dataesr/scientific-paragraphs-categorization huggingface dataset:
, 2014; Safieddine et al. , 2015; Scannell et al. , 2012; Toihir et al. , 2015). These papers report that the comparisons between IASI and UV instruments show a positive bias from IASI for the total column ranging from ∼ 3 % (Brewer-Dobson) to ∼ 6 % (Global Ozone Monitoring Experiment-2A -GOME-2A) on the global scale. For the vertical profile, the bias is generally lower than 10 %, except in the 10-25 km altitude range where a positive bias of 10-15 % is reported  (Dufour et al. , 2012; Gazeaux et al. , 2013). However, these different studies focused on a particular region and/or a relatively short period of time. The purpose of the present paper is to provide an update on the O 3 retrievals using the Fast Optimal Retrievals on Layers for IASI (FORLI) software  (Hurtmans et al. , 2012)  that allows one to systematically retrieve global distributions of O 3 vertical profiles in a near-real-time mode.
IASI ozone retrievals 2. 1 The IASI instrument IASI was designed for operational meteorology and for monitoring atmospheric chemistry and climate. It is a TIR Fourier transform spectrometer  (Clerbaux et al. , 2009 (Clerbaux et al. , , 2015) )  on board the MetOp-A and B satellites, which were launched in October 2006 and September 2012 respectively. The launch of the third and last satellite (MetOp-C) is scheduled for 2018. The role of MetOp-C is to ensure the continuity of observations from a polar orbit started at the beginning of the MetOp mission. The IASI instruments will provide homogeneous long-term data sets of 15 years related to atmospheric composition. Both IASI-A and B instruments have been operationally sounding the atmosphere since October 2007 and March 2013 respectively. The MetOp-A and B satellites are on a polar, sun-synchronous orbit (about 817 km altitude) with Equator crossing times of 09:30 (21:30) local mean solar time for the descending (ascending) part of the orbit.
Ozone retrievals with FORLI Retrievals of O 3 global distributions have been systematically performed in a near-real-time mode using the FORLI-O3 v20140922 software  (Hurtmans et al. , 2012) , which was until a few weeks ago the reference FORLI version. In this study we used the IASI-A and IASI-B O 3 data retrieved from January 2008 and from March 2013, respectively, until December 2014. FORLI-O3 is based on the optimal estimation method (OEM)  (Rodgers, 2000)  and relies on tabulated absorption cross sections at various pressures and temperatures to speed up the radiative transfer calculation. The OEM uses a priori information to constrain ill-posed problems such as O 3 concentration retrievals from nadir-viewing spaceborne sounders. The OEM also provides an error budget associated with the retrievals and diagnostic variables allowing accurate comparisons with other data.
5 × 10 -8 W cm -2 sr cm -1 ). For a full description of the FORLI-O3 software and the OEM algorithm the reader is referred to  Hurtmans et al. (2012). Figure  1  illustrates an example of averaging kernels for one midlatitude IASI observation on 15 July 2014. The averaging kernels present four maxima located around 2, 8, 15, and 22 km, and the total DOFS is 4. 2. As shown in previous studies, the IASI sensitivity to tropospheric O 3 peaks between 6 and 8 km, with some seasonal variability (e. g. ,  Clerbaux et al. , 2015). However, in case of significant thermal contrast (i. e. , the difference of temperature between the ground and the atmospheric layer just above it), the sensitivity of IASI increases near the surface  (Boynard et al. , 2014). For the example illustrated in Fig. 1 , the measurement is performed at a location associated with a large thermal contrast (18 K) and hence the averaging kernels corresponding to the  troposphere exhibit two maxima, allowing the separation of the boundary layer and the free tropospheric O 3 concentrations.
6 nm overcoming the spectral interference of sulfur dioxide with O 3  (Kerr et al. , 1984; Kerr, 2002). The Dobson and Brewer stations considered in this paper and the criteria used for the selection of the stations have been extensively used in a series of validation papers of satellite total O 3 measurements (e. g. ,  Weber et al. , 2005; Balis et al. , 2007a, b; Koukouli et al. , 2012 Koukouli et al. , , 2015)). For the comparisons with IASI TOCs from FORLI, only direct sun observations are used as those are the most reliable for both the Dobson and the Brewer spectrophotometers, the latter offering an accuracy of about 1 % at moderate solar zenith angles (e. g. ,  Kerr, 2002). All data available for the period 2008-2014 have been extracted. The data format currently used consists of daily total O 3 values expressed in Dobson units (DU).
