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Services for smart cities are required to improve productivity, sustainability, and quality of life. They can maximise resource usage, enhance public safety, accelerate economic growth, and promote civic engagement. In the past, cities relied on unreliable and limited-range radio and wired telephone networks. The capabilities of networked city services have significantly increased with the development of technologies like Ethernet and passive optical network (PON). These technologies enable real-time data collecting and analysis by delivering higher data transfer speeds and greater coverage areas. PON connections offer higher bandwidth, greater reliability, and longer lifetimes; 50 Gigabit-PON has the capacity to support different commercial services with notable performance to meet service requirements; and Ethernet networks have lower deployment costs as well as greater flexibility in terms of adding or removing devices. The various use-case scenarios of high-speed network technologies are evaluated. The technology ultimately chosen will be determined by the specific requirements and objectives of the smart city project.

In this paper, advanced DC-Link (DCL) based reversing voltage type Multilevel Inverter (MLI) topologies by compensating the difficulties in the conventional MLIs are reviewed. These topologies consist of less switching components and driver circuits when compared with conventional MLIs predominantly in higher levels. Consequently, installation area, total cost and hardware difficulties are reduced by increasing the voltage levels. The unipolar based Pulse Width Modulation Schemes (PWMS) will improve DCL inverters performance. This paper presents unipolar Multi-Reference (MR) based sine and space vector PWMS with single triangular carrier wave for generating required levels in output voltage. Comparison between UMR sine and space vector PWMS for DCL inverter topologies is presented in terms of Fundamental Output Voltage (FOV) and Total Harmonic Distortion (THD). The research tries to establish the survey analysis for single-phase 7-level DCL based reversing voltage type MLI topologies with UMR based sine and space vector PWMs. Finally, to confirm the feasibility of proposed DCL-MLIs in terms of FOV and THD the simulation results are incorporated. Further, the prototype model is developed for single-phase 7-level DCL inverter with Field Programmable Gate Array (FPGA) based UMR sine and space vector PWMS to authenticate simulation results. The efficiency of the proposed cascaded MLI achieves the value of 99.003%.

Objectives: Microcirculation is bound to be altered during cardiac surgery due to multiple factors, mainly the intense systemic inflammatory response syndrome which peaks in the first 24-h postoperatively. Decreased microvascular flow associated with increased postoperative morbidity has been reported. The literature suggests a potential independence of macrocirculation and microcirculation during fluid loading. The present study was conducted to assess thenar muscle tissue oxygen saturation (StO2) changes during vascular occlusion test (VOT) in response to hypovolemia and to assess the dynamic responses of the StO2 variables post-volume expansion (VE). Material and Methods: Thirty-five adult post-cardiac surgical patients, with stroke volume (SV) variation >12% were included in the study. Fifty-two fluid challenges were studied. Functional evaluation of microcirculation using VOT and near infrared spectroscopy (NIRS) variables along with monitoring of macrocirculatory indices was performed before and after VE. Statistical analysis was done using Student t-test. Results: Post-VE, 34 were responders with increase in SV ≥15% and 18 were non-responders (SV P = 0.0293 vs. P = 0.1480). However, macrocirculatory indices including cardiac output, SV, and delivery of oxygen showed significant improvement in both responders and non-responders. Conclusion: Preload dependence is associated with significant change in the StO2 recovery slope measured at the thenar eminence in volume responders. Functional evaluation of microcirculation using VOT and StO2 can be a useful complimentary tool along with the macrocirculatory indices for optimal fluid rescuscitaion in adult post-cardiac surgical patients.

In this paper, a multistring-multilevel inverter (M-MLI) for renewable-energy-source applications has been proposed with reduced switch count and harmonics along with single-switch fault analysis for various levels. It requires only ‘m+1’ power switches for ‘m’ voltage levels. The proposed work achieves the fine-tuning of switching angles using a metaheuristic technique, i.e. the teaching–learning-based optimization algorithm (TLBOA), to mitigate the total harmonic distortion (THD) of the M-MLI. Furthermore, the proposed TLBOA has been compared with conventional modulation techniques such as equal phase (EP), half-equal phase (HEP), near-level control (NLC) and Newton–Raphson (NR) to verify the effectiveness of TLBOA for various voltage levels in terms of % voltage-THD (%V-THD), computational time and methodology. By fine-tuning the switching angles, the %V-THD is improved significantly when compared with EP, HEP, NLC and NR modulation techniques. For an 11-level single-phase M-MLI, the %V-THD using TLBOA at 0.91 modulation index (MI) is 5.051%. The lower-order harmonics, i.e. 5, 7, 11 and 13, are eliminated to improve the power quality. Furthermore, MLIs are often prone to failure, resulting in waveform distortion. The extreme reduction in power quality impacts the load and significant damage is likely. The location of the open-circuit fault to be identified becomes more tedious under the faulty conditions with increased switch counts and voltage levels since the mathematical modelling fails to address the scenario in less computational time. Hence, the machine-learning approach, i.e. support vector machine (SVM) with Bayesian optimization, has been discussed to locate the faulty switch. Finally, the proposed M-MLI configuration has been modelled, simulated and validated using MATLAB® and Simulink®. The results of the M-MLI configuration have been verified for 7, 9 and 11 levels using TLBOA along with fault analysis using the SVM approach.

