dataesr/scientific-paragraphs-categorization huggingface dataset:
Because the safety profiles are non-monovalent binding manner. MGD009 contains a mutated human presentation in pre-clinical models. α-TEA is being evaluated for overlapping, the combination was not anticipated to have significant IgG1 Fc domain to reduce/eliminate binding to Fc gamma receptors safety and tolerability in a first-in-human phase I trial in patients with increased toxicity. To address these hypotheses, a phase Ib/II study (FcγRs) and complement, but retains binding to the neonatal Fc re- advanced cancers (NCT02192346). Tumor types in the ongoing trial evaluating the safety and efficacy of T-VEC plus ipilimumab for Stage ceptor (FcRn) enabling use of the IgG salvage pathway to prolong its include renal cancer, esophageal adenocarcinoma, thyroid cancer, III-IV metastatic melanoma was initiated.
Shamim Ahmad 1 , Mason Webb 1 , Rasha Abu-Eid 1 , Rajeev Shrimali 1 , Vivek Verma 1 , Atbin Doroodchi 1 , Zuzana Berrong 1 , David Yashar 1 , Raed Samara 2 , Mikayel Mkrtichyan 1 , Samir Khleif 1 Our findings provide a strategy for the selective targeting of Tregs in the frame of cancer combination immunotherapy. Conclusions These findings provide a new insight into CD4 T cell biology and offer a new strategy for selective targeting of Tregs in the frame of development of anti-cancer immunotherapies. Steven Powell 1 , Mark Gitau 2 , Christopher Sumey 1 , Andrew Terrell 2 , Michele Lohr 1 , Ryan K Nowak 1 , Steven McGraw 3 , Ash Jensen 2 , Miran Blanchard 2 , Kathryn A Gold 4 , Ezra EW Cohen 4 , Christie Ellison 1 , Lora Black 1 , John Lee 5 , William Chad Spanos 1 1 Sanford Cancer Center, Sioux Falls, SD, USA; 2 Sanford Roger Maris Cancer Center, Fargo, ND, USA 3 Sanford Health, Sioux Falls, SD, USA; Combinations: Immunotherapy/ Standard of Care P18 To determine if this com-bination would be of value in human patients, we have initiated a phase Ib/II clinical trial (NCT02523469) to assess the combination of Pembrolizumab in combination with chemoradiotherapy (CRT) for locally-advanced squamous cell carcinoma of the head and neck (SCCHN): Interim safety analysis (ISA) anti-PD-1 mAb (nivoluamb) in combination with ALT-803 in patients with refractory advanced NSCLC.
27 [0. 14-0. 53]; P < 0. 0001), and EVS (0. 33 [0. 22-0. 49]; P < 0. 0001). In stage II CC pts (1433), the differ- Trial Registration ClinicalTrials. gov identifier: NCT01909752 P23 An open-label phase I/IIa escalating dose study to evaluate safety and T cell immunogenicity of PDS0101 in subjects with cervical intraepithelial neoplasia (CIN) and high-risk HPV infection Frank Bedu-Addo 1 , Greg Conn 1 , Michael King 1 , Panna Dutta 1 , Robert Background Shepard 2 , Mark Einstein 3 Application of TLR7 activator imiquimod (IMQ) onto BCC of the skin 1 PDS Biotech, New Brunswick, NJ, USA; 2 PDS Biotech, Miami Beach, FL, leads to an early tumoral transcriptional profile of immunological re- USA; 3 Rutgers, NJ Medical School, Newark, NJ, USA jection (ICR) preceding complete remission as shown in a random- Correspondence: Robert Shepard (RShepard@Post.
Harvard. edu) ized trial [1]. Methods Journal for ImmunoTherapy of Cancer 2016, 4(Suppl 2):P23 Background Current HPV vaccines are effective at preventing infection. However, there are no therapeutic vaccines to treat the infection or commonly associated diseases e. g. CIN, cervical, anal and oral cancers. A therapy that is simple, effective and safe enough to be administered to CIN and early-stage cancer patients could be important in achieving the goal of effective cancer prevention and treatment of pre-metastatic Clinical trial (NCT01421017): for patients with metastatic breast can- cancer. We assessed whether PDS0101, a combination of modified cer to the skin. Treatment: topical IMQ to one metastasis, IMQ and multi-epitope HPV16 peptides (HPVmix) and escalating doses of the RT to another metastasis.
