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Luo, Peng, Timothy A. DeVol, and Julia L. Sharp. "Sequential Probability Ratio Test Using Scaled Time-Intervals for Environmental Radiation Monitoring." IEEE Transactions on Nuclear Science 57, no. 6 (June 2010): 1556–62. http://dx.doi.org/10.1109/tns.2010.2045900.
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Sequential probability ratio test (SPRT) of scaled time-interval data (time to record N radiation pulses),SPRT_scaled, was evaluated against commonly used single-interval test (SIT) and SPRT with a fixed counting interval,SPRT_fixed, on experimental and simulated data. Experimental data were acquired with a DGF-4C (XIA, Inc) system in list mode. Simulated time-interval data were obtained using Monte Carlo techniques to perform a random radiation sampling of the Poisson distribution. The three methods (SIT, SPRT_fixed and SPRT_scaled) were compared in terms of detection probability and average time to make a decision regarding the source of radiation. For both experimental and simulated data, SPRT_scaled provided similar detection probabilities as other tests, but was able to make a quicker decision with fewer pulses at relatively higher radiation levels. SPRT_scaled has a provision for varying the sampling time depending on the radiation level, which may further shorten the time needed for radiation monitoring. Parameter adjustments to the SPRT_scaled method for increased detection probability are discussed.
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Savic, Radomir, Dragan Radojkovic, Nenad Stojiljkovic, Nenad Parunovic, Marija Gogic, and Cedomir Radovic. "Effect of breed of performance tested boars on ejaculate traits." Biotehnologija u stocarstvu 36, no. 3 (2020): 309–16. http://dx.doi.org/10.2298/bah2003309s.
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The main objective of the study was to determine the influence of breed on the traits of boar ejaculate: ejaculate volume (VOL, ml), sperm concentration (CON, x106 sperm/ml), total sperm count in ejaculate (TNS, x109 spermatozoa), sperm motility in native ejaculate (MON, %), sperm motility after dilution (MOD, %) and number of doses produced (NPD). The aim was also to evaluate the correlation of the boar performance test traits: average life daily gain (g), backfat thickness measured in two locations (mm), depth of longissimus dorsi muscle (mm) and carcass meat content (%) with ejaculate traits. Total of 931 ejaculates of 36 boars during reproductive exploitation were analysed (16 Landrace boars and 20 Large White boars). The effect was assessed using the procedure of the general linear model of the statistical package SAS 9.1.3 (SAS Inst. Inc., 2002- 2003). The model for analysis included the influence of breed, season and the linear regression influence of body weight at the end of the performance test. The correlation of the traits was determined by applying the Pearson?s correlation coefficient. Most of the examined ejaculate traits (VOL, CON, MOD and NPD) varied under the influence of boar breed (p<0.01; p<0.001). Weight at the end of the test (p<0.05; p<0.01; p<0.001) affected all examined traits, except CON and TNS. A weak association was found between production performance and ejaculate traits.
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Li, Xing, Xiaoping Wan, Zhaoxia Wang, Yanan Liang, Zhuo Jia, Xu Zhang, and Limin Liao. "Frequency-Dependent Effects on Bladder Reflex by Saphenous Nerve Stimulation and a Possible Action Mechanism of Tibial Nerve Stimulation in Cats." International Neurourology Journal 25, no. 2 (June 30, 2021): 128–36. http://dx.doi.org/10.5213/inj.2040304.152.
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Purpose: The present study determined the effects of saphenous nerve stimulation (SNS) at different stimulation frequencies on bladder reflex and explored a possible action mechanism of tibial nerve stimulation (TNS) on bladder activity in cats.Methods: Two bipolar nerve cuff electrodes were implanted on the saphenous nerve and the contralateral tibial nerve in 13 cats, respectively. Multiple cystometrograms were obtained to determine the effects of single SNS at different frequencies and that of combined SNS and TNS on the micturition reflex by infusing normal saline.Results: SNS at 1 Hz significantly reduced the bladder capacity (BC) to 59.8%±7.7% and 59.3%±5.8% of the control level at the intensity threshold (T) and 2T, respectively (P<0.05), while that at 20 Hz significantly increased the BC to 130.6%±4.2% of the control level at 6T (P<0.05). The TNS and SNS at 20 Hz did not significantly change the BCs at 1T (P>0.05), while combined stimulation at 1T significantly increased the BC to 122.7%±1.9% of the control level and induced an inhibitory effect which was similar to that TNS at 2T.Conclusions: The current study revealed that SNS reduced and increased BC depending on different stimulation frequencies. The combined SNS and TNS maximized the clinical efficacy at a low intensity. Also, SNS may be a potential therapeutic mechanism of TNS.
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Wang, Xiaoqiang, Karineh Petrossian, Miao-Juei Huang, Kohei Saeki, Noriko Kanaya, Gregory Chang, Somlo George, and Shiuan Chen. "AR Is Not an Independent Marker for TNBC: The Lesson We Learn From Two PDX Models." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A804—A805. http://dx.doi.org/10.1210/jendso/bvab048.1636.
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Abstract Extensive efforts, through cell line-based models, have been made to characterize the androgen receptor (AR) signaling pathway in triple-negative breast cancer (TNBC). However, these efforts have not yet reached a consensus with regards to the mechanism of AR in TNBC. On the other hand, patient-derived xenografts (PDXs) are generally considered more appropriate than cell line-based models for recapitulating the structural and molecular features of a patient’s tumor, but only a few have been reported to be AR-positive TNBC. In our study, we identified and molecularly characterized two new, AR-positive TNBC PDX models and assessed the impacts of AR agonist (DHT) and antagonist (enzalutamide) on tumor growth and gene expression profiles by utilizing immunohistochemistry (IHC), western blots, and RNA-Seq and TNBC subtyping analyses. Two PDX models, termed TN1 and TN2, were derived from two grade 3 TNBC tumors, each containing 1~5% of AR positive tumor cells. DHT activated AR in both PDX tumors by increasing AR nuclear localization and protein levels. However, the endpoint tumor volume of DHT-treated TN1 was 3-folds smaller than that of non-treated TN1 tumors. Conversely, the endpoint tumor volume of DHT-treated TN2 was 2-folds larger than that of non-treated TN2. Moreover, enzalutamide failed to antagonize DHT-induced tumor growth in TN2. The RNA-Seq analyses revealed that DHT suppressed gene expression in TN1 (961 down-regulated genes versus 149 up-regulated genes), while the DHT promoted gene expression in TN2 (673 up-regulated genes versus192 down-regulated genes). TNBC subtyping analyses based on RNA-Seq data predicted distinct molecular subtypes of TN1 and TN2: TN1 correlated to a basal-like 1 (BL1) subtype, and TN2 correlated to a basal-like 2 (BL2) subtype. These analyses suggest that TN1 and TN2, which both express functional AR, are two molecularly distinct PDX models that expand our current knowledge of AR-positive TNBC. Our results do not support that AR is a suitable therapeutic target in TNBC. To our best knowledge, the molecular mechanisms of AR in TNBC are equivocal and should be evaluated using clinically relevant models, considering both the heterogeneous expression of AR in TNBC and the general complexities of AR signaling.
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Baber, Jessica R., Jason E. Sawyer, Ben P. Holland, Kendall J. Karr, Alyssa B. Word, and Tryon A. Wickersham. "Net protein contribution of beef feedlots from 2006 to 2017." Translational Animal Science 3, no. 4 (July 1, 2019): 1575–84. http://dx.doi.org/10.1093/tas/txz142.
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Abstract: Feedlot efficiency increases as technologies are adopted and new feed ingredients, especially byproducts, become available and incorporated into diets. Byproduct availability increased in response to the renewable fuels standard of 2005, creating substantial amounts of feedstuffs best used by ruminants. Cereal grains have been partially replaced with human-inedible byproducts, as they provide comparable levels of energy in cattle diets. To evaluate the effects of changes in diet and feedlot production practices on net protein contribution (NPC) and human-edible protein conversion efficiency (HePCE) across time, a deterministic NPC model was used. NPC was assessed for the feedlot industry using lot level production data from 2006 to 2017 for eight commercial feedlots. Ingredient and nutrient composition was collected for a representative starter and finisher diet fed for each year from each feedlot. NPC was calculated by multiplying human-edible protein (HeP) in beef produced per unit of HeP in feed by the protein quality ratio (PQR). Systems with NPC >1 positively contribute to meeting human protein requirements; NPC < 1 indicates competition with humans for HeP. NPC was regressed on year to evaluate temporal change in NPC. Feedlots were categorized as increasing NPC (INC; slope > 0) or constant NPC (CON; slope = 0) according to regression parameter estimates. Four feedlots were categorized as INC and four were CON. The rate of change in PQR was similar for CON and INC (P ≥ 0.79), although rates of change among INC and CON differed for byproduct and cereal grain inclusion (P ≤ 0.01) across years evaluated. Feedlots categorized as INC reduced HeP consumed by 2.39% per year, but CON feedlots did not reduce HeP consumed each year (0.28%). Cattle received and shipped by INC were lighter than those in CON feedlots (P < 0.01). Across years, INC produced more HeP (20.9 vs. 19.2 kg/hd) than CON (P < 0.01), and both feedlot types tended to improve HeP gained over time (0.1 kg per year; P = 0.10). Differences in slope over time for INC and CON were observed for conversion efficiency of HeP (P < 0.01). NPC increased 0.027 units per year for INC (P < 0.01) and was 0.94 in 2017. NPC by the feedlot sector improved from 2006 to 2017, decreasing the amount of human-edible feeds required to produce more high-quality protein from beef.
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Knuutila, Sakari, Katja Merkkiniemi, Mikko Rönty, Aino Wirtanen, Satu Maria Remes, Stuart Bloor, Kaisa Salmenkivi, Aija Knuuttila, and Virinder Kaur Sarhadi. "Targeted deep sequencing as a diagnostic and research method for detecting EGFR and ALK pathway driver genes in FFPE tissue of lung and colorectal carcinomas." Journal of Clinical Oncology 30, no. 30_suppl (October 20, 2012): 39. http://dx.doi.org/10.1200/jco.2012.30.30_suppl.39.
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39 Background: Molecular targeted tyrosine kinase inhibitor (TKI) treatments have made it crucial to perform diagnostic tests of multiple molecular targets. In lung carcinoma there are close to ten clinically relevant gene mutations, copy number alterations and/or gene fusions, such as ALK, EGFR, ERBB2, KRAS, BRAF, MET, PTEN, PI3KCA, ROS1 and RET. Presently, several different tests are utilized, requiring a high amount of tumor material and long turnaround time. Next generation sequencing or targeted deep sequencing (TDS) has opened a new era for rapid genome-wide analyses of mutations, copy number alterations and gene fusions. Our aimwas to 1) prove feasibility for applying TDS to FFPE samples, 2) compare mutations detected by prevalent methods & TDS, and 3) mine novel clinically and biologically relevant genes in lung and colorectal carcinoma. Methods: For TDS, we selected 192 lung carcinoma and colorectal carcinoma related genes and microRNA genes, focusing on the EGFR and ALK pathways. In total, 98 FFPE specimens were studied. Agilent SureSelect system and Illumina sequencing was adopted for the analysis. For diagnostic validation the following genes were selected: EGFR, KRAS, BRAF, PTEN, PI3K, RET and ALK. TDS results were confirmed by PCR, FISH and IHC. Results: We focused on the genes selected for diagnostic validation. Successful results were obtained from all specimens. The results from TDS correlated significantly with those obtained from PCR, FISH, and IHC. Importantly, TDS revealed novel mutations not detected by targeted PCR. Conclusions: An enormous advantage of TDS is that multiple mutation screening can be achieved in one analysis (saving time and material), and most importantly, provides enormous amounts of novel information, for example understanding mechanisms for drug resistance. This study was supported by Finnish Academy, Sigrid Jusélius Foundation, Finnish Cancer Organizations, the special governmental subsidy research funds appropriated to the Helsinki and Uusimaa Hospital District (HUS EVO), Pfizer Oy, AstraZeneca AS, Lab21 Ltd, Abbott Molecular Inc.
