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1
Breuer, Lothar. "Occupation Times for Markov-Modulated Brownian Motion." Journal of Applied Probability 49, no. 2 (June 2012): 549–65. http://dx.doi.org/10.1239/jap/1339878804.
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In this paper we determine the distributions of occupation times of a Markov-modulated Brownian motion (MMBM) in separate intervals before a first passage time or an exit from an interval. We derive the distributions in terms of their Laplace transforms, and we also distinguish between occupation times in different phases. For MMBMs with strictly positive variation parameters, we further propose scale functions.
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Breuer, Lothar. "Occupation Times for Markov-Modulated Brownian Motion." Journal of Applied Probability 49, no. 02 (June 2012): 549–65. http://dx.doi.org/10.1017/s0021900200009268.
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In this paper we determine the distributions of occupation times of a Markov-modulated Brownian motion (MMBM) in separate intervals before a first passage time or an exit from an interval. We derive the distributions in terms of their Laplace transforms, and we also distinguish between occupation times in different phases. For MMBMs with strictly positive variation parameters, we further propose scale functions.
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Breuer, Lothar. "Exit Problems for Reflected Markov-Modulated Brownian Motion." Journal of Applied Probability 49, no. 3 (September 2012): 697–709. http://dx.doi.org/10.1239/jap/1346955327.
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Let (X, J) denote a Markov-modulated Brownian motion (MMBM) and denote its supremum process by S. For some a > 0, let σ(a) denote the time when the reflected process Y := S - X first surpasses the level a. Furthermore, let σ−(a) denote the last time before σ(a) when X attains its current supremum. In this paper we shall derive the joint distribution of Sσ(a), σ−(a), and σ(a), where the latter two will be given in terms of their Laplace transforms. We also provide some remarks on scale matrices for MMBMs with strictly positive variation parameters. This extends recent results for spectrally negative Lévy processes to MMBMs. Due to well-known fluid embedding and state-dependent killing techniques, the analysis applies to Markov additive processes with phase-type jumps as well. The result is of interest to applications such as the dividend problem in insurance mathematics and the buffer overflow problem in queueing theory. Examples will be given for the former.
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Breuer, Lothar. "Exit Problems for Reflected Markov-Modulated Brownian Motion." Journal of Applied Probability 49, no. 03 (September 2012): 697–709. http://dx.doi.org/10.1017/s0021900200009475.
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Let (X, J) denote a Markov-modulated Brownian motion (MMBM) and denote its supremum process by S. For some a > 0, let σ(a) denote the time when the reflected process Y := S - X first surpasses the level a. Furthermore, let σ−(a) denote the last time before σ(a) when X attains its current supremum. In this paper we shall derive the joint distribution of S σ(a), σ−(a), and σ(a), where the latter two will be given in terms of their Laplace transforms. We also provide some remarks on scale matrices for MMBMs with strictly positive variation parameters. This extends recent results for spectrally negative Lévy processes to MMBMs. Due to well-known fluid embedding and state-dependent killing techniques, the analysis applies to Markov additive processes with phase-type jumps as well. The result is of interest to applications such as the dividend problem in insurance mathematics and the buffer overflow problem in queueing theory. Examples will be given for the former.
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Xu, Ning, Nicole Ng, Mingjie Li, Erin Yu, Eric Sanchez, Sean Bujarski, Zhengyi Yin, et al. "The JAK1/2 Inhibitor Ruxolitinib Downregulates the Immune Checkpoint Protein B7-H3 in Multiple Myeloma." Blood 134, Supplement_1 (November 13, 2019): 1824. http://dx.doi.org/10.1182/blood-2019-131047.
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Introduction: The JAKSTAT pathway plays a critical role in the regulation of hematopoietic pathways and immunological cytokine signaling. The JAK pathway is also involved in tumor cell proliferation and drug resistance in multiple myeloma (MM). Thus, inhibition of the JAK pathway should be a potentially effective strategy for treating MM patients. B7-H3 is an immune checkpoint protein in the B7 superfamily and has been shown overexpressed in several tumors. Immune checkpoint blockade may suppress tumor progression or enhance anti-tumor immune responses. In this study, we investigated the effects of the JAK1/2 inhibitor ruxolitinib (Rux) on B7-H3 in MM. Materials and Methods: Bone marrow mononuclear cells (BMMCs) were collected from MM patients after obtaining IRB approval. Single-cell suspensions were prepared from human MM LAGλ-1A xenografts which had been grown in severe combined immunodeficient mice. HS-5 stromal and SUP-T1 T cells were purchased from ATCC. The cells were cultured and treated with or without RUX and then subjected to qRT-PCR, flow cytometric analysis, and western blot analysis. For qRT-PCR, total RNA was extracted and applied to cDNA synthesis, followed by qPCR. Gene expression was analyzed in MM BMMCs alone or co-cultured with stromal cells or T cells with or without Rux treatment (1μM) in vitro. Results: We identified increased B7-H3 expression in MMBMMCs from patients with progressive disease (PD) patients compared to those in complete remission (CR). Rux significantly reduced B7-H3 expression in MMBMMCs in patients with PD, MM cells (U266), and BM from patients in PD when co-cultured with stromal cells (HS-5) after 48-72 hours. Rux decreased B7H3 expression in the human MM xenograft model LAGλ-1A when cultured ex vivo. In addition, Rux suppressed B7-H3 at protein levels as shown with flow cytometric analysis and western blotting, consistent with the gene expression results. Next, we tested whether B7-H3 blockade by Rux could potentially restore exhausted T cell activity against myeloma cells in MMBM. We found that Rux can increase IL-2 and CD8 gene expression in MMBM with lower plasma percentages (< 30%) but not among those with higher plasma cell percentages (>70%). Rux also elevated IL-2 and CD8 gene expression in BM when it was cocultured with T cells (SUP-T1), suggesting Rux may mediate immunological cytokine signaling. B7-H3-neutralizing antibody increased CD8 gene expression in MMBM in vitro, suggesting that one of the mechanisms through which Rux upregulates CD8 T cells in MMBM may be via downregulation of B7-H3. Conclusion: The immune checkpoint protein B7-H3 is overexpressed in MMBM in PD compared to CR patients. The JAK1/2 inhibitor Rux can decrease B7-H3 expression and increase IL-2 and CD8 expression in BM in vitro. Our results provide evidence for Rux inhibiting the immune checkpoint protein B7-H3 which may potentially restore exhausted T-cell activity in the MMBM tumoral microenvironment. Disclosures Chen: Oncotraker Inc: Equity Ownership. Berenson:Amgen: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Sanofi: Consultancy; Sanofi: Consultancy; Amag: Consultancy, Speakers Bureau; Amag: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; OncoTracker: Equity Ownership, Other: Officer; OncoTracker: Equity Ownership, Other: Officer; Bristol-Myers Squibb: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Incyte Corporation.: Consultancy, Research Funding; Incyte Corporation.: Consultancy, Research Funding; Takeda: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau.
