail: hattan@z.phys.nagoya-u.ac.jp, E-mail: shogo.nishiyama@nao.ac.jp [Department of Astronomical Sciences, Graduate University for Advanced Studies (Sokendai), Mitaka, Tokyo 181-8858 (Japan)

2013-04-15

Near-infrared polarimetric imaging observations toward the Galactic center (GC) have been carried out to examine the efficiency and wavelength dependence of interstellar polarization. A total area of about 5.7 deg{sup 2} is covered in the J, H, and K{sub S} bands. We examined the polarization efficiency, defined as the ratio of the degree of polarization to color excess. The interstellar medium between the GC and us shows a polarization efficiency lower than that in the Galactic disk by a factor of three. Moreover we investigated the spatial variation of the polarization efficiency by comparing it with that of the color excess, degree of polarization, and position angle. The spatial variations of color excess and degree of polarization depend on the Galactic latitude, while the polarization efficiency varies independently of the Galactic structure. Position angles are nearly parallel to the Galactic plane, indicating a longitudinal magnetic field configuration between the GC and us. The polarization efficiency anticorrelates with dispersions of position angles. The low polarization efficiency and its spatial variation can be explained by the differences in the magnetic field directions along the line of sight. From the lower polarization efficiency, we suggest a higher strength of a random component relative to a uniform component of the magnetic field between the GC and us. We also derived the ratios of degree of polarization p{sub H} /p{sub J} = 0.581 {+-} 0.004 and p{sub K{sub S}}/p{sub H} = 0.620 {+-} 0.002. The power-law indices of the wavelength dependence of polarization are {beta}{sub JH} = 2.08 {+-} 0.02 and {beta}{sub HK{sub S}} = 1.76 {+-} 0.01. Therefore, the wavelength dependence of interstellar polarization exhibits flattening toward longer wavelengths in the range of 1.25-2.14 {mu}m. The flattening would be caused by aligned large-size dust grains.

Plasma depletion layer: its dependence on solar wind conditions and the Earth dipole tilt

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Y. L. Wang

2004-12-01

Full Text Available The plasma depletion layer (PDL is a layer on the sunward side of the magnetopause with lower plasma density and higher magnetic field compared to their corresponding upstream magnetosheath values. It is believed that the PDL is controlled jointly by conditions in the solar wind plasma and the (IMF. In this study, we extend our former model PDL studies by systematically investigating the dependence of the PDL and the slow mode front on solar wind conditions using global MHD simulations. We first point out the difficulties for the depletion factor method and the plasma β method for defining the outer boundary of the plasma depletion layer. We propose to use the N/B ratio to define the PDL outer boundary, which can give the best description of flux tube depletion. We find a strong dependence of the magnetosheath environment on the solar wind magnetosonic Mach number. A difference between the stagnation point and the magnetopause derived from the open-closed magnetic field boundary is found. We also find a strong and complex dependence of the PDL and the slow mode front on the IMF B_z. A density structure right inside the subsolar magnetopause for higher IMF B_z;might be responsible for some of this dependence. Both the IMF tilt and clock angles are found to have little influence on the magnetosheath and the PDL structures. However, the IMF geometry has a much stronger influence on the slow mode fronts in the magnetosheath. Finally, the Earth dipole tilt is found to play a minor role for the magnetosheath geometry and the PDL along the Sun-Earth line. A complex slow mode front geometry is found for cases with different Earth dipole tilts. Comparisons between our results with those from some former studies are conducted, and consistencies and inconsistencies are found.

Key words. Magnetospheric physics (magnetosheath, solar wind-magnetosphere interactions – Space plasma physics (numerical

Towards Polarization Diversity on the SOI Platform With Simple Fabrication Process

DEFF Research Database (Denmark)

Ding, Yunhong; Liu, Liu; Peucheret, Christophe

2011-01-01

We present a polarization diversity circuit built on the silicon-on-insulator (SOI) platform, which can be fabricated by a simple process. The polarization diversity is based on two identical air-clad asymmetrical directional couplers, which simultaneously play the roles of polarization splitter...... and rotator. A silicon polarization diversity circuit with a single microring resonator is fabricated on the SOI platform. Only ${1-dB polarization-dependent loss is demonstrated. A significant improvement of the polarization dependence is obtained for 20-Gb/s nonreturn-to-zero differential phase-shift keying...

Frequency dependent loss analysis and minimization of system losses in switchmode audio power amplifiers

DEFF Research Database (Denmark)

Yamauchi, Akira; Knott, Arnold; Jørgensen, Ivan Harald Holger

2014-01-01

In this paper, frequency dependent losses in switch-mode audio power amplifiers are analyzed and a loss model is improved by taking the voltage dependence of the parasitic capacitance of MOSFETs into account. The estimated power losses are compared to the measurement and great accuracy is achieved...

Polarization correction in the theory of energy losses by charged particles

Energy Technology Data Exchange (ETDEWEB)

Makarov, D. N., E-mail: makarovd0608@yandex.ru; Matveev, V. I. [Lomonosov Northern (Arctic) Federal University (Russian Federation)

2015-05-15

A method for finding the polarization (Barkas) correction in the theory of energy losses by charged particles in collisions with multielectron atoms is proposed. The Barkas correction is presented in a simple analytical form. We make comparisons with experimental data and show that applying the Barkas correction improves the agreement between theory and experiment.

Coherent active polarization control without loss

Science.gov (United States)

Ye, Yuqian; Hay, Darrick; Shi, Zhimin

2017-11-01

We propose a lossless active polarization control mechanism utilizing an anisotropic dielectric medium with two coherent inputs. Using scattering matrix analysis, we derive analytically the required optical properties of the anisotropic medium that can behave as a switchable polarizing beam splitter. We also show that such a designed anisotropic medium can produce linearly polarized light at any azimuthal direction through coherent control of two inputs with a specific polarization state. Furthermore, we present a straightforward design-on-demand procedure of a subwavelength-thick metastructure that can possess the desired optical anisotropy at a flexible working wavelength. Our lossless coherent polarization control technique may lead to fast, broadband and integrated polarization control elements for applications in imaging, spectroscopy, and telecommunication.

thermally poled channel waveguides with polarization independent electro-optic effect

DEFF Research Database (Denmark)

Ren, Yitao; Marckmann, Carl Johan; Arentoft, Jesper

2002-01-01

We present a systematic investigation of the poling-induced electrooptic (EO) effect in germanium and nitrogen codoped channel waveguides. The channel waveguides show attractive properties: (1) almost polarization independent EO effect; (2) a flat frequency response with the modulation frequency up...... to 100 kHz; and (3) low linear loss and low polarization dependent loss, which demonstrate great technological potential...

No evidence for dualism in function and receptors: PD-L2/B7-DC is an inhibitory regulator of human T cell activation.

Science.gov (United States)

Pfistershammer, Katharina; Klauser, Christoph; Pickl, Winfried F; Stöckl, Johannes; Leitner, Judith; Zlabinger, Gerhard; Majdic, Otto; Steinberger, Peter

2006-05-01

The B7 family member programmed-death-1-ligand 2 (PD-L2/B7-DC) is a ligand for programmed-death-receptor 1 (PD-1), a receptor involved in negative regulation of T cell activation. Several independent studies have reported that PD-L2, however, can also potently costimulate murine T cells via an additional yet unidentified receptor. In this study, we evaluated the contribution of PD-L2 to the activation of human T cells using a novel system of engineered T cell stimulators that expresses membrane-bound anti-CD3 antibodies. Analyzing early activation markers, cytokine production and proliferation, we found PD-L2 to consistently inhibit T cell activation. PD-L2 inhibition affected CD4+ and CD8+ T cells and was not abrogated by costimulation via CD28. Blocking PD-1 reverted the inhibitory effect of PD-L2, demonstrating involvement of this pathway. In human T cells, we found no evidence for any of the costimulatory effects described for PD-L2 in murine systems. In line with our functional data that do not point to stimulatory PD-L2-ligands, we show that binding of PD-L2-immunoglobulin to activated human T cells is abrogated by PD-1 antibodies. Our results demonstrate that PD-L2 negatively regulates human T cell activation and thus might be a candidate molecule for immunotherapeutic approaches aimed to attenuate pathological immune responses.

Dependence of extinction cross-section on incident polarization state and particle orientation

International Nuclear Information System (INIS)

Yang Ping; Wendisch, Manfred; Bi Lei; Kattawar, George; Mishchenko, Michael; Hu, Yongxiang

2011-01-01

This note reports on the effects of the polarization state of an incident quasi-monochromatic parallel beam of radiation and the orientation of a hexagonal ice particle with respect to the incident direction on the extinction process. When the incident beam is aligned with the six-fold rotational symmetry axis, the extinction is independent of the polarization state of the incident light. For other orientations, the extinction cross-section for linearly polarized light can be either larger or smaller than its counterpart for an unpolarized incident beam. Therefore, the attenuation of a quasi-monochromatic radiation beam by an ice cloud depends on the polarization state of the beam if ice crystals within the cloud are not randomly oriented. Furthermore, a case study of the extinction of light by a quartz particle is also presented to illustrate the dependence of the extinction cross-section on the polarization state of the incident light.

Polarization-dependent solitons in the strong coupling regime of semiconductor microcavities

International Nuclear Information System (INIS)

Fu, Y.; Zhang, W.L.; Wu, X.M.

2015-01-01

This paper studies the influence of polarization on formation of vectorial polariton soliton in semiconductor microcavities through numerical simulations. It is found that the polariton solution greatly depends on the polarization of both the pump and exciting fields. By properly choosing the pump and exciting field polarization, bright–bright or bright–dark vectorial polariton solitons can be formed. Especially, when the input conditions of pump or exciting field of the two opposite polarizations are slightly asymmetric, an interesting phenomenon that the dark solitons transform into bright solitons occurs in the branch of soliton solutions.

Crystal clear: visualizing the intervention mechanism of the PD-1/PD-L1 interaction by two cancer therapeutic monoclonal antibodies

Directory of Open Access Journals (Sweden)

Shuguang Tan

2016-11-01

Full Text Available Abstract Antibody-based PD-1/PD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast to prior approaches to generate or boost tumor-specific T-cell responses, antibody-based PD-1/PD-L1 blockade targets tumor-induced T-cell defects and restores pre-existing T-cell function to modulate antitumor immunity. In this review, the fundamental knowledge on the expression regulations and inhibitory functions of PD-1 and the present understanding of antibody-based PD-1/PD-L1 blockade therapies are briefly summarized. We then focus on the recent breakthrough work concerning the structural basis of the PD-1/PD-Ls interaction and how therapeutic antibodies, pembrolizumab targeting PD-1 and avelumab targeting PD-L1, compete with the binding of PD-1/PD-L1 to interrupt the PD-1/PD-L1 interaction. We believe that this structural information will benefit the design and improvement of therapeutic antibodies targeting PD-1 signaling.

Intestinal APCs of the endogenous nanomineral pathway fail to express PD-L1 in Crohn's disease.

Science.gov (United States)

Robertson, Jack; Haas, Carolin T; Pele, Laetitia C; Monie, Tom P; Charalambos, Charles; Parkes, Miles; Hewitt, Rachel E; Powell, Jonathan J

2016-05-26

Crohn's disease is a chronic inflammatory condition most commonly affecting the ileum and colon. The aetiology of Crohn's disease is complex and may include defects in peptidoglycan recognition, and/or failures in the establishment of intestinal tolerance. We have recently described a novel constitutive endogenous delivery system for the translocation of nanomineral-antigen-peptidoglycan (NAP) conjugates to antigen presenting cells (APCs) in intestinal lymphoid patches. In mice NAP conjugate delivery to APCs results in high surface expression of the immuno-modulatory molecule programmed death receptor ligand 1 (PD-L1). Here we report that NAP conjugate positive APCs in human ileal tissues from individuals with ulcerative colitis and intestinal carcinomas, also have high expression of PD-L1. However, NAP-conjugate positive APCs in intestinal tissue from patients with Crohn's disease show selective failure in PD-L1 expression. Therefore, in Crohn's disease intestinal antigen taken up by lymphoid patch APCs will be presented without PD-L1 induced tolerogenic signalling, perhaps initiating disease.

Coherent active polarization control without loss

Directory of Open Access Journals (Sweden)

Yuqian Ye

2017-11-01

Full Text Available We propose a lossless active polarization control mechanism utilizing an anisotropic dielectric medium with two coherent inputs. Using scattering matrix analysis, we derive analytically the required optical properties of the anisotropic medium that can behave as a switchable polarizing beam splitter. We also show that such a designed anisotropic medium can produce linearly polarized light at any azimuthal direction through coherent control of two inputs with a specific polarization state. Furthermore, we present a straightforward design-on-demand procedure of a subwavelength-thick metastructure that can possess the desired optical anisotropy at a flexible working wavelength. Our lossless coherent polarization control technique may lead to fast, broadband and integrated polarization control elements for applications in imaging, spectroscopy, and telecommunication.

Role of PD1/PDL1 pathway, and TH17 and treg cells in maternal tolerance to the fetus

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Sudipta Tripathi

2015-02-01

Full Text Available Tolerance of the fetus by the maternal immune system is regulated through various mechanisms involving the different immune cells, both in the periphery and locally at the feto-maternal interface. The maternal T lymphocytes are aware of the paternal fetal antigens and a state of dynamic T cell homeostasis is maintained in the uterus during gestation, which involves increase in antigen-specific regulatory T cell (Treg proliferation, increase in apoptosis of antigen-specific effector T cells, and inhibition of excessive inflammation post successful implantation to ensure tolerance to the fetus. The Tregs play an important role in the maintenance of tolerance during gestation. Recently, the inflammatory T helper type 17 (Th17 cells are reported to have a role in loss of tolerance to the fetus. The interaction between costimulatory molecule programmed death 1 (PD1 and its ligand PDL1 is known to play a role in regulating both the Tregs and Th17 cells. Here we discuss how the PD1/PDL1 pathway affects these two T cell populations and its role in feto-maternal tolerance.

PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: updated survival data.

Science.gov (United States)

Aguiar, Pedro N; De Mello, Ramon Andrade; Hall, Peter; Tadokoro, Hakaru; Lima Lopes, Gilberto de

2017-05-01

The treatment of non-small-cell lung cancer has changed after the development of the immune checkpoint inhibitors. Although the most studied biomarker is PD-L1 expression, its clinical significance is still debatable. In this article, we show the updated survival analysis of all published data. We searched in network and conference data sources for relevant clinical studies of immunotherapy for non-small-cell lung cancer that assessed the PD-L1 expression even as an exploratory analysis. The updated survival hazard ratios (HR) were included in the analysis. 14 studies with 2857 patients were included (2019 treated with immunotherapy). The response rate was as higher among PD-L1-positive patients (RR: 2.19, 95% CI: 1.63-2.94). PD-L1 expression was also related to better progression-free survival (HR: 0.69, 95% CI: 0.57-0.85) and better overall survival (HR: 0.77, 95% CI: 0.67-0.89). PD-L1 overexpression predicts activity as well as better survival for patients treated with immune checkpoint inhibitors.

Polarization-dependent photoluminescence studies of semipolar and nonpolar InGaN quantum wells

Energy Technology Data Exchange (ETDEWEB)

Schade, Lukas; Schwarz, Ulrich [IAF, Freiburg (Germany); Wernicke, Tim; Weyers, Markus [FBH, Berlin (Germany); Kneissl, Michael [FBH, Berlin (Germany); Institute of Solid State Physics, TU Berlin (Germany)

2010-07-01

Light emitted from optical devices based on semi- and nonpolar GaN quantum well (QW) structures is partially or totally polarized, as a consequence of crystal symmetry and band structure. This can be an additional advantage over polar (0001)GaN in specific applications, e.g. in LED backlighting. Fundamentally, the polarized emission stems from breaking the isotropic symmetry of the hexagonal c-plane, resulting in two discrete semi- and nonpolar directions (parallel and normal to the projection of (0001)). We use the k.p method to simulate the crystal-direction dependent emission. The resulting transition matrix elements assign a specific (partial) polarization for each subband. The thermal occupation of the subbands results in a temperature dependent effective polarization of the light emission. We study MOVPE grown homoepitactical polar, semi- and nonpolar samples, measuring the polarization properties of the resonantly excited photoluminescence from the QW. With the complete polarization of the subbands for nonpolar devices it is possible to measure the energetic difference of the first two valence band levels. In contrast to our calculations we find a higher degree of polarization also in semipolar directions. A possible explanation could be a higher energetic subband difference than computed.

Identification of a novel splice variant of human PD-L1 mRNA encoding an isoform-lacking Igv-like domain.

Science.gov (United States)

He, Xian-hui; Xu, Li-hui; Liu, Yi

2005-04-01

To investigate the expression and regulation of PD-1 ligand 1 (PD-L1) in peripheral blood mononuclear cells (PBMC). The cDNA encoding human PD-L1 precursor was cloned from the total RNA extracted from the resting and phorbol dibutyrate plus ionomycin- or phytohemagglutinin-activated PBMC, by reverse transcription polymerase chain reaction (RT-PCR), and independent clones were sequenced and analyzed. The expression and subcellular localization were examined in transiently transfected cells. The PD-L1 gene expression in different PBMC was also analyzed by RT-PCR. A novel human PD-L1 splice variant was identified from the activated PBMC. It was generated by splicing out exon? encoding an immunoglobulin variable domain (Igv)-like domain but retaining all other exons without a frame-shift. Consequently, the putative translated protein contained all other domains including the transmembrane region except for the Igv-like domain. Furthermore, the conventional isoform was expressed on the plasma surface whereas the novel isoform showed a pattern of intracellular membrane distribution in transiently transfected K562 cells. In addition, the expression pattern of the PD-L1 splice variant was variable in different individuals and in different cellular status. PD-L1 expression may be regulated at the posttranscriptional level through alternative splicing, and modulation of the PD-L1 isoform expression may influence the outcome of specific immune responses in the peripheral tissues.

Polarization dependent effects in photo-fragmentation dynamics of free molecules

International Nuclear Information System (INIS)

Mocellin, A.; Marinho, R.R.T.; Coutinho, L.H.; Burmeister, F.; Wiesner, K.; Naves de Brito, A.

2003-01-01

We present multicoincidence spectra of nitrogen, formic acid and methyl methacrylate. We demonstrate how to probe the local symmetry of molecular orbitals from molecules core excited with linearly polarized synchrotron radiation. The intensity distribution of the photoelectron photo-ion photo-ion coincidence (PEPIPICO) spectrum reflects the selectivity and localization of core excitation by polarized light. By simulating the spectra the angular dependence of the fragmentation is determined

Polarization dependent effects in photo-fragmentation dynamics of free molecules

Energy Technology Data Exchange (ETDEWEB)

Mocellin, A.; Marinho, R.R.T.; Coutinho, L.H.; Burmeister, F.; Wiesner, K.; Naves de Brito, A

2003-04-01

We present multicoincidence spectra of nitrogen, formic acid and methyl methacrylate. We demonstrate how to probe the local symmetry of molecular orbitals from molecules core excited with linearly polarized synchrotron radiation. The intensity distribution of the photoelectron photo-ion photo-ion coincidence (PEPIPICO) spectrum reflects the selectivity and localization of core excitation by polarized light. By simulating the spectra the angular dependence of the fragmentation is determined.

Wave-vector and polarization dependence of conical refraction.

Science.gov (United States)

Turpin, A; Loiko, Yu V; Kalkandjiev, T K; Tomizawa, H; Mompart, J

2013-02-25

We experimentally address the wave-vector and polarization dependence of the internal conical refraction phenomenon by demonstrating that an input light beam of elliptical transverse profile refracts into two beams after passing along one of the optic axes of a biaxial crystal, i.e. it exhibits double refraction instead of refracting conically. Such double refraction is investigated by the independent rotation of a linear polarizer and a cylindrical lens. Expressions to describe the position and the intensity pattern of the refracted beams are presented and applied to predict the intensity pattern for an axicon beam propagating along the optic axis of a biaxial crystal.

Polarization-dependent thin-film wire-grid reflectarray for terahertz waves

Energy Technology Data Exchange (ETDEWEB)

Niu, Tiaoming [School of Electrical and Electronic Engineering, The University of Adelaide, Adelaide, South Australia 5005 (Australia); School of Information Science and Engineering, Lanzhou University, Lanzhou 730000 (China); Upadhyay, Aditi; Bhaskaran, Madhu; Sriram, Sharath [Functional Materials and Microsystems Research Group, RMIT University, Melbourne, Victoria 3001 (Australia); Withayachumnankul, Withawat [School of Electrical and Electronic Engineering, The University of Adelaide, Adelaide, South Australia 5005 (Australia); Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, 2-12-1-S9-3, Ookayama, Meguro-ku, Tokyo 152-8552 (Japan); Headland, Daniel; Abbott, Derek; Fumeaux, Christophe, E-mail: cfumeaux@eleceng.adelaide.edu.au [School of Electrical and Electronic Engineering, The University of Adelaide, Adelaide, South Australia 5005 (Australia)

2015-07-20

A thin-film polarization-dependent reflectarray based on patterned metallic wire grids is realized at 1 THz. Unlike conventional reflectarrays with resonant elements and a solid metal ground, parallel narrow metal strips with uniform spacing are employed in this design to construct both the radiation elements and the ground plane. For each radiation element, a certain number of thin strips with an identical length are grouped to effectively form a patch resonator with equivalent performance. The ground plane is made of continuous metallic strips, similar to conventional wire-grid polarizers. The structure can deflect incident waves with the polarization parallel to the strips into a designed direction and transmit the orthogonal polarization component. Measured radiation patterns show reasonable deflection efficiency and high polarization discrimination. Utilizing this flexible device approach, similar reflectarray designs can be realized for conformal mounting onto surfaces of cylindrical or spherical devices for terahertz imaging and communications.

Pyruvate Kinase M2 Is Required for the Expression of the Immune Checkpoint PD-L1 in Immune Cells and Tumors

Directory of Open Access Journals (Sweden)

Eva M. Palsson-McDermott

2017-10-01

Full Text Available Blocking interaction of the immune checkpoint receptor PD-1 with its ligand PD-L1 is associated with good clinical outcomes in a broad variety of malignancies. High levels of PD-L1 promote tumor growth by restraining CD8+ T-cell responses against tumors. Limiting PD-L1 expression and function is therefore critical for allowing the development of antitumor immune responses and effective tumor clearance. Pyruvate kinase isoform M2 (PKM2 is also a key player in regulating cancer as well as immune responses. PKM2 catalyzes the final rate-limiting step of glycolysis. Furthermore, PKM2 as a dimer translocates to the nucleus, where it stimulates hypoxia-inducible factor 1α (Hif-1α transactivation domain function and recruitment of p300 to the hypoxia response elements (HRE of Hif-1α target genes. Here, we provide the first evidence of a role for PKM2 in regulating the expression of PD-L1 on macrophages, dendritic cells (DCs, T cells, and tumor cells. LPS-induced expression of PD-L1 in primary macrophages was inhibited by the PKM2 targeting compound TEPP-46. Furthermore, RNA silencing of PKM2 inhibited LPS-induced PD-L1 expression. This regulation occurs through direct binding of PKM2 and Hif-1α to HRE sites on the PD-L1 promoter. Moreover, TEPP-46 inhibited expression of PD-L1 on macrophages, DCs, and T cells as well as tumor cells in a mouse CT26 cancer model. These findings broaden our understanding of how PKM2 may contribute to tumor progression and may explain the upregulation of PD-L1 in the tumor microenvironment.

The PDL1-PD1 Axis Converts Human Th1 Cells Into Regulatory T Cells

Science.gov (United States)

Amarnath, Shoba; Mangus, Courtney W.; Wang, James C.M.; Wei, Fang; He, Alice; Kapoor, Veena; Foley, Jason E.; Massey, Paul R.; Felizardo, Tania C.; Riley, James L.; Levine, Bruce L.; June, Carl H.; Medin, Jeffrey A.; Fowler, Daniel H.

2011-01-01

Immune surveillance by T helper type 1 (Th1) cells is critical for the host response to tumors and infection, but also contributes to autoimmunity and graft-versus-host disease (GvHD) after transplantation. The inhibitory molecule programmed death ligand-1 (PDL1) has been shown to anergize human Th1 cells, but other mechanisms of PDL1-mediated Th1 inhibition such as the conversion of Th1 cells to a regulatory phenotype have not been well characterized. We hypothesized that PDL1 may cause Th1 cells to manifest differentiation plasticity. Conventional T cells or irradiated K562 myeloid tumor cells overexpressing PDL1 converted TBET+ Th1 cells into FOXP3+ regulatory T cells (TREGS) in vivo, thereby preventing human-into-mouse xenogeneic GvHD (xGvHD). Either blocking PD1 expression on Th1 cells by siRNA targeting or abrogation of PD1 signaling by SHP1/2 pharmacologic inhibition stabilized Th1 cell differentiation during PDL1 challenge and restored the capacity of Th1 cells to mediate lethal xGVHD. PD1 signaling therefore induces human Th1 cells to manifest in vivo plasticity, resulting in a TREG phenotype that severely impairs cell-mediated immunity. Converting human Th1 cells to a regulatory phenotype with PD1 signaling provides a potential way to block GvHD after transplantation. Moreover, because this conversion can be prevented by blocking PD1 expression or pharmacologically inhibiting SHP1/2, this pathway provides a new therapeutic direction for enhancing T cell immunity to cancer and infection. PMID:22133721

Chemical ozone losses in Arctic and Antarctic polar winter/spring season derived from SCIAMACHY limb measurements 2002–2009

Directory of Open Access Journals (Sweden)

T. Sonkaew

2013-02-01

Full Text Available Stratospheric ozone profiles are retrieved for the period 2002–2009 from SCIAMACHY measurements of limb-scattered solar radiation in the Hartley and Chappuis absorption bands of ozone. This data set is used to determine the chemical ozone losses in both the Arctic and Antarctic polar vortices by averaging the ozone in the vortex at a given potential temperature. The chemical ozone losses at isentropic levels between 450 K and 600 K are derived from the difference between observed ozone abundances and the ozone modelled taking diabatic cooling into account, but no chemical ozone loss. Chemical ozone losses of up to 30–40% between mid-January and the end of March inside the Arctic polar vortex are reported. Strong inter-annual variability of the Arctic ozone loss is observed, with the cold winters 2004/2005 and 2006/2007 showing chemical ozone losses inside the polar vortex at 475 K, where 1.7 ppmv and 1.4 ppmv of ozone were removed, respectively, over the period from 22 January to beginning of April and 0.9 ppmv and 1.2 ppmv, respectively, during February. For the winters of 2007/2008 and 2002/2003, ozone losses of about 0.8 ppmv and 0.4 ppmv, respectively are estimated at the 475 K isentropic level for the period from 22 January to beginning of April. Essentially no ozone losses were diagnosed for the relatively warm winters of 2003/2004 and 2005/2006. The maximum ozone loss in the SCIAMACHY data set was found in 2007 at the 600 K level and amounted to about 2.1 ppmv for the period between 22 January and the end of April. Enhanced losses close to this altitude were found in all investigated Arctic springs, in contrast to Antarctic spring. The inter-annual variability of ozone losses and PSC occurrence rates observed during Arctic spring is consistent with the known QBO effects on the Arctic polar vortex, with exception of the unusual Arctic winter 2008/2009.

The maximum total ozone mass loss of about 25 million tons was found in the

PD-L1 peptide co-stimulation increases immunogenicity of a dendritic cell-based cancer vaccine

DEFF Research Database (Denmark)

Munir Ahmad, Shamaila; Martinenaite, Evelina; Hansen, Morten

2016-01-01

elicited by the DC vaccine even further. Consequently, we observed a significant increase in the number of vaccine-reacting T cells in vitro. In conclusion, activation of PD-L1-specific T cells may directly modulate immunogenicity of DC vaccines. Addition of PD-L1 epitopes may thus be an easily applicable...... and attractive option to augment the effectiveness of cancer vaccines and other immunotherapeutic agents....

Analytical investigation of a novel interrogation approach of fiber Bragg grating sensors using Optical Frequency Domain Reflectometry

Science.gov (United States)

Yüksel, Kivilcim; Pala, Deniz

2016-06-01

This work presents a novel approach in interrogating Polarization Dependent Loss (PDL) of cascaded identical FBGs using Optical Frequency Domain Reflectometer (OFDR). The fundamentals of both polarisation properties of uniform FBGs and polarisation-sensitive OFDR are explained and the benefits of this novel approach in measuring transversal load are discussed. The numerical programs computing the spectral evolution of PDL of the FBGs in the array as a function of grating parameters (grating length and birefringence) are presented. Our simulation results show an excellent agreement with the previously reported simulation (and experimental) results in the literature obtained on a single FBG by using classical state-of-the-art measurement techniques. As an envisaged application, the proposed system shows the feasibility of measuring the residual stresses during manufacturing process of composite materials which is not straightforward by amplitude spectrum measurements and/or considering only the axial strains.

Immunohistochemical analysis and prognostic significance of PD-L1, PD-1, and CD8+ tumor-infiltrating lymphocytes in Ewing's sarcoma family of tumors (ESFT).

Science.gov (United States)

Machado, Isidro; López-Guerrero, Jose Antonio; Scotlandi, Katia; Picci, Piero; Llombart-Bosch, Antonio

2018-05-01

Ewing's sarcoma family of tumors (ESFT) are aggressive neoplasms with scant tumor-infiltrating lymphocytes. We analyzed the immunohistochemical (IHC) expression of PD-L1 and PD-1 and their prognostic significance in clinically localized neoplasms in a cohort of 370 ESFT. Slides prepared from tissue microarrays were stained for PD-L1, PD-1, and CD8. Membranous/cytoplasmic staining over 5% of tumor cells was regarded as positive for PD-L1 and PD-1. Prognostic analysis was done considering only clinically localized tumors (n = 217). PD-L1 expression was present in 19% of ESFT, while PD-1 was expressed in 26%. Forty-eight percent of tumors were negative and 12% were positive for both PD-L1 and PD-1. Metastatic tumors displayed higher expression of PD-L1 (p < 0.0001). Histological subtypes were not correlated with PD-L1 or PD-1 positivity. ESFT with elevated proliferation index (Ki-67) were associated with higher PD-L1 expression (p = 0.049). Regarding prognosis, no significant association was found between PD-L1 expression and progression-free survival (PFS) or overall survival (OS), whereas lack of PD-1 expression in tumor cells was correlated with both poor PFS (p = 0.02) and poor OS (p = 0.004). Tumor-infiltrating CD8(+) T lymphocytes were observed in 15.4% of ESFT with informative results (347 tumors). No correlation was found between tumor-infiltrating CD8(+) T lymphocytes and ESFT histological subtypes, tumor location, or PD-1 and PD-L1 expression, nor with PFS (p = 0.473) or OS (p = 0.087). PD-L1 expression was not significantly related to prognosis. PD-1 was expressed in 26% of ESFT tumor cells and may have prognostic and therapeutic implications. CD8 expression in tumor-infiltrating lymphocytes was not related to prognosis.

PD-L1 expression is associated with p16INK4A expression in non-oropharyngeal head and neck squamous cell carcinoma

Science.gov (United States)

Chen, San-Chi; Chang, Peter Mu-Hsin; Wang, Hsiao-Jung; Tai, Shyh-Kuan; Chu, Pen-Yuan; Yang, Muh-Hwa

2018-01-01

PD-L1 expression is critical in helping tumor cells evade the immune system. However, the level of PD-L1 expression in non-oropharyngeal head and neck squamous cell carcinoma (non-OPHNSCC) and its association with patient prognosis remains unclear. A retrospective clinicopathological analysis was performed on 106 patients with non-OPHNSCC diagnosed between 2007 and 2014. In the current study, tissue arrays from paraffin-embedded non-OPHNSCC samples obtained from patients were constructed, and PD-L1 and p16INK4A expression were determined using immunohistochemistry. Systemic inflammatory factors, including C-reactive protein, serum white blood cell, neutrophil, monocyte and lymphocyte counts were also analyzed. The current study demonstrated that PD-L1 was overexpressed in 32.1% (34/106) and p16INK4A in 20.8% (22/106) of patients. The expression of PD-L1 was associated with p16INK4A expression (P<0.01) but was not associated with levels of systemic inflammatory factors. Tumor stage was determined to be a significant prognostic value (stage I/II vs. III/IV, P=0.03), however, PD-L1, p16INK4A or other clinicopathological factors were not. The current study identified an association between PD-L1 and p16INK4A expression in non-OPHNSCC. This may facilitate the development of anti-PD1/PDL1 therapies to treat patients with head and neck cancer. PMID:29434933

PD-L1 protein expression assessed by immunohistochemistry is neither prognostic nor predictive of benefit from adjuvant chemotherapy in resected non-small cell lung cancer.

Science.gov (United States)

Tsao, M-S; Le Teuff, G; Shepherd, F A; Landais, C; Hainaut, P; Filipits, M; Pirker, R; Le Chevalier, T; Graziano, S; Kratze, R; Soria, J-C; Pignon, J-P; Seymour, L; Brambilla, E

2017-04-01

The expression of programmed death (PD) ligand 1 (PD-L1) protein expression assessed by immunohistochemistry (IHC) has been correlated with response and survival benefit from anti-PD-1/PD-L1 immune checkpoint inhibitor therapies in advanced non-small cell lung carcinoma (NSCLC). The efficacy of several agents appears correlated with PD-L1 expression. It remains controversial whether PD-L1 is prognostic in NSCLC. We assessed the prognostic value of PD-L1 IHC and its predictive role for adjuvant chemotherapy in early stage NSCLC. Tumor sections from three pivotal adjuvant chemotherapy trials (IALT, JBR.10, CALGB 9633) using the E1L3N antibody were studied in this pooled analysis. PD-L1 staining intensity and percentage in both tumor cells (TCs) and immune cells (ICs) were scored by two pathologists. The average or consensus PD-L1 expression levels across intensities and/or percent cells stained were correlated with clinicopathological and molecular features, patient survivals and potential benefit of adjuvant chemotherapy. Results from 982 patients were available for analysis. Considering staining at any intensities for overall PD-L1 expression, 314 (32.0%), 204 (20.8%) and 141 (14.3%) tumor samples were positive for PD-L1 staining on TCs using cut-offs at ≥1%, ≥10% and ≥25%, respectively. For PD-L1 expressing ICs, 380 (38.7%), 308 (31.4%) and 148 (15.1%) were positive at ≥ 1%, ≥10% and 25% cut-offs, respectively. Positive PD-L1 was correlated with squamous histology, intense lymphocytic infiltrate, and KRAS but not with TP53 mutation. EGFR mutated tumors showed statistically non-significant lower PD-L1 expression. PD-L1 expression was neither prognostic with these cut-offs nor other exploratory cut-offs, nor were predictive for survival benefit from adjuvant chemotherapy. PD-L1 IHC is not a prognostic factor in early stage NSCLC patients. It is also not predictive for adjuvant chemotherapy benefit in these patients. © The Author 2017. Published by

Polarization dependent femtosecond laser modification of MBE-grown III-V nanostructures on silicon

OpenAIRE

Zandbergen, Sander R.; Gibson, Ricky; Amirsolaimani, Babak; Mehravar, Soroush; Keiffer, Patrick; Azarm, Ali; Kieu, Khanh

2017-01-01

We report a novel, polarization dependent, femtosecond laser-induced modification of surface nanostructures of indium, gallium, and arsenic grown on silicon via molecular beam epitaxy, yielding shape control from linear and circular polarization of laser excitation. Linear polarization causes an elongation effect, beyond the dimensions of the unexposed nanostructures, ranging from 88 nm to over 1 um, and circular polarization causes the nanostructures to flatten out or form loops of material,...

PD-L1 Expression Induced by the 2009 Pandemic Influenza A(H1N1 Virus Impairs the Human T Cell Response

Directory of Open Access Journals (Sweden)

Nuriban Valero-Pacheco

2013-01-01

Full Text Available PD-L1 expression plays a critical role in the impairment of T cell responses during chronic infections; however, the expression of PD-L1 on T cells during acute viral infections, particularly during the pandemic influenza virus (A(H1N1pdm09, and its effects on the T cell response have not been widely explored. We found that A(H1N1pdm09 virus induced PD-L1 expression on human dendritic cells (DCs and T cells, as well as PD-1 expression on T cells. PD-L1 expression impaired the T cell response against A(H1N1pdm09 by promoting CD8+ T cell death and reducing cytokine production. Furthermore, we found increased PD-L1 expression on DCs and T cells from influenza-infected patients from the first and second 2009 pandemic waves in Mexico City. PD-L1 expression on CD8+ T cells correlated inversely with T cell proportions in patients infected with A(H1N1pdm09. Therefore, PD-L1 expression on DCs and T cells could be associated with an impaired T cell response during acute infection with A(H1N1pdm09 virus.

Polarization dependence of Na* + Na* associative ionization revisited

NARCIS (Netherlands)

Meijer, H.A.J.; Meulen, H.P. v.d.; Morgenstern, R.; Hertel, I.V.; Meyer, E.; Witte, R.

1986-01-01

The dependence of the associative ionization process Na 3 2P3/2 + Na 3 2P3/2 → Na2+ + e- on the polarization of the laser light used for Na excitation was independently investigated in Utrecht and Berlin. The purpose of this paper is to clarify discrepancies between two other earlier experimental

Energy-dependent losses in pulsed-feedback preamplifiers

International Nuclear Information System (INIS)

Landis, D.A.; Madden, N.W.; Goulding, F.S.

1978-11-01

Energy dependent counting losses occur in most pulsed-feedback preamplifiers due to the loss of those pulses which activate the recharge system. A pulsed-feedback system that overcomes this inefficiency is described. Pulsed-light feedback as used with germanium gamma-ray spectrometers is discussed as used at high energies and high rates where those losses become significant. Experimental results are presented

Stop-loss premiums under dependence

NARCIS (Netherlands)

Albers, Willem/Wim

1999-01-01

Stop-loss premiums are typically calculated under the assumption that the insured lives in the underlying portfolio are independent. Here we study the effects of small departures from this assumption. Using Edgeworth expansions, it is made transparent which configurations of dependence parameters

Dependence of polar effect on parameters of coaxial plasma-erosive switches

International Nuclear Information System (INIS)

Bystritskij, V.M.; Ivanov, I.B.; Krasik, Ya.E.; Ryzhakin, N.N.; Sinebryukhov, A.A.; Tolmacheva, V.G.

1988-01-01

The results of experimental investigations and numerical simulation of the polar effect in a coaxial plasma-erosive switch (PES) established in a circuit of a strong-current nanosecond accelerator are presented. PES characteristics (energy losses, impedance, rate of its increase, etc.) are investigated depending on mutual direction of accelerator current and plasma flow as well as on the cathode radius in the PES region. It is experimentally shown that the magnetic fields near the cathode determined by this electrode radius influences mainly on PES characteristics. Mutual direction of accelerator current and plasma flow is the second significance factor influencing on PES characteristics. The optimal mode of PES operation is realized when providing the less with respect to the positive electrode, cathode radius and coinciding in direction accelerator current and plasma flow. Numerical simulation of dynamic processes in coaxial PES for different ratios of cathode and anode radii and mutual directions of accelerator current and plasma flow gives qualitative agreement with the experimental results

Expression of PD-L1 and presence of CD8-positive T cells in pre-treatment specimens of locally advanced cervical cancer.

Science.gov (United States)

Enwere, Emeka K; Kornaga, Elizabeth N; Dean, Michelle; Koulis, Theodora A; Phan, Tien; Kalantarian, Maria; Köbel, Martin; Ghatage, Prafull; Magliocco, Anthony M; Lees-Miller, Susan P; Doll, Corinne M

2017-04-01

Several of the cancer immunotherapies under investigation or in clinical use target the programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) signaling axis. PD-L1 expression in tumor samples has been used as a predictive marker for response to these therapeutics, and may also have independent prognostic utility when assessed along with immune cell markers. Our objectives were to assess the expression of PD-L1 in tumor specimens from a uniformly treated patient cohort with locally advanced cervical cancer, and to determine its prognostic significance along with the density of tumor-infiltrating T cells. We identified 120 patients with locally advanced cervical cancer treated with radical chemoradiotherapy, and built tissue microarrays from their formalin-fixed, paraffin-embedded pre-treatment biopsies. We used conventional brightfield and fluorescence immunohistochemistry to detect PD-L1, and quantified protein expression using both manual pathologist scoring and automated software analysis. We also evaluated the effect of PD-L1 expression in tumors, along with the presence and density of intra-tumoral CD8 + T cells, on patient survival outcomes. Approximately 96% of the tumor samples expressed PD-L1, as determined using quantitative software analysis. Neither expression of PD-L1 nor density of CD8 + T cells was associated with progression-free or overall survival. However, there was a trend towards worse progression-free survival in patients whose tumors expressed PD-L1 but lacked CD8 + T cells (hazard ratio=0.43 (0.18-1.01), P=0.053). Nevertheless, the high percentage of cervical cancer tumor samples expressing PD-L1 suggests that anti-PD-L1 or anti-PD-1 therapies are potential treatment options for this patient population.

Polarization dependence of two-photon transition intensities in rare-earth doped crystals

Energy Technology Data Exchange (ETDEWEB)

Le Nguyen, An-Dien [Univ. of California, Berkeley, CA (United States)

1996-05-01

A polarization dependence technique has been developed as a tool to investigate phonon scattering (PS), electronic Raman scattering (ERS), and two-photon absorption (TPA) transition intensities in vanadate and phosphate crystals. A general theory for the polarization dependence (PD) of two-photon transition intensities has been given. Expressions for the polarization dependent behavior of two-photon transition intensities have been tabulated for the 32 crystallographic point groups. When the wavefunctions for the initial and final states of a rare-earth doped in crystals are known, explicit PD expressions with no unknown parameters can be obtained. A spectroscopic method for measuring and interpreting phonon and ERS intensities has been developed to study PrVO₄, NdVO₄, ErVO₄, and TmVO₄ crystals. Relative phonon intensities with the polarization of the incident and scattered light arbitrarily varied were accurately predicted and subsequently used for alignment and calibration in ERS measurements in these systems for the first time. Since ERS and PS intensities generally follow different polarization curves as a function of polar angles, the two can be uniquely identified by comparing their respective polarization behavior. The most crucial application of the technique in ERS spectroscopy is the establishment of a stringent test for the Axe theory. For the first time, the F₁/F₂ ratio extracted from the experimental fits of the ERS intensities were compared with those predicted by theories which include both the second- and third-order contributions. Relatively good agreement between the fitted values of F₁/F₂ and the predicted values using the second-order theory has been found.

Observation of interface dependent spin polarized photocurrents in InAs/GaSb superlattice

Energy Technology Data Exchange (ETDEWEB)

Li, Yuan, E-mail: liyuan12@semi.ac.cn; Liu, Yu; Zhu, Laipan; Qin, Xudong; Wu, Qing; Huang, Wei; Chen, Yonghai, E-mail: yhchen@semi.ac.cn [Key Laboratory of Semiconductor Materials Science, Institute of Semiconductors, Chinese Academy of Sciences, 100083 Beijing (China); Niu, Zhichuan; Xiang, Wei; Hao, Hongyue [The State Key Laboratory of Superlattices and Microstructures, Institute of Semiconductors, Chinese Academy of Sciences, 100083 Beijing (China)

2015-05-11

In this letter, we investigated the spin polarized photocurrents excited by mid-infrared radiation and near-infrared radiation, respectively, in InAs/GaSb type II superlattices with different kinds of interfaces. By periodically varying the polarization state of the radiation, we analyzed Rashba-type and Dresselhaus-type spin polarized photocurrents, which present different features depending on the interface types and excitation conditions. Under mid-infrared excitation, the ratio of Rashba-type and Dresselhaus-type spin polarized photocurrents of the superlattice with InSb-like interface is obviously larger than that of the superlattice with GaAs-like interface, the ratio of the superlattice with alternate interface is in the middle. Whereas under near-infrared excitation, the ratios of the three superlattices are nearly the same. Further researches reveal the synactic effects of interface dependent strain and asymmetric interface potential on the spin splitting. Besides, the polarized Raman spectroscopies of these structures were also analyzed.

Observation of interface dependent spin polarized photocurrents in InAs/GaSb superlattice

International Nuclear Information System (INIS)

Li, Yuan; Liu, Yu; Zhu, Laipan; Qin, Xudong; Wu, Qing; Huang, Wei; Chen, Yonghai; Niu, Zhichuan; Xiang, Wei; Hao, Hongyue

2015-01-01

In this letter, we investigated the spin polarized photocurrents excited by mid-infrared radiation and near-infrared radiation, respectively, in InAs/GaSb type II superlattices with different kinds of interfaces. By periodically varying the polarization state of the radiation, we analyzed Rashba-type and Dresselhaus-type spin polarized photocurrents, which present different features depending on the interface types and excitation conditions. Under mid-infrared excitation, the ratio of Rashba-type and Dresselhaus-type spin polarized photocurrents of the superlattice with InSb-like interface is obviously larger than that of the superlattice with GaAs-like interface, the ratio of the superlattice with alternate interface is in the middle. Whereas under near-infrared excitation, the ratios of the three superlattices are nearly the same. Further researches reveal the synactic effects of interface dependent strain and asymmetric interface potential on the spin splitting. Besides, the polarized Raman spectroscopies of these structures were also analyzed

MUC1-C integrates PD-L1 induction with repression of immune effectors in non-small-cell lung cancer.

Science.gov (United States)

Bouillez, A; Rajabi, H; Jin, C; Samur, M; Tagde, A; Alam, M; Hiraki, M; Maeda, T; Hu, X; Adeegbe, D; Kharbanda, S; Wong, K-K; Kufe, D

2017-07-13

Immunotherapeutic approaches, particularly programmed death 1/programmed death ligand 1 (PD-1/PD-L1) blockade, have improved the treatment of non-small-cell lung cancer (NSCLC), supporting the premise that evasion of immune destruction is of importance for NSCLC progression. However, the signals responsible for upregulation of PD-L1 in NSCLC cells and whether they are integrated with the regulation of other immune-related genes are not known. Mucin 1 (MUC1) is aberrantly overexpressed in NSCLC, activates the nuclear factor-κB (NF-κB) p65→︀ZEB1 pathway and confers a poor prognosis. The present studies demonstrate that MUC1-C activates PD-L1 expression in NSCLC cells. We show that MUC1-C increases NF-κB p65 occupancy on the CD274/PD-L1 promoter and thereby drives CD274 transcription. Moreover, we demonstrate that MUC1-C-induced activation of NF-κB→︀ZEB1 signaling represses the TLR9 (toll-like receptor 9), IFNG, MCP-1 (monocyte chemoattractant protein-1) and GM-CSF genes, and that this signature is associated with decreases in overall survival. In concert with these results, targeting MUC1-C in NSCLC tumors suppresses PD-L1 and induces these effectors of innate and adaptive immunity. These findings support a previously unrecognized central role for MUC1-C in integrating PD-L1 activation with suppression of immune effectors and poor clinical outcome.