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Ramos Parrací, Carlos Alberto, Elvia Constanza Palomino Devia, and Nelson Rodríguez Arias. "Aptitud cardiorrespiratoria y adiposidad frente al nivel de actividad física." Educación Física y Ciencia 19, no. 1 (June 29, 2017): 020. http://dx.doi.org/10.24215/23142561e020.
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Con el objetivo de determinar el comportamiento de la Aptitud Cardiorrespiratoria y la adiposidad frente al nivel de actividad física de la población adulta de la ciudad de Neiva, se evaluaron 972 sujetos entre 18 a 75 años de edad. Estudio Descriptivo Correlacional. Los datos se analizaron en SPSS-23 e InfoStat/Profesional 1,2. La metodología partió de la descripción de variables, posteriormente el grado de asociación entre ellas (coeficiente de correlación de Pearson), los grupos conformados se compararon (Prueba ANOVA y comparación multiple LSD Fisher); por último, se estableció el grado de agrupamiento entre las variables (Prueba Average Linkage). Los resultados evidenciaron diferencias significativas en índice de masa corporal (IMC), Frecuencia Cardiaca Reposo (FCR) y Consumo Máximo de Oxigeno (VO2máx.), entre activos e inactivos; asociación del 5%, entre el IMC con FCR y VO2máx, índice cintura–cadera (ICC) y porcentaje grasa corporal (%GC); del ICC con %GC, VO2máx, Tensión Arterial Sistólica (TAS) y Diastólica (TAD); del %GC con FCR, TAD y VO2máx; la FCR con VO2máx; la TAS con TAD y VO2máx rechazando la hipótesis de independencia. Concluyendo que los indicadores de adiposidad y aptitud cardiorrespiratoria evidencian la combinación de factores de riesgo de enfermedades de índole hipocinético en la población.
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Malik, Harbani, Ben Buelow, Udaya Rangaswamy, Aarti Balasubramani, Andrew Boudreau, Kevin Dang, Laura Davison, et al. "TNB-486, a Novel Fully Human Bispecific CD19 x CD3 Antibody That Kills CD19-Positive Tumor Cells with Minimal Cytokine Secretion." Blood 134, Supplement_1 (November 13, 2019): 4070. http://dx.doi.org/10.1182/blood-2019-123226.
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Introduction The restricted expression of CD19 in the B-cell lineage makes it an attractive target for the therapeutic treatment of B-cell malignancies. Many monoclonal antibodies and antibody drug conjugates targeting CD19 have been developed, including bispecific T-cell redirecting antibodies (T-BsAbs). In addition, anti-CD19 chimeric antigen receptor T-cells (CAR-T) have been approved to treat leukemia and lymphoma. However, despite the impressive depth of responses achieved by T-cell redirecting approaches such as T-BsAbs and CAR-T cells, toxicity from over-activation of T-cells remains a substantial limitation for this type of therapy, in particular neurotoxicity. In designing TNB-486, a novel CD19 x CD3 T-BsAb, we endeavored to retain activity against CD19-positive tumor cells while limiting the cytokine secretion thought to underlie toxicity from T-cell redirecting therapies. Utilizing TeneoSeek, a next generation sequencing (NGS)-based discovery pipeline that leverages in silico analysis of heavy chain only/fixed light chain antibody (HCA/Flic, respectively) sequences to enrich for antigen specific antibodies, we made a high affinity αCD19 HCA and a library of αCD3 Flic antibodies that showed a >2 log range of EC50s for T cell activation in vitro. Of note, the library contained a low-activating αCD3 that induced minimal cytokine secretion even at concentrations that mediated saturating T-cell dependent lysis of lymphoma cells (when paired with an αCD19 HCA). We characterized the relative efficacy and potential therapeutic window of this unique molecule, TNB-486, in vitro and in vivo and compared it to two strongly activating bispecific CD19 x CD3 antibodies similar to those currently available and in clinical development. Methods Affinity measurements of the αCD19 moiety were made via Biacore (protein) and flow cytometry (cell surface). Stability measurements were made by subjecting the molecule to thermal stress and the %aggregation was measured by Size Exclusion Chromatography. T-cell activation was measured via flow cytometry (CD69 and CD25 expression) and cytokine was measured by ELISA (IL-2, IL-6, IL-10, INF-ɣ, and TNFα) in vitro. Lysis of B-cell tumor cell lines (Raji, RI-1, and Nalm6) was measured via flow cytometry in vitro. In vivo, NOG mice were engrafted subcutaneously with NALM-6 or SUDHL-10 cells and intravenously with human peripheral blood mononuclear cells (huPBMC), and the mice treated with multiple doses of TNB-486 or negative or positive control antibody. Tumor burden was evaluated via caliper measurement. Pharmacodynamic/Pharmacokinetic (PK/PD) studies were performed in NOG mice. A pharmacokinetic (PK) study was performed in BALB/c mice, and a tolerability and PK study are ongoing in cynomolgus monkeys. Results TNB-486 bound to cell surface CD19 with single digit nanomolar affinity (~3nM). EC50s for cytotoxicity were in the single-digit nanomolar range for TNB-486, and sub-nanomolar for the strongly activating controls; TNB-486 maximum achievable lysis was identical to the positive controls. TNB-486 induced significantly less cytokine release for all cytokines tested compared to the positive controls even at doses saturating for tumor lysis. No off-target activation was observed in the absence of CD19 expressing target cells. In vivo, TNB-486 eradicated all CD19-positive tumors tested (NALM-6 and SUDHL10) at doses as little as 1µg administered every four days after tumors had reached ~200mm3. TNB-486 showed a PK profile consistent with other IgG molecules in mice (T1/2 ~6 days in mice). Conclusions TNB-486 induced comparable lysis of CD19-positive tumor cells as the strongly activating control bispecific antibodies while inducing significantly reduced cytokine secretion, even at doses saturating for tumor lysis in vitro. In vivo TNB-486 eradicated all tested CD19 positive tumor cell lines in established tumor models. No off-target binding was observed. In summary, TNB-486 shows promise as a lymphoma therapeutic differentiated from T-cell targeted therapies currently in the clinic and in clinical trials. Disclosures Malik: Teneobio, Inc.: Employment, Equity Ownership. Buelow:Teneobio, Inc.: Employment, Equity Ownership. Rangaswamy:Teneobio, Inc.: Employment, Equity Ownership. Balasubramani:Teneobio, Inc.: Employment, Equity Ownership. Boudreau:Teneobio, Inc.: Employment, Equity Ownership. Dang:Teneobio, Inc.: Employment, Equity Ownership. Davison:Teneobio, Inc.: Employment, Equity Ownership. Force Aldred:Teneobio, Inc.: Equity Ownership. Iyer:Teneobio, Inc.: Employment, Equity Ownership. Jorgensen:Teneobio, Inc.: Employment, Equity Ownership. Pham:Teneobio, Inc.: Employment, Equity Ownership. Prabhakar:Teneobio, Inc.: Employment, Equity Ownership. Schellenberger:Teneobio, Inc.: Employment, Equity Ownership. Ugamraj:Teneobio, Inc.: Employment, Equity Ownership. Trinklein:Teneobio, Inc.: Employment, Equity Ownership. Van Schooten:Teneobio, Inc.: Employment, Equity Ownership.
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Peffault De Latour, Regis, Jaroslaw P. Maciejewski, Austin G. Kulasekararaj, Loree Larratt, Ronald S. Go, David Dingli, Amanda Wilson, Philippe Gustovic, and Aleksandr Kulagin. "Prognostic Value of Clone Size in Paroxysmal Nocturnal Hemoglobinuria (PNH) for Thrombotic Events in Untreated Patients in the International PNH Registry." Blood 132, Supplement 1 (November 29, 2018): 1038. http://dx.doi.org/10.1182/blood-2018-99-111324.
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Abstract Background/Objective: The association between paroxysmal nocturnal hemoglobinuria (PNH) granulocyte clone size at disease onset and outcomes in patients with PNH remains unclear. Most but not all reports examining the relationship have shown a positive correlation between clone size and thrombotic events [TEs] in patients with PNH, but without a clear temporal association showing the prognostic value of clone size on the risk of TEs. The ongoing International PNH Registry (NCT01374360) is the largest prospective, observational study of patients with PNH conducted to date. The objective of this analysis was to examine the relationship between PNH granulocyte clone size at disease onset and risk of thrombosis after disease onset while untreated with a complement inhibitor in patients enrolled in the Registry. Methods: The current analysis included patients enrolled in the Registry as of April 2018 who had known demographics, were untreated with complement inhibitor therapy at enrollment, and had ≥12 months of untreated follow-up after disease onset. Baseline was defined as disease onset (earliest of a reported PNH clone, date of PNH diagnosis, or reported PNH symptom), and patients were stratified into 5 cohorts based on clone size at baseline (using the earliest reported clone prior to enrollment): cohort 1, clone size: 0.01-1%; cohort 2, clone size: >1-5%; cohort 3, clone size: >5-10%; cohort 4, clone size: >10-50%; cohort 5, clone size: >50%. Event rates for TEs and all major adverse vascular events (MAVEs; including TEs) were calculated for the time period from baseline to last follow-up. Other outcomes of interest included LDH ratio (LDH/LDH upper limit of normal [ULN]), hemoglobin levels, platelet counts, absolute neutrophil counts, and absolute reticulocyte counts at last follow-up. Results: A total of 2489 patients were eligible for the analysis. The majority of patients in the overall study population were female (54.0% [1343/2489]) and white (79.2% [1967/2484]). Mean (standard deviation [SD]) age at PNH start ranged from 36.4 (16.53) in cohort 5 to 44.2 (20.70) in cohort 1. Median time from baseline to last follow-up was 3.7 years in cohort 1, 4.3 years in cohort 2, 4.7 years in cohort 3, 5.6 years in cohort 4, and 6.8 years in cohort 5. Results for the outcomes of interest are summarized in the Table. All cohorts showed a risk of MAVE and TE during follow-up. Although estimated rates of MAVE and TE were highest in the >50% clone size cohort, there was no difference in the rate of MAVE or TE during follow-up across the 4 cohorts with clone size <50% at disease onset. Mean LDH ratio (LDH/LDH ULN) at last follow-up showed a statistically significant difference by clone size at baseline among the cohorts, ranging from a mean (SD) of 1.1 (1.34) in the patients with clone size <1% and increasing to 5.1 (3.81) in the patients with clone size >50% (P<0.0001). No difference in hemoglobin level at last follow-up was observed in the smaller clone size cohorts, although mean hemoglobin level was lower in patients with clone size >50% (P<0.0001). Similar trends were seen in mean platelet and absolute neutrophil counts across the smaller clone size cohorts, while patients with clone size >50% showed higher values (P<0.0001). Mean absolute reticulocyte count at last follow-up was lowest in patients with clone size 0.01-1%, and were incrementally higher in each successive clone-size cohort (P<0.0001). Conclusions: In this study, all patients with a PNH clone at disease onset were at risk for TEs and other MAVEs. Patients in the highest baseline PNH clone size strata (clone size >50%) had an approximately 2-times higher risk of TEs than patients with smaller clone sizes; Patients with small clone sizes (0.01-1%) were older and showed a higher prevalence of BMD. There was no difference in the prognostic value of clone size at disease onset on the risk of TEs and other MAVEs in patients with small (0.01-1% and 1-5%) versus medium-sized (5-10% or 10-50%) clones. Table Table. Disclosures Peffault De Latour: Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Pfizer Inc.: Consultancy, Honoraria, Research Funding; Amgen Inc.: Research Funding. Maciejewski:Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Apellis Pharmaceuticals: Consultancy; Apellis Pharmaceuticals: Consultancy; Ra Pharmaceuticals, Inc: Consultancy; Ra Pharmaceuticals, Inc: Consultancy. Kulasekararaj:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Other: Travel Support . Larratt:Alexion Pharmaceuticals, Inc.: Honoraria, Research Funding. Dingli:Millennium Takeda: Research Funding; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.. Wilson:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Gustovic:Alexion Pharma GmbH: Employment, Equity Ownership. Kulagin:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria.
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Janicak, Paul, Karen Heart, and Bridget McGugan. "166 Post Market Rate of Seizures During TMS Treatment with NeuroStar® System Appears to Be Lower than Previously Estimated." CNS Spectrums 25, no. 2 (April 2020): 306. http://dx.doi.org/10.1017/s1092852920000826.