7 %, while the SAOZ total accuracy is 5. 9 %  (Hendrick et al. , 2011). In this study, eight SAOZ stations deployed at all latitudes from the Arctic to the Antarctic (see Table  3  for their locations) have been used for IASI TOC validation. Sunrise (sunset) SAOZ measurements are compared to co-located daytime (nighttime) IASI daily data averaged in a 300 km diameter semicircular area located to the east (west) of the groundbased station. Note that similar results are found for dayand nighttime measurements, so only the results related to daytime data are shown here. In order to ensure consistency in the product validation and intercomparison of the different products, the SAOZ data set was reduced to contain only the common co-locations between the two IASI instruments and the respective SAOZ one during the period March 2013-December 2014.
Fifty-five ozonesonde stations in midlatitude, polar, and tropical regions were considered for the comparison. Figure  13  (left panel) presents a map of the ozonesonde stations used in the validation exercise, showing that most of sonde stations used in this study are located in the northern midlatitudes. Figure  13  (right panel) shows the distribution of the amount of IASI-ozonesonde coinci- dences available for this study as a function of latitude. More than 6600 sonde measurements and 68 000 coincident clearsky IASI observations during a period extending from January 2008 to December 2014 were found with more than half of them located in the northern midlatitudes. To allow for a meaningful comparison with the high vertical resolution profiles measured by ozonesondes, the difference in vertical resolution and sensitivity between the two data sets has to be accounted for.
6 Towards a decrease in the bias In order to compute new products related to radiative forcing studies  (Doniki et al. , 2015) , new developments were made in the FORLI-O3 retrieval software. Look-up tables (LUTs) were recalculated to cover a larger spectral range (960-1105 cm -1 ) using the HITRAN 2012 spectroscopic database  (Rothman et al. , 2013)  instead of the HITRAN 2004 database  (Rothman et al. , 2005)  and correcting numerical implementation, especially with regard to the LUTs at higher altitude. Here we assess the new FORLI-O3 retrievals performed for 12 days (the 15th of each month) in 2011. In the following, the updated version of FORLI-O3 is called v20151001, and the relative difference between both versions of FORLI-O3 is calculated as 100 × (v20140922 -v20151001) / v20151001 (%).
Only common pixels of IASI-A are used for the comparison between the two versions of FORLI-O3. The current version of the HITRAN database between 960 and 1105 cm -1 includes 52970 O 3 entries of five isotopologues. The line lists of the two databases HITRAN 2012 and HITRAN 2004 differ by 15 transitions of the very weak hot band ν 1 +2ν 2 +ν 3 -2ν 2 -ν 3 in the mentioned above spectral range, where ν 1 , ν 2 , and ν 3 are the three vibrational modes of ozone. The line positions and line intensities of all other transitions are identical in both lists. The difference between the two data sets is in the broadening parameters (γ air and γ self ) and in temperature-dependent exponent coefficient n for γ air. The actual values of the γ air , γ self , and n parameters in the HITRAN 2012 database are based on the results of  Wagner et al.
FORLI-O3 v20151001 gives lower concentrations of O 3 in the MS (above 30 hPa/25 km) but higher concentrations in UTLS region. In the MS, the differences vary as a function of latitude: the largest differences are found at high latitudes (up to 20 %) and the lowest differences are found in the tropics (less than 10 %). In the lower troposphere the differences between both versions of FORLI-O3 are smaller (< 5 %). This suggests that the changes made in FORLI v20151001 will impact more the MS where most of O 3 is located than the UTLS characterized by lower amount of O 3. Similar results are found for nighttime measurements (not shown here). TOCs obtained from FORLI-O3 v20151001 were compared to GOME-2A data for the 12 days of 2011. Data (daytime only) were averaged over a 1 • × 1 • grid. Figure  19  shows the global distribution of the relative difference of TOCs between FORLI-O3 v20140922 (left panel) and v20151001 (right panel) against GOME-2A data.
No significant changes are found in the troposphere. These preliminary results show that the improvement in the retrieved IASI TOCs from FORLI v20151001 is mostly related to the improvement in retrieved O 3 in the MS above 30 hPa/25 km. This is mainly due to the use of updated LUTs calculated over an extended spectral range, with corrections of numerical implementation, especially with regard to the LUTs at higher altitude. son spectrophotometers, and SAOZ spectrometer data was performed. For the validation of O 3 vertical profiles against ozonesonde measurements, the ozonesonde vertical profiles were smoothed according to the IASI averaging kernel and a priori constraints, which leads to a vertical profile representing what IASI would measure for the same sonde sampled atmospheric air mass.