Update of the Polar SWIFT model for polar stratospheric ozone loss (Polar SWIFT version 2)

Science.gov (United States)

Wohltmann, Ingo; Lehmann, Ralph; Rex, Markus

2017-07-01

The Polar SWIFT model is a fast scheme for calculating the chemistry of stratospheric ozone depletion in polar winter. It is intended for use in global climate models (GCMs) and Earth system models (ESMs) to enable the simulation of mutual interactions between the ozone layer and climate. To date, climate models often use prescribed ozone fields, since a full stratospheric chemistry scheme is computationally very expensive. Polar SWIFT is based on a set of coupled differential equations, which simulate the polar vortex-averaged mixing ratios of the key species involved in polar ozone depletion on a given vertical level. These species are O3, chemically active chlorine (ClOx), HCl, ClONO2 and HNO3. The only external input parameters that drive the model are the fraction of the polar vortex in sunlight and the fraction of the polar vortex below the temperatures necessary for the formation of polar stratospheric clouds. Here, we present an update of the Polar SWIFT model introducing several improvements over the original model formulation. In particular, the model is now trained on vortex-averaged reaction rates of the ATLAS Chemistry and Transport Model, which enables a detailed look at individual processes and an independent validation of the different parameterizations contained in the differential equations. The training of the original Polar SWIFT model was based on fitting complete model runs to satellite observations and did not allow for this. A revised formulation of the system of differential equations is developed, which closely fits vortex-averaged reaction rates from ATLAS that represent the main chemical processes influencing ozone. In addition, a parameterization for the HNO3 change by denitrification is included. The rates of change of the concentrations of the chemical species of the Polar SWIFT model are purely chemical rates of change in the new version, whereas in the original Polar SWIFT model, they included a transport effect caused by the

Polarization effects in polymer FBGs: study and use for transverse force sensing

DEFF Research Database (Denmark)

Hu, Xuehao; Saez-Rodriguez, David; Marques, Carlos

2015-01-01

Bragg gratings photo-inscribed in polymer optical fibers (POFs) are more sensitive to temperature and pressure than their silica counterparts, because of their larger thermo-optic coefficient and smaller Young's modulus. Polymer optical fiber Bragg gratings (POFBGs) are most often photo-written i...... the PDL response of FBGs manufactured in step-index POFs. As the force induced birefringence adds to the photo-induced one, a force dependent evolution of the PDL maximum value was noticed, with a good temperature-insensitivity. (C) 2015 Optical Society of America...

Intestinal APCs of the endogenous nanomineral pathway fail to express PD-L1 in Crohn’s disease

Science.gov (United States)

Robertson, Jack; Haas, Carolin T.; Pele, Laetitia C.; Monie, Tom P.; Charalambos, Charles; Parkes, Miles; Hewitt, Rachel E.; Powell, Jonathan J.

2016-01-01

Crohn’s disease is a chronic inflammatory condition most commonly affecting the ileum and colon. The aetiology of Crohn’s disease is complex and may include defects in peptidoglycan recognition, and/or failures in the establishment of intestinal tolerance. We have recently described a novel constitutive endogenous delivery system for the translocation of nanomineral-antigen-peptidoglycan (NAP) conjugates to antigen presenting cells (APCs) in intestinal lymphoid patches. In mice NAP conjugate delivery to APCs results in high surface expression of the immuno-modulatory molecule programmed death receptor ligand 1 (PD-L1). Here we report that NAP conjugate positive APCs in human ileal tissues from individuals with ulcerative colitis and intestinal carcinomas, also have high expression of PD-L1. However, NAP-conjugate positive APCs in intestinal tissue from patients with Crohn’s disease show selective failure in PD-L1 expression. Therefore, in Crohn’s disease intestinal antigen taken up by lymphoid patch APCs will be presented without PD-L1 induced tolerogenic signalling, perhaps initiating disease. PMID:27226337

Epstein-Barr virus-encoded EBNA2 alters immune checkpoint PD-L1 expression by downregulating miR-34a in B-cell lymphomas.

Science.gov (United States)

Anastasiadou, Eleni; Stroopinsky, Dina; Alimperti, Stella; Jiao, Alan L; Pyzer, Athalia R; Cippitelli, Claudia; Pepe, Giuseppina; Severa, Martina; Rosenblatt, Jacalyn; Etna, Marilena P; Rieger, Simone; Kempkes, Bettina; Coccia, Eliana M; Sui, Shannan J Ho; Chen, Christopher S; Uccini, Stefania; Avigan, David; Faggioni, Alberto; Trivedi, Pankaj; Slack, Frank J

2018-06-26

Cancer cells subvert host immune surveillance by altering immune checkpoint (IC) proteins. Some Epstein-Barr virus (EBV)-associated tumors have higher Programmed Cell Death Ligand, PD-L1 expression. However, it is not known how EBV alters ICs in the context of its preferred host, the B lymphocyte and in derived lymphomas. Here, we found that latency III-expressing Burkitt lymphoma (BL), diffuse large B-cell lymphomas (DLBCL) or their EBNA2-transfected derivatives express high PD-L1. In a DLBCL model, EBNA2 but not LMP1 is sufficient to induce PD-L1. Latency III-expressing DLBCL biopsies showed high levels of PD-L1. The PD-L1 targeting oncosuppressor microRNA miR-34a was downregulated in EBNA2-transfected lymphoma cells. We identified early B-cell factor 1 (EBF1) as a repressor of miR-34a transcription. Short hairpin RNA (shRNA)-mediated knockdown of EBF1 was sufficient to induce miR-34a transcription, which in turn reduced PD-L1. MiR-34a reconstitution in EBNA2-transfected DLBCL reduced PD-L1 expression and increased its immunogenicity in mixed lymphocyte reactions (MLR) and in three-dimensional biomimetic microfluidic chips. Given the importance of PD-L1 inhibition in immunotherapy and miR-34a dysregulation in cancers, our findings may have important implications for combinatorial immunotherapy, which include IC inhibiting antibodies and miR-34a, for EBV-associated cancers.

Imaging of Polarization-dependent Photocurrent in Graphene Photodevices

Science.gov (United States)

Kim, Minjung; Yoon, Duhee; Ang Yoon, Ho; Lee, Sang Wook; Cheong, Hyeonsik

2012-02-01

Recently, a metal-graphene-metal photodetector for high-speed optical communications was reported. In addition, a graphene-based photodetector was reported to be able to absorb broadband light owing to the unique band structure of graphene [Mueller et al., Nature Photonics 4, 297 (2010)]. We investigated the polarization dependence of the photocurrent generated in metal-graphene-metal junctions. The graphene photodevice was fabricated by depositing Pd/Au and Ti/Au electrodes on single-layer graphene samples. When the polarization of incident laser beam is rotated with respect to the metal-graphene-metal junction, the photocurrent is significantly modulated. In addition, we measured the exact positions where the photocurrent is generated by measuring the photocurrent and Raman images of the graphene photodevices simultaneously.

Characterization of the gacA-dependent surface and coral mucus colonization by an opportunistic coral pathogen Serratia marcescens PDL100.

Science.gov (United States)

Krediet, Cory J; Carpinone, Emily M; Ritchie, Kim B; Teplitski, Max

2013-05-01

Opportunistic pathogens rely on global regulatory systems to assess the environment and to control virulence and metabolism to overcome host defenses and outcompete host-associated microbiota. In Gammaproteobacteria, GacS/GacA is one such regulatory system. GacA orthologs direct the expression of the csr (rsm) small regulatory RNAs, which through their interaction with the RNA-binding protein CsrA (RsmA), control genes with functions in carbon metabolism, motility, biofilm formation, and virulence. The csrB gene was controlled by gacA in Serratia marcescens PDL100. A disruption of the S. marcescens gacA gene resulted in an increased fitness of the mutant on mucus of the host coral Acropora palmata and its high molecular weight fraction, whereas the mutant was as competitive as the wild type on the low molecular weight fraction of the mucus. Swarming motility and biofilm formation were reduced in the gacA mutant. This indicates a critical role for gacA in the efficient utilization of specific components of coral mucus and establishment within the surface mucopolysaccharide layer. While significantly affecting early colonization behaviors (coral mucus utilization, swarming motility, and biofilm formation), gacA was not required for virulence of S. marcescens PDL100 in either a model polyp Aiptasia pallida or in brine shrimp Artemia nauplii. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Wavelength Dependence of the Polarization Singularities in a Two-Mode Optical Fiber

Directory of Open Access Journals (Sweden)

V. V. G. Krishna Inavalli

2012-01-01

Full Text Available We present here an experimental demonstration of the wavelength dependence of the polarization singularities due to linear combination of the vector modes excited directly in a two-mode optical fiber. The coherent superposition of the vector modes excited by linearly polarized Gaussian beam as offset skew rays propagated in a helical path inside the fiber results in the generation of phase singular beams with edge dislocation in the fiber output. The polarization character of these beams is found to change dramatically with wavelength—from left-handed elliptically polarized edge dislocation to right-handed elliptically polarized edge-dislocation through disclinations. The measured behaviour is understood as being due to intermodal dispersion of the polarization corrections to the propagating vector modes, as the wavelength of the input beam is scanned.

Quantum-well exciton dipolar interaction: Polarization-dependence and Z-LT splitting

International Nuclear Information System (INIS)

Nguyen Ba An.

1996-12-01

We calculate the exciton dipolar interaction in a semiconductor quantum well. The explicit polarization-dependence, i.e, the dependence on both the exciton dipole moment μ-vector and its inplane wavevector k-vector is derived. The obtained results for the three modes (L, T and Z modes) of the long-range part of the dipolar interaction satisfy the polarization sum rule for any parameters. In the long wavelength limit there is a Z-LT splitting which decreases as the well width increases reflecting a crossover from strict 2D to quasi-2D. A rough crossover from quasi-2D to 3D is also described. (author). 18 refs, 4 figs

Electron Beam Polarization Measurement Using Touschek Lifetime Technique

Energy Technology Data Exchange (ETDEWEB)

Sun, Changchun; /Duke U., DFELL; Li, Jingyi; /Duke U., DFELL; Mikhailov, Stepan; /Duke U., DFELL; Popov, Victor; /Duke U., DFELL; Wu, Wenzhong; /Duke U., DFELL; Wu, Ying; /Duke U., DFELL; Chao, Alex; /SLAC; Xu, Hong-liang; /Hefei, NSRL; Zhang, Jian-feng; /Hefei, NSRL

2012-08-24

Electron beam loss due to intra-beam scattering, the Touschek effect, in a storage ring depends on the electron beam polarization. The polarization of an electron beam can be determined from the difference in the Touschek lifetime compared with an unpolarized beam. In this paper, we report on a systematic experimental procedure recently developed at Duke FEL laboratory to study the radiative polarization of a stored electron beam. Using this technique, we have successfully observed the radiative polarization build-up of an electron beam in the Duke storage ring, and determined the equilibrium degree of polarization and the time constant of the polarization build-up process.

PD-1/PD-L signaling pathway in chronic hepatitis B

Directory of Open Access Journals (Sweden)

TAO Lilin

2016-12-01

Full Text Available Hepatitis B is one of the major diseases that affect the health of Chinese people, and chronic hepatitis B virus (HBV infection can lead to disease progression. Programmed death-1 (PD-1 discovered in recent years is an important coordinated stimulus molecule which belongs to the B7/CD28 family. After its binding with programmed death ligand (PD-L, it can regulate the activation, differentiation, and proliferation of T lymphocytes. PD-1 and its ligand are differently expressed in different stages of chronic HBV infection. The interaction between PD-1 and its ligand in different immune cells induces immune tolerance in human body and finally leads to the chronicity of HBV infection. Blocking the PD-1/PD-L signaling pathway through different ways can improve T cell exhaustion, suggesting that this might be one of the directions of antiviral therapy in future.

A Unified Framework for Creating Domain Dependent Polarity Lexicons from User Generated Reviews.

Directory of Open Access Journals (Sweden)

Muhammad Zubair Asghar

Full Text Available The exponential increase in the explosion of Web-based user generated reviews has resulted in the emergence of Opinion Mining (OM applications for analyzing the users' opinions toward products, services, and policies. The polarity lexicons often play a pivotal role in the OM, indicating the positivity and negativity of a term along with the numeric score. However, the commonly available domain independent lexicons are not an optimal choice for all of the domains within the OM applications. The aforementioned is due to the fact that the polarity of a term changes from one domain to other and such lexicons do not contain the correct polarity of a term for every domain. In this work, we focus on the problem of adapting a domain dependent polarity lexicon from set of labeled user reviews and domain independent lexicon to propose a unified learning framework based on the information theory concepts that can assign the terms with correct polarity (+ive, -ive scores. The benchmarking on three datasets (car, hotel, and drug reviews shows that our approach improves the performance of the polarity classification by achieving higher accuracy. Moreover, using the derived domain dependent lexicon changed the polarity of terms, and the experimental results show that our approach is more effective than the base line methods.

Time-dependent theoretical model of the polar wind: Preliminary results

International Nuclear Information System (INIS)

Gombosi, T.I.; Cravens, T.E.; Nagy, A.F.

1985-01-01

The coupled time dependent continuity, momentum and energy equations of a two ion (O + and H + ) quasineutral plasma were solved in order to extend our understanding of polar wind behavior. This numerical code allows studies of the time dependent behavior of polar wind-type flows into and out of the ionosphere. Initial studies indicate that the typical time constants for electron and ion temperature changes are of the order of minutes and tens of minutes, respectively. The response time of the minor high altitude ion O + is less than an hour, whereas that of the major ion, H + , is many hours. The initial test runs also demonstrate the fact that temporary supersonic flows of both O + and H + are possible, especially in the presence of significant ion heating

Greenhouse gas mitigation can reduce sea-ice loss and increase polar bear persistence

Science.gov (United States)

Steven C. Amstrup; Eric T. DeWeaver; David C. Douglas; Bruce G. Marcot; George M. Durner; Cecilia M. Bitz; David A. Bailey

2010-01-01

On the basis of projected losses of their essential sea-ice habitats, a United States Geological Survey research team concluded in 2007 that two-thirds of the world's polar bears (Ursus maritimus) could disappear by mid-century if business-as-usual greenhouse gas emissions continue. That projection, however, did not consider the possible...

Polarization Dependent Dynamics of CO2 Trapped in AN Optical Centrifuge

Science.gov (United States)

Toro, Carlos; Echebiri, Geraldine; Liu, Qingnan; Mullin, Amy S.

2012-06-01

An optical centrifuge (Yuan {et al}. {PNAS} 2011, 108, 6872) has been employed to prepare carbon dioxide molecules in very high rotational states (``hot'' rotors, J ˜220) in order to investigate how collisions relax ensembles of molecules with an overall angular momentum that is spatially oriented. We have performed polarization-dependent high resolution transient IR absorption measurements to study the spatial dependence of the relaxation dynamics. Our results show that the net angular momentum of the initially centrifuged molecules persists for at least 10 gas kinetic collisions and that the translational energy distributions are dependent on the probe orientation and polarization. These studies indicate that the centrifuged molecules tend to maintain the orientation of their initial angular momentum for the first set of collisions and that relatively large changes in J are involved in the first collisions.

PD-1 blocks lytic granule polarization with concomitant impairment of integrin outside-in signaling in the natural killer cell immunological synapse.

Science.gov (United States)

Huang, Yu; Chen, Zhiying; Jang, Joon Hee; Baig, Mirza S; Bertolet, Grant; Schroeder, Casey; Huang, Shengjian; Hu, Qian; Zhao, Yong; Lewis, Dorothy E; Qin, Lidong; Zhu, Michael Xi; Liu, Dongfang

2018-04-18

The inhibitory receptor programmed cell death protein 1 (PD-1) is upregulated on a variety of immune cells, including natural killer (NK) cells, during chronic viral infection and tumorigenesis. Blockade of PD-1 or its ligands produces durable clinical responses with tolerable side effects in patients with a broad spectrum of cancers. However, the underlying molecular mechanisms of how PD-1 regulates NK cell function remain poorly characterized. We sought to determine the effect of PD-1 signaling on NK cells. PD-1 was overexpressed in CD16-KHYG-1 (a human NK cell line with both antibody-dependent cellular cytotoxicity through CD16 and natural cytotoxicity through NKG2D) cells and stimulated by exposing the cells to NK-sensitive target cells expressing programmed death ligand 1 (PD-L1). PD-1 engagement by PD-L1 specifically blocked NK cell-mediated cytotoxicity without interfering with the conjugation between NK cells and target cells. Further examination showed that PD-1 signaling blocked lytic granule polarization in NK cells, which was accompanied by failure of integrin-linked kinase, a key molecule in the integrin outside-in signaling pathway, to accumulate in the immunological synapse after NK-target cell conjugation. Our results suggest that NK cell cytotoxicity is inhibited by PD-1 engagement, which blocks lytic granule polarization to the NK cell immunological synapse with concomitant impairment of integrin outside-in signaling. This study provides novel mechanistic insights into how PD-1 inhibition disrupts NK cell function. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A Longitudinal Analysis of IDO and PDL1 Expression during Immune- or Targeted Therapy in Advanced Melanoma

Directory of Open Access Journals (Sweden)

Lukas Krähenbühl

2018-02-01

Full Text Available A deepened understanding of the cellular and molecular processes in the tumor microenvironment is necessary for the development of precision immunotherapy (IT. We simultaneously investigated CD3, PDL1, and IDO by immunohistochemistry in paired biopsies from various organs of 43 metastatic melanoma patients treated with IT and targeted therapy (TT. Intraindividual biopsies taken after a period of weeks to months demonstrate discordant results in 30% of the cases. Overlap of IDO and PDL1 increased after therapy. IT only marginally impacted PDL1 expression over time in contrast to TT. Standardized repeated assessments of multiple immune markers in repeated biopsies will generate detailed insights in melanoma's immune evolution and adaption during therapies and might be used to support treatment decisions.

Prognostic effect of different PD-L1 expression patterns in squamous cell carcinoma and adenocarcinoma of the cervix

NARCIS (Netherlands)

Heeren, A. Marijne; Punt, Simone; Bleeker, Maaike Cg; Gaarenstroom, Katja N.; van der Velden, Jacobus; Kenter, Gemma G.; de Gruijl, Tanja D.; Jordanova, Ekaterina S.

2016-01-01

Programmed death-ligand 1 (PD-L1) is expressed in various immune cells and tumor cells, and is able to bind to PD-1 on T lymphocytes, thereby inhibiting their function. At present, the PD-1/PD-L1 axis is a major immunotherapeutic target for checkpoint inhibition in various cancer types, but

MLH1 expression predicts the response to preoperative therapy and is associated with PD-L1 expression in esophageal cancer.

Science.gov (United States)

Momose, Kota; Yamasaki, Makoto; Tanaka, Koji; Miyazaki, Yasuhiro; Makino, Tomoki; Takahashi, Tsuyoshi; Kurokawa, Yukinori; Nakajima, Kiyokazu; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

2017-07-01

Programmed death-ligand 1 (PD-1/PD-L1) inhibition therapy demonstrates potential as a future treatment for esophageal cancer. Mismatch repair status and tumor PD-L1 expression are the candidate predictive biomarkers for response to this therapy. In colorectal cancer, mismatch repair-deficient tumors are associated with improved survival, although they are not sensitive to 5-fluorouracil-based chemotherapy. The purpose of the present study was to investigate the association between MutL homolog 1 (MLH1) expression and prognosis, response to therapy and PD-L1 expression in esophageal cancer. Immunohistochemistry was used to evaluate MLH1 and PD-L1 expression in 251 resected specimens. Of the specimens, 30.3% exhibited low MLH1 expression and 15.5% exhibited high PD-L1 expression. The 5-year overall survival rates for the high MLH1 expression group and the low MLH1 expression group were 51.3 and 55.6%, respectively (P=0.5260). The responder ratio was 45.7% in the high MLH1 expression group and 15.4% in the low MLH1 expression group (PMLH1 expression group (P=0.0064) and 25.0% in the low MLH1 expression group. MLH1 expression may be a predictive factor for the response to preoperative therapy in esophageal cancer, and esophageal cancer with low MLH1 expression may have a mechanism that assists in promoting tumor PD-L1 expression.

Blocking of PDL-1 interaction enhances primary and secondary CD8 T cell response to herpes simplex virus-1 infection.

Directory of Open Access Journals (Sweden)

Rudragouda Channappanavar

Full Text Available The blocking of programmed death ligand-1 (PDL-1 has been shown to enhance virus-specific CD8 T cell function during chronic viral infections. Though, how PDL-1 blocking at the time of priming affects the quality of CD8 T cell response to acute infections is not well understood and remains controversial. This report demonstrates that the magnitude of the primary and secondary CD8 T cell responses to herpes simplex virus-1 (HSV-1 infection is subject to control by PDL-1. Our results showed that after footpad HSV-1 infection, PD-1 expression increases on immunodominant SSIEFARL peptide specific CD8 T cells. Additionally, post-infection, the level of PDL-1 expression also increases on CD11c+ dendritic cells. Intraperitoneal administration of anti-PDL-1 monoclonal antibody given one day prior to and three days after cutaneous HSV-1 infection, resulted in a marked increase in effector and memory CD8 T cell response to SSIEFARL peptide. This was shown by measuring the quantity and quality of SSIEFARL-specific CD8 T cells by making use of ex-vivo assays that determine antigen specific CD8 T cell function, such as intracellular cytokine assay, degranulation assay to measure cytotoxicity and viral clearance. Our results are discussed in terms of the beneficial effects of blocking PDL-1 interactions, while giving prophylactic vaccines, to generate a more effective CD8 T cell response to viral infection.

Polarization retention loss in PbTiO3 ferroelectric films due to leakage currents

NARCIS (Netherlands)

Morelli, A.; Venkatesan, Sriram; Palasantzas, G.; Kooi, B. J.; De Hosson, J. Th. M.

2007-01-01

The relationship between retention loss in single crystal PbTiO3 ferroelectric thin films and leakage currents is demonstrated by piezoresponse and conductive atomic force microscopy measurements. It was found that the polarization reversal in the absence of an electric field followed a stretched

The Role of Programmed Cell Death Ligand-1 (PD-L1/CD274) in the Development of Graft versus Host Disease

Science.gov (United States)

Al-Chaqmaqchi, Heevy; Sadeghi, Behnam; Abedi-Valugerdi, Manuchehr; Al-Hashmi, Sulaiman; Fares, Mona; Kuiper, Raoul; Lundahl, Joachim

2013-01-01

Programmed cell death ligand-1 (PD-L1/CD274) is an immunomodulatory molecule involved in cancer and complications of bone marrow transplantation, such as graft rejection and graft-versus-host disease. The present study was designed to assess the dynamic expression of this molecule after hematopoietic stem cell transplantation in relation to acute graft-versus-host disease. Female BALB/c mice were conditioned with busulfan and cyclophosphamide and transplanted with either syngeneic or allogeneic (male C57BL/6 mice) bone marrow and splenic cells. The expression of PD-L1 was evaluated at different time points employing qPCR, western blot and immunohistochemistry. Allogeneic- but not syngeneic-transplanted animals exhibited a marked up-regulation of PD-L1 expression in the muscle and kidney, but not the liver, at days 5 and 7 post transplantation. In mice transplanted with allogeneic bone marrow cells, the enhanced expression of PD-L1 was associated with high serum levels of IFNγ and TNFα at corresponding intervals. Our findings demonstrate that PD-L1 is differently induced and expressed after allogeneic transplantation than it is after syngeneic transplantation, and that it is in favor of target rather than non-target organs at the early stages of acute graft-versus-host disease. This is the first study to correlate the dynamics of PD-L1 at the gene-, protein- and activity levels with the early development of acute graft-versus-host disease. Our results suggest that the higher expression of PD-L1 in the muscle and kidney (non-target tissues) plays a protective role in skeletal muscle during acute graft-versus-host disease. PMID:23593203

Polarization and collision velocity dependence of associative ionization in cold Na (3p)-Na(3p) collisions

NARCIS (Netherlands)

Meijer, H.A.J.

1990-01-01

We studied the polarization dependence of the associative ionization (AI) process Na(3p) + Na(3p) → Na2+ at collision velocities between 100 and 700 m/s (5 and 200 K), using linearly and circularly polarized light for the excitation. We found that the polarization dependence varies strongly in the

Near infrared photoimmunotherapy with avelumab, an anti-programmed death-ligand 1 (PD-L1) antibody

OpenAIRE

Nagaya, Tadanobu; Nakamura, Yuko; Sato, Kazuhide; Harada, Toshiko; Choyke, Peter L.; Hodge, James W.; Schlom, Jeffrey; Kobayashi, Hisataka

2016-01-01

Near Infrared-Photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photo-absorber conjugate (APC). Programmed cell death protein-1 ligand (PD-L1) is emerging as a molecular target. Here, we describe the efficacy of NIR-PIT, using fully human IgG1 anti-PD-L1 monoclonal antibody (mAb), avelumab, conjugated to the photo-absorber, IR700DX, in a PD-L1 expressing H441 cell line, papillary adenocarcinoma of lung. Avelumab-IR700 showed specific binding and cell-...

Update of the Polar SWIFT model for polar stratospheric ozone loss (Polar SWIFT version 2

Directory of Open Access Journals (Sweden)

I. Wohltmann

2017-07-01

Full Text Available The Polar SWIFT model is a fast scheme for calculating the chemistry of stratospheric ozone depletion in polar winter. It is intended for use in global climate models (GCMs and Earth system models (ESMs to enable the simulation of mutual interactions between the ozone layer and climate. To date, climate models often use prescribed ozone fields, since a full stratospheric chemistry scheme is computationally very expensive. Polar SWIFT is based on a set of coupled differential equations, which simulate the polar vortex-averaged mixing ratios of the key species involved in polar ozone depletion on a given vertical level. These species are O3, chemically active chlorine (ClOx, HCl, ClONO2 and HNO3. The only external input parameters that drive the model are the fraction of the polar vortex in sunlight and the fraction of the polar vortex below the temperatures necessary for the formation of polar stratospheric clouds. Here, we present an update of the Polar SWIFT model introducing several improvements over the original model formulation. In particular, the model is now trained on vortex-averaged reaction rates of the ATLAS Chemistry and Transport Model, which enables a detailed look at individual processes and an independent validation of the different parameterizations contained in the differential equations. The training of the original Polar SWIFT model was based on fitting complete model runs to satellite observations and did not allow for this. A revised formulation of the system of differential equations is developed, which closely fits vortex-averaged reaction rates from ATLAS that represent the main chemical processes influencing ozone. In addition, a parameterization for the HNO3 change by denitrification is included. The rates of change of the concentrations of the chemical species of the Polar SWIFT model are purely chemical rates of change in the new version, whereas in the original Polar SWIFT model, they included a transport effect

Flatland Position-Dependent-Mass: Polar Coordinates, Separability and Exact Solvability

Directory of Open Access Journals (Sweden)

Omar Mustafa

2010-10-01

Full Text Available The kinetic energy operator with position-dependent-mass in plane polar coordinates is obtained. The separability of the corresponding Schrödinger equation is discussed. A hypothetical toy model is reported and two exactly solvable examples are studied.

Characterization of a magnetic trap by polarization dependent Zeeman spectroscopy

DEFF Research Database (Denmark)

Nielsen, Carsten Vandel; Lyngsøe, Jens Kristian; Thorseth, Anders

2008-01-01

This paper demonstrates a detailed experimental study of our cloverleaf magnetic trap for sodium atoms. By using polarization dependent Zeeman spectroscopy of our atomic beam, passing the magnetic trap region, we have determined important trap parameters such as gradients, their curvatures...

PD-L1 Is a Therapeutic Target of the Bromodomain Inhibitor JQ1 and, Combined with HLA Class I, a Promising Prognostic Biomarker in Neuroblastoma.

Science.gov (United States)

Melaiu, Ombretta; Mina, Marco; Chierici, Marco; Boldrini, Renata; Jurman, Giuseppe; Romania, Paolo; D'Alicandro, Valerio; Benedetti, Maria C; Castellano, Aurora; Liu, Tao; Furlanello, Cesare; Locatelli, Franco; Fruci, Doriana

2017-08-01

Purpose: This study sought to evaluate the expression of programmed cell death-ligand-1 (PD-L1) and HLA class I on neuroblastoma cells and programmed cell death-1 (PD-1) and lymphocyte activation gene 3 (LAG3) on tumor-infiltrating lymphocytes to better define patient risk stratification and understand whether this tumor may benefit from therapies targeting immune checkpoint molecules. Experimental Design: In situ IHC staining for PD-L1, HLA class I, PD-1, and LAG3 was assessed in 77 neuroblastoma specimens, previously characterized for tumor-infiltrating T-cell density and correlated with clinical outcome. Surface expression of PD-L1 was evaluated by flow cytometry and IHC in neuroblastoma cell lines and tumors genetically and/or pharmacologically inhibited for MYC and MYCN. A dataset of 477 human primary neuroblastomas from GEO and ArrayExpress databases was explored for PD-L1, MYC, and MYCN correlation. Results: Multivariate Cox regression analysis demonstrated that the combination of PD-L1 and HLA class I tumor cell density is a prognostic biomarker for predicting overall survival in neuroblastoma patients ( P = 0.0448). MYC and MYCN control the expression of PD-L1 in neuroblastoma cells both in vitro and in vivo Consistently, abundance of PD-L1 transcript correlates with MYC expression in primary neuroblastoma. Conclusions: The combination of PD-L1 and HLA class I represents a novel prognostic biomarker for neuroblastoma. Pharmacologic inhibition of MYCN and MYC may be exploited to target PD-L1 and restore an efficient antitumor immunity in high-risk neuroblastoma. Clin Cancer Res; 23(15); 4462-72. ©2017 AACR . ©2017 American Association for Cancer Research.

Polarization-dependent interfacial coupling modulation of ferroelectric photovoltaic effect in PZT-ZnO heterostructures.

Science.gov (United States)

Pan, Dan-Feng; Bi, Gui-Feng; Chen, Guang-Yi; Zhang, Hao; Liu, Jun-Ming; Wang, Guang-Hou; Wan, Jian-Guo

2016-03-08

Recently, ferroelectric perovskite oxides have drawn much attention due to potential applications in the field of solar energy conversion. However, the power conversion efficiency of ferroelectric photovoltaic effect currently reported is far below the expectable value. One of the crucial problems lies in the two back-to-back Schottky barriers, which are formed at the ferroelectric-electrode interfaces and blocking most of photo-generated carriers to reach the outside circuit. Herein, we develop a new approach to enhance the ferroelectric photovoltaic effect by introducing the polarization-dependent interfacial coupling effect. Through inserting a semiconductor ZnO layer with spontaneous polarization into the ferroelectric ITO/PZT/Au film, a p-n junction with strong polarization-dependent interfacial coupling effect is formed. The power conversion efficiency of the heterostructure is improved by nearly two orders of magnitude and the polarization modulation ratio is increased about four times. It is demonstrated that the polarization-dependent interfacial coupling effect can give rise to a great change in band structure of the heterostructure, not only producing an aligned internal electric field but also tuning both depletion layer width and potential barrier height at PZT-ZnO interface. This work provides an efficient way in developing highly efficient ferroelectric-based solar cells and novel optoelectronic memory devices.

High-power laser diodes with high polarization purity

Science.gov (United States)

Rosenkrantz, Etai; Yanson, Dan; Peleg, Ophir; Blonder, Moshe; Rappaport, Noam; Klumel, Genady

2017-02-01

Fiber-coupled laser diode modules employ power scaling of single emitters for fiber laser pumping. To this end, techniques such as geometrical, spectral and polarization beam combining (PBC) are used. For PBC, linear polarization with high degree of purity is important, as any non-perfectly polarized light leads to losses and heating. Furthermore, PBC is typically performed in a collimated portion of the beams, which also cancels the angular dependence of the PBC element, e.g., beam-splitter. However, we discovered that single emitters have variable degrees of polarization, which depends both on the operating current and far-field divergence. We present data to show angle-resolved polarization measurements that correlate with the ignition of high-order modes in the slow-axis emission of the emitter. We demonstrate that the ultimate laser brightness includes not only the standard parameters such as power, emitting area and beam divergence, but also the degree of polarization (DoP), which is a strong function of the latter. Improved slow-axis divergence, therefore, contributes not only to high brightness but also high beam combining efficiency through polarization.

Intracluster dust, circumstellar shells, and the wavelength dependence of polarization in orion

International Nuclear Information System (INIS)

Breger, M.

1977-01-01

The wavelength dependence of polarization of 21 polarized stars near the Orion Nebula has been measured. Most stars fit the standard interstellar law. The wavelength of maximum linear polarization, lambda/sub max/, ranges from normal values to 0.71μm. The polarimetric, spectroscopic, and photometric data support a normal reddening law (Rapprox. =3) for most Orion stars, and present evidence for unusually large grain sizes in front of some Orion stars. For the stars BR 545 and BR 885 large values of lambda/sub max/ are associated with unusually large values of total to selective extinction.A division of the observed polarization into intracluster dust and circumstellar shell components shows that the presence of shells does not usually lead to linear polarization in the optical wavelength region. Also, no association of polarization with known light variability could be found. The nature of the intracluster dust clouds is discussed briefly.The results of searches for circular polarization as well as short-period variability are presented in two appendices

Immunohistochemical Analysis of PD-L1 Expression in Canine Malignant Cancers and PD-1 Expression on Lymphocytes in Canine Oral Melanoma.

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Maekawa, Naoya; Konnai, Satoru; Okagawa, Tomohiro; Nishimori, Asami; Ikebuchi, Ryoyo; Izumi, Yusuke; Takagi, Satoshi; Kagawa, Yumiko; Nakajima, Chie; Suzuki, Yasuhiko; Kato, Yukinari; Murata, Shiro; Ohashi, Kazuhiko

2016-01-01

Spontaneous cancers are common diseases in dogs. Among these, some malignant cancers such as oral melanoma, osteosarcoma, hemangiosarcoma, and mast cell tumor are often recognized as clinical problems because, despite their high frequencies, current treatments for these cancers may not always achieve satisfying outcomes. The absence of effective systemic therapies against these cancers leads researchers to investigate novel therapeutic modalities, including immunotherapy. Programmed death 1 (PD-1) is a costimulatory receptor with immunosuppressive function. When it binds its ligands, PD-ligand 1 (PD-L1) or PD-L2, PD-1 on T cells negatively regulates activating signals from the T cell receptor, resulting in the inhibition of the effector function of cytotoxic T lymphocytes. Aberrant PD-L1 expression has been reported in many human cancers and is considered an immune escape mechanism for cancers. In clinical trials, anti-PD-1 or anti-PD-L1 antibodies induced tumor regression for several malignancies, including advanced melanoma, non-small cell lung carcinoma, and renal cell carcinoma. In this study, to assess the potential of the PD-1/PD-L1 axis as a novel therapeutic target for canine cancer immunotherapy, immunohistochemical analysis of PD-L1 expression in various malignant cancers of dogs was performed. Here, we show that dog oral melanoma, osteosarcoma, hemangiosarcoma, mast cell tumor, mammary adenocarcinoma, and prostate adenocarcinoma expressed PD-L1, whereas some other types of cancer did not. In addition, PD-1 was highly expressed on tumor-infiltrating lymphocytes obtained from oral melanoma, showing that lymphocytes in this cancer type might have been functionally exhausted. These results strongly encourage the clinical application of PD-1/PD-L1 inhibitors as novel therapeutic agents against these cancers in dogs.

Immunohistochemical Analysis of PD-L1 Expression in Canine Malignant Cancers and PD-1 Expression on Lymphocytes in Canine Oral Melanoma.

Directory of Open Access Journals (Sweden)

Naoya Maekawa

Full Text Available Spontaneous cancers are common diseases in dogs. Among these, some malignant cancers such as oral melanoma, osteosarcoma, hemangiosarcoma, and mast cell tumor are often recognized as clinical problems because, despite their high frequencies, current treatments for these cancers may not always achieve satisfying outcomes. The absence of effective systemic therapies against these cancers leads researchers to investigate novel therapeutic modalities, including immunotherapy. Programmed death 1 (PD-1 is a costimulatory receptor with immunosuppressive function. When it binds its ligands, PD-ligand 1 (PD-L1 or PD-L2, PD-1 on T cells negatively regulates activating signals from the T cell receptor, resulting in the inhibition of the effector function of cytotoxic T lymphocytes. Aberrant PD-L1 expression has been reported in many human cancers and is considered an immune escape mechanism for cancers. In clinical trials, anti-PD-1 or anti-PD-L1 antibodies induced tumor regression for several malignancies, including advanced melanoma, non-small cell lung carcinoma, and renal cell carcinoma. In this study, to assess the potential of the PD-1/PD-L1 axis as a novel therapeutic target for canine cancer immunotherapy, immunohistochemical analysis of PD-L1 expression in various malignant cancers of dogs was performed. Here, we show that dog oral melanoma, osteosarcoma, hemangiosarcoma, mast cell tumor, mammary adenocarcinoma, and prostate adenocarcinoma expressed PD-L1, whereas some other types of cancer did not. In addition, PD-1 was highly expressed on tumor-infiltrating lymphocytes obtained from oral melanoma, showing that lymphocytes in this cancer type might have been functionally exhausted. These results strongly encourage the clinical application of PD-1/PD-L1 inhibitors as novel therapeutic agents against these cancers in dogs.

PD-L1 Expression of Tumor Cells, Macrophages, and Immune Cells in Non-Small Cell Lung Cancer Patients with Malignant Pleural Effusion.

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Tseng, Yen-Han; Ho, Hsiang-Ling; Lai, Chiung-Ru; Luo, Yung-Hung; Tseng, Yen-Chiang; Whang-Peng, Jacqueline; Lin, Yi-Hsuan; Chou, Teh-Ying; Chen, Yuh-Min

2018-03-01

Whether immunohistochemical staining of programmed death ligand 1 (PD-L1) on cells of pleural effusion could be used to predict response to immunotherapy treatment has not been reported. We retrospectively enrolled patients who had undergone malignant pleural effusion drainage and had effusion cell block specimens from 2014 to 2016. Immunohistochemical staining for PD-L1 was performed with tumor cells, immune cells, and macrophages of all cell block specimens. Immunoactivity was scored as 0 for absence of staining and 1+ for faint, 2+ for moderate, and 3+ for intense membranous staining. Patients' clinicopathological characteristics were also collected. PD-L1 expression of pleural effusion tumor cells was associated with the PD-L1 expression of macrophages (p = 0.003) and immune cells (p pleural effusion tumor cells and macrophages. The low intensity of PD-L1 expression in immune cells is associated with the poor survival of patients with lung cancer with malignant pleural effusion. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Polarization dependence of the optical modal gain in ZnO

International Nuclear Information System (INIS)

Kim, Bumjin; Kyhm, Kwangseuk; Cho, Chaeryong

2010-01-01

The modal gain spectrum due to the electron-hole plasma in ZnO was measured using a variable stripe length method. A modal gain contour map for energy and stripe length allowed the modal gain saturation to be analyzed in terms of the spectral and the stripe length dependences. The modal gain was observed to be more significant in the TE mode than in the TM mode due to the polarization asymmetry of the wurtzite structure. We also found that the degree of polarization are enhanced as the stripe length increased, despite of modal gain saturation.

The polarization dependence of γγ absorption—implications for γ-ray bursts and blazars

International Nuclear Information System (INIS)

Böttcher, M.

2014-01-01

This paper presents an analysis of the dependence of the opacity for high-energy γ-rays to γγ absorption by low-energy photons on the polarization of the γ-ray and target photons. This process has so far only been considered using the polarization-averaged γγ absorption cross section. It is demonstrated that in the case of polarized γ-ray emission, subject to source-intrinsic γγ absorption by polarized target photons, this may lead to a slight overestimation of the γγ opacity by up to ∼10% in the case of a perfectly ordered magnetic field. Thus, for realistic astrophysical scenarios with partially ordered magnetic fields, the use of the polarization-averaged γγ cross section is justified for practical purposes, such as estimates of minimum Doppler factors inferred for γ-ray bursts and blazars, based on γγ transparency arguments; this paper quantifies the small error incurred by the unpolarized-radiation approximation. Furthermore, it is shown that polarization-dependent γγ absorption of initially polarized γ-rays can lead to a slight increase in the polarization beyond the spectral break caused by γγ absorption. This amount is distinctly different from the change in polarization expected if the same spectral break were produced by a break in the underlying electron distribution. This may serve as a diagnostic of whether γγ absorption is relevant in sources such as γ-ray bursts and blazars where the γ-ray emission may be intrinsically highly polarized.

The Significance of the PD-L1 Expression in Non-Small-Cell Lung Cancer: Trenchant Double Swords as Predictive and Prognostic Markers.

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Takada, Kazuki; Toyokawa, Gouji; Shoji, Fumihiro; Okamoto, Tatsuro; Maehara, Yoshihiko

2018-03-01

Lung cancer is the leading cause of death due to cancer worldwide. Surgery, chemotherapy, and radiotherapy have been the standard treatment for lung cancer, and targeted molecular therapy has greatly improved the clinical course of patients with non-small-cell lung cancer (NSCLC) harboring driver mutations, such as in epidermal growth factor receptor and anaplastic lymphoma kinase genes. Despite advances in such therapies, the prognosis of patients with NSCLC without driver oncogene mutations remains poor. Immunotherapy targeting programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) has recently been shown to improve the survival in advanced NSCLC. The PD-L1 expression on the surface of tumor cells has emerged as a potential biomarker for predicting responses to immunotherapy and prognosis after surgery in NSCLC. However, the utility of PD-L1 expression as a predictive and prognostic biomarker remains controversial because of the existence of various PD-L1 antibodies, scoring systems, and positivity cutoffs. In this review, we summarize the data from representative clinical trials of PD-1/PD-L1 immune checkpoint inhibitors in NSCLC and previous reports on the association between PD-L1 expression and clinical outcomes in patients with NSCLC. Furthermore, we discuss the future perspectives of immunotherapy and immune checkpoint factors. Copyright © 2017 Elsevier Inc. All rights reserved.

Tackling Cancer Resistance by Immunotherapy: Updated Clinical Impact and Safety of PD-1/PD-L1 Inhibitors

Directory of Open Access Journals (Sweden)

Shifaa M. Abdin

2018-01-01

Full Text Available Cancer therapy has been constantly evolving with the hope of finding the most effective agents with the least toxic effects to eradicate tumors. Cancer immunotherapy is currently among the most promising options, fulfilling this hope in a wide range of tumors. Immunotherapy aims to activate immunity to fight cancer in a very specific and targeted manner; however, some abnormal immune reactions known as immune-related adverse events (IRAEs might occur. Therefore, many researchers are aiming to define the most proper protocols for managing these complications without interfering with the anticancer effect. One of these targeted approaches is the inhibition of the interaction between the checkpoint protein, programmed death-receptor 1 (PD-1, and its ligand, programmed death-ligand 1 (PD-L1, via a class of antibodies known as PD-1/PD-L1 inhibitors. These antibodies achieved prodigious success in a wide range of malignancies, including those where optimal treatment is not yet fully identified. In this review, we have critically explored and discussed the outcome of the latest PD-1 and PD-L1 inhibitor studies in different malignancies compared to standard chemotherapeutic alternatives with a special focus on the clinical efficacy and safety. The approval of the clinical applications of nivolumab, pembrolizumab, atezolizumab, avelumab, and durvalumab in the last few years clearly highlights the hopeful future of PD-1/PD-L1 inhibitors for cancer patients. These promising results of PD-1/PD-L1 inhibitors have encouraged many ongoing preclinical and clinical trials to explore the extent of antitumor activity, clinical efficacy and safety as well as to extend their applications.

Tackling Cancer Resistance by Immunotherapy: Updated Clinical Impact and Safety of PD-1/PD-L1 Inhibitors.

Science.gov (United States)

Abdin, Shifaa M; Zaher, Dana M; Arafa, El-Shaimaa A; Omar, Hany A

2018-01-25

Cancer therapy has been constantly evolving with the hope of finding the most effective agents with the least toxic effects to eradicate tumors. Cancer immunotherapy is currently among the most promising options, fulfilling this hope in a wide range of tumors. Immunotherapy aims to activate immunity to fight cancer in a very specific and targeted manner; however, some abnormal immune reactions known as immune-related adverse events (IRAEs) might occur. Therefore, many researchers are aiming to define the most proper protocols for managing these complications without interfering with the anticancer effect. One of these targeted approaches is the inhibition of the interaction between the checkpoint protein, programmed death-receptor 1 (PD-1), and its ligand, programmed death-ligand 1 (PD-L1), via a class of antibodies known as PD-1/PD-L1 inhibitors. These antibodies achieved prodigious success in a wide range of malignancies, including those where optimal treatment is not yet fully identified. In this review, we have critically explored and discussed the outcome of the latest PD-1 and PD-L1 inhibitor studies in different malignancies compared to standard chemotherapeutic alternatives with a special focus on the clinical efficacy and safety. The approval of the clinical applications of nivolumab, pembrolizumab, atezolizumab, avelumab, and durvalumab in the last few years clearly highlights the hopeful future of PD-1/PD-L1 inhibitors for cancer patients. These promising results of PD-1/PD-L1 inhibitors have encouraged many ongoing preclinical and clinical trials to explore the extent of antitumor activity, clinical efficacy and safety as well as to extend their applications.

Differential expression of c-Met between primary and metastatic sites in clear-cell renal cell carcinoma and its association with PD-L1 expression.

Science.gov (United States)

Lalani, Aly-Khan A; Gray, Kathryn P; Albiges, Laurence; Callea, Marcella; Pignon, Jean-Christophe; Pal, Soumitro; Gupta, Mamta; Bhatt, Rupal S; McDermott, David F; Atkins, Michael B; Woude, G F Vande; Harshman, Lauren C; Choueiri, Toni K; Signoretti, Sabina

2017-11-28

In preclinical models, c-Met promotes survival of renal cancer cells through the regulation of programmed death-ligand 1 (PD-L1). However, this relationship in human clear cell renal cell carcinoma (ccRCC) is not well characterized. We evaluated c-Met expression in ccRCC patients using paired primary and metastatic samples and assessed the association with PD-L1 expression and other clinical features. Areas with predominant and highest Fuhrman nuclear grade (FNG) were selected. c-Met expression was evaluated by IHC using an anti-Met monoclonal antibody (MET4 Ab) and calculated by a combined score (CS, 0-300): intensity of c-Met staining (0-3) x % of positive cells (0-100). PD-L1 expression in tumor cells was previously assessed by IHC and PD-L1+ was defined as PD-L1 > 0% positive cells. Our cohort consisted of 45 pairs of primary and metastatic ccRCC samples. Overall, c-Met expression was higher in metastatic sites compared to primary sites (average c-Met CS: 55 vs. 28, p = 0.0003). Higher c-Met expression was associated with higher FNG (4 vs. 3) in primary tumors (average c-Met CS: 52 vs. 20, p = 0.04). c-Met expression was numerically greater in PD-L1+ vs. PD-L1- tumors. Higher c-Met expression in metastatic sites compared to primary tumors suggests that testing for biomarkers of response to c-Met inhibitors should be conducted in metastases. While higher c-Met expression in PD-L1+ tumors requires further investigation, it supports exploring these targets in combination clinical trials.

Constraints on cosmological birefringence energy dependence from CMB polarization data

International Nuclear Information System (INIS)

Gubitosi, G.; Paci, F.