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Abstract:Objective: NeuroStar® Advanced Therapy System is a transcranial magnetic stimulation (TMS) device with FDA-clearance for the treatment of Major Depressive Disorder (MDD) in adult patients who have failed to receive satisfactory improvement from prior antidepressant medication in the current episode. With TMS, magnetic pulses are transmitted into the brain. Though the exact mechanism of action is unknown, it is postulated that resulting neuronal depolarization and changes in brain functional activity may be associated with various physiologic changes that lead to relief of depression in the indicated population. The type of magnetic field generated with TMS is not intended to induce a seizure during therapeutic use, but unintentional seizures have been reported during TMS treatment.No seizures were reported with the use of the NeuroStar® system in clinical trials conducted prior to FDA clearance. The estimated risk of seizure in the NeuroStar® label is approximately 1 in 30,000 treatments or 1 in 1,000 patients. Since introduction of the NeuroStar® system into clinical practice, the rate at which seizures have been reported is even lower.Methods:We conducted a review of literature that named the NeuroStar® Advanced Therapy System as the device used for TMS treatment and reviewed all seizure events reported to Neuronetics, Inc., directly or through FDA MedWatch through June 30, 2019. Articles reporting seizures in subjects with epilepsy during TMS treatment were excluded.Results:Previous comprehensive reviews of seizures induced by treatment with any TMS device by Wasserman et al. (1998) and Rossi et al. (2009) revealed that the rate of seizures is low. Many subjects that developed seizures during TMS had either received stimulation at parameters beyond current recommendations or had been predisposed to develop seizures in some way. Some of the events reported as seizures may, in fact, have been non-epileptic events.Our literature review and analysis of seizures reported to Neuronetics, Inc. revealed that the rate of seizures during TMS treatment with the NeuroStar® appears to be lower than the rate that is published in the NeuroStar® Advanced Therapy prescribing information.Conclusions:Seizures that take place during TMS treatment with the NeuroStar® system are rare. The rate of seizures reported directly to Neuronetics, Inc. is lower than that included in the NeuroStar® prescribing information. Our literature review validated seizures during TMS treatment with the NeuroStar® system reported in published literature have described either non-epileptic events (syncope) or occurred with risk factors for seizure induction, such as other predisposing clinical factors or treatment parameters outside the guideline recommend “safe” ranges.Funding Acknowledgements:Neuronetics, Inc.
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Jeong, Jae-Han, Jung-Soo Pyo, Nae-Yu Kim, and Dong-Wook Kang. "Diagnostic Roles of Immunohistochemistry in Thymic Tumors: Differentiation between Thymic Carcinoma and Thymoma." Diagnostics 10, no. 7 (July 6, 2020): 460. http://dx.doi.org/10.3390/diagnostics10070460.
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Background: The present study aims to evaluate the diagnostic roles of various immunohistochemical (IHC) markers in thymic tumors, including thymic carcinoma (TC) and thymoma (TM). Methods: Eligible studies were obtained by searching the PubMed databases and screening the searched articles. Thirty-eight articles were used in the present meta-analysis and included 636 TCs and 1861 TMs. Besides, for IHC markers with statistical significance, a diagnostic test accuracy review was performed. Results: The comparison of various IHC expressions between TC and TM was performed for 32 IHC markers. Among these IHC markers, there were significant differences between TC and TM for beta-5t, B-cell lymphoma 2 (Bcl-2), calretinin, CD1a, CD5, carcinoembryonic antigen (CEA), cytokeratin19 (CK19), CD117, glucose transporter 1 (Glut-1), insulin-like growth factor 1 receptor (IGF-1R), mesothelin, MOC31, mucin1 (MUC1), p21, and terminal deoxynucleotidyl transferase (TdT). Markers with higher expressions in TCs were Bcl-2, calretinin, CD5, CEA, CD117, Glut-1, IGF-1R, mesothelin, MOC31, MUC1, and p21. Among these markers, there were no significant differences between TC and TM type B3 in immunohistochemistries for Bcl-2 and CK19. On the other hand, β-catenin and CD205 showed a considerable difference in IHC expressions between TC and TM type B3, but not between TC and overall TM. In diagnostic test accuracy review, MUC1 and beta-5t were the most useful markers for TC and TM, respectively. Conclusions: Taken together, our results showed that the expression rates for various IHC markers significantly differed between TC and TM. The IHC panel can be useful for differentiation from limited biopsied specimens in daily practice.
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DOLGIN, ELIE S., BRIAN CHARLESWORTH, and ASHER D. CUTTER. "Population frequencies of transposable elements in selfing and outcrossingCaenorhabditisnematodes." Genetics Research 90, no. 4 (August 2008): 317–29. http://dx.doi.org/10.1017/s0016672308009440.
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SummaryPopulation genetics theory predicts that differences in breeding systems should be an important factor in the dynamics of selfish genetic elements, because of different intensities of selection on both hosts and elements. We examined population frequencies of transposable elements (TEs) in natural populations of the self-fertilizing nematodeCaenorhabditis elegansand its outcrossing relativeCaenorhabditis remanei. We identified a Tc1-like class of elements in theC. remaneigenome with homology to the terminal inverted repeats of theC. elegansTc1 transposon, which we name mTcre1. We measured levels of insertion polymorphism for all 32 Tc1 elements present in the genome sequence of theC. elegansN2 strain, and 16 mTcre1 elements from the genome sequence of theC. remaneiPB4641 strain. We show that transposons are less polymorphic and segregate at higher frequencies inC. eleganscompared withC. remanei. Estimates of the intensity of selection based on the population frequencies of polymorphic elements suggest that transposons are selectively neutral inC. elegans, but subject to purifying selection inC. remanei. These results are consistent with a reduced efficacy of natural selection against TEs in selfing populations, but may in part be explained by non-equilibrium TE dynamics.
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Zhou, Zhengjun, Pengcheng Wang, Rongqi Sun, Jia Li, Zhiqiang Hu, Haoyang Xin, Chubin Luo, Jian Zhou, Jia Fan, and Shaolai Zhou. "Tumor-associated neutrophils and macrophages interaction contributes to intrahepatic cholangiocarcinoma progression by activating STAT3." Journal for ImmunoTherapy of Cancer 9, no. 3 (March 2021): e001946. http://dx.doi.org/10.1136/jitc-2020-001946.
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BackgroundTumor-associated neutrophils (TANs) and macrophages (TAMs) can each influence cancer growth and metastasis, but their combined effects in intrahepatic cholangiocarcinoma (ICC) remain unclear.MethodsWe explored the distributions of TANs and TAMs in patient-derived ICC samples by multiplex immunofluorescent staining and tested their separate and combined effects on ICC in vitro and in vivo. We then investigated the mechanistic basis of the effects using PCR array, western blot analysis and ELISA experiments. Finally, we validated our results in a tissue microarray composed of primary tumor tissues from 359 patients with ICC.ResultsThe spatial distributions of TANs and TAMs were correlated with each other in patient-derived ICC samples. Interaction between TANs and TAMs enhanced the proliferation and invasion abilities of ICC cells in vitro and tumor progression in a mouse xenograft model of ICC. TANs and TAMs produced higher levels of oncostatin M and interleukin-11, respectively, in co-culture than in monoculture. Both of those cytokines activated STAT3 signaling in ICC cells. Knockdown of STAT3 abolished the protumor effect of TANs and TAMs on ICC. In tumor samples from patients with ICC, increased TAN and TAM levels were correlated with elevated p-STAT3 expression. All three of those factors were independent predictors of patient outcomes.ConclusionsTANs and TAMs interact to promote ICC progression by activating STAT3.
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Louie, Ted. "Mrs T's Mysterious Fever." Infectious Diseases in Clinical Practice 15, no. 3 (May 2007): 141–42. http://dx.doi.org/10.1097/01.idc.0000269901.36790.6b.
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Grah, Christian, Konstantin Afanaciev, Igor Emeliantchik, Ulrich Harder, Hans Henschel, Alexandr Ignatenko, Ekaterina Kouznetsova, et al. "Polycrystalline CVD Diamonds for the Beam Calorimeter of the ILC." IEEE Transactions on Nuclear Science 56, no. 2 (April 2009): 462–67. http://dx.doi.org/10.1109/tns.2009.2013853.
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Shinde, Omkar A., Ankita Bansal, Angela Banerjee, and Supriya Sarkar. "Bioremediation of steel plant wastewater and enhanced electricity generation in microbial desalination cell." Water Science and Technology 77, no. 8 (March 17, 2018): 2101–12. http://dx.doi.org/10.2166/wst.2018.126.
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Abstract Microbial desalination cell (MDC) is a propitious technology towards water desalination by utilizing wastewater as an energy source. In this study, a multi-chambered MDC was used to bioremediate steel plant wastewater using the same wastewater as a fuel for anodic bacteria. A pure culture of Pseudomonas putida MTCC 1194 was isolated and inoculated to remove toxic phenol. Three different inoculum conditions, namely P. putida (INC-A), a mixture of P. putida and activated sludge (INC-B), and activated sludge alone (INC-C) were employed in an anodic chamber to mainly compare the electricity generation and phenol degradation in MDCs. The study revealed the maximum phenol removal of 82 ± 2.4%, total dissolved solids (TDS) removal of 68 ± 1.5%, and power generation of 10.2 mW/m2 using INC-B. The synergistic interactions between microorganisms, can enhance the toxic phenol degradation and also electricity generation in MDC for onsite wastewater application.
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Partridge, Sally R., Heidi J. Brown, H. W. Stokes, and Ruth M. Hall. "Transposons Tn1696 and Tn21and Their Integrons In4 and In2 Have Independent Origins." Antimicrobial Agents and Chemotherapy 45, no. 4 (April 1, 2001): 1263–70. http://dx.doi.org/10.1128/aac.45.4.1263-1270.2001.
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ABSTRACT The first 13.6 kb of the mercury and multidrug resistance transposon Tn1696, which includes the class 1 integron In4, has been sequenced. In4 is 8.33 kb long and contains the 5′-conserved segment (5′-CS) and 2.24 kb of the 3′-conserved segment (3′-CS) flanking four integrated cassettes. The 3′-CS region is followed by one full copy and an adjacent partial copy of the insertion sequence IS6100 flanked, in inverse orientation, by two short segments (123 and 152 bp) from the outer right-hand end of class 1 integrons. This structure is representative of a distinct group of class 1 integrons that differs from In2, found in Tn21, and other related class 1 integrons. In4 does not include transposition genes but is bounded by characteristic 25-bp inverted repeats and flanked by a direct duplication of 5 bp of the target sequence, indicating that it was inserted by a transpositional mechanism. In4 lies between the resII and resIsites of a backbone mercury resistance transposon which is >99.5% identical to Tn5036. Although Tn21 and Tn1696 are both classified as members of the Tn21 subfamily of the Tn3 transposon family, the backbone mercury resistance transposons are only 79 to 96% identical. Tn21 also contains a region of about 0.7 kb not found in Tn1696. The integrons In2 and In4 carrying the antibiotic resistance genes have been inserted at different locations into distinct ancestral mercury resistance transposons. Thus, Tn21 and Tn1696 have independent histories and origins. Other transposons (Tn1403 and Tn1412) that include a class 1 integron also have independent origins. In all except Tn21, the integron is located within theres region of the backbone transposon.
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Reuen, L., R. Kohrs, J. J. Velthuis, L. Andricek, P. Fischer, F. Giesen, H. Kruger, et al. "Performance of a DEPFET prototype module for the ILC vertex detector." IEEE Transactions on Nuclear Science 53, no. 3 (June 2006): 1719–25. http://dx.doi.org/10.1109/tns.2006.873079.
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Johnson, Mark I., and Ghazala Tabasam. "An Investigation Into the Analgesic Effects of Interferential Currents and Transcutaneous Electrical Nerve Stimulation on Experimentally Induced Ischemic Pain in Otherwise Pain-Free Volunteers." Physical Therapy 83, no. 3 (March 1, 2003): 208–23. http://dx.doi.org/10.1093/ptj/83.3.208.