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Chen, Haiming, Mingjie Li, Eric Sanchez, Nicole Ng, Erin Yu, Sean Bujarski, Zhengyi Yin, et al. "The JAK1/2 Inhibitor Ruxolitinib Downregulates CXCL12 Secretion from Bone Marrow Stromal Cells and M2 Macrophage Polarization in Multiple Myeloma." Blood 134, Supplement_1 (November 13, 2019): 4352. http://dx.doi.org/10.1182/blood-2019-131324.
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Introduction: The JAKSTAT pathway plays a critical role in the regulation of hematopoietic pathways and immunological cytokine signaling. The JAK pathway is also involved in tumor cell proliferation and drug resistance in multiple myeloma (MM). Thus, inhibition of the JAK pathway should be a potentially effective strategy for treating MM patients. B7-H3 is an immune checkpoint protein in the B7 superfamily and has been shown overexpressed in several tumors. Immune checkpoint blockade may suppress tumor progression or enhance anti-tumor immune responses. In this study, we investigated the effects of the JAK1/2 inhibitor ruxolitinib (Rux) on B7-H3 in MM. Materials and Methods: Bone marrow mononuclear cells (BMMCs) were collected from MM patients after obtaining IRB approval. Single-cell suspensions were prepared from human MM LAGλ-1A xenografts which had been grown in severe combined immunodeficient mice. HS-5 stromal and SUP-T1 T cells were purchased from ATCC. The cells were cultured and treated with or without RUX and then subjected to qRT-PCR, flow cytometric analysis, and western blot analysis. For qRT-PCR, total RNA was extracted and applied to cDNA synthesis, followed by qPCR. Gene expression was analyzed in MM BMMCs alone or co-cultured with stromal cells or T cells with or without Rux treatment (1μM) in vitro. Results: We identified increased B7-H3 expression in MMBMMCs from patients with progressive disease (PD) patients compared to those in complete remission (CR). Rux significantly reduced B7-H3 expression in MMBMMCs in patients with PD, MM cells (U266), and BM from patients in PD when co-cultured with stromal cells (HS-5) after 48-72 hours. Rux decreased B7-H3 expression in the human MM xenograft model LAGλ-1A when cultured ex vivo. In addition, Rux suppressed B7-H3 at protein levels as shown with flow cytometric analysis and western blotting, consistent with the gene expression results. Next, we tested whether B7-H3 blockade by Rux could potentially restore exhausted T cell activity against myeloma cells in MMBM. We found that Rux can increase IL-2 and CD8 gene expression in MMBM with lower plasma percentages (< 30%) but not among those with higher plasma cell percentages (>70%). Rux also elevated IL-2 and CD8 gene expression in BM when it was cocultured with T cells (SUP-T1), suggesting Rux may mediate immunological cytokine signaling. B7-H3-neutralizing antibody increased CD8 gene expression in MMBM in vitro, suggesting that one of the mechanisms through which Rux upregulates CD8 T cells in MMBM may be via downregulation of B7-H3. Conclusion: The immune checkpoint protein B7-H3 is overexpressed in MMBM in PD compared to CR patients. The JAK1/2 inhibitor Rux can decrease B7-H3 expression and increase IL-2 and CD8 expression in BM in vitro. Our results provide evidence for Rux inhibiting the immune checkpoint protein B7-H3 which may potentially restore exhausted T-cell activity in the MMBM tumoral microenvironment. Disclosures Chen: Oncotraker Inc: Equity Ownership. Berenson:OncoTracker: Equity Ownership, Other: Officer; OncoTracker: Equity Ownership, Other: Officer; Bristol-Myers Squibb: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Incyte Corporation.: Consultancy, Research Funding; Incyte Corporation.: Consultancy, Research Funding; Takeda: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Amag: Consultancy, Speakers Bureau; Amag: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Sanofi: Consultancy; Sanofi: Consultancy.
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Pires, Paulo Fernandes, Elisa Bizetti Pelai, Marcio de Moraes, Ester Moreira de Castro Carletti, Fabiana Foltran Mescollotto, Fausto Berzin, and Delaine Rodrigues Bigaton. "Maximum bilateral bite strength and RMS EMG for the diagnosis of myogenic TMD." Brazilian Journal of Oral Sciences 22 (March 24, 2023): e238358. http://dx.doi.org/10.20396/bjos.v22i00.8668358.
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Aim: The study aimed to evaluate the accuracy of the maximum bilateral molar bite force and the Root Mean Square (RMS) Electromyography (EMG) index of the masticatory muscles in the maximum bilateral molar bite (MMBMax) of women with myogenic Temporomandibular Disorder (TMD) and asymptomatic. Methods: This is a cross-sectional study, composed of 86 women allocated to the TMD Group (n=43) and Control Group (n=43) diagnosis through the Diagnostic Criteria for Temporomandibular Disorders. The maximum bilateral molar bite force was evaluated using a bite dynamometer and the RMS EMG index of the masticatory muscles (anterior temporalis, masseter) during 5 seconds of the MMBMax task. Student t-test was used for data comparison between accuracy of the bite force and RMS EMG of masticatory muscles during the MMBMax. Results: The maximum bilateral molar bite force showed high accuracy (AUC=0.99) for the diagnosis of women with myogenic TMD and asymptomatic women, and the RMS EMG index evaluated during the MMBMax showed a moderate level of accuracy for all masticatory muscles (AUC=0.70 to 0.75). Conclusion: The bilateral bite dynamometer with a surface EMG during bilateral bite can be used to diagnose TMD in young women.