2013-01-01

We study the possibility of constraining the energy dependence of cosmological birefringence by using CMB polarization data. We consider four possible behaviors, characteristic of different theoretical scenarios: energy-independent birefringence motivated by Chern-Simons interactions of the electromagnetic field, linear energy dependence motivated by a 'Weyl' interaction of the electromagnetic field, quadratic energy dependence, motivated by quantum gravity modifications of low-energy electrodynamics, and inverse quadratic dependence, motivated by Faraday rotation generated by primordial magnetic fields. We constrain the parameters associated to each kind of dependence and use our results to give constraints on the models mentioned. We forecast the sensitivity that Planck data will be able to achieve in this respect

Polarization dependent dispersion and its impact on optical parametric process in high nonlinear microstructure fibre

International Nuclear Information System (INIS)

Xiao Li; Zhang Wei; Huang Yidong; Peng Jiangde

2008-01-01

High nonlinear microstructure fibre (HNMF) is preferred in nonlinear fibre optics, especially in the applications of optical parametric effects, due to its high optical nonlinear coefficient. However, polarization dependent dispersion will impact the nonlinear optical parametric process in HNMFs. In this paper, modulation instability (MI) method is used to measure the polarization dependent dispersion of a piece of commercial HNMF, including the group velocity dispersion, the dispersion slope, the fourth-order dispersion and group birefringence. It also experimentally demonstrates the impact of the polarization dependent dispersion on the continuous wave supercontinuum (SC) generation. On one axis MI sidebands with symmetric frequency detunings are generated, while on the other axis with larger MI frequency detuning, SC is generated by soliton self-frequency shift

The advantages of PD1 activating chimeric receptor (PD1-ACR) engineered lymphocytes for PDL1(+) cancer therapy.

Science.gov (United States)

Tang, Xiaolong; Li, Qingguo; Zhu, Yongqiang; Zheng, Donghui; Dai, Jingjing; Ni, Wenxuan; Wei, Jia; Xue, Yubao; Chen, Ke; Hou, Wei; Zhang, Chao; Feng, Xiaojun; Liang, Yong

2015-01-01

Tumors exploit immunoregulatory checkpoints to attenuate T cell responses as a means of circumventing immunologic rejection. By activating the inhibitory costimulatory pathway of Programmed Death 1 (PD1)/PDL1 which provides tumor cells an escape mechanism from immune surveillance, Programmed Death Ligand1 (PDL1)(+) tumors hamper activated tumor-specific T cell functions and render them functionally exhausted. To overcome the inhibitory costimulatory effects of PDL1 on the adoptively transferred T cells, we sought to convert PD1 to a T cell costimulatory receptor by exchanging its transmembrane and cytoplasmic tail with CD28 and 4-1BB signaling domains (PD1-CD28-4-1BB, PD1-ACR), anticipating the genetically modified effector T lymphocytes expressing PD1-ACR would exhibit enhanced functional attributes. And the results showed that PD1-ACR expressed T cells retained the ability to bind PDL1, resulting in T cell activation as evidenced by the elevated activity of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), the augmentation of cytokine secretion and the increased proliferative capacity. Moreover, when systemically administered in the mouse model of glioblastoma metastases, PD1-ACR T cells localized at the area of U87 invasive tumor, which results in suppressed tumor growth and enhanced survival of mice with established U87 glioblastoma. Together, these data demonstrated that PD1-ACR has a high potential to serve as a novel strategy to overcome PDL1 mediated immunosuppression of T cells for cancer therapy.

Longitudinal fluctuations in PD1 and PD-L1 expression in association with changes in anti-viral immune response in chronic hepatitis B

Directory of Open Access Journals (Sweden)

Wenjin Zhang

2012-08-01

Full Text Available Abstract Background Controversy exists regarding the role of PD1 and its ligand PD-L1 in chronic hepatitis B infection. In some studies, persistent HBV infection has been attributed to high levels of PD-1 and PD-L1 expression on HBV-specific T-cells and antigen-presenting cells (APCs respectively. Other studies revealed that the up-regulation of PD-1 and PD-L1 during an acute inflammation phase is required to offset increasing positive co-stimulatory signals to avoid severe damage by an over-vigorous immune response. Methods Fifteen chronic hepatitis B patients, with inflammatory flare episode, were recruited prospectively. Based on serum HBV-DNA, HBsAg load, and ALT values, inflammatory flare episode were divided into initial, climax, decline and regression phase. Blood sample and liver biopsy tissues from each individual were taken in these 4 phases respectively. Circulating and intra-hepatic PD1 and PD-L1 expression levels were monitored throughout the inflammatory flare episode by flow cytometry and immunostaining and these expression levels were related to the HBV-specific T-cell changes, expression of pro-inflammatory cytokines, HBV-DNA replication and HBV antigen load. Results ]The levels of PD-1 and PD-L1 expressions were significantly up-regulated in the inflammation ascending phase, initial and climax period and in parallel with HBV-specific colon expansion. It showed increasing the level of serum ALT and decreasing the HBV-DNA loads. As the level of inflammation reduced, the circulating and intra-hepatic PD1 and circulating PD-L1 decreased progressively in concordance with serum ALT, HBV-DNA and HBsAg loads decreased except intra-hepatic PD-1 expression. Intra-hepatic PD-L1 expression did not decrease significantly during the regression phase of inflammation compared to that in prior period. The intra-hepatic PD-L1 expression remained relatively on higher level when serum HBV-DNA load and ALT decreased to approximately normal range

BIP induces mice CD19(hi) regulatory B cells producing IL-10 and highly expressing PD-L1, FasL.

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Tang, Youfa; Jiang, Qing; Ou, Yanghui; Zhang, Fan; Qing, Kai; Sun, Yuanli; Lu, Wenjie; Zhu, Huifen; Gong, Feili; Lei, Ping; Shen, Guanxin

2016-01-01

Many studies have shown that B cells possess a regulatory function in mouse models of autoimmune diseases. Regulatory B cells can modulate immune response through many types of molecular mechanisms, including the production of IL-10 and the expression of PD-1 Ligand and Fas Ligand, but the microenvironmental factors and mechanisms that induce regulatory B cells have not been fully identified. BIP (binding immunoglobulin protein), a member of the heat shock protein 70 family, is a type of evolutionarily highly conserved protein. In this article, we have found that IL-10(+), PD-L1(hi) and FasL(hi) B cells are discrete cell populations, but enriched in CD19(hi) cells. BIP can induce IL-10-producing splenic B cells, IL-10 secretion and B cells highly expressing PD-L1 and FasL. CD40 signaling acts in synergy with BIP to induce regulatory B cells. BIP increased surface CD19 molecule expression intensity and IL-10(+), PD-L1(hi) and FasL(hi) B cells induced by BIP share the CD19(hi) phenotype. Furthermore, B cells treated with BIP and anti-CD40 can lead to suppression of T cell proliferation and the effect is partially IL-10-dependent and mainly BIP-induced. Taken together, our findings identify a novel function of BIP in the induction of regulatory B cells and add a new reason for the therapy of autoimmune disorders or other inflammatory conditions. Copyright © 2015. Published by Elsevier Ltd.

Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity.

Science.gov (United States)

Hamilton, Gerhard; Rath, Barbara

2017-04-01

Immune checkpoint inhibition holds great promise for selected tumors. The human monoclonal antibody (mAB) avelumab is directed to programmed death ligand-1 (PD-L1) and is supposed to inhibit the immunosuppressive PD-L1/PD-1 interaction and, furthermore, effect antibody-dependent cytotoxicity (ADCC) lysis of tumor cells. Areas covered: This article presents an overview of the current means to activate the antitumor immune defense by targeting PD-1 or PD-L1 with mABs and their possible role in ADCC-mediated tumor cell elimination. Expert opinion: Avelumab contains a Fc region which can bind cognate receptors on immune effector cells and induce ADCC-mediated tumor cell lysis, in contrast to other mABs directed to PD-1/PD-L1 which lack the ability to trigger ADCC due to belonging to the IgG4 subclass or possessing a mutated Fc region. Preclinical and clinical data indicate that avelumab can be safely administered to cancer patients with a toxicity profile comparable to other mABs and without lysis of PD-L1-positive activated immune cells. This antibody yielded durable responses in a phase II trial in advanced Merkel cell carcinoma patients. Tumor cell lysis by avelumab prevents cells from resorting to alternative checkpoints as shown by targeting PD-1 and the upregulation of TIM-3.

Programmed Death Ligand 1 (PD-L1 Tumor Expression Is Associated with a Better Prognosis and Diabetic Disease in Triple Negative Breast Cancer Patients

Directory of Open Access Journals (Sweden)

Gerardo Botti

2017-02-01

Full Text Available Triple Negative Breast Cancers (TNBC subtype is an aggressive disease with poor clinical outcome. The only treatment available is surgery followed by chemotherapy or radiotherapy. Programmed death-ligand 1 (PD-L1 is a trans-membrane protein expressed on a wide variety of cells including immune cells, epithelial and vascular endothelial cells. Recently, PD-1/PD-L1 pathway signaling was described as an adaptive immune resistance mechanism enacted by the tumor cells to evade the immune response. Its presence on tumor cell membranes, acquired for this reason, through time, is an important prognostic value. However, data available in the literature about PD-L1 immunohistochemical expression in breast cancer are often discordant and not uniform, probably for the use of different antibodies clones and the high molecular heterogeneity of the different tumor types. The absence of target therapies, in particular for TNBC, has shifted the clinical attention mainly on the role of PD-L1 in this subtype of breast cancer. In this study, we evaluated tumor and TIL (tumor infiltrating lymphocytes PDL-1 expression in a series of TNBC, included in Tissue Micro Arrays (TMAs, to define its real prognostic value, optimizing immunohistochemistry method with an “approved for diagnostic assay” antibody. PD-L1 expression directly correlated with proliferation index (Ki-67, glycemia, the presence of diabetes and indirectly with menopausal status, presence of lymph node metastasis and relapse. The analysis of Kaplan–Meier showed that an increased PD-L1 expression was strongly associated with better disease-free survival (DFS but not correlated with overall survival (OS. Our data confirmed that PD-L1 could be an important marker for prognostic stratification and for planning immune checkpoint inhibitors therapies in patients with TNBC.

Polarization dependence of two-photon absorption coefficient and nonlinear susceptibility tensor in InP

International Nuclear Information System (INIS)

Matsusue, Toshio; Bando, Hiroyuki; Fujita, Shoichi; Takayama, Yusuke

2011-01-01

Two-photon absorption (TPA) effect in (001) InP is investigated using fs laser. Its dependences on wavelength and polarization are clarified by single and double beam methods with linearly polarized lights. Characteristic features are revealed and discussed with scaling law, crystal bonding and mutual relation of polarizations for double beams. The results are successfully analyzed on the basis of the third-order susceptibility tensor for comprehensive understanding of TPA effect at any polarization geometry. (copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

Reference-dependent preferences and loss aversion

Directory of Open Access Journals (Sweden)

Einat Neuman

2008-02-01

Full Text Available This study employs a Discrete Choice Experiment (DCE in the health-care sector to test the loss aversion theory that is derived from reference-dependent preferences: The absolute subjective value of a deviation from a reference point is generally greater when the deviation represents a loss than when the same-sized change is perceived as a gain. As far as is known, this paper is the first to use a DCE to test the loss aversion theory. A DCE is a highly suitable tool for such testing because it estimates the marginal valuations of attributes, based onextit{ deviations from a reference point} (a constant scenario. Moreover, loss aversion can be examined for extit{each attribute separately}. Another advantage of a DCE is that is can be applied toextit{ non-traded goods with non-tangible attributes}. A health-care event is used for empirical illustration: The loss aversion theory is tested within the context of preference structures for maternity-ward attributes, estimated using data gathered from 3850 observations made by a sample of 542 women who had recently given birth. Seven hypotheses are presented and tested. Overall, significant support for behavioral loss aversion theories was found. %JEL codes: D01, D12, I19

On Polarization and Frequency Dependence of Diffuse Indoor Propagation

DEFF Research Database (Denmark)

Nielsen, Jesper Ødum; Andersen, Jørgen Bach; Pedersen, Gert Frølund

2011-01-01

The room electromagnetics (RE) theory describes the radio propagation in a single room assuming diffuse scat- tering. A main characteristic is the exponential power-delay profile (PDP) decaying with the so-called reverberation time (RT) parameter, depending only on the wall area, the volume...... of the room and an absorption coefficient. The PDP is independent on the location in the room, except for the arrival time. Based on measurements in a room with a spherical array of 16 dual- polarized wideband horn antennas, the current work studies how the RE parameters depend on the receiver (Rx) antenna...

Intense field stabilization in circular polarization: Three-dimensional time-dependent dynamics

International Nuclear Information System (INIS)

Choi, Dae-Il; Chism, Will

2002-01-01

We investigate the stabilization of hydrogen atoms in a circularly polarized laser field. We use a three-dimensional, time-dependent approach to study the quantum dynamics of hydrogen atoms subject to high-intensity, short-wavelength, laser pulses. We find an enhanced survival probability as the field is increased under fixed envelope conditions. We also confirm wave packet behaviors previously seen in two-dimensional time-dependent computations

CD3+/CD8+ T-cell density and tumoral PD-L1 predict survival irrespective of rituximab treatment in Chinese diffuse large B-cell lymphoma patients.

Science.gov (United States)

Shi, Yunfei; Deng, Lijuan; Song, Yuqin; Lin, Dongmei; Lai, Yumei; Zhou, LiXin; Yang, Lei; Li, Xianghong

2018-05-10

To investigate the prognostic value of tumor-infiltrating T-cell density and programmed cell death ligand-1 (PD-L1) expression in diffuse large B cell lymphoma (DLBCL). One-hundred-twenty-five Chinese DLBCL patients were enrolled in our study and provided samples; 76 of all cases were treated with rituximab (R). Tumor tissues were immunostained and analyzed for CD3+ and CD8+ tumor-infiltrating T-cell density, tumoral PD-L1, and microenvironmental PD-L1 (mPD-L1). The density of CD3 was rated as high in 33.6% cases, while 64.0% of DLBCLs were classified as high CD8 density. Of all cases, 16.8% were PD-L1+. Of the remaining PD-L1-DLBCLs, 29.8% positively expressed mPD-L1. Both CD3 high density and CD8 high density were associated with mPD-L1 positivity (P = 0.001 and P = 0.0001). In multivariate analysis, independently, high CD3 density predicted better OS (P = 0.023), while CD8 high density and PD-L1 positivity were both associated with prolonged PFS (P = 0.013 and P = 0.036, respectively). Even in the subgroup treated with R, univariate analyses indicated that high CD3 density and PD-L1 positivity were associated with better OS (P = 0.041) and PFS (P = 0.033), respectively. The infiltrating densities of CD3+ T-cells, CD8+ T-cells, and PD-L1 expression are predictive of survival in DLBCLs, irrespective of R usage.

Spin dependent fragmentation functions for heavy flavor baryons and single heavy hyperon polarization

CERN Document Server

Goldstein, G R

2001-01-01

Spin dependent fragmentation functions for heavy flavor quarks to fragment into heavy baryons are calculated in a quark-diquark model. The production of intermediate spin 1/2 and 3/2 excited states is explicity included. $\\Lambda_b$ , $\\Lambda_c$ and $\\Xi_c$ production rate and polarization at LEP energies are calculated and, where possible, compared with experiment. A different approach, also relying on a heavy quark-diquark model, is proposed for the small momentum transfer inclusive production of polarized heavy flavor hyperons. The predicted $\\Lambda_c$ polarization is roughly in agreement with experiment.

Polarization dependent switching of asymmetric nanorings with a circular field

Directory of Open Access Journals (Sweden)

Nihar R. Pradhan

2016-01-01

Full Text Available We experimentally investigated the switching from onion to vortex states in asymmetric cobalt nanorings by an applied circular field. An in-plane field is applied along the symmetric or asymmetric axis of the ring to establish domain walls (DWs with symmetric or asymmetric polarization. A circular field is then applied to switch from the onion state to the vortex state, moving the DWs in the process. The asymmetry of the ring leads to different switching fields depending on the location of the DWs and direction of applied field. For polarization along the asymmetric axis, the field required to move the DWs to the narrow side of the ring is smaller than the field required to move the DWs to the larger side of the ring. For polarization along the symmetric axis, establishing one DW in the narrow side and one on the wide side, the field required to switch to the vortex state is an intermediate value.

Polarity dependent photoisomerization of ether substituted azodyes: Synthesis and photoswitching behavior.

Science.gov (United States)

Gan, Siew Mei; Pearl, Zynia Fernandes; Yuvaraj, A R; Lutfor, M R; Gurumurthy, Hegde

2015-10-05

Two new ether substituted azodyes were synthesized and characterized by different spectral analysis such as (1)H NMR, (13)C NMR, FTIR and UV/Vis. Synthesized compounds were used to study the photoisomerization phenomenon by using UV-Vis spectro-photometer. Interesting polarity dependent effect is observed for the first time on these materials. Trans-cis (E-Z) and cis-trans (Z-E) conversion occurred within 41 s and 445 min, respectively for both the compounds in solutions. Polarizing optical microscopy studies revealed that there is no liquid crystal phase for both the compounds. The dramatic variation in the optical property is speculated to be the polarity of the chemical species. These derivatives are useful to fabricate optical data storage devices. Copyright © 2015 Elsevier B.V. All rights reserved.

Age-Dependence and Aging-Dependence: Neuronal Loss and Lifespan in a C. elegans Model of Parkinson's Disease.

Science.gov (United States)

Apfeld, Javier; Fontana, Walter

2017-12-23

It is often assumed, but not established, that the major neurodegenerative diseases, such as Parkinson's disease, are not just age-dependent (their incidence changes with time) but actually aging-dependent (their incidence is coupled to the process that determines lifespan). To determine a dependence on the aging process requires the joint probability distribution of disease onset and lifespan. For human Parkinson's disease, such a joint distribution is not available, because the disease cuts lifespan short. To acquire a joint distribution, we resorted to an established C. elegans model of Parkinson's disease in which the loss of dopaminergic neurons is not fatal. We find that lifespan is not correlated with the loss of individual neurons. Therefore, neuronal loss is age-dependent and aging-independent. We also find that a lifespan-extending intervention into insulin/IGF1 signaling accelerates the loss of specific dopaminergic neurons, while leaving death and neuronal loss times uncorrelated. This suggests that distinct and compartmentalized instances of the same genetically encoded insulin/IGF1 signaling machinery act independently to control neurodegeneration and lifespan in C. elegans . Although the human context might well be different, our study calls attention to the need to maintain a rigorous distinction between age-dependence and aging-dependence.

Analysis of proton exchange membrane fuel cell polarization losses at elevated temperature 120 C and reduced relative humidity

Energy Technology Data Exchange (ETDEWEB)

Xu, Hui; Kunz, H. Russell [Department of Chemical Engineering, University of Connecticut, Storrs, CT (United States); Fenton, James M. [Florida Solar Energy Center, University of Central Florida, Cocoa, FL (United States)

2007-03-01

Polarization losses of proton exchange membrane (PEM) fuel cells at 120 C and reduced relative humidity (RH) were analyzed. Reduced RH affects membrane and electrode ionic resistance, catalytic activity and oxygen transport. For a cell made of Nafion {sup registered} 112 membrane and electrodes that have 35 wt.% Nafion {sup registered} and 0.3 mg/cm{sup 2} platinum supported on carbon, membrane resistance at 20%RH was 0.407 {omega} cm{sup 2} and electrode resistance 0.203 {omega} cm{sup 2}, significantly higher than 0.092 and 0.041 {omega} cm{sup 2} at 100%RH, respectively. In the kinetically controlled region, 20%RH resulted in 96 mV more cathode activation loss than 100%RH. Compared to 100%, 20%RH also produced significant oxygen transport loss across the ionomer film in the electrode, 105 mV at 600 mA/cm{sup 2}. The significant increase in polarization losses at elevated temperature and reduced RH indicates the extreme importance of designing electrodes for high temperature PEM fuel cells since membrane development has always taken most emphasis. (author)

Anomolous, intensity dependent losses in Au(32+) beams

International Nuclear Information System (INIS)

Blaskiewicz, M.; Ahrens, L.; Calvani, H.

1997-01-01

The AGS Booster is a rapid cycling proton and heavy ion synchrotron. Anomolous, intensity dependent losses in Au(32+) beams have been observed in the AGS Booster. No collective signal is expected, or observed, but increasing the number of injected ions decreases the beam lifetime. The loss rates for Au(32+) are compared with those for Au(15+)

Joint PDL and In-band OSNR Monitoring Supported by Data-Aided Channel Estimation

DEFF Research Database (Denmark)

Pittalà, Fabio; Hauske, Fabian N.; Ye, Yabin

2012-01-01

Employing a known training sequence robust and precise PDL and OSNR monitoring is demonstrated over a wide range of combined distortions. The proposed in-service monitoring technique is insensitive to CD, PMD and SOP rotation....

Loss of aPKCλ in differentiated neurons disrupts the polarity complex but does not induce obvious neuronal loss or disorientation in mouse brains.

Directory of Open Access Journals (Sweden)

Tomoyuki Yamanaka

Full Text Available Cell polarity plays a critical role in neuronal differentiation during development of the central nervous system (CNS. Recent studies have established the significance of atypical protein kinase C (aPKC and its interacting partners, which include PAR-3, PAR-6 and Lgl, in regulating cell polarization during neuronal differentiation. However, their roles in neuronal maintenance after CNS development remain unclear. Here we performed conditional deletion of aPKCλ, a major aPKC isoform in the brain, in differentiated neurons of mice by camk2a-cre or synapsinI-cre mediated gene targeting. We found significant reduction of aPKCλ and total aPKCs in the adult mouse brains. The aPKCλ deletion also reduced PAR-6β, possibly by its destabilization, whereas expression of other related proteins such as PAR-3 and Lgl-1 was unaffected. Biochemical analyses suggested that a significant fraction of aPKCλ formed a protein complex with PAR-6β and Lgl-1 in the brain lysates, which was disrupted by the aPKCλ deletion. Notably, the aPKCλ deletion mice did not show apparent cell loss/degeneration in the brain. In addition, neuronal orientation/distribution seemed to be unaffected. Thus, despite the polarity complex disruption, neuronal deletion of aPKCλ does not induce obvious cell loss or disorientation in mouse brains after cell differentiation.

Polarization-Insensitive Surface Plasmon Polarization Electro-Absorption Modulator Based on Epsilon-Near-Zero Indium Tin Oxide

Science.gov (United States)

Jin, Lin; Wen, Long; Liang, Li; Chen, Qin; Sun, Yunfei

2018-02-01

CMOS-compatible plasmonic modulators operating at the telecom wavelength are significant for a variety of on-chip applications. Relying on the manipulation of the transverse magnetic (TM) mode excited on the metal-dielectric interface, most of the previous demonstrations are designed to response only for specific polarization state. In this case, it will lead to a high polarization dependent loss, when the polarization-sensitive modulator integrates to a fiber with random polarization state. Herein, we propose a plasmonic modulator utilizing a metal-oxide indium tin oxide (ITO) wrapped around the silicon waveguide and investigate its optical modulation ability for both the vertical and horizontal polarized guiding light by tuning electro-absorption of ITO with the field-induced carrier injection. The electrically biased modulator with electron accumulated at the ITO/oxide interface allows for epsilon-near-zero (ENZ) mode to be excited at the top or lateral portion of the interface depending on the polarization state of the guiding light. Because of the high localized feature of ENZ mode, efficient electro-absorption can be achieved under the "OFF" state of the device, thus leading to large extinction ratio (ER) for both polarizations in our proposed modulator. Further, the polarization-insensitive modulation is realized by properly tailoring the thickness of oxide in two different stacking directions and therefore matching the ER values for device operating at vertical and horizontal polarized modes. For the optimized geometry configuration, the difference between the ER values of two polarization modes, i.e., the ΔER, as small as 0.01 dB/μm is demonstrated and, simultaneously with coupling efficiency above 74%, is obtained for both polarizations at a wavelength of 1.55 μm. The proposed plasmonic-combined modulator has a potential application in guiding and processing of light from a fiber with a random polarization state.

Low-loss polarization-maintaining fusion splicing of single-mode fibers and hollow-core photonic crystal fibers, relevant for monolithic fiber laser pulse compression

DEFF Research Database (Denmark)

Kristensen, Jesper Toft; Houmann, Andreas; Liu, Xiaomin

2008-01-01

of the splicing process. We also demonstrate that the higher splice loss compromises the PM properties of the splice. Our splicing technique was successfully applied to the realization of a low-loss, environmentally stable monolithic PM fiber laser pulse compressor, enabling direct end-of-the-fiber femtosecond......We report on highly reproducible low-loss fusion splicing of polarization-maintaining single-mode fibers (PM-SMFs) and hollow-core photonic crystal fibers (HC-PCFs). The PM-SMF-to-HC-PCF splices are characterized by the loss of 0.62 ± 0.24 dB, and polarization extinction ratio of 19 ± 0.68 d...... pulse delivery...

Field and polarity dependence of time-to-resistance increase in Fe-O films studied by constant voltage stress method

International Nuclear Information System (INIS)

Eriguchi, Koji; Ohta, Hiroaki; Ono, Kouichi; Wei Zhiqiang; Takagi, Takeshi

2009-01-01

Constant voltage stress (CVS) was applied to Fe-O films prepared by a sputtering process to investigate a stress-induced resistance increase leading to a fundamental mechanism for switching behaviors. Under the CVS, an abrupt resistance increase was found for both stress polarities. A conduction mechanism after the resistance increase exhibited non-Ohmic transport. The time-to-resistance increase (t r ) under the CVS was revealed to strongly depend on stress voltage as well as the polarity. From a polarity-dependent resistance increase determined by a time-zero measurement, the voltage and polarity-dependent t r were discussed on the basis of field- and structure-enhanced thermochemical reaction mechanisms

Mesenchymal stem cells increase skin graft survival time and up-regulate PD-L1 expression in splenocytes of mice.

Science.gov (United States)

Moravej, Ali; Geramizadeh, Bita; Azarpira, Negar; Zarnani, Amir-Hassan; Yaghobi, Ramin; Kalani, Mehdi; Khosravi, Maryam; Kouhpayeh, Amin; Karimi, Mohammad-Hossein

2017-02-01

Recently, mesenchymal stem cells (MSCs) have gained considerable interests as hopeful therapeutic cells in transplantation due to their immunoregulatory functions. But exact mechanisms underlying MSCs immunoregulatory function is not fully understood. Herein, in addition to investigate the ability of MSCs to prolong graft survival time, the effects of them on the expression of PD-L1 and IDO immunomodulatory molecules in splenocytes of skin graft recipient mice was clarified. To achieve this goal, full-thickness skins were transplanted from C57BL/6 to BALB/c mice. MSCs were isolated from bone marrow of BALB/c mice and injected to the recipient mice. Skin graft survival was monitored daily to determine graft rejection time. On days 2, 5 and 10 post skin transplantation, serum cytokine levels and expression of PD-L1 and IDO mRNA and protein in the splenocytes of recipient mice were evaluated. The results showed that administration of MSCs prolonged skin graft survival time from 11 to 14 days. On days 2 and 5 post transplantation, splenocytes PD-L1 expression and IL-10 serum level in MSCs treated mice were higher than those in the controls, while IL-2 and IFN-γ levels were lower. Rejection in MSCs treated mice was accompanied by an increase in IL-2 and IFN-γ, and decrease in PD-L1 expression and IL-10 level. No difference in the expression of IDO between MSCs treated mice and controls was observed. In conclusion, we found that one of the mechanisms underlying MSCs immunomodulatory function could be up-regulating PD-L1 expression. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Anti-tumor immunotherapy by blockade of the PD-1/PD-L1 pathway with recombinant human PD-1-IgV.

Science.gov (United States)

Zhang, C; Wu, S; Xue, X; Li, M; Qin, X; Li, W; Han, W; Zhang, Y

2008-01-01

Blockade of the programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) pathway can delay tumor growth and prolong the survival of tumor-bearing mice. The extracellular immunoglobulin (Ig) V domain of PD-1 is important for the interaction between PD-1 and PD-L1, suggesting that PD-1-IgV may be a potential target for anti-tumor immunotherapy. The extracellular sequence of human PD-1-IgV (hPD-1-IgV) was expressed in Escherichia coli and purified. The anti-tumor effect of hPD-1-IgV on tumor-bearing mice was tested. hPD-1-IgV recombinant protein could bind PD-L1 at molecular and cellular levels and enhance Cytotoxic T Lymphocyte (CTL) activity and anti-tumor effect on tumor-bearing mice in vivo. The percentage of CD4(+)CD25(+) T cells in tumor-bearing mice was decreased compared with control mice after administration of the recombinant protein. Our results suggest that inhibition of the interaction between PD-1 and PD-L1 by hPD-1-IgV may be a promising strategy for specific tumor immunotherapy.

SEA-LEVEL RISE. Sea-level rise due to polar ice-sheet mass loss during past warm periods.

Science.gov (United States)

Dutton, A; Carlson, A E; Long, A J; Milne, G A; Clark, P U; DeConto, R; Horton, B P; Rahmstorf, S; Raymo, M E

2015-07-10

Interdisciplinary studies of geologic archives have ushered in a new era of deciphering magnitudes, rates, and sources of sea-level rise from polar ice-sheet loss during past warm periods. Accounting for glacial isostatic processes helps to reconcile spatial variability in peak sea level during marine isotope stages 5e and 11, when the global mean reached 6 to 9 meters and 6 to 13 meters higher than present, respectively. Dynamic topography introduces large uncertainties on longer time scales, precluding robust sea-level estimates for intervals such as the Pliocene. Present climate is warming to a level associated with significant polar ice-sheet loss in the past. Here, we outline advances and challenges involved in constraining ice-sheet sensitivity to climate change with use of paleo-sea level records. Copyright © 2015, American Association for the Advancement of Science.

Antiferroelectric polarization switching and dynamic scaling of energy storage: A Monte Carlo simulation

Science.gov (United States)

Huang, B. Y.; Lu, Z. X.; Zhang, Y.; Xie, Y. L.; Zeng, M.; Yan, Z. B.; Liu, J.-M.

2016-05-01

The polarization-electric field hysteresis loops and the dynamics of polarization switching in a two-dimensional antiferroelectric (AFE) lattice submitted to a time-oscillating electric field E(t) of frequency f and amplitude E0, is investigated using Monte Carlo simulation based on the Landau-Devonshire phenomenological theory on antiferroelectrics. It is revealed that the AFE double-loop hysteresis area A, i.e., the energy loss in one cycle of polarization switching, exhibits the single-peak frequency dispersion A(f), suggesting the unique characteristic time for polarization switching, which is independent of E0 as long as E0 is larger than the quasi-static coercive field for the antiferroelectric-ferroelectric transitions. However, the dependence of recoverable stored energy W on amplitude E0 seems to be complicated depending on temperature T and frequency f. A dynamic scaling behavior of the energy loss dispersion A(f) over a wide range of E0 is obtained, confirming the unique characteristic time for polarization switching of an AFE lattice. The present simulation may shed light on the dynamics of energy storage and release in AFE thin films.

Near infrared photoimmunotherapy with avelumab, an anti-programmed death-ligand 1 (PD-L1) antibody.

Science.gov (United States)

Nagaya, Tadanobu; Nakamura, Yuko; Sato, Kazuhide; Harada, Toshiko; Choyke, Peter L; Hodge, James W; Schlom, Jeffrey; Kobayashi, Hisataka

2017-01-31

Near Infrared-Photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photo-absorber conjugate (APC). Programmed cell death protein-1 ligand (PD-L1) is emerging as a molecular target. Here, we describe the efficacy of NIR-PIT, using fully human IgG1 anti-PD-L1 monoclonal antibody (mAb), avelumab, conjugated to the photo-absorber, IR700DX, in a PD-L1 expressing H441 cell line, papillary adenocarcinoma of lung. Avelumab-IR700 showed specific binding and cell-specific killing was observed after exposure of the cells to NIR in vitro. In the in vivo study, avelumab-IR700 showed high tumor accumulation and high tumor-background ratio. Tumor-bearing mice were separated into 4 groups: (1) no treatment; (2) 100 μg of avelumab-IR700 i.v.; (3) NIR light exposure only, NIR light was administered; (4) 100 μg of avelumab-IR700 i.v., NIR light was administered. Tumor growth was significantly inhibited by NIR-PIT treatment compared with the other groups (p avelumab, is suitable as an APC for NIR-PIT. Furthermore, NIR-PIT with avelumab-IR700 is a promising candidate of the treatment of PD-L1-expressing tumors that could be readily translated to humans.

Multiple Scattering Approach to Polarization Dependence of F K-Edge XANES Spectra for Highly Oriented Polytetrafluoroethylene (PTFE) Thin Film

International Nuclear Information System (INIS)

Nagamatsu, S.; Ono, M.; Kera, S.; Okudaira, K. K.; Fujikawa, T.; Ueno, N.

2007-01-01

The polarization dependence of F K-edge X-ray absorption near edge structure (XANES) spectra of highly-oriented thin-film of polytetrafluoroethylene (PTFE) has been analyzed by using multiple scattering theory. The spectra show clear polarization dependence due to the highly-oriented structure. The multiple scattering calculations reflects a local structure around an absorbing atom. The calculated results obtained by considering intermolecular-interactions are in good agreement with the observed polarization-dependence. We have also analyzed structural models of the radiation damaged PTFE films

High speed true random number generator with a new structure of coarse-tuning PDL in FPGA

Science.gov (United States)

Fang, Hongzhen; Wang, Pengjun; Cheng, Xu; Zhou, Keji

2018-03-01

A metastability-based TRNG (true random number generator) is presented in this paper, and implemented in FPGA. The metastable state of a D flip-flop is tunable through a two-stage PDL (programmable delay line). With the proposed coarse-tuning PDL structure, the TRNG core does not require extra placement and routing to ensure its entropy. Furthermore, the core needs fewer stages of coarse-tuning PDL at higher operating frequency, and thus saves more resources in FPGA. The designed TRNG achieves 25 Mbps @ 100 MHz throughput after proper post-processing, which is several times higher than other previous TRNGs based on FPGA. Moreover, the robustness of the system is enhanced with the adoption of a feedback system. The quality of the designed TRNG is verified by NIST (National Institute of Standards and Technology) and also accepted by class P1 of the AIS-20/31 test suite. Project supported by the S&T Plan of Zhejiang Provincial Science and Technology Department (No. 2016C31078), the National Natural Science Foundation of China (Nos. 61574041, 61474068, 61234002), and the K.C. Wong Magna Fund in Ningbo University, China.

Stratospheric cooling and polar ozone loss due to H2 emissions of a global hydrogen economy

Science.gov (United States)

Feck, T.; Grooß, J.-U.; Riese, M.; Vogel, B.

2009-04-01

"Green" hydrogen is seen as a major element of the future energy supply to reduce greenhouse gas emissions substantially. However, due to the possible interactions of hydrogen (H2) with other atmospheric constituents there is a need to analyse the implications of additional atmospheric H2 that could result from hydrogen leakage of a global hydrogen infrastructure. Emissions of molecular H2 can occur along the whole hydrogen process chain which increase the tropospheric H2 burden. Across the tropical tropopause H2 reaches the stratosphere where it is oxidised and forms water vapour (H2O). This causes increased IR-emissions into space and hence a cooling of the stratosphere. Both effects, the increase of stratospheric H2O and the cooling, enhances the potential of chlorine activation on liquid sulfate aerosol and polar stratospheric clouds (PSCs), which increase polar ozone destruction. Hence a global hydrogen economy could provoke polar ozone loss and could lead to a substantial delay of the current projected recovery of the stratospheric ozone layer. Our investigations show that even if 90% of the current global fossil primary energy input could be replaced by hydrogen and approximately 9.5% of the product gas would leak to the atmosphere, the ozone loss would be increased between 15 to 26 Dobson Units (DU) if the stratospheric CFC loading would retain unchanged. A consistency check of the used approximation methods with the Chemical Lagrangian Model of the Stratosphere (CLaMS) shows that this additional ozone loss can probably be treated as an upper limit. Towards more realistic future H2 leakage rate assumptions (< 3%) the additional ozone loss would be rather small (? 10 DU). However, in all cases the full damage would only occur if stratospheric CFC-levels would retain unchanged. Due to the CFC-prohibition as a result of the Montreal Protocol the forecasts suggest a decline of the stratospheric CFC loading about 50% until 2050. In this case our calculations

Low-frequency (0.7-7.4 mHz geomagnetic field fluctuations at high latitude: frequency dependence of the polarization pattern

Directory of Open Access Journals (Sweden)

L. Cafarella

2001-06-01

Full Text Available A statistical analysis of the polarization pattern of low-frequency geomagnetic field fluctuations (0.7-7.4 mHz covering the entire 24-h interval was performed at the Antarctic station Terra Nova Bay (80.0°S geomagnetic latitude throughout 1997 and 1998. The results show that the polarization pattern exhibits a frequency dependence, as can be expected from the frequency dependence of the latitude where the coupling between the magnetospheric compressional mode and the field line resonance takes place. The polarization analysis of single pulsation events shows that wave packets with different polarization sense, depending on frequency, can be simultaneously observed.

Polarization-dependent imaging contrast in abalone shells

Science.gov (United States)

Metzler, Rebecca A.; Zhou, Dong; Abrecht, Mike; Chiou, Jau-Wern; Guo, Jinghua; Ariosa, Daniel; Coppersmith, Susan N.; Gilbert, P. U. P. A.

2008-02-01

Many biominerals contain micro- or nanocrystalline mineral components, organized accurately into architectures that confer the material with improved mechanical performance at the macroscopic scale. We present here an effect which enables us to observe the relative orientation of individual crystals at the submicron scale. We call it polarization-dependent imaging contrast (PIC), as it is an imaging development of the well-known x-ray linear dichroism. Most importantly, PIC is obtained in situ, in biominerals. We present here PIC in the prismatic and nacreous layers of Haliotis rufescens (red abalone), confirm it in geologic calcite and aragonite, and corroborate the experimental data with theoretical simulated spectra. PIC reveals different and unexpected aspects of nacre architecture that have inspired theoretical models for nacre formation.

Polarized Line Formation in Arbitrary Strength Magnetic Fields Angle-averaged and Angle-dependent Partial Frequency Redistribution

Energy Technology Data Exchange (ETDEWEB)

Sampoorna, M.; Nagendra, K. N. [Indian Institute of Astrophysics, Koramangala, Bengaluru 560 034 (India); Stenflo, J. O., E-mail: sampoorna@iiap.res.in, E-mail: knn@iiap.res.in, E-mail: stenflo@astro.phys.ethz.ch [Institute of Astronomy, ETH Zurich, CH-8093 Zurich (Switzerland)

2017-08-01

Magnetic fields in the solar atmosphere leave their fingerprints in the polarized spectrum of the Sun via the Hanle and Zeeman effects. While the Hanle and Zeeman effects dominate, respectively, in the weak and strong field regimes, both these effects jointly operate in the intermediate field strength regime. Therefore, it is necessary to solve the polarized line transfer equation, including the combined influence of Hanle and Zeeman effects. Furthermore, it is required to take into account the effects of partial frequency redistribution (PRD) in scattering when dealing with strong chromospheric lines with broad damping wings. In this paper, we present a numerical method to solve the problem of polarized PRD line formation in magnetic fields of arbitrary strength and orientation. This numerical method is based on the concept of operator perturbation. For our studies, we consider a two-level atom model without hyperfine structure and lower-level polarization. We compare the PRD idealization of angle-averaged Hanle–Zeeman redistribution matrices with the full treatment of angle-dependent PRD, to indicate when the idealized treatment is inadequate and what kind of polarization effects are specific to angle-dependent PRD. Because the angle-dependent treatment is presently computationally prohibitive when applied to realistic model atmospheres, we present the computed emergent Stokes profiles for a range of magnetic fields, with the assumption of an isothermal one-dimensional medium.

pt and xF dependence of the polarization of Σ+ hyperons produced by 800 GeV/c protons

International Nuclear Information System (INIS)

Morelos, A.; Albuquerque, I.F.; Bondar, N.F.; Carrigan, R. Jr.; Chen, D.; Cooper, P.S.; Lisheng, D.; Denisov, A.S.; Dobrovolsky, A.V.; Dubbs, T.; Endler, A.M.F.; Escobar, C.O.; Foucher, M.; Golovtsov, V.L.; Gottschalk, H.; Gouffon, P.; Grachev, V.T.; Khanzadeev, A.V.; Kubantsev, M.A.; Kuropatkin, N.P.; Lach, J.; Lang Pengfei; Lebedenko, V.N.; Li Chengze; Li Yunshan; Luksys, M.; Mahon, J.R.P.; McCliment, E.; Newsom, C.; Pommot Maia, M.C.; Samsonov, V.M.; Schegelsky, V.A.; Shi Huanzhang; Smith, V.J.; Fukun, T.; Terentyev, N.K.; Timm, S.; Tkatch, I.I.; Uvarov, L.N.; Vorobyov, A.A.; Yan Jie; Wenheng, Z.; Zheng Shuchen; Zhong Yuanyuan

1995-01-01

We utilize the angle and momentum resolution of our apparatus to study the polarization of 375 GeV/c Σ + hyperons produced by 800 GeV/c protons incident on a Cu target. By examining in detail two of our high statistics data samples, we find evidence for structure in the p t dependence of Σ + polarization and are able to extract the x F dependence of the Σ + polarization and compare it with x F behavior in the Λ 0 and Ξ - systems

Dynamic spin polarization by orientation-dependent separation in a ferromagnet-semiconductor hybrid

Science.gov (United States)

Korenev, V. L.; Akimov, I. A.; Zaitsev, S. V.; Sapega, V. F.; Langer, L.; Yakovlev, D. R.; Danilov, Yu. A.; Bayer, M.

2012-07-01

Integration of magnetism into semiconductor electronics would facilitate an all-in-one-chip computer. Ferromagnet/bulk semiconductor hybrids have been, so far, mainly considered as key devices to read out the ferromagnetism by means of spin injection. Here we demonstrate that a Mn-based ferromagnetic layer acts as an orientation-dependent separator for carrier spins confined in a semiconductor quantum well that is set apart from the ferromagnet by a barrier only a few nanometers thick. By this spin-separation effect, a non-equilibrium electron-spin polarization is accumulated in the quantum well due to spin-dependent electron transfer to the ferromagnet. The significant advance of this hybrid design is that the excellent optical properties of the quantum well are maintained. This opens up the possibility of optical readout of the ferromagnet's magnetization and control of the non-equilibrium spin polarization in non-magnetic quantum wells.

Experimental dependence of ECR plasma breakdown on wave polarization in the TJ-II stellarator

International Nuclear Information System (INIS)

Cappa, A.; Castejon, F.; Tabares, F.; Fernandez, A.; Tafalla, D.; Cal, E. de la; Estrada, T.; Nagasaki, K.

2005-01-01

Recently, second harmonic ECRH plasma breakdown and its dependence on the initial conditions such as neutral gas pressure, injected power or beam polarization has been the subject of theoretical as well as experimental work. Although those studies have been carried out in the context of stellarators, they are particularly relevant in the case of large tokamaks, such as ITER, where conventional inductive breakdown is expected to be strongly improved if ECRH is used. A matter of interest is the dependence of breakdown time on wave polarization. In the existing theoretical models, wave polarization is not taken into account because it is assumed that the injected ECRH power is initially scrambled by the vessel walls and that the energy source for breakdown is only due to the non-linear wave-particle interaction between deeply trapped electrons and the averaged electric field. However, while this seems reasonable for the very beginning of the discharge, it may not be so as we progress towards breakdown. Actually, as experiments in Heliotron J have demonstrated, wave polarization must be taken into account in the description of the energy source. Breakdown experiments in TJ-II were performed in order to get a deep insight into this matter and part of the results of breakdown dependence on wave polarization were already discussed. In particular, it was demonstrated that the hypothesis about the energy source used in the models is failing long before full ionization is completed. But more information in relation with our understanding of the second harmonic ECRH breakdown, such as the toroidal and radial breakdown propagation, which is seen to be non-diffusive, can be extracted. Thus, the experiment results provide valuable data that can be used not only to improve the energy source but also to include spatial dimensions in the breakdown models. (author)

arXiv Black hole superradiance and polarization-dependent bending of light

CERN Document Server

Plascencia, Alexis D.

2018-04-27

An inhomogeneous pseudo-scalar field configuration behaves like an optically active medium. Consequently, if a light ray passes through an axion cloud surrounding a Kerr black hole, it may experience a polarization-dependent bending. We explore the size and relevance of such effect considering both the QCD axion and a generic axion-like particle.

arXiv Black hole superradiance and polarization-dependent bending of light

CERN Document Server

Plascencia, Alexis D.

2017-01-01

An inhomogeneous pseudo-scalar field configuration behaves like an optically active medium. Consequently, if a light ray passes through an axion cloud surrounding a Kerr black hole, it may experience a polarization-dependent bending. We explore the size and relevance of such effect considering both the QCD axion and a generic axion-like particle.

Heliographic latitude dependence of the IMF dominant polarity in 1972--1973 using Pioneer 10 data

International Nuclear Information System (INIS)

Rosenberg, R.L.

1975-01-01

The heliographic latitude dependence of the interplanetary magnetic field (IMF) was studied by using Pioneer 10 data taken from March 1972 through June 1973 over Bartels solar rotation (SR) periods 1896--1913. The daily IMF sector polarities were plotted for each of these SR periods. Then the number of days of positive polarity (''away'' directed fields) per SR was plotted versus the average heliographic latitude. The dominant polarity behaved in accordance with the latitude effects found by Rosenberg and Coleman in 1969. The phase of the cycle has reversed from what it was prior to the sunspot maximum in 1968. The polarity is now predominantly positive at northern heliographic latitudes. (auth)

Dystroglycan loss disrupts polarity and beta-casein induction inmammary epithelial cells by perturbing laminin anchoring

Energy Technology Data Exchange (ETDEWEB)

Weir, M. Lynn; Oppizzi, Maria Luisa; Henry, Michael D.; Onishi,Akiko; Campbell, Kevin P.; Bissell, Mina J.; Muschler, John L.

2006-02-17

Precise contact between epithelial cells and their underlying basement membrane is critical to the maintenance of tissue architecture and function. To understand the role that the laminin receptor dystroglycan (DG) plays in these processes, we assayed cell responses to laminin-111 following conditional ablation of DG expression in cultured mammary epithelial cells (MECs). Strikingly, DG loss disrupted laminin-111-induced polarity and {beta}-casein production, and abolished laminin assembly at the step of laminin binding to the cell surface. DG re-expression restored these deficiencies. Investigations of mechanism revealed that DG cytoplasmic sequences were not necessary for laminin assembly and signaling, and only when the entire mucin domain of extracellular DG was deleted did laminin assembly not occur. These results demonstrate that DG is essential as a laminin-111 co-receptor in MECs that functions by mediating laminin anchoring to the cell surface, a process that allows laminin polymerization, tissue polarity, and {beta}-casein induction. The observed loss of laminin-111 assembly and signaling in DG-/-MECs provides insights into the signaling changes occurring in breast carcinomas and other cancers, where DG's laminin-binding function is frequently defective.