bstract: In the scenario of large organizations device management and maintenance plays an important role in proper functioning of network connected devices. SNMP (Simple NetworkManagement Protocol) is an internet Protocol running in the application layer of the OSI modelthat governs the functioning of the network devices such as routers, switches and access points. The implementation of SNMP is done mainly using UDP (User Datagram Protocol) which is best effort protocol leaving the responsibility of error correction to the application layer. Whatcan be gathered from the local device and what may be modified and set are specified by SNMPManagement Information Bases, or MIBs for short.

In this paper, the Enhanced Z-Source Switched Capacitor Multi-Level Inverter (EZSC-MLI) is presented, which can generate a greater number of levels and magnitude in output. The proposed MLI has greater recognition due to its low harmonic profile, fewer switching components, compact size, low switch stress, isolated DC supply, high efficiency, and low cost. A high voltage boost factor is achieved by using the Z-Source. The Switched Capacitor module is used for charging all the capacitors to equal voltage magnitude based on a self-balanced scheme. The proposed topology for grid integration requires dual control loops, a primary voltage control loop, and a secondary current control loop. The performance of the proposed 7-level topology for grid integrated systems is verified with multi-carrier advanced modulation schemes and by simulations carried out in Matlab/Simulink.

Solar photovoltaic (SPV) modules have a low output voltage and are load-dependent. Therefore, it is critical that the SPV system has an adequate DC–DC converter to regulate and improve the output voltage to get maximum output voltage. To meet load requirements, the voltage must be increased, necessitating the use of energy-efficient power electronic converters. The performance of an SPV system coupled to a high-gain quadratic boost converter (HG-QBC) with a load is investigated in this paper. The suggested HG-QBC for the SPV system at a lower value of duty ratio provides high voltage gain with a boost factor of four times. An analytical comparison is carried out with the various existing boost converters in terms of the components and the boost factor. The issue of locating the maximum power generation point from the SPV system is crucial. As a result, choosing an appropriate maximum power point tracker (MPPT)-based technique to obtain the peak power output of the SPV system under the rapidly varying atmospheric conditions is vital. To determine the highest output power of an SPV system, a hybrid-based MPPT with a neural network assisted by a perturb and observe (P&O) technique is proposed. For the HG-QBC, a comparison of the proposed MPPT with a traditional P&O-based MPPT is illustrated. The comparative analysis takes into account rise time, settling time and voltage ripples. The output voltage and power characteristics of the proposed model are analysed under constant and varying irradiation conditions using MATLAB®/Simulink®. The results of a hybrid-based MPPT show that the oscillations are minimum at the maximum power point with fewer ripples of 0.20% and a settling time of 1.2 s in comparison with the other two techniques.

In this paper, the performance of a permanent magnet synchronous generator (PMSG)-based wind energy conversion system (WECS) supplied to an uncontrolled rectifier-fed boost converter (BC) interfaced with a three-phase T-type three-level inverter (TLI) has been analysed. The proposed WECS involves three converters, namely an uncontrolled rectifier that is used for conversion from AC to DC; a BC supplied by a PMSG-fed rectifier used to enhance the voltage gain; and a grid-connected three-phase T-type TLI is proposed to eliminate power-quality issues with synchronization of grid voltage and current. The main goal of this research is to model and control the grid-connected T-type TLI using a d–q synchronous frame for wind energy for regulating the DC-link voltage and transferring the generated wind power from the BC to the grid. Furthermore, the perturb & observe (P&O)-based maximum power point (MPP) approach is recommended to keep track of the MPP for a BC that is supplied from a PMSG-based WECS under constant and variable wind speeds. The proposed PMSG-based WECS interfaced with grid-connected T-type TLI using d–q control has been computationally modelled, simulated and validated with constant and variable speeds using MATLAB® and Simulink®. It is confirmed that the P&O-based MPP approach ensures maximum power for varying wind speeds, and the total harmonic distortion of the T-type TLI grid current value is 3.18%, which is within IEEE-519 limits. Furthermore, with grid synchronization, the power factor of the T-type TLI is maintained at unity to avoid power-quality issues.