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Madenjian, Charles P., Steven R. Chipps, and Paul J. Blanchfield. "Time to refine mercury mass balance models for fish." FACETS 6, no. 1 (January 1, 2021): 272–86. http://dx.doi.org/10.1139/facets-2020-0034.
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Mercury mass balance models (MMBMs) for fish are powerful tools for understanding factors affecting growth and food consumption by free-ranging fish in rivers, lakes, and oceans. Moreover, MMBMs can be used to predict the consequences of global mercury reductions, overfishing, and climate change on mercury (Hg) concentration in commercially and recreationally valuable species of fish. Such predictions are useful in decision-making by resource managers and public health policy makers, because mercury is a neurotoxin and the primary route of exposure of mercury to humans is via consumption of fish. Recent evidence has emerged to indicate that the current-day version of MMBMs overestimates the rate at which fish eliminate mercury from their bodies. Consequently, MMBMs overestimate food consumption by fish and underestimate Hg concentration in fish. In this perspective, we explore underlying reasons for this overestimation of Hg-elimination rate, as well as consequences and implications of this overestimation. We highlight emerging studies that distinguish species and sex as contributing factors, in addition to body weight and water temperature, that can play an important role in how quickly Hg is eliminated from fish. Future research directions for refining MMBMs are discussed.
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Breuer, Lothar. "The Resolvent and Expected Local Times for Markov-Modulated Brownian Motion with Phase-Dependent Termination Rates." Journal of Applied Probability 50, no. 2 (June 2013): 430–38. http://dx.doi.org/10.1239/jap/1371648951.
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We consider a Markov-modulated Brownian motion (MMBM) with phase-dependent termination rates, i.e. while in a phase i the process terminates with a constant hazard rate ri ≥ 0. For such a process, we determine the matrix of expected local times (at zero) before termination and hence the resolvent. The results are applied to some recent questions arising in the framework of insurance risk. We further provide expressions for the resolvent and the local times at zero of an MMBM reflected at its infimum.
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Breuer, Lothar. "The Resolvent and Expected Local Times for Markov-Modulated Brownian Motion with Phase-Dependent Termination Rates." Journal of Applied Probability 50, no. 02 (June 2013): 430–38. http://dx.doi.org/10.1017/s0021900200013462.
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We consider a Markov-modulated Brownian motion (MMBM) with phase-dependent termination rates, i.e. while in a phase i the process terminates with a constant hazard rate r i ≥ 0. For such a process, we determine the matrix of expected local times (at zero) before termination and hence the resolvent. The results are applied to some recent questions arising in the framework of insurance risk. We further provide expressions for the resolvent and the local times at zero of an MMBM reflected at its infimum.
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Gallo, Valeria, Pierpaolo Tomai, Valerio Di Lisio, Chiara Dal Bosco, Paola D’Angelo, Chiara Fanali, Giovanni D’Orazio, Ilaria Silvestro, Yolanda Picó, and Alessandra Gentili. "Application of a Low Transition Temperature Mixture for the Dispersive Liquid–Liquid Microextraction of Illicit Drugs from Urine Samples." Molecules 26, no. 17 (August 28, 2021): 5222. http://dx.doi.org/10.3390/molecules26175222.
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The use of psychoactive substances is a serious problem in today’s society and reliable methods of analysis are necessary to confirm their occurrence in biological matrices. In this work, a green sample preparation technique prior to HPLC-MS analysis was successfully applied to the extraction of 14 illicit drugs from urine samples. The isolation procedure was a dispersive liquid–liquid microextraction based on the use of a low transition temperature mixture (LTTM), composed of choline chloride and sesamol in a molar ratio 1:3 as the extracting solvent. This mixture was classified as LTTM after a thorough investigation carried out by FTIR and DSC, which recorded a glass transition temperature at −71 °C. The extraction procedure was optimized and validated according to the main Food and Drug Administration (FDA) guidelines for bioanalytical methods, obtaining good figures of merit for all parameters: the estimated lower limit of quantitation (LLOQ) values were between 0.01 µg L−1 (bk-MMBDB) and 0.37 µg L−1 (PMA); recoveries, evaluated at very low spike levels (in the ng-µg L−1 range), spanned from 55% (MBDB) to 100% (bk-MMBDB and MDPV); finally, both within-run and between-run precisions were lower than 20% (LLOQ) and 15% (10xLLOQ).
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Gallar, Angeles. "Macro y microcosmos. Un paseo desde el Big Bang hasta el interior de las células." UMH Sapiens Divulgación Científica, no. 26 (February 2020): 20–23. http://dx.doi.org/10.21134/22553568.2020.26.mmbb.
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Nguyen, Giang T., and Oscar Peralta. "Rate of strong convergence to Markov-modulated Brownian motion." Journal of Applied Probability 59, no. 1 (January 18, 2022): 1–16. http://dx.doi.org/10.1017/jpr.2021.30.
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AbstractLatouche and Nguyen (2015b) constructed a sequence of stochastic fluid processes and showed that it converges weakly to a Markov-modulated Brownian motion (MMBM). Here, we construct a different sequence of stochastic fluid processes and show that it converges strongly to an MMBM. To the best of our knowledge, this is the first result on strong convergence to a Markov-modulated Brownian motion. Besides implying weak convergence, such a strong approximation constitutes a powerful tool for developing deep results for sophisticated models. Additionally, we prove that the rate of this almost sure convergence is $o(n^{-1/2} \log n)$ . When reduced to the special case of standard Brownian motion, our convergence rate is an improvement over that obtained by a different approximation in Gorostiza and Griego (1980), which is $o(n^{-1/2}(\log n)^{5/2})$ .
