Optimal Induction Research Articles

Thermal Design, Optimization, and Packaging of Planar Magnetic Components

This article is focused on the thermal design and three-dimensional (3-D) package optimization of planar magnetic components (PMCs), including transformers and inductors for application in an electric vehicle composite boost dc-dc converter. Each PMC comprises electrical windings in printed circuit board (PCB) form in combination with a ferrite core. Multiple features of each PMC package are thermally optimized for the proposed device configurations with given core size, core loss distribution, number of turns in the PCB winding, winding copper thickness, and winding loss distribution. These heuristically optimized features include a lower level cold plate structure with a conformal base for enhanced convective heat transfer, an upper level PMC cap structure for doubled-sided cooling through conductive heat flow to the cold plate, the implementation of functionally distributed copper thermal and electrothermal vias in the PCB winding for improved cross-plane thermal conductance, and judicious implementation of select materials at various locations and interfaces within the package. Detailed numerical modeling reveals the combined effect of this 3-D packaging strategy with a 79.3 °C and 48.5 °C maximum temperature reduction in the core and PCB winding, respectively, relative to a baseline device configuration. Select PMC experimental validation confirms the expected thermal performance of an optimized PCB design. The thermal design approach is relevant for a range of high-power-density electronics PMC packaging applications.

Numerical Modeling of Soil Water–Heat Transport under Oxo-Biodegradable Film Mulch and the Optimal Mulching Period

Timely monitoring and regulation of the transport and distribution of soil water and heat are appropriate methods to ensure and improve crop yields. With the degradation of the oxo-biodegradable film, the upper boundary condition is a time-variable boundary, and soil water-heat transport is more complicated, comparing with conventional plastic film. Based on HYDRUS-2D version 2.02 and the characteristics of mulching films, a soil water-heat coupled transport mathematical model of drip irrigation was established, and the simulated soil water content and temperature were tested against three-year field observations for calibration and validation purposes. The model prediction demonstrated that the induction periods of oxo-biodegradable film mulching differed in different hydrological years. In normal flow years, an induction period of 50–80 days had higher water use efficiency. While the window would increase to 50–100 days in low flow years. As for temperature, comparing with conventional plastic film mulching, the decreasing trend of temperature started to slow down when the induction period increased to 70 days. Therefore, the optimal induction period of the oxo-biodegradable film is 50–70 days.

Program complex for optimization of surface hardening of steel billets

The aim of the paper is to develop program complex in software MATLAB with integrated numerical 2D nonlinear FLUX model, which is used for solving optimal inductor design and control problems for heating stage of surface induction hardening. Considered program complex is based on alternance method, that allows to write systems of transcendental equations, closed with respect to all unknown design and control parameters of the process. The suggestion for implementation of obtained optimal control algorithm is presented.

Parameter Optimization of Double LCC MCRWPT System Based on ZVS

At present, magnetically coupled resonance wireless power transfer (MCRWPT) is the main technology used in electric vehicle wireless power transfer (WPT) due to its advantages of high transmission power and high efficiency. The resonant compensation circuit of the system generally adopts the double LCC (DLCC) structure, which has many capacitor and inductor components. Therefore, it is necessary to optimize the circuit parameters to improve the transmission performance of the system. In this study, the DLCC compensation circuit was modeled and analyzed to lay the foundation for parameter optimization. Secondly, the size parameters of the energy transmitting and receiving coil were determined, and the influence of the change of the primary and secondary compensation inductance on the circuit element stress and output performance was analyzed to determine the optimal compensation inductance value. Thirdly, the realization condition of zero voltage switching (ZVS) was analyzed, the relationship between the input impedance angle of the compensation circuit and the component parameter value was obtained, and a parameter optimization control strategy for realizing ZVS was proposed. Finally, through simulation and experiment, it was concluded that under different power levels, the efficiency of the parameter optimization strategy proposed in this study is as high as 91.86%, increasing by about 1%. Therefore, the research undertaken in this study can promote the development of WPT technology and has certain practical significance.

Advances in treatment of elderly primary central nervous system lymphoma.