cationic lipid with 2. 4 mg of HPVmix. Each subject received one SC Gene expression: Affymetrix Human GeneArray 1. 0 ST/Partek Genom- dose every 3 weeks for a total of 3 doses. T cell response was evalu- ics suite software with special emphasis on expected immune ated by IFN-γ and granzyme-b ELISpot using blood drawn from the signature. subjects pre-vaccination, 2 weeks after each vaccination and 90 days Results after vaccination 3. The trial is registered at ClinicalTrials. gov (number Serial FNA samples are available from 18 patients. Gene expression NCT02065973). profiles of baseline biopsy treated with IMQ/RT identified 2309 differ- Results entially expressed genes (p < 0. 005) between CR and PR. Among No serious adverse events were reported. No IND safety reports were them, ICR genes such as GZMB, GZMH, PRF1, GNLY, CD8A and TBX21 submitted.
correlated with complete local response, which validates the ICR hy- evaluated in larger phase II trials. Methods pothesis in metastatic breast cancer. Systemic response consistent Trial Registration The Society for Immunotherapy of Cancer (SITC) led an international with induction and/or boosting of adaptive immunity is predicted by ClinicalTrials. gov identifier: NCT02065973 significant enrichment of immune signature. consortium, initiated with 23 expert centers from 17 countries, to evaluate the Immunoscore in routine clinical settings. CC patients (pts) stages I/II/III with no prior neo-adjuvant treatment were included in this study. Overall, 3855 pts split into a training set (TS), internal validation set (IVS), and external validation set (EVS) were quantified for IM using immunohistochemistry with CD3/ence in TTR was significant between the Low and High-Immunoscore groups (0.
The dynamic exclusion was set to a mass width of ±20 ppm and a duration of 45 s. To achieve high mass accuracy, the AGC (Automatic Gain Control) was set to 1 × 10 6 for the full MS survey in the Orbitrap, and to 5000 for the MS/MS in the LTQ Velos, both with a maximum injection time of 200 ms. The raw data were analyzed by MaxQuant software, version 1. 2. 2. 5 for both protein identification and protein quantification. The Andromeda search engine was used to search the MS/MS spectra using the following parameters: trypsin/P with maximum missed cleavage sites; peptide mass tolerance at first search was set at 20 ppm; MS/MS fragment mass tolerance at 0. 50 Da, top 6 MS/MS peaks per 100 Da, and a minimum peptide length of 6 amino acids. Fixed modification for carbamidomethylation of cysteines and variable modifications for acetylation of protein N-termini, deamidation of asparagines and glutamines and oxidation of methionines were used.
Identified peptides were searched against the available protein sequences from S. flexneri (SHIFL and SHIF8 protein databases) and S. sonnei (SHISS and SHISO databases) downloaded from UniProt (www. uniprot. org). One identified and quantified peptide was considered sufficient to call a protein present based on the fact that several predicted small proteins contained only observable peptide. However most (2181 of 2306 proteins) were identified on the basis of multiple peptides (Table  S1 ). False discovery rates were estimated based on the target-decoy approach  (Balgley et al. , 2007)  using matches to reversed sequences in a concatenated database. The false discovery rate was set to 1% for proteins and peptides. Protein groups with a posterior error probability value over 0. 01 or groups containing entries from the decoy database or contaminants were discarded.
Since multiple databases were used, the software occasionally assigned homologs into different protein groups, e. g. where one detected peptide spanned a polymorphic region. To group genuine homologs and identify the protein group duplications, peptide IDs for each protein were matched with the peptide ID for all other proteins. The protein sequences of the members of the matching protein groups were then aligned to ensure that these were indeed genuine homologs and all members combined in a single protein group.
Bioinformatics The sequences of the identified proteins were analyzed by different bioinformatics tools. The prediction of the sub-cellular protein localization was carried out using LIPO  (Berven et al. , 2006)  to look for inner and outer membrane lipoproteins. Proteins not identified as lipoproteins or scored as low probability lipoproteins were analyzed with PSORTb v3. 0  (Yu et al. , 2010). Finally, proteins still not assigned a definitive location were analyzed by SignalP 4. 1  (Petersen et al. , 2011)  using a combination of artificial neural networks trained on proteins with signal peptides from Gram-negative bacteria. Proteins found to have a signal peptide were assumed to be periplasmic. 21 cases were manually checked, where peptides identified by mass spectrometry matched pairs of orthologs in the databases that had different predicted locations.
For several of these, the different databases had assumed a different gene structure with different start codons. Where this occurred both members of the pair were assigned the same location based on the following: if one of the pair had a well-defined lipobox or signal peptide both members of the pair were assigned to a lipoprotein or periplasmic location, respectively. For proteins still unresolved, the pair was assigned the location of the member with the highest PSORTb prediction score. For proteins that were identified only in S. sonnei 53G or only in S. flexneri 2a 2457T GMMA or Lysates the theoretical presence in the predicted proteome of the other strain was first assessed using protein BLAST (National library of Medicine, http://blast. st-va. ncbi. nlm. nih. gov/Blast. cgi). If no homologous protein was identified in the strain of interest, nucleotide BLAST of the corresponding gene was used.