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Adamia, Sophia, Sigitas J. Verselis, Teru Hideshima, Michael P. Chu, Shruti Bhatt, David P. Steensma, Daniel J. Deangelo, et al. "Cell Type-Specific Deregulation of Polypyrimidine Tract- Binding Proteins (PTBPs) Drive Aberrant Splicing in Multiple Myeloma (MM) and Acute Myeloid Leukemia (AML)." Blood 132, Supplement 1 (November 29, 2018): 3895. http://dx.doi.org/10.1182/blood-2018-99-118501.
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Abstract Genome-wide transcriptome profiling detected an increased splicing alterations in MM and AML. While these malignancies are derived from different cell linages, their tumor cells acquire similar aberrant splicing (AbSp), mostly intron retentions. To delineate AbSp mechanism in MM/AML, we focused on PTBPs (1/2/3) that play a critical role in intron excision. We have previously reported deregulated expression of splicing factors (SFs) in MM/AML patient and healthy donor (HD) bone marrow (BM). As MM progressed, PTBP1/2 progressively increased, and PTBP3 gradually decreased (ASH 2017). In AML, PTBP2/3 upregulation and PTBP1 downregulation were detected in patient samples in which increased intron retentions were identified by genome-wide splicing analysis (CCR 2015). Here, these findings were validated by TaqMan assays for PTBPs in 48 MM and 325 AML patient samples, 16 MM/AML cell lines, and in plasma cells (PCs) and CD34+cells from 14 HDBM. Results were consistent with differential expressions of PTBPs in MM/AML previously analyzed. Upregulation of PTBP1/2 and PTBP2/3 proteins were detected in MM and AML cell lines, respectively. PTBP1/2 upregulation was pronounced when MM cell lines were cocultured with BM stromal cells (MMBMSC) derived from MM patients' BM. Importantly, we detected increased proliferation and decreased apoptosis in MM/AML cell lines overexpressing PTBPs. These effects were most evident after coculturing MM cell lines with MMBMSC as compared to HDBMSC. To evaluate PTBP effects on AbSp, we knocked down and/or overexpressed PTBPs in MM/AML cell lines and assessed PDL1 splicing in MM, and NOTCH2 and FLT3 splicing in AML. PDL1 is spliced in ~ 30% of 90 MM patients; while NOTCH2/FLT3/CD13 are spliced in 78%/50% of 387 AML patients, respectively. After PTBP1/2 knockdown in MM cells we detected 4- to 11-fold downregulation of PDL1 splice variants, with proportional upregulation of wild-type PDL1 levels; concurrently, MM cell proliferation was decreased and apoptosis increased. To evaluate MM specific splicing alterations in the context of the MM BM microenvironment, PDL1 splicing, and PTBP1/2 mRNA/protein expressions, were monitored in MM cell lines cocultured with MMBMSC or HDBMSC. We observed time-dependent PDL1 splice variant upregulation, and higher levels of PTBP1/2 in MM cells. We also noted time-dependent PDL1 variant expression switching in association with PTBP1/2 deregulation in the BM microenvironment. RNA-seq analysis and western blotting showed that MMBMSC culture with tumor cells increased intron retention, and altered SF expressions, including PTBPs in BMSC. We next monitored PTBP effects on splicing in AML cells by evaluating NOTCH2 and FLT3 splicing in an TF1, an AML cell line that overexpresses PTBP2/3. RT-PCR analysis showed association between PTBP3 overexpression and NOTCH2 and FLT3 AbSp in TF1 cells. For further validation, we developed an ex vivo splicing assay composed of an FLT3/CD13 splicing cassette with a GFP reporter, which allows for evaluation of splicing events by flow cytometry (FACS) and microscopy. In this assay, cells overexpressing PTBP2/3 caused FLT3/CD13 minigene splicing similar to that detected in AML patients. Also, by RT-PCR, we showed that overexpression of PTBPs caused intron retention, that was confirmed by cloning and sequencing of PCR products and consistent with the FACS analysis and microscopy. Finally, we have tested effects of PTBPs using in vivo AML models (BMT and xenograft). In the BMT model, animal median survival was 48 days post-BMT for MLL-AF9/PTBP3 and 56 days in the control group. In the xenograft model, animal median survival was 66, 94, & 106 days after injection of TF1-PTBP3, TF1-PTBP2, and TF1 cells in mice, respectively (P>0.0001). These studies suggest that PTBP3 overexpression in partnership with the MLL-AF9 promotes occurrence of AML in mice. Tumor RNA samples harvested from these animals were subjected to RNA-seq analysis, which showed increased AbSp association with PTBP3 overexpression. Our studies indicate that deregulated PTBP1/2 expression in MM and of PTBP2/3 in AML drive time-dependent AbSp (intron retention) and splice variant switching, which in MM is induced by culture with BMSC; and conversely, that analogous changes are induced in BMSC cultured with tumor cells. They define role of deregulated expression of the PTBPs in MM/AML pathogenesis, and suggest novel targets for therapeutic intervention. Disclosures Stone: Pfizer: Consultancy; Jazz: Consultancy; Fujifilm: Consultancy; Merck: Consultancy; Cornerstone: Consultancy; Celgene: Consultancy, Other: Data and Safety Monitoring Board, Steering Committee; Novartis: Consultancy, Research Funding; Sumitomo: Consultancy; Ono: Consultancy; Orsenix: Consultancy; Otsuka: Consultancy; AbbVie: Consultancy; Agios: Consultancy, Research Funding; Amgen: Consultancy; Argenx: Other: Data and Safety Monitoring Board; Arog: Consultancy, Research Funding; Astellas: Consultancy. Griffin:Astellas Pharma: Consultancy; Novartis Pharma: Other: Grant, Patents & Royalties: Royalties ; Analysis Group: Consultancy; Sun Pharmaceuticals: Consultancy; RXi Pharmaceuticals: Consultancy; Lilly Pharmaceuticals: Other: Grant; Myeloproliferative Neoplasia Foundation: Other: Grant . Anderson:C4 Therapeutics: Equity Ownership, Other: Scientific founder; Celgene: Consultancy; OncoPep: Equity Ownership, Other: Scientific founder; Bristol Myers Squibb: Consultancy; Gilead: Membership on an entity's Board of Directors or advisory committees; Millennium Takeda: Consultancy.