The management of older individuals (≥60years) with primary central nervous system lymphoma remains a clinical challenge. Identification of optimal therapy and delivering adequate dose intensity are two of the major issues in treating elderly patients. Premorbid performance status and comorbidities influence individualised treatment approaches and geriatric assessment tools are increasingly utilised. Optimal induction treatment remains high-dose methotrexate-based immunochemotherapy, delivery is feasible in the majority of patients and the goal of treatment remains achieving complete remission. Consolidation strategies are also relevant in the elderly, aiming to maximise duration of response and quality of life (QoL). Potential options include high-dose therapy with haematopoietic stem cell consolidation, non-myeloablative chemotherapy and whole-brain radiotherapy. Efficacy of novel agents, such as Bruton tyrosine kinase inhibitors and lenalidomide, have been reported; these represent an alternative for elderly patients unfit for chemotherapy. Prognosis remains poor, improvement of outcomes in this age group is urgently needed.

Tetraploid induction of Crassostrea hongkongensis and C. sikamea by inhibiting the polar body 1 release in diploid fertilized eggs.

The production of an all-triploid population by mating tetraploid males with diploid females is the best and most fundamental method for the large-scale production of triploid oysters. Obtaining a stable tetraploid population is essential for guaranteed production in industrialized triploid cultivation. C. hongkongensis and C. sikamea are important oyster breeding species in southern China, and have great economic value. However, there are not any published data on inducing tetraploid C. hongkongensis or C. sikamea. Therefore, we investigated tetraploid induction in these two oyster species by inhibiting the PB1 release in diploid fertilized eggs using Cytochalasin B (CB) under 31°C, 15 ‰ salinity. The results confirmed that the optimal tetraploid induction conditions for C. hongkongensis were a CB concentration of 0.50mg/L with induction starting at 9.0min after fertilization, and stopping at 21.0min after fertilization; the induction efficiency index reached 0.123 under these conditions. The optimal tetraploid induction conditions for C. sikamea were a CB concentration of 0.50mg/L, with induction starting at 7.5min after fertilization and stopping at 18min after fertilization; the induction efficiency index could be as high as 0.281 under these conditions. However, we confirmed that the tetraploid rate decreased with larval growth, and no tetraploids were detected in the juvenile period of either C. hongkongensis or C. sikamea. This may be attributed to the very low survival of the tetraploid larvae induced by this method, especially as most tetraploid larvae died during the first three days. In summary, it is simple to directly induce tetraploid C. hongkongensis and C. sikamea larvae by inhibiting the PB1 release of diploid zygotes, but the low survival rate makes it challenging to obtain viable juvenile tetraploids.

In Vitro Production and Exudation of 20-Hydroxymaytenin from Gymnosporia heterophylla (Eckl. and Zeyh.) Loes. Cell Culture.

The metabolite 20-Hydroxymaytenin (20-HM) is a member of the quinone-methide pentacyclic triterpenoids (QMTs) group. This metabolite group is present only in Celastraceae plants, and it has shown various biological activities from antioxidant to anticancer properties. However, most QMTs metabolites including 20-HM cannot be synthesized in a laboratory. Therefore, we optimized a plant tissue culture protocol and examined the potential of Gymnosporia heterophylla (synonym. Maytenus heterophylla) to produce 20-HM in an in vitro experiment. For the first time, we reported the optimum callus induction medium with a high percentage success rate of 82% from the combination of 1 mg/L indole-3-butyric acid and 5 mg/L naphthalene acetic acid. Later, our cell suspension culture cultivated in the optimum medium provided approximately 0.35 mg/g fresh weight of 20-HM. This concentration is roughly 87.5 times higher than a concentration of 20-HM presenting in Elaeodendron croceum (Celastraceae) leaves. In addition, we also found that 20-HM presented in a cultivation medium, suggesting that G. heterophylla cells secreted 20-HM as an exudate in our experiment. Noticeably, 20-HM was missing when Penicillium cf. olsonii occurred in the medium. These findings hint at an antifungal property of 20-HM.