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Abstract Background and Purpose. Interferential currents (IFC) and transcutaneous electrical nerve stimulation (TENS) are used for pain management. This study compared the analgesic effects of IFC and TENS on experimentally induced ischemic pain in otherwise pain-free subjects using a modified version of the submaximal-effort tourniquet technique. Subjects. The subjects were 30 volunteers (18 male, 12 female) without known pathology that could cause pain. Their mean age was 33.5 years (SD=9.9, range=21–54). Method. A single-blind, sham-controlled, parallel-group method was used. The primary outcome measure was the change in the self-report of pain intensity during 1 of 3 possible interventions: (1) IFC, (2) TENS, or (3) sham electrotherapy. The IFC and TENS were administered on the forearm, and the sham electrotherapy group received no current output via a dummy stimulator. Results. A 2-way repeated-measures analysis of variance revealed that there was no change in pain intensity during treatment when all 3 groups were considered together. Further analysis revealed that IFC reduced pain intensity when compared with sham electrotherapy but not when compared only with TENS. Discussion and Conclusion. There were no differences in the magnitude of analgesia between IFC and TENS. Interferential currents reduced pain intensity to a greater extent than sham electrotherapy.
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Dyshkant, Alexandre, G. Blazey, K. Francis, D. Hedin, V. Zutshi, H. Fisk, C. Milstene, and R. Abrams. "MAPMT H7546B Anode Current Response Study for an ILC SiD Muon System Prototype." IEEE Transactions on Nuclear Science 55, no. 3 (June 2008): 1691–94. http://dx.doi.org/10.1109/tns.2008.924088.
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Mannai, S., K. Manai, E. Cortina, and I. Laktineh. "Energy Reconstruction in a High Granularity Semi-Digital Hadronic Calorimeter for ILC Experiments." IEEE Transactions on Nuclear Science 63, no. 6 (December 2016): 2880–86. http://dx.doi.org/10.1109/tns.2016.2614946.
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Barber, Stephen. "Charles Williams and T.S. Eliot: Friends and Rivals." Journal of Inklings Studies 9, no. 1 (April 2019): 1–18. http://dx.doi.org/10.3366/ink.2019.0024.
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Williams and Eliot were close in age and both worked in publishing as well having careers as poets and freelance writers. However, their backgrounds were very different: Williams came from humble origins and was not able to complete a university degree, whereas Eliot at first seemed to set to become an academic philosopher. They first met in the early 1930s, by which time Williams had been both confused and influenced by The Waste Land. Eliot started to read Williams's novels and was in turn greatly influenced by them. They became increasingly close until Williams's death in 1945. Eliot showed the greatest influence of Williams in his 1949 play The Cocktail Party. Their Christian sensibility had some important features in common and, in the end, Williams's concept of the Affirmative Way became a great influence on Eliot.
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Traversi, Gianluca, Antonio Bulgheroni, Massimo Caccia, Marcin Jastrzab, Massimo Manghisoni, Enrico Pozzati, Lodovico Ratti, and Valerio Re. "Design and Performance of a DNW CMOS Active Pixel Sensor for the ILC Vertex Detector." IEEE Transactions on Nuclear Science 56, no. 5 (October 2009): 3002–9. http://dx.doi.org/10.1109/tns.2009.2025885.
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Rhee, Lesley, Stephen F. Murphy, Lauren E. Kolodziej, Wesley A. Grimm, Christopher R. Weber, James P. Lodolce, Jonathan E. Chang, et al. "Expression of TNFAIP3 in intestinal epithelial cells protects from DSS- but not TNBS-induced colitis." American Journal of Physiology-Gastrointestinal and Liver Physiology 303, no. 2 (July 15, 2012): G220—G227. http://dx.doi.org/10.1152/ajpgi.00077.2012.
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Intestinal epithelial cells (IEC) maintain gastrointestinal homeostasis by providing a physical and functional barrier between the intestinal lumen and underlying mucosal immune system. The activation of NF-κB and prevention of apoptosis in IEC are required to maintain the intestinal barrier and prevent colitis. How NF-κB activation in IEC prevents colitis is not fully understood. TNFα-induced protein 3 (TNFAIP3) is a NF-κB-induced gene that acts in a negative-feedback loop to inhibit NF-κB activation and also to inhibit apoptosis; therefore, we investigated whether TNFAIP3 expression in the intestinal epithelium impacts susceptibility of mice to colitis. Transgenic mice expressing TNFAIP3 in IEC (villin-TNFAIP3 Tg mice) were exposed to dextran sodium sulfate (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS), and the severity and characteristics of mucosal inflammation and barrier function were compared with wild-type mice. Villin-TNFAIP3 Tg mice were protected from DSS-induced colitis and displayed reduced production of NF-κB-dependent inflammatory cytokines. Villin-TNFAIP3 Tg mice were also protected from DSS-induced increases in intestinal permeability and induction of IEC death. Villin-TNFAIP3 Tg mice were not protected from colitis induced by TNBS. These results indicate that TNFAIP3 expression in IEC prevents colitis involving DSS-induced IEC death, but not colitis driven by T cell-mediated inflammation. As TNFAIP3 inhibits NF-κB activation and IEC death, expression of TNFAIP3 in IEC may provide an avenue to inhibit IEC NF-κB activation without inducing IEC death and inflammation.
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Niu, Xiao-Min, Yong-Chao Xu, Zi-Wen Li, Yu-Tao Bian, Xing-Hui Hou, Jia-Fu Chen, Yu-Pan Zou, et al. "Transposable elements drive rapid phenotypic variation inCapsella rubella." Proceedings of the National Academy of Sciences 116, no. 14 (March 15, 2019): 6908–13. http://dx.doi.org/10.1073/pnas.1811498116.
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Rapid phenotypic changes in traits of adaptive significance are crucial for organisms to thrive in changing environments. How such phenotypic variation is achieved rapidly, despite limited genetic variation in species that experience a genetic bottleneck is unknown.Capsella rubella, an annual and inbreeding forb (Brassicaceae), is a great system for studying this basic question. Its distribution is wider than those of its congeneric species, despite an extreme genetic bottleneck event that severely diminished its genetic variation. Here, we demonstrate that transposable elements (TEs) are an important source of genetic variation that could account for its high phenotypic diversity. TEs are (i) highly enriched inC. rubellacompared with its outcrossing sister speciesCapsella grandiflora, and (ii) 4.2% of polymorphic TEs inC. rubellaare associated with variation in the expression levels of their adjacent genes. Furthermore, we show that frequent TE insertions atFLOWERING LOCUS C (FLC)in natural populations ofC. rubellacould explain 12.5% of the natural variation in flowering time, a key life history trait correlated with fitness and adaptation. In particular, we show that a recent TE insertion at the 3′ UTR ofFLCaffects mRNA stability, which results in reducing its steady-state expression levels, to promote the onset of flowering. Our results highlight that TE insertions can drive rapid phenotypic variation, which could potentially help with adaptation to changing environments in a species with limited standing genetic variation.
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Nozoe, Tadahiro, Emiko Mori, Tomohiro Iguchi, and Takahiro Ezaki. "New Criteria to Predict Tumor Recurrence in Invasive Ductal Carcinoma of the Breast." International Surgery 98, no. 4 (October 1, 2013): 283–88. http://dx.doi.org/10.9738/intsurg-d-12-00029.1.
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Abstract Incidence of triple-negative breast cancer (TNBC), which is cancer without expression of ER, PgR, and HER2, and nuclear grade (NG) are closely correlated with malignant potential of breast cancer. However, criteria to determine aggressiveness of breast cancer based on these factors have not been elucidated. The aim of this study was to create criteria using these factors to predict tumor recurrence in invasive ductal carcinoma (IDC) of the breast. One hundred and seventy-nine patients with IDC of the breast, which had been treated by surgical resection, were included. One point was added for each factor of the two categories of TNBC and NG 3. The sum of the scores (TGS 0, 1, or 2) was calculated. Significant difference was observed between TGS and the incidence of tumor recurrence (P < 0.0001). Moreover, significant differences were observed regarding relapse-free survival (RFS) between patients with TGS 0 and TGS 1 (P < 0.0001) and patients with TGS 1 and TGS 2 (P = 0.024). TGS might contain a clinical advantage as a useful predictor for tumor recurrence of IDC of the breast and could classify prognosis of the patients with a preferable stratification.
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Cui, Huanqin, Yi Yao, Zhunan Xu, Zhenli Gao, Jitao Wu, Zhongbao Zhou, and Yuanshan Cui. "Role of Transcutaneous Electrical Nerve Stimulation in Treating Children With Overactive Bladder From Pooled Analysis of 8 Randomized Controlled Trials." International Neurourology Journal 24, no. 1 (March 31, 2020): 84–94. http://dx.doi.org/10.5213/inj.1938232.116.
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Purpose: Transcutaneous electrical neural stimulation (TENS), as a non-invasive modality, has been clinically used as an alternative treatment for children with overactive bladder (OAB). We conducted a pooled analysis to explore the effect of TENS on OAB.Methods: The Preferred Reporting Items for Systematic Reviews and Meta-analysis guideline was followed in this study. The MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases, as well as the reference lists of the retrieved studies, were used to find trials relevant for assessing the use of TENS to treat OAB.Results: Of the 246 records identified, 8 publications were analyzed in our study. Our analysis found that TENS resulted in a greater decrease of wet days/wk, daily voiding frequency, daily incontinence episodes, and daily number of voids than was observed in the control group. Furthermore, TENS-treated patients showed similar visual analogue scale (VAS) scores to patients in the control group, demonstrating that the application of TENS did not increase patients’ discomfort and pain. TENS had a relative advantage in the number of partial responses, but no clear differences were found in frequency of no response or a full response compared to the control group. In urodynamic testing, TENS led to obvious improvements in average voided volume and maximum voided volume in children with OAB.Conclusions: TENS had a remarkable effect on the improvement of urodynamic indexes and objective OAB symptoms without a significant increase in VAS scores for children with OAB.
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Rarbi, Fatah, Daniel Dzahini, and Laurent Gallin-Martel. "A Power Efficient 12-bit and 25-MS/s Pipelined ADC for the ILC/Ecal Integrated Readout." IEEE Transactions on Nuclear Science 57, no. 5 (October 2010): 2798–804. http://dx.doi.org/10.1109/tns.2010.2067226.
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PENG, Chang-yan, Quan ZHANG, and Chao-jing TANG. "Design and analysis of IBC-based TLS handshake protocol." Journal of Computer Applications 29, no. 3 (May 6, 2009): 633–37. http://dx.doi.org/10.3724/sp.j.1087.2009.00633.
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Morsi, Iman, and Mohamed Mansour Mohamed Mostafa. "Wireless Gas Detector System Using Microcontrollers, PLC and SCADA System for Monitoring Environmental Pollution." Applied Mechanics and Materials 249-250 (December 2012): 247–55. http://dx.doi.org/10.4028/www.scientific.net/amm.249-250.247.
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Gas identification represents a big challenge for improving detection and pattern recognition of each gas by using inexpensive gas sensor. This paper presents a gas detector system which is built to monitor, and measure gas pollutant emissions in the air and also used to detect different gases. The pollutants are ethane (C2H6) and methane (CH4) which are located beside the fertilizer factories in Alexandria Egypt and some other gases as hydrogen (H2), propane (C3H8) and isobutane (C4H10).The gas sensors TGS-2611, TGS-816, TGS-2620 and TGS-823 from Figaro Engineering Inc. are used to build agas detector system and it is located in the site of measurements. The data of each sensor is transmitted and received wirelessly using XBee module (DigiXBee 802.15.4) and microcontroller PIC 18F4620. The system is controlled and monitored by using programmable logic controllerPLC Step 7-200 from Siemens and Supervisory Control and Data Acquisition SCADA systems respectively. The principal component analysis PCA method is applied for clustering and distinguishing among different gases. The results indicate thatmethane can be detected using TGS-2611 better than other sensors.Isobutane can be detected by using TGS-2620 and TGS-2611 better than others. Propane can be detected by using TGS-816 and TGS-823 better than others. Hydrogen can be detected using TGS-2620, TGS-816 and TGS-823 better than others
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Díaz-Flores, Lucio, Ricardo Gutiérrez, Miriam González-Gómez, Maria Pino García, Lucio Díaz-Flores, José Luís Carrasco, and Pablo Martín-Vasallo. "CD34+ Stromal Cells/Telocytes as a Source of Cancer-Associated Fibroblasts (CAFs) in Invasive Lobular Carcinoma of the Breast." International Journal of Molecular Sciences 22, no. 7 (April 1, 2021): 3686. http://dx.doi.org/10.3390/ijms22073686.