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Yan, Ke, Ruizhi Chen, Guangyi Guo, and Liang Chen. "Locating Smartphone Indoors by Using Tightly Coupling Bluetooth Ranging and Accelerometer Measurements." Remote Sensing 14, no. 14 (July 19, 2022): 3468. http://dx.doi.org/10.3390/rs14143468.
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High-precision, low-cost, and wide coverage indoor positioning technology is the key to indoor and outdoor integrated location-based services, and it has broad market prospects and social value. However, achieving sub-meter level positioning accuracy in indoor environments remains a real challenge due to the blockage of indoor Global Navigation Satellite System (GNSS) signals, the complexity of indoor environments, and the unpredictability of user behavior. In this paper, we introduce a multi-module BLE broadcaster (MMBB)-based indoor positioning solution in which a tightly coupled fusion architecture is implemented on a smartphone. The solution integrates ranging measurements from multiple MMBB and the measurements of the accelerometer built into a smartphone. It becomes an instant positioning solution without any training phase by adopting a calibrated linearly segmented path loss model for ranging. We apply the pedestrian walking speed derived by the smartphone accelerometer to constrain an unscented Kalman filter method that is used to estimate the location and speed. The accuracy of the proposed method is 50% at 0.79 m and 95% at 1.6 m at in terms of horizontal error distance. Position update frequency is 10 Hz and the time to first fix is 0.1 s. The system can easily adapt a global coordinator system so that it can seamlessly work together with the GNSS to form an indoor/outdoor positioning solution.
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Meng, Fan Bo, Tai Yi Fu, Jun Nan Wang, Jing Tao Yu, and Chan Nan Zhu. "Performance Evaluation of Ethernet Passive Optical Network for Smart Grid." Applied Mechanics and Materials 667 (October 2014): 149–52. http://dx.doi.org/10.4028/www.scientific.net/amm.667.149.
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As a mature access technology for the communication in smart grid, Ethernet Passive Optical Network (EPON) is widely considered as a promising solution due to high bandwidth capacity and stability. In recent years, EPON technology has received much attention and introduced into smart grid. The particularity of smart grid largely depends on bandwidth allocation. In this paper, we evaluate the performances of smart grid with three bandwidth allocation algorithms, i.e., Poll with Stop (PS), Max and Min Bandwidth Bounds (MMBB) and Cyclic Strategy (CS), respectively. The simulation results in this paper show the advantages of CS algorithm in terms of packet delay and throughput.
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Silva, Rodrigo Alves da, Sidnei Junior Guadanhim, and Ercilia Hitomi Hirota. "Mendes da Rocha – Relação entre bibliografia recente e projeto da Fiesp." Risco Revista de Pesquisa em Arquitetura e Urbanismo (Online) 19 (November 25, 2021): 1–27. http://dx.doi.org/10.11606/1984-4506.risco.2021.134058.
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Este artigo relaciona as estratégias de projeto de estudos recentes em torno do processo de projeto de Paulo Mendes da Rocha, verificando sua pertinência em relação ao projeto de remodelação das áreas de acolhimento do edifício da Fiesp, realizado em colaboração com a equipe MMBB Arquitetos. Para isso, foram analisados o edifício construído e o discurso dos arquitetos Ângelo Bucci, Milton Braga, Marta Moreira e Mendes da Rocha e do engenheiro calculista Jorge Zaven Kurkdjian. O estudo aponta convergência entre informações apresentadas na bibliografia existente e neste caso, trazendo novas informações sobre as etapas do desenvolvimento do processo de projeto de Mendes da Rocha juntamente com os arquitetos colaboradores.
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Padang, Monica Jupiter Arung, and Zita Letviany Sarungallo. "PENGARUH FORMULASI MALTODEKSTRIN TERHADAP STABILITAS MIKROENKAPSULAT MINYAK BUAH MERAH (Pandanus conoideus Lamk.)." Jurnal Teknologi Pangan dan Kesehatan (The Journal of Food Technology and Health) 4, no. 2 (December 12, 2022): 67–74. http://dx.doi.org/10.36441/jtepakes.v4i2.1323.
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ABSTRAK: Pemanfaatan minyak buah merah sebagai bahan tambahan pangan, baik sebagai fortifikan atau pewarna dalam bentuk mikroenkapsulat (bubuk kering), dapat memudahkan penggunaanya dalam berbagai produk pangan maupun dikonsumsi secara langsung, karena memiliki kelarutan yang cukup tinggi dalam air. Penelitian ini bertujuan untuk mempelajari pengaruh konsentrasi maltodekstrin sebagai penyalut terhadap kestabilan mikroenkapsulat yang dihasilkan. Mikroenkapsulat minyak buah merah (MMBM) dibuat dengan perlakuan perbandingan maltodekstrin dan air, dalam empat formula yaitu: M1 (16% : 59,5%), M2 (17% : 58,5), M3 (18% :57,5%) dan M4 (19% : 56,5%), dengan menggunakan Gum Arab (2%), Gelatin (1,5%), dan CMC (1%). Hasil penelitian menunjukkan bahwa mikroenkapsulat minyak buah merah yang stabil dapat dihasilkan pada konsentrasi minyak 20% dengan konsentrasi maltodekstrin sebagai penyalut pada kisaran 16-18%. Penggunaan konsentrasi maltodekstrin 18% (M3) menghasilkan produk MMBM dengan kestabilan tertinggi, berwarna oranye, rendemen 32,1%, dan kelarutan 92,1%.ABSTRACT: Utilization of red fruit oil as a food additive, either as a fortificant or as a colorant in the form of microencapsulated, can facilitate its use in various food products or be consumed directly, because it has a high solubility in water. This study aims to evaluate the effect of maltodextrin concentration as a coating on the stability of the resulting microencapsulates. Red fruit oil microencapsulates were prepared with a ratio of maltodextrin and water, in four formulas, namely: M1 (16% : 59.5%), M2 (17% : 58.5), M3 (18% : 57.5%) and M4 (19% : 56.5%). The results of this study showed that the stable red fruit oil microencapsulates can be produced at 20% oil concentration with maltodextrin concentration as a coating in the range of 16-18%. The use of 18% maltodextrin concentration (M3) can produce the red fruit oil microencapsulates with the highest stability, orange in color, 32.1% yield, and 92.1% solubility.