The COVID-19 pandemic has recently become a threat all across the globe with the rising cases every day and many countries experiencing its outbreak. According to the WHO, the virus is capable of spreading at an exponential rate across countries, and India is now one of the worst-affected country in the world. Researchers all around the world are racing to come up with a cure or treatment for COVID-19, and this is creating extreme pressure on the policy makers and epidemiologists. However, in India the recovery rate has been far better than in other countries, and is steadily improving. Still in such a difficult situation with no effective medicine, it is essential to know if a patient with the COVID-19 is going to recover or die. To meet this end, a model has been developed in this article to estimate the probability of a recovery of a patient based on the demographic characteristics. The study used data published by the Ministry of Health and Family Welfare of India for the empirical analysis.

Solar Photovoltaic (SPV) and wind energy are two major sources of renewable energy that are intermittent in nature. A hybrid system consisting of SPV and Wind Energy Conversion System (WECS) can meet the energy needs as either of the sources continues to generate energy, in the absence of the other, that is reliable and cost-effective. The paper presents detailed mathematical modeling, simulation, and performance analysis of a single cell SPV and Permanent Magnet Synchronous Generator (PMSG) based WECS. These two sources are integrated to form a hybrid renewable energy system. The hybrid model is simulated and the overall performance is analyzed using MATLAB/Simulink for varying temperature/irradiation conditions and varying wind speeds for SPV and WECS respectively. Performance characteristics of the hybrid PV and WECS are presented. The paper also presents as a case study, the annual energy generation for a chosen location from individual SPV and WECS systems based on the real time data collected from the Solacast website. This study evaluates the feasibility of the implementation of a hybrid system at the site.

Malnad Gidda cattle with specific qualities like disease resistance, heat tolerance, ability to survive and productionunder stress and low input conditions needs to be conserved for future. They are found to be less susceptible forfoot and mouth disease (FMD) and are normally not vaccinated for FMD. The present study was conducted todetermine the genetic polymorphism at MHC DRB3.2 loci and cellular immune responsiveness to FMD vaccinationin Malnad Gidda compared to Hallikar × HF crossbred cattle. A total of 12 cattle, of which six Malnad Gidda andsix Hallikar × Holstein Friesian crossbred animals aged between one to three years were selected. The genomicDNA was isolated and utilized to determine the genetic polymorphism at MHC DRB3.2 loci. The blood sampleswere collected from the same animals for estimation of CD4 and CD8 lymphocytes by flow cytometry to determinethe cellular immune responsiveness to FMD vaccination. The data obtained were subjected to statistical analysisGraphPad Prism Version 5.01. The two allelic variants MHC DRB3.2*117 and *219 present between MalnadGidda and Holstein Friesian crossbred cattle could be responsible for better cellular immune responsiveness withsignificantly higher CD4 lymphocytes population to FMD vaccination in Malnad Gidda cattle compared to Hallikar× HF crossbred cattle.

Nanostring miRNA data

Supplementary Figure 1. Representative OVCAR3-inoculated mice after aflibercept, Dll4-Fc, and the combination. Supplementary Figure 2. In vivo study of Dll4 blockade, aflibercept, and docetaxel, alone and in combinations, in A2780 and HeyA8 models. Supplementary Figure 3. Immunohistochemical staining of CX3CL1 in the tumor stroma of mice inoculated with A2780 ovarian cancer cells. Supplementary Figure 4. Quantitative real-time PCR of CX3CL1 expression in A2780 cells cultured with primary dendritic cells isolated from C57/BL6 mice. Supplementary Figure 5. ELISA analysis of plasma IFN-gamma in the mice inoculated with A2780 ovarian cancer cells. Supplementary Figure 6. RT-PCR analysis of E-cadherin expression in tumors (tumor cells and stroma) obtained from A2780 mice treated with a single agent or a combination.

Supplementary Figure 1. In vitro effects of PR silencing on onapristone sensitivity in PR-high-expressing uterine cancer cell line (Ishikawa). Supplementary Figure 2. In vitro effects of onapristone and trametinib in PR-weak-expressing uterine cancer cell line (SKUT2). Supplementary Figure 3. In vivo effects of therapy with onapristone in uterine cancer model. Supplementary Figure 4. In vivo effect of onapristone, trametinib, and the combination of both drugs on total PR expression in the ISHIKAWA model.