Azimuthal and polar angle dependence of L X-ray differential cross-sections of Yb at 59.54 keV photon energy

Energy Technology Data Exchange (ETDEWEB)

Akkuş, T.; Şahin, Y.; Yılmaz, D., E-mail: ddemir@atauni.edu.tr

2016-01-01

Highlights: • The azimuthal and polar angle dependence of L X-ray for Yb is investigated. • The azimuthal angle dependence of Ll and Lα X-rays are observed. • The azimuthal anisotropy of Lβ and Lγ X-rays are not observed. • The polar anisotropy of Ll and Lα X-rays are observed. • The polar anisotropy of Lβ and Lγ X-rays are not observed. - Abstract: The azimuthal and polar angle dependence of L X-ray was investigated in the same experimental setup to remove the existing ambiguity about alignments measurements. We measured Ll, Lα, Lβ and Lγ X-ray differential cross sections of Yb for several different azimuthal angles (30°, 20°, 10°, 0°, −10° and −20°) and polar angles (90°, 100°, 110°, 120°, 130° and 140°) at 59.54 keV photon energy by using a Si(Li) detector. The azimuthal angle dependence of Ll and Lα X-rays were observed. The azimuthal anisotropy of Lβ and Lγ X-rays were not observed. On the other hand, differential cross-sections for Lβ and Lγ X-rays were found independent on the polar angle within experimental error, those for Ll and Lα X-rays depended on the polar angles. Azimuthal and polar angles dependence of L X-ray differential cross-sections contrast with the other experimental and theoretical results, which report evidence of the isotropic emission of Ll and Lα X-rays following photoionization.

Optical properties of polarization-dependent geometrical phase elements with partially polarized light

International Nuclear Information System (INIS)

Gorodetski, Y.; Biener, G.; Niv, A.; Kleiner, V.; Hasman, E.

2005-01-01

Full Text:The behavior of geometrical phase elements illuminated with partially polarized monochromatic beams is being theoretically as well as experimentally investigated. The element discussed in this paper is composed of wave plates with retardation and space-variant orientation angle. We found that a beam emerging from such an element comprises two polarization orders of right and left-handed circularly polarized states with conjugate geometrical phase modification. This phase equals twice the orientation angle of the space-variant wave plate comprising the element. Apart from the two polarization orders, the emerging beam coherence polarization matrix comprises a matrix termed as the vectorial interference matrix. This matrix contains the information concerning the correlation between the two orthogonal circularly polarized portions of the incident beam. In this paper we measure this correlation by a simple interference experiment. Furthermore, we found that the equivalent mutual intensity of the emerging beam is being modulated according to the geometrical phase induced by the element. Other interesting phenomena along propagation will be discussed theoretically and experimentally demonstrated. We demonstrate experimentally our analysis by using a spherical geometrical phase element, which is realized by use of space-variant sub wavelength grating and illuminated with a CO 2 laser radiation of 10.6μm wavelength

Targeting CD28, CTLA-4 and PD-L1 costimulation differentially controls immune synapses and function of human regulatory and conventional T-cells.

Directory of Open Access Journals (Sweden)

Nahzli Dilek

Full Text Available CD28, CTLA-4 and PD-L1, the three identified ligands for CD80/86, are pivotal positive and negative costimulatory molecules that, among other functions, control T cell motility and formation of immune synapse between T cells and antigen-presenting cells (APCs. What remains incompletely understood is how CD28 leads to the activation of effector T cells (Teff but inhibition of suppression by regulatory T cells (Tregs, while CTLA-4 and PD-L1 inhibit Teff function but are crucial for the suppressive function of Tregs. Using alloreactive human T cells and blocking antibodies, we show here by live cell dynamic microscopy that CD28, CTLA-4, and PD-L1 differentially control velocity, motility and immune synapse formation in activated Teff versus Tregs. Selectively antagonizing CD28 costimulation increased Treg dwell time with APCs and induced calcium mobilization which translated in increased Treg suppressive activity, in contrast with the dampening effect on Teff responses. The increase in Treg suppressive activity after CD28 blockade was also confirmed with polyclonal Tregs. Whereas CTLA-4 played a critical role in Teff by reversing TCR-induced STOP signals, it failed to affect motility in Tregs but was essential for formation of the Treg immune synapse. Furthermore, we identified a novel role for PD-L1-CD80 interactions in suppressing motility specifically in Tregs. Thus, our findings reveal that the three identified ligands of CD80/86, CD28, CTLA-4 and PD-L1, differentially control immune synapse formation and function of the human Teff and Treg cells analyzed here. Individually targeting CD28, CTLA-4 and PD-L1 might therefore represent a valuable therapeutic strategy to treat immune disorders where effector and regulatory T cell functions need to be differentially targeted.

Analysis of proton exchange membrane fuel cell polarization losses at elevated temperature 120 {sup o}C and reduced relative humidity

Energy Technology Data Exchange (ETDEWEB)

Xu, Hui [Department of Chemical Engineering, University of Connecticut, Storrs, CT (United States)]. E-mail: huixu@lanl.gov; Kunz, H. Russell [Department of Chemical Engineering, University of Connecticut, Storrs, CT (United States); Fenton, James M. [Florida Solar Energy Center, University of Central Florida, Cocoa, FL (United States)

2007-03-01

Polarization losses of proton exchange membrane (PEM) fuel cells at 120 {sup o}C and reduced relative humidity (RH) were analyzed. Reduced RH affects membrane and electrode ionic resistance, catalytic activity and oxygen transport. For a cell made of Nafion (registered) 112 membrane and electrodes that have 35 wt.% Nafion (registered) and 0.3 mg/cm{sup 2} platinum supported on carbon, membrane resistance at 20%RH was 0.407 {omega} cm{sup 2} and electrode resistance 0.203 {omega} cm{sup 2}, significantly higher than 0.092 and 0.041 {omega} cm{sup 2} at 100%RH, respectively. In the kinetically controlled region, 20%RH resulted in 96 mV more cathode activation loss than 100%RH. Compared to 100%, 20%RH also produced significant oxygen transport loss across the ionomer film in the electrode, 105 mV at 600 mA/cm{sup 2}. The significant increase in polarization losses at elevated temperature and reduced RH indicates the extreme importance of designing electrodes for high temperature PEM fuel cells since membrane development has always taken most emphasis.

Influence of wavelength-dependent-loss on dispersive wave in nonlinear optical fibers.

Science.gov (United States)

Herrera, Rodrigo Acuna

2012-11-01

In this work, we study numerically the influence of wavelength-dependent loss on the generation of dispersive waves (DWs) in nonlinear fiber. This kind of loss can be obtained, for instance, by the acousto-optic effect in fiber optics. We show that this loss lowers DW frequency in an opposite way that the Raman effect does. Also, we see that the Raman effect does not change the DW frequency too much when wavelength-dependent loss is included. Finally, we show that the DW frequency is not practically affected by fiber length.

Transverse momentum dependent quark distributions and polarized Drell-Yan processes

OpenAIRE

Zhou, Jian; Yuan, Feng; Liang, Zuo-Tang

2009-01-01

We study the spin-dependent quark distributions at large transverse momentum. We derive their transverse momentum behaviors in the collinear factorization approach in this region. We further calculate the angular distribution of the Drell-Yan lepton pair production with polarized beams and present the results in terms of the collinear twist-three quark-gluon correlation functions. In the intermediate transverse momentum region, we find that the two pproaches: the collinear factorization and t...

The MLL1-H3K4me3 Axis-Mediated PD-L1 Expression and Pancreatic Cancer Immune Evasion.

Science.gov (United States)

Lu, Chunwan; Paschall, Amy V; Shi, Huidong; Savage, Natasha; Waller, Jennifer L; Sabbatini, Maria E; Oberlies, Nicholas H; Pearce, Cedric; Liu, Kebin

2017-01-01

Pancreatic cancer is one of the cancers where anti-PD-L1/PD-1 immunotherapy has been unsuccessful. What confers pancreatic cancer resistance to checkpoint immunotherapy is unknown. The aim of this study is to elucidate the underlying mechanism of PD-L1 expression regulation in the context of pancreatic cancer immune evasion. Pancreatic cancer mouse models and human specimens were used to determine PD-L1 and PD-1 expression and cancer immune evasion. Histone methyltransferase inhibitors, RNAi, and overexpression were used to elucidate the underlying molecular mechanism of PD-L1 expression regulation. All statistical tests were two-sided. PD-L1 is expressed in 60% to 90% of tumor cells in human pancreatic carcinomas and in nine of 10 human pancreatic cancer cell lines. PD-1 is expressed in 51.2% to 52.1% of pancreatic tumor-infiltrating cytotoxic T lymphocytes (CTLs). Tumors grow statistically significantly faster in FasL-deficient mice than in wild-type mice (P = .03-.001) and when CTLs are neutralized (P = .03-evasion. Targeting the MLL1-H3K4me3 axis is an effective approach to enhance the efficacy of checkpoint immunotherapy against pancreatic cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Targeting the PD-1/PD-L1 Immune Evasion Axis With DNA Aptamers as a Novel Therapeutic Strategy for the Treatment of Disseminated Cancers.

Science.gov (United States)

Prodeus, Aaron; Abdul-Wahid, Aws; Fischer, Nicholas W; Huang, Eric H-B; Cydzik, Marzena; Gariépy, Jean

2015-04-28

Blocking the immunoinhibitory PD-1:PD-L1 pathway using monoclonal antibodies has led to dramatic clinical responses by reversing tumor immune evasion and provoking robust and durable antitumor responses. Anti-PD-1 antibodies have now been approved for the treatment of melanoma, and are being clinically tested in a number of other tumor types as both a monotherapy and as part of combination regimens. Here, we report the development of DNA aptamers as synthetic, nonimmunogenic antibody mimics, which bind specifically to the murine extracellular domain of PD-1 and block the PD-1:PD-L1 interaction. One such aptamer, MP7, functionally inhibits the PD-L1-mediated suppression of IL-2 secretion in primary T-cells. A PEGylated form of MP7 retains the ability to block the PD-1:PD-L1 interaction, and significantly suppresses the growth of PD-L1+ colon carcinoma cells in vivo with a potency equivalent to an antagonistic anti-PD-1 antibody. Importantly, the anti-PD-1 DNA aptamer treatment was not associated with off-target TLR-9-related immune responses. Due to the inherent advantages of aptamers including their lack of immunogenicity, low cost, long shelf life, and ease of synthesis, PD-1 antagonistic aptamers may represent an attractive alternative over antibody-based anti PD-1 therapeutics.

Targeting the PD-1/PD-L1 Immune Evasion Axis With DNA Aptamers as a Novel Therapeutic Strategy for the Treatment of Disseminated Cancers

Directory of Open Access Journals (Sweden)

Aaron Prodeus

2015-01-01

Full Text Available Blocking the immunoinhibitory PD-1:PD-L1 pathway using monoclonal antibodies has led to dramatic clinical responses by reversing tumor immune evasion and provoking robust and durable antitumor responses. Anti-PD-1 antibodies have now been approved for the treatment of melanoma, and are being clinically tested in a number of other tumor types as both a monotherapy and as part of combination regimens. Here, we report the development of DNA aptamers as synthetic, nonimmunogenic antibody mimics, which bind specifically to the murine extracellular domain of PD-1 and block the PD-1:PD-L1 interaction. One such aptamer, MP7, functionally inhibits the PD-L1-mediated suppression of IL-2 secretion in primary T-cells. A PEGylated form of MP7 retains the ability to block the PD-1:PD-L1 interaction, and significantly suppresses the growth of PD-L1+ colon carcinoma cells in vivo with a potency equivalent to an antagonistic anti-PD-1 antibody. Importantly, the anti-PD-1 DNA aptamer treatment was not associated with off-target TLR-9-related immune responses. Due to the inherent advantages of aptamers including their lack of immunogenicity, low cost, long shelf life, and ease of synthesis, PD-1 antagonistic aptamers may represent an attractive alternative over antibody-based anti PD-1 therapeutics.

Glass-based integrated optical splitters: engineering oriented research

Science.gov (United States)

Hao, Yinlei; Zheng, Weiwei; Yang, Jianyi; Jiang, Xiaoqing; Wang, Minghua

2010-10-01

Optical splitter is one of most typical device heavily demanded in implementation of Fiber To The Home (FTTH) system. Due to its compatibility with optical fibers, low propagation loss, flexibility, and most distinguishingly, potentially costeffectiveness, glass-based integrated optical splitters made by ion-exchange technology promise to be very attractive in application of optical communication networks. Aiming at integrated optical splitters applied in optical communication network, glass ion-exchange waveguide process is developed, which includes two steps: thermal salts ion-exchange and field-assisted ion-diffusion. By this process, high performance optical splitters are fabricated in specially melted glass substrate. Main performance parameters of these splitters, including maximum insertion loss (IL), polarization dependence loss (PDL), and IL uniformity are all in accordance with corresponding specifications in generic requirements for optic branching components (GR-1209-CORE). In this paper, glass based integrated optical splitters manufacturing is demonstrated, after which, engineering-oriented research work results on glass-based optical splitter are presented.

Wavelength dependence of interstellar polarization and ratio of total to selective extinction

International Nuclear Information System (INIS)

Serkowski, K.; Mathewson, D.S.; Ford, V.L.

1975-01-01

Wavelength dependence of interstellar linear polarization has been observed for about 180 stars, mostly southern, in the UBVR spectral regions. A multichannel polarimeter-photometer, in which spectral regions are separated by dichroic filters, was used. Normalized wavelength dependence of interstellar linear polarization p follows closely a single empirical curve p (lambda)/p /sub max/=exp-1.15 ln 2 (lambda/sub max//lambda), where the wavelength lambda/sub max/ at which the maximum interstellar linear polarization p/sub max/ occurs takes values from 0.45 μ to 0.8 μ. Wavelength lambda/sub max/ is well correlated with the ratios of color excesses E/sub V-K//E/sub B-V/, E/sub V-K//E/sub V-R/, and E/sub V-I//E/sub V-R/. These correlations indicate that the ratio R of total to selective interstellar extinction can be found for any individual star from the relationship R = 5.5 lambda/sub max/. Polarimetry seems to be the most practical method of estimating R. A map of distribution of lambda/sub max/ on the sky, based on values for about 350 stars, indicates several well defined regions with lambda/sub max/, and hence R, clearly larger (or smaller) than the median value lambda/sub max/ = π.545 μ, corresponding to R = 3.0. The predominance of larger than average values of lambda/sub max/ among stars nearer than 0.4 kpc and the negative correlation between lambda/sub max/ and E/sub B-V/ are explained by selection effects. There is evidence of negative correlation between lambda/sub max/ and p/sub max//E/sub B-V/ suggested by Kruszewski. The lower limits for color excess of Praesepe, M67, and several globular clusters are set by their linear polarization. The largest known values of interstellar circular polarization, parallel q parallel approximately equal to 0.06 percent, were found in near-infrared for two stars with exceptionally small lambda/sub max/: star No. 12 in association VI Cygni and HD 204827. (U.S.)

An on-chip polarization splitter based on the radiation loss in the bending hybrid plasmonic waveguide structure

Science.gov (United States)

Sun, Chengwei; Rong, Kexiu; Gan, Fengyuan; Chu, Saisai; Gong, Qihuang; Chen, Jianjun

2017-09-01

Polarization beam splitters (PBSs) are one of the key components in the integrated photonic circuits. To increase the integration density, various complex hybrid plasmonic structures have been numerically designed to shrink the footprints of the PBSs. Here, to decrease the complexity of the small hybrid structures and the difficulty of the hybrid micro-nano fabrications, the radiation losses are utilized to experimentally demonstrate an ultra-small, broadband, and efficient PBS in a simple bending hybrid plasmonic waveguide structure. The hybrid plasmonic waveguide comprising a dielectric strip on the metal surface supports both the transverse-magnetic (TM) and transverse-electric (TE) waveguide modes. Because of the different field confinements, the TE waveguide mode has larger radiation loss than the TM waveguide mode in the bending hybrid strip waveguide. Based on the different radiation losses, the two incident waveguide modes of orthogonal polarization states are efficiently split in the proposed structure with a footprint of only about 2.2 × 2.2 μm2 on chips. Since there is no resonance or interference in the splitting process, the operation bandwidth is as broad as Δλ = 70 nm. Moreover, the utilization of the strongly confined waveguide modes instead of the bulk free-space light (with the spot size of at least a few wavelengths) as the incident source considerably increases the coupling efficiency, resulting in a low insertion loss of <3 dB.

Low-loss ultracompact optical power splitter using a multistep structure.

Science.gov (United States)

Huang, Zhe; Chan, Hau Ping; Afsar Uddin, Mohammad

2010-04-01

We propose a low-loss ultracompact optical power splitter for broadband passive optical network applications. The design is based on a multistep structure involving a two-material (core/cladding) system. The performance of the proposed device was evaluated through the three-dimensional finite-difference beam propagation method. By using the proposed design, an excess loss of 0.4 dB was achieved at a full branching angle of 24 degrees. The wavelength-dependent loss was found to be less than 0.3 dB, and the polarization-dependent loss was less than 0.05 dB from O to L bands. The device offers the potential of being mass-produced using low-cost polymer-based embossing techniques.

Parallel Low-Loss Measurement of Multiple Atomic Qubits.

Science.gov (United States)

Kwon, Minho; Ebert, Matthew F; Walker, Thad G; Saffman, M

2017-11-03

We demonstrate low-loss measurement of the hyperfine ground state of rubidium atoms by state dependent fluorescence detection in a dipole trap array of five sites. The presence of atoms and their internal states are minimally altered by utilizing circularly polarized probe light and a strictly controlled quantization axis. We achieve mean state detection fidelity of 97% without correcting for imperfect state preparation or background losses, and 98.7% when corrected. After state detection and correction for background losses, the probability of atom loss due to the state measurement is state is preserved with >98% probability.

HLA class I antigen processing machinery (APM) component expression and PD-1:PD-L1 pathway activation in HIV-infected head and neck cancers.

Science.gov (United States)

Pai, Sara I; Jack Lee, J; Carey, Thomas E; Westra, William H; Ferrone, Soldano; Moore, Charles; Mosunjac, Marina B; Shin, Dong M; Ferris, Robert L

2018-02-01

Human immunodeficiency virus (HIV)-infected individuals are at increased risk for developing several non-AIDS related malignancies and are often excluded from cancer immunotherapy regimens. To evaluate the immune competence of this cancer patient population, we evaluated HLA class I antigen presenting machinery (APM) component expression and PD-1:PD-L1 pathway upregulation in HIV(+) and HIV(-) head and neck cancers (HNCs). Sixty-two HIV(+) and 44 matched HIV(-) controls diagnosed with HNC between 1991 and 2011 from five tertiary care referral centers in the United States were identified. HLA class I APM component, PD-1, and PD-L1 expression were analyzed by immunohistochemical staining with monoclonal antibodies (mAbs). Clinical data was abstracted from the medical records. There was no significant difference between the cases and controls in LMP2, TAP1, HLA-A and HLA-B/C, as well as PD-1 and PD-L1 expression. Overall, 62% of all subjects had high PD-1 expression and 82% of the subjects expressed PD-L1 within the tumor microenvironment. LMP2, HLA-A and HLA-B/C expression were significantly associated with moderate to high PD-1 expression in the HIV(+) HNC cases (p = .004, p = .026, and p = .006, respectively) but not in the HIV(-) controls. In addition, HLA-A expression was significantly associated with PD-L1 expression in the HIV(+) HNC cases only (p = .029). HIV-infected individuals diagnosed with HNC do not have any detectable defects in HLA class I APM component expression and in PD-1:PD-L1 pathway activation. Given the current successes of HAART therapy in maintaining immune cell counts, HIV(+) patients diagnosed with cancer may benefit from the recently FDA-approved immune checkpoint blockade therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Polarity-dependence of the defect formation in c-axis oriented ZnO by the irradiation of an 8 MeV proton beam

Science.gov (United States)

Koike, Kazuto; Yano, Mitsuaki; Gonda, Shun-ichi; Uedono, Akira; Ishibashi, Shoji; Kojima, Kazunobu; Chichibu, Shigefusa F.

2018-04-01

The polarity dependence of the radiation hardness of single-crystalline ZnO bulk crystals is studied by irradiating the Zn-polar and O-polar c-planes with an 8 MeV proton beam up to the fluence of 4.2 × 1016 p/cm2. To analyze the hardness, radiation-induced defects were evaluated using positron annihilation (PA) analysis, and the recovery by post-annealing was examined using continuous-wave photoluminescence (PL) and time-resolved photoluminescence (TRPL) measurements. It was suggested by the PA and PL analyses that the major defects in both polarities were VZnVO divacancies. While the PA data did not show the clear dependence on the polarity, the PL and TRPL results showed that the Zn-polar c-plane had a little higher radiation tolerance than that of the O-polar c-plane, which was consistent with the result that the increase in the electrical resistance by proton beam irradiation was smaller for the former one. Considering these results in total, the polarity dependence is considered to be not so large, but the Zn-polar c-plane has a little higher tolerance than that of the O-polar one.

Nuclear-optical methods for production of polarized photons with energies of a few hundred GeV

International Nuclear Information System (INIS)

Ispiryan, K.A.; Ispiryan, M.K.

1985-01-01

The absorption coefficients of linearly polarized photons passing through a crystal in parallel to its crystallographic planes are calculated. The methods of determination of the obtainable degree of polarization as well as of the intensity losses for the cases when non-polarized photon beams pass through various crystals in parallel to the planes (110) are described. The energy dependence of the thickness of the quarter-wave plate crystals transforming the linear polarization of the beam into circular one is obtained

Performance of wireless optical communication systems under polarization effects over atmospheric turbulence

Science.gov (United States)

Zhang, Jiankun; Li, Ziyang; Dang, Anhong

2018-06-01

It has been recntly shown that polarization state of propagation beam would suffer from polarization fluctuations due to the detrimental effects of atmospheric turbulence. This paper studies the performance of wireless optical communication (WOC) systems in the presence of polarization effect of atmosphere. We categorize the atmospheric polarization effect into polarization rotation, polarization-dependent power loss, and phase shift effect, with each effect described and modeled with the help of polarization-coherence theory and the extended Huygens-Fresnelprinciple. The channel matrices are derived to measure the cross-polarization interference of the system. Signal-to-noise ratio and bit error rate for polarization multiplexing system and polarization modulation system are obtained to assess the viability using the approach of M turbulence model. Monte Carlo simulation results show the performance of polarization based WOC systems to be degraded by atmospheric polarization effect, which could be evaluated precisely using the proposed model with given turbulent strengths.

π--induced single charge exchange on polarized 3He

International Nuclear Information System (INIS)

Zhao, Q.; Burleson, S.; Blanchard, T.

1995-01-01

Asymmetries, A y , for the (π - ,π 0 ) reaction on polarized 3 He were measured using the pion beam of the P3W channel at LAMPF. The π 0 were detected with the new Neutral Meson Spectrometer (NMS) in coincidence with recoiling tritons. The recoil detector consisted of scintillation-counter telescopes and a wire chamber that provided energy-loss and direction information, respectively. The polarized gaseous 3 He target developed at TRIUMF was modified and run with the use of two diode lasers. Polarizations were typically 50%. The A y taken at T π = 200 MeV between 60 and 105 degrees were found to be strongly angle-dependent. The results will be compared with the theoretical predictions

Fast online simultaneous monitoring of PMD and chromatic dispersion with reduced polarization dependent gain

Science.gov (United States)

Ning, G.; Shum, P.; Aditya, S.; Gong, Yandong

2006-09-01

We use the expression relating the output state of polarization and PMD vector. Based on this expression we get the power fading including first-order PMD and chromatic dispersion, which is dependent on the angle of precession of output state of polarization around the PMD vector. From the expression for power fading, we get the average power penalty for chromatic dispersion and PMD. We propose a novel and fast PMD and chromatic dispersion monitoring technology. Measured results agree well with theoretical analysis.

Range contraction and increasing isolation of a polar bear subpopulation in an era of sea-ice loss.

Science.gov (United States)

Laidre, Kristin L; Born, Erik W; Atkinson, Stephen N; Wiig, Øystein; Andersen, Liselotte W; Lunn, Nicholas J; Dyck, Markus; Regehr, Eric V; McGovern, Richard; Heagerty, Patrick

2018-02-01

Climate change is expected to result in range shifts and habitat fragmentation for many species. In the Arctic, loss of sea ice will reduce barriers to dispersal or eliminate movement corridors, resulting in increased connectivity or geographic isolation with sweeping implications for conservation. We used satellite telemetry, data from individually marked animals (research and harvest), and microsatellite genetic data to examine changes in geographic range, emigration, and interpopulation connectivity of the Baffin Bay (BB) polar bear ( Ursus maritimus ) subpopulation over a 25-year period of sea-ice loss. Satellite telemetry collected from n  = 43 (1991-1995) and 38 (2009-2015) adult females revealed a significant contraction in subpopulation range size (95% bivariate normal kernel range) in most months and seasons, with the most marked reduction being a 70% decline in summer from 716,000 km 2 (SE 58,000) to 211,000 km 2 (SE 23,000) ( p  Bears in the 2000s were less likely to leave BB, with significant reductions in the numbers of bears moving into Davis Strait (DS) in winter and Lancaster Sound (LS) in summer. Harvest recoveries suggested both short and long-term fidelity to BB remained high over both periods (83-99% of marked bears remained in BB). Genetic analyses using eight polymorphic microsatellites confirmed a previously documented differentiation between BB, DS, and LS; yet weakly differentiated BB from Kane Basin (KB) for the first time. Our results provide the first multiple lines of evidence for an increasingly geographically and functionally isolated subpopulation of polar bears in the context of long-term sea-ice loss. This may be indicative of future patterns for other polar bear subpopulations under climate change.

The PD1:PD-L1/2 Pathway from Discovery to Clinical Implementation.

Science.gov (United States)

Bardhan, Kankana; Anagnostou, Theodora; Boussiotis, Vassiliki A

2016-01-01

The immune system maintains a critically organized network to defend against foreign particles, while evading self-reactivity simultaneously. T lymphocytes function as effectors and play an important regulatory role to orchestrate the immune signals. Although central tolerance mechanism results in the removal of the most of the autoreactive T cells during thymic selection, a fraction of self-reactive lymphocytes escapes to the periphery and pose a threat to cause autoimmunity. The immune system evolved various mechanisms to constrain such autoreactive T cells and maintain peripheral tolerance, including T cell anergy, deletion, and suppression by regulatory T cells (T Regs ). These effects are regulated by a complex network of stimulatory and inhibitory receptors expressed on T cells and their ligands, which deliver cell-to-cell signals that dictate the outcome of T cell encountering with cognate antigens. Among the inhibitory immune mediators, the pathway consisting of the programed cell death 1 (PD-1) receptor (CD279) and its ligands PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC, CD273) plays an important role in the induction and maintenance of peripheral tolerance and for the maintenance of the stability and the integrity of T cells. However, the PD-1:PD-L1/L2 pathway also mediates potent inhibitory signals to hinder the proliferation and function of T effector cells and have inimical effects on antiviral and antitumor immunity. Therapeutic targeting of this pathway has resulted in successful enhancement of T cell immunity against viral pathogens and tumors. Here, we will provide a brief overview on the properties of the components of the PD-1 pathway, the signaling events regulated by PD-1 engagement, and their consequences on the function of T effector cells.

The PD1: PD-L1/2 pathway from discovery to clinical implementation

Directory of Open Access Journals (Sweden)

Kankana Bardhan

2016-12-01

Full Text Available The immune system has the difficult challenge of discerning and defending against a diversity of microbial pathogens, while simultaneously avoiding self-reactivity. T lymphocytes function as effectors and regulators of the immune system. While central tolerance mechanism results in deletion of the majority of self-reactive T lymphocytes during thymic selection, a fraction of self reactive lymphocytes escapes to the periphery and retains the potential to inflict destructive autoimmune pathology. The immune system evolved various mechanisms to restrain such auto-reactive T cells and maintain peripheral tolerance, including T cell anergy, deletion, and suppression by regulatory T cells (TRegs. These effects are regulated by a complex network of stimulatory and inhibitory receptors expressed on T cells and their ligands, which deliver cell-to-cell signals that dictate the outcome of T cell encountering with cognate antigens. Among the inhibitory immune mediators, the pathway consisting of the programmed cell death 1 (PD-1 receptor (CD279 and its ligands PD-L1 (B7-H1, CD274 and PD-L2 (B7-DC; CD273 plays a vital role in the induction and maintenance of peripheral tolerance and for the maintenance of T cell homeostasis. In contrast to its beneficial role in self-tolerance, the PD-1: PD-L1/L2 pathway mediates potent inhibitory signals that prevent the expansion and function of T effector cells and have detrimental effects on antiviral and antitumor immunity. Therapeutic targeting of this pathway has resulted in successful enhancement of T cell immunity against viral pathogens and tumors. Here, we will provide a brief overview on the properties of the components of the PD-1 pathway, the signaling events that are regulated by PD-1 triggering, and their consequences on the function of T effector cells.

A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma.

Science.gov (United States)

Maekawa, Naoya; Konnai, Satoru; Takagi, Satoshi; Kagawa, Yumiko; Okagawa, Tomohiro; Nishimori, Asami; Ikebuchi, Ryoyo; Izumi, Yusuke; Deguchi, Tatsuya; Nakajima, Chie; Kato, Yukinari; Yamamoto, Keiichi; Uemura, Hidetoshi; Suzuki, Yasuhiko; Murata, Shiro; Ohashi, Kazuhiko

2017-08-21

Immunotherapy targeting immune checkpoint molecules, programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), using therapeutic antibodies has been widely used for some human malignancies in the last 5 years. A costimulatory receptor, PD-1, is expressed on T cells and suppresses effector functions when it binds to its ligand, PD-L1. Aberrant PD-L1 expression is reported in various human cancers and is considered an immune escape mechanism. Antibodies blocking the PD-1/PD-L1 axis induce antitumour responses in patients with malignant melanoma and other cancers. In dogs, no such clinical studies have been performed to date because of the lack of therapeutic antibodies that can be used in dogs. In this study, the immunomodulatory effects of c4G12, a canine-chimerised anti-PD-L1 monoclonal antibody, were evaluated in vitro, demonstrating significantly enhanced cytokine production and proliferation of dog peripheral blood mononuclear cells. A pilot clinical study was performed on seven dogs with oral malignant melanoma (OMM) and two with undifferentiated sarcoma. Objective antitumour responses were observed in one dog with OMM (14.3%, 1/7) and one with undifferentiated sarcoma (50.0%, 1/2) when c4G12 was given at 2 or 5 mg/kg, every 2 weeks. c4G12 could be a safe and effective treatment option for canine cancers.

Structural basis for small molecule targeting of the programmed death ligand 1 (PD-L1)

NARCIS (Netherlands)

Zak, Krzysztof M.; Grudnik, Przemyslaw; Guzik, Katarzyna; Zieba, Bartosz J.; Musielak, Bogdan; Dömling, Alexander; Dubin, Grzegorz; Holak, Tad A.

2016-01-01

Targeting the PD-1/PD-L1 immunologic checkpoint with monoclonal antibodies has provided unprecedented results in cancer treatment in the recent years. Development of chemical inhibitors for this pathway lags the antibody development because of insufficient structural information. The first

Effect of magnetic field and radiative condensation on the Jeans instability of dusty plasma with polarization force

International Nuclear Information System (INIS)

Prajapati, R.P.

2013-01-01

The Jeans instability of self-gravitating dusty plasma with polarization force is investigated considering the effects of magnetic field, dust temperature and radiative condensation. The condition of Jeans instability and expression of critical Jeans wave number are obtained which depend upon polarization force and dust temperature but these are unaffected by the presence of magnetic field. The radiative heat-loss functions also modify the Jeans condition of instability and expression of critical Jeans wave number. It is observed that the polarization force and ratio of radiative heat-loss functions have destabilizing while magnetic field and dust temperature have stabilizing influence on the growth rate of Jeans instability.

The impact of PD-L1 on survival and value of the immune check point inhibitors in non-small-cell lung cancer; proposal, policies and perspective.

Science.gov (United States)

Guirgis, Helmy M

2018-02-20

The impact of programmed death receptor-ligand1 (PD-L1) on costs and value of the immune check point inhibitors (ICPI) has received minimal attention. 1- Design a sliding scale to grade survival in 2nd-line non-small-cell lung cancer (NSCLC). 2- Compare costs and value of Nivolumab (Nivo), Atezolizumab (Atezo) and Pembrolizumab (Pembro) vs. Docetaxel (Doc). Previously reported median overall survival (OS) and prices posted by parent company were utilized. The OS gains over controls in days were graded (gr) from A+ to D. Docetaxel costs were calculated for 6-12 cycles and the ICPI for 1 year. Adverse events treatment costs (AEsTC) were reported separately. The cost/life-year gain (C/LYG) was computed as drug yearly-cost/OS gain over control in days × 360 days. The relative value of the ICPI were expressed as $100,000/C/LYG. Costs of Doc 6 cycles were $23,868, OS/gr 87/C, AEs gr ¾ > 20%, AEsTC $1978 and 6- 12 cycle C/LYG $98,764 -$197,528. Nivo, Atezo and Pembro gr ¾ were  10%. Atezolizumab OS/g were 87/B and C/LYG $551,407 improving in enriched PD-L1 to 162/A and $332,020 respectively. Pembrolizumab in PD-L1 > 1.0% demonstrated OS/g 57/C and C/LYG $659,059 improving in > 50% PD-L1 to 201/A and $186,897. PD-L1 enrichment increased RV of Nivo from 0.18 to 0.56, Atezo from 0.16 to 0.66 and Pembro from 0.15 to 0.53. Simplified methodology to grade OS and weigh value of anticancer drugs was proposed. In 2nd-line non-squamous NSCLC, value of Doc, Nivo, Atezo and Pembro regardless of PDL-1 expression were limited and modest. Enrichment of PD-L1 resulted in unprecedented OS, improved grades and enhanced value at seemingly justifiable costs.

Novel antibody-based drugs for PD-L1 and TRAIL-R targeted cancer immunotherapy

NARCIS (Netherlands)

Hendriks, Djoke

2017-01-01

Immunotherapy aims to destroy cancer cells using cells or molecules of the immune system. This can be achieved by either targeting cancer cells directly or by improving an ongoing anticancer immune response in the patient. It was recently discovered that cancer cells overexpress PD-L1 protein on

The effect of PD-L1 testing on the cost-effectiveness and economic impact of immune checkpoint inhibitors for the second-line treatment of NSCLC.

Science.gov (United States)

Aguiar, P N; Perry, L A; Penny-Dimri, J; Babiker, H; Tadokoro, H; de Mello, R A; Lopes, G L

2017-09-01

Immune checkpoint inhibitors improve outcomes compared with chemotherapy in lung cancer. Tumor PD-L1 receptor expression is being studied as a predictive biomarker. The objective of this study was to assess the cost-effectiveness and economic impact of second-line treatment with nivolumab, pembrolizumab, and atezolizumab with and without the use of PD-L1 testing for patient selection. We developed a decision-analytic model to determine the cost-effectiveness of PD-L1 assessment and second-line immunotherapy versus docetaxel. The model used outcomes data from randomized clinical trials (RCTs) and drug acquisition costs from the United States. Thereafter, we used epidemiologic data to estimate the economic impact of the treatment. We included four RCTs (2 with nivolumab, 1 with pembrolizumab, and 1 with atezolizumab). The incremental quality-adjusted life year (QALY) for nivolumab was 0.417 among squamous tumors and 0.287 among non-squamous tumors and the incremental cost-effectiveness ratio (ICER) were $155 605 and $187 685, respectively. The QALY gain in the base case for atezolizumab was 0.354 and the ICER was $215 802. Compared with treating all patients, the selection of patients by PD-L1 expression improved incremental QALY by up to 183% and decreased the ICER by up to 65%. Pembrolizumab was studied only in patients whose tumors expressed PD-L1. The QALY gain was 0.346 and the ICER was $98 421. Patient selection also reduced the budget impact of immunotherapy. The use of PD-L1 expression as a biomarker increases cost-effectiveness of immunotherapy but also diminishes the number of potential life-years saved. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Reactive glia promote development of CD103+ CD69+ CD8+ T-cells through programmed cell death-ligand 1 (PD-L1).

Science.gov (United States)

Prasad, Sujata; Hu, Shuxian; Sheng, Wen S; Chauhan, Priyanka; Lokensgard, James R

2018-06-01

Previous work from our laboratory has demonstrated in vivo persistence of CD103 + CD69 + brain resident memory CD8 + T-cells (bT RM ) following viral infection, and that the PD-1: PD-L1 pathway promotes development of these T RM cells within the brain. Although glial cells express low basal levels of PD-L1, its expression is upregulated upon IFN-γ-treatment, and they have been shown to modulate antiviral T-cell effector responses through the PD-1: PD-L1 pathway. We performed flow cytometric analysis of cells from co-cultures of mixed glia and CD8 + T-cells obtained from wild type mice to investigate the role of glial cells in the development of bT RM . In this study, we show that interactions between reactive glia and anti-CD3 Ab-stimulated CD8 + T-cells promote development of CD103 + CD69 + CD8 + T-cells through engagement of the PD-1: PD-L1 pathway. These studies used co-cultures of primary murine glial cells obtained from WT animals along with CD8 + T-cells obtained from either WT or PD-1 KO mice. We found that αCD3 Ab-stimulated CD8 + T-cells from WT animals increased expression of CD103 and CD69 when co-cultured with primary murine glial cells. In contrast, significantly reduced expression of CD103 and CD69 was observed using CD8 + T-cells from PD-1 KO mice. We also observed that reactive glia promoted high levels of CD127, a marker of memory precursor effector cells (MPEC), on CD69 + CD8 + T-cells, which promotes development of T RM cells. Interestingly, results obtained using T-cells from PD-1 KO animals showed significantly reduced expression of CD127 on CD69 + CD8 + cells. Additionally, blocking of glial PD-L1 resulted in decreased expression of CD103, along with reduced CD127 on CD69 + CD8 + T-cells. Taken together, these results demonstrate a role for activated glia in promoting development of bT RM through the PD-1: PD-L1 pathway. © 2018 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

Durable Clinical Benefit in Metastatic Renal Cell Carcinoma Patients Who Discontinue PD-1/PD-L1 Therapy for Immune-Related Adverse Events.

Science.gov (United States)

Martini, Dylan J; Hamieh, Lana; McKay, Rana R; Harshman, Lauren C; Brandao, Raphael; Norton, Craig K; Steinharter, John A; Krajewski, Katherine M; Gao, Xin; Schutz, Fabio A; McGregor, Bradley; Bossé, Dominick; Lalani, Aly-Khan A; De Velasco, Guillermo; Michaelson, M Dror; McDermott, David F; Choueiri, Toni K

2018-04-01

The current standard of care for treatment of metastatic renal cell carcinoma (mRCC) patients is PD-1/PD-L1 inhibitors until progression or toxicity. Here, we characterize the clinical outcomes for 19 mRCC patients who experienced an initial clinical response (any degree of tumor shrinkage), but after immune-related adverse events (irAE) discontinued all systemic therapy. Clinical baseline characteristics, outcomes, and survival data were collected. The primary endpoint was time to progression from the date of treatment cessation (TTP). Most patients had clear cell histology and received anti-PD-1/PD-L1 therapy as second-line or later treatment. Median time on PD-1/PD-L1 therapy was 5.5 months (range, 0.7-46.5) and median TTP was 18.4 months (95% CI, 4.7-54.3) per Kaplan-Meier estimation. The irAEs included arthropathies, ophthalmopathies, myositis, pneumonitis, and diarrhea. We demonstrate that 68.4% of patients ( n = 13) experienced durable clinical benefit off treatment (TTP of at least 6 months), with 36% ( n = 7) of patients remaining off subsequent treatment for over a year after their last dose of anti-PD-1/PD-L1. Three patients with tumor growth found in a follow-up visit, underwent subsequent surgical intervention, and remain off systemic treatment. Nine patients (47.4%) have ongoing irAEs. Our results show that patients who benefitted clinically from anti-PD-1/PD-L1 therapy can experience sustained beneficial responses, not needing further therapies after the initial discontinuation of treatment due to irAEs. Investigation of biomarkers indicating sustained benefit to checkpoint blockers are needed. Cancer Immunol Res; 6(4); 402-8. ©2018 AACR . ©2018 American Association for Cancer Research.

Circularly polarized harmonic generation by intense bicircular laser pulses: electron recollision dynamics and frequency dependent helicity

Science.gov (United States)

Bandrauk, André D.; Mauger, François; Yuan, Kai-Jun

2016-12-01

Numerical solutions of time-dependent Schrödinger equations for one and two electron cyclic molecules {{{H}}}nq+ exposed to intense bichromatic circularly polarized laser pulses of frequencies {ω }1 and {ω }2, such that {ω }1/{ω }2={n}1/{n}2 (integer) produce circularly polarized high order harmonics with a cut-off recollision maximum energy at and greater than the linear polarization law (in atomic units) {N}m{ω }1={I}p+3.17{U}p, where I p is the ionization potential and {U}p={(2{E}0)}2/4{ω }2 is the ponderomotive energy defined by the field E 0 (intensity I={{cE}}02/8π ) from each pulse and mean frequency ω =({ω }1+{ω }2)/2 . An electron recollision model in a rotating frame at rotating frequency {{Δ }}ω =({ω }1-{ω }2)/2 predicts this simple result as a result of recollision dynamics in a combination of bichromatic circularly polarized pulses. The harmonic helicities and their intensities are shown to depend on compatible symmetries of the net pulse electric fields with that of the molecules.

Quantum mechanical aspects of dynamical neutron polarization

International Nuclear Information System (INIS)

Betz, T.; Badurek, G.; Jericha, E.

2007-01-01

Dynamic Neutron Polarization (DNP) is a concept which allows to achieve complete polarization of slow neutrons, virtually without any loss of intensity. There the neutrons pass through a combination of a static and a rotating magnetic field in resonance, like in a standard NMR apparatus. Depending on their initial spin state, they end up with different kinetic energies and therefore different velocity. In a succeeding magnetic precession field this distinction causes a different total precession angle. Tuning the field strength can lead to a final state where two original anti-parallel spin states are aligned parallel and hence to polarization. The goal of this work is to describe the quantum mechanical aspects of DNP and to work out the differences to the semi-classical treatment. We show by quantum mechanical means, that the concept works and DNP is feasible, indeed. Therefore, we have to take a closer look to the behavior of neutron wave functions in magnetic fields. In the first Section we consider a monochromatic continuous beam. The more realistic case of a pulsed, polychromatic beam requires a time-dependent field configuration and will be treated in the second Section. In particular the spatial separation of the spin up- and down-states is considered, because it causes an effect of polarization damping so that one cannot achieve a fully polarized final state. This effect is not predicted by the semi-classical treatment of DNP. However, this reduction of polarization is very small and can be neglected in realistic DNP-setups

In vitro and in vivo antivirus activity of an anti-programmed death-ligand 1 (PD-L1 rat-bovine chimeric antibody against bovine leukemia virus infection.

Directory of Open Access Journals (Sweden)

Asami Nishimori

Full Text Available Programmed death-1 (PD-1, an immunoinhibitory receptor on T cells, is known to be involved in immune evasion through its binding to PD-ligand 1 (PD-L1 in many chronic diseases. We previously found that PD-L1 expression was upregulated in cattle infected with bovine leukemia virus (BLV and that an antibody that blocked the PD-1/PD-L1 interaction reactivated T-cell function in vitro. Therefore, this study assessed its antivirus activities in vivo. First, we inoculated the anti-bovine PD-L1 rat monoclonal antibody 4G12 into a BLV-infected cow. However, this did not induce T-cell proliferation or reduction of BLV provirus loads during the test period, and only bound to circulating IgM+ B cells until one week post-inoculation. We hypothesized that this lack of in vivo effects was due to its lower stability in cattle and so established an anti-PD-L1 rat-bovine chimeric antibody (Boch4G12. Boch4G12 was able to bind specifically with bovine PD-L1, interrupt the PD-1/PD-L1 interaction, and activate the immune response in both healthy and BLV-infected cattle in vitro. Therefore, we experimentally infected a healthy calf with BLV and inoculated it intravenously with 1 mg/kg of Boch4G12 once it reached the aleukemic (AL stage. Cultivation of peripheral blood mononuclear cells (PBMCs isolated from the tested calf indicated that the proliferation of CD4+ T cells was increased by Boch4G12 inoculation, while BLV provirus loads were significantly reduced, clearly demonstrating that this treatment induced antivirus activities. Therefore, further studies using a large number of animals are required to support its efficacy for clinical application.

Fractal structure of hadrons in processes with polarized protons at SPD NICA (proposal for experiment)

International Nuclear Information System (INIS)

Tokarev, M.V.; Aparin, A.A.; Zborovsky, I.

2014-01-01

The concept of z-scaling previously developed for analysis of inclusive reactions in proton-proton collisions is applied for description of processes with polarized protons at the planned Spin Physics Detector NICA in Dubna. A hypothesis of self-similarity and fractality of the proton spin structure is discussed. The possibilities to extract information on spin-dependent fractal dimensions of hadrons and fragmentation process from asymmetries and coefficients of polarization transfer are justified. The double longitudinal spin asymmetry A LL of π 0 -meson production and the coefficient of the polarization transfer D LL of Λ hyperon production in proton-proton collisions measured at RHIC are analyzed in the framework of z-scaling. The spin-dependent fractal dimensions of proton and fragmentation process with polarized Λ hyperon are estimated. A study of the spin-dependent constituent energy loss as a function of transverse momentum of the inclusive hadron and collision energy is suggested.

Polarization-dependent single-beam laser-induced grating-like effects on titanium films

International Nuclear Information System (INIS)

Camacho-Lopez, Santiago; Evans, Rodger; Escobar-Alarcon, Luis; Camacho-Lopez, Miguel A.; Camacho-Lopez, Marco A.

2008-01-01

In this paper we present results on polarization-dependent laser-induced effects on titanium (Ti) thin films. We irradiated the titanium films, in ambient air, using a nanosecond Nd:YAG laser (532 nm, 9 ns pulse duration, 10 Hz). Using a series of pulses of fluence well below the ablation threshold, it was possible to form grating-like structures, whose grooves run parallel to the linear polarization of the incident beam. No grating-like structures were obtained when circularly polarized light was used. Our results revealed the remarkable formation of tiny (100 nm and even smaller diameter) craters, which self-arrange quasi-periodically along the ridges (never on the valleys) of the grating-like structure. Optical and scanning electron microscopy were used to study the laser-induced changes on the surface of the titanium films. Micro-Raman spectroscopy was used to analyze the irradiated areas on the titanium films. The Raman analysis demonstrated that the grooves in the grating-like structure, build up from the laser-induced oxidation of titanium. This is the first time, to the best of our knowledge, that periodic surface structures are reported to be induced below the ablation threshold regime, with the grooves made of crystalline metal oxide, in this case TiO 2 in the well-known Rutile phase. The laser irradiated areas on the film acquired selective (upon recording polarization) holographic reflectance

Polarization-dependent single-beam laser-induced grating-like effects on titanium films

Energy Technology Data Exchange (ETDEWEB)

Camacho-Lopez, Santiago [Departamento de Optica, Centro de Investigacion Cientifica y de Educacion Superior de Ensenada, Km 107 Carretera Tijuana-Ensenada, Ensenada, Baja California 22860 (Mexico)], E-mail: camachol@cicese.mx; Evans, Rodger [Departamento de Optica, Centro de Investigacion Cientifica y de Educacion Superior de Ensenada, Km 107 Carretera Tijuana-Ensenada, Ensenada, Baja California 22860 (Mexico); Escobar-Alarcon, Luis [Departamento de Fisica, Instituto Nacional de Investigaciones Nucleares, Apdo. Postal 18-1027, Mexico DF 11801 (Mexico); Camacho-Lopez, Miguel A. [Facultad de Medicina, Universidad Autonoma del Estado de Mexico, Paseo Tollocan s/n, esq. Jesus Carranza, Toluca, Estado de Mexico 50120 (Mexico); Camacho-Lopez, Marco A. [Facultad de Quimica, Universidad Autonoma del Estado de Mexico, Tollocan s/n, esq. Paseo Colon, Toluca, Estado de Mexico, 50110 (Mexico)

2008-12-30

In this paper we present results on polarization-dependent laser-induced effects on titanium (Ti) thin films. We irradiated the titanium films, in ambient air, using a nanosecond Nd:YAG laser (532 nm, 9 ns pulse duration, 10 Hz). Using a series of pulses of fluence well below the ablation threshold, it was possible to form grating-like structures, whose grooves run parallel to the linear polarization of the incident beam. No grating-like structures were obtained when circularly polarized light was used. Our results revealed the remarkable formation of tiny (100 nm and even smaller diameter) craters, which self-arrange quasi-periodically along the ridges (never on the valleys) of the grating-like structure. Optical and scanning electron microscopy were used to study the laser-induced changes on the surface of the titanium films. Micro-Raman spectroscopy was used to analyze the irradiated areas on the titanium films. The Raman analysis demonstrated that the grooves in the grating-like structure, build up from the laser-induced oxidation of titanium. This is the first time, to the best of our knowledge, that periodic surface structures are reported to be induced below the ablation threshold regime, with the grooves made of crystalline metal oxide, in this case TiO{sub 2} in the well-known Rutile phase. The laser irradiated areas on the film acquired selective (upon recording polarization) holographic reflectance.