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Czarna, Irmina, Adam Kaszubowski, Shu Li, and Zbigniew Palmowski. "Fluctuation identities for Omega-killed spectrally negative Markov additive processes and dividend problem." Advances in Applied Probability 52, no. 2 (June 2020): 404–32. http://dx.doi.org/10.1017/apr.2020.2.
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AbstractIn this paper, we solve exit problems for a one-sided Markov additive process (MAP) which is exponentially killed with a bivariate killing intensity $\omega(\cdot,\cdot)$ dependent on the present level of the process and the current state of the environment. Moreover, we analyze the respective resolvents. All identities are expressed in terms of new generalizations of classical scale matrices for MAPs. We also remark on a number of applications of the obtained identities to (controlled) insurance risk processes. In particular, we show that our results can be applied to the Omega model, where bankruptcy takes place at rate $\omega(\cdot,\cdot)$ when the surplus process becomes negative. Finally, we consider Markov-modulated Brownian motion (MMBM) as a special case and present analytical and numerical results for a particular choice of piecewise intensity function $\omega(\cdot,\cdot)$ .
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Silva, Rodrigo Alves da, Sidnei Junior Guadanhim, and Ercilia Hitomi Hirota. "Paulo Mendes da Rocha:." Pós. Revista do Programa de Pós-Graduação em Arquitetura e Urbanismo da FAUUSP 25, no. 47 (September 27, 2018): 12–33. http://dx.doi.org/10.11606/issn.2317-2762.v25i47p12-33.
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Este artigo enfoca a pesquisa em Metodologia de Projeto e pretende apresentar as estratégias adotadas por Paulo Mendes da Rocha e equipe MMBB Arquitetos, durante o projeto de remodelação das áreas de acolhimento do edifício da FIESP, que ocorreu entre os anos de 1996 e 1998. O mapeamento desse processo de projeto tem como objetivo apresentar as ações adotadas sobre os problemas decorrentes deste projeto específico, na visão dos arquitetos Paulo Mendes da Rocha, Milton Braga, Marta Moreira, Angelo Bucci e do engenheiro Jorge Zaven Kurkdjian. O resultado do estudo aponta para um processo caracterizado pela reflexão sobre os valores a serem construídos à situação e a estruturação inicial do problema de forma isolada por Mendes da Rocha que busca potencialidades da situação, sendo essas potencialidades intrínsecas à sua personalidade, que valoriza a inteligência das técnicas de construção, o funcionamento racional do projeto, a ligação do edifício ao contexto urbano e a proporcionalidade dos elementos que compõem o edifício...
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MacKay, M. D., F. Seglenieks, D. Verseghy, E. D. Soulis, K. R. Snelgrove, A. Walker, and K. Szeto. "Modeling Mackenzie Basin Surface Water Balance during CAGES with the Canadian Regional Climate Model." Journal of Hydrometeorology 4, no. 4 (August 2003): 748–67. http://dx.doi.org/10.1175/1525-7541(2003)004<0748:mmbswb>2.0.co;2.
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Nys, Charlotte, Colin R. Janssen, and Karel A. C. De Schamphelaere. "Development and validation of a metal mixture bioavailability model (MMBM) to predict chronic toxicity of Ni-Zn-Pb mixtures to Ceriodaphnia dubia." Environmental Pollution 220 (January 2017): 1271–81. http://dx.doi.org/10.1016/j.envpol.2016.10.104.
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Canez, Anna Paula Moura, Alex Carvalho Brino, Débora Saldanha De Avila, and Carolina Gottert Knies. "Butantã versus mariante." Latin American Journal of Development 3, no. 5 (September 1, 2021): 2820–31. http://dx.doi.org/10.46814/lajdv3n5-005.
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Trata-se de um estudo com foco no projeto como investigação de duas casas construídas em São Paulo, uma repetidamente identificada como pertencente à Escola Paulista Brutalista e a outra celebrada em diversas e recentes publicações como exemplar no universo contemporâneo da arquitetura brasileira, construídas em momentos muito distintos da nossa história. A primeira é a chamada Casa Butantã (1964-1966), pois situada no bairro que lhe deu o nome, de Paulo Mendes da Rocha - em realidade, duas casas lado a lado, uma realizada para o próprio arquiteto e a outra para a sua irmã, e a segunda é a casa Mariante, projetada 37 anos depois (2001-2002) por Angelo Bucci, do SPBR Arquitetos, e Marta Moreira, Fernando de Mello Franco e Milton Braga, do MMBB Arquitetos, localizada dentro de um condomínio fechado, distante 40 quilômetros do centro de São Paulo. O objetivo do trabalho foi buscar decifrar as duas obras escolhidas para análise, compreendê-las através de descrições apoiadas graficamente em material produzido pelo grupo de trabalho, cujo foco principal foi o saber propriamente arquitetônico. Revelar escolhas e descobrir o conceito, partindo do que suscitam através do redesenho e da revisão da bibliografia existente e, aí sim, compará-las com o propósito de apontar caminhos convergentes e divergentes.
This is a study focusing on the project as an investigation of two houses built in São Paulo, one repeatedly identified as belonging to the Paulista Brutalist School and the other celebrated in several recent publications as exemplary in the contemporary universe of Brazilian architecture, built at very different times in our history. The first one is the so-called Butantã House (1964-1966), since it is located in the neighborhood that gave it its name, by Paulo Mendes da Rocha - in reality, two houses side by side, one built for the architect himself and the other for his sister, and the second is the Mariante house, designed 37 years later (2001-2002) by Angelo Bucci, from SPBR Arquitetos, and Marta Moreira, Fernando de Mello Franco and Milton Braga, from MMBB Arquitetos, located in a private condominium 40 kilometers from downtown São Paulo. The objective of the work was to decipher the two works chosen for analysis, to understand them through descriptions graphically supported by material produced by the working group, whose main focus was the architectural knowledge itself. Revealing choices and discovering the concept, starting from what they raise through the redesign and the revision of the existing bibliography and, then, comparing them with the purpose of pointing out convergent and divergent paths.