VqBGH40a isolated from Chinese wild Vitis quinquangularis degrades trans-piceid and enhances trans-resveratrol

Resveratrol (3,5,4’-trihydroxy-stilbene) is a phytoalexin that can prevent plants from pathogen attacks. Piceid is the glycosylation product of resveratrol and the main storage form of stilbenes in grapevines. Here, we reported the function of a β-glycoside hydrolase gene, VqBGH40a, from the Chinese wild grapevine Vitis quinquangularis accession Danfeng-2 in the regulation of plant resistance to powdery mildew (Uncinula necator). VqBGH40a belonging to β-glycoside hydrolase family 1 encoded 506 amino acids and was located on the cytomembrane. Its optimal induction condition was 28 or 30℃, for 4 h, with 0.1 mM IPTG in a prokaryotic expression system. Enzyme activity detection showed that purified VqBGH40a could hydrolyze trans-piceid to form trans-resveratrol in vitro. VqBGH40a was transiently overexpressed in Danfeng-2 leaves and then artificially inoculated with powdery mildew showed that VqBGH40a protein could hydrolyze trans-piceid in vivo. Additionally, a comparative family analysis between VqBGH40a and 38 VviBGHs was performed. Overall, these results demonstrate that VqBGH40a can hydrolyze trans-piceid, enhance trans-resveratrol content, and participate in the defense mechanism of grapevine against powdery mildew.

Inductance Calculation and Structural Optimization of Toroidal Circular Disk-Type Inductors in IPPS

In inductive pulsed power supplies (IPPSs), the toroidal circular disk-type inductors have the advantages of high energy density, good symmetry, and slight magnetic field interference. However, the inductance calculation of the toroidal coils with a different geometric structure and electrical connection is very complicated, let alone the overall optimization of the IPPS system using structure parameters as variables. In this article, a systematic quick calculation method for the toroidal circular disk-type inductor with any geometric structure and electrical connection has been summarized and elaborated. Some improvements in accelerating the calculation speed have been proposed and verified. The error between the proposed calculation method and measurement is less than 1.1%. Finally, with the quick calculation methods, the genetic algorithm (GA) is used to optimize a 20-stage inductor for an XRAM generator with a total energy of 1.25 MJ. After 12 400 calculations, the energy density of the obtained optimal toroidal coil reaches 14.54 MJ/m <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> .

An International Multicenter Retrospective Comparison of Induction Chemoimmunotherapy Regimens on Outcomes in Patients with Transplant-Eligible Mantle Cell Lymphoma

IntroductionThe optimal induction and conditioning regimen for patients with transplant eligible mantle cell lymphoma (MCL) remains unknown. Common approaches include the Nordic MCL2 regimen (rituximab (R), cyclophosphamide, vincristine, doxorubicin, prednisone (R-maxi-CHOP)) alternating with high-dose cytarabine (Geisler, Blood 2006) and R-Hyper CVAD/R-MA (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high dose methotrexate/cytarabine) (Romaguera JCO 2005). The aim of this study was to compare the efficacy of different induction and conditioning regimens in transplant eligible MCL patients.MethodsWe performed a multi-center retrospective analysis of MCL patients treated with induction chemo-immunotherapy and deemed fit enough for autologous stem cell transplant (ASCT) between December 2001 and December 2015. Patients were excluded if they did not receive rituximab with induction chemotherapy. Transplant eligibility was determined by the treating physician and patients were included if fit enough to undergo ASCT regardless of whether it was subsequently performed. Patient characteristics, prognostic factors and outcomes following treatment were collected. We used appropriate descriptive statistics to compare baseline characteristics between treatment groups, and calculated progression free (PFS), overall survival (OS) and follow up from date of diagnosis to date of disease progression or death from any cause, or death from any cause, respectively. Patients alive at last observation were censored. We used univariate Cox regression to identify associations between prognostic factors and outcomes, and covariates with P-values <0.1 were included in a Cox multivariate regression.ResultsWe identified 228 patients and grouped them according to induction regimen received. Their baseline characteristics, treatment and outcomes are summarized in Table 1. Overall, the 5 groups were mostly balanced in terms of baseline characteristics. Patients who underwent Nordic-like and Hyper-CVAD regimens were younger than the other groups. After a median follow up of 4.2 years (range 0.4-15), among the entire cohort the 4-year PFS was 62% (95%CI 54-69%) and OS was 84% (95%CI 78-88%). By univariate analysis, c-MIPI (combined MCL International Prognostic Index biologic index, with MIPI if Ki67 was not available), B symptoms, stage and bone marrow involvement at diagnosis were significantly associated with PFS; c-MIPI, blastoid histology, and B symptoms for OS.Induction chemo-immunotherapy regimen was not associated with PFS (Fig A) or OS (Fig B) by multivariate analysis and only c-MIPI high-risk group (HR=1.8 [95%CI 0.9-3.7], P=0.09) showed an adverse trend for PFS and similarly for OS (HR=2.7 [95%CI 1.1-6.4], P=0.02). Cytarabine-containing induction regimens were not significantly associated with PFS (HR=0.9 [95%CI 0.5-1.6], P=0.72) or OS (HR=1.5 [95%CI 0.7-3.0], P=0.27) by multivariate analysis. Considering only patients who received an ASCT, induction therapy was still not associated with PFS (P=0.81) or OS (P=0.51).Among patients who responded to induction and did not experience disease progression within 6 months of diagnosis, delivery of ASCT was associated with favorable PFS (P=0.01) (Fig C) and OS (P=0.07) by univariate analysis. PFS (HR=1.3 [95%CI 0.8-2.0], P=0.19) (Fig D) or OS (HR=0.9 [95%CI 0.5-1.6], P=0.75) were not affected by conditioning regimen among the same cohort. Use of the BEAM (carmustine, etoposide, cytarabine, melphalan) conditioning regimen was associated with inferior PFS relative to BuMel (busulfan and melphalan) (HR=2.0 [95%CI 1.1-3.6], P=0.02) but not OS (HR=1.1 [95%CI 0.5-2.3] P=0.77). Maintenance rituximab among transplanted patients was associated with neither PFS (P=0.94) nor OS (P=0.46) but numbers treated were low.ConclusionWithin the limits of a retrospective study and modest power for some comparisons, induction therapy did not influence ORR, PFS or OS. BuMel conditioning may result in superior disease control. Large prospective studies are required to define the optimal chemo-immunotherapy induction and conditioning regimen for MCL patients. [Display omitted] DisclosuresBishton:Roche: Other: Travel Sponsorship. Ritchie:Amgen Inc.: Honoraria. Schwarer:Novartis: Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Roche: Honoraria; Amgen: Honoraria; Specialised Therapeutics: Honoraria. Tam:Janssen Cilag: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Roche: Honoraria, Research Funding. Opat:Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Beigene: Research Funding; Mundipharma: Consultancy; Amgen: Research Funding. Hawkes:Roche: Other: Travel expenses; Bristol-Myers Squibb: Research Funding; Roche: Other: Travel expenses, Research Funding; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Other: Travel expenses; Merck Serono: Research Funding; Merck Sharpe Dohme: Research Funding.