Variation in the response of an Arctic top predator experiencing habitat loss: feeding and reproductive ecology of two polar bear populations.

Science.gov (United States)

Rode, Karyn D; Regehr, Eric V; Douglas, David C; Durner, George; Derocher, Andrew E; Thiemann, Gregory W; Budge, Suzanne M

2014-01-01

Polar bears (Ursus maritimus) have experienced substantial changes in the seasonal availability of sea ice habitat in parts of their range, including the Beaufort, Chukchi, and Bering Seas. In this study, we compared the body size, condition, and recruitment of polar bears captured in the Chukchi and Bering Seas (CS) between two periods (1986-1994 and 2008-2011) when declines in sea ice habitat occurred. In addition, we compared metrics for the CS population 2008-2011 with those of the adjacent southern Beaufort Sea (SB) population where loss in sea ice habitat has been associated with declines in body condition, size, recruitment, and survival. We evaluated how variation in body condition and recruitment were related to feeding ecology. Comparing habitat conditions between populations, there were twice as many reduced ice days over continental shelf waters per year during 2008-2011 in the SB than in the CS. CS polar bears were larger and in better condition, and appeared to have higher reproduction than SB bears. Although SB and CS bears had similar diets, twice as many bears were fasting in spring in the SB than in the CS. Between 1986-1994 and 2008-2011, body size, condition, and recruitment indices in the CS were not reduced despite a 44-day increase in the number of reduced ice days. Bears in the CS exhibited large body size, good body condition, and high indices of recruitment compared to most other populations measured to date. Higher biological productivity and prey availability in the CS relative to the SB, and a shorter recent history of reduced sea ice habitat, may explain the maintenance of condition and recruitment of CS bears. Geographic differences in the response of polar bears to climate change are relevant to range-wide forecasts for this and other ice-dependent species. © 2013 John Wiley & Sons Ltd.

Variation in the response of an Arctic top predator experiencing habitat loss: Feeding and reproductive ecology of two polar bear populations

Science.gov (United States)

Rode, Karyn D.; Regehr, Eric V.; Douglas, David C.; Durner, George M.; Derocher, Andrew E.; Thiemann, Gregory W.; Budge, Suzanne M.

2014-01-01

Polar bears (Ursus maritimus) have experienced substantial changes in the seasonal availability of sea ice habitat in parts of their range, including the Beaufort, Chukchi, and Bering Seas. In this study, we compared the body size, condition, and recruitment of polar bears captured in the Chukchi and Bering Seas (CS) between two periods (1986–1994 and 2008–2011) when declines in sea ice habitat occurred. In addition, we compared metrics for the CS population 2008–2011 with those of the adjacent southern Beaufort Sea (SB) population where loss in sea ice habitat has been associated with declines in body condition, size, recruitment, and survival. We evaluated how variation in body condition and recruitment were related to feeding ecology. Comparing habitat conditions between populations, there were twice as many reduced ice days over continental shelf waters per year during 2008–2011 in the SB than in the CS. CS polar bears were larger and in better condition, and appeared to have higher reproduction than SB bears. Although SB and CS bears had similar diets, twice as many bears were fasting in spring in the SB than in the CS. Between 1986–1994 and 2008–2011, body size, condition, and recruitment indices in the CS were not reduced despite a 44-day increase in the number of reduced ice days. Bears in the CS exhibited large body size, good body condition, and high indices of recruitment compared to most other populations measured to date. Higher biological productivity and prey availability in the CS relative to the SB, and a shorter recent history of reduced sea ice habitat, may explain the maintenance of condition and recruitment of CS bears. Geographic differences in the response of polar bears to climate change are relevant to range-wide forecasts for this and other ice-dependent species.

Polarization-dependent Character of 1x3 Beam Splitter Using Self-Imaging Phenomena in Air-Slab PhCW

DEFF Research Database (Denmark)

Zhang, Min; Malureanu, Radu; Kristensen, Martin

2010-01-01

A 1x3 beam splitter in PhCWs using multi-mode interference (MMI) based on self-imaging principle is investigated. The 1x3 splitter is polarization-dependent. The total TE-polarized transmission of the 1x3 splitter is almost equal to the corresponding length of W1 PhCW. The TE-polarized input power...... is distributed equally be-tween the output ports within 1dB from 1541nm to 1552nm....

Survival and breeding of polar bears in the southern Beaufort Sea in relation to sea ice.

Science.gov (United States)

Regehr, Eric V; Hunter, Christine M; Caswell, Hal; Amstrup, Steven C; Stirling, Ian

2010-01-01

1. Observed and predicted declines in Arctic sea ice have raised concerns about marine mammals. In May 2008, the US Fish and Wildlife Service listed polar bears (Ursus maritimus) - one of the most ice-dependent marine mammals - as threatened under the US Endangered Species Act. 2. We evaluated the effects of sea ice conditions on vital rates (survival and breeding probabilities) for polar bears in the southern Beaufort Sea. Although sea ice declines in this and other regions of the polar basin have been among the greatest in the Arctic, to date population-level effects of sea ice loss on polar bears have only been identified in western Hudson Bay, near the southern limit of the species' range. 3. We estimated vital rates using multistate capture-recapture models that classified individuals by sex, age and reproductive category. We used multimodel inference to evaluate a range of statistical models, all of which were structurally based on the polar bear life cycle. We estimated parameters by model averaging, and developed a parametric bootstrap procedure to quantify parameter uncertainty. 4. In the most supported models, polar bear survival declined with an increasing number of days per year that waters over the continental shelf were ice free. In 2001-2003, the ice-free period was relatively short (mean 101 days) and adult female survival was high (0.96-0.99, depending on reproductive state). In 2004 and 2005, the ice-free period was longer (mean 135 days) and adult female survival was low (0.73-0.79, depending on reproductive state). Breeding rates and cub litter survival also declined with increasing duration of the ice-free period. Confidence intervals on vital rate estimates were wide. 5. The effects of sea ice loss on polar bears in the southern Beaufort Sea may apply to polar bear populations in other portions of the polar basin that have similar sea ice dynamics and have experienced similar, or more severe, sea ice declines. Our findings therefore are

SDF-1/CXCR4 expression in bladder cancer tissue and the correlation with negative costimulatory molecule PD-L1, cell apoptosis and invasion

Directory of Open Access Journals (Sweden)

Ming-Bao Ye

2017-06-01

Full Text Available Objective: To study the SDF-1/CXCR4 expression in bladder cancer tissue and the correlation with negative costimulatory molecule PD-L1, cell apoptosis and invasion. Methods: A total of 118 cases of bladder cancer tissue and para-carcinoma tissue surgically removed in our hospital between May 2014 and May 2016 were selected as the research samples, the RNA was extracted and then reverse-transcribed into cDNA, and the expression levels of SDF-1/ CXCR4, PD-L1/PD-1, cell apoptosis-related molecules and cell invasion-related molecules were detected. Results: SDF-1 and CXCR4 mRNA expression in bladder cancer tissue were significantly higher than those in para-carcinoma tissue; PD-L1, PD-1, Rec1, Survivin, MRPS5, Nanog, BCAPP2Ac, TRPM8, TRPV2, ILK, β-catenin and GUGBP1 mRNA expression in bladder cancer tissue were significantly higher than those in para-carcinoma tissue and positively correlated with SDF-1 and CXCR4 mRNA expression. Conclusion: Highly expressed SDF-1/CXCR4 in bladder cancer tissue are closely related to the high expression of negative costimulatory molecule PD-L1, pro-proliferation molecules and proinvasion molecules, and SDF-1/CXCR4 can promote the immune escape, proliferation and invasion of bladder cancer cells.

Surface waves at the interface with an antisymmetric gain/loss profile

International Nuclear Information System (INIS)

Ctyroky, Jiri; Kuzmiak, Vladimir; Eyderman, Sergey

2010-01-01

We studied properties of strongly guiding two-mode waveguides with antisymmetric gain/loss profile which constitute photonic analogues of quantum mechanical structures with parity-time symmetry breaking. For both TE and TM polarizations, the dependences of effective indices of the guided modes vs. gain/loss coefficient exhibit a degenerate critical point that defines two regimes with profoundly different behavior. In addition, we have shown that the interface between the two media supports propagation of a strongly confined non-attenuated TM polarized surface wave. We examined the properties of the surface wave obtained by both the modal and FDTD method and discuss the differences between the results obtained by both techniques as both the material and geometrical parameters are varied.

Polarization-Dependent Measurements of Molecular Super Rotors with Oriented Angular Momenta

Science.gov (United States)

Murray, Matthew J.; Toro, Carlos; Liu, Qingnan; Mullin, Amy S.

2014-05-01

Controlling molecular motion would enable manipulation of energy flow between molecules. Here we have used an optical centrifuge to investigate energy transfer between molecular super rotors with oriented angular momenta. The polarizable electron cloud of the molecules interacts with the electric field of linearly polarized light that angularly accelerates over the time of the optical pulse. This process drives molecules into high angular momentum states that are oriented with the optical field and have energies far from equilibrium. High resolution transient IR spectroscopy reveals the dynamics of collisional energy transfer for these super excited rotors. The results of this study leads to a more fundamental understanding of energy balance in non-equilibrium environments and the physical and chemical properties of gases in a new regime of energy states. Results will be presented for several super rotor species including carbon monoxide, carbon dioxide, and acetylene. Polarization-dependent measurements reveal the extent to which the super rotors maintain spatial orientation of high angular momentum states.

Fine-Scale Layering of Mars Polar Deposits and Signatures of Ice Content in Nonpolar Material From Multiband SHARAD Data Processing

Science.gov (United States)

Campbell, Bruce A.; Morgan, Gareth A.

2018-02-01

The variation of Shallow Radar (SHARAD) echo strength with frequency reveals material dielectric losses and polar layer properties. Loss tangents for Elysium and Amazonis Planitiae deposits are consistent with volcanic flows and sediments, while the Medusae Fossae Formation, lineated valley fill, and lobate debris aprons have low losses consistent with a major component of water ice. Mantling materials in Arcadia and Utopia Planitiae have higher losses, suggesting they are not dominated by ice over large fractions of their thickness. In Gemina Lingula, there are frequent deviations from a simple dependence of loss on depth. Within reflector packets, the brightest reflectors are often different among the frequency subbands, and there are cases of reflectors that occur in only the high- or low-frequency echoes. Many polar radar reflections must arise from multiple thin interfaces, or single deposits of appropriate thickness, that display resonant scattering behaviors. Reflector properties may be linked to climate-controlled polar dust deposition.

Polarization-dependent Imaging Contrast (PIC) mapping reveals nanocrystal orientation patterns in carbonate biominerals

Energy Technology Data Exchange (ETDEWEB)

Gilbert, Pupa U.P.A., E-mail: pupa@physics.wisc.edu [University of Wisconsin-Madison, Departments of Physics and Chemistry, Madison, WI 53706 (United States)

2012-10-15

Highlights: Black-Right-Pointing-Pointer Nanocrystal orientation shown by Polarization-dependent Imaging Contrast (PIC) maps. Black-Right-Pointing-Pointer PIC-mapping of carbonate biominerals reveals their ultrastructure at the nanoscale. Black-Right-Pointing-Pointer The formation mechanisms of biominerals is discovered by PIC-mapping using PEEM. -- Abstract: Carbonate biominerals are one of the most interesting systems a physicist can study. They play a major role in the CO{sub 2} cycle, they master templation, self-assembly, nanofabrication, phase transitions, space filling, crystal nucleation and growth mechanisms. A new imaging modality was introduced in the last 5 years that enables direct observation of the orientation of carbonate single crystals, at the nano- and micro-scale. This is Polarization-dependent Imaging Contrast (PIC) mapping, which is based on X-ray linear dichroism, and uses PhotoElectron Emission spectroMicroscopy (PEEM). Here we present PIC-mapping results from biominerals, including the nacre and prismatic layers of mollusk shells, and sea urchin teeth. We describe various PIC-mapping approaches, and show that these lead to fundamental discoveries on the formation mechanisms of biominerals.

Resilience and risk: a demographic model to inform conservation planning for polar bears

Science.gov (United States)

Regehr, Eric V.; Wilson, Ryan R.; Rode, Karyn D.; Runge, Michael C.

2015-01-01

Climate change is having widespread ecological effects, including loss of Arctic sea ice. This has led to listing of the polar bear (Ursus maritimus) and other ice-dependent marine mammals under the U.S. Endangered Species Act (ESA). Methods are needed to evaluate the effects of climate change on population persistence to inform recovery planning for listed species. For polar bears, this includes understanding interactions between climate and secondary factors, such as subsistence harvest, which provide economic, nutritional, or cultural value to humans.

Multiport optical circulator by using polarizing beam splitter cubes as spatial walk-off polarizers.

Science.gov (United States)

Chen, Jing-Heng; Chen, Kun-Huang; Lin, Jiun-You; Hsieh, Hsiang-Yung

2010-03-10

Optical circulators are necessary passive devices applied in optical communication systems. In the design of optical circulators, the implementation of the function of spatial walk-off polarizers is a key technique that significantly influences the performance and cost of a device. This paper proposes a design of a multiport optical circulator by using polarizing beam splitter cubes as spatial walk-off polarizers. To show the feasibility of the design, a prototype of a six-port optical circulator was fabricated. The insertion losses are 0.94-1.49 dB, the isolations are 25-51 dB, and return losses are 27.72 dB.

The molecular orientation of CO on Pd(1 1 1): a polarization-dependent SFG study

Science.gov (United States)

Galletto, Paolo; Unterhalt, Holger; Rupprechter, Günther

2003-01-01

The molecular orientation of carbon monoxide adsorbed on Pd(1 1 1) was examined by sum frequency generation (SFG) vibrational spectroscopy utilizing different polarization combinations of the visible and SFG light. This allows to determine the CO tilt angle with respect to the substrate, provided that a proper optical model for the interface can be defined. It is demonstrated that it is essential to invoke the βaac hyperpolarizability into the analysis and that polarization-dependent SFG of CO/Pd(1 1 1) yields information on βaac/ βccc rather than the tilt angle.

Immune-Related Adverse Events Associated with Anti-PD-1/PD-L1 Treatment for Malignancies: A Meta-Analysis

Directory of Open Access Journals (Sweden)

Peng-Fei Wang

2017-10-01

Full Text Available Background: Treatment of cancers with programmed cell death protein 1 (PD-1 pathway inhibitors can lead to immune-related adverse events (irAEs, which could be serious and even fetal. Therefore, clinicians should be aware of the characteristics of irAEs associated with the use of such drugs.Methods: The MEDLINE, EMBASE, and Cochrane databases were searched to find potential studies using the following strategies: anti-PD-1/PD-L1 treatment; irAEs; and cancer. R© package Meta was used to pool incidence.Results: Forty-six studies representing 12,808 oncologic patients treated with anti-PD-1/PD-L1 agents were included in the meta-analysis. The anti-PD-1/PD-L1 agents included nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, and BMS-936559. The tumor types were melanomas, Hodgkin lymphomas, urothelial carcinomas, breast cancers, non-small cell lung cancers, renal cell carcinomas (RCC, colorectal cancers, and others. We described irAEs according to organ systems, namely, the skin (pruritus, rash, maculopapular rash, vitiligo, and dermatitis, endocrine system (hypothyroidism, hyperthyroidism, hypophysitis, thyroiditis, and adrenal insufficiency, digestive system (colitis, diarrhea, pancreatitis, and increased AST/ALT/bilirubin, respiratory system (pneumonitis, lung infiltration, and interstitial lung disease, and urinary system (increased creatinine, nephritis, and renal failure. In patients treated with the PD-1 signaling inhibitors, the overall incidence of irAEs was 26.82% (95% CI, 21.73–32.61; I2, 92.80 in any grade and 6.10% (95% CI, 4.85–7.64; I2, 52.00 in severe grade, respectively. The development of irAEs was unrelated to the dose of anti-PD-1/PD-L1 agents. The incidence of particular irAEs varied when different cancers were treated with different drugs. The incidence of death due to irAEs was around 0.17%.Conclusion: The occurrence of irAEs was organ-specific and related to drug and tumor types.

CEA/CD3-bispecific T cell-engaging (BiTE) antibody-mediated T lymphocyte cytotoxicity maximized by inhibition of both PD1 and PD-L1.

Science.gov (United States)

Osada, Takuya; Patel, Sandip P; Hammond, Scott A; Osada, Koya; Morse, Michael A; Lyerly, H Kim

2015-06-01

Bispecific T cell-engaging (BiTE) antibodies recruit polyclonal cytotoxic T cells (CTL) to tumors. One such antibody is carcinoembryonic antigen (CEA) BiTE that mediates T cell/tumor interaction by simultaneously binding CD3 expressed by T cells and CEA expressed by tumor cells. A widely operative mechanism for mitigating cytotoxic T cell-mediated killing is the interaction of tumor-expressed PD-L1 with T cell-expressed PD-1, which may be partly reversed by PD-1/PD-L1 blockade. We hypothesized that PD-1/PD-L1 blockade during BiTE-mediated T cell killing would enhance CTL function. Here, we determined the effects of PD-1 and PD-L1 blockade during initial T cell-mediated killing of CEA-expressing human tumor cell lines in vitro, as well as subsequent T cell-mediated killing by T lymphocytes that had participated in tumor cell killing. We observed a rapid upregulation of PD-1 expression and diminished cytolytic function of T cells after they had engaged in CEA BiTE-mediated killing of tumors. T cell cytolytic activity in vitro could be maximized by administration of anti-PD-1 or anti-PD-L1 antibodies alone or in combination if applied prior to a round of T cell killing, but T cell inhibition could not be fully reversed by this blockade once the T cells had killed tumor. In conclusion, our findings demonstrate that dual blockade of PD-1 and PD-L1 maximizes T cell killing of tumor directed by CEA BiTE in vitro, is more effective if applied early, and provides a rationale for clinical use.

Polarization at SLC

International Nuclear Information System (INIS)

Swartz, M.L.

1988-07-01

The SLAC Linear Collider has been designed to readily accommodate polarized electron beams. Considerable effort has been made to implement a polarized source, a spin rotation system, and a system to monitor the beam polarization. Nearly all major components have been fabricated. At the current time, several source and polarimeter components have been installed. The installation and commissioning of the entire system will take place during available machine shutdown periods as the commissioning of SLC progresses. It is expected that a beam polarization of 45% will be achieved with no loss in luminosity. 13 refs., 15 figs

Efficient propagation of TM polarized light in photonic crystal components exhibiting band gaps for TE polarized light

DEFF Research Database (Denmark)

Borel, Peter Ingo; Frandsen, Lars Hagedorn; Thorhauge, Morten

2003-01-01

We have investigated the properties of TM polarized light in planar photonic crystal waveguide structures, which exhibit photonic band gaps for TE polarized light. Straight and bent photonic crystal waveguides and couplers have been fabricated in silicon-on-insulator material and modelled using a 3......D finite-difference-time-domain method. The simulated spectra are in excellent agreement with the experimental results, which show a propagation loss as low as 2.5±4 dB/mm around 1525 nm and bend losses at 2.9±0.2 dB for TM polarized light. We demonstrate a high coupling for TM polarized light...

Barrier heights, polarization switching, and electrical fatigue in Pb(Zr,Ti)O3 ceramics with different electrodes

Science.gov (United States)

Chen, Feng; Schafranek, Robert; Wachau, André; Zhukov, Sergey; Glaum, Julia; Granzow, Torsten; von Seggern, Heinz; Klein, Andreas

2010-11-01

The influence of Pt, tin-doped In2O3, and RuO2 electrodes on the electrical fatigue of bulk ceramic Pb(Zr,Ti)O3 (PZT) has been studied. Schottky barrier heights at the ferroelectric/electrode interfaces vary by more than one electronvolt for different electrode materials and do not depend on crystallographic orientation of the interface. Despite different barrier heights, hysteresis loops of polarization, strain, permittivity, and piezoelectric constant and the switching kinetics are identical for all electrodes. A 20% reduction in polarization after 106 bipolar cycles is observed for all the samples. In contrast to PZT thin films, the loss of remanent polarization with bipolar switching cycles does not significantly depend on the electrode material.

Polarization Effects at a Muon Collider

International Nuclear Information System (INIS)

Parsa, Z.

1998-01-01

For Muon Colliders, Polarization will be a useful tool if high polarization is achievable with little luminosity loss. Formulation and effects of beam polarization and luminosity including polarization effects in Higgs resonance studies are discussed for improving precision measurements and Higgs resonance ''discovery'' capability e.g. at the First Muon Collider (FMC)

Electromagnetic ion cyclotron waves observed in the plasma depletion layer

Science.gov (United States)

Anderson, B. J.; Fuselier, S. A.; Murr, D.

1991-01-01

Observations from AMPTE/CCE in the earth's magnetosheath on October 5, 1984 are presented to illustrate 0.1 - 4.0 Hz magnetic field pulsations in the subsolar plasma depletion layer (PDL) for northward sheath field during a magnetospheric compression. The PDL is unambiguously identified by comparing CCE data with data from IRM in the upstream solar wind. Pulsations in the PDL are dominated by transverse waves with F/F(H+) 1.0 or less and a slot in spectral power at F/F(H+) = 0.5. The upper branch is left hand polarized while the lower branch is linearly polarized. In the sheath the proton temperature anisotropy is about 0.6 but it is about 1.7 in the PDL during wave occurrence. The properties and correlation of waves with increased anisotropy indicate that they are electromagnetic ion cyclotron waves.

Globo H expression is associated with driver mutations and PD-L1 expressions in stage I non-small cell lung cancer.

Science.gov (United States)

Yang, Ching-Yao; Lin, Mong-Wei; Chang, Yih-Leong; Wu, Chen-Tu

2017-12-12

Globo H is a tumor-associated carbohydrate antigen exclusively expressed in cancer cells rather than normal tissue. Globo H has been found on many cancers of epithelial origins, and become an attractive target for cancer vaccine. We aimed to study the expression of Globo H in non-small cell lung cancer (NSCLC) patients, and correlated its expression with common driver mutations, clinical outcomes, and status of immune checkpoint, programmed death-ligand 1 (PD-L1). The study enrolled 228 patients with surgically resected stage I NSCLC, including 139 patients with adenocarcinoma (ADC) and 89 patients with squamous cell carcinoma (SqCC). Using immunohistochemistry, tumors with moderate to strong membranous staining in ⩾ 1% tumor cells per section were scored as positive Globo H expression. Driver mutations including EGFR, KRAS, BRAF were detected by direct sequencing, while ALK, PI3KCA, FGFR1 and PD-L1 expression was detected by immunohistochemical (IHC) staining. Positive Globo H expression was detected in 88 of the 228 (38.6%) patients. These included 51 of 139 (36.7%) patients with ADC and 37 of 89 (41.6%) patients with SqCC. Positive Globo H expression was significantly associated with EGFR mutation and PD-L1 expression in the ADC group, and PI3KCA overexpression in the SqCC group. The survival analysis showed that Globo H expression was not an independent prognostic factor in stage I NSCLC. Globo H expression was correlated with specific driver mutations in ADC and SqCC NSCLC tumors, as well as PD-L1 status. Immunotherapy targeting Globo H may have potential application in lung cancer treatment.

Thickness, humidity, and polarization dependent ferroelectric switching and conductivity in Mg doped lithium niobate

Energy Technology Data Exchange (ETDEWEB)

Neumayer, Sabine M.; Rodriguez, Brian J., E-mail: brian.rodriguez@ucd.ie [School of Physics, University College Dublin, Belfield, Dublin 4 (Ireland); Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4 (Ireland); Strelcov, Evgheni; Kravchenko, Ivan I.; Kalinin, Sergei V. [Center for Nanophase Materials Sciences, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 (United States); Manzo, Michele; Gallo, Katia [Department of Applied Physics, KTH - Royal Institute of Technology, Roslagstullbacken 21, 10691 Stockholm (Sweden); Kholkin, Andrei L. [Department of Physics and CICECO-Aveiro Institute of Materials, 3810-193 Aveiro, Portugal and Institute of Natural Sciences, Ural Federal University, 620000 Ekaterinburg (Russian Federation)

2015-12-28

Mg doped lithium niobate (Mg:LN) exhibits several advantages over undoped LN such as resistance to photorefraction, lower coercive fields, and p-type conductivity that is particularly pronounced at domain walls and opens up a range of applications, e.g., in domain wall electronics. Engineering of precise domain patterns necessitates well founded knowledge of switching kinetics, which can differ significantly from that of undoped LN. In this work, the role of humidity and sample composition in polarization reversal has been investigated under application of the same voltage waveform. Control over domain sizes has been achieved by varying the sample thickness and initial polarization as well as atmospheric conditions. In addition, local introduction of proton exchanged phases allows for inhibition of domain nucleation or destabilization, which can be utilized to modify domain patterns. Polarization dependent current flow, attributed to charged domain walls and band bending, demonstrates the rectifying ability of Mg:LN in combination with suitable metal electrodes that allow for further tailoring of conductivity.

Thickness, humidity, and polarization dependent ferroelectric switching and conductivity in Mg doped lithium niobate

International Nuclear Information System (INIS)

Neumayer, Sabine M.; Rodriguez, Brian J.; Strelcov, Evgheni; Kravchenko, Ivan I.; Kalinin, Sergei V.; Manzo, Michele; Gallo, Katia; Kholkin, Andrei L.

2015-01-01

Mg doped lithium niobate (Mg:LN) exhibits several advantages over undoped LN such as resistance to photorefraction, lower coercive fields, and p-type conductivity that is particularly pronounced at domain walls and opens up a range of applications, e.g., in domain wall electronics. Engineering of precise domain patterns necessitates well founded knowledge of switching kinetics, which can differ significantly from that of undoped LN. In this work, the role of humidity and sample composition in polarization reversal has been investigated under application of the same voltage waveform. Control over domain sizes has been achieved by varying the sample thickness and initial polarization as well as atmospheric conditions. In addition, local introduction of proton exchanged phases allows for inhibition of domain nucleation or destabilization, which can be utilized to modify domain patterns. Polarization dependent current flow, attributed to charged domain walls and band bending, demonstrates the rectifying ability of Mg:LN in combination with suitable metal electrodes that allow for further tailoring of conductivity

Cocaine dependent individuals discount future rewards more than future losses for both cocaine and monetary outcomes.

Science.gov (United States)

Johnson, Matthew W; Bruner, Natalie R; Johnson, Patrick S

2015-01-01

Cocaine dependence and other forms of drug dependence are associated with steeper devaluation of future outcomes (delay discounting). Although studies in this domain have typically assessed choices between monetary gains (e.g., receive less money now versus receive more money after a delay), delay discounting is also applicable to decisions involving losses (e.g., small loss now versus larger delayed loss), with gains typically discounted more than losses (the "sign effect"). It is also known that drugs are discounted more than equivalently valued money. In the context of drug dependence, however, relatively little is known about the discounting of delayed monetary and drug losses and the presence of the sign effect. In this within-subject, laboratory study, delay discounting for gains and losses was assessed for cocaine and money outcomes in cocaine-dependent individuals (n=89). Both cocaine and monetary gains were discounted at significantly greater rates than cocaine and monetary losses, respectively (i.e., the sign effect). Cocaine gains were discounted significantly more than monetary gains, but cocaine and monetary losses were discounted similarly. Results suggest that cocaine is discounted by cocaine-dependent individuals in a systematic manner similar to other rewards. Because the sign effect was shown for both cocaine and money, delayed aversive outcomes may generally have greater impact than delayed rewards in shaping present behavior in this population. Copyright © 2014. Published by Elsevier Ltd.

Polarized proton beams

International Nuclear Information System (INIS)

Roser, T.

1995-01-01

The acceleration of polarized proton beams in circular accelerators is complicated by the presence of numerous depolarizing spin resonances. Careful and tedious minimization of polarization loss at each of these resonances allowed acceleration of polarized proton beams up to 22 GeV. It has been the hope that Siberian Snakes, which are local spin rotators inserted into ring accelerators, would eliminate these resonances and allow acceleration of polarized beams with the same ease and efficiency that is now routine for unpolarized beams. First tests at IUCF with a full Siberian Snake showed that the spin dynamics with a Snake can be understood in detail. The author now has results of the first tests of a partial Siberian Snake at the AGS, accelerating polarized protons to an energy of about 25 GeV. These successful tests of storage and acceleration of polarized proton beams open up new possibilities such as stored polarized beams for internal target experiments and high energy polarized proton colliders

Antibody-dependent cellular cytotoxicity (ADCC) activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells

OpenAIRE

Boyerinas, Benjamin; Jochems, Caroline; Fantini, Massimo; Heery, Christopher R.; Gulley, James L.; Tsang, Kwong Yok; Schlom, Jeffrey

2015-01-01

Several anti-PD1/PD-L1 monoclonal antibodies (MAb) are currently providing evidence of clinical benefit in subsets of cancer patients. The mode of action of these MAbs is to inhibit PD1 on immune cells interacting with PD-L1 on tumor cells. These MAbs are either designed or engineered to eliminate antibody-dependent cell-mediated cytotoxicity (ADCC), which, however, has been implicated as an important mechanism in several highly effective MAb-mediated cancer therapies. A fully human anti-PD-L...

Polarization-dependent NEXAFS study of adsorption of long-chain surfactants on mechanically milled iron powder

Energy Technology Data Exchange (ETDEWEB)

Syugaev, A.V., E-mail: syual@mail.ru; Maratkanova, A.N.

2014-08-15

Highlights: • Plate-like particles modified with surfactant molecules were obtained under high-energy ball milling. • Adsorption layers were studied with polarization-dependent NEXAFS spectroscopy. • For the first time, arrangement of surfactants molecules on the powdered metal surface has been determined. • Tails of surfactant molecules (C-F/C-H) are shown to be oriented perpendicular to the particle surface. • Arrangement of carboxylate groups on the particle surfaces is discussed. - Abstract: In this work we have demonstrated the possibility of using the polarization-dependent NEXAFS spectra to study the structure of organic layers at the surface of powdered materials with plate-like shaped particles. The polarization dependence of the NEXAFS spectra may be easily obtained by just changing the angle between the X-ray beam direction and the substrate onto which the powder particles are set. For the first time, we have carried out a detailed study of the surfactant layers (n-perfluorononanoic and stearic acid), which are formed at the surface of iron plate-like particles under mechanical milling of iron powder with an addition of corresponding surfactants. The surfactant molecules are predominantly oriented perpendicular to the surface of the mechanically milled particles. Such orientation is similar to the arrangement of the molecules in the layers formed under equilibrium conditions, e.g. deposition from solutions. The changes in the chemical environment occurring in the molecule tails (defluorination or dehydrogenation) under mechanochemical treatment, do not result in a significant change in the molecular orientation and disordering of the adsorbed layer.

Context dependency and saturating effects of loss of rare soil microbes on plant productivity

Directory of Open Access Journals (Sweden)

Gera eHol

2015-06-01

Full Text Available Land use intensification is associated with loss of biodiversity and altered ecosystem functioning. Until now most studies on the relationship between biodiversity and ecosystem functioning focused on random loss of species, while loss of rare species that usually are the first to disappear received less attention. Here we test if the effect of rare microbial species loss on plant productivity depends on the origin of the microbial soil community. Soils were sampled from three land use types at two farms. Microbial communities with increasing loss of rare species were created by inoculating sterilized soils with serially diluted soil suspensions. After 8 months of incubation, the effects of the different soil communities on abiotic soil properties, soil processes, microbial community composition and plant productivity was measured. Dilution treatments resulted in increasing species loss, which was in relation to abundance of bacteria in the original field soil, without affecting most of the other soil parameters and processes. Microbial species loss affected plant biomass positively, negatively or not at all, depending on soil origin, but not on land use history. Even within fields the effects of dilution on plant biomass varied between replicates, suggesting heterogeneity in microbial community composition. The effects of medium and severe species loss on plant biomass were similar, pointing towards a saturating effect of species loss. We conclude that changes in the composition of the soil microbial community, including rare species loss, can affect plant productivity, depending on the composition of the initial microbial community. Future work on the relation between function and species loss effects should address this variation by including multiple sampling origins.

Context dependency and saturating effects of loss of rare soil microbes on plant productivity.

Science.gov (United States)

Hol, W H Gera; de Boer, Wietse; de Hollander, Mattias; Kuramae, Eiko E; Meisner, Annelein; van der Putten, Wim H

2015-01-01

Land use intensification is associated with loss of biodiversity and altered ecosystem functioning. Until now most studies on the relationship between biodiversity and ecosystem functioning focused on random loss of species, while loss of rare species that usually are the first to disappear received less attention. Here we test if the effect of rare microbial species loss on plant productivity depends on the origin of the microbial soil community. Soils were sampled from three land use types at two farms. Microbial communities with increasing loss of rare species were created by inoculating sterilized soils with serially diluted soil suspensions. After 8 months of incubation, the effects of the different soil communities on abiotic soil properties, soil processes, microbial community composition, and plant productivity was measured. Dilution treatments resulted in increasing species loss, which was in relation to abundance of bacteria in the original field soil, without affecting most of the other soil parameters and processes. Microbial species loss affected plant biomass positively, negatively or not at all, depending on soil origin, but not on land use history. Even within fields the effects of dilution on plant biomass varied between replicates, suggesting heterogeneity in microbial community composition. The effects of medium and severe species loss on plant biomass were similar, pointing toward a saturating effect of species loss. We conclude that changes in the composition of the soil microbial community, including rare species loss, can affect plant productivity, depending on the composition of the initial microbial community. Future work on the relation between function and species loss effects should address this variation by including multiple sampling origins.

Spin-polarized hydrogen Rydberg time-of-flight: Experimental measurement of the velocity-dependent H atom spin-polarization

International Nuclear Information System (INIS)

Broderick, Bernadette M.; Lee, Yumin; Doyle, Michael B.; Chernyak, Vladimir Y.; Suits, Arthur G.; Vasyutinskii, Oleg S.

2014-01-01

We have developed a new experimental method allowing direct detection of the velocity dependent spin-polarization of hydrogen atoms produced in photodissociation. The technique, which is a variation on the H atom Rydberg time-of-flight method, employs a double-resonance excitation scheme and experimental geometry that yields the two coherent orientation parameters as a function of recoil speed for scattering perpendicular to the laser propagation direction. The approach, apparatus, and optical layout we employ are described here in detail and demonstrated in application to HBr and DBr photolysis at 213 nm. We also discuss the theoretical foundation for the approach, as well as the resolution and sensitivity we achieve

Epithelial cell polarity, stem cells and cancer

DEFF Research Database (Denmark)

Martin-Belmonte, Fernando; Perez-Moreno, Mirna

2011-01-01

, deregulation of adhesion and polarity proteins can cause misoriented cell divisions and increased self-renewal of adult epithelial stem cells. In this Review, we highlight some advances in the understanding of how loss of epithelial cell polarity contributes to tumorigenesis.......After years of extensive scientific discovery much has been learned about the networks that regulate epithelial homeostasis. Loss of expression or functional activity of cell adhesion and cell polarity proteins (including the PAR, crumbs (CRB) and scribble (SCRIB) complexes) is intricately related...

Charge transport in non-polar and semi-polar III-V nitride heterostructures

International Nuclear Information System (INIS)

Konar, Aniruddha; Verma, Amit; Fang, Tian; Zhao, Pei; Jana, Raj; Jena, Debdeep

2012-01-01

Compared to the intense research focus on the optical properties, the transport properties in non-polar and semi-polar III-nitride semiconductors remain relatively unexplored to date. The purpose of this paper is to discuss charge-transport properties in non-polar and semi-polar orientations of GaN in a comparative fashion to what is known for transport in polar orientations. A comprehensive approach is adopted, starting from an investigation of the differences in the electronic bandstructure along different polar orientations of GaN. The polarization fields along various orientations are then discussed, followed by the low-field electron and hole mobilities. A number of scattering mechanisms that are specific to non-polar and semi-polar GaN heterostructures are identified, and their effects are evaluated. Many of these scattering mechanisms originate due to the coupling of polarization with disorder and defects in various incarnations depending on the crystal orientation. The effect of polarization orientation on carrier injection into quantum-well light-emitting diodes is discussed. This paper ends with a discussion of orientation-dependent high-field charge-transport properties including velocity saturation, instabilities and tunneling transport. Possible open problems and opportunities are also discussed. (paper)

The Black Queen Hypothesis: evolution of dependencies through adaptive gene loss.

Science.gov (United States)

Morris, J Jeffrey; Lenski, Richard E; Zinser, Erik R

2012-01-01

Reductive genomic evolution, driven by genetic drift, is common in endosymbiotic bacteria. Genome reduction is less common in free-living organisms, but it has occurred in the numerically dominant open-ocean bacterioplankton Prochlorococcus and "Candidatus Pelagibacter," and in these cases the reduction appears to be driven by natural selection rather than drift. Gene loss in free-living organisms may leave them dependent on cooccurring microbes for lost metabolic functions. We present the Black Queen Hypothesis (BQH), a novel theory of reductive evolution that explains how selection leads to such dependencies; its name refers to the queen of spades in the game Hearts, where the usual strategy is to avoid taking this card. Gene loss can provide a selective advantage by conserving an organism's limiting resources, provided the gene's function is dispensable. Many vital genetic functions are leaky, thereby unavoidably producing public goods that are available to the entire community. Such leaky functions are thus dispensable for individuals, provided they are not lost entirely from the community. The BQH predicts that the loss of a costly, leaky function is selectively favored at the individual level and will proceed until the production of public goods is just sufficient to support the equilibrium community; at that point, the benefit of any further loss would be offset by the cost. Evolution in accordance with the BQH thus generates "beneficiaries" of reduced genomic content that are dependent on leaky "helpers," and it may explain the observed nonuniversality of prototrophy, stress resistance, and other cellular functions in the microbial world.

Competition and coexistence of polar and non-polar states in Sr1-x Ca x TiO3: an investigation using pressure dependent Raman spectroscopy

Science.gov (United States)

Tyagi, Shekhar; Sharma, Gaurav; Sathe, Vasant G.

2018-03-01

The competition and cooperation between ferroelectric and anti-ferro-distortion (AFD) instabilities are studied using pressure dependent Raman spectroscopy on polycrystalline powder samples of Sr1-x Ca x TiO3(x  =  0.0, 0.06, 0.25, 0.35). For x  =  0.0 composition, a broad polar mode is detected in the Raman spectra above 6 GPa, while for x  =  0.06 composition, the polar modes appear well above 9 GPa where the AFD modes showed strong suppression. In x  =  0.25 and 0.35 composition, the application of small pressure resulted in the appearance of strong AFD modes suppressing the polar modes. At elevated pressures, re-entrant polar modes are observed along with the broad AFD modes and some new peaks are also observed, signifying the lowering of local symmetry. The reappearance of polar modes is found to be related to pressure induced symmetry disorder at local level, suggesting its electronic origin. The re-entrant polar modes observed at higher pressure values are found to be significantly broad and asymmetric in nature, signifying the development of ferroelectric micro regions/nano domains coexisting with AFD. The lower symmetry at local length scale provides a conducive atmosphere for coexisting AFD and FE instabilities.

Survival and breeding of polar bears in the southern Beaufort Sea in relation to sea ice

Science.gov (United States)

Regehr, E.V.; Hunter, C.M.; Caswell, H.; Amstrup, Steven C.; Stirling, I.

2010-01-01

1. Observed and predicted declines in Arctic sea ice have raised concerns about marine mammals. In May 2008, the US Fish and Wildlife Service listed polar bears (Ursus maritimus) - one of the most ice-dependent marine mammals - as threatened under the US Endangered Species Act. 2. We evaluated the effects of sea ice conditions on vital rates (survival and breeding probabilities) for polar bears in the southern Beaufort Sea. Although sea ice declines in this and other regions of the polar basin have been among the greatest in the Arctic, to date population-level effects of sea ice loss on polar bears have only been identified in western Hudson Bay, near the southern limit of the species' range. 3. We estimated vital rates using multistate capture-recapture models that classified individuals by sex, age and reproductive category. We used multimodel inference to evaluate a range of statistical models, all of which were structurally based on the polar bear life cycle. We estimated parameters by model averaging, and developed a parametric bootstrap procedure to quantify parameter uncertainty. 4. In the most supported models, polar bear survival declined with an increasing number of days per year that waters over the continental shelf were ice free. In 2001-2003, the ice-free period was relatively short (mean 101 days) and adult female survival was high (0 ∙ 96-0 ∙ 99, depending on reproductive state). In 2004 and 2005, the ice-free period was longer (mean 135 days) and adult female survival was low (0 ∙ 73-0 ∙ 79, depending on reproductive state). Breeding rates and cub litter survival also declined with increasing duration of the ice-free period. Confidence intervals on vital rate estimates were wide. 5. The effects of sea ice loss on polar bears in the southern Beaufort Sea may apply to polar bear populations in other portions of the polar basin that have similar sea ice dynamics and have experienced similar, or more severe, sea ice declines. Our findings

Mechanisms of PD-L1/PD-1-mediated CD8 T-cell dysfunction in the context of aging-related immune defects in the Eµ-TCL1 CLL mouse model.

Science.gov (United States)

McClanahan, Fabienne; Riches, John C; Miller, Shaun; Day, William P; Kotsiou, Eleni; Neuberg, Donna; Croce, Carlo M; Capasso, Melania; Gribben, John G

2015-07-09

T-cell defects, immune suppression, and poor antitumor immune responses are hallmarks of chronic lymphocytic leukemia (CLL), and PD-1/PD-L1 inhibitory signaling has emerged as a major immunosuppressive mechanism. However, the effect of different microenvironments and the confounding influence of aging are poorly understood. The current study uses the Eμ-TCL1 mouse model, which replicates human T-cell defects, as a preclinical platform to longitudinally examine patterns of T-cell dysfunction alongside developing CLL and in different microenvironments, with a focus on PD-1/PD-L1 interactions. The development of CLL was significantly associated with changes in T-cell phenotype across all organs and function. Although partly mirrored in aging wild-type mice, CLL-specific T-cell changes were identified. Murine CLL cells highly expressed PD-L1 and PD-L2 in all organs, with high PD-L1 expression in the spleen. CD3(+)CD8(+) T cells from leukemic and aging healthy mice highly expressed PD-1, identifying aging as a confounder, but adoptive transfer experiments demonstrated CLL-specific PD-1 induction. Direct comparisons of PD-1 expression and function between aging CLL mice and controls identified PD-1(+) T cells in CLL as a heterogeneous population with variable effector function. This is highly relevant for therapeutic targeting of CD8(+) T cells, showing the potential of reprogramming and selective subset expansion to restore antitumor immunity. © 2015 by The American Society of Hematology.

The spectral properties of (--epigallocatechin 3-O-gallate (EGCG fluorescence in different solvents: dependence on solvent polarity.

Directory of Open Access Journals (Sweden)

Vladislav Snitsarev

Full Text Available (--Epigallocatechin 3-O-gallate (EGCG a molecule found in green tea and known for a plethora of bioactive properties is an inhibitor of heat shock protein 90 (HSP90, a protein of interest as a target for cancer and neuroprotection. Determination of the spectral properties of EGCG fluorescence in environments similar to those of binding sites found in proteins provides an important tool to directly study protein-EGCG interactions. The goal of this study is to examine the spectral properties of EGCG fluorescence in an aqueous buffer (AB at pH=7.0, acetonitrile (AN (a polar aprotic solvent, dimethylsulfoxide (DMSO (a polar aprotic solvent, and ethanol (EtOH (a polar protic solvent. We demonstrate that EGCG is a highly fluorescent molecule when excited at approximately 275 nm with emission maxima between 350 and 400 nm depending on solvent. Another smaller excitation peak was found when EGCG is excited at approximately 235 nm with maximum emission between 340 and 400 nm. We found that the fluorescence intensity (FI of EGCG in AB at pH=7.0 is significantly quenched, and that it is about 85 times higher in an aprotic solvent DMSO. The Stokes shifts of EGCG fluorescence were determined by solvent polarity. In addition, while the emission maxima of EGCG fluorescence in AB, DMSO, and EtOH follow the Lippert-Mataga equation, its fluorescence in AN points to non-specific solvent effects on EGCG fluorescence. We conclude that significant solvent-dependent changes in both fluorescence intensity and fluorescence emission shifts can be effectively used to distinguish EGCG in aqueous solutions from EGCG in environments of different polarity, and, thus, can be used to study specific EGCG binding to protein binding sites where the environment is often different from aqueous in terms of polarity.

Polar bears (Ursus maritimus mating during late June on the pack ice of northern Svalbard, Norway

Directory of Open Access Journals (Sweden)

Thomas G. Smith

2015-03-01

Full Text Available Polar bears are seasonal breeders and typically mate from late March to early May. Implantation is, however, delayed until autumn, which can allow plasticity in the date of mating. As for other seasonal breeders, a rapid return to estrus after the loss of dependent offspring can be expected, even into the summer. A few earlier observations and dissections of dead animals suggest that polar bears are able to mate in summer. We report on a mating incident on 29 June 2014, the first documented mating this late in the season among wild polar bears. The female had lost her dependent cub during the period prior to the mating event. We speculate that she lost this cub late in the mating season, entered estrus and successfully mated in late June.

The phenomenology of optically pumped 13C NMR in diamond at 7.05 T: Room temperature polarization, orientation dependence, and the effect of defect concentration on polarization dynamics

Science.gov (United States)

Scott, Eric; Drake, Melanie; Reimer, Jeffrey A.

2016-03-01

Room temperature optical illumination of NV- imbibed single crystal diamonds with a 532 nm laser produces 13C polarization enhancements up to 200 times greater than that of the thermal equilibrium value at 7.05 T. We report high field NV- mediated 13C polarization as a function of the number and type (NV- and P1) of defects in commercially available diamonds. Surprisingly, both positive and negative 13C polarizations are observed depending on the orientation of the crystal with respect to the external magnetic field and the electric field vector of the optical illumination. The data reported herein cannot be explained by a previously proposed mechanism.