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Several origins have been proposed for cancer-associated fibroblasts (CAFs), including resident CD34+ stromal cells/telocytes (CD34+SCs/TCs). The characteristics and arrangement of mammary CD34+SCs/TCs are well known and invasive lobular carcinoma of the breast (ILC) is one of the few malignant epithelial tumours with stromal cells that can express CD34 or αSMA, which could facilitate tracking these cells. Our objective is to assess whether tissue-resident CD34+SCs/TCs participate in the origin of CAFs in ILCs. For this purpose, using conventional and immunohistochemical procedures, we studied stromal cells in ILCs (n:42) and in normal breasts (n:6, also using electron microscopy). The results showed (a) the presence of anti-CD34+ or anti-αSMA+ stromal cells in varying proportion (from very rare in one of the markers to balanced) around nests/strands of neoplastic cells, (b) a similar arrangement and location of stromal cells in ILC to CD34+SCs/TCs in the normal breast, (c) both types of stromal cells coinciding around the same nest of neoplastic cells and (d) the coexpression of CD34 and αSMA in stromal cells in ILC. In conclusion, our findings support the hypothesis that resident CD34+SCs/TCs participate as an important source of CAFs in ILC. Further studies are required in this regard in other tumours.
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Yoganandarajah, Vithushiya, Josie Patel, Bede van Schaijik, Nicholas Bockett, Helen D. Brasch, Erin Paterson, Dalice Sim, et al. "Identification of Cancer Stem Cell Subpopulations in Head and Neck Metastatic Malignant Melanoma." Cells 9, no. 2 (January 30, 2020): 324. http://dx.doi.org/10.3390/cells9020324.
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Cancer stem cells (CSCs) have been identified in many cancer types. This study identified and characterized CSCs in head and neck metastatic malignant melanoma (HNmMM) to regional lymph nodes using induced pluripotent stem cell (iPSC) markers. Immunohistochemical (IHC) staining performed on 20 HNmMM tissue samples demonstrated expression of iPSC markers OCT4, SOX2, KLF4, and c-MYC in all samples, while NANOG was expressed at low levels in two samples. Immunofluorescence (IF) staining demonstrated an OCT4+/SOX2+/KLF4+/c-MYC+ CSC subpopulation within the tumor nests (TNs) and another within the peritumoral stroma (PTS) of HNmMM tissues. IF also showed expression of NANOG by some OCT4+/SOX2+/KLF4+/c-MYC+ cells within the TNs in an HNmMM tissue sample that expressed NANOG on IHC staining. In situ hybridization (n = 6) and reverse-transcription quantitative polymerase chain reaction (n = 5) on the HNmMM samples confirmed expression of all five iPSC markers. Western blotting of primary cell lines derived from four of the 20 HNmMM tissue samples showed expression of SOX2, KLF4, and c-MYC but not OCT4 and NANOG, and three of these cell lines formed tumorspheres in vitro. We demonstrate the presence of two putative CSC subpopulations within HNmMM, which may be a novel therapeutic target in the treatment of this aggressive cancer.
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Nagai, Noriaki, Ryusuke Sakamoto, Seiji Yamamoto, Saori Deguchi, Hiroko Otake, and Tadatoshi Tanino. "Solid Nanocrystals of Rebamipide Promote Recovery from Indomethacin-Induced Gastrointestinal Bleeding." International Journal of Molecular Sciences 20, no. 20 (October 9, 2019): 4990. http://dx.doi.org/10.3390/ijms20204990.
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Indomethacin (IMC)-induced gastrointestinal (GI) injuries are more common in rheumatoid arthritis (RA) patients than in other IMC users, and the overexpression of nitric oxide (NO) via inducible NO synthase (iNOS) is related to the seriousness of IMC-induced GI injuries. However, sufficient strategies to prevent IMC-induced GI injuries have not yet been established. In this study, we designed dispersions of rebamipide (RBM) solid nanocrystals (particle size: 30–190 nm) by a bead mill method (RBM-NDs), and investigated whether the oral administration of RBM-NDs is useful to prevent IMC-induced GI injuries. The RBM nanocrystals were spherical and had a solubility 4.71-fold greater than dispersions of traditional RBM powder (RBM-TDs). In addition, the RBM-NDs were stable for 1 month after preparation. The RBM contents in the stomach, jejunum, and ileum of rats orally administered RBM-NDs were significantly higher than in rats administered RBM-TDs. Moreover, the oral administration of RBM-NDs decreased the NO levels via iNOS and area of the GI lesions in IMC-stimulated RA (adjuvant-induced arthritis rat) rats in comparison with the oral administration of RBM-TDs. Thus, we show that the oral administration of RBM-NDs provides a high drug supply to the GI mucosa, resulting in a therapeutic effect on IMC-induced GI injuries. Solid nanocrystalline RBM preparations may offer effective therapy for RA patients.
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Urbano-Ispizua, Álvaro, Austin G. Kulasekararaj, Marije Bartels, Christopher J. Patriquin, Britta Hoechsmann, Alexey A. Maschan, Amanda Wilson, Philippe Gustovic, and Hubert Schrezenmeier. "Efficacy of Eculizumab in Pediatric Patients with Paroxysmal Nocturnal Hemoglobinuria in the International PNH Registry." Blood 132, Supplement 1 (November 29, 2018): 3614. http://dx.doi.org/10.1182/blood-2018-99-111306.
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Abstract Background/Objective: Paroxysmal nocturnal hemoglobinuria (PNH) is an extremely rare disease and is even more rare in children; pediatric cases are estimated to account for <5% of all PNH cases (Ware RE, et al. N Engl J Med. 1991;325:991-996). There is a paucity of published data on outcomes in children with PNH treated with eculizumab. The International PNH Registry (NCT01374360) is a prospective, observational study of patients with PNH regardless of age, and represents the largest cohort of pediatric PNH patients. The objective of this analysis was to evaluate outcomes after initiation of eculizumab in pediatric patients and adult patients enrolled in the Registry. Methods: The analysis included eculizumab-treated patients enrolled in the Registry as of May 2017. Patients were stratified by age at baseline (defined as the date of eculizumab initiation; age categories, <18 and ≥18 years of age) and assessed at baseline and at last follow-up. Age at the time of disease onset, as defined by earliest reported PNH granulocyte clone, disease diagnosis, or PNH symptom, was also recorded. Patients needed ≥6 months of follow-up post-baseline to be eligible for analyses of change from baseline to last follow-up on eculizumab. Results: Of 4903 patients enrolled in the Registry as of May 1, 2017, 1725 had been treated with eculizumab and had data available on demographics and enrollment date (<18 years of age at baseline, n=47; ≥18 years of age at baseline, n=1678). In both age groups, the majority of patients were female (66.0%, pediatric cohort; 52.6%, adult cohort), and the majority were white (89.1% and 81.6%, respectively). Median (quartile [Q]1, Q3) age at disease onset was 14.7 (11.0, 15.8) in the pediatric cohort and 33.3 (23.7, 48.2) in the adult cohort; median (Q1, Q3) ages at baseline were 15.8 (14.9, 17.3) and 42.0 (30.8, 57.0), respectively. Fewer pediatric patients had history of thrombotic events (TEs) and other major adverse vascular events (MAVEs) at baseline compared with the adult cohort (Table), which is consistent with findings from a previous Registry analysis (Urbano-Ispizua A, et al. Haematologica. 2017;102:e76-e79). Most patients had ≥6 months of follow-up (n=44/47 [93.6%] and n=1532/1678 [91.3%], respectively) after baseline. Median (minimum, maximum) duration of time between baseline and last follow-up on eculizumab was 3.7 (0.1, 8.7) years in the pediatric cohort and 3.9 (0.0, 12.1) years in the adult cohort. Results for outcomes of interest are summarized in the Table. In both cohorts, mean lactate dehydrogenase ratio decreased from >5 times the upper limit of normal at baseline to normal or near normal range at last follow-up in both age cohorts. There were no TEs reported in the pediatric cohort after baseline, but 2/43 patients (4.7%) with no history of MAVEs at baseline experienced non-TE MAVEs after baseline. Among adult patients, 19/1497 (1.3%) with no history of TEs and 7/1497 (0.5%) with history of TEs experienced TEs after baseline. Non-TE MAVEs after baseline in patients with no history of MAVEs were experienced by 17/1492 patients (1.1%) and non-TE MAVEs after baseline in patients with history of MAVEs were experienced by 15/1492 patients (1.0%). The proportion of patients requiring transfusion was lower at last follow-up in both cohorts compared with baseline (23.0% at last follow-up vs 49.3% at baseline for adults and 32.3% at last follow-up vs 48.4% at baseline for pediatric patients). A similar proportion of patients became transfusion-independent after treatment with eculizumab in both age cohorts (32.3% [10/31] in the pediatric cohort compared with 33.8% [370/1095] in the adult cohort). The proportion of patients with PNH-related symptoms decreased after baseline in both cohorts for most of the symptoms assessed, although fewer than 10 pediatric patients had symptom data available at both baseline and last follow-up. Conclusions: The effectiveness of eculizumab for reducing intravascular hemolysis and transfusion requirements, and preventing MAVEs (including TEs) was similar in these large cohorts of pediatric patients with PNH and adults with PNH. The higher proportion of patients transfusion-dependent among the pediatric cohort may be associated with the higher likelihood of underlying aplastic anemia in pediatric patients with PNH. Table. Table. Disclosures Urbano-Ispizua: Alexion Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees. Kulasekararaj:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Other: Travel Support . Bartels:Alexion Pharmaceuticals, Inc.: Honoraria, Other: Travel Support and is site investigator for clinical trials with the company, Research Funding. Patriquin:Ra Pharmaceuticals: Consultancy, Research Funding; Octapharma: Honoraria; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Other: Travel Support and is site investigator for clinical trials with the company. Hoechsmann:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding. Wilson:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Gustovic:Alexion Pharma GmbH: Employment, Equity Ownership. Schrezenmeier:Alexion Pharmaceuticals, Inc.: Honoraria, Research Funding.
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Shibayama, Mitsuhiro, Takuro Matsunaga, and Michihiro Nagao. "Evaluation of incoherent scattering intensity by transmission and sample thickness." Journal of Applied Crystallography 42, no. 4 (June 30, 2009): 621–28. http://dx.doi.org/10.1107/s0021889809022456.
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The H atom has a large incoherent scattering cross section and is a major source of incoherent scattering intensity, (dΣ/dΩ)inc, in small-angle neutron scattering. By taking account of multiple scattering from H atoms, a useful method (the transmission method orTmethod) is proposed for the estimation of (dΣ/dΩ)incfor various types of hydrogen-containing systems. The incoherent scattering intensity is calculated simply from the transmission,T, and the thickness of the sample,t,i.e.(dΣ/dΩ)inc≅ [exp(Σtott) − 1]/(4πt) = (1 −T)/(4πtT), where Σtot≡ −(lnT)/tis the macroscopic total cross section per unit volume. This method provides a reasonably accurate value of incoherent scattering intensity for various systems. The validity and the extent of applicability of theTmethod are examined for several samples, including light/heavy water mixtures, polymer gels and surfactant aqueous dispersions.
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Aminah, Nonoh Siti. "KARAKTERISTIK METODE PENYETARAAN SKOR TES UNTUK DATA DIKOTOMOS." Jurnal Penelitian dan Evaluasi Pendidikan 16 (January 14, 2013): 88–101. http://dx.doi.org/10.21831/pep.v16i0.1107.