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Khasabulli, Buyela Daniel, Musyimi David Mutisya, Sikuku Phoebe Anyango, Bonface Ombasa Manono, and Duncan George Odhiambo. "Soil Microbial Biomass, Microbial Population and Diversity in Maize-Banana Based Agroforestry System in Kisii County, Kenya." Asian Journal of Research in Crop Science 8, no. 4 (August 4, 2023): 230–39. http://dx.doi.org/10.9734/ajrcs/2023/v8i4203.
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Soil microbes are involved in many important ecosystem processes including nutrient acquisition, biogeochemical cycling and soil aggregation. Soil microbial diversity affects the soil belowground dynamics and fate of carbon and nutrients. Soil microbes are important for agricultural and plant production systems, hence understanding the effects of agroforestry systems on the soil microbes, is necessary in order to improve on soil health and fertility. The objective of the study was to determine the soil microbial biomass, microbial populations and microbial diversity in maize-banana based agroforestry system. The study was conducted at Kenya Agricultural and Livestock Research Organization farm in Kisii County. The experiment was laid out in a randomized complete block design with maize and banana intercropped with agroforestry trees. The treatments were; Maize, banana (MMBB), Maize-banana, Calliandra (MBCC), Maize (MM), banana (BB), Maize-banana, Leucaena (MBLL), Maize-banana, Sesbania (MBSS) and Maize, fertilizer (MMF). Soil samples were collected from the agroforestry fields using a soil auger. Soil microbial biomass was measured using the chloroform fumigation extraction. Fungi and bacteria were enumerated by serial dilution plate method.Shannon diversity index (H’) and Simpson diversity index (1 - D) were used for the calculation of species diversity. SAS (version 9) statistical software was used for analysis. The treatments with agroforestry tree species had significantly higher soil microbial biomass (MBSS-86.33, MBCC-52.66 and MBLL- 47.0MgC/Kg) populations of bacteria (MBSS-197, MBCC-128.0 and MBLL-111.25x108cfu g-1soil) and fungi (MBSS-50.83, MBCC-29.167 and MBLL-14.0x105cfu g-1 soil) and diversity of bacteria (MBSS- (H' =1.61, D = 1), MBCC- (H' =1.04, D = 0.83), MBLL (H' = 0.52, D = 0.5) and fungi MBSS (H' =1.39, D = 1) MBCC (H' =1.04, D= 0.83), MBLL (H' =1.56, D = 0.93). MBSS increased microbial biomass, microbial populations and microbial diversity significantly an indication of improved soil health and hence recommended for adoption by farmers.
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Gorgun, Gullu, Teru Hideshima, Noopur S. Raje, Naoya Mimura, James E. Bradner, Diana Cirstea, Loredana Santo, et al. "Immunomodulatory Effects of Histone Deacetylase 6 Inhibition in Suppressor Immune Cells in Multiple Myeloma." Blood 118, no. 21 (November 18, 2011): 128. http://dx.doi.org/10.1182/blood.v118.21.128.128.
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Abstract Abstract 128 The interaction of myeloma (MM) cells with bone marrow accessory cells and/or the extracellular matrix induces genomic, epigenomic and functional changes which promote tumor development, progression, cell adhesion mediated-drug resistance (CAM-DR), and immune suppression. To develop the most efficient anti-MM treatment strategy and prevent tumor escape from immune recognition, both enhancing anti-MM effector immune response and overcoming MM-induced immune suppression is essential. Suppressive immune cells including myeloid derived suppressor cells (MDSC), regulatory T cells (Treg) and IL-17 secreting Th (Th17) cells act as tumor promoters and suppressors of effector immune response, and therefore represent a significant barrier to current anti-tumor therapeutic strategies. Since, we and others have reported increased numbers of Treg and Th17 cells in MM, we here assessed MDSCs in both peripheral blood (PBMC) and bone marrow (BMMC) of patients with MM compared to healthy donors. Phenotypic analysis by flow cytometry showed a significant increase in CD14−CD11b+HLA-DRlowCD15+ MDSCs in both PBMC and BMMC from MM patients compared to healthy donors (p<0.01). Furthermore, coculture of MM cell lines with healthy PBMCs for 6 days demonstrated that MM cells significantly induce MDSC differentiation in healthy PBMCs (p<0.03). Recent studies have demonstrated that histone deacytlase 6 (HDAC6) is an important regulator of monocyte/macrophage-mediated immune response. We therefore next analysed the immunomodulatory effects of WT-161, a novel small molecule inhibitor of HDAC6, alone or in combination with lenalidomide (len) and bortezomib (bort), on suppressive immune cells in the MMBM microenvironment. To keep cell-cell interaction intact reflective of the MMBM microenvironment, PBMCs or BMMCs from MM patients were cultured in the absence or presence of WT-161 (0.5–5uM), len (1–10uM), and/or bort (2–5nM), and individual cell populations were analysed by flow cytometry. Phenotypic characterization of suppressive immune cells showed a significant decrease in both CD4+CD25+Foxp3+ Treg cells and MDSCs in MM-PBMCs and MM-BMMCs cultured with WT-161, alone or in combination with len or bort (p<0.01); however, there was no change in the expression of Th17 cells. To determine the functional mechanism of immune suppression, MDSC and Treg cells were isolated by magnetic-Ab sorting and cultured for 6 days with autologous T cells (TCR/IL-2 stimulated), with or without WT-161, len and bort, alone or in combination. T cell proliferation (by 3H-thymidine assay) was significantly inhibited in the presence of MDSCs, whereas WT-161 notably reversed MDSC-mediated T cell suppression. In contrast, len and bort did not show any significant effect. Intracellular reactive oxygen species (ROS, an MDSC-derived metabolic immune inhibitory molecule) expression was significantly decreased in MDSCs from MM cultured with WT-161, alone or together with len and bort (p<0.05). Additionally, WT-161 also reversed Treg-mediated T cell suppression as well as len. Cytokine profiling by intracellular flow cytometric analysis demonstrated that WT-161 significantly decreased IL-6 and GM-CSFR expression in MDSCs, whereas it induced IFNγ and IL-12 production in effector CD4T, CD8T and NKT cells. Finally, unstimulated or IL-2 prestimulated (36h) PBMCs or NK cells were cultured with MM cell lines (MM1.S, RPMI8226), in the absence or presence of WT-161 alone or with len and bort (4h), and anti-MM cytotoxic activity was determined by Cr51-release cytotoxicity assay. While len (48% killing) and WT-161 (39% killing) induced CTL-mediated cytotoxicity, WT-161 (53% killing) and len (56% killing) induced more potent NK cell-mediated anti-MM cytotoxicity. These data suggest that HDAC6 may have an immune regulatory function, and that inhibition of HDAC6 induces changes in suppressor immune cells leading to enhanced anti-MM immune response in MM microenvironment. Ongoing analysis of the effects of HDAC6 inhibition on immune cells in the tumor microenvironment will further define the role of HDAC6 in disease pathogenesis and suggest novel immune-based epigenetic-targeted therapies. Disclosures: Hideshima: Acetylon: Consultancy. Raje:Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Acetylon: Research Funding. Bradner:Acetylon: Scientific Founder. Richardson:Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or advisory committees. Munshi:Celgene: Membership on an entity's Board of Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy, Membership on an entity's Board of Directors or advisory committees. Anderson:Novartis: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Acetylon: Membership on an entity's Board of Directors or advisory committees.