In silico translation (ExPASy Biofinformatics Resources Portal, http://web. expasy. org/translate/) was used to assess if a nucleotide BLAST hit is likely to be a functional protein coding gene (e. g. absence of frame shifts). For positive hits, a cut-off of 90% coverage and 95% identity of the protein sequence were used to call the protein theoretically present. The cut-off was based on the observed variation of proteins within selected protein groups. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium  (Vizcaino et al. , 2014)  via the PRIDE partner repository with the dataset identifier PXD002517.
aeruginosa (10%  (Choi et al. , 2011) ) and N. meningitidis (6. 2%  (Lappann et al. , 2013) ). The "purity" of the GMMA with respect to outer membrane and periplasmic proteins is likely to be even higher than the initial analysis suggested: Two proteins, Tail-specific protease and YajG, highly enriched in GMMA but not predicted to be outer membrane or periplasmic proteins (Fig. 1 ) appear to be misclassified using the sequences from the Shigella database. Tail-specific protease is known to be a soluble periplasmic protease in E. coli  (Keiler and Sauer, 1996)  and the YajG homologue in E. coli is a lipoprotein with a classic LIPO box  (Boudet et al. , 2007). Taking this into account, 98. 1% and 99. 3% of Sf2a and Ss GMMA, respectively, would be periplasmic or outer membrane localized proteins.
Acknowledgements We thank  Thomas Connor  ( WTSI ) for discussion and help with genomic analyses and  Calman MacLennan  ( NVGH ) for discussion and critically reading the manuscript. The research received funding from the  Wellcome Trust , grant  WT098051 , the  European Union Seventh Framework Programme  [ FP7/2007[FP7/ -2013] ] under Grant Agreement 261472  'STOPENTERICS'. This work was also partially funded by a grant from  Novartis  to the  Novartis Vaccines Institute of Global Health , prior to its sale to GSK. The funders had no role in the design of the experiments, the interpretation of the data, writing this paper or the decision to publish.
outer membrane and periplasmic localized proteins with at least 0. 01% mass in Ss GMMA not found in Sf2a GMMA SS53G 2461 PP Maltose-binding periplasmic protein E7JZV4 SHISO 0. 799 -** + SS53G 0290 OM lipo TonB-dependent Receptor Plug domain protein E7JTU0 SHISO 0. 732 - - SS53G 3463 OM Iron(III) dicitrate transport protein fecA E7K2N5 SHISO 0. 589 - - cirA OM OM receptor for iron-regulated colicin I receptor Q3Z051 SHISS 0. 430 - - exc OM lipo Entry exclusion protein 2 A4SH43 SHISS 0. 423 - - SS53G 3761 OM Ferrichrome-iron receptor E7K3K6 SHISO 0. 396 - - SS53G 2464 PP Maltose operon periplasmic protein E7JZV7 SHISO 0. 337 - + ycdO PP UPF0409 protein ycdO YCDO SHISS 0. 276 - + SS53G 0127 OM Putative tonB-dependent receptor yncD E7JTC8 SHISO 0. 159 - - hdeA PP Putative uncharacterized protein hdeA Q3YWI4 SHISS 0.
SANS measurements were performed using the D11 instrument (Institut Laue Langevin, Grenoble, France). A neutron beam, with a fixed wavelength of 10 Å and divergence of Δλ/λ = 9%, allowed measurements over a large range in Q [Q = 4πsin(θ/2)/λ] range of 0. 01 to 0. 3 Å -1 , by using two sample-detector distances. The data were reduced to 1D scattering curves of intensity vs Q using the facility provided software. The electronic background was subtracted, the full detector images for all data were normalized and scattering from the empty cell was subtracted. The scattering from D 2 O was also measured and subtracted from the data. The data were radially averaged to produce the 1D curves for each detector position. The instrument-independent data were then fitted to the CorrLength model in the SasView software package.
Dark-field and spectroscopic measurements were performed using a Titan 60-300 microscope (FEI), equipped with an Enfinium (Gatan) spectrometer, and operated at an acceleration voltage of 120 kV in scanning transmission mode. This allows acquisition of a low-energy-loss spectrum for each scan position with high energy-resolution and including the zero-loss peak information for computing single-scattering distributions by Fourier-log deconvolution. Before recording spectral imaging data sets, the scanned areas were exposed to a constant, small electron dose to avoid varying amounts of initial damage for different samples, which could influence the electronic structure of the organic semiconductors and thus the optical excitation signals. This ensures that material contrast based on plasmon maps is insensitive to varying damage induced signals.