Lenalidomide, Bortezomib, and Dexamethasone (RVD) As Induction Therapy in Newly Diagnosed Multiple Myeloma (MM)

Background: Lenalidomide, bortezomib and dexamethasone (RVD) was demonstrated to be an effective and well tolerated induction regimen in both transplant eligible and ineligible patients. Two large randomized phase III trials show an overall response rate (ORR) >95% (Durie et al, Attal et al) supporting the combination. We have evaluated our institutional data of patients treated with RVD induction therapy.Methods: 751 newly diagnosed MM patients were treated with RVD induction therapy [R - 25 mg/day (days 1-14), V - 1.3 mg/m2 (days 1, 4 8, 11) and D - 40 mg once/twice weekly as tolerated every 21 days] from January 2008 until April 2015. Dose-adjustments were made based on the treating physicians discretion and patient tolerability. Demographic and outcomes data for the patients were obtained from our IRB approved myeloma database and responses were evaluated per IMWG Uniform Response Criteria.Results: The median age was 61 years (range 22-83). Other patient characteristics include: M/F 54%/46%; W/AA 58%/30%; ISS I/II/III 36%/24%/19%; Isotype IgG/IgA/FLC 56%/21%/17%; high risk/standard risk 28%/62%. Among the standard risk patients, t(11;14):13%, del (13): 30% comprised majority of the patients. Among high risk patients, the distribution of high risk cytogenetic abnormalities are t(4;14)/t(14;16)/del(17p): 5%/2.5%/10.5%. Complex karyoptye by conventional metaphase karyotyping was seen in 16% of the patients. A total of 562 patients (74.8%) underwent ASCT1 and 165 patients (22%) were offered deferred transplant. Among the patients that opted for deferred transplant, 56 patients (33.9%) received ASCT1 at first relapse. Median time to receive ASCT1 among these relapsed patients was 30 months (3-96 months). For others, median time for patients to receive ASCT1 was 5 months (range, 1-64 months). Post-ASCT, 70% patients were on maintenance therapy tailored to their risk (R-54%; RVD-8%; V-4%). This differed from the deferred ASCT patient population (mostly standard risk patients), where 66% of the patients received revlimid based maintenance. Median PFS1 among the deferred group was 73 months (range, 54.3-91.62). At a median follow up of 44 months for the entire cohort, the estimated median PFS was 56 months (49.85-62.15 months). Median PFS for standard risk patients was 68 months (60.62-75.37) versus 33 months for the high-risk patients (28-37.9 months), p<0.001 and median OS has not been reached, but encouraging results were seen for both high-risk and standard risk cohort with 64% and 77% of patients alive at the 84-month mark, respectively (Fig 1). Response rates are summarized in table 1.Conclusions: This is the largest reported cohort of myeloma patients treated with RVD regimen and highlights the activity of this induction regimen with superior response rates of close to 90% ≥VGPR rates post-ASCT. This regimen should serve as an important bench mark for future studies designing optimal induction regimens. [Display omitted] DisclosuresHeffner:ADC Therapeutics: Research Funding. Boise:Abbvie: Consultancy; Eli Lilly and Company: Research Funding. Kaufman:Amgen, Novartis: Research Funding; Amgen, Roche, BMS, Seattle Genetics, Sutro Biopharma, Pharmacyclics: Consultancy. Nooka:Amgen, Novartis, Spectrum, Adaptive tecnologies: Consultancy.