4. The larger differences found at high latitudes are attributed to reduced IASI sensitivity associated with high latitudes (low brightness temperature) and the temperature profiles used in FORLI that are less reliable in Antarctica. The larger bias found in the UTLS, also found with other TIR sounders (e. g. ,  Nassar et al. , 2008; Worden et al. , 2007) , is not fully understood but some possible explanations are the limited IASI vertical resolution, spectroscopic uncertainties on ozone line, or the use of inadequate a priori information. Further investigations on the retrievals processing need to be performed. 5. The FORLI retrieval software has been updated with LUTs recalculated to cover a larger spectral range (960-1105 cm -1 ) using HITRAN 2012 spectroscopy database instead of HITRAN 2004 and correcting numerical implementation, especially with regard to the LUTs at higher altitude.
Acknowledgements. IASI is a joint mission of  EUMETSAT  and the  Centre National d'Etudes Spatiales (CNES, France). The IASI L1C data are distributed in near real time by  EUMETSAT  through the EUMETCast system distribution. The authors acknowledge the Aeris data infrastructure for providing access to the IASI L1C data and L2 temperature data used in this study. This work was undertaken in the framework of the EUMETSAT O3M- SAF  project (http://o3msaf. fmi. fi), the  European Space Agency   O3   Climate Change Initiative  ( O3-CCI , www. esa-ozone-cci. org),and the  EU-FP7   PANDA  project (http://www. marcopolo-panda. eu/). The French scientists are grateful to  CNES  and  Centre National de la Recherche Scientifique (CNRS)  for financial support. We acknowledge the  World Ozone and Ultraviolet Data Centre (WOUDC , http://woudc.
Data availability The Aeris data infrastructure (http://www. aeris-data. fr; Aeris, 2016) provides the IASI L1C data and L2 temperature data along with the IASI O 3 products processed with FORLI-O3 v20151001. The O3M SAF and O3-CCI GOME-2 data are available at http://o3msaf. fmi. fi (O3M SAF, 2016) and www. esa-ozone-cci. org (O3-CCI, 2016), respectively. The Brewer, Dobson, and ozonesonde data are available at the WOUDC (http://www. woudc. org; WOUDC, 2016). The SAOZ data are available at http://saoz. obs. uvsq. fr (SAOZ, 2016). The HITRAN spectroscopic database is available at http://hitran. org  (HITRAN, 2016). www. atmos-meas-tech. net/9/4327/2016/ Atmos. Meas. Tech. , 9, 4327-4353, 2016.
k of f 6 k on /. k U 6 k F / D K d. overall/: Since K d. overall/ was obtained by SPR and ITC, we used both estimates. The results are in Table  1 , which shows that model #1 led to good agreement between the two techniques despite their great difference, and despite the very small number of really free parameters used for extracting kinetic results from the OH cleavage curves. Particular examples of the joint fit of all cleavage curves are in Fig. 3B. k on D (3. 26 § 0. 16)£10 4 M ¡1 s ¡1 , k of f D (1. 09 § 0. 02) £ 10 ¡3 s ¡1 , k F D (0. 39 § 0. 03)£10 ¡3 s ¡1 and k U D (1. 30 § 0. 08) £ 10 ¡3 s ¡1 (thus k F C k U D (1. 7 § 0. 1)£10 ¡3 s ¡1 ) (Fig. For ECthiC mutP1 , we compared the SPR and kinITC results reported in. 22 However, in  22  the SPR data were processed with a classical single-step mechanism whereas the kinITC data were processed with model #1 only.
ITC experiments Experiments were performed at various temperatures on an ITC 200 apparatus (Microcal, GE-Healhtcare Northampton MA, USA). Renatured RNA was loaded in the cell (from 20 to 60 mM) and the TPP in the syringe (buffer used: sodium cacodylate pH 6. 5, 50 mM; potassium acetate 100 mM; magnesium acetate 5 mM). To obtain thermodynamic information ITC was used in the classical multiple-injection mode. Experimental data processing was performed with our own methods and programs. We have taken steps for their introduction into the program AFFINImeter (S4SD, Santiago de Compostela, Spain). We also made use of kinITC  22  to obtain complete kinetic information (see below). Raw kinetic information was also obtained for ATthiC through experiments in the single-injection mode (at different temperatures).