For spectral data sets the step size for the scanning was set to 3 nm with a dwell time of 0. 5 ms. The resulting dose was 250 e per Å 2. The convergence angle was set to 10 mrad to increase the probe diameter and contrast in dark-field imaging. The collection angle was set to 40 mrad. Spectral imaging data sets were imported into HyperSpy (http://hyperspy. org), an open-source Python library for interactive data analysis of multidimensional data. With HyperSpy all following data treatment steps were realized. First, shifts between spectra were corrected followed by Fourier-log deconvolution using a custom script. Second, plasmon peaks were fitted by a Lorentzian function, in the interval of 12-32 eV. The resulting model parameters include one parameter for the peak center. This center positions were stored in a map and color coded to visualize compositional variations at the nanoscale.
For segmentation of the multidimensional data sets, the deconvolved data were imported into ilastik, an interactive tool for image classification, segmentation, and analysis. [65] Segmentation into three classes was done as described elsewhere  [44]  applying a nonlinear technique for dimensionality reduction. Cross-sections were prepared using a Helios Nanolab 650 (FEI), a DualBeam system for ion-milling and high-resolution scanning electron microscopy. To record electron energy-loss spectra of iodine signal from the DIO (see Supporting Information), the same microscope and spectrometer were used. Molecular Dynamics Methods: The PTB7 polymer, PC 60 BM, and PC 70 BM fullerene derivatives have been modeled using the General Amber Force Field (GAFF)  [66]  successfully applied to study organic  [67]  as well as organic-inorganic systems.
Acknowledgements The authors acknowledge financial support by the  French Fond Unique Interministériel (FUI)  under the project " SFUMATO " (grant number:  F1110019V/201308815 ) as well as by the  European Commission  under the Project " SUNFLOWER " ( FP7-ICT-2011-7 , grant number:  287594 ). Generalitat Valenciana (ISIC/2012/008  Institute of Nanotechnologies for Clean Energies ) is also acknowledged for providing financial support. The authors further acknowledge financial support via  ERC Starting Grant Colouratoms  ( 335078 ).
The gel lanes were sliced into 26 pieces, the proteins were subjected to in-gel trypsin digestion, and the hydrolysates were analyzed by LC-MS/MS. The proteins identified by at least two peptides were classified for both function and cellular localization based on their GO terms (Uniprot KB database). cellular localization), whereas the remaining proteins were mainly assigned to the membrane (12. 40%), mitochondrion (5. 81%), and endoplasmic reticulum (3. 49%) categories. The LC-MS/MS analysis allowed the identification of 395 proteins (peptide FDR = 0. 11%) in MFGMs (Supplemental Table  S1 , MFGM) with an average recovery of ∼40% and up to 70% for known major MFG proteins, such as BTN1, fatty acid synthase, XOR, MFG-E8, PLIN2, CIDE-A, cluster of differentiation 36, and mucin1 (Muc1) with previous studies  (Wu et al.
Peptide identification and data analysis A database search was performed with X!Tandem (v2010. 12. 01. 1; www. thegpm. org/TANDEM/) using the X!Tandem pipeline (version 3. 1. 3; pappso. inra. fr/bioinfo/xtandempipeline/). The enzymatic cleavage was declared to be a trypsin digestion with one possible miscleavage. Cys carboxyamidomethylation and Met oxidation were set to static and possible modifications, respectively. Precursor mass and fragment mass tolerance were 10 ppm and 0. 5 Da, respectively. A refinement search was performed with similar parameters, except that semitryptic peptides and possible N-ter protein acetylation were searched.
47q software  (Schneider et al. , 2012;  http://rsb. info. nih. gov/ij/). database  (trypsin, keratins, etc. ). The identified proteins were filtered according to the following restrictions: 1) a minimum of two different peptides was required with an E value <0. 05, and 2) a protein E value (product of unique peptide E values) <10 -4. The mass spectrometry proteomics data have been deposited with the Proteom-eXchange Consortium  (Vizcaíno et al. , 2014)  via the PRIDE partner repository with the data set identifier PXD001024 and DOI 10. 6019/ PXD001024. For further analysis, only the specific protein isoforms (difference of at least two peptides) from the groups identified by LC-MS/MS were manually annotated in the context of GO to assign them a unique relevant function and cellular localization.