Multiple Myeloma and Renal Impairment: Analysis of Induction Therapy Strategies and Outcome after Autologous Stem Cell Transplantation

Introduction: Multiple Myeloma (MM) is frequently accompanied by renal impairment (RI) at diagnosis. As MM-specific therapeutic strategies have evolved drastically within the past decades, we aimed at delivering a re-evaluation of applied treatments and outcomes according to renal function at diagnosis.Methods: In this multicenter, retrospective cohort analysis, we analyzed 366 patients who were diagnosed with MM between 1997-2016 and subsequently underwent autologous stem cell transplantation (ASCT). RI at diagnosis was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2. We carried out statistical analysis of patient groups stratified by renal function with regard to induction therapy defined as conventional chemotherapy (CT) versus immuno-chemotherapy (ICT) including either a proteasome inhibitor and/or an immunomodulator. Further, overall and progression-free survival (OS, PFS) were analyzed in the defined subgroups.Results: Of 366 patients, 287 received ICT versus 79 who had CT alone. The choice of the applied treatment strategy was highly dependent on diagnosis date, as all patients diagnosed before the year 2000 received chemotherapy alone, while all but 4 patients diagnosed after 2006 received ICT. Patients with renal impairment were just as likely to receive ICT as those without (75.9 vs. 79.5%, p=0.259). On OS analysis in the patient groups A) normal renal function/ICT (n=202), B) normal renal function/CT (n=52), C) impaired renal function/ICT (n=85), D) impaired renal function/CT (n=27), a longer survival was observed in groups A and B; however without statistical significance (p=0.080; Figure 1). On analysis of PFS, no differences were observed (p=0.784; Figure 2).Conclusions: Impaired renal function confers only a slight and statistically insignificant OS disadvantage in newly diagnosed MM patients receiving ASCT. On analysis of treatment strategy, however, it is evident that ICT attains better OS outcomes compared to CT alone. Therefore, while renal impairment remains common in patients with MM, an interdisciplinary mode of action between hemato/oncologists and nephrologists concerning the optimal induction therapy prior to ASCT is of pivotal clinical importance. The application of an adequate immuno-chemotherapy should conquer the fear of the negative impact of renal failure on outcome in patients with MM. [Display omitted] DisclosuresGisslinger:Janssen Cilag: Honoraria; Shire: Honoraria; PharmaEssentia: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; AOP Orphan Pharmaceuticals AG: Consultancy, Honoraria; Takeda: Honoraria. Krauth:Takeda: Honoraria; Janssen Cilag: Honoraria; Novartis: Honoraria; Amgen: Honoraria; AOP Orphan Pharmaceuticals AG: Honoraria; Celgene: Honoraria; BMS: Honoraria.

HnRNPA1 enhances FOXP3 stability to promote the differentiation and functions of regulatory T cells.