SPR experiments SPR experiments with ATthiC were performed on a Biacore 2000 instrument using Research Grade CM5 sensor chips (GE Healthcare). RNA constructs were prepared and experiments conditions were conducted as described for ECthiC mutP1 in  22  (same buffer as for the ITC experiments). Experimental data were acquired in single-cycle mode  53  and processed with our own program, either with the 2-step 'induced-fit' model #1, or conformational selection model #2. The equations necessary for this processing are described in the following. The theoretical SPR signal in Resonance Units (RU) was considered to be proportional to R 1 t ð Þ C R 2 t ð Þ for model #1, and to R 2 t ð Þ for model #2 (equations 1a-b, 2b ). The kinetic parameters were derived from a joint fit of 2 experimental data sets.
I. INTRODUCTION The increasing demand for multimedia applications, such as real-time conferencing, multiview video and video streaming, pushes data networks to their operational limits and motivates efficient resource allocation schemes. Multicast is a candidate method for delivering multimedia streams to multiple users across a network. To optimize individual user experience, it is desired to employ multi-rate multicast transmissions and use layered multimedia coding schemes to adapt users' perceived quality to allowable data rates, see  [2] ,  [3]. Since different receivers may require different data rates, we study the problem of per-receiver Network Utility Maximization A part of this work is published in IEEE INFOCOM 2014  [1]. This work makes use of results produced by the SmartFIRE project, which is supported by the International Research & Development Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (MSIP, Korea) (Grant number: K2013078191) and the Seventh Framework Programme (FP7) funded by the European Commission (Grant number: 611165).
This work was supported by NSF grants CNS-0915988 and CNS-1116209, and ONR grant N00014-12-1-0064. The work of Chih-Ping Li was done when he was at MIT. The work of G. Paschos was done when he was at MIT and it was supported in part by the WiNC project of the Action: Supporting Postdoctoral Researchers, funded by national and Community funds (European Social Fund). Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the United States Government, nor of the companies Huawei, and Qualcomm. (NUM) in multi-rate multicast, where each receiver is assigned a potentially different utility function. Controlling multicast streams is challenging; the optimal network resource allocation and stream rate adaptation depends on the network state, which includes channel quality, network congestion, user demand and device capabilities.
Results We examined the expression of PS on immune cells infiltrating B16 melanomas. CD11b + myeloid cells expressed the highest levels of PS on their surface whereas T cells and B16 tumor cells express little to no PS. These data suggest that targeting PS in B16 melanoma would induce a pro-inflammatory myeloid tumor microenvironment. We hypothesize that therapies that induce apoptotic cell death on tumor cells would enhance the activity of PS-targeting antibodies. We therefore examined the effects of combining a PS-targeting antibody with local tumor radiation. We found that the PS-targeting antibody synergizes with both anti-PD-1 and radiation therapy to improve anti-cancer activity and overall survival. In addition, the triple combination of the PS-targeting antibody, tumor radiation and anti-PD-1 treatment displayed even greater anti-cancer and survival benefit.
A better understanding of the coordinate interaction between these receptors and ligands in tumors will be informative for the appropriate application of checkpoint-therapy combinations. Background CC-122 binds the E3 ubiquitin ligase CRL4 CRBN resulting in the degradation of the transcription factor Aiolos and activation of T cells. Preclinical and clinical data obtained in hematologic malignancies indicate that CC-122 exerts immunomodulatory activity through enhanced antibody dependent cell-mediated cytotoxicity and a shift in T cell subsets from a naïve to effector and memory subsets. CC-122 is in clinical development in multiple hematologic diseases and in solid tumors such as hepatocellular carcinoma (HCC) as a single agent (NCT01421524) and in combination with nivolumab (nivo). The effects of combining CC-122 with immune checkpoint antibodies in in vitro models of T cell activation and immune co-culture models with HCC cells were examined.
Of 6 evaluable patients previously exposed to anti-PD-1/PD-L1, best response includes 3 SD and 3 PD. Of 11 evaluable anti-PD-1/PD-L1 naïve patients, best response includes 1 PR, 1 SD and 9 PD. A reduction in peripheral MDSC levels was observed between pre-treatment and Cycle 2 Day 1 in 7 of 11 patients assessed (median decrease of 40. 7 % PMN-MDSCs; 67. 3 % M-MDSCs). Conclusions 5 mg ENT weekly combined with PEMBRO has a manageable safety profile, expected pharmacodynamic effects on reducing MDSCs, and will be further explored in the phase II expansion cohorts including NSCLC and melanoma. Trial Registration ClinicalTrials. gov identifier NCT02437136.