POLARIZED BEAMS: 2 - Partial Siberian Snake rescues polarized protons at Brookhaven

International Nuclear Information System (INIS)

Huang, Haixin

1994-01-01

To boost the level of beam polarization (spin orientation), a partial 'Siberian Snake' was recently used to overcome imperfection depolarizing resonances in the Brookhaven Alternating Gradient Synchrotron (AGS). This 9-degree spin rotator recently permitted acceleration with no noticeable polarization loss. The intrinsic AGS depolarizing resonances (which degrade the polarization content) had been eliminated by betatron tune jumps, but the imperfection resonances were compensated by means of harmonic orbit corrections. However, at high energies these orbit corrections are difficult and tedious and a Siberian Snake became an attractive alternative

Mathematical modelling of frequency-dependent hysteresis and energy loss of FeBSiC amorphous alloy

International Nuclear Information System (INIS)

Koprivica, Branko; Milovanovic, Alenka; Mitrovic, Nebojsa

2017-01-01

The aim of this paper is to present a novel mathematical model of frequency-dependent magnetic hysteresis. The major hysteresis loop in this model is represented by the ascending and descending curve over an arctangent function. The parameters of the hysteresis model have been calculated from a measured hysteresis loop of the FeBSiC amorphous alloy sample. A number of measurements have been performed with this sample at different frequencies of the sinusoidal excitation magnetic field. A variation of the coercive magnetic field with the frequency has been observed and used in the modelling of frequency-dependent hysteresis with the proposed model. A comparison between measured and modelled hysteresis loops has been presented. Additionally, the areas of the obtained hysteresis loops, representing the energy loss per unit volume, have been calculated and the dependence of the energy loss on the frequency is shown. Furthermore, two models of the frequency dependence of the coercivity and two models of the energy loss separation have been used for fitting the experimental and simulation results. The relations between these models and their parameters have been observed and analysed. Also, the relations between parameters of the hysteresis model and the parameters of the energy loss separation models have been analysed and discussed. - Highlights: • A mathematical model of frequency-dependent hysteresis is proposed. • Dependence of coercivity and energy loss per unit volume on frequency is modelled. • Equivalence between models and relation between model parameters are presented.

Effect of 3D Polarization profiles on polarization measurements and colliding beam experiments

Energy Technology Data Exchange (ETDEWEB)

Fischer, W.; Bazilevsky, A.

2011-08-18

The development of polarization profiles are the primary reason for the loss of average polarization. Polarization profiles have been parametrized with a Gaussian distribution. We derive the effect of 3-dimensional polarization profiles on the measured polarization in polarimeters, as well as the observed polarization and the figure of merit in single and double spin experiments. Examples from RHIC are provided. The Relativistic Heavy Ion Collider (RHIC) is the only collider of spin polarized protons. During beam acceleration and storage profiles of the polarization P develop, which affect the polarization measured in a polarimeter, and the polarization and figure of merit (FOM) in colliding beam experiments. We calculate these for profiles in all dimensions, and give examples for RHIC. Like in RHIC we call the two colliding beams Blue and Yellow. We use the overbar to designate intensity-weighted averages in polarimeters (e.g. {bar P}), and angle brackets to designate luminosity-weighted averages in colliding beam experiments (e.g.

).

Effect of 3D Polarization profiles on polarization measurements and colliding beam experiments

International Nuclear Information System (INIS)

Fischer, W.; Bazilevsky, A.

2011-01-01

The development of polarization profiles are the primary reason for the loss of average polarization. Polarization profiles have been parametrized with a Gaussian distribution. We derive the effect of 3-dimensional polarization profiles on the measured polarization in polarimeters, as well as the observed polarization and the figure of merit in single and double spin experiments. Examples from RHIC are provided. The Relativistic Heavy Ion Collider (RHIC) is the only collider of spin polarized protons. During beam acceleration and storage profiles of the polarization P develop, which affect the polarization measured in a polarimeter, and the polarization and figure of merit (FOM) in colliding beam experiments. We calculate these for profiles in all dimensions, and give examples for RHIC. Like in RHIC we call the two colliding beams Blue and Yellow. We use the overbar to designate intensity-weighted averages in polarimeters (e.g. (bar P)), and angle brackets to designate luminosity-weighted averages in colliding beam experiments (e.g. ).

Biomechanical Loading Modulates Proinflammatory and Bone Resorptive Mediators in Bacterial-Stimulated PDL Cells

Directory of Open Access Journals (Sweden)

Andressa Vilas Boas Nogueira

2014-01-01

Full Text Available The present study aimed to evaluate in vitro whether biomechanical loading modulates proinflammatory and bone remodeling mediators production by periodontal ligament (PDL cells in the presence of bacterial challenge. Cells were seeded on BioFlex culture plates and exposed to Fusobacterium nucleatum ATCC 25586 and/or cyclic tensile strain (CTS of low (CTSL and high (CTSH magnitudes for 1 and 3 days. Synthesis of cyclooxygenase-2 (COX2 and prostaglandin E2 (PGE2 was evaluated by ELISA. Gene expression and protein secretion of osteoprotegerin (OPG and receptor activator of nuclear factor kappa-B ligand (RANKL were evaluated by quantitative RT-PCR and ELISA, respectively. F. nucleatum increased the production of COX2 and PGE2, which was further increased by CTS. F. nucleatum-induced increase of PGE2 synthesis was significantly (P<0.05 increased when CTSH was applied at 1 and 3 days. In addition, CTSH inhibited the F. nucleatum-induced upregulation of OPG at 1 and 3 days, thereby increasing the RANKL/OPG ratio. OPG and RANKL mRNA results correlated with the protein results. In summary, our findings provide original evidence that CTS can enhance bacterial-induced syntheses of molecules associated with inflammation and bone resorption by PDL cells. Therefore, biomechanical, such as orthodontic or occlusal, loading may enhance the bacterial-induced inflammation and destruction in periodontitis.

Effect of EBI3 on radiation-induced immunosuppression of cervical cancer HeLa cells by regulating Treg cells through PD-1/PD-L1 pathway.

Science.gov (United States)

Zhang, Song-An; Niyazi, Hu-Er-Xi-Dan; Hong, Wen; Tuluwengjiang, Gu-Li-Xian; Zhang, Lei; Zhang, Yang; Su, Wei-Peng; Bao, Yong-Xing

2017-03-01

This study aimed to investigate the effect of EBI3 on radiation-induced immunosuppression of cervical cancer HeLa cells by regulating Treg cells through PD-1/PD-L1 signaling pathway. A total of 43 adult female Wistar rats were selected and injected with HeLa cells in the caudal vein to construct a rat model of cervical cancer. All model rats were randomly divided into the radiotherapy group ( n = 31) and the control group ( n = 12). The immunophenotype of Treg cells was detected by the flow cytometry. The protein expressions of EBI3, PD-1, and PD-L1 in cervical cancer tissues were tested by the streptavidin-peroxidase method. HeLa cells in the logarithmic growth phase were divided into four groups: the blank, the negative control group, the EBI3 mimics group, and the EBI3 inhibitors group. Western blotting was used to detect PD-1 and PD-L1 protein expressions. MTT assay was performed to measure the proliferation of Treg cells. Flow cytometry was used to detect cell cycle and apoptosis, and CD4 + /CD8 + T cell ratio in each group. Compared with before and 1 week after radiotherapy, the percentages of CD4 + T cells and CD8 + T cells were significantly decreased in the radiotherapy group at 1 month after radiotherapy. Furthermore, down-regulation of EBI3 and up-regulation of PD-1 and PD-L1 were observed in cervical cancer tissues at 1 month after radiotherapy. In comparison to the blank and negative control groups, increased expression of EBI3 and decreased expressions of PD-1 and PD-L1 were found in the EBI3 mimics group. However, the EBI3 inhibitors group had a lower expression of EBI3 and higher expressions of PD-1 and PD-L1 than those in the blank and negative control groups. The EBI3 mimics group showed an increase in the optical density value (0.43 ± 0.05), while a decrease in the optical density value (0.31 ± 0.02) was found in the EBI3 inhibitors group. Moreover, compared with the blank and negative control groups, the apoptosis rates

Spin flipping a stored polarized proton beam

International Nuclear Information System (INIS)

Caussyn, D.D.; Derbenev, Y.S.; Ellison, T.J.P.; Lee, S.Y.; Rinckel, T.; Schwandt, P.; Sperisen, F.; Stephenson, E.J.; von Przewoski, B.; Blinov, B.B.; Chu, C.M.; Courant, E.D.; Crandell, D.A.; Kaufman, W.A.; Krisch, A.D.; Nurushev, T.S.; Phelps, R.A.; Ratner, L.G.; Wong, V.K.; Ohmori, C.

1994-01-01

We recently studied the spin flipping of a vertically polarized, stored 139-MeV proton beam. To flip the spin, we induced an rf depolarizing resonance by sweeping our rf solenoid magnet's frequency through the resonance frequency. With multiple spin flips, we found a polarization loss of 0.0000±0.0005 per spin flip under the best conditions; this loss increased significantly for small changes in the conditions. Minimizing the depolarization during each spin flip is especially important because frequent spin flipping could significantly reduce the systematic errors in stored polarized-beam experiments

Changing Arctic Ecosystems: Updated forecast: Reducing carbon dioxide (CO2) emissions required to improve polar bear outlook

Science.gov (United States)

Oakley, Karen L.; Atwood, Todd C.; Mugel, Douglas N.; Rode, Karyn D.; Whalen, Mary E.

2015-01-01

The Arctic is warming faster than other regions of the world due to the loss of snow and ice, which increases the amount of solar energy absorbed by the region. The most visible consequence has been the rapid decline in sea ice over the last 3 decades-a decline projected to bring long ice-free summers if greenhouse gas (GHG) emissions are not significantly reduced. The polar bear (Ursus maritimus) depends on sea ice over the biologically productive continental shelves of the Arctic Ocean as a platform for hunting seals. In 2008, the U.S. Fish and Wildlife Service listed the polar bear as threatened under the Endangered Species Act (ESA) due to the threat posed by sea ice loss. The polar bear was the first species to be listed due to forecasted population declines from climate change.

Suomi National Polar-Orbiting Partnership Visible Infrared Imaging Radiometer Suite Polarization Sensitivity Analysis

Science.gov (United States)

Sun, Junqiang; Xiong, Xiaoxiong; Waluschka, Eugene; Wang, Menghua

2016-01-01

The Visible Infrared Imaging Radiometer Suite (VIIRS) is one of five instruments onboard the Suomi National Polar-Orbiting Partnership (SNPP) satellite that launched from Vandenberg Air Force Base, California, on October 28, 2011. It is a whiskbroom radiometer that provides +/-56.28deg scans of the Earth view. It has 22 bands, among which 14 are reflective solar bands (RSBs). The RSBs cover a wavelength range from 410 to 2250 nm. The RSBs of a remote sensor are usually sensitive to the polarization of incident light. For VIIRS, it is specified that the polarization factor should be smaller than 3% for 410 and 862 nm bands and 2.5% for other RSBs for the scan angle within +/-45deg. Several polarization sensitivity tests were performed prelaunch for SNPP VIIRS. The first few tests either had large uncertainty or were less reliable, while the last one was believed to provide the more accurate information about the polarization property of the instrument. In this paper, the measured data in the last polarization sensitivity test are analyzed, and the polarization factors and phase angles are derived from the measurements for all the RSBs. The derived polarization factors and phase angles are band, detector, and scan angle dependent. For near-infrared bands, they also depend on the half-angle mirror side. Nevertheless, the derived polarization factors are all within the specification, although the strong detector dependence of the polarization parameters was not expected. Compared to the Moderate Resolution Imaging Spectroradiometer on both Aqua and Terra satellites, the polarization effect on VIIRS RSB is much smaller.

Enhancement of PSMA-Directed CAR Adoptive Immunotherapy by PD-1/PD-L1 Blockade

Directory of Open Access Journals (Sweden)

Inna Serganova

2017-03-01

Full Text Available Chimeric antigen receptor (CAR T cell therapy in hematologic malignancies has shown remarkable responses, but the same level of success has not been observed in solid tumors. A new prostate cancer model (Myc-CaP:PSMA(+ and a second-generation anti-hPSMA human CAR T cells expressing a Click Beetle Red luciferase reporter were used to study hPSMA targeting and assess CAR T cell trafficking and persistence by bioluminescence imaging (BLI. We investigated the antitumor efficacy of human CAR T cells targeting human prostate-specific membrane antigen (hPSMA, in the presence and absence of the target antigen; first alone and then combined with a monoclonal antibody targeting the human programmed death receptor 1 (anti-hPD1 mAb. PDL-1 expression was detected in Myc-CaP murine prostate tumors growing in immune competent FVB/N and immune-deficient SCID mice. Endogenous CD3+ T cells were restricted from the centers of Myc-CaP tumor nodules growing in FVB/N mice. Following anti-programmed cell death protein 1 (PD-1 treatment, the restriction of CD3+ T cells was reversed, and a tumor-treatment response was observed. Adoptive hPSMA-CAR T cell immunotherapy was enhanced when combined with PD-1 blockade, but the treatment response was of comparatively short duration, suggesting other immune modulation mechanisms exist and restrict CAR T cell targeting, function, and persistence in hPSMA expressing Myc-CaP tumors. Interestingly, an “inverse pattern” of CAR T cell BLI intensity was observed in control and test tumors, which suggests CAR T cells undergo changes leading to a loss of signal and/or number following hPSMA-specific activation. The lower BLI signal intensity in the hPSMA test tumors (compared with controls is due in part to a decrease in T cell mitochondrial function following T cell activation, which may limit the intensity of the ATP-dependent Luciferin-luciferase bioluminescence signal.

Polarization of lanthanum nucleus by dynamic polarization method

International Nuclear Information System (INIS)

Adachi, Toshikazu; Ishimoto, Shigeru; Masuda, Yasuhiro; Morimoto, Kimio

1989-01-01

Preliminary studies have been carried out concerning the application of a dynamic polarization method to polarizing lanthanum fluoride single crystal to be employed as target in experiments with time reversal invariance. The present report briefly outlines the dynamic polarization method and describes some preliminary studies carried out so far. Dynamic polarization is of particular importance because no techniques are currently available that can produce highly polarized static nucleus. Spin interaction between electrons and protons (nuclei) plays a major role in the dynamic polarization method. In a thermal equilibrium state, electrons are polarized almost completely while most protons are not polarized. Positively polarized proton spin is produced by applying microwave to this system. The most hopeful candidate target material is single crystal of LaF 3 containing neodymium because the crystal is chemically stable and easy to handle. The spin direction is of great importance in experiments with time reversal invariance. The spin of neutrons in the target can be cancelled by adjusting the external magnetic field applied to a frozen polarized target. In a frozen spin state, the polarity decreases slowly with a relaxation time that depends on the external magnetic field and temperature. (N.K.)

Investigation of photon detection probability dependence of SPADnet-I digital photon counter as a function of angle of incidence, wavelength and polarization

Energy Technology Data Exchange (ETDEWEB)

Játékos, Balázs, E-mail: jatekosb@eik.bme.hu; Ujhelyi, Ferenc; Lőrincz, Emőke; Erdei, Gábor

2015-01-01

SPADnet-I is a prototype, fully digital, high spatial and temporal resolution silicon photon counter, based on standard CMOS imaging technology, developed by the SPADnet consortium. Being a novel device, the exact dependence of photon detection probability (PDP) of SPADnet-I was not known as a function of angle of incidence, wavelength and polarization of the incident light. Our targeted application area of this sensor is next generation PET detector modules, where they will be used along with LYSO:Ce scintillators. Hence, we performed an extended investigation of PDP in a wide range of angle of incidence (0° to 80°), concentrating onto a 60 nm broad wavelength interval around the characteristic emission peak (λ=420 nm) of the scintillator. In the case where the sensor was optically coupled to a scintillator, our experiments showed a notable dependence of PDP on angle, polarization and wavelength. The sensor has an average PDP of approximately 30% from 0° to 60° angle of incidence, where it starts to drop rapidly. The PDP turned out not to be polarization dependent below 30°. If the sensor is used without a scintillator (i.e. the light source is in air), the polarization dependence is much less expressed, it begins only from 50°.

Polarization-dependent asymmetric hysteresis behavior in ZnCrO layers

International Nuclear Information System (INIS)

Lee, Youngmin; Kim, Deukyoung; Lee, Sejoon; Fu, Dejun

2012-01-01

A ZnCrO layer grown on a Pt (111)/Al 2 O 3 (0001) substrate exhibits a lattice displacement induced ferroelectric behavior due to a modulation in the lattice translation symmetry. The top-to-bottom Pt/ZnCrO/Pt structure shows asymmetric hysteresis loops in positive and negative voltage bias regions. This is attributed to a change in the Schottky emission rate due to the nonlinear polarization of the ZnCrO barrier. The characteristics of the hysteresis loops depend on the film textures of ZnCrO, which vary with the oxygen partial pressure during the growth stage of the ZnCrO layers. The results suggest that ZnCrO has efficacy characteristics for applications in the non-volatile resistive-switching systems.

Predicting 21st-century polar bear habitat distribution from global climate models

Science.gov (United States)

Durner, George M.; Douglas, David C.; Nielson, R.M.; Amstrup, Steven C.; McDonald, T.L.; Stirling, I.; Mauritzen, Mette; Born, E.W.; Wiig, O.; Deweaver, E.; Serreze, Mark C.; Belikov, Stanislav; Holland, M.M.; Maslanik, J.; Aars, Jon; Bailey, D.A.; Derocher, A.E.

2009-01-01

Projections of polar bear (Ursus maritimus) sea ice habitat distribution in the polar basin during the 21st century were developed to understand the consequences of anticipated sea ice reductions on polar bear populations. We used location data from satellitecollared polar bears and environmental data (e.g., bathymetry, distance to coastlines, and sea ice) collected from 1985 to 1995 to build resource selection functions (RSFs). RSFs described habitats that polar bears preferred in summer, autumn, winter, and spring. When applied to independent data from 1996 to 2006, the RSFs consistently identified habitats most frequently used by polar bears. We applied the RSFs to monthly maps of 21st-century sea ice concentration projected by 10 general circulation models (GCMs) used in the Intergovernmental Panel of Climate Change Fourth Assessment Report, under the A1B greenhouse gas forcing scenario. Despite variation in their projections, all GCMs indicated habitat losses in the polar basin during the 21st century. Losses in the highest-valued RSF habitat (optimal habitat) were greatest in the southern seas of the polar basin, especially the Chukchi and Barents seas, and least along the Arctic Ocean shores of Banks Island to northern Greenland. Mean loss of optimal polar bear habitat was greatest during summer; from an observed 1.0 million km2 in 1985-1995 (baseline) to a projected multi-model mean of 0.32 million km2 in 2090-2099 (-68% change). Projected winter losses of polar bear habitat were less: from 1.7 million km2 in 1985-1995 to 1.4 million km2 in 2090-2099 (-17% change). Habitat losses based on GCM multi-model means may be conservative; simulated rates of habitat loss during 1985-2006 from many GCMs were less than the actual observed rates of loss. Although a reduction in the total amount of optimal habitat will likely reduce polar bear populations, exact relationships between habitat losses and population demographics remain unknown. Density and energetic

Nuclear polarization and neutrons

International Nuclear Information System (INIS)

Glaettli, H.

1985-01-01

Different possibilities for the use of polarized nuclei in thermal neutron scattering on condensed matter are reviewed. Highly polarized nuclei are the starting point for studying dipolar magnetic order. Systematic measurement of spin-dependent scattering lengths is possible on samples with polarized nuclei. Highly polarized hydrogen should help to unravel complicated structures in chemistry and biology. The use of polarized proton targets as an energy-independent neutron polarizer in the thermal and epithermal region should be considered afresh. (author)

Temperature dependence of low-frequency polarized Raman scattering spectra in TlInS{sub 2}

Energy Technology Data Exchange (ETDEWEB)

Paucar, Raul; Wakita, Kazuki [Electronics and Computer Engineering, Chiba Institute of Technology, Chiba (Japan); Shim, YongGu; Mimura, Kojiro [Graduate School of Engineering, Osaka Prefecture University, Osaka (Japan); Alekperov, Oktay; Mamedov, Nazim [Institute of Physics, Azerbaijan National Academy of Sciences, Baku (Azerbaijan)

2017-06-15

In this work, we examined phase transitions in the layered ternary thallium chalcogenide TlInS{sub 2} by studying the temperature dependence of polarized Raman spectra with the aid of the Raman confocal microscope system. The Raman spectra were measured over the temperature range of 77-320 K (which includes the range of successive phase transitions) in the low-frequency region of 35-180 cm{sup -1}. The optical phonons that showed strong temperature dependence were identified as interlayer vibrations related to phase transitions, while the phonons that showed weak temperature dependence were identified as intralayer vibrations. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Dependence of Polarization of the near-Earth Asteroids (1036) Ganymed and (5143) Heracles on Wavelength and Phase Angle

Science.gov (United States)

Maleszewski, C.; McMillan, R.; Smith, P.

2012-12-01

We are measuring the polarization of asteroids with the SPOL polarimeter of Steward Observatory. With monthly access to the instrument, we can obtain many observations throughout phase angle. This is in contrast to other recent work that had to rely on aggregate properties of targets of similar taxonomic type. Comparing individual objects to these aggregate results may reveal differences of regolith properties from object to object. Both the phase angle and spectral dependence of polarization are being measured. SPOL provides simultaneous coverage from 0.40-0.75 microns, equivalent to BVR filters. Three phase curves thus reveal differences of phase angle dependences with respect to wavelength. The spectral dependence of the linear polarization is determined according to a linear trend previously used to describe the dependence for Main Belt Asteroids (MBAs) in various taxonomic classes (Belskaya et al. 2009). The slopes of these linear trends vs. phase angle are also investigated as was also done in the Belskaya analysis for MBAs in the C-, M-, and S-types. Two initial objects of interest are the NEAs (1036) Ganymed and (5143) Heracles. The taxonomic types of Ganymed and Heracles are S-type and Q-type respectively (DeMeo et al. 2009). For Ganymed, twelve observations were made between 2011 September and 2012 March. These include observations below ten degrees phase angle, which are currently lacking in the polarimetric databases. The positive branch of Ganymed's polarization phase curve behaved similarly across SPOL's wavelength range. But for wavelengths associated with a typical B-filter, the negative branch is more shallow and narrow. The negative phase branch of Ganymed is smaller compared to the aggregate phase curve of S-types determined by Gil-Hutton and Cañada-Assandri (2011). The linear polarization decreases with increasing wavelength at all observed phase angles. As the phase angle increases, the slope of the wavelength dependence of polarization

Multi-user distribution of polarization entangled photon pairs

Energy Technology Data Exchange (ETDEWEB)

Trapateau, J.; Orieux, A.; Diamanti, E.; Zaquine, I., E-mail: isabelle.zaquine@telecom-paristech.fr [LTCI, CNRS, Télécom ParisTech, Université Paris-Saclay, 75013 Paris (France); Ghalbouni, J. [Applied Physics Laboratory, Faculty of Sciences 2, Lebanese University, Campus Fanar, BP 90656 Jdeidet (Lebanon)

2015-10-14

We experimentally demonstrate multi-user distribution of polarization entanglement using commercial telecom wavelength division demultiplexers. The entangled photon pairs are generated from a broadband source based on spontaneous parametric down conversion in a periodically poled lithium niobate crystal using a double path setup employing a Michelson interferometer and active phase stabilisation. We test and compare demultiplexers based on various technologies and analyze the effect of their characteristics, such as losses and polarization dependence, on the quality of the distributed entanglement for three channel pairs of each demultiplexer. In all cases, we obtain a Bell inequality violation, whose value depends on the demultiplexer features. This demonstrates that entanglement can be distributed to at least three user pairs of a network from a single source. Additionally, we verify for the best demultiplexer that the violation is maintained when the pairs are distributed over a total channel attenuation corresponding to 20 km of optical fiber. These techniques are therefore suitable for resource-efficient practical implementations of entanglement-based quantum key distribution and other quantum communication network applications.

Time-dependent shock acceleration of energetic electrons including synchrotron losses

International Nuclear Information System (INIS)

Fritz, K.; Webb, G.M.

1990-01-01

The present investigation of the time-dependent particle acceleration problem in strong shocks, including synchrotron radiation losses, solves the transport equation analytically by means of Laplace transforms. The particle distribution thus obtained is then transformed numerically into real space for the cases of continuous and impulsive injections of particles at the shock. While in the continuous case the steady-state spectrum undergoes evolution, impulsive injection is noted to yield such unpredicted features as a pile-up of high-energy particles or a steep power-law with time-dependent spectral index. The time-dependent calculations reveal varying spectral shapes and more complex features for the higher energies which may be useful in the interpretation of outburst spectra. 33 refs

Polarization-sensitive color in butterfly scales: polarization conversion from ridges with reflecting elements.

Science.gov (United States)

Zhang, Ke; Tang, Yiwen; Meng, Jinsong; Wang, Ge; Zhou, Han; Fan, Tongxiang; Zhang, Di

2014-11-03

Polarization-sensitive color originates from polarization-dependent reflection or transmission, exhibiting abundant light information, including intensity, spectral distribution, and polarization. A wide range of butterflies are physiologically sensitive to polarized light, but the origins of polarized signal have not been fully understood. Here we systematically investigate the colorful scales of six species of butterfly to reveal the physical origins of polarization-sensitive color. Microscopic optical images under crossed polarizers exhibit their polarization-sensitive characteristic, and micro-structural characterizations clarify their structural commonality. In the case of the structural scales that have deep ridges, the polarization-sensitive color related with scale azimuth is remarkable. Periodic ridges lead to the anisotropic effective refractive indices in the parallel and perpendicular grating orientations, which achieves form-birefringence, resulting in the phase difference of two different component polarized lights. Simulated results show that ridge structures with reflecting elements reflect and rotate the incident p-polarized light into s-polarized light. The dimensional parameters and shapes of grating greatly affect the polarization conversion process, and the triangular deep grating extends the outstanding polarization conversion effect from the sub-wavelength period to the period comparable to visible light wavelength. The parameters of ridge structures in butterfly scales have been optimized to fulfill the polarization-dependent reflection for secret communication. The structural and physical origin of polarization conversion provides a more comprehensive perspective on the creation of polarization-sensitive color in butterfly wing scales. These findings show great potential in anti-counterfeiting technology and advanced optical material design.

All-optical clocked flip-flops and random access memory cells using the nonlinear polarization rotation effect of low-polarization-dependent semiconductor optical amplifiers

Science.gov (United States)

Wang, Yongjun; Liu, Xinyu; Tian, Qinghua; Wang, Lina; Xin, Xiangjun

2018-03-01

Basic configurations of various all-optical clocked flip-flops (FFs) and optical random access memory (RAM) based on the nonlinear polarization rotation (NPR) effect of low-polarization-dependent semiconductor optical amplifiers (SOA) are proposed. As the constituent elements, all-optical logic gates and all-optical SR latches are constructed by taking advantage of the SOA's NPR switch. Different all-optical FFs (AOFFs), including SR-, D-, T-, and JK-types as well as an optical RAM cell were obtained by the combination of the proposed all-optical SR latches and logic gates. The effectiveness of the proposed schemes were verified by simulation results and demonstrated by a D-FF and 1-bit RAM cell experimental system. The proposed all-optical clocked FFs and RAM cell are significant to all-optical signal processing.

Co-targeting aurora kinase with PD-L1 and PI3K abrogates immune checkpoint mediated proliferation in peripheral T-cell lymphoma: a novel therapeutic strategy.

Science.gov (United States)

Islam, Shariful; Vick, Eric; Huber, Bryan; Morales, Carla; Spier, Catherine; Cooke, Laurence; Weterings, Eric; Mahadevan, Daruka

2017-11-21

Peripheral T-cell non-Hodgkin lymphoma (PTCL) are heterogeneous, rare, and aggressive diseases mostly incurable with current cell cycle therapies. Aurora kinases (AKs) are key regulators of mitosis that drive PTCL proliferation. Alisertib (AK inhibitor) has a response rate ∼30% in relapsed and refractory PTCL (SWOG1108). Since PTCL are derived from CD4 + /CD8 + cells, we hypothesized that Program Death Ligand-1 (PD-L1) expression is essential for uncontrolled proliferation. Combination of alisertib with PI3Kα (MLN1117) or pan-PI3K inhibition (PF-04691502) or vincristine (VCR) was highly synergistic in PTCL cells. Expression of PD-L1 relative to PD-1 is high in PTCL biopsies (∼9-fold higher) and cell lines. Combination of alisertib with pan-PI3K inhibition or VCR significantly reduced PD-L1, NF-κB expression and inhibited phosphorylation of AKT, ERK1/2 and AK with enhanced apoptosis. In a SCID PTCL xenograft mouse model, alisertib displayed high synergism with MLN1117. In a syngeneic PTCL mouse xenograft model alisertib demonstrated tumor growth inhibition (TGI) ∼30%, whilst anti-PD-L1 therapy alone was ineffective. Alisertib + anti-PD-L1 resulted in TGI >90% indicative of a synthetic lethal interaction. PF-04691502 + alisertib + anti-PD-L1 + VCR resulted in TGI 100%. Overall, mice tolerated the treatments well. Co-targeting AK, PI3K and PD-L1 is a rational and novel therapeutic strategy for PTCL.

Planck intermediate results. XXII. Frequency dependence of thermal emission from Galactic dust in intensity and polarization

DEFF Research Database (Denmark)

Cardoso, J. F.; Delabrouille, J.; Ganga, K.

2015-01-01

)% from 353 to 70 GHz. We discuss this result within the context of existing dust models. The decrease in p could indicate differences in polarization efficiency among components of interstellar dust (e.g., carbon versus silicate grains). Our observational results provide inputs to quantify and optimize......Planck has mapped the intensity and polarization of the sky at microwave frequencies with unprecedented sensitivity. We use these data to characterize the frequency dependence of dust emission. We make use of the Planck 353 GHz I, Q, and U Stokes maps as dust templates, and cross-correlate them...... of the cosmic microwave background. We use a mask that focuses our analysis on the diffuse interstellar medium at intermediate Galactic latitudes. We determine the spectral indices of dust emission in intensity and polarization between 100 and 353 GHz, for each sky patch. Both indices are found to be remarkably...

Polarized X-Ray Emission from Magnetized Neutron Stars: Signature of Strong-Field Vacuum Polarization

Science.gov (United States)

Lai, Dong; Ho, Wynn C.

2003-08-01

In the atmospheric plasma of a strongly magnetized neutron star, vacuum polarization can induce a Mikheyev-Smirnov-Wolfenstein type resonance across which an x-ray photon may (depending on its energy) convert from one mode into the other, with significant changes in opacities and polarizations. We show that this vacuum resonance effect gives rise to a unique energy-dependent polarization signature in the surface emission from neutron stars. The detection of polarized x rays from neutron stars can provide a direct probe of strong-field quantum electrodynamics and constrain the neutron star magnetic field and geometry.

Polarized x-ray emission from magnetized neutron stars: signature of strong-field vacuum polarization.

Science.gov (United States)

Lai, Dong; Ho, Wynn C G

2003-08-15

In the atmospheric plasma of a strongly magnetized neutron star, vacuum polarization can induce a Mikheyev-Smirnov-Wolfenstein type resonance across which an x-ray photon may (depending on its energy) convert from one mode into the other, with significant changes in opacities and polarizations. We show that this vacuum resonance effect gives rise to a unique energy-dependent polarization signature in the surface emission from neutron stars. The detection of polarized x rays from neutron stars can provide a direct probe of strong-field quantum electrodynamics and constrain the neutron star magnetic field and geometry.

Dependence of US hurricane economic loss on maximum wind speed and storm size

International Nuclear Information System (INIS)

Zhai, Alice R; Jiang, Jonathan H

2014-01-01

Many empirical hurricane economic loss models consider only wind speed and neglect storm size. These models may be inadequate in accurately predicting the losses of super-sized storms, such as Hurricane Sandy in 2012. In this study, we examined the dependences of normalized US hurricane loss on both wind speed and storm size for 73 tropical cyclones that made landfall in the US from 1988 through 2012. A multi-variate least squares regression is used to construct a hurricane loss model using both wind speed and size as predictors. Using maximum wind speed and size together captures more variance of losses than using wind speed or size alone. It is found that normalized hurricane loss (L) approximately follows a power law relation with maximum wind speed (V max ) and size (R), L = 10 c V max a R b , with c determining an overall scaling factor and the exponents a and b generally ranging between 4–12 and 2–4 respectively. Both a and b tend to increase with stronger wind speed. Hurricane Sandy’s size was about three times of the average size of all hurricanes analyzed. Based on the bi-variate regression model that explains the most variance for hurricanes, Hurricane Sandy’s loss would be approximately 20 times smaller if its size were of the average size with maximum wind speed unchanged. It is important to revise conventional empirical hurricane loss models that are only dependent on maximum wind speed to include both maximum wind speed and size as predictors. (letters)

Extreme Unconditional Dependence Vs. Multivariate GARCH Effect in the Analysis of Dependence Between High Losses on Polish and German Stock Indexes

Science.gov (United States)

Rokita, Pawel

Classical portfolio diversification methods do not take account of any dependence between extreme returns (losses). Many researchers provide, however, some empirical evidence for various assets that extreme-losses co-occur. If the co-occurrence is frequent enough to be statistically significant, it may seriously influence portfolio risk. Such effects may result from a few different properties of financial time series, like for instance: (1) extreme dependence in a (long-term) unconditional distribution, (2) extreme dependence in subsequent conditional distributions, (3) time-varying conditional covariance, (4) time-varying (long-term) unconditional covariance, (5) market contagion. Moreover, a mix of these properties may be present in return time series. Modeling each of them requires different approaches. It seams reasonable to investigate whether distinguishing between the properties is highly significant for portfolio risk measurement. If it is, identifying the effect responsible for high loss co-occurrence would be of a great importance. If it is not, the best solution would be selecting the easiest-to-apply model. This article concentrates on two of the aforementioned properties: extreme dependence (in a long-term unconditional distribution) and time-varying conditional covariance.

Monoclonal Antibody L1Mab-13 Detected Human PD-L1 in Lung Cancers.

Science.gov (United States)

Yamada, Shinji; Itai, Shunsuke; Nakamura, Takuro; Yanaka, Miyuki; Chang, Yao-Wen; Suzuki, Hiroyoshi; Kaneko, Mika K; Kato, Yukinari

2018-04-01

Programmed cell death ligand-1 (PD-L1) is a type I transmembrane glycoprotein expressed on antigen-presenting cells. It is also expressed in several tumor cells such as melanoma and lung cancer cells. A strong correlation has been reported between human PD-L1 (hPD-L1) expression in tumor cells and negative prognosis in cancer patients. Here, a novel anti-hPD-L1 monoclonal antibody (mAb) L 1 Mab-13 (IgG 1 , kappa) was produced using a cell-based immunization and screening (CBIS) method. We investigated hPD-L1 expression in lung cancer using flow cytometry, Western blot, and immunohistochemical analyses. L 1 Mab-13 specifically reacted hPD-L1 of hPD-L1-overexpressed Chinese hamster ovary (CHO)-K1 cells and endogenous hPD-L1 of KMST-6 (human fibroblast) in flow cytometry and Western blot. Furthermore, L 1 Mab-13 reacted with lung cancer cell lines (EBC-1, Lu65, and Lu99) in flow cytometry and stained lung cancer tissues in a membrane-staining pattern in immunohistochemical analysis. These results indicate that a novel anti-hPD-L1 mAb, L 1 Mab-13, is very useful for detecting hPD-L1 of lung cancers in flow cytometry, Western blot, and immunohistochemical analyses.

Investigations of Polarization Dependent Loss in Polarization Modulated Analog Optical Links

Science.gov (United States)

2015-12-29

performance analog optical links for military applications primarily rely on the most common link architecture employing intensity modulation with...axis as bisector of DD and Ss•) PP = fl i p ( rr, PPO] ; (• flip the P vector imaqe on the PA •) PPh a t = unit[PP ) ; PHI = ArcCos [ PPha t .unit...DD ) ); AA = ((Cos ( PHI / 2])𔃼 • t p (Sin [ PHI / 2 ])𔃼 ) PP • tpDDhat / 2 ; CC2 =- ( MM · AA . SS • (AA . I!M) (I!M. SS)) ; CC3 = AA . SS; ln

Modeling optical and UV polarization of AGNs. IV. Polarization timing

Science.gov (United States)

Rojas Lobos, P. A.; Goosmann, R. W.; Marin, F.; Savić, D.

2018-03-01

Context. Optical observations cannot resolve the structure of active galactic nuclei (AGN), and a unified model for AGN was inferred mostly from indirect methods, such as spectroscopy and variability studies. Optical reverberation mapping allowed us to constrain the spatial dimension of the broad emission line region and thereby to measure the mass of supermassive black holes. Recently, reverberation was also applied to the polarized signal emerging from different AGN components. In principle, this should allow us to measure the spatial dimensions of the sub-parsec reprocessing media. Aim. We conduct numerical modeling of polarization reverberation and provide theoretical predictions for the polarization time lag induced by different AGN components. The model parameters are adjusted to the observational appearance of the Seyfert 1 galaxy NGC 4151. Methods: We modeled scattering-induced polarization and tested different geometries for the circumnuclear dust component. Our tests included the effects of clumpiness and different dust prescriptions. To further extend the model, we also explored the effects of additional ionized winds stretched along the polar direction, and of an equatorial scattering ring that is responsible for the polarization angle observed in pole-on AGN. The simulations were run using a time-dependent version of the STOKES code. Results: Our modeling confirms the previously found polarization characteristics as a function of the observer`s viewing angle. When the dust adopts a flared-disk geometry, the lags reveal a clear difference between type 1 and type 2 AGN. This distinction is less clear for a torus geometry where the time lag is more sensitive to the geometry and optical depth of the inner surface layers of the funnel. The presence of a scattering equatorial ring and ionized outflows increased the recorded polarization time lags, and the polar outflows smooths out dependence on viewing angle, especially for the higher optical depth of the

Measurement of polarization-transfer to bound protons in carbon and its virtuality dependence

Science.gov (United States)

Izraeli, D.; Brecelj, T.; Achenbach, P.; Ashkenazi, A.; Böhm, R.; Cohen, E. O.; Distler, M. O.; Esser, A.; Gilman, R.; Kolar, T.; Korover, I.; Lichtenstadt, J.; Mardor, I.; Merkel, H.; Mihovilovič, M.; Müller, U.; Olivenboim, M.; Piasetzky, E.; Ron, G.; Schlimme, B. S.; Schoth, M.; Sfienti, C.; Širca, S.; Štajner, S.; Strauch, S.; Thiel, M.; Weber, A.; Yaron, I.; A1 Collaboration

2018-06-01

We measured the ratio Px /Pz of the transverse to longitudinal components of polarization transferred from electrons to bound protons in 12C by the 12C (e → ,e‧ p →) process at the Mainz Microtron (MAMI). We observed consistent deviations from unity of this ratio normalized to the free-proton ratio, (Px /Pz) 12C /(Px /Pz) 1H, for both s- and p-shell knocked out protons, even though they are embedded in averaged local densities that differ by about a factor of two. The dependence of the double ratio on proton virtuality is similar to the one for knocked out protons from 2H and 4He, suggesting a universal behavior. It further implies no dependence on average local nuclear density.

Polarization-dependent asymmetric hysteresis behavior in ZnCrO layers

Energy Technology Data Exchange (ETDEWEB)

Lee, Youngmin; Kim, Deukyoung; Lee, Sejoon [Dongguk University, Seoul (Korea, Republic of); Fu, Dejun [Wuhan University, Wuhan (China)

2012-06-15

A ZnCrO layer grown on a Pt (111)/Al{sub 2}O{sub 3} (0001) substrate exhibits a lattice displacement induced ferroelectric behavior due to a modulation in the lattice translation symmetry. The top-to-bottom Pt/ZnCrO/Pt structure shows asymmetric hysteresis loops in positive and negative voltage bias regions. This is attributed to a change in the Schottky emission rate due to the nonlinear polarization of the ZnCrO barrier. The characteristics of the hysteresis loops depend on the film textures of ZnCrO, which vary with the oxygen partial pressure during the growth stage of the ZnCrO layers. The results suggest that ZnCrO has efficacy characteristics for applications in the non-volatile resistive-switching systems.

Possibility of determining gluon polarization via polarized top pairs in gamma-proton scattering

International Nuclear Information System (INIS)

Atag, S.; Billur, A.A.

2009-01-01

We study the possibility for directly measuring the polarized gluon distribution in the process γp→t-bar t. It is shown that polarization asymmetry of the final top quarks is proportional to the gluon polarization. With available energy and luminosity, the collision of a polarized proton beam and a Compton backscattered photon beam can create polarized top quarks which carry the spin information of the process. Energy dependence and angular distributions of the polarization asymmetry of the top pairs has been discussed including statistical uncertainty.

Distance Dependence of Path Loss for Millimeter Wave Inter-Vehicle Communications

Directory of Open Access Journals (Sweden)

M. Fujise

2004-12-01

Full Text Available Millimeter-wave path loss between two cars was measured to obtainthe general applicable distance for inter-vehicle communication systemsin real environments. An abrupt and substantial increase in path lossdue to interruption, curves, and different-lane traveling has been amajor concern in inter-vehicle communications. The path lossmeasurements were carried out using 60-GHz CW radiowaves and standardhorn antennas on metropolitan highways and regular roads. Because thepropagation loss is traffic-dependent, the highways were classifiedinto uncrowded and crowded highways, and the regular roads wereclassified into uncrowded and crowded roads. The path loss for thehighways exhibited 2nd-power-law attenuation and that for the regularroads exhibited 1st-power-law attenuation with an increase ininter-vehicle distance. Additional losses of 15 dB for the highways and5 dB for the regular roads were observed when the inter-vehicledistance was more than approximately 30 m. Thus, we were able todemonstrate millimeter-wave inter-vehicle communications at aninter-vehicle distance of more than 100 m.

Polarization extinction ratio of the polarization crosstalk caused by point pressure force in the polarization-maintaining fiber

Science.gov (United States)

Mukhtubayev, Azamat B.; Aksarin, Stanislav M.; Strigalev, Vladimir E.

2017-11-01

A study of the orthogonal polarization modes crosstalk changes in the point of different mechanical actions (pressure force) in the polarization-maintaining fiber with straining elliptical cladding is presented. It was found that by increasing of the pressure force the polarization extinction ratio increases nonlinearly. Also revealed the dependence of the extinction coefficient and the angle between vector of the mechanical action and polarization axes of the test fiber, which leads to change the extinction coefficient variable from -57 dB to -25 dB under the pressure force of 0.7 N. Also it was found that the cross angle of the fiber axes doesn't influence on the extinction ratio value of the mechanical induced polarization crosstalk.

Analysis of CMOS Compatible Cu-Based TM-Pass Optical Polarizer

KAUST Repository

Ng, Tien Khee; Khan, Mohammed Zahed Mustafa; Al-Jabr, Ahmad Ali; Ooi, Boon S.

2012-01-01

for the polarizer, it was found that the metal-insulator-metal (MIM) polarizer structure is superior compared to the insulator-metal-insulator polarizer structure due to its higher polarization extinction ratio (PER) and low insertion loss. An optimized MIM TM

A Si nanocube array polarizer

Science.gov (United States)

Chen, Linghua; Jiang, Yingjie; Xing, Li; Yao, Jun

2017-10-01

We have proposed a full dielectric (silicon) nanocube array polarizer based on a silicon dioxide substrate. Each polarization unit column includes a plurality of equal spaced polarization units. By optimizing the length, the width, the height of the polarization units and the center distance of adjacent polarization unit (x direction and y direction), an extinction ratio (ER) of higher than 25dB was obtained theoretically when the incident light wavelength is 1550nm. while for applications of most polarization optical elements, ER above 10dB is enough. With this condition, the polarizer we designed can work in a wide wavelength range from 1509.31nm to 1611.51nm. Compared with the previous polarizer, we have introduced a polarizer which is a full dielectric device, which solves the problems of low efficiency caused by Ohmic loss and weak coupling. Furthermore, compared with the existing optical polarizers, our polarizer has the advantages of thin thickness, small size, light weight, and low processing difficulty, which is in line with the future development trend of optical elements.

Tunable and switchable dual-wavelength passively mode-locked Bi-doped all-fiber ring laser based on nonlinear polarization rotation

International Nuclear Information System (INIS)

Luo, A-P; Luo, Z-C; Xu, W-C; Dvoyrin, V V; Mashinsky, V M; Dianov, E M

2011-01-01

We demonstrate a tunable and switchable dual-wavelength passively mode-locked Bi-doped all-fiber ring laser by using nonlinear polarization rotation (NPR) technique. Exploiting the spectral filtering effect caused by the combination of the polarizer and intracavity birefringence, the wavelength separation of dual-wavelength mode-locked pulses can be flexibly tuned between 2.38 and 20.45 nm. Taking the advantage of NPR-induced intensity-dependent loss to suppress the mode competition, the stable dual-wavelength pulses output is obtained at room temperature. Moreover, the dual-wavelength switchable operation is achieved by simply rotating the polarization controllers (PCs)

Deep-etched sinusoidal polarizing beam splitter grating.

Science.gov (United States)

Feng, Jijun; Zhou, Changhe; Cao, Hongchao; Lv, Peng

2010-04-01

A sinusoidal-shaped fused-silica grating as a highly efficient polarizing beam splitter (PBS) is investigated based on the simplified modal method. The grating structure depends mainly on the ratio of groove depth to grating period and the ratio of incident wavelength to grating period. These ratios can be used as a guideline for the grating design at different wavelengths. A sinusoidal-groove PBS grating is designed at a wavelength of 1310 nm under Littrow mounting, and the transmitted TM and TE polarized waves are mainly diffracted into the zeroth order and the -1st order, respectively. The grating profile is optimized by using rigorous coupled-wave analysis. The designed PBS grating is highly efficient (>95.98%) over the O-band wavelength range (1260-1360 nm) for both TE and TM polarizations. The sinusoidal grating can exhibit higher diffraction efficiency, larger extinction ratio, and less reflection loss than the rectangular-groove PBS grating. By applying wet etching technology on the rectangular grating, which was manufactured by holographic recording and inductively coupled plasma etching technology, the sinusoidal grating can be approximately fabricated. Experimental results are in agreement with theoretical values.

Modulation of NADP(+)-dependent isocitrate dehydrogenase in aging.

Science.gov (United States)

Kil, In Sup; Lee, Young Sup; Bae, Young Seuk; Huh, Tae Lin; Park, Jeen-Woo

2004-01-01

NADPH is an important cofactor in many biosynthesis pathways and the regeneration of reduced glutathione, critically important in cellular defense against oxidative damage. It is mainly produced by glucose-6-phosphate dehydrogenase, malic enzyme, and NADP(+)-specific isocitrate dehydrogenases (ICDHs). Here, we investigated age-related changes in ICDH activity and protein expression in IMR-90 human diploid fibroblast cells and tissues from Fischer 344 rats. We found that in IMR-90 cells the activity of cytosolic ICDH (IDPc) gradually increased with age up to the 46-48 population doubling level (PDL) and then gradually decreased at later PDL. 2',7'-Dichloro-fluorescein fluorescence which reflects intracellular ROS generation was increased with aging in IMR-90 cells. In ad libitum-fed rats, we noted age-related, tissue-specific modulations of IDPc and mitochondrial ICDH (IDPm) activities and protein expression in the liver, kidney and testes. In contrast, ICDH activities and protein expression were not significantly modulated in diet-restricted rats. These data suggest that modulation of ICDH is an age-dependent and a tissue-specific phenomenon.