Regulatory T cells (Tregs) are indispensable for the maintenance of immunological self-tolerance and homeostasis. Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is required for optimal Treg induction. Here, we reveal that human-induced Tregs (iTregs) lacking hnRNPA1 show reduced expression of the transcription factor FOXP3, increased ubiquitination level of FOXP3, and impaired suppressive abilities. Human naïve CD4 T cells with hnRNPA1 knockdown show a decreased Treg differentiation ratio. hnRNPA1 could interact with FOXP3 as well as with the E3 ligase Stub1. The phosphorylation at hnRNPA1 S199 could increase both interactions. The overexpression of FOXP3 in Tregs containing shhnRNPA1 could not recover the phenotype caused by hnRNPA1 knockdown. Therefore, there might be multiple essential pathways regulated by hnRNPA1 in Tregs. In conclusion, we present a new role of hnRNPA1 in promoting Treg function, indicating it as a promising target for tumor therapies.

A Live-Attenuated Equine Influenza Vaccine Stimulates Innate Immunity in Equine Respiratory Epithelial Cell Cultures That Could Provide Protection From Equine Herpesvirus 1.

Equine herpesvirus 1 (EHV-1) ubiquitously infects horses worldwide and causes respiratory disease, abortion, and equine herpesvirus myeloencephalopathy. Protection against EHV-1 disease is elusive due to establishment of latency and immune-modulatory features of the virus. These include the modulation of interferons, cytokines, chemokines, antigen presentation, and cellular immunity. Because the modulation of immunity likely occurs at the site of first infection—the respiratory epithelium, we hypothesized that the mucosal influenza vaccine Flu Avert® I.N. (Flu Avert), which is known to stimulate strong antiviral responses, will enhance antiviral innate immunity, and that these responses would also provide protection from EHV-1 infection. To test our hypothesis, primary equine respiratory epithelial cells (ERECs) were treated with Flu Avert, and innate immunity was evaluated for 10 days following treatment. The timing of Flu Avert treatment was also evaluated for optimal effectiveness to reduce EHV-1 replication by modulating early immune responses to EHV-1. The induction of interferons, cytokine and chemokine mRNA expression, and protein secretion was evaluated by high-throughput qPCR and multiplex protein analysis. Intracellular and extracellular EHV-1 titers were determined by qPCR. Flu Avert treatment resulted in the modulation of IL-8, CCL2, and CXCL9 starting at days 5 and 6 post-treatment. Coinciding with the timing of optimal chemokine induction, our data also suggested the same timing for reduction of EHV-1 replication. In combination, our results suggest that Flu Avert may be effective at counteracting some of the immune-modulatory properties of EHV-1 at the airway epithelium and the peak for this response occurs 5–8 days post-Flu Avert treatment. Future in vivo studies are needed to investigate Flu Avert as a prophylactic in situations where EHV-1 exposure may occur.

High-frequency shoot regeneration from flower bud derived callus of Gymnostachyum febrifugum Benth., an endemic medicinal plant to the Western Ghats

Gymnostachyum febrifugum Benth. is a small, scapigerous, rare and endemic medicinal herb indigenous to India, and belonging to the family Acanthaceae. This study reports an efficient protocol for high-frequency flower bud-derived callus induction and shoot organogenesis in G. febrifugum. Flower buds at 7 days before anthesis (dBA) were excised from the inflorescence and cultured on MS medium supplemented with various concentrations of 2,4-dichlorophenoxy acetic acid (2,4-D; 2.275–9.1 µM) for callus induction. The optimum callus induction (78%) was obtained on MS medium supplemented with 6.825 µM 2,4-D. The calli when subcultured on MS medium supplemented with different concentrations of thidiazuron (TDZ; 2.275–11.375 µM) or 6-benzylaminopurine (BAP; 2.22–11.1 µM) alone or in combination with 1- naphthaleneacetic acid (NAA; 1.074–3.759 µM) induced shoots. The highest frequency (94%) and number of shoots (44.6 shoots/unit callus) were obtained on MS medium supplemented with 9.1 µM TDZ and 2.685 µM NAA. The optimum rooting frequency (95%) and number of roots (10.2) were observed on ½ MS medium supplemented with 14.76 µM indole-3-butyric acid (IBA). The rooted plantlets were acclimatized and transferred to soil with 94% success. A protocol for high-frequency shoot induction from flower bud derived calli has been standardized for G. febrifugum,an endemic medicinal herb to the Western Ghats.