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Chen, Haiming, Mingjie Li, Eric Sanchez, Nicole Ng, Erin Yu, Sean Bujarski, Zhengyi Yin, et al. "Ruxolitinib Reverses Checkpoint Inhibition By Downregulating PD-L1 and PD-L2 Expression on Both Tumor and Stromal Cells in Multiple Myeloma." Blood 134, Supplement_1 (November 13, 2019): 4402. http://dx.doi.org/10.1182/blood-2019-130888.
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Introduction: Multiple myeloma (MM) tumor cells evade host immunity through the interaction of PD-L1 and PD-L2 to PD-1 on T-cells. This creates an immunosuppressive milieu in the bone marrow (BM) microenvironment. The immune inhibitory proteins PD-L1 and PD-L2 are highly expressed in MM BM. Moreover, increased expression of these proteins are associated with resistance to treatment in MM. Ruxolitinib (RUX) is a JAK1/2 inhibitor that is effective for the treatment of myeloproliferative diseases. In this study, we examined PD-L1 and PD-L2 gene and protein expression in the BM of MM patients with progressive disease (PD) or in complete remission (CR). We further investigated the effects of RUX on expression of PD-L1 and PD-L2 in MMBM, and the effect of RUX in combination with anti-MM agents in vitro and in vivo. Material and Methods: BM mononuclear cells (MCs) and serum were collected from MM patients and healthy subjects after obtaining IRB approval. Single-cell suspensions were prepared from human MM LAGκ-1A xenografts which had been grown in the mice. The cells were cultured and treated with or without RUX and then were determined by qPCR, flow cytometric analysis, ELISA, and western blot. Results and Discussion: The results from qPCR and flow cytometric assays showed that PD-L1 and PD-L2 gene expression was markedly increased in BMMCs from MM patients with PD compared with patients in CR or with healthy controls. We further investigated the effects of RUX on PD-L1 and PD-L2 expression in primary and stromal cells from MM patients' BM samples in vitro. RUX treatment markedly reduced PD-L1and PD-L2 gene and protein expression in the MM tumor cells cultured alone or co-cultured with stromal cells in a concentration dependent pattern. We then determined whether RUX can augment the anti-MM effects of T-cells in vitro. RUX (0, 0.1, 0.5, 1, and 5 µM) increased MM cell apoptosis in the presence of IL-2 stimulated T-cells in a concentration dependent fashion, to a similar degree to anti-PD-1 (0, 0.5, 1, 5, and 10 µg/ml) or anti-PD-L1 (0, 0.5, 1, 5, and 10 µg/ml) antibody treatment. Moreover, the combination of RUX with anti-PD-1 or anti-PD-L1 antibody increased T-cell-induced MM cell apoptosis more than the agents alone. To evaluate the efficacy of drugs in vivo, severe combined immune deficient mice implanted with the human MM xenograft LAGκ-2 were treated with RUX (30mg/kg). The results showed PD-L1 expression in the xenograft was significantly decreased in RUX-treated mice compared with the untreated control group. In contrast, RUX had no effect on PD-1 expression on T-cells. Conclusion: The PD-L1/PD-1 pathway delivers inhibitory signals that regulate both peripheral and central tolerance, and inhibit anti-tumor immune-mediated responses. This study demonstrated that the JAK inhibitor RUX downregulated PD-L1 and PD-L2 expression in both MM tumor and stromal cells. We also demonstrated that RUX alone increased T-cell-induced apoptosis of MM cells; and, moreover, the combination of RUX with anti-PD-1 and anti-PD-L1 further increased apoptosis. The results suggest that JAK inhibitors may be effective for treating MM patients through their ability to reduce expression of checkpoint proteins involved in the development of immune resistance. Thus, JAK inhibitors should help overcome the immune resistance generated by these proteins for patients with this B-cell malignancy. Disclosures Chen: Oncotraker Inc: Equity Ownership. Berenson:Amgen: Consultancy, Speakers Bureau; Sanofi: Consultancy; Takeda: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Incyte Corporation.: Consultancy, Research Funding; Sanofi: Consultancy; Amag: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; OncoTracker: Equity Ownership, Other: Officer; Incyte Corporation.: Consultancy, Research Funding; Janssen: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Research Funding; Amag: Consultancy, Speakers Bureau.
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Braga, Milton. "MMBB arquitectos." ARQ (Santiago), no. 51 (July 2002). http://dx.doi.org/10.4067/s0717-69962002005100009.
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