Atmospheric loss from the dayside open polar region and its dependence on geomagnetic activity: implications for atmospheric escape on evolutionary timescales

Directory of Open Access Journals (Sweden)

R. Slapak

2017-06-01

Full Text Available We have investigated the total O+ escape rate from the dayside open polar region and its dependence on geomagnetic activity, specifically Kp. Two different escape routes of magnetospheric plasma into the solar wind, the plasma mantle, and the high-latitude dayside magnetosheath have been investigated separately. The flux of O+ in the plasma mantle is sufficiently fast to subsequently escape further down the magnetotail passing the neutral point, and it is nearly 3 times larger than that in the dayside magnetosheath. The contribution from the plasma mantle route is estimated as  ∼ 3. 9 × 1024exp(0. 45 Kp [s−1] with a 1 to 2 order of magnitude range for a given geomagnetic activity condition. The extrapolation of this result, including escape via the dayside magnetosheath, indicates an average O+ escape of 3 × 1026 s−1 for the most extreme geomagnetic storms. Assuming that the range is mainly caused by the solar EUV level, which was also larger in the past, the average O+ escape could have reached 1027–28 s−1 a few billion years ago. Integration over time suggests a total oxygen escape from ancient times until the present roughly equal to the atmospheric oxygen content today.

TM-pass polarizer based on multilayer graphene polymer waveguide

Science.gov (United States)

Cai, Ke-su; Li, Yue-e.; Wei, Wen-jing; Mu, Xi-jiao; Ma, A.-ning; Wang, Zhong; Song, Dan-ming

2018-05-01

A TM-pass polarizer based on multilayer graphene polymer waveguide is proposed and theoretically analyzed. The mode properties, the extinction ratio, the insertion loss and the bandwidth are also discussed. The results show that a TM-pass polarizer, which only guides the TM mode, can be achieved by multilayer graphene polymer waveguide. With length of 150 μm, the proposed polarizer can achieve extinction ratio of 33 dB and insertion loss of 0.5 dB at optical wavelength of 1.55 μm. This device has an excellent performance, including large extinction ratio and low insertion loss within the spectral range from 1.45 μm to 1.6 μm.

Field and polarity dependence of time-to-resistance increase in Fe–O films studied by constant voltage stress method

OpenAIRE

Eriguchi, Koji; Wei, Zhiqiang; Takagi, Takeshi; Ohta, Hiroaki; Ono, Kouichi

2009-01-01

Constant voltage stress (CVS) was applied to Fe–O films prepared by a sputtering process to investigate a stress-induced resistance increase leading to a fundamental mechanism for switching behaviors. Under the CVS, an abrupt resistance increase was found for both stress polarities. A conduction mechanism after the resistance increase exhibited non-Ohmic transport. The time-to-resistance increase (tr) under the CVS was revealed to strongly depend on stress voltage as well as the polarity. Fro...

Measurement of the permittivity and loss of high-loss materials using a Near-Field Scanning Microwave Microscope

International Nuclear Information System (INIS)

Gregory, A.P.; Blackburn, J.F.; Lees, K.; Clarke, R.N.; Hodgetts, T.E.; Hanham, S.M.; Klein, N.

2016-01-01

In this paper improvements to a Near-Field Scanning Microwave Microscope (NSMM) are presented that allow the loss of high loss dielectric materials to be measured accurately at microwave frequencies. This is demonstrated by measuring polar liquids (loss tangent tanδ≈1) for which traceable data is available. The instrument described uses a wire probe that is electromagnetically coupled to a resonant cavity. An optical beam deflection system is incorporated within the instrument to allow contact mode between samples and the probe tip to be obtained. Liquids are contained in a measurement cell with a window of ultrathin glass. The calibration process for the microscope, which is based on image-charge electrostatic models, has been adapted to use the Laplacian ‘complex frequency’. Measurements of the loss tangent of polar liquids that are consistent with reference data were obtained following calibration against single-crystal specimens that have very low loss. - Highlights: • Design of a microwave microscope with resolution on the micron scale. • Improved theory for obtaining permittivity and loss tangent of high loss materials. • Polar reference liquids are used as test samples. • Traceable measurements with accuracy approximately ±10% in ε′ and ±20% in tan δ.

Enhancing virus-specific immunity in vivo by combining therapeutic vaccination and PD-L1 blockade in chronic hepadnaviral infection.

Directory of Open Access Journals (Sweden)

Jia Liu

2014-01-01

Full Text Available Hepatitis B virus (HBV persistence is facilitated by exhaustion of CD8 T cells that express the inhibitory receptor programmed cell death-1 (PD-1. Improvement of the HBV-specific T cell function has been obtained in vitro by inhibiting the PD-1/PD-ligand 1 (PD-L1 interaction. In this study, we examined whether in vivo blockade of the PD-1 pathway enhances virus-specific T cell immunity and leads to the resolution of chronic hepadnaviral infection in the woodchuck model. The woodchuck PD-1 was first cloned, characterized, and its expression patterns on T cells from woodchucks with acute or chronic woodchuck hepatitis virus (WHV infection were investigated. Woodchucks chronically infected with WHV received a combination therapy with nucleoside analogue entecavir (ETV, therapeutic DNA vaccination and woodchuck PD-L1 antibody treatment. The gain of T cell function and the suppression of WHV replication by this therapy were evaluated. We could show that PD-1 expression on CD8 T cells was correlated with WHV viral loads during WHV infection. ETV treatment significantly decreased PD-1 expression on CD8 T cells in chronic carriers. In vivo blockade of PD-1/PD-L1 pathway on CD8 T cells, in combination with ETV treatment and DNA vaccination, potently enhanced the function of virus-specific T cells. Moreover, the combination therapy potently suppressed WHV replication, leading to sustained immunological control of viral infection, anti-WHs antibody development and complete viral clearance in some woodchucks. Our results provide a new approach to improve T cell function in chronic hepatitis B infection, which may be used to design new immunotherapeutic strategies in patients.

Differences in histological features and PD-L1 expression between sporadic microsatellite instability and Lynch-syndrome-associated disease in Japanese patients with colorectal cancer.

Science.gov (United States)

Yamada, Rin; Yamaguchi, Tatsuro; Iijima, Takeru; Wakaume, Rika; Takao, Misato; Koizumi, Koichi; Hishima, Tsunekazu; Horiguchi, Shin-Ichiro

2018-06-01

The field of immunotherapy has recently focused on cancers with microsatellite instability (MSI). These cancers include both Lynch-syndrome-associated tumors, which are caused by mismatch repair (MMR) germline mutations, and sporadic MSI tumors, which are mainly attributed to MLH1 promoter methylation. The present study aimed to clarify differences in the histological and PD-L1 expression profiles between these two types of MSI cancers in Japanese patients. Among 908 cases of colorectal cancer treated via surgical resection from 2008 to 2014, we identified 64 MSI cancers, including 36 sporadic MSI and 28 Lynch-syndrome-associated cancers, using a BRAF V600E mutation analysis and MLH1 methylation analysis. Of the latter subgroup, 21 (75%) harbored MMR germline mutations. The following were more frequent with sporadic MSI than with Lynch syndrome associated cancers: poor differentiation (50.0 vs. 7.1%, P = 0.0002), especially solid type (30.6 vs. 3.6%, P = 0.0061); medullary morphology (19.4 and 0%, P = 0.015), Crohn-like lymphoid reaction (50.0 vs. 25.0%, P = 0.042), and PD-L1 expression (25.0 vs. 3.6%, P = 0.034). However, the groups did not differ in terms of the mean invasive front and intratumoral CD8-positive cell densities. In a logistic regression analysis, PD-L1 expression correlated with poor differentiation (odds ratio: 7.65, 95% confidence interval: 1.55-37.7, P = 0.012), but not with the difference between sporadic MSI cancer and Lynch-syndrome-associated cancer (odds ratio: 4.74, 95% confidence interval: 0.50-45.0, P = 0.176). Therefore, compared with Lynch-syndrome-associated cancers, sporadic MSI cancers are more frequently solid, poorly differentiated medullary cancers that express PD-L1.

Study of Jupiter polarization properties

International Nuclear Information System (INIS)

Bolkvadze, O.R.

1980-01-01

Investigations into polarization properties of the Jupiter reflected light were carried on at the Abastumani astrophysical observatory in 1967, 1968 and 1969 in the four spectral ranges: 4000, 4800, 5400 and 6600 A deg. Data on light polarization in different parts of the Jupiter visible disk are given. Curves of dependence of the planet light polarization degree on a phase angle are plotted. It is shown that in the central part of the visible planet disk the polarization degree is low. Atmosphere is in a stable state in this part of Jupiter. Mean radius of particles of a cloud layer is equal to 0.26μ, and optical thickness of overcloud atmosphere tau=0.05. Height of transition boundary of the cloud layer into overcloud gas atmosphere changes from year to year at the edges of the equatorial zone. Optical thickness of overcloud atmosphere changes also with changing height of a transient layer. The polar Jupiter regions possess a high degree of polarization which depends on a latitude. Polarization increases monotonously with the latitude and over polar regions accepts a maximum value [ru

Apico-basal polarity complex and cancer

Indian Academy of Sciences (India)

Loss of cell polarity is a hallmark for carcinoma, and its underlying molecular mechanism is beginning to emerge from studies on model organisms and cancer cell lines. Moreover, deregulated expression of apico-basal polarity complex components has been reported in human tumours. In this review, we provide an ...

Periodontal healing complications following extrusive and lateral luxation in the permanent dentition: a longitudinal cohort study

DEFF Research Database (Denmark)

Hermann, Nuno Vibe; Lauridsen, Eva Fejerskov; Christensen, Søren Steno Ahrensburg

2012-01-01

To analyze the risk of tooth loss and complications in periodontal ligament (PDL) healing following extrusive and lateral luxation in the permanent dentition.......To analyze the risk of tooth loss and complications in periodontal ligament (PDL) healing following extrusive and lateral luxation in the permanent dentition....

Solvent Dependency of the UV-Vis Spectrum of Indenoisoquinolines: Role of Keto-Oxygens as Polarity Interaction Probes

Science.gov (United States)

Coletta, Andrea; Castelli, Silvia; Chillemi, Giovanni; Sanna, Nico; Cushman, Mark; Pommier, Yves; Desideri, Alessandro

2013-01-01

Indenoisoquinolines are the most promising non-campthotecins topoisomerase IB inhibitors. We present an integrated experimental/computational investigation of the UV-Vis spectra of the IQNs parental compound (NSC314622) and two of its derivatives (NSC724998 and NSC725776) currently undergoing Phase I clinical trials. In all the three compounds a similar dependence of the relative absorption intensities at 270 nm and 290 nm on solvent polarity is found. The keto-oxygens in positions 5 and 11 of the molecular scaffold of the molecule are the principal chromophores involved in this dependence. Protic interactions on these sites are also found to give rise to absorptions at wavelength <250 nm observed in water solution, due to the stabilization of highly polarized tautomers of the molecule. These results suggest that the keto-oxygens are important polarizable groups that can act as useful interactors with the molecular receptor, providing at the same time an useful fingerprint for the monitoring of the drug binding to topoisomerase IB. PMID:24086299

Instrumentation with polarized neutrons

International Nuclear Information System (INIS)

Boeni, P.; Muenzer, W.; Ostermann, A.

2009-01-01

Neutron scattering with polarization analysis is an indispensable tool for the investigation of novel materials exhibiting electronic, magnetic, and orbital degrees of freedom. In addition, polarized neutrons are necessary for neutron spin precession techniques that path the way to obtain extremely high resolution in space and time. Last but not least, polarized neutrons are being used for fundamental studies as well as very recently for neutron imaging. Many years ago, neutron beam lines were simply adapted for polarized beam applications by adding polarizing elements leading usually to unacceptable losses in neutron intensity. Recently, an increasing number of beam lines are designed such that an optimum use of polarized neutrons is facilitated. In addition, marked progress has been obtained in the technology of 3 He polarizers and the reflectivity of large-m supermirrors. Therefore, if properly designed, only factors of approximately 2-3 in neutron intensity are lost. It is shown that S-benders provide neutron beams with an almost wavelength independent polarization. Using twin cavities, polarized beams with a homogeneous phase space and P>0.99 can be produced without significantly sacrificing intensity. It is argued that elliptic guides, which are coated with large m polarizing supermirrors, provide the highest flux.

First-principles calculation of the polarization-dependent force driving the Eg mode in bismuth under optical excitation.

Science.gov (United States)

Murray, Eamonn; Fahy, Stephen

2014-03-01

Using first principles electronic structure methods, we calculate the induced force on the Eg (zone centre transverse optical) phonon mode in bismuth immediately after absorption of polarized light. When radiation with polarization perpendicular to the c-axis is absorbed in bismuth, the distribution of excited electrons and holes breaks the three-fold rotational symmetry and leads to a net force on the atoms in the direction perpendicular to the axis. We calculate the initial excited electronic distribution as a function of photon energy and polarization and find the resulting transverse and longitudinal forces experienced by the atoms. Using the measured, temperature-dependent rate of decay of the transverse force[2], we predict the approximate amplitude of induced atomic motion in the Eg mode as a function of temperature and optical fluence. This work is supported by Science Foundation Ireland and a Marie Curie International Incoming Fellowship.

Few-body experiments with polarized beams and polarized targets

International Nuclear Information System (INIS)

Simmons, J.E.

1983-01-01

A survey is presented concerning recent polarization experiments in the elastic p-d, p- 3 He, and p- 4 He systems. Mention is made of selected neutron experiments. The nominal energy range is 10 to 1000 MeV. Recent results and interpretations of the p-d system near 10 MeV are discussed. New experiments on the energy dependence of back angle p-d tensor polarization are discussed with respect to resolution of discrepancies and difficulty of theoretical interpretation. Progress is noted concerning multiple scattering interpretation of forward p-d deuteron polarization. Some new results are presented concerning the p- 3 He system and higher energy p- 4 He polarization experiments. 52 references

Loss-cone-driven ion cyclotron waves in the magnetosphere

International Nuclear Information System (INIS)

Denton, R.E.; Hudson, M.K.; Roth, I.

1992-01-01

The theoretical properties of linear ion cyclotron waves propagating in the magnetosphere at arbitrary angles to the background magnetic field are explored. It is found that in some cases the linear wave growth of modes with oblique propagation can dominate that of the parallel propagating electromagnetic ion cyclotron (EMIC) wave. In particular, when the hot ring current protons have a loss cone and their temperature anisotropy A ≡ T perpendicular /T parallel - 1 is reduced, the parallel propagating EMIC wave becomes stable, while the obliquely propagating loss-cone-driven mode persists. The growth rate of the loss-cone-driven model depends strongly on the depth of the loss cone. Unlike the parallel propagating EMIC wave, it can be unstable with A = 0. Other conditions that favor the loss-cone-driven mode in comparison to the parallel mode are stronger background magnetic field, lower density of cold hydrogen, and a lower temperature for the hot anisotropic component of hydrogen. A simple analytical theory is presented which explains the scaling of the growth rate of the oblique mode with respect to various parameters. The loss-cone-driven mode is an electromagnetic mode which is preferentially nearly linearly polarized. It is nearly electrostatic in the sense that the wave electric field is aligned with the perpendicular (to B 0 ) component of the wave vector k and k perpendicular > k parallel . Since the electric and magnetic wave fields are perpendicular to B 0 , they would be difficult to distinguish from those of a linearly polarized parallel propagating electromagnetic wave with the same k parallel

Rotational state dependence of ion-polar molecule reactions at very low temperature

International Nuclear Information System (INIS)

Dubernet, M.L.; McCarroll, R.

1989-01-01

The adiabatic rotational state method is used to investigate the rotational state dependence of the rate coefficients for ion-polar molecule reactions in the very low temperature regime characteristic of interstellar molecular clouds. Results obtained for the systems H 3 + +HCl and H 3 + +HCN indicate that all the methods based on the adiabatic separation of the rotational and radial motion of the collision complex - adiabatic capture centrifugal sudden approximation (ACCSA), statistical adiabatic channel model, classical adiabatic invariance method - agree very satisfactorily in the low temperature limit. Discrepancies observed between some of the published data would appear to arise from numerical inaccuracies rather than from any defect of the theory. (orig.)

Dynamic polarization of radioactive nuclei

International Nuclear Information System (INIS)

Kiselev, Yu.F.; Lyuboshits, V.L.; )

2001-01-01

Radioactive nuclei, embedded into a frozen polarized proton target, atr proposed to polarize by means of some dynamic polarization methods. Angular distributions of γ-quanta emitted ny 22 Na(3 + ) in the cascade β-γ-radiation are calculated. It is shown that this distribution does not depend on the spin temperature sing at the Boltzmann distribution of populations among the Zeeman magnetic substates, whereas the tensor polarization of quadrupole nuclei, placed in the electric field of the crystal, causes the considerable sing dependence. The new method promises wide opportunities for the magnetic structure investigations as well as for the study of spin-spin interaction dynamics of rare nuclei in dielectrics. Physical-technical advantages and disadvantages of the given method are discussed for the polarization of heavy nuclei in the on-line implantation mode [ru

Polarization digital holographic microscopy using low-cost liquid crystal polarization rotators

Science.gov (United States)

Dovhaliuk, Rostyslav Yu

2018-02-01

Polarization imaging methods are actively used to study anisotropic objects. A number of methods and systems, such as imaging polarimeters, were proposed to measure the state of polarization of light that passed through the object. Digital holographic and interferometric approaches can be used to quantitatively measure both amplitude and phase of a wavefront. Using polarization modulation optics, the measurement capabilities of such interference-based systems can be extended to measure polarization-dependent parameters, such as phase retardation. Different kinds of polarization rotators can be used to alternate the polarization of a reference beam. Liquid crystals are used in a rapidly increasing number of different optoelectronic devices. Twisted nematic liquid crystals are widely used as amplitude modulators in electronic displays and light valves or shutter glass. Such devices are of particular interest for polarization imaging, as they can be used as polarization rotators, and due to large-scale manufacturing have relatively low cost. A simple Mach-Zehnder polarized holographic setup that uses modified shutter glass as a polarization rotator is demonstrated. The suggested approach is experimentally validated by measuring retardation of quarter-wave film.

Substrate dependence of TM-polarized light emission characteristics of BAlGaN/AlN quantum wells

Science.gov (United States)

Park, Seoung-Hwan; Ahn, Doyeol

2018-06-01

To study the substrate dependence of light emission characteristics of transverse-magnetic (TM)-polarized light emitted from BAlGaN/AlN quantum wells (QWs) grown on GaN and AlN substrates were investigated theoretically. It is found that the topmost valence subband for QW structures grown on AlN substrate, is heavy hole state (HH1) while that for QW structures grown on GaN substrate is crystal-field split off light hole state (CL1), irrespective of the boron content. Since TM-polarized light emission is associated with the light hole state, the TM-polarized emission peak of BAlGaN/AlN QW structures grown on GaN substrate is expected to be much larger than that of the QW structure grown on AlN substrate. Also, both QW structures show that the spontaneous emission peak of BAlGaN/AlN QW structures would be improved with the inclusion of the boron. However, it rapidly begins to decrease when the boron content exceeds a critical value.

T-odd polarization observables in deuteron electrodisintegration

International Nuclear Information System (INIS)

Rekalo, M.P.; Gakh, G.I.; Rekalo, A.P.

1996-01-01

It is considered such simplest T-odd polarization observables of the deuteron disintegration as proton polarization in d(e, e' p-bar)n and the asymmetry in the scattering of unpolarized electrons by a vector-polarized target, d-bar (e, e' p)n. The θ dependence of theses observables has been studied. The procedure of making the conserved electromagnetic current has an essential influence on the final θ dependence of the T-odd polarization observables [ru

Simulation of Probe Position-Dependent Electron Energy-Loss Fine Structure

Energy Technology Data Exchange (ETDEWEB)

Oxley, M. P.; Kapetanakis, M. D.; Prange, Micah P.; Varela, M.; Pennycook, Stephen J.; Pantelides, Sokrates T.

2014-03-31

We present a theoretical framework for calculating probe-position-dependent electron energy-loss near-edge structure for the scanning transmission electron microscope by combining density functional theory with dynamical scattering theory. We show how simpler approaches to calculating near-edge structure fail to include the fundamental physics needed to understand the evolution of near-edge structure as a function of probe position and investigate the dependence of near-edge structure on probe size. It is within this framework that density functional theory should be presented, in order to ensure that variations of near-edge structure are truly due to local electronic structure and how much from the diffraction and focusing of the electron beam.

Expression of TLR4 in Non-Small Cell Lung Cancer Is Associated with PD-L1 and Poor Prognosis in Patients Receiving Pulmonectomy

Directory of Open Access Journals (Sweden)

Xiubao Ren

2017-04-01

Full Text Available Currently, the effect of inflammation on tumorigenesis and progression has been widely noted. As a member of pattern recognition receptors, toll-like receptor 4 (TLR4 plays a pivotal role in tumor immune microenvironment and has been increasingly investigated. In the present study, we evaluated TLR4 expression and its association with programmed cell death ligand 1 (PD-L1 in non-small cell lung cancer (NSCLC tissues and assessed the predicting value of TLR4 on postoperative outcome. A total of 126 NSCLC patients receiving complete pulmonary resection and systematic lymph node dissection between April 2008 and August 2014 were enrolled. All the patients had integrated clinicopathological records and follow-up data. TLR4 and PD-L1 expression on NSCLC samples were determined by immunohistochemistry, and serum soluble TLR4 (sTLR4 levels were measured by enzyme-linked immunosorbent assay. Results showed that TLR4 expression level in cancer tissue was significantly higher than that in para-cancer tissue. Elevated TLR4 expression was significantly associated with histological type (adenocarcinoma higher than squamous cell carcinoma, P = 0.041, increased clinical TNM stage (P < 0.001, and presence of lymphatic invasion (P < 0.001. Besides, TLR4 expression level in cancer samples was inversely correlated with serum sTLR4 level in patients with early-stage NSCLC (r = −0.485, P = 0.003. TLR4 expression level was also positively correlated with the PD-L1 expression level (r = 0.545, P < 0.0001. Multivariate analysis showed that expression level of TLR4 was an independent prognostic factor and TLR4 overexpression indicated a poor overall survival and disease-free survival. Taken together, we conclude that expression of TLR4 in lung cancer is associated with PD-L1 and could predict the outcome of patients with NSCLC receiving pulmonary resection for cancer.

Magnetic field-dependent polarization of (111)-oriented PZT–Co ferrite nanobilayer: Effect of Co ferrite composition

Energy Technology Data Exchange (ETDEWEB)

Khodaei, M. [Advanced Magnetic Materials Research Center, School of Metallurgy and Materials, College of Engineering, University of Tehran, Tehran (Iran, Islamic Republic of); Faculty of Materials Science and Engineering, K. N. Toosi University of Technology, Tehran (Iran, Islamic Republic of); Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang 790-784 (Korea, Republic of); Seyyed Ebrahimi, S.A., E-mail: saseyyed@ut.ac.ir [Advanced Magnetic Materials Research Center, School of Metallurgy and Materials, College of Engineering, University of Tehran, Tehran (Iran, Islamic Republic of); Jun Park, Yong [Pohang Accelerator Laboratory, Pohang University of Science and Technology (POSTECH), Pohang 790-784 (Korea, Republic of); Son, Junwoo; Baik, Sunggi [Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang 790-784 (Korea, Republic of)

2015-05-15

The perfect (111)-oriented PZT/CFO (CFO=CoFe{sub 2}O{sub 4}, Co{sub 0.8}Fe{sub 2.2}O{sub 4} and Co{sub 0.6}Mn{sub 0.2}Fe{sub 2.2}O{sub 4}) bilayer multiferroic thin films were grown on Pt(111)/Si substrate at 600 °C using pulsed laser deposition technique. The precision X-ray diffraction analysis (avoiding the shift of peak due to the sample misalignment) revealed that the CFO films on Pt(111)/Si substrate were under an out-of-plane contraction and deposition of PZT top layer led to more increase in the out-of-plane contraction, i.e. increase in the residual stresses. The PZT and CFO layers have significant effects on magnetic and ferroelectric properties of PZT/CFO bilayer films, respectively, leading to an enhanced in-plane magnetic anisotropy as well as increased and asymmetric polarization. The effect of composition of CFO layer on magnetic field-dependent polarization of PZT/CFO bilayer films was investigated by applying the magnetic field during P-E measurement. The polarization of PZT films were increased by applying the magnetic field as a result of strain transferred from magnetostrictive CFO underlayer. This increase in polarization for PZT/Co{sub 0.6}Mn{sub 0.2}Fe{sub 2.2}O{sub 4} was higher than that for PZT/Co{sub 0.8}Fe{sub 2.2}O{sub 4} and both of them were significantly higher than that for PZT/CoFe{sub 2}O{sub 4} bilayer film, which was discussed based on their magnetostriction properties. - Highlights: • The effect of composition of CFO on P–E characteristics of PZT/CFO films was investigated. • The polarization of PZT films were increased by applying the magnetic field. • The increasing polarization was a result of strain from magnetostrictive CFO underlayer.

Polarization-Dependent Quasi-Far-Field Superfocusing Strategy of Nanoring-Based Plasmonic Lenses.

Science.gov (United States)

Sun, Hao; Zhu, Yechuan; Gao, Bo; Wang, Ping; Yu, Yiting

2017-12-01

The two-dimensional superfocusing of nanoring-based plasmonic lenses (NRPLs) beyond the diffraction limit in the far-field region remains a great challenge at optical wavelengths. In this paper, in addition to the modulation of structural parameters, we investigated the polarization-dependent focusing performance of a NRPL employing the finite-difference time-domain (FDTD) method. By utilizing the state of polarization (SOP) of incident light, we successfully realize the elliptical-, donut-, and circular-shape foci. The minimum full widths at half maximum (FWHMs) of these foci are ~0.32, ~0.34, and ~0.42 λ 0 in the total electric field, respectively, and the depth of focus (DOF) lies in 1.41~1.77 λ 0 . These sub-diffraction-limit foci are well controlled in the quasi-far-field region. The underlying physical mechanism on the focal shift and an effective way to control the focusing position are proposed. Furthermore, in the case of a high numerical aperture, the longitudinal component, which occupies over 80% of the electric-field energy, decides the focusing patterns of the foci. The achieved sub-diffraction-limit focusing can be widely used for many engineering applications, including the super-resolution imaging, particle acceleration, quantum optical information processing, and optical data storage.

Study on Frequency Dependency of ON-Resistance and Pulse-Loss Calculation of MOSFETs for Switch Mode Power Supply

Science.gov (United States)

Yamamura, Hideho; Sato, Ryohei; Iwata, Yoshiharu

Global efforts toward energy conservation, increasing data centers, and the increasing use of IT equipments are leading to a demand in reduced power consumption of equipments, and power efficiency improvement of power supply units is becoming a necessity. MOSFETs are widely used for their low ON-resistances. Power efficiency is designed using time-domain circuit simulators, except for transformer copper-loss, which has frequency dependency which is calculated separately using methods based on skin and proximity effects. As semiconductor technology reduces the ON-resistance of MOSFETs, frequency dependency due to the skin effect or proximity effect is anticipated. In this study, ON-resistance of MOSFETs are measured and frequency dependency is confirmed. Power loss against rectangular current pulse is calculated. The calculation method for transformer copper-loss is expanded to MOSFETs. A frequency function for the resistance model is newly developed and parametric calculation is enabled. Acceleration of calculation is enabled by eliminating summation terms. Using this method, it is shown that the frequency dependent component of the measured MOSFETs increases the dissipation from 11% to 32% at a switching frequency of 100kHz. From above, this paper points out the importance of the frequency dependency of MOSFETs' ON-resistance, provides means of calculating its pulse losses, and improves loss calculation accuracy of SMPSs.

Energy Band Gap Dependence of Valley Polarization of the Hexagonal Lattice

Science.gov (United States)

Ghalamkari, Kazu; Tatsumi, Yuki; Saito, Riichiro

2018-02-01

The origin of valley polarization of the hexagonal lattice is analytically discussed by tight binding method as a function of energy band gap. When the energy gap decreases to zero, the intensity of optical absorption becomes sharp as a function of k near the K (or K') point in the hexagonal Brillouin zone, while the peak intensity at the K (or K') point keeps constant with decreasing the energy gap. When the dipole vector as a function of k can have both real and imaginary parts that are perpendicular to each other in the k space, the valley polarization occurs. When the dipole vector has only real values by selecting a proper phase of wave functions, the valley polarization does not occur. The degree of the valley polarization may show a discrete change that can be relaxed to a continuous change of the degree of valley polarization when we consider the life time of photo-excited carrier.

In-plane polarization dependence of (Bi,Pb){sub 2}Sr{sub 2}CaCu{sub 2}O{sub 8+δ} single crystals studied by X-ray absorption spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Ghafari, A., E-mail: ghafari@physik.hu-berlin.de [Institute of Physics, Humboldt University of Berlin, Newtonstr., 15, D-12489 Berlin (Germany); Elettra Sincrotrone Trieste, Strada Statale 14 km 163.5, I-34149 Trieste (Italy); Ariffin, A.K. [Institute of Physics, Humboldt University of Berlin, Newtonstr., 15, D-12489 Berlin (Germany); Department of Physics, Universiti Pendidikan Sultan Idris, 35900 Tanjong Malim (Malaysia); Janowitz, C., E-mail: christoph.janowitz@physik.hu-berlin.de [Institute of Physics, Humboldt University of Berlin, Newtonstr., 15, D-12489 Berlin (Germany); Dwelk, H.; Krapf, A.; Manzke, R. [Institute of Physics, Humboldt University of Berlin, Newtonstr., 15, D-12489 Berlin (Germany)

2014-06-15

The effects of in-plane polarization change on the determination of the hole density of weakly under-doped (Bi, Pb)-2212 single crystals has been studied by x-ray absorption spectroscopy (XAS). The XAS signal at the CuL{sub 3} edge (925–940 eV) and O K edge (525 eV to 539 eV) were recorded under continuous rotation of the CuO{sub 2} plane from 0° to 180° with a minimum increment of 1.8°, yielding experimentally an in-plane polarization dependence for the absorption signals at the respective threshold. From that the in-plane angular dependence of the hole density (n{sub H}(φ)) could be determined. Fermi's golden rule was then used for the evaluation of the in-plane polarization dependence showing the expected polarization independence in disaccord to the experimental observations. Possible scenarios to solve this issue are discussed. Our results propose that polarization dependence could be due to inhomogeneous distribution of holes in the CuO{sub 2} planes which is also supported by models. Second, the role of out of plane orbitals has to be taken into account for interpretation.

Targeting PD-1/PD-L1 in lung cancer: current perspectives

Directory of Open Access Journals (Sweden)

González-Cao M

2015-07-01

Full Text Available María González-Cao,1 Niki Karachaliou,1 Santiago Viteri,1 Daniela Morales-Espinosa,1 Cristina Teixidó,2 Jesús Sánchez Ruiz,3 Miquel Ángel Molina-Vila,2 Mariacarmela Santarpia,4 Rafael Rosell1,2,5,61Translational Cancer Research Unit, Instituto Oncológico Dr Rosell, Quirón Dexeus University Hospital, Barcelona, Spain; 2Pangaea Biotech SL, Barcelona, Spain; 3Centro Nacional de Investigación Oncología (CNIO, Madrid, Spain; 4Medical Oncology Unit, Human Pathology Department, University of Messina, Messina, Italy; 5Cancer Biology and Precision Medicine Program, Catalan Institute of Oncology, Germans Trias i Pujol Health Sciences Institute and Hospital, Campus Can Ruti, Badalona, Barcelona, Spain; 6Fundación Molecular Oncology Research, Barcelona, SpainAbstract: Increased understanding of tumor immunology has led to the development of effective immunotherapy treatments. One of the most important advances in this field has been due to pharmacological design of antibodies against immune checkpoint inhibitors. Anti-PD-1/PD-L1 antibodies are currently in advanced phases of clinical development for several tumors, including lung cancer. Results from Phase I–III trials with anti-PD-1/PD-L1 antibodies in non-small-cell lung cancer have demonstrated response rates of around 20% (range, 16%–50%. More importantly, responses are long-lasting (median duration of response, 18 months and fast (50% of responses are detected at time of first tumor evaluation with very low grade 3–4 toxicity (less than 5%. Recently, the anti-PD-1 antibody pembrolizumab received US Food and Drug Administration (FDA breakthrough therapy designation for treatment of non-small-cell lung cancer, supported by data from a Phase Ib trial. Another anti-PD-1 antibody, nivolumab, has also been approved for lung cancer based on survival advantage demonstrated in recently released data from a Phase III trial in squamous cell lung cancer.Keywords: immunotherapy, immunoncology

Spin tune dependence on closed orbit in RHIC

International Nuclear Information System (INIS)

Ptitsyn, V.; Bai, M.; Roser, T.

2010-01-01

Polarized proton beams are accelerated in RHIC to 250 GeV energy with the help of Siberian Snakes. The pair of Siberian Snakes in each RHIC ring holds the design spin tune at 1/2 to avoid polarization loss during acceleration. However, in the presence of closed orbit errors, the actual spin tune can be shifted away from the exact 1/2 value. It leads to a corresponding shift of locations of higher-order ('snake') resonances and limits the available betatron tune space. The largest closed orbit effect on the spin tune comes from the horizontal orbit angle between the two snakes. During RHIC Run in 2009 dedicated measurements with polarized proton beams were taken to verify the dependence of the spin tune on the local orbits at the Snakes. The experimental results are presented along with the comparison with analytical predictions.

n value and Jc distribution dependence of AC transport current losses in HTS conductors

International Nuclear Information System (INIS)

Ogawa, Jun; Sawai, Yusuke; Nakayama, Haruki; Tsukamoto, Osami; Miyagi, Daisuke

2004-01-01

Compared with LTS materials, HTS materials have some peculiarities affecting AC loss characteristics of the conductors. We measured the AC transport current losses in YBCO thin film coated conductors and a Bi2223/Ag sheathed tape. Comparing the measured data with analytical calculations, the dependence of the AC transport current losses on the n value and critical current density distributions are studied. It is shown that, considering the n values and J c distributions, the peculiarities in the HTS materials can be taken into consideration and the transport current losses in HTS conductors can be calculated by the same analytical method used for LTS

Frequency dependence of magnetic ac loss in a Roebel cable made of YBCO on a Ni-W substrate

Science.gov (United States)

Lakshmi, L. S.; Staines, M. P.; Badcock, R. A.; Long, N. J.; Majoros, M.; Collings, E. W.; Sumption, M. D.

2010-08-01

We have investigated the frequency dependent contributions to the magnetic ac loss in a 10 strand Roebel cable with 2 mm wide non-insulated strands and a transposition length of 90 mm. This cable is made from 40 mm wide YBCO coated conductor tape manufactured by AMSC and stabilized by electroplating 25 µm thick copper on either side prior to the mechanical punching of the cable strands. The measurements were carried out in both perpendicular and parallel field orientation, at frequencies in the range of 30-200 Hz. While the loss in the perpendicular orientation is predominantly hysteretic in nature, we observe some frequency dependence of the loss when the cable approaches full flux penetration at high field amplitudes. The magnitude is consistent with eddy current losses in the copper stabilization layer. This supports the fact that the inter-strand coupling loss is not significant in this frequency range. In the parallel field orientation, the hysteresis loss in the Ni-W alloy substrate dominates, but we see an unusually strong frequency dependent contribution to the loss which we attribute to intra-strand current loops.

Reduction of coating induced polarization aberrations by controlling the polarization state variation

International Nuclear Information System (INIS)

Li, Yanghui; Shen, Weidong; Zheng, Zhenrong; Zhang, Yueguang; Liu, Xu; Hao, Xiang

2011-01-01

The mechanism of coating induced polarization state variation is analysed by the Jones matrix. Pauli spin matrices are used to establish the relationship between coating induced polarization state variation and polarization aberrations. To reduce coating induced polarization aberrations, we propose that δ = 0 and T s = T p at arbitrary incident angle should be appended as two additional optimization goals of optical coating design when the requirements of transmittance are met. Two typical anti-reflection (AR) coatings are designed and the polarization state variation induced by them is simulated. The MTF (modulation transfer function) calculated by polarization ray tracing is applied to evaluate the polarization aberrations of the practical lithography objective system with the two AR coatings. All the obtained results show that the coating induced polarization aberrations can be reduced by optimizing the angle dependent properties of the optical coating without additional optical elements

Temperature dependence of Kerr coefficient and quadratic polarized optical coefficient of a paraelectric Mn:Fe:KTN crystal

Directory of Open Access Journals (Sweden)

Qieni Lu

2015-08-01

Full Text Available We measure temperature dependence on Kerr coefficient and quadratic polarized optical coefficient of a paraelectric Mn:Fe:KTN crystal simultaneously in this work, based on digital holographic interferometry (DHI. And the spatial distribution of the field-induced refractive index change can also be visualized and estimated by numerically retrieving sequential phase maps of Mn:Fe:KTN crystal from recording digital holograms in different states. The refractive indices decrease with increasing temperature and quadratic polarized optical coefficient is insensitive to temperature. The experimental results suggest that the DHI method presented here is highly applicable in both visualizing the temporal and spatial behavior of the internal electric field and accurately measuring electro-optic coefficient for electrooptical media.

Polarization-insensitive quantum-dot coupled quantum-well semiconductor optical amplifier

International Nuclear Information System (INIS)

Huang Lirong; Yu Yi; Tian Peng; Huang Dexiu

2009-01-01

The optical gain of a quantum-dot semiconductor optical amplifier is usually seriously dependent on polarization; we propose a quantum-dot coupled tensile-strained quantum-well structure to obtain polarization insensitivity. The tensile-strained quantum well not only serves as a carrier injection layer of quantum dots but also offers gain to the transverse-magnetic mode. Based on the polarization-dependent coupled carrier rate-equation model, we study carrier competition among quantum well and quantum dots, and study the polarization dependence of the quantum-dot coupled quantum-well semiconductor optical amplifier. We also analyze polarization-dependent photon-mediated carrier distribution among quantum well and quantum dots. It is shown that polarization-insensitive gain can be realized by optimal design

Polarity-dependent resistance switching in GeSbTe phase-change thin films : The importance of excess Sb in filament formation

NARCIS (Netherlands)

Pandian, Ramanathaswamy; Kooi, Bart J.; Oosthoek, Jasper L. M.; van den Dool, Pim; Palasantzas, George; Pauza, Andrew

2009-01-01

We show that polarity-dependent resistance switching in GeSbTe thin films depends strongly on Sb composition by comparing current-voltage characteristics in Sb-excess Ge(2)Sb(2+x)Te(5) and stoichiometric Ge(2)Sb(2)Te(5) samples. This type of switching in Ge(2)Sb(2+x)Te(5) films is reversible with

Airborne Laser Polarization Sensor

Science.gov (United States)

Kalshoven, James, Jr.; Dabney, Philip

1991-01-01

Instrument measures polarization characteristics of Earth at three wavelengths. Airborne Laser Polarization Sensor (ALPS) measures optical polarization characteristics of land surface. Designed to be flown at altitudes of approximately 300 m to minimize any polarizing or depolarizing effects of intervening atmosphere and to look along nadir to minimize any effects depending on look angle. Data from measurements used in conjunction with data from ground surveys and aircraft-mounted video recorders to refine mathematical models used in interpretation of higher-altitude polarimetric measurements of reflected sunlight.

Direct measurement of bull's-eye nanoantenna metal loss

Science.gov (United States)

Hassani Nia, Iman; Jang, Sung J.; Memis, Omer G.; Gelfand, Ryan; Mohseni, Hooman

2013-09-01

The loss in optical antennas can affect their performance for their practical use in many branches of science such as biological and solar cell applications. However the big question is that how much loss is due to the joule heating in the metals. This would affect the efficiency of solar cells and is very important for single photon detection and also for some applications where high heat generation in nanoantennas is desirable, for example, payload release for cancer treatment. There are few groups who have done temperature measurements by methods such as Raman spectroscopy or fluorescence polarization anisotropy. The latter method, which is more reliable than Raman spectroscopy, requires the deposition of fluorescent molecules on the antenna surface. The molecules and the polarization of radiation rotate depending upon the surface temperature. The reported temperature measurement accuracy in this method is about 0.1° C. Here we present a method based on thermo-reflectance that allows better temperature accuracy as well as spatial resolution of 500 nm. Moreover, this method does not require the addition of new materials to the nanoantenna. We present the measured heat dissipation from bull's-eye nanoantennas and compare them with 3D simulation results.

Relevance of intracellular polarity to accuracy of eukaryotic chemotaxis

International Nuclear Information System (INIS)

Hiraiwa, Tetsuya; Nishikawa, Masatoshi; Shibata, Tatsuo; Nagamatsu, Akihiro; Akuzawa, Naohiro

2014-01-01

Eukaryotic chemotaxis is usually mediated by intracellular signals that tend to localize at the front or back of the cell. Such intracellular polarities frequently require no extracellular guidance cues, indicating that spontaneous polarization occurs in the signal network. Spontaneous polarization activity is considered relevant to the persistent motions in random cell migrations and chemotaxis. In this study, we propose a theoretical model that connects spontaneous intracellular polarity and motile ability in a chemoattractant solution. We demonstrate that the intracellular polarity can enhance the accuracy of chemotaxis. Chemotactic accuracy should also depend on chemoattractant concentration through the concentration-dependent correlation time in the polarity direction. Both the polarity correlation time and the chemotactic accuracy depend on the degree of responsiveness to the chemical gradient. We show that optimally accurate chemotaxis occurs at an intermediate responsiveness of intracellular polarity. Experimentally, we find that the persistence time of randomly migrating Dictyostelium cells depends on the chemoattractant concentration, as predicted by our theory. At the optimum responsiveness, this ameboid cell can enhance its chemotactic accuracy tenfold. (paper)

Real-time photonic sampling with improved signal-to-noise and distortion ratio using polarization-dependent modulators

Science.gov (United States)

Liang, Dong; Zhang, Zhiyao; Liu, Yong; Li, Xiaojun; Jiang, Wei; Tan, Qinggui

2018-04-01

A real-time photonic sampling structure with effective nonlinearity suppression and excellent signal-to-noise ratio (SNR) performance is proposed. The key points of this scheme are the polarization-dependent modulators (P-DMZMs) and the sagnac loop structure. Thanks to the polarization sensitive characteristic of P-DMZMs, the differences between transfer functions of the fundamental signal and the distortion become visible. Meanwhile, the selection of specific biases in P-DMZMs is helpful to achieve a preferable linearized performance with a low noise level for real-time photonic sampling. Compared with the quadrature-biased scheme, the proposed scheme is capable of valid nonlinearity suppression and is able to provide a better SNR performance even in a large frequency range. The proposed scheme is proved to be effective and easily implemented for real time photonic applications.

Spin-polarization dependent carrier recombination dynamics and spin relaxation mechanism in asymmetrically doped (110) n-GaAs quantum wells

Science.gov (United States)

Teng, Lihua; Jiang, Tianran; Wang, Xia; Lai, Tianshu

2018-05-01

Carrier recombination and electron spin relaxation dynamics in asymmetric n-doped (110) GaAs/AlGaAs quantum wells are investigated with time-resolved pump-probe spectroscopy. The experiment results reveal that the measured carrier recombination time depends strongly on the polarization of pump pulse. With the same pump photon flux densities, the recombination time of spin-polarized carriers is always longer than that of the spin-balanced carriers except at low pump photon flux densities, this anomaly originates from the polarization-sensitive nonlinear absorption effect. Differing from the traditional views, in the low carrier density regime, the D'yakonov-Perel' (DP) mechanism can be more important than the Bir-Aronov-Pikus (BAP) mechanism, since the DP mechanism takes effect, the spin relaxation time in (110) GaAs QWs is shortened obviously via asymmetric doping.

Constrained Combinatorial Libraries of Gp2 Proteins Enhance Discovery of PD-L1 Binders.

Science.gov (United States)

Kruziki, Max A; Sarma, Vidur; Hackel, Benjamin J

2018-06-05

Engineered protein ligands are used for molecular therapy, diagnostics, and industrial biotechnology. The Gp2 domain is a 45-amino acid scaffold that has been evolved for specific, high-affinity binding to multiple targets by diversification of two solvent-exposed loops. Inspired by sitewise enrichment of select amino acids, including cysteine pairs, in earlier Gp2 discovery campaigns, we hypothesized that the breadth and efficiency of de novo Gp2 discovery will be aided by sitewise amino acid constraint within combinatorial library design. We systematically constructed eight libraries and comparatively evaluated their efficacy for binder discovery via yeast display against a panel of targets. Conservation of a cysteine pair at the termini of the first diversified paratope loop increased binder discovery 16-fold ( p libraries with conserved cysteine pairs, within the second loop or an interloop pair, did not aid discovery thereby indicating site-specific impact. Via a yeast display protease resistance assay, Gp2 variants from the loop one cysteine pair library were 3.3 ± 2.1-fold ( p = 0.005) more stable than nonconstrained variants. Sitewise constraint of noncysteine residues-guided by previously evolved binders, natural Gp2 homology, computed stability, and structural analysis-did not aid discovery. A panel of binders to programmed death ligand 1 (PD-L1), a key target in cancer immunotherapy, were discovered from the loop 1 cysteine constraint library. Affinity maturation via loop walking resulted in strong, specific cellular PD-L1 affinity ( K d = 6-9 nM).

Jet suppression and the flavor dependence of partonic energy loss with ATLAS

Energy Technology Data Exchange (ETDEWEB)

Kosek, Tomas

2016-12-15

In relativistic heavy ion collisions, a hot medium with a high density of unscreened color charges is produced. One manifestation of the energy loss of jets propagating through the medium is a lower yield of jets and hadrons emerging from this medium than expected in the absence of medium effects. Therefore modifications of the jet yield are directly sensitive to the energy loss mechanism. Furthermore, jets with different flavor content are expected to be affected by the medium in different ways. In this publication, the latest ATLAS results on single hadron suppression along with the complementary measurements of single jet suppression are presented. Rapidity dependence, which is sensitive to the relative energy loss between quark and gluon jets, is discussed. Finally, a new measurement of jet fragmentation functions is presented.

Magnetic loss, permeability, and anisotropy compensation in CoO-doped Mn-Zn ferrites

Science.gov (United States)

Beatrice, Cinzia; Dobák, Samuel; Tsakaloudi, Vasiliki; Ragusa, Carlo; Fiorillo, Fausto; Martino, Luca; Zaspalis, Vassilis

2018-04-01

Mn-Zn ferrite samples prepared by conventional solid state reaction method and sintering at 1325 °C were Co-enriched by addition of CoO up to 6000 ppm and characterized versus frequency (DC - 1GHz), peak polarization (2 mT - 200 mT), and temperature (23 °C - 120 °C). The magnetic losses at room temperature are observed to pass through a deep minimum value around 4000 ppm CoO at all polarizations values. This trend is smoothed out either by approaching the MHz range or by increasing the temperature. Conversely, the initial permeability attains its maximum value around the same CoO content, while showing moderate monotonical decrease with increasing CoO at the typical working temperatures of 80 - 100 °C. The energy losses, measured by a combination of fluxmetric and transmission line methods, are affected by the eddy currents, on the conventional 5 mm thick ring samples, only beyond a few MHz. Their assessment relies on the separation of rotational and domain wall processes, which can be done by analysis of the complex permeability and its frequency behavior. This permits one, in particular, to calculate the magnetic anisotropy and its dependence on CoO content and temperature and bring to light its decomposition into the host lattice and Co2+ temperature dependent contributions. The temperature and doping dependence of initial permeability and magnetic losses can in this way be qualitatively justified, without invoking the passage through zero value of the effective anisotropy constant upon doping.