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Penelitian ini bertujuan untuk menemukan: 1) akurasi estimasi parameter item pada test equating menggunakan metode Item Characteristic Curve (ICC). 2) sensitivitas metode linear yang terdiri atas Tucker - Levine score method dan Levine true score method applied to observed scores serta metode equipercentile yang terdiri atas metode Braun-Holland linear dan chained equipercentile. Data empiris yang digunakan yaitu respons siswa peserta Ulangan Akhir Semester V Mata Pelajaran Ilmu Pengetahuan Alam (IPA) SMP Tahun Ajaran 2009/2010. Penyetaraan tes menggunakan anchor test design. Anchor test bersifat external, anchor test berfungsi sebagai pengait antara tes yang disetarakan. Item anchor berisi 10 item materi Fisika. Banyak item pada tes A 55 item, tes B 55 item dan tes C 50 item. Pola penyetaraan yang digunakan pola kelompok, sehingga banyak item hasil penyetaraan berjumlah 140 item terdiri atas 10 anchor item milik bersama, 45 item berasal dari tes A, 45 item berasal dari tes B, dan 40 item berasal dari tes C. Hasil penelitian menunjukkan bahwa: 1) Estimasi parameter item pada penyetaraan tes menggunakan metode Item Characteristic Curva (ICC) menghasilkan formula indeks kesulitan item, 2) urutan sensitivitas metode penyetaraan dari paling tinggi sampai paling rendah yaitu Tucker – Levine method, Levine method, Braun - Holland linear method. Chained Equipercentile Equating method.Kata kunci: Test equating, anchor test, external anchor test, RMSD, RMSE______________________________________________________________ THE CHARACTERISTICS OF TEST EQUATING METHODS FOR DICHOTOMOUS DATAAbstract This study aims: 1) to find out the accuracy of item parameter estimates in test equating by means of the Item Characteristic Curve (ICC) method, and 2) to find out the sensivity of the linear methods consisting of the Tucker-Levine score method and the Levine true score method applied to observed scores and the equipercentile methods consisting of the Braun-Holland linear method the chained equipercentile equating method. The data were empirical data obtained from the response patterns of the junior high school students taking the final test of Natural Sciences in the odd semester of the academic year of 2009/2010. The test equating employed the external anchor test design. The anchor test served to unite the equated tests. The anchor test consisted of 10 physics items. The test A had 55 items, the test B had 55 items, and the test C had 50 items. The equating pattern employed the group pattern, so that in the equating there were 140 items, consisting of 10 common anchor items, 45 items from tests A, 45 items from tests B, and 40 items from tests C. The results of the study are as follows. 1) The item parameter estimate in the test score equating by means of the Item Characteristic Curve (ICC) method yields the formula for the item difficulty index, and 2) urutan sensitivitas metode penyetaraan dari paling tinggi sampai paling rendah yaitu The order of the sensitivity of the equating methods from the highest to the lowest is Tucker- Levine method, Levine method, Braun-Holland linear method. Chained Equipercentile Equating method.Keywords: test equating, anchor test, external anchor test, RMSD, RMSE
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Borowik, Piotr, Leszek Adamowicz, Rafał Tarakowski, Przemysław Wacławik, Tomasz Oszako, Sławomir Ślusarski, and Miłosz Tkaczyk. "Development of a Low-Cost Electronic Nose for Detection of Pathogenic Fungi and Applying It to Fusarium oxysporum and Rhizoctonia solani." Sensors 21, no. 17 (August 31, 2021): 5868. http://dx.doi.org/10.3390/s21175868.
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Electronic noses can be applied as a rapid, cost-effective option for several applications. This paper presents the results of measurements of samples of two pathogenic fungi, Fusarium oxysporum and Rhizoctonia solani, performed using two constructions of a low-cost electronic nose. The first electronic nose used six non-specific Figaro Inc. metal oxide gas sensors. The second one used ten sensors from only two models (TGS 2602 and TGS 2603) operating at different heater voltages. Sets of features describing the shapes of the measurement curves of the sensors’ responses when exposed to the odours were extracted. Machine learning classification models using the logistic regression method were created. We demonstrated the possibility of applying the low-cost electronic nose data to differentiate between the two studied species of fungi with acceptable accuracy. Improved classification performance could be obtained, mainly for measurements using TGS 2603 sensors operating at different voltage conditions.
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Bardischewsky, Frank, and Cornelius G. Friedrich. "Identification of ccdA inParacoccus pantotrophus GB17: Disruption ofccdA Causes Complete Deficiency inc-Type Cytochromes." Journal of Bacteriology 183, no. 1 (January 1, 2001): 257–63. http://dx.doi.org/10.1128/jb.183.1.257-263.2001.
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ABSTRACT A transposon Tn5-mob insertional mutant ofParacoccus pantotrophus GB17, strain TP43, was unable to oxidize thiosulfate aerobically or to reduce nitrite anaerobically, and the cellular yields were generally decreased by 11 to 20%. Strain TP43 was unable to form functional c-type cytochromes, as determined by difference spectroscopy and heme staining. However, formation of apocytochromes and their transport to the periplasm were not affected, as seen with SoxD, a c-type cytochrome associated with the periplasmic sulfite dehydrogenase homologue. The Tn5-mob-containing DNA region of strain TP43 was cloned into pSUP205 to produce pE18TP43. With the aid of pE18TP43 the corresponding wild-type gene region of 15 kb was isolated from a heterogenote recombinant to produce pEF15. Sequence analysis of 2.8 kb of the relevant region uncovered three open reading frames, designated ORFA, ccdA, and ORFB, with the latter being oriented divergently. ORFA and ccdA were constitutively cotranscribed as determined by primer extension analysis. In strain TP43 Tn5-mob was inserted into ccdA. The deduced ORFA product showed no similarity to any protein in databases. However, the ccdA gene product exhibited similarities to proteins assigned to different functions in bacteria, such as cytochrome c biogenesis. For these proteins at least six transmembrane helices are predicted with the potential to form a channel with two conserved cysteines. This structural identity suggests that these proteins transfer reducing equivalents from the cytoplasm to the periplasm and that the cysteines bring about this transfer to enable the various specific functions via specific redox mediators such as thioredoxins. CcdA of P. pantotrophus is 42% identical to a protein predicted by ORF2, and its location within thesox gene cluster coding for lithotrophic sulfur oxidation suggested a different function.
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Salles, Gilles A., Thomas E. Boyd, Franck Morschhauser, Clemens-Martin Wendtner, Michael Hallek, Barbara F. Eichhorst, Mark Kozloff, et al. "Updated Safety and Preliminary Efficacy Data from a Phase 1b Study Combining Venetoclax (GDC-0199, ABT-199) with Bendamustine/Rituximab in Patients with Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia." Blood 126, no. 23 (December 3, 2015): 829. http://dx.doi.org/10.1182/blood.v126.23.829.829.
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Abstract Introduction BCL2 is an anti-apoptotic protein overexpressed in CLL and critical in the pathogenesis of the disease; venetoclax (VEN) is an orally available, selective BCL2 inhibitor. Bendamustine (B) and rituximab (R) combination has demonstrated efficacy in relapsed/refractory (R/R) and previously untreated (frontline, 1L) patients (pts) with CLL. Preclinical data suggest that VEN+BR may provide synergistic activity in pts with CLL. Clinical data from VEN, both as a single-agent and in combination with R, support VEN+BR combination in CLL. We report an ongoing phase 1b study (NCT01671904) that is evaluating as primary objectives the maximum tolerated dose (MTD) of VEN when combined with BR, plus safety, tolerability, and order of administration to reduce toxicities of this combination in R/R or 1L CLL pts. Methods Pts with ECOG PS ≤1, 0-3 prior chemotherapy lines, and adequate marrow, hepatic, renal and coagulation function are being enrolled in dose finding cohorts and subsequent safety expansion cohorts, ranging from VEN 100 to 400 mg/day (3+3 dose escalation design). Pts are assigned to one of two dosing schedules (Fig 1) with VEN (Schedule A) or BR (Schedule B) introduced first; both include a gradual VEN dose ramp-up and other prophylactic measures to reduce the risk of tumor lysis syndrome (TLS) and risk stratification for TLS (high, intermediate and low). On completing combination therapy, pts continue single-agent VEN until disease progression (R/R CLL) or up to 18 months (1L CLL). Dose-limiting toxicity (DLT) data are reviewed after all pts in a cohort have completed 21 days of combination treatment at the target VEN dose and focus on TLS and cytopenias. Efficacy is assessed by investigators (iwCLL guidelines; Hallek et al. 2008). Results At data cutoff (April 30, 2015), 30 pts have been treated; 20 R/R pts, 12 on Schedule A (3 at 100 mg, 3 at 200 mg, and 6 at 400 mg) and 8 on Schedule B (all at 400 mg), and 10 1L pts, 6 on Schedule A and 4 on Schedule B (all at 400 mg). Baseline characteristics are shown in Fig 2. Of 10 pts with reported cytogenetics, 2 have del(17p). Median time on study is 5.5 (range, 0.03-15.2) months. No safety difference between Schedules A and B was seen in the DLT observation period for R/R CLL pts; neither schedule exhibited any toxicities precluding choice of the highest administered dose of 400 mg daily VEN. Schedule B was chosen for R/R safety expansion due to potential for tumor debulking prior to VEN. Dose finding in 1L Schedule A also selected 400 mg; dose finding for Schedule B is ongoing. Of 30 safety-evaluable, 27 (90%) pts experienced any adverse event (AEs; Fig 3). Most common AEs were neutropenia and nausea. Most G3 AEs were hematological toxicities; common non-hematological included diarrhea and hypertension. No TLS events (laboratory or clinical) were observed. There were 13 serious AEs in 10 (33.3%) pts, 8 (26.7%) due to study treatment. No deaths were reported. Of all 30 pts, 25 received VEN, with 5 still completing the BR only portion of Schedule B. Dose interruptions were seen in 13 pts mainly due to neutropenia for both VEN and BR; 8 pts had a VEN dose reduction. Early drug discontinuations (any reason): VEN, 2pts (gastroenteritis norovirus, progressive disease); BR together, 3 pts; B, 7 pts (commonly for neutropenia or physician decision); R, 1 pt. Across cohorts, 17/20 R/R CLL pts had response assessments; 100% responded, with 3 CRi. Response evaluation for 1L pts is early and evaluation across all cohorts and patients is ongoing. Full MRD data will be presented at the meeting, but early analysis shows pts exhibiting MRD negativity in peripheral blood, many as early as Cycle 4. Conclusion These early results report the first study evaluating the VEN+BR combination in pts with CLL. Daily VEN 400 mg can be safely combined with BR in patients with R/R CLL using both administration schedules (VEN or BR first), with 400 mg also established as safe for 1L pts with CLL under Schedule A. No TLS was observed with either administration schedule, despite many pts at medium (53%) or high (33%) TLS risk. VEN+BR is, as expected, associated with frequent hematologic toxicity, which appears manageable in most pts being treated, although 10 pts discontinued either B or BR prior to completing 6 cycles of administration. Early response and MRD data are promising. Disclosures Salles: Celgene Corporation; Roche: Speakers Bureau; Celgene Corporation; Roche and Gilead Sciences: Research Funding; Calistoga Pharmaceuticals, Inc.; Celgene Corporation; Genentech, Inc.; Janssen Pharmaceutica Products, L.P.; Roche: Consultancy. Off Label Use: Venetoclax is an investigational drug that is not yet approved in this indication. Boyd:Genentech, Inc.: Research Funding; Celgene: Speakers Bureau; US Oncology: Research Funding. Morschhauser:Genentech Inc./Roche: Other: Advisory boards. Wendtner:Roche: Consultancy, Honoraria, Research Funding; Genentech, Inc.: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Hallek:Janssen: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Pharmacyclics: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Celgene: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Boehringher Ingelheim: Honoraria, Other: Speakers Bureau and/or Advisory Boards; AbbVie: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Roche: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Gilead: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Mundipharma: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding. Eichhorst:AbbVie: Consultancy; Mundipharma: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau. Kozloff:Genentech: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; AbbVie: Consultancy. Cartron:Gilead: Honoraria; GSK: Honoraria; Celgene: Honoraria; Roche: Consultancy, Honoraria; Sanofi: Honoraria. Li:Genentech, Inc.: Employment. Hilger:Genentech, Inc.: Employment. Mobasher:Genentech, Inc.: Employment. Stilgenbauer:Roche: Honoraria, Research Funding.
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Cavaleri, Rocco, Siobhan M. Schabrun, and Lucy S. Chipchase. "Determining the Optimal Number of Stimuli per Cranial Site during Transcranial Magnetic Stimulation Mapping." Neuroscience Journal 2017 (February 26, 2017): 1–8. http://dx.doi.org/10.1155/2017/6328569.