Viperin interacts with PEX19 to mediate peroxisomal augmentation of the innate antiviral response.

Peroxisomes are recognized as significant platforms for the activation of antiviral innate immunity where stimulation of the key adapter molecule mitochondrial antiviral signaling protein (MAVS) within the RIG-I like receptor (RLR) pathway culminates in the up-regulation of hundreds of ISGs, some of which drive augmentation of multiple innate sensing pathways. However, whether ISGs can augment peroxisome-driven RLR signaling is currently unknown. Using a proteomics-based screening approach, we identified Pex19 as a binding partner of the ISG viperin. Viperin colocalized with numerous peroxisomal proteins and its interaction with Pex19 was in close association with lipid droplets, another emerging innate signaling platform. Augmentation of the RLR pathway by viperin was lost when Pex19 expression was reduced. Expression of organelle-specific MAVS demonstrated that viperin requires both mitochondria and peroxisome MAVS for optimal induction of IFN-β. These results suggest that viperin is required to enhance the antiviral cellular response with a possible role to position the peroxisome at the mitochondrial/MAM MAVS signaling synapse, furthering our understanding of the importance of multiple organelles driving the innate immune response against viral infection.

OP31 RESTORE: Interim analysis of a Phase 2 study of QBECO SSI for the induction and maintenance of clinical and endoscopic remission in subjects with Moderate to Severe Crohn’s Disease

Abstract Background Innate immune defects play a role in the pathogenesis of CD. Enhancing innate immune competency and restoring mucosal barrier function provide a novel approach to treat CD. QBECO SSI is a first-in-class immunotherapy designed to correct innate immune dysfunction underlying CD. This analysis is from subjects in the open label portion of a planned controlled trial. Objectives were to assess endoscopic response at Wks 16 and 26, and select the optimal induction timepoint for the RCT. Safety and treatment compliance were also evaluated. Methods 20 pts with moderate-to-severe CD were enrolled and received QBECO SSI by sc injection every other day for up to 52 wks. Minimum eligibility: Simple Endoscopic Score for CD (SES-CD) ≥7 (ileitis ≥4), abdominal pain (AP) score &amp;gt;21 (11-point scale) or liquid/very soft stools (SF) (BFS Type 6 or 7) &amp;gt;10 for 7 consecutive days during screening. Pts were evaluated for clinical symptoms and endoscopy at Wks 16, 26, and 52. After evaluation at the induction period (Wk 26) pts could continue in maintenance up to Wk 52. Endoscopies were evaluated by central blinded read and pts reported daily symptoms. Endoscopic response defined as ≥50% reduction in SES-CD from baseline. Clinical remission defined as AP and SF ≤21. Results Mean age was 43.6 (SD 13.6) yrs; 60% men and 60% previously treated with biologics. Mean yrs since CD diagnosis was 14.4 (10.1), AP score 30.4 (15.8), SF score 36.2 (19.1) and mean SES-CD at baseline was 12.5 (6.7) indicating a more difficult to treat population. Endoscopic response rate by central read during the induction period was 30% (6/20) overall, 38% (3/8) for biologic naïve and 25% (3/12) biologic experienced pts (ITT analysis). Similar number of pts achieved endoscopic response at Wk 16 (4 pts) as 26 (3 pts). Mean SES-CD improved through Wk 26 with a 0.6 point greater reduction at Wk 26 compared to 16. Change in SES-CD from baseline in biologic naïve pts was -2.9 (5.8) at Wk 16 and -4.1 (6.7) at 26. Clinical remission was achieved by 45% (9/20) of pts at Wk 16 and 40% (8/20) at Wk 26; 16 pts continued into the maintenance phase of the study. By central evaluation, 13% (2/16) were in endoscopic response at Wk 52. QBECO SSI was very well tolerated. 8/20 (40%) pts reported AEs related to treatment. Most frequency reported related AE was injection site erythema (2/20, 10% pts). Majority of AEs were mild and no other related AE was reported by more than 1 patient. Conclusion Week 26 was the optimal endoscopic evaluation timepoint for QBECO SSI treatment and will be utilized in the larger RCT. Both biologics naïve and experienced patients showed response to QBECO SSI treatment by Weeks 26 and 52, with higher response rates in biologics naïve patients. QBECO SSI was well tolerated.