Advanced peritoneal carcinomatosis including high-grade ovarian cancer has poor prognoses and a poor response rate to current checkpoint inhibitor immunotherapies; thus, there is an unmet need for effective therapeutics that would provide benefit to these patients. Here we present the preclinical development of SENTI-101, a cell preparation of bone marrow-derived mesenchymal stromal (also known as stem) cells (MSC), which are engineered to express two potent immune-modulatory cytokines, IL12 and IL21. Intraperitoneal administration of SENTI-101 results in selective tumor-homing and localized and sustained cytokine production in murine models of peritoneal cancer. SENTI-101 has extended half-life, reduced systemic distribution, and improved antitumor activity when compared with recombinant cytokines, suggesting that it is more effective and has lower risk of systemic immunotoxicities. Treatment of tumor-bearing immune-competent mice with a murine surrogate of SENTI-101 (mSENTI-101) results in a potent and localized immune response consistent with increased number and activation of antigen presenting cells, T cells and B cells, which leads to antitumor response and memory-induced long-term immunity. Consistent with this mechanism of action, co-administration of mSENTI-101 with checkpoint inhibitors leads to synergistic improvement in antitumor response. Collectively, these data warrant potential clinical development of SENTI-101 for patients with peritoneal carcinomatosis and high-grade ovarian cancer.Graphical abstract: SENTI-101 schematic and mechanism of actionSENTI-101 is a novel cell-based immunotherapeutic consisting of bone marrow–derived mesenchymal stromal cells (BM-MSC) engineered to express IL12 and IL21 intended for the treatment of peritoneal carcinomatosis including high-grade serous ovarian cancer. Upon intraperitoneal administration, SENTI-101 homes to peritoneal solid tumors and secretes IL12 and IL21 in a localized and sustained fashion. The expression of these two potent cytokines drives tumor infiltration and engagement of multiple components of the immune system: antigen-presenting cells, T cells, and B cells, resulting in durable antitumor immunity in preclinical models of cancer.

For mucinous ovarian cancer (MOC), standard platinum-based therapy is largely ineffective. We sought to identify possible mechanisms of oxaliplatin resistance of MOC and develop strategies to overcome this resistance. A kinome-based siRNA library screen was carried out using human MOC cells to identify novel targets to enhance the efficacy of chemotherapy. In vitro and in vivo validations of antitumor effects were performed using mouse MOC models. Specifically, the role of PRKRA/PACT in oxaliplatin resistance was interrogated. We focused on PRKRA, a known activator of PKR kinase, and its encoded protein PACT because it was one of the five most significantly downregulated genes in the siRNA screen. In orthotopic mouse models of MOC, we observed a significant antitumor effect of PRKRA siRNA plus oxaliplatin. In addition, expression of miR-515-3p was regulated by PACT–Dicer interaction, and miR-515-3p increased the sensitivity of MOC to oxaliplatin. Mechanistically, miR-515-3p regulated chemosensitivity, in part, by targeting AXL. The PRKRA/PACT axis represents an important therapeutic target in MOC to enhance sensitivity to oxaliplatin.

Delta-like ligand 4 (Dll4), one of the Notch ligands, is overexpressed in ovarian cancer, especially in tumors resistant to anti-VEGF therapy. Here, we examined the biologic effects of dual anti-Dll4 and anti-VEGF therapy in ovarian cancer models. Using Dll4-Fc blockade and anti-Dll4 antibodies (murine REGN1035 and human REGN421), we evaluated the biologic effects of Dll4 inhibition combined with aflibercept or chemotherapy in orthotopic mouse models of ovarian cancer. We also examined potential mechanisms by which dual Dll4 and VEGF targeting inhibit tumor growth using immunohistochemical staining for apoptosis and proliferation markers. Reverse-phase protein arrays were used to identify potential downstream targets of Dll4 blockade. Dual targeting of VEGF and Dll4 with murine REGN1035 showed superior antitumor effects in ovarian cancer models compared with either monotherapy. In the A2780 model, REGN1035 (targets murine Dll4) or REGN421 (targets human Dll4) reduced tumor weights by 62% and 82%, respectively; aflibercept alone reduced tumor weights by 90%. Greater therapeutic effects were observed for Dll4 blockade (REGN1035) combined with either aflibercept or docetaxel (P < 0.05 for the combination vs. aflibercept). The superior antitumor effects of REGN1035 and aflibercept were related to increased apoptosis in tumor cells compared with the monotherapy. We also found that GATA3 expression was significantly increased in tumor stroma from the mice treated with REGN1035 combined with docetaxel or aflibercept, suggesting an indirect effect of these combination treatments on the tumor stroma. These findings identify that dual targeting of Dll4 and VEGF is an attractive therapeutic approach. Mol Cancer Ther; 15(6); 1344–52. ©2016 AACR.