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The delivery of five stimuli to each cranial site is recommended during transcranial magnetic stimulation (TMS) mapping. However, this time-consuming practice restricts the use of TMS mapping beyond the research environment. While reducing the number of stimuli administered to each cranial site may improve efficiency and decrease physiological demand, doing so may also compromise the procedure’s validity. Therefore, the aim of this study was to determine the minimum number of stimuli per cranial site required to obtain valid outcomes during TMS mapping. Map volume and centre of gravity (CoG) recordings obtained using five stimuli per cranial site were retrospectively compared to those obtained using one, two, three, and four stimuli per cranial site. For CoG longitude, one stimulus per cranial site produced valid recordings (ICC = 0.91, 95% CI 0.82 to 0.95). However, this outcome is rarely explored in isolation. As two stimuli per cranial site were required to obtain valid CoG latitude (ICC = 0.99, 95% CI 0.99 to 0.99) and map volume (ICC = 0.99, 95% CI 0.99 to 0.99) recordings, it is recommended that a minimum of two stimuli be delivered to each cranial site during TMS mapping in order to obtain valid outcomes.
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Ledermann, B., J. Kaminski, S. Kappler, and T. Muller. "Studies With a GEM-TPC Prototype for the ILC: Dependencies of Spatial Resolution for Short Drift Distances in a 4 T Magnetic Field." IEEE Transactions on Nuclear Science 53, no. 5 (October 2006): 2936–43. http://dx.doi.org/10.1109/tns.2006.880113.
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Wetherill, Marianna S., Mary B. Williams, Tori Taniguchi, Alicia L. Salvatore, Tvli Jacob, Tamela Cannady, Mandy Grammar, et al. "A Nutrition Environment Measure to Assess Tribal Convenience Stores: The THRIVE Study." Health Promotion Practice 21, no. 3 (September 21, 2018): 410–20. http://dx.doi.org/10.1177/1524839918800968.
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In rural American Indian (AI) communities, where supermarkets are rare, tribally owned and operated convenience stores are an important food source. Food environment measures for these settings are needed to understand and address the significant diet-related disparities among AIs. Through a tribal-university partnership that included tribal health and commerce representatives from two Native Nations in rural southeastern Oklahoma, we developed the Nutrition Environment Measures Survey for Tribal Convenience Stores (NEMS-TCS) to inform the development and evaluation of a healthy food retail intervention. The NEMS-TCS assessed four scored domains of the rural convenience store food environment—food availability, pricing, quality, and placement—and included 11 food categories that emphasized ready-to-eat food items. Trained raters administered the NEMS-TCS using a sample of 18 rural convenience stores (primarily ranging between 2,400 and 3,600 square feet). We assessed interrater reliability with kappa statistics for dichotomized variables and intraclass correlation coefficients (ICC) for continuous variables. NEMS-TCS demonstrated high inter-rater reliability for all food categories (>85% agreement), subscores (ICC = 0.73-1.00), and the total score (ICC = 0.99). The NEMS-TCS responds to recent calls for reliable measures for rural food environments and may be valuable for studying food environments of large convenience stores in other Native Nations as well as other rural settings.
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Yamaguchi, Yuji, Toshiya Sanami, Yusuke Koba, and Yusuke Uozumi. "Double-differential cross section measurement with low threshold detector for proton production induced by several tens of MeV protons." EPJ Web of Conferences 239 (2020): 01038. http://dx.doi.org/10.1051/epjconf/202023901038.
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We have developed a low threshold detector consisting of Bragg curve counter (BCC), two siliconsurface barrier detectors (SSDs) and BGO scintillator to obtain experimental double-differential cross section (DDX) data for low energy proton production. Since the BCC offers advantage of self particle identification capability and a few μm-thick entrance window, protons produced by nuclear reactions down to 1 MeV have been identified. The capability of the detector is demonstrated in measurements using 70-MeV protons. Measured spectra are compared with calculation results of intra-nuclear cascade (INC) plus evaporation models and nuclear data library.
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Pipher, Judith L., Craig W. McMurtry, Mario S. Cabrera, and William J. Forrest. "Mid-Infrared Detector Array Technologies for SOFIA and Sub-Orbital Observatory Instruments." Journal of Astronomical Instrumentation 10, no. 02 (May 26, 2021): 2150008. http://dx.doi.org/10.1142/s2251171721500082.
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The status of various photovoltaic, photoconductive, BIB/IBC, superlattice, TES and KID technologies to produce arrays sensitive from 15 to [Formula: see text]m (Mid-infrared) will be reviewed to assess where reasonable investments should be made for SOFIA and other sub-orbital observatory instruments. These include HgCdTe, Si:As IBC, Si:Sb BIB, Ge:Ga, type 2 superlattice arrays of both III–V and II–VI materials and both TES and KID arrays. KID technologies for this wavelength region show promise, although to date there are no published experimental data on KID arrays for the mid-infrared.
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Buelow, Ben, Anita D'Souza, Cesar Rodriguez, Ravi Vij, Rajneesh Nath, Melinda Snyder, Duy Pham, Ashwin Patel, and Suhasini Iyer. "TNB383B.0001: A Multicenter, Phase 1, Open-Label, Dose-Escalation Andexpansion Study of TNB-383B, a Bispecific Antibodytargeting BCMA in Subjects with Relapsed or Refractorymultiple Myeloma." Blood 134, Supplement_1 (November 13, 2019): 1874. http://dx.doi.org/10.1182/blood-2019-123220.
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Introduction Multiple myeloma (MM) is an incurable plasma cell malignancy with an estimated incidence in 2019 of ~32,000 in the United States. Although median survival is greater than 8 years, treatment options are limited for patients who relapse on or are refractory to standard treatment regimens containing proteasome inhibitors, immune-modulating drugs and anti-CD38 antibodies (triple refractory). Novel therapies are critical to the treatment of these patients. Chimeric antigen receptor T cells (CAR-Ts) and T-cell redirecting Bispecific Antibodies (T-BsAbs) targeting B-cell maturation antigen (BCMA) -a protein found exclusively on the surface of plasma cells- have shown efficacy against relapsed/refractory MM in early phase clinical trials. However, toxicity from over-activation of T-cells still hinders these approaches. Utilizing Teneobio's proprietary next generation sequencing (NGS)-based discovery tool incorporating in silico analysis of heavy chain only/fixed light chain antibody sequences (HCA/Flic, respectively) to enrich for antigen specific antibodies, we made a high affinity αBCMA HCA and a library of αCD3 Flic antibodies that showed a >2 log range of EC50s for T cell activation in vitro. TNB-383B combines a high affinity αBCMA HCA with a low-activating αCD3 Flic; in preclinical studies TNB-383B showed equivalent anti-tumor efficacy but significantly reduced cytokine secretion compared to BCMA-targeted T-BsAbs incorporating a strongly-activating αCD3 (similar in strength to the αCD3s used in other T-BsAbs currently in clinical trials). A Phase 1 study investigating the safety, pharmacokinetics, and preliminary activity of TNB-383B in patients with relapsed/refractory multiple myeloma (RRMM) is ongoing and described. This trial represents, to the best of our knowledge, the first reported clinical trial of a HCA/Flic hybrid antibody in humans. Study Design TNB383B.0001 (NCT03933735) is an open-label, multi-center study of TNB-383B in patients with RRMM. The study is divided into escalation (Arm A, N=24) and expansion (Arm B, N=48) arms. Subjects who have received 3 or more prior lines of therapy with exposure to a PI, an IMiD, and an anti-CD38 antibody are eligible for this study. Documentation of BCMA expression by tumor cells is not required for entry, although prior treatment with a BCMA-targeted agent is an exclusion criterion. Other key inclusion/exclusion criteria include EGFR of >30ml/min, ANC ≥1000/mm3 and platelets ≥50,000/mm3 and minimal bone marrow biopsy requirements on-study. Subjects must be admitted for 48 hours following the 1st dose in Cycle 1 (21-day cycle length), but TNB-383B may be administered on an outpatient basis thereafter. Dose Escalation TNB-383B is administered as an intravenous infusion. Dose escalation is proceeding via a 3+3 design with fixed (as opposed to weight based) doses per protocol. Arm B will be initiated once the maximum tolerated dose (MTD, or recommended phase 2 dose, RP2D) has been selected. Patients will be treated until progression, unacceptable toxicity, or other discontinuation criteria are met. One patient has been enrolled thus far. Statistical Methods and Study Endpoints In Arm A occurrence of dose limiting toxicities (DLTs) will drive identification of the MTD (or RP2D in line with standard practices. In Arm B accrual will be suspended if more than 33% of subjects experience a DLT event. Adverse events, laboratory profiles, physical exams, and vital signs will be assessed throughout the study. Adverse events will be graded according to the NCI CTCAE, version 5.0. Concentrations of TNB-383B and Anti-Drug Antibodies (ADA) will be determined at designated time points throughout the study. Values for standard pharmacokinetic parameters of TNB-383B including the maximum observed serum concentration (Cmax), the time to Cmax, area under the concentration-time curve, clearance, and terminal half-life will be determined using non-compartmental methods. The activity endpoints (determined using the IMWG uniform response criteria) include overall response rate, progression-free survival and overall survival. The relationship between biomarkers, including soluble BCMA and A Proliferation Inducing Ligand (APRIL; the endogenous ligand for BCMA), and activity will be assessed. Disclosures Buelow: Teneobio, Inc.: Employment, Equity Ownership. Rodriguez:Takeda, Amgen: Consultancy, Speakers Bureau. Vij:Janssen: Honoraria; Celgene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Genentech: Honoraria; Takeda: Honoraria, Research Funding; Karyopharm: Honoraria; Sanofi: Honoraria. Nath:Teneobio, Inc.: Consultancy. Snyder:Teneobio, Inc.: Consultancy. Pham:Teneobio, Inc.: Employment, Equity Ownership. Patel:Teneobio, Inc.: Employment, Equity Ownership. Iyer:Teneobio, Inc.: Employment, Equity Ownership.
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Foureau, David M., Manisha Bhutani, Myra Robinson, Fei Guo, Duy Pham, Shelley Force Aldred, Ben Buelow, et al. "Ex Vivo Assessment of Tnb-383B, a Bcma-Bispecific Antibody, Against Primary Tumor and Endogenous T Cells from Relapsing Multiple Myeloma Patients." Blood 132, Supplement 1 (November 29, 2018): 1940. http://dx.doi.org/10.1182/blood-2018-99-118881.