Methods Based on these preclinical data, we developed a phase I/II clinical trial (UPCI 10-131/NCT01545141) to determine the safety and local effectiveness of intravenous infusion of rintatolimod (Ampligen; selective TLR3 ligand) combined with Intron A and oral celecoxib, in patients with resectable recurrent colorectal cancer. Our phase I/II trial UPCI 11-128 (NCT02432378) evaluates the safety, feasibility and local effectiveness of the intraperitoneal delivery of rintatolimod and Intron A (with oral celecoxib) in cisplatin-treated patients with recurrent ovarian cancer.
Methods RNA sequencing data were obtained from 475 melanoma patients (The Cancer Genome Atlas database). Additionally, C57BL/6 mice were subcutaneously injected with 100,000 B16-F10 cells in the flank and sacrificed at day 14 for flow cytometry analysis. Anti-PD-1 + anti-CTLA-4 blocking antibodies or PBS were injected intraperitoneally at days 5, 8 and 11 after tumor inoculation.
In contrast, the proliferation of FoxP3+ Tregs and TGFb was decreased. AM0010 alone or with anti-PD-1 induced oligoclonal expansion of T cell clones in the blood without affecting total lymphocyte counts. In particular, selected T cells clones previously not detected in the blood of patients before treatment were strongly expanded (de novo amplification). Conclusions AM0010 alone or in combination with anti-PD-1 is well-tolerated. The clinical activity and the observed CD8+ T cell activation encourages the continued exploration of AM0010 in phase III studies. Trial Registration ClinicalTrials. gov identifier NCT02009449. Background LAG-3 is a transmembrane receptor that negatively regulates T cell activation. Signaling through LAG-3 and other T cell inhibitory receptors, including programmed death-1 (PD-1), can lead to T cell exhaustion and is a mechanism of immune escape for tumors.
Methods This is a phase I/II study (NCT02291055) of AXAL + durvalumab in patients (≥18 years) with either recurrent/metastatic cervical cancer or metastatic HPV+ SCCHN, who progressed on ≥1 platinum-based therapy. The primary objectives of the phase I, Part A dose escalation are to determine the safety/tolerability and establish the combination recommended phase II dose (RP2D) of AXAL (1 × 10 9 colony-forming units q4wk) and durvalumab (3 mg/kg or 10 mg/kg q2wk) following a 3 + 3 design. Part A includes a SCCHN expansion cohort (N = 20) at the RP2D to evaluate efficacy. Part B will evaluate tumor response (RECIST and immune-related RECIST) of durvalumab monotherapy and AXAL + durvalumab combination therapy at the RP2D in recurrent/metastatic cervical cancer. Preliminary results of phase I dose escalation are reported.
Conclusions The data presented shows IT administration of the TLR7/8 agonist MEDI9197 is retained in the tumor, modulates the tumor microenvironment in a manner consistent with an antitumor signature, and inhibits tumor growth in multiple mouse cancer models. Finally, the antitumor effects of MEDI9197 are further enhanced by combination therapy with checkpoint blockade therapies. MEDI9197 is currently being evaluated for safety and efficacy in human clinical trials (ClinicalTrials. gov Identifier: NCT02556463).
Conclusions Autologous DCs co-electroporated with MART-1 RNA/CD40L RNA exhibit a similar MOA in vitro to AGS-003 administered in vivo, whereby both DC preparations induce antigen-specific multi-functional CTLs. Understanding the MOA of AGS-003 in vitro, allows for the testing of a broad range of potential combination therapies to provide feasibility data to support clinical trials of combination therapy for mRCC. Data provided show that most, but not all, kinase inhibitors are compatible with the MOA of AGS-003, the induction of effector/memory CTL responses, and that each therapeutic agent warrants testing. Trial Registration ClinicalTrials. gov identifier NCT01582672.
Preliminary results show signs of tumor activity following 2 doses of Cy/CRS-207 prior to chemotherapy (36 % tumor shrinkage) and the combination with chemotherapy resulted in 86 % disease control and 50 % response rate compared to published response rates of 20-41 % with chemotherapy alone. Immune analyses and further follow-up are warranted to evaluate the Cy/CRS-207 + chemotherapy regimen as a treatment for MPM. Trial Registration ClinicalTrials. gov identifier NCT01675765.