Supplementary Figure1 shows MSC homing to tumor and other organs in vivo using a bioluminescent reporter. Supplementary Figure 2. Characterization of tumor immune infiltrate of syngeneic preclinical intraperitoneal tumor models CT26-ip and B16F10-ip using IHC and flow cytometry. Supplementary Figure 3. Kaplan Meier Survival in B16F10-ip model comparing multiple combinations of effector cytokines expressed by MSCs. Supplementary Figure 4. Shows data supporting the construct optimization for SENTI-101 including promoter, orientation and signal sequence changes. Supplementary Figure 5. IL-21 functional validation using UO2S IL-21 receptor dimerization reporter assay. Supplementary Table 1. Shows the DNA sequence of SB00880, the lentiviral construct used to engineer SENTI-101. Supplementary Figure 6. Shows the SENTI-101 manufacturing process overview. Supplementary Figure 7. Shows supporting data for the study of pharmacokinetics and pharmacodynamics of SENTI-101. Supplementary Figure 8. Shows individual tumor burden for each mouse measured by bioluminescence imaging (BLI) after treatment with SENTI-101 or controls. Supplementary Figure 9. Percent change in mouse body weight after treatment. Supplementary Figure 10. Shows the controls and supporting data for the selective depletion of immune cell types. Supplementary Figure 11. Characterization of tumor infiltrating lymphocytes (TILs) in the B16F10-ip tumor model after treatment with mSENTI-101. Supplementary Figure 12. Anti-tumor immune response induced by SENTI-101 in CT-26ip model. Supplementary Figure 13. Shows individual tumor burden for each mouse measured by BLI after treatment with SENTI-101 and in combination with checkpoint inhibitor anti-PD-1.

Despite being among the most common oncogenes in human cancer, to date, there are no effective clinical options for inhibiting KRAS activity. We investigated whether systemically delivered KRAS siRNAs have therapeutic potential in KRAS-mutated cancer models. We identified KRAS siRNA sequences with notable potency in knocking down KRAS expression. Using lung and colon adenocarcinoma cell lines, we assessed antiproliferative effects of KRAS silencing in vitro. For in vivo experiments, we used a nanoliposomal delivery platform, DOPC, for systemic delivery of siRNAs. Various lung and colon cancer models were used to determine efficacy of systemic KRAS siRNA based on tumor growth, development of metastasis, and downstream signaling. KRAS siRNA sequences induced >90% knockdown of KRAS expression, significantly reducing viability in mutant cell lines. In the lung cancer model, KRAS siRNA treatment demonstrated significant reductions in primary tumor growth and distant metastatic disease, while the addition of CDDP was not additive. Significant reductions in Ki-67 indices were seen in all treatment groups, whereas significant increases in caspase-3 activity were only seen in the CDDP treatment groups. In the colon cancer model, KRAS siRNA reduced tumor KRAS and pERK expression. KRAS siRNAs significantly reduced HCP1 subcutaneous tumor growth, as well as outgrowth of liver metastases. Our studies demonstrate a proof-of-concept approach to therapeutic KRAS targeting using nanoparticle delivery of siRNA. This study highlights the potential translational impact of therapeutic RNA interference, which may have broad applications in oncology, especially for traditional “undruggable” targets. Mol Cancer Ther; 13(12); 2876–85. ©2014 AACR.

Supplementary figure 1 provides a schematic of DOPC:siRNA nanoliposomal preparation, and Supplementary figure 2 shows tumor volumetric measurements of the A549 orthotopic lung cancer therapeutic experiment described in the main figure 2.

Although progesterone receptor (PR)–targeted therapies are modestly active in patients with uterine cancer, their underlying molecular mechanisms are not well understood. The clinical use of such therapies is limited because of the lack of biomarkers that predict response to PR agonists (progestins) or PR antagonists (onapristone). Thus, understanding the underlying molecular mechanisms of action will provide an advance in developing novel combination therapies for cancer patients. Nuclear translocation of PR has been reported to be ligand-dependent or -independent. Here, we identified that onapristone, a PR antagonist, inhibited nuclear translocation of ligand-dependent or -independent (EGF) phospho-PR (S294), whereas trametinib inhibited nuclear translocation of EGF-induced phospho-PR (S294). Using orthotopic mouse models of uterine cancer, we demonstrated that the combination of onapristone and trametinib results in superior antitumor effects in uterine cancer models compared with either monotherapy. These synergistic effects are, in part, mediated through inhibiting the nuclear translocation of EGF-induced PR phosphorylation in uterine cancer cells. Targeting MAPK-dependent PR activation with onapristone and trametinib significantly inhibited tumor growth in preclinical uterine cancer models and is worthy of further clinical investigation. Mol Cancer Ther; 17(2); 464–73. ©2017 AACR.