Nrf2 Regulates Anti-Inflammatory A20 Deubiquitinase Induction by LPS in Macrophages in Contextual Manner.

The aberrant regulation of inflammatory gene transcription following oxidant and inflammatory stimuli can culminate in unchecked systemic inflammation leading to organ dysfunction. The Nrf2 transcription factor dampens cellular stress and controls inflammation by upregulating antioxidant gene expression and TNFα-induced Protein 3 (TNFAIP3, aka A20) deubiquitinase by controlling NF-kB signaling dampens tissue inflammation. Here, we report that Nrf2 is required for A20 induction by inflammatory stimuli LPS in monocyte/bone marrow derived macrophages (MDMΦs) but not in lung-macrophages (LDMΦs). LPS-induced A20 expression was significantly lower in Nrf2−/− MDMΦs and was not restored by antioxidant supplementation. Nrf2 deficiency markedly impaired LPS-stimulated A20 mRNA expression Nrf2−/− MDMΦs and ChIP assays showed Nrf2 enrichment at the promoter Nrf2−/− MDMΦs upon LPS stimulation, demonstrating that Nrf2 directly regulates A20 expression. Contrary to MDMΦs, LPS-stimulated A20 expression was not largely impaired in Nrf2−/− LDMΦs ex vivo and in vivo and ChIP assays showed lack of increased Nrf2 binding at the A20 promoter in LDMΦ following LPS treatment. Collectively, these results demonstrate a crucial role for Nrf2 in optimal A20 transcriptional induction in macrophages by endotoxin, and this regulation occurs in a contextual manner.

Logistic Step Size Based Artificial Bee Colony Algorithm for Optimum Induction Motor Speed Control

Background: The disruption in the parameters of Induction Motor (IM) is quite frequent. In case of substantial parameter disruption, the IM becomes unreliable. Methods: To deal with this complication of parameter disruption, the Proportional-Integral (PI) controllers are utilized. The selection of PI controller parameters is process dependent and any inappropriate selection of controller setting may diverge to instability. Nowadays, the tuning of PI controller parameters for IM is executed using a significant SI algorithm namely, Artificial Bee Colony (ABC) algorithm. Further, the ABC algorithm is amended based on inspiration from the mathematical logistic formula. Results and Conclusion: The propound algorithm is titled as a logistic ABC algorithm and is applied for PI controller tuning of IM. The outcomes reveal that the propound algorithm performs better as compared to other state-of-art strategies available in the literature.

The effects and mechanism of α-mangostin on chemosensitivity of gastric cancer cells.

This work investigated the effect of α-mangostin (α-M) on gastric cancer (GC) cell chemoresistance and its underlying mechanisms. Different concentrations of α-M and CDDP were applied to treat GC cells (SGC7901) and CDDP-resistant GC cells (SGC7901/CDDP) for 24 or 48 h. CCK-8 assays were used to measure the inhibitory effect of CDDP or α-M on SGC7901 and SGC7901/CDDP cells as well as the half-maximal inhibitory concentrations (IC50) of α-M for SGC7901 and SGC7901/CDDP cells. The optimal concentration and induction time of CDDP or α-M were determined. SGC7901/CDDP cells were treated with CDDP or/and α-M, where some of them were transfected with pcDNA3.1 or pcDNA3.1-EBI3. Cell proliferation and apoptosis were assessed as well as the levels of EBI3, STAT3, p-STAT3, autophagy-related proteins, and apoptosis-related proteins. CDDP inhibited SGC7901 cell proliferation in a dose-dependent manner. The IC50 of α-M for SGC7901 cells was 12.86 μM and that for SGC7901/CDDP cells was 13.69 μM. The optimal concentrations of CDDP and α-M for SGC7901/CDDP cells were 2 and 15 μM, respectively, and the optimal time was 48 h. The SGC7901/CDDP cells in the CDDP+/α-M+ group had elevated inhibition of proliferation and apoptosis rates. Western blot analysis revealed enhanced levels of LC3-II/I and Beclin1, reduced p62 level, decreased Bcl2 level, and increased levels of Bax and cleaved caspase-3/9. The EBI3/STAT3 pathway was implicated in the effect of α-M on SGC7901/CDDP cell development. α-M increases the chemosensitivity of GC cells by facilitating autophagy and inactivating the EBI3/STAT3 pathway.