Slides were mounted with Vectashield (Vector Laboratories LTD, United Kingdom) containing DAPI and stored at 4°C until observation. For some experiments, tissue sections or MFGs were also labeled for actin with rhodamine-conjugated phalloidin (Molecular Probes), GM1 ganglioside with Alexa 594-conjugated CTxB (Invitrogen), or free CH using filipin (Sigma-Aldrich). Each experiment was performed at least twice and included control sections incubated without primary antibody or with irrelevant primary antibodies (i. e. , against nucleolin or ARK2/Aurora). Epifluorescence microscopy was performed with a Leica Leitz DMRB microscope equipped with standard filters for FITC, rhodamine, and DAPI emissions, a 63× oilimmersion objective (numerical aperture [NA] 1. 3), and a DP50 imaging camera (Olympus, Rungis, France) coupled to the CellˆF software.
ACKNOWLEDGMENTS We are grateful to  P. Adenot  from the  INRA MIMA2 imaging core facility  ( INRA, Jouy-en-Josas, France ), the staff of the IERP unit ( UE 0907 ,  INRA, Jouy-en-Josas, France ),  J. Castille  for animal care and facilities, and the  Plateau d'Analyse Protéomique par Séquençage et Spectrométrie de Masse  ( UMR 1319  MICALIS,  INRA, Jouy-en-Josas, France ) for analysis of our samples by MS. We also thank  J. Ayala-Sanmartin ,  N. Beaujean ,  I. H. Mather ,  M. C. Neville ,  S. Tooze , and  M. Zerial  for providing very useful antibodies. We acknowledge  N. Bouhmarou ,  C. Cébo , and  A. Pauloin  for technical help and advice, as well as  K. Kiêu  for help in statistical analysis of the data. We warmly thank  E. Chanat  for discussing some of the results and reading the first version of the manuscript and  F.
CEVA Santé Animale, Libourne, France) and anesthetized (0. 01 ml/g of body weight) with a solution of 10% Imalgene 1000 (Merial, Lyon, France) and 5% Rompun (Bayer Pharma, Puteaux, France) in saline. Mouse milk was manually collected in a sterile tube kept on ice and eventually stored at -80°C for MFGM protein preparation. For WB analysis, milk samples were diluted with water in a 1:4 (vol:vol) ratio, skimmed by centrifugation (10,000 × g, 4°C, 15 min), and stored at -80°C. Several databases were used: the Uniprot KB Mus musculus, C57BL6 database (49,728 entries, version March 2011 from EBI [www. ebi. ac. uk/integr8]) and the contaminant of synthetic oxytocin (.
Introduction: In a Cochrane group meta-analysis steroid sparing strategy was associated with increased risk of acute rejection and lower long term kidney survival. Therefore our steroid withdrawal (SW) strategy relies on a surveillance biopsy (SB) performed at 3 month. When this SB is normal the steroid are tapered off, but usually kept otherwise. The impact of this strategy in terms of risk of acute rejection, decline of eGFR and transplant survival was analyzed. Methodology: Retrospective analysis of prospectively collected data since 2007, including 461 kidney transplant performed from 1/1/07 until 30/4/2015. Among those, 373 SB were performed when steroid had been tapered to the lowest level. SB were scored according to BANFF 2013 classification, 287 were deemed adequate and are further analyzed here after.
Introduction: Calcineurin inhibitors (CNI) blood level variability raises the question of therapeutic adherence after transplantation. The aim of the present study was to identify factors associated with this variability assessed by the coefficient of variation (CV). Material & Methods: We followed prospectively a cohort of recipients who received a renal transplantation for more than 1 year. For all patients we recorded: clinical data, data from a constructed clinical pharmacist (CP) interview and data from 6 self-reports measuring: non-adherence (The Compliance Evaluation Test, CET), satisfaction (SatMed-Q), behaviors (The Theory Planed Behavior, TPB), beliefs about medications (BMQ), perception of the illness (Brief IPQ) and social vulnerability (EPICE). Results: 408 recipients were enrolled (59.
In France, since 2012, the Agency of biomedicine (ABM) has recommended the use of machines perfusion (MP) to preserve kidneys from this donor population to improve kidney preservation and the transplantation outcomes, with the creation of a specific lump sum financing the additional costs of this strategy. This study evaluates the impact of MP vs cold storage (CS), for the period 2011-2014 with kidneys from ECD. From the ABM database (Cristal), the effect of MP on the delayed graft function (DGF) was analyzed using a multivariate logistic model excluding preemptive transplants and primary non functions (PNF). In addition, transplants from the same donor, whose one kidney preserved by MP and the other by CS (population of twins), were analyzed using a mixed model. Co-morbidities of recipients are more frequent and the age of donors and recipients is significantly higher for kidney preserved by MP (n = 801) vs CS (n = 3515).