Table S1 shows antibody concentrations. Table S2 shows siRNA sequences. Table S3 shows qPCR primers sequences. Table S5 shows IC50 values of oxaliplatin.

Mounting clinical and preclinical evidence supports a key role for sustained adrenergic signaling in the tumor microenvironment as a driver of tumor growth and progression. However, the mechanisms by which adrenergic neurotransmitters are delivered to the tumor microenvironment are not well understood. Here we present evidence for a feed-forward loop whereby adrenergic signaling leads to increased tumoral innervation. In response to catecholamines, tumor cells produced brain-derived neurotrophic factor (BDNF) in an ADRB3/cAMP/Epac/JNK-dependent manner. Elevated BDNF levels in the tumor microenvironment increased innervation by signaling through host neurotrophic receptor tyrosine kinase 2 receptors. In patients with cancer, high tumor nerve counts were significantly associated with increased BDNF and norepinephrine levels and decreased overall survival. Collectively, these data describe a novel pathway for tumor innervation, with resultant biological and clinical implications.Significance: Sustained adrenergic signaling promotes tumor growth and metastasis through BDNF-mediated tumoral innervation. Cancer Res; 78(12); 3233–42. ©2018 AACR.

Supplementary Figure 1 Functional genomic analysis of HeyA8 and SKOV3ip ovarian cancer cells 4 h after exposure to norepinephrine and compared to control cells. Supplementary Figure 2 A, Western blot analysis of ADRB1, ADRB2, ADRB3, and DUSP1 expression in 10 epithelial ovarian cancer cell lines and one breast cancer cell line (MDA-231), using non-transformed ovarian epithelium cells (HIO-180) as control. B, DUSP1 mRNA levels of cells exposed to norepinephrine 10 μM for 4 h. Supplementary Figure 3 A, DUSP1 silencing. Two commercially available siRNAs that directly target the DUSP1 gene were transfected to norepinephrine-treated HeyA8 cells. B, DUSP1 overexpression. SKOV3ip1 cells were transiently transfected with a DUSP1-myc/DDK-tagged expression vector (Origene). Supplementary Figure 4 SKOV3ip1 cells were treated with paclitaxel alone (10nM) or in combination with norepinephrine (NE; 10μM) or vascular endothelial growth factor (VEGF; 10ng/ml or 50ng/ml). NE or VEGF was administered 30 minutes prior to paclitaxel exposure.

CARS imaging of ex vivo ovarian cancer samples

Fig. S1. Sustained adrenergic signaling increases nerve counts in tumors. Fig. S2. Characterization of tumoral innervation. Fig. S3. NE induces BDNF expression. Fig. S4. NE-induced BDNF expression is mediated by ADRB3/Epac/Jnk. Fig. S5. BDNF increases nerve counts. Fig. S6. Adrenergic-mediated mTrkB activation leads to increased in vivo tumor nodule counts. Table S1. Alteration in pathways associated with neuronal growth and function after NE treatment (HeyA8 and SKOV3ip1 cells). Table S2. Association of Clinicopathologic variables with BDNF protein expression. Table S3. Association of Clinicopathologic variables with Nerve Counts.

Supplementary Figures S1-5, Tables S1-5. Figure S1 The Cytotoxic Effect of KPT-185 is Tumor Suppressor-independent. Figure S2 Combination Index of KPT-185 with Chemotherapeutic Agents. Figure S3 1D Gel Analysis of Cytoplasmic Protein. Figure S4 Effects of Selinexor (KPT-330) in an Ovarian Cancer Mouse Model. Figure S5 The Efficacy of Selinexor (KPT-330) on Tumor Regression and Metastasis Table S1 p53 status and IC50 concentration of KPT-185 after 72 hours of incubation in human cancer cell lines Table S2 Combination index (CI) of KPT-185 with cytotoxic agents Table S3 Proteins showing altered mitochondrial localization after treatment with KPT-185 Table S4 1D Proteomic analysis of cytoplasmic proteins immunoprecipitated with eIF5A Table S5 siRNA Sequences