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Abstract INTRODUCTION: The human B-Cell maturation antigen (BCMA) is a surface marker that is highly expressed on plasma cells and has been recognized as a novel target in multiple myeloma (MM). TNB-383B is a fully human bispecific monoclonal IgG4 antibody. TNB-383B consists of 2 heavy and 1 light chain(s) paired through knob-in-hole technology. The first heavy chain and a kappa light chain form the paratope to recognize and bind human CD3. The second heavy chain is comprised of two identical VH domains in sequence and targets human BCMA with high affinity and avidity. Herein, we describe the ability of TNB-383B to mediate killing of patient-derived tumor cell lysis by endogenous T-cells was assessed ex vivo. METHODS: Bone marrow mononuclear cells (BMMCs) were isolated by density gradient centrifugation from 7 relapsed MM patients enrolled in an IRB-approved biospecimen collection protocol. Freshly isolated BMMC subsets were characterized by flow cytometry, specifically plasma cell (PC) / cytotoxic T cell (CTL) distribution, PC BCMA expression and PC viability were determined. BMMCs were then incubated for 24h (± 2h) with TNB-383B, or negative control, at concentrations ranging from 0.001-1μg. Following incubation, PC lysis, viability, BCMA expression, as well as CTL distribution and degranulation were assessed by flow cytometry. Tukey's sequential trend test was performed for each measured variable, utilizing ANOVA models and contrast statements, to detect linear dose response trends to TNB-383B or negative control treatments. Additionally, a parametric model (EMax) was used for each measured variable to estimate dose response curves, interpolating between tested doses. Two-way factorial ANOVA was utilized to compare the main effects of E:T ratio (or PC phenotype) and dose level and the interaction effect between E:T ratio and dose level on measured variables. RESULTS: Dose-dependent PC lysis was triggered by TNB-383B at concentrations as low as 0.001μg (p=0.0102) while no significant loss of PC was observed with negative control (Figure). This effect was coupled with significant CTL degranulation as expressed by increased CD107a mean fluorescence intensity (MFI) specific to TNB-383B treatment (p=0.0153 at 1μg). Although apoptotic rates (7-AAD+, Annexin V+) of the remaining PC tend to increase among TNB-383B treated compared with isotype control-treated cells, this trend was not significant. As opposed to CTL degranulation, CTL proliferation was not significantly triggered by TNB-383B but was significantly increased when BMMCs were exposed to negative control antibody (p=0.0057 at 0.001 μg). BMMC containing effector to target (E:T) ratio >10 contained lower viable (7-AAD-) PC and higher apoptotic PC counts compared with BMMC specimen with E:T ratio <10 (p<0.001). Using CD45 expression as a surrogate marker of PC maturation and BCMA expression, CD45+ PC displayed higher BCMA expression than CD45- PC (p=0.0189) and were more sensitive TNB-383B-induced killing (p<0.001). Noticeably, overall BCMA expression pre/post TNB-383B exposure remained unaltered. CONCLUSION: Taken together, our findings demonstrate TNB-383B triggers primary PC lysis and CTL degranulation in a dose-dependent fashion ex vivo. The ex vivo bispecific monoclonal antibody assay employed in this study allowed us to identify underlying biological drivers of PC killing efficacy by TNB-383B and may provide a valuable preclinical platform to screen bispecific antibodies and clinical platform to identify mechanism of primary or acquired resistance to the drug. Enrollment of patients with relapsed/refractory MM into a phase I clinical trial with TNB-383B is expected in early 2019. Figure. Figure. Disclosures Foureau: Teneobio Inc.: Research Funding. Pham:Teneobio Inc.: Employment. Force Aldred:Teneobio Inc.: Employment. Buelow:Teneobio Inc.: Employment. Voorhees:Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: served on an IRC; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Other: served on an IRC; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: served on an IRC; Amgen Inc.: Speakers Bureau; TeneoBio: Consultancy, Membership on an entity's Board of Directors or advisory committees. Usmani:Abbvie, Amgen, Celgene, Genmab, Merck, MundiPharma, Janssen, Seattle Genetics: Consultancy; Amgen, BMS, Celgene, Janssen, Merck, Pharmacyclics,Sanofi, Seattle Genetics, Takeda: Research Funding.
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Gandahi, Noor Samad, Botao Ding, Yonghong Shi, Xuebing Bai, Jameel Ahmed Gandahi, Waseem Ali Vistro, Qiusheng Chen, and Ping Yang. "Identification of Telocytes in the Pancreas of Turtles—A role in Cellular Communication." International Journal of Molecular Sciences 21, no. 6 (March 17, 2020): 2057. http://dx.doi.org/10.3390/ijms21062057.
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The existence of telocytes (TCs) has not yet been established in the pancreases of aquatic reptiles. Here, we report TCs in the exocrine pancreas of Pelodiscus sinensis using transmission electron microscope (TEM), immunohistochemistry (IHC), and immunofluorescence (IF) techniques. TCs surrounded the acini and ducts of the connective tissue of the exocrine pancreas and between lobules and gland cells. The cells were located preferably close to the blood vessels, interlobular ducts, and nerve fibers. Ultrastructurally, TCs exhibited small and large bodies with thick and thin portions, podoms, and podomers, and prolongations that form dichotomous branching with hetero-cellular and homo-cellular junctions. The podom (thick) portions showed caveolae, mitochondria, rough endoplasmic reticulum, and vesicles. The nucleus carries heterochromatin and is irregular in shape. The shape of TCs depends on the number of telopodes (Tps) bearing long, short, spindle, triangular, and “beads on a string” shapes with twisted, tortuous prolongations and ramifications. Shed extracellular vesicles and exosomes were found frequently released from projections and Tps within connective tissue in the vicinity of the acini and collagen fibers. IHC and IF results showed CD34+, α-SMA+, and vimentin+, long and triangle-shaped TCs, consistent with the TEM findings. The presence of shaded vesicles from TCs might implicate their possible role in immune surveillance, tissue regeneration as well as regulatory functions in the reptilian pancreas.
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Lee, Min Ho, Yu Seob Shin, and Sung Chul Kam. "Correlation Between Testosterone Replacement Treatment and Lower Urinary Tract Symptoms." International Neurourology Journal 25, no. 1 (March 31, 2021): 12–22. http://dx.doi.org/10.5213/inj.2040234.117.
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Lower urinary tract symptoms (LUTS) are a cluster of voiding symptoms, such as weak stream, hesitancy, intermittency, urinary frequency, urgency, and nocturia. LUTS are frequent in elderly men and it considered the ultimate clinical symptoms of benign prostatic hyperplasia. With aging, male hypogonadism is increased which is defined as decreased ability of the testes to produce sperm and sex steroids because of a pituitary/hypothalamic, or testicular deficiency. In academic andrology associations, the term “male hypogonadism” is commonly used to categorize testosterone deficiency. Testosterone deficiency syndrome (TDS) is defined as a decrease in serum testosterone accompanied by symptoms such as libido decrease, depressive disorder, erectile dysfunction, and fatigue. Although the mechanism about testosterone-replacement therapy (TRT) effects on men with hypogonadism is not yet identified, TRT has been shown to effectively relieve the symptoms of TDS as well as LUTS by several studies. Although the present review demonstrates the effectiveness and safety of TRT in men with TDS by prior studies, future large scale of clinical trials should be conducted to present more high-quality evidence to clinicians and patients.
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Flinn, Ian W., Mark Brunvand, Michael Y. Choi, Martin J. S. Dyer, John Gribben, Peter Hillmen, Jeffrey Jones, et al. "Safety and Efficacy of a Combination of Venetoclax (GDC-0199/ABT-199) and Obinutuzumab in Patients with Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia - Results from a Phase 1b Study (GP28331)." Blood 126, no. 23 (December 3, 2015): 494. http://dx.doi.org/10.1182/blood.v126.23.494.494.
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Abstract Introduction Treatment of patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) with the combination of venetoclax (VEN), an oral, selective Bcl-2 inhibitor, and rituximab yielded an ORR of 84% (Roberts et al. Haematologica 2015). Treatment of such pts with VEN in combination with obinutuzumab (Gazyva®, Gazyvaro™, G), a Type II, glycoengineered anti-CD20 antibody, may yield even better treatment outcomes. We present preliminary efficacy and updated safety data from an ongoing phase 1b study (NCT01685892) evaluating this combination in R/R or treatment-naïve (TN) pts with CLL in alternate treatment schedules. Methods Pts with CLL with an ECOG PS ≤1 and adequate organ function are enrolled in a study with a 3+3 design and cohorts ranging from 100 to 600 mg/day of VEN. Pts are assigned to one of two dosing schedules, starting treatment with either VEN (Schedule A) or G (Schedule B). Both schedules include tumor lysis syndrome (TLS) risk mitigation based on disease burden at screening, which includes a gradual VEN ramp-up to the assigned cohort dose. Six cycles of combination therapy will be given and then pts with R/R disease continue single-agent VEN until disease progression; TN pts will receive single-agent VEN for an additional 6 months. Dose-limiting toxicities (DLTs) are identified during the first 21 days of combination therapy in Schedule A or the first 35 days of combination therapy in Schedule B, and focus on TLS, infusion related reactions, and cytopenias. Based on a safety review of data from this trial, the 600 mg cohort will not be explored. Response is first assessed before Cycle 4 according to 2008 International Workshop on CLL guidelines. Results As of April 20, 2015, 32 pts (26 R/R and 6 TN) have been enrolled. Four R/R pts were unenrolled after a sponsor-initiated clinical hold secondary to TLS events in other VEN studies. Patient characteristics include a median age 62.5 (range, 45-80) years, and 62.5% male pts. TLS risk was assessed in 28 pts following protocol modifications adopted after a Sponsor-initiated clinical hold; 96.4% were at medium or high risk for TLS. The highest VEN dose administered in this study was 400 mg/day (administered to 11 R/R and 6 TN pts). Median time on study was 5.5 (range, 0.1-19.6) mo. for all pts and 2.8 (range, 0.9-2.8) mo. for TN pts. Among pts exposed to VEN, dose interruptions were observed in 17/27 (63%) pts. A summary of AEs is presented in Figure 1. Laboratory TLS was observed in 4/32 (12.5%) pts and all were able to continue study treatment after resolution of electrolyte changes; no cases of clinical TLS occurred. One pt with R/R disease in cohort 1 discontinued study participation following disease progression (the pt completed 6 cycles of combination treatment). A second pt with R/R disease in cohort 1 died secondary to acute respiratory failure; Richter's transformation also was suspected in this pt but not confirmed. Twenty pts with R/R disease and 6 TN pts remain on the study. At least 1 response evaluation has been performed in 17 pts with R/R disease. The overall response rate (ORR) by investigator assessment was 100%; 4/17 (23.5%) pts achieved complete response/complete response with incomplete bone marrow recovery (CR/CRi). Among the 13 (76.5%) pts with PRs after 3 cycles of therapy, 3 have improved to CR/CRi at assessments 28 days after completing C6D1. Full MRD data will be available in the near future but early analyses suggest some patients may achieve MRD negative status by Cycle 4. Conclusion These preliminary data suggest that VEN + G can be safely administered in pts with CLL with no difference in tolerability between R/R and TN subgroups. AEs appear to be manageable and no pt has discontinued study participation secondary to cytopenia, the most frequently observed AE. Data suggests that the TLS prophylaxis measures are effective even in patients with a higher disease burden. An expansion phase is planned using a 400 mg per day dose of VEN in R/R and TN pts following a review of safety data assessing potential differences between dosing schedules. The preliminary efficacy data suggest this regimen may be an important option in patients with CLL; a phase 3 study evaluating VEN+G is ongoing. Disclosures Flinn: Cephalon, Inc; Teva Pharmaceutical Industries Ltd; Genentech, inc; Gilead: Research Funding. Off Label Use: Venetoclax is an investigational drug that is not yet approved in this indication. Brunvand:Celgene: Speakers Bureau; Millenium: Speakers Bureau. Choi:Gilead: Consultancy, Other: Advisory Board, Speakers Bureau; AbbVie: Consultancy, Other: Advisory Board, Research Funding. Dyer:Roche Pharmaceuticals: Speakers Bureau; ONO Pharmaceuticals: Research Funding; Gilead: Research Funding. Gribben:Janssen: Honoraria; Celgene: Consultancy, Honoraria; Gilead: Honoraria; Roche/Genentech: Honoraria; Pharmacyclics: Honoraria. Hillmen:Janssen: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Roche Pharmaceuticals: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Pharmacyclics LLC, an AbbVie Company: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Celgene: Research Funding. Jones:Acerta Pharma BV: Research Funding. Li:Genentech, Inc.: Employment. Mobasher:Genentech, Inc.: Employment. Vosganian:Genentech, Inc.: Employment. Kipps:Pharmacyclics Abbvie Celgene Genentech Astra Zeneca Gilead Sciences: Other: Advisor; Pharmacyclics Abbvie Celgene Genentech Astra Zeneca Gilead Sciences: Other: Advisor.
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Lam, JunHuy, Sang-Gon Lee, Hoon-Jae Lee, and Yustus Eko Oktian. "Securing SDN Southbound and Data Plane Communication with IBC." Mobile Information Systems 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/1708970.
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In software-defined network (SDN), the southbound protocol defines the communication between the control plane and the data plane. The agreed protocol, OpenFlow, suggests securing the southbound communication with Transport Layer Security (TLS). However, most current SDN projects do not implement the security segment, with only a few exceptions such as OpenDayLight, HP VAN SDN, and ONOS implementing TLS in the southbound communication. From the telecommunication providers’ perspective, one of the major SDN consumers besides data centers, the data plane becomes much more complicated with the addition of wireless data plane as it involves numerous wireless technologies. Therefore, the complicated resource management along with the security of such a data plane can hinder the migration to SDN. In this paper, we propose securing the distributed SDN communication with a multidomain capable Identity-Based Cryptography (IBC) protocol, particularly for the southbound and wireless data plane communication. We also analyze the TLS-secured Message Queuing Telemetry Transport (MQTT) message exchanges to find out the possible bandwidth saved with IBC.