Polarized particles in storage rings

International Nuclear Information System (INIS)

Derbenev, Ya.S.; Kondratenko, A.M.; Serednyakov, S.I.; Skrinskij, A.N.; Tumajkin, G.M.; Shatunov, Yu.M.

1977-01-01

Experiments with polarized beams on the VEPP-2M and SPEAK storage rings are described. Possible methods of producing polarized particle beams in storage rings as well as method of polarization monitoring are counted. Considered are the processes of radiation polarization of electrons and positrons. It is shown, that to preserve radiation polarization the introduction of regions with a strong sign-variable magnetic field is recommended. Methods of polarization measurement are counted. It is suggested for high energies to use dependence of synchrotron radiation power on transverse polarization of electrons and positrons. Examples of using polarizability of colliding beams in storage rings are presented

Tumoral immune-infiltrate (IF), PD-L1 expression and role of CD8/TIA-1 lymphocytes in localized osteosarcoma patients treated within protocol ISG-OS1.

Science.gov (United States)

Palmerini, Emanuela; Agostinelli, Claudio; Picci, Piero; Pileri, Stefano; Marafioti, Teresa; Lollini, Pier-Luigi; Scotlandi, Katia; Longhi, Alessandra; Benassi, Maria Serena; Ferrari, Stefano

2017-12-19

We hypothesized that immune-infiltrates were associated with superior survival, and examined a primary osteosarcoma tissue microarrays (TMAs) to test this hypothesis. 129 patients (pts) with localized osteosarcoma treated within protocol ISG-OS1 were included in the study. Clinical characteristics, expression of CD8, CD3, FOXP3, CD20, CD68/CD163 (tumor associated macrophage, TAM), Tia-1 (cytotoxic T cell), CD303 (plasmacytoid dendritic cells: pDC), Arginase-1 (myeloid derived suppressor cells: MDSC), PD-1 on immune-cells (IC), and PD-L1 on tumoral cells (TC) and IC were analysed and correlated with outcome. Most of the cases presented tumor infiltrating lymphocytes (TILs) (CD3+ 90%; CD8+ 86%). Tia-1 was detected in 73% of the samples. PD-L1 expression was found in 14% patients in IC and 0% in TC; 22% showed PD-1 expression in IC.With a median follow-up of 8 years (range 1-13), the 5-year overall survival (5-year OS) was 74% (95% CI 64-85). Univariate analysis showed better 5-year OS for: a) pts with a good histologic response to neoadjuvant chemotherapy (p = 0.0001); b) pts with CD8/Tia1 tumoral infiltrates (p = 0.002); c) pts with normal alkaline phosphatas (sALP) (p = 0.04). After multivariate analysis, histologic response (p = 0.007) and CD8/Tia1 infiltration (p = 0.01) were independently correlated with survival. In the subset of pts with CD8+ infiltrate, worse (p 0.02) OS was observed for PD-L1(IC)+ cases. Our findings support the hypothesis that CD8/Tia1 infiltrate in tumor microenvironment at diagnosis confers superior survival for pts with localized osteosarcoma, while PD-L1 expression is associated with worse survival.

Detecting spin polarization of nano-crystalline manganese doped zinc oxide thin film using circular polarized light

Energy Technology Data Exchange (ETDEWEB)

El-Sayed, H.M., E-mail: h_m_elsaid@hotmail.com

2016-02-01

The presence of spin polarization in Mn-doped ZnO thin film is very important for spintronic applications. Spin polarization was detected using simple method. This method depends on measuring the optical transmittance using circular polarized light in visible and near infra-red region. It was found that, there is a difference in the optical energy gap of the film for circular left and circular polarized light. For temperatures > 310 K the difference in energy gap is vanished. This result is confirmed by measuring the magnetic hysteresis of the film. This work introduces a promising method for measuring the ferromagnetism in diluted magnetic semiconductors. - Highlights: • Highly oriented c-axis of Mn-ZnO thin film doped with nitrogen is prepared. • The optical energy gap depends on the state of circularly polarized light. • The presence of spin polarization is confirmed using simple optical method. • Magnetic measurements are consistent with the results of the optical method.

Trajectory-dependent energy loss for swift He atoms axially scattered off a silver surface

Energy Technology Data Exchange (ETDEWEB)

Ríos Rubiano, C.A. [Instituto de Astronomía y Física del Espacio (CONICET-UBA), Casilla de correo 67, sucursal 28, 1428 Buenos Aires (Argentina); Bocan, G.A. [Centro Atómico Bariloche, Comisión Nacional de Energía Ató mica, and Consejo Nacional de Investigaciones Científicas y Técnicas, S.C. de Bariloche, Río Negro (Argentina); Juaristi, J.I. [Departamento de Física de Materiales, Facultad de Químicas, UPV/EHU, 20018 San Sebastián (Spain); Donostia International Physics Center (DIPC) and Centro de Física de Materiales CFM/MPC (CSIC-UPV/EHU), 20018 San Sebastián (Spain); Gravielle, M.S., E-mail: msilvia@iafe.uba.ar [Instituto de Astronomía y Física del Espacio (CONICET-UBA), Casilla de correo 67, sucursal 28, 1428 Buenos Aires (Argentina)

2014-12-01

Angle- and energy-loss-resolved distributions of helium atoms grazingly scattered from a Ag(110) surface along low indexed crystallographic directions are investigated considering impact energies in the few keV range. Final projectile distributions are evaluated within a semi-classical formalism that includes dissipative effects due to electron–hole excitations through a friction force. For mono-energetic beams impinging along the [11{sup ¯}0],[11{sup ¯}2] and [001] directions, the model predicts the presence of multiple peak structures in energy-loss spectra. Such structures provide detailed information about the trajectory-dependent energy loss. However, when the experimental dispersion of the incident beam is taken into account, these energy-loss peaks are completely washed out, giving rise to a smooth energy-loss distribution, in fairly good agreement with available experimental data.

All-fiber polarization switch

Science.gov (United States)

Knape, Harald; Margulis, Walter

2007-03-01

We report an all-fiber polarization switch made out of silica-based microstructured fiber suitable for Q-switching all-fiber lasers. Nanosecond high-voltage pulses are used to heat and expand an internal electrode to cause λ/2-polarization rotation in less than 10 ns for 1.5 μm light. The 10 cm long component has an experimentally measured optical insertion loss of 0.2 dB and a 0-10 kHz repetition frequency capacity and has been durability tested for more than 109 pulses.

Transient, polarity-dependent dielectric response in a twisted nematic liquid crystal under very low frequency excitation.

Science.gov (United States)

Krishnamurthy, K S

2015-09-01

The electric Freedericksz transition is a second-order quadratic effect, which, in a planarly aligned nematic liquid crystal layer, manifests above a threshold field as a homogeneous symmetric distortion with maximum director-tilt in the midplane. We find that, upon excitation by a low frequency (wave field, the instability becomes spatially and temporally varying. This is demonstrated using calamitic liquid crystals, initially in the 90°-twisted planar configuration. The distortion occurs close to the negative electrode following each polarity switch and, for low-voltage amplitudes, decays completely in time. We use the elastically favorable geometry of Brochard-Leger walls to establish the location of maximum distortion. Thus, at successive polarity changes, the direction of extension of both annular and open walls switches between the alignment directions at the two substrates. For high voltages, this direction is largely along the midplane director, while remaining marginally oscillatory. These results are broadly understood by taking into account the time-varying and inhomogeneous field conditions that prevail soon after the polarity reverses. Polarity dependence of the instability is traced to the formation of intrinsic double layers that lead to an asymmetry in field distribution in the presence of an external bias. Momentary field elevation near the negative electrode following a voltage sign reversal leads to locally enhanced dielectric and gradient flexoelectric torques, which accounts for the surface-like phenomenon observed at low voltages. These spatiotemporal effects, also found earlier for other instabilities, are generic in nature.

SLC polarized beam source electron optics design

International Nuclear Information System (INIS)

Eppley, K.R.; Lavine, T.L.; Early, R.A.; Herrmannsfeldt, W.B.; Miller, R.H.; Schultz, D.C.; Spencer, C.M.; Yeremian, A.D.

1991-05-01

This paper describes the design of the beam-line from the polarized electron gun to the linac injector in the Stanford Linear Collider (SLC). The polarized electron source is a GaAs photocathode, requiring 10 -11 -Torr-range pressure for adequate quantum efficiency and longevity. The photocathode is illuminated by 3-nsec-long laser pulses. The quality of the optics for the 160-kV beam is crucial since electron-stimulated gas desorption from beam loss in excess of 0.1% of the 20-nC pulses may poison the photocathode. Our design for the transport line consists of a differential pumping region isolated by a pair of valves. Focusing is provided by a pair of Helmholtz coils and by several iron-encased solenoidal lenses. Our optics design is based on beam transport simulations using 2 1/2-D particle-in-cell codes to model the gun and to solve the fully-relativistic time-dependent equations of motion in three dimensions for electrons in the presence of azimuthally symmetric electromagnetic fields. 6 refs., 6 figs

Corrosion rate of construction materials in hot phosphoric acid with the contribution of anodic polarization

Energy Technology Data Exchange (ETDEWEB)

Kouril, M. [Institute of Chemical Technology, Technicka 5, 166 28 Prague (Czech Republic); Christensen, E. [Technical University of Denmark, Kemitorvet, 2800 Kgs. Lyngby (Denmark); Eriksen, S.; Gillesberg, B. [Tantaline A/S, Nordborgvej 81, 6430 Nordborg (Denmark)

2012-04-15

The paper is focused on selection of a proper material for construction elements of water electrolysers, which make use of a 85% phosphoric acid as an electrolyte at temperature of 150 C and which might be loaded with anodic polarization up to 2.5 V versus a saturated Ag/AgCl electrode (SSCE). Several grades of stainless steels were tested as well as tantalum, niobium, titanium, nickel alloys and silicon carbide. The corrosion rate was evaluated by means of mass loss at free corrosion potential as well as under various levels of polarization. The only corrosion resistant material in 85% phosphoric acid at 150 C and at polarization of 2.5 V/SSCE is tantalum. In that case, even a gentle cathodic polarization is harmful in such an acidic environment. Hydrogen reduction leads to tantalum hydride formation, to loss of mechanical properties and to complete disintegration of the metal. Contrary to tantalum, titanium is free of any corrosion resistance in hot phosphoric acid. Its corrosion rate ranges from tens of millimetres to metres per year depending on temperature of the acid. Alloy bonded tantalum coating was recognized as an effective corrosion protection for both titanium and stainless steel. Its serviceability might be limited by slow dissolution of tantalum that is in order of units of mm/year. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Polarity effects and apparent ion recombination in microionization chambers

Energy Technology Data Exchange (ETDEWEB)

Miller, Jessica R., E-mail: miller@humonc.wisc.edu [Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53705 and Department of Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin 53792 (United States); Hooten, Brian D. [Standard Imaging, Middleton, Wisconsin 53562 (United States); Micka, John A.; DeWerd, Larry A. [Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53705 (United States)

2016-05-15

Purpose: Microchambers demonstrate anomalous voltage-dependent polarity effects. Existing polarity and ion recombination correction factors do not account for these effects. As a result, many commercial microchamber models do not meet the specification of a reference-class ionization chamber as defined by the American Association of Physicists in Medicine. The purpose of this investigation is to determine the cause of these voltage-dependent polarity effects. Methods: A series of microchamber prototypes were produced to isolate the source of the voltage-dependent polarity effects. Parameters including ionization-chamber collecting-volume size, stem and cable irradiation, chamber assembly, contaminants, high-Z materials, and individual chamber components were investigated. Measurements were performed with electrodes coated with graphite to isolate electrode conductivity. Chamber response was measured as the potential bias of the guard electrode was altered with respect to the collecting electrode, through the integration of additional power supplies. Ionization chamber models were also simulated using COMSOL Multiphysics software to investigate the effect of a potential difference between electrodes on electric field lines and collecting volume definition. Results: Investigations with microchamber prototypes demonstrated that the significant source of the voltage-dependent polarity effects was a potential difference between the guard and collecting electrodes of the chambers. The voltage-dependent polarity effects for each prototype were primarily isolated to either the guard or collecting electrode. Polarity effects were reduced by coating the isolated electrode with a conductive layer of graphite. Polarity effects were increased by introducing a potential difference between the electrodes. COMSOL simulations further demonstrated that for a given potential difference between electrodes, the collecting volume of the chamber changed as the applied voltage was altered

Non-linear dielectric signatures of entropy changes in liquids subject to time dependent electric fields

Energy Technology Data Exchange (ETDEWEB)

Richert, Ranko [School of Molecular Sciences, Arizona State University, Tempe, Arizona 85287-1604 (United States)

2016-03-21

A model of non-linear dielectric polarization is studied in which the field induced entropy change is the source of polarization dependent retardation time constants. Numerical solutions for the susceptibilities of the system are obtained for parameters that represent the dynamic and thermodynamic behavior of glycerol. The calculations for high amplitude sinusoidal fields show a significant enhancement of the steady state loss for frequencies below that of the low field loss peak. Also at relatively low frequencies, the third harmonic susceptibility spectrum shows a “hump,” i.e., a maximum, with an amplitude that increases with decreasing temperature. Both of these non-linear effects are consistent with experimental evidence. While such features have been used to conclude on a temperature dependent number of dynamically correlated particles, N{sub corr}, the present result demonstrates that the third harmonic susceptibility display a peak with an amplitude that tracks the variation of the activation energy in a model that does not involve dynamical correlations or spatial scales.

Liraglutide 3.0 mg for weight management: weight-loss dependent and independent effects.

Science.gov (United States)

Bays, Harold; Pi-Sunyer, Xavier; Hemmingsson, Joanna Uddén; Claudius, Birgitte; Jensen, Christine B; Van Gaal, Luc

2017-02-01

As an adjunct to a reduced-calorie diet and increased physical activity, treatment with liraglutide 3.0 mg for weight management provides a statistically significant and clinically meaningful weight loss of 5.7%-8.0% compared to 1.6%-2.6% with placebo. The objective of this post hoc analysis was to quantify the relative contribution of weight loss to the treatment effects of liraglutide 3.0 mg on key efficacy endpoints. The analysis utilized data from 4725 participants across three randomized, placebo-controlled, double-blind trials that evaluated the efficacy and safety of liraglutide 3.0 mg versus placebo, as an adjunct to a reduced-calorie diet and increased physical activity (ClinicalTrials.gov identifiers: NCT01272219, NCT01272232 and NCT01557166). The duration of two of the trials was 56 weeks; one trial was of 32 weeks' duration. A mediation analysis was performed, which ranked the relative contribution of weight loss to the treatment effects of liraglutide 3.0 mg on key cardiometabolic efficacy endpoints, Apnea-Hypopnea Index (AHI) and health-related quality of life (QoL). A limitation of this type of analysis is that it cannot conclusively prove a causal relationship. In individuals without type 2 diabetes mellitus (T2DM), endpoints predominantly driven by liraglutide-induced weight loss included waist circumference, diastolic blood pressure, triglycerides, high density lipoprotein cholesterol, AHI, and Impact of Weight on Quality of Life-Lite total and physical function scores. Endpoints predominantly independent of weight loss included the glycemic endpoints hemoglobin A1c and fasting plasma glucose in individuals with and without T2DM. Regardless of the degree of dependence on weight loss according to the mediation analysis, greater weight loss was associated with greater improvement in all endpoints. Treatment with liraglutide 3.0 mg contributes to improved cardiometabolic parameters, AHI and health-related QoL through both weight-loss

Spin flipping a stored polarized proton beam at the IUCF cooler ring

International Nuclear Information System (INIS)

Phelps, R.A.

1995-01-01

We recently studied the spin flip of a vertically polarized 139 MeV proton beam stored in the IUCF Cooler Ring. We used an rf solenoid to induce a depolarizing resonance in the ring; we flipped the spin by varying the solenoid field's frequency through this resonance. We found a polarization loss after multiple spin flips less than 0.1% per flip; we also found that this loss increased for very slow frequency changes. This spin flip could reduce systematic errors in stored polarization beam experiments by allowing frequent beam polarization reversals during the experiment. copyright 1995 American Institute of Physics

Photon beam polarization and non-dipolar angular distributions

International Nuclear Information System (INIS)

Peshkin, M.

1996-01-01

Angular distributions of ejecta from unoriented atoms and molecules depend upon the polarization state of the incident x-rays as well as upon the dynamics of the physical systems being studied. I recommend a simple geometrical way of looking at the polarization and its effects upon angular distributions. The polarization is represented as a vector in a parameter space that faithfully represents the polarization of the beam. The simple dependence of the angular dependence of the angular distributions on the polarization vector enables easy extraction of the dynamical information contained in those angular distributions. No new physical results emerge from this geometrical approach, but known consequences of the symmetries appear in an easily visualized form that I find pleasing and that has proved to be useful for planning experiments and for analyzing data

Optical neutron polarizers

International Nuclear Information System (INIS)

Hayter, J.B.

1990-01-01

A neutron wave will be refracted by an appropriately varying potential. Optical neutron polarizers use spatially varying, spin- dependent potentials to refract neutrons of opposite spin states into different directions, so that an unpolarized beam will be split into two beams of complementary polarization by such a device. This paper will concentrate on two methods of producing spin-dependent potentials which are particularly well-suited to polarizing cold neutron beams, namely thin-film structures and field-gradient techniques. Thin-film optical devices, such as supermirror multilayer structures, are usually designed to deviate only one spin-state, so that they offer the possibility of making insertion (transmission) polarizers. Very good supermirrors may now be designed and fabricated, but it is not always straightforward to design mirror-based devices which are useful in real (divergent beam) applications, and some practical configurations will be discussed. Field-gradient devices, which are usually based on multipolar magnets, have tended to be too expensive for general use, but this may change with new developments in superconductivity. Dipolar and hexapolar configurations will be considered, with emphasis on the focusing characteristics of the latter. 21 refs., 7 figs

Prickle isoforms control the direction of tissue polarity by microtubule independent and dependent mechanisms

Directory of Open Access Journals (Sweden)

Katherine A. Sharp

2016-03-01

Full Text Available Planar cell polarity signaling directs the polarization of cells within the plane of many epithelia. While these tissues exhibit asymmetric localization of a set of core module proteins, in Drosophila, more than one mechanism links the direction of core module polarization to the tissue axes. One signaling system establishes a polarity bias in the parallel, apical microtubules upon which vesicles containing core proteins traffic. Swapping expression of the differentially expressed Prickle isoforms, Prickle and Spiny-legs, reverses the direction of core module polarization. Studies in the proximal wing and the anterior abdomen indicated that this results from their differential control of microtubule polarity. Prickle and Spiny-legs also control the direction of polarization in the distal wing (D-wing and the posterior abdomen (P-abd. We report here that this occurs without affecting microtubule polarity in these tissues. The direction of polarity in the D-wing is therefore likely determined by a novel mechanism independent of microtubule polarity. In the P-abd, Prickle and Spiny-legs interpret at least two directional cues through a microtubule-polarity-independent mechanism.

The Hanle effect in a random magnetic field. Dependence of the polarization on statistical properties of the magnetic field

Science.gov (United States)

Frisch, H.; Anusha, L. S.; Sampoorna, M.; Nagendra, K. N.

2009-07-01

Context: The Hanle effect is used to determine weak turbulent magnetic fields in the solar atmosphere, usually assuming that the angular distribution is isotropic, the magnetic field strength constant, and that micro-turbulence holds, i.e. that the magnetic field correlation length is much less than a photon mean free path. Aims: To examine the sensitivity of turbulent magnetic field measurements to these assumptions, we study the dependence of Hanle effect on the magnetic field correlation length, its angular, and strength distributions. Methods: We introduce a fairly general random magnetic field model characterized by a correlation length and a magnetic field vector distribution. Micro-turbulence is recovered when the correlation length goes to zero and macro-turbulence when it goes to infinity. Radiative transfer equations are established for the calculation of the mean Stokes parameters and they are solved numerically by a polarized approximate lambda iteration method. Results: We show that optically thin spectral lines and optically very thick ones are insensitive to the correlation length of the magnetic field, while spectral lines with intermediate optical depths (around 10-100) show some sensitivity to this parameter. The result is interpreted in terms of the mean number of scattering events needed to create the surface polarization. It is shown that the single-scattering approximation holds good for thin and thick lines but may fail for lines with intermediate thickness. The dependence of the polarization on the magnetic field vector probability density function (PDF) is examined in the micro-turbulent limit. A few PDFs with different angular and strength distributions, but equal mean value of the magnetic field, are considered. It is found that the polarization is in general quite sensitive to the shape of the magnetic field strength PDF and somewhat to the angular distribution. Conclusions: The mean field derived from Hanle effect analysis of

Preliminary Analysis of Chinese GF-3 SAR Quad-Polarization Measurements to Extract Winds in Each Polarization

Directory of Open Access Journals (Sweden)

Lin Ren

2017-11-01

Full Text Available This study analyzed the noise equivalent sigma zero (NESZ and ocean wind sensitivity for Chinese C-band Gaofen-3 (GF-3 quad-polarization synthetic aperture radar (SAR measurements to facilitate further operational wind extraction from GF-3 data. Data from the GF-3 quad-polarization SAR and collocated winds from both NOAA/NCEP Global Forecast System (GFS atmospheric model and National Data Buoy Center (NDBC buoys were used in the analysis. For NESZ, the co-polarization was slightly higher compared to the cross-polarization. Regarding co-polarization and cross-polarization, NESZ was close to RadarSAT-2 and Sentinel-1 A. Wind sensitivity was analyzed by evaluating the dependence on winds in terms of normalized radar cross-sections (NRCS and polarization combinations. The closest geophysical model function (GMF and the polarization ratio (PR model to GF-3 data were determined by comparing data and the model results. The dependence of co-polarized NRCS on wind speed and azimuth angle was consistent with the proposed GMF models. The combination of CMOD5 and CMOD5.N was considered to be the closest GMF in co-polarization. The cross-polarized NRCS exhibited a strong linear relationship with moderate wind speeds higher than 4 m·s−1, but a weak correlation with the azimuth angle. The proposed model was considered as the closest GMF in cross-polarization. For polarization combinations, PR and polarization difference (PD were considered. PR increased only with the incidence angle, whereas PD increased with wind speed and varied with azimuth angle. There were three very close PR models and each can be considered as the closest. Preliminary results indicate that GF-3 quad-polarization data are valid and have the ability to extract winds in each polarization.

Effect of nonlinearity of spin interaction with electromagnetic resonance field on characteristics of polarized nuclear target

International Nuclear Information System (INIS)

Vertij, A.A.; Gavrilov, S.P.; Shestopalov, V.P.

1990-01-01

Interaction of incident nuclear particle beam with J = 1/2 (neutrons) spin and (J = 1/2) protons with the target substance is considered. It is shown that neutron polarization at the target exit and neutron transparency (G) of the target depend significantly on incident wave amplitude level and physical parameter values which characterize the target, such as target temperature, resonator mirror reflection factor, number of spins interacting with the field, etc. Under interaction of neutrons with a target resonator which features a high mirror reflection factor and low losses for absorption which is not related to magnetic dipole absorption, a bistable response of neutron polarization and G manifests itself. 1 ref

Self-collimating photonic crystal polarization beam splitter.

Science.gov (United States)

Zabelin, V; Dunbar, L A; Le Thomas, N; Houdré, R; Kotlyar, M V; O'Faolain, L; Krauss, T F

2007-03-01

We present theoretical and experimental results of a polarization splitter device that consists of a photonic crystal (PhC) slab, which exhibits a large reflection coefficient for TE and a high transmission coefficient for TM polarization. The slab is embedded in a PhC tile operating in the self-collimation mode. Embedding the polarization-discriminating slab in a PhC with identical lattice symmetry suppresses the in-plane diffraction losses at the PhC-non-PhC interface. The optimization of the PhC-non-PhC interface is thereby decoupled from the optimization of the polarizing function. Transmissions as high as 35% for TM- and 30% for TE-polarized light are reported.

Detection of high PD-L1 expression in oral cancers by a novel monoclonal antibody L1Mab-4.

Science.gov (United States)

Yamada, Shinji; Itai, Shunsuke; Kaneko, Mika K; Kato, Yukinari

2018-03-01

Programmed cell death-ligand 1 (PD-L1), which is a ligand of programmed cell death-1 (PD-1), is a type I transmembrane glycoprotein that is expressed on antigen-presenting cells and several tumor cells, including melanoma and lung cancer cells. There is a strong correlation between human PD-L1 (hPD-L1) expression on tumor cells and negative prognosis in cancer patients. In this study, we produced a novel anti-hPD-L1 monoclonal antibody (mAb), L 1 Mab-4 (IgG 2b , kappa), using cell-based immunization and screening (CBIS) method and investigated hPD-L1 expression in oral cancers. L 1 Mab-4 reacted with oral cancer cell lines (Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4) in flow cytometry and stained oral cancers in a membrane-staining pattern. L 1 Mab-4 stained 106/150 (70.7%) of oral squamous cell carcinomas, indicating the very high sensitivity of L 1 Mab-4. These results indicate that L 1 Mab-4 could be useful for investigating the function of hPD-L1 in oral cancers.

CLASSIFICATION FOR ANGLE-DEPENDENT POLARIZED PHOTOEMISSION SPECTRA USING MAGNETIC-MOMENTS ANALYSIS

NARCIS (Netherlands)

VANDERLAAN, G; THOLE, BT

The angular distribution of photoelectrons from a core level or localized valence level excited with circularly or linearly polarized Xrays is shown to contain the complete one-electron information of the ground state of a magnetic polarized atom. We generalize the definition of the fundamental

Temperature-dependent time-resolved photoluminescence measurements of (1-101)-oriented semi-polar AlGaN/GaN MQWs

Science.gov (United States)

Rosales, Daniel; Gil, Bernard; Monavarian, Morteza; Zhang, Fan; Okur, Serdal; Izyumskaya, Natalia; Avrutin, Vitaliy; Özgür, Ümit; Morkoç, Hadis

2015-03-01

We studied the temperature dependence and the recombination dynamics of the photoluminescence of (1-101)-oriented semi-polar Al0.2Ga0.8N/GaN multiple quantum wells (MQW). The polarized low-temperature PL measurements reveal that radiative recombination exhibit an anisotropic behavior. The PL intensity at room temperature is reduced by one order of magnitude with respect to low temperature. The radiative decay time exhibits a mixed behavior: it is roughly constant between 8K to ranging near 140-150K and then rapidly increases with a slope of 10 ps.K-1. This behavior is indicative of coexistence of localized excitons and free excitons which relative proportion are statistically computed.

How to measure a complete set of polarization-dependent differential cross sections in a scattering experiment with aligned reagents?

International Nuclear Information System (INIS)

Wang, Fengyan; Lin, Jui-San; Liu, Kopin

2014-01-01

Polarization-dependent differential cross section (PDDCS) is one of the three-vector correlations (k, k ′ , j) in molecular collisions, which provides the most detailed insights into the steric requirements of chemical reactions, i.e., how the reactivity depends on the polarization of reagents. Only quite recently has such quantity been fully realized experimentally in the study of the reaction of the aligned CHD 3 (v 1 = 1, |jK〉 = |10〉) molecules with Cl( 2 P 3/2 ) atoms. Theoretically, PDDCS is a relatively new concept; experimental realization of the theoretical construct requires some careful considerations that are not readily available in the literature. Here, we present the “know-how” behind the full PDDCS measurements to fill the gaps and to provide a clear roadmap for future applications. To make the connection apparent between the methodology presented here and the stereodynamics revealed in previous reports, the same Cl + aligned CHD 3 reaction is used for illustration

Polar bear and walrus response to the rapid decline in Arctic sea ice

Science.gov (United States)

Oakley, K.; Whalen, M.; Douglas, David C.; Udevitz, Mark S.; Atwood, Todd C.; Jay, C.

2012-01-01

The Arctic is warming faster than other regions of the world due to positive climate feedbacks associated with loss of snow and ice. One highly visible consequence has been a rapid decline in Arctic sea ice over the past 3 decades - a decline projected to continue and result in ice-free summers likely as soon as 2030. The polar bear (Ursus maritimus) and the Pacific walrus (Odobenus rosmarus divergens) are dependent on sea ice over the continental shelves of the Arctic Ocean's marginal seas. The continental shelves are shallow regions with high biological productivity, supporting abundant marine life within the water column and on the sea floor. Polar bears use sea ice as a platform for hunting ice seals; walruses use sea ice as a resting platform between dives to forage for clams and other bottom-dwelling invertebrates. How have sea ice changes affected polar bears and walruses? How will anticipated changes affect them in the future?

Low-Temperature Dynamic Nuclear Polarization at 9.4 Tesla With a 30 Milliwatt Microwave Source

Science.gov (United States)

Thurber, Kent R.; Yau, Wai-Ming; Tycko, Robert

2010-01-01

Dynamic nuclear polarization (DNP) can provide large signal enhancements in nuclear magnetic resonance (NMR) by transfer of polarization from electron spins to nuclear spins. We discuss several aspects of DNP experiments at 9.4 Tesla (400 MHz resonant frequency for 1H, 264 GHz for electron spins in organic radicals) in the 7–80 K temperature range, using a 30 mW, frequency-tunable microwave source and a quasi-optical microwave bridge for polarization control and low-loss microwave transmission. In experiments on frozen glycerol/water doped with nitroxide radicals, DNP signal enhancements up to a factor of 80 are observed (relative to 1H NMR signals with thermal equilibrium spin polarization). The largest sensitivity enhancements are observed with a new triradical dopant, DOTOPA-TEMPO. Field modulation with a 10 G root-mean-squared amplitude during DNP increases the nuclear spin polarizations by up to 135%. Dependencies of 1H NMR signal amplitudes, nuclear spin relaxation times, and DNP build-up times on the dopant and its concentration, temperature, microwave power, and modulation frequency are reported and discussed. The benefits of low-temperature DNP can be dramatic: the 1H spin polarization is increased approximately 1000-fold at 7 K with DNP, relative to thermal polarization at 80 K. PMID:20392658

PD-1 and PD-L1 as emerging therapeutic targets in gastric cancer: current evidence

Directory of Open Access Journals (Sweden)

Tran PN

2017-05-01

Full Text Available Phu N Tran,1* Sarmen Sarkissian,1* Joseph Chao,2 Samuel J Klempner3,4 1Division of Hematology-Oncology, University of California Irvine, Orange, 2Department of Medical Oncology and Developmental Therapeutics, City of Hope, Duarte, 3Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 4The Angeles Clinic and Research Institute, Los Angeles, CA, USA *These authors contributed equally to this work Abstract: Gastric adenocarcinoma is a leading cause of global cancer-related morbidity and mortality, and new therapeutic approaches are needed. Despite the improved outcomes with monoclonal antibodies targeting human epidermal growth factor receptor 2 and vascular endothelial growth factor receptor 2, durable responses are uncommon. Targeting immune checkpoints including PD-1, PD-L1 and CTLA-4 have led to improved survival across several tumor types, frequently characterized by prolonged benefit in responding patients. Tumoral and lymphocyte-derived immunohistochemical staining for PD-1, PD-L1, and tumor mutational burden have shown potential as predictive response biomarkers in several tumor types. Optimal incorporation of immune-mediated therapies into gastric cancer (GC is an area of intense ongoing investigation and benefit has been demonstrated in smaller studies of advanced patients. Important questions of biomarker selection, roles for molecular characterization, optimal combinatorial approaches, and therapeutic sequencing remain. In this study, current data are reviewed for immune checkpoint inhibitors in GC, and putative biomarkers, ongoing trials, and future considerations are discussed. Keywords: immunotherapy, stomach cancer, checkpoint inhibitor, nivolumab, pembrolizumab, tumor mutational burden

Jeans instability in collisional strongly coupled dusty plasma with radiative condensation and polarization force

International Nuclear Information System (INIS)

Prajapati, R. P.; Bhakta, S.; Chhajlani, R. K.

2016-01-01

The influence of dust-neutral collisions, polarization force, and electron radiative condensation is analysed on the Jeans (gravitational) instability of partially ionized strongly coupled dusty plasma (SCDP) using linear perturbation (normal mode) analysis. The Boltzmann distributed ions, dynamics of inertialess electrons, charged dust and neutral particles are considered. Using the plane wave solutions, a general dispersion relation is derived which is modified due to the presence of dust-neutral collisions, strong coupling effect, polarization force, electron radiative condensation, and Jeans dust/neutral frequencies. In the long wavelength perturbations, the Jeans instability criterion depends upon strong coupling effect, polarization interaction parameter, and thermal loss, but it is independent of dust-neutral collision frequency. The stability of the considered configuration is analysed using the Routh–Hurwitz criterion. The growth rates of Jeans instability are illustrated, and stabilizing influence of viscoelasticity and dust-neutral collision frequency while destabilizing effect of electron radiative condensation, polarization force, and Jeans dust-neutral frequency ratio is observed. This work is applied to understand the gravitational collapse of SCDP with dust-neutral collisions.

Polarization diversity scheme on spectral polarization coding optical code-division multiple-access network

Science.gov (United States)

Yen, Chih-Ta; Huang, Jen-Fa; Chang, Yao-Tang; Chen, Bo-Hau

2010-12-01

We present an experiment demonstrating the spectral-polarization coding optical code-division multiple-access system introduced with a nonideal state of polarization (SOP) matching conditions. In the proposed system, the encoding and double balanced-detection processes are implemented using a polarization-diversity scheme. Because of the quasiorthogonality of Hadamard codes combining with array waveguide grating routers and a polarization beam splitter, the proposed codec pair can encode-decode multiple code words of Hadamard code while retaining the ability for multiple-access interference cancellation. The experimental results demonstrate that when the system is maintained with an orthogonal SOP for each user, an effective reduction in the phase-induced intensity noise is obtained. The analytical SNR values are found to overstate the experimental results by around 2 dB when the received effective power is large. This is mainly limited by insertion losses of components and a nonflattened optical light source. Furthermore, the matching conditions can be improved by decreasing nonideal influences.

Enhanced killing of chordoma cells by antibody-dependent cell-mediated cytotoxicity employing the novel anti-PD-L1 antibody avelumab.

Science.gov (United States)

Fujii, Rika; Friedman, Eitan R; Richards, Jacob; Tsang, Kwong Y; Heery, Christopher R; Schlom, Jeffrey; Hodge, James W

2016-06-07

Chordoma, a rare bone tumor derived from the notochord, has been shown to be resistant to conventional therapies. Checkpoint inhibition has shown great promise in immune-mediated therapy of diverse cancers. The anti-PD-L1 mAb avelumab is unique among checkpoint inhibitors in that it is a fully human IgG1 capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC) of PD-L1-expressing tumor cells. Here, we investigated avelumab as a potential therapy for chordoma. We examined 4 chordoma cell lines, first for expression of PD-L1, and in vitro for ADCC killing using NK cells and avelumab. PD-L1 expression was markedly upregulated by IFN-γ in all 4 chordoma cell lines, which significantly increased sensitivity to ADCC. Brachyury is a transcription factor that is uniformly expressed in chordoma. Clinical trials are ongoing in which chordoma patients are treated with brachyury-specific vaccines. Co-incubating chordoma cells with brachyury-specific CD8+ T cells resulted in significant upregulation of PD-L1 on the tumor cells, mediated by the CD8+ T cells' IFN-γ production, and increased sensitivity of chordoma cells to avelumab-mediated ADCC. Residential cancer stem cell subpopulations of chordoma cells were also killed by avelumab-mediated ADCC to the same degree as non-cancer stem cell populations. These findings suggest that as a monotherapy for chordoma, avelumab may enable endogenous NK cells, while in combination with T-cell immunotherapy, such as a vaccine, avelumab may enhance NK-cell killing of chordoma cells via ADCC.

Therapeutic efficacy of PD-L1 blockade in a breast cancer model is enhanced by cellular vaccines expressing B7-1 and glycolipid-anchored IL-12.

Science.gov (United States)

Bozeman, Erica N; He, Sara; Shafizadeh, Yalda; Selvaraj, Periasamy

2016-01-01

Immunotherapeutic approaches have emerged as promising strategies to treat various cancers, including breast cancer. A single approach, however, is unlikely to effectively combat the complex, immune evasive strategies found within the tumor microenvironment, thus novel, effective combination treatments must be explored. In this study, we investigated the efficacy of a combination therapy consisting of PD-L1 immune checkpoint blockade and whole cell vaccination in a HER-2 positive mouse model of breast cancer. We demonstrate that tumorigenicity is completely abrogated when adjuvanted with immune stimulatory molecules (ISMs) B7-1 and a cell-surface anchored (GPI) form of IL-12 or GM-CSF. Irradiated cellular vaccines expressing the combination of adjuvants B7-1 and GPI-IL-12 completely inhibited tumor formation which was correlative with robust HER-2 specific CTL activity. However, in a therapeutic setting, both cellular vaccination and PD-L1 blockade induced only 10-20% tumor regression when administered alone but resulted in 50% tumor regression as a combination therapy. This protection was significantly hindered following CD4 or CD8 depletion indicating the essential role played by cellular immunity. Collectively, these pre-clinical studies provide a strong rationale for further investigation into the efficacy of combination therapy with tumor cell vaccines adjuvanted with membrane-anchored ISMs along with PD-L1 blockade for the treatment of breast cancer.

Can polar bear hairs absorb environmental energy?

Directory of Open Access Journals (Sweden)

He Ji-Huan

2011-01-01

Full Text Available A polar bear (Ursus maritimus has superior ability to survive in harsh Arctic regions, why does the animal have such an excellent thermal protection? The present paper finds that the unique labyrinth cavity structure of the polar bear hair plays an important role. The hair can not only prevent body temperature loss but can also absorb energy from the environment.

Particle Events as a Possible Source of Large Ozone Loss during Magnetic Polarity Transitions

Science.gov (United States)

vonKoenig, M.; Burrows, J. P.; Chipperfield, M. P.; Jackman, C. H.; Kallenrode, M.-B.; Kuenzi, K. F.; Quack, M.

2002-01-01

The energy deposition in the mesosphere and stratosphere during large extraterrestrial charged particle precipitation events has been known for some time to contribute to ozone losses due to the formation of potential ozone destroying species like NO(sub x), and HO(sub x). These impacts have been measured and can be reproduced with chemistry models fairly well. In the recent past, however, even the impact of the largest solar proton events on the total amount of ozone has been small compared to the dynamical variability of ozone, and to the anthropogenic induced impacts like the Antarctic 'ozone hole'. This is due to the shielding effect of the magnetic field. However, there is evidence that the earth's magnetic field may approach a reversal. This could lead to a decrease of magnetic field strength to less than 25% of its usual value over a period of several centuries . We show that with realistic estimates of very large solar proton events, scenarios similar to the Antarctic ozone hole of the 1990s may occur during a magnetic polarity transition.

Magnetic x-ray circular dichroism in spin-polarized photoelectron diffraction

International Nuclear Information System (INIS)

Waddill, G.D.; Tobin, J.G.

1994-01-01

The first structural determination with spin-polarized, energy-dependent photoelectron diffraction using circularly-polarized x-rays is reported for Fe films on Cu(001). Circularly-polarized x-rays produced spin-polarized photoelectrons from the Fe 2p doublet, and intensity asymmetries in the 2p 3/2 level are observed. Fully spin-specific multiple scattering calculations reproduced the experimentally-determined energy and angular dependences. A new analytical procedure which focuses upon intensity variations due to spin-dependent diffraction is introduced. A sensitivity to local geometric and magnetic structure is demonstrated

Tests of a polarized source of hydrogen and deuterium based on spin-exchange optical pumping and a storage cell for polarized deuterium

International Nuclear Information System (INIS)

Holt, R.J.; Gilman, R.; Kinney, E.R.

1988-01-01

A novel laser-driven polarized source of hydrogen and deuterium which is based on the principle of spin-exchange optical pumping has been developed at Argonne. The advantages of this method over conventional polarized sources for internal target experiments is discussed. At present, the laser-driven polarized source delivers hydrogen 8 x 10 16 atoms/s with a polarization of 24% and deuterium at 6 x 10 16 atoms/s with a polarization of 25%. A passive storage cell for polarized deuterium was tested in the VEPP-3 electron storage ring. The storage cell was found to increase the target thickness by approximately a factor of three and no loss in polarization was observed. 10 refs., 4 figs., 2 tabs

Polarization and ellipticity of high-order harmonics from aligned molecules generated by linearly polarized intense laser pulses

International Nuclear Information System (INIS)

Le, Anh-Thu; Lin, C. D.; Lucchese, R. R.

2010-01-01

We present theoretical calculations for polarization and ellipticity of high-order harmonics from aligned N 2 , CO 2 , and O 2 molecules generated by linearly polarized lasers. Within the rescattering model, the two polarization amplitudes of the harmonics are determined by the photo-recombination amplitudes for photons emitted with polarization parallel or perpendicular to the direction of the same returning electron wave packet. Our results show clear species-dependent polarization states, in excellent agreement with experiments. We further note that the measured polarization ellipse of the harmonic furnishes the needed parameters for a 'complete' experiment in molecules.

Dynamic nuclear polarization of irradiated target materials

International Nuclear Information System (INIS)

Seely, M.L.

1982-01-01

Polarized nucleon targets used in high energy physics experiments usually employ the method of dynamic nuclear polarization (DNP) to polarize the protons or deuterons in an alcohol. DNP requires the presence of paramagnetic centers, which are customarily provided by a chemical dopant. These chemically doped targets have a relatively low polarizable nucleon content and suffer from loss of polarization when subjected to high doses of ionizing radiation. If the paramagnetic centers formed when the target is irradiated can be used in the DNP process, it becomes possible to produce targets using materials which have a relatively high polarizable nucleon content, but which are not easily doped by chemical means. Furthermore, the polarization of such targets may be much more radiation resistant. Dynamic nuclear polarization in ammonia, deuterated ammonia, ammonium hydroxide, methylamine, borane ammonia, butonal, ethane and lithium borohydride has been studied. These studies were conducted at the Stanford Linear Accelerator Center using the Yale-SLAC polarized target system. Results indicate that the use of ammonia and deuterated ammonia as polarized target materials would make significant increases in polarized target performance possible

Polarized semi-inclusive deep-inelastic scattering on transversely and longitudinally polarized nucleons at HERMES

International Nuclear Information System (INIS)

Hommes, B.

2005-01-01

The HERMES experiment has measured double spin asymmetries in the cross section for deep-inelastic scattering of longitudinal polarized positrons off longitudinal polarized hydrogen and deuterium targets. From these asymmetries, based on inclusive and semi-inclusive measurements, polarized quark distributions were extracted as a function of x. Single-spin azimuthal asymmetries in semi-inclusive pion production were measured by the HERMES experiment for the first time, with a transversely polarized hydrogen target. Two different sine-dependencies were extracted which can be related to the quark transversity distribution h q 1 (x) and the Sivers function (Author)

Nuclear-physical investigations with oriented nuclei and polarized neutrons

International Nuclear Information System (INIS)

Alfimenkov, V.P.; Pikel'ner, L.B.; Sharapov, Eh.I.

1980-01-01

Several experiments with oriented nuclei and polarized neutrons are considered, as well as some methods of polarization of neutrons and nuclei. Experiments on the study of spin dependence of neutron cross sections for fissionable and nonfissionable nuclei interaction of polarized neutrons with polarized nuclei as well as measurement of magnetic momenta of compound-states of rare-earth nuclei. Described are some investigations with thermal neutrons: study on spin dependence of neutron scattering length with nuclei and gamma radiation of neutron radiation capture. Difficulties of production of high-intensive polarized neutron beams and construction of oriented targets are noted. Neutron polarization by transmission of them through a polarized proton target is the most universal method (out of existing methods) in the energy range under consideration [ru

Experimental Evidence on the Dependence of the Standard GPS Phase Scintillation Index on the Ionospheric Plasma Drift Around Noon Sector of the Polar Ionosphere

Science.gov (United States)

Wang, Y.; Zhang, Q.-H.; Jayachandran, P. T.; Moen, J.; Xing, Z.-Y.; Chadwick, R.; Ma, Y.-Z.; Ruohoniemi, J. M.; Lester, M.

2018-03-01

First experimental proof of a clear and strong dependence of the standard phase scintillation index (σφ) derived using Global Positioning System measurements on the ionospheric plasma flow around the noon sector of polar ionosphere is presented. σφ shows a strong linear dependence on the plasma drift speed measured by the Super Dual Auroral Radar Network radars, whereas the amplitude scintillation index (S4) does not. This observed dependence can be explained as a consequence of Fresnel frequency dependence of the relative drift and the used constant cutoff frequency (0.1 Hz) to detrend the data for obtaining standard σφ. The lack of dependence of S4 on the drift speed possibly eliminates the plasma instability mechanism(s) involved as a cause of the dependence. These observations further confirm that the standard phase scintillation index is much more sensitive to plasma flow; therefore, utmost care must be taken when identifying phase scintillation (diffractive phase variations) from refractive (deterministic) phase variations, especially in the polar region where the ionospheric plasma drift is much larger than in equatorial and midlatitude regions.

Role of quantum-confined stark effect on bias dependent photoluminescence of N-polar GaN/InGaN multi-quantum disk amber light emitting diodes

Science.gov (United States)

Tangi, Malleswararao; Mishra, Pawan; Janjua, Bilal; Prabaswara, Aditya; Zhao, Chao; Priante, Davide; Min, Jung-Wook; Ng, Tien Khee; Ooi, Boon S.

2018-03-01

We study the impact of quantum-confined stark effect (QCSE) on bias dependent micro-photoluminescence emission of the quantum disk (Q-disk) based nanowires light emitting diodes (NWs-LED) exhibiting the amber colored emission. The NWs are found to be nitrogen polar (N-polar) verified using KOH wet chemical etching and valence band spectrum analysis of high-resolution X-ray photoelectron spectroscopy. The crystal structure and quality of the NWs were investigated by high-angle annular dark field - scanning transmission electron microscopy. The LEDs were fabricated to acquire the bias dependent micro-photoluminescence spectra. We observe a redshift and a blueshift of the μPL peak in the forward and reverse bias conditions, respectively, with reference to zero bias, which is in contrast to the metal-polar InGaN well-based LEDs in the literature. Such opposite shifts of μPL peak emission observed for N-polar NWs-LEDs, in our study, are due to the change in the direction of the internal piezoelectric field. The quenching of PL intensity, under the reverse bias conditions, is ascribed to the reduction of electron-hole overlap. Furthermore, the blueshift of μPL emission with increasing excitation power reveals the suppression of QCSE resulting from the photo-generated carriers. Thereby, our study confirms the presence of QCSE for NWs-LEDs from both bias and power dependent μPL measurements. Thus, this study serves to understand the QCSE in N-polar InGaN Q-disk NWs-LEDs and other related wide-bandgap nitride nanowires, in general.