Purpose: Chronic adrenergic activation has been shown to associate with adverse clinical outcomes in cancer patients, but the underlying mechanisms are not well understood. The focus of the current study was to determine the functional and biologic effects of adrenergic pathways on response to chemotherapy in the context of ovarian cancer.Experimental Design: Increased DUSP1 production by sympathetic nervous system mediators (e.g., norepinephrine) was analyzed by real-time quantitative RT-PCR and by Western blotting. In vitro chemotherapy-induced cell apoptosis was examined by flow cytometry. For in vivo therapy, a well-characterized model of chronic stress was used.Results: Catecholamines significantly inhibited paclitaxel- and cisplatin-induced apoptosis in ovarian cancer cells. Genomic analyses of cells treated with norepinephrine identified DUSP1 as a potential mediator. DUSP1 overexpression resulted in reduced paclitaxel-induced apoptosis in ovarian cancer cells compared with control; conversely, DUSP1 gene silencing resulted in increased apoptosis compared with control cells. DUSP1 gene silencing in vivo significantly enhanced response to paclitaxel and increased apoptosis. In vitro analyses indicated that norepinephrine-induced DUSP1 gene expression was mediated through ADRB2 activation of cAMP–PLC–PKC–CREB signaling, which inhibits JNK-mediated phosphorylation of c-Jun and protects ovarian cancer cells from apoptosis. Moreover, analysis of The Cancer Genome Atlas data showed that increased DUSP1 expression was associated with decreased overall (P = 0.049) and progression-free (P = 0.0005) survival.Conclusions: These findings provide a new understanding of the mechanisms by which adrenergic pathways can impair response to chemotherapy and have implications for cancer management. Clin Cancer Res; 22(7); 1713–24. ©2015 AACR.

CARS imaging of ex vivo ovarian cancer samples

This paper analyses the performance of a multiple gain boost converter (MGBC) connected to a solar photovoltaic (SPV) system with a grid-tied inverter. The capacitor inductor capacitor (CLC)-based MGBC is integrated to lift the output voltage of the SPV to the required level. The voltage lifts/levels in a boost converter (BC) are based on the number of CLC cells. The suggested MGBC is compared with various conventional BCs in terms of boost factor and component count. A hybrid fuzzy logic–perturb & observe maximum power point tracker (HFL–P&O MPPT) developed is used to monitor Pmax (maximum power) generated by the SPV. Also, a comparative analysis of the suggested MPPT with a conventional P&O and fuzzy logic-based (FLB) MPPT for a CLC-based MGBC is presented. The comparison is made in terms of rise time, voltage ripples (%), steady-state time and boost factor. The output characteristics of the developed model for different irradiation conditions are analysed using the MATLAB/Simulink tool. The MPPT simulation result exhibits minimum oscillations at MPP and a significantly better rise time of 0.015 s when compared with a conventional MPPT and FLB MPPT. The proposed CLC-MGBC gives an appreciable boost factor of 4. The generated SPV power is supplied to the grid through a conventional inverter and synchronized using a phase-locked loop system. The total harmonic distortion of 1.66% obtained in the output current of the inverter is within the permissible range of the IEEE standards.

We cannot deny that internet and many applications running on internet are growing at an exponential rate. It has become more important for network administrators to have an understanding of the different types of network traffic. This paper reviews the topic of exploratory data analysis of captured network traffic. There has been an exponential rise in the use of web apps such as social media sites, e-commerce, video streaming services, blogs, e-banking lately. These application has now become the day-to-day mode of communication all over the world and its importance is ever growing. In this paper, we explore and investigate the data being transmitted by 75 apps and segregate the users of these apps based on network usage and try to determine the most used apps. The output of this exploratory data analysis can be applied in various fields.

Advanced peritoneal carcinomatosis including high-grade ovarian cancer has poor prognoses and a poor response rate to current checkpoint inhibitor immunotherapies; thus, there is an unmet need for effective therapeutics that would provide benefit to these patients. Here we present the preclinical development of SENTI-101, a cell preparation of bone marrow-derived mesenchymal stromal (also known as stem) cells (MSC), which are engineered to express two potent immune-modulatory cytokines, IL12 and IL21. Intraperitoneal administration of SENTI-101 results in selective tumor-homing and localized and sustained cytokine production in murine models of peritoneal cancer. SENTI-101 has extended half-life, reduced systemic distribution, and improved antitumor activity when compared with recombinant cytokines, suggesting that it is more effective and has lower risk of systemic immunotoxicities. Treatment of tumor-bearing immune-competent mice with a murine surrogate of SENTI-101 (mSENTI-101) results in a potent and localized immune response consistent with increased number and activation of antigen presenting cells, T cells and B cells, which leads to antitumor response and memory-induced long-term immunity. Consistent with this mechanism of action, co-administration of mSENTI-101 with checkpoint inhibitors leads to synergistic improvement in antitumor response. Collectively, these data warrant potential clinical development of SENTI-101 for patients with peritoneal carcinomatosis and high-grade ovarian cancer. Graphical abstract: SENTI-101 schematic and mechanism of action SENTI-101 is a novel cell-based immunotherapeutic consisting of bone marrow–derived mesenchymal stromal cells (BM-MSC) engineered to express IL12 and IL21 intended for the treatment of peritoneal carcinomatosis including high-grade serous ovarian cancer. Upon intraperitoneal administration, SENTI-101 homes to peritoneal solid tumors and secretes IL12 and IL21 in a localized and sustained fashion. The expression of these two potent cytokines drives tumor infiltration and engagement of multiple components of the immune system: antigen-presenting cells, T cells, and B cells, resulting in durable antitumor immunity in preclinical models of cancer.

Bimetallic nanoparticles (BNPs) have drawn significant attention due to their numerous applications. They demonstrate enhanced optical, electrical, thermal, and catalytic properties due to the synergistic effects of monometals present in them. In this work, CuAg and AuAg BNPs have been synthesized using a facile and economical chemical reduction method. Optical characterization was carried out using UV–visible spectroscopy, and effect of pH on optical absorbance was studied. For CuAg and AuAg BNPs, optimum pH was observed to be at 9.4 and 6.39, respectively. Morphological investigation confirms the average diameters of CuAg and AuAg BNPs were to be 65 nm and 30 nm, respectively. Photocatalytic property illustrates the reduction of 4-nitrophenol to 4-aminophenol with a 92% conversion percentage in the presence of CuAg BNPs in 4 min, and rate constant for the reaction was measured to be 8.98 × 10–3 s−1. But for the AuAg BNPs, the conversion percentage was 97% in 8 min and rate constant was found to be 7.95 × 10–3 s−1. Thermal conductivity and viscosity measurements of the nanofluids obtained with CuAg and AuAg BNPs have ascertained them to be efficient candidates for the heat transfer and catalytic applications. Graphic abstract

A single-pulse shock tube study of the four pentene isomers is carried out at 2¿±¿0.16¿bar and 900¿1600¿K. C1 to C6 species profiles were recorded using gas chromatography mass spectrometry analyses. The species are identified using mass spectrometry and quantified by flame ionization detection. High-pressure limiting and pressure-dependent rate constants for 2M1B, 2M2B and 3M1B¿+¿¿ were calculated using RRKM theory with a Master Equation (ME) analysis using the Master Equation System Solver, MESS. A mechanism was formulated based on rate rules and theoretical calculations. Comparisons between experimental results and model simulations are provided for all of the five pentene isomers investigated with satisfactory agreement. Furthermore, an insight is provided into the influence of molecular structure on the reactivity of pyrolysis chemistry. Interestingly, it is found that the HACA mechanism is much less prominent for benzene formation compared to the role of cyclopentadienyl radical recombination with methyl radicals and also the recombination of propargyl radicals. The authors would like to acknowledge Science Foundation Ireland for funding via project numbers 15/IA/3177 and 16/SP/3829. The work at LLNL was performed under the auspices of the U.S. Department of Energy (DOE), Contract DE-AC52-07NA27344, and was supported by the U.S. Department of Energy, Vehicle Technologies Office, program managers, Mike Weismiller and Gurpreet Singh. peer-reviewed

To improve our understanding of the combustion characteristics of propyne, new experimental data for ignition delay times (IDTs), pyrolysis speciation profiles and flame speed measurements are presented in this study. IDTs for propyne ignition were obtained at equivalence ratios of 0.5, 1.0, and 2.0 in `air¿ at pressures of 10 and 30¿bar, over a wide range of temperatures (690¿1460¿K) using a rapid compression machine and a high-pressure shock tube. Moreover, experiments were performed in a single-pulse shock tube to study propyne pyrolysis at 2¿bar pressure and in the temperature range 1000¿1600¿K. In addition, laminar flame speeds of propyne were studied at an unburned gas temperature of 373¿K and at 1 and 2¿bar for a range of equivalence ratios. A detailed chemical kinetic model is provided to describe the pyrolytic and combustion characteristics of propyne across this wide-ranging set of experimental data. This new mechanism shows significant improvements in the predictions for the IDTs, fuel pyrolysis and flame speeds for propyne compared to AramcoMech3.0. The improvement in fuel reactivity predictions in the new mechanism is due to the inclusion of the propyne¿+¿H¿2 reaction system along with ¿H radical addition to the triple bonds of propyne and subsequent reactions. The authors would like to acknowledge Science Foundation Ireland for funding via project numbers 15/IA/3177 and 16/SP/3829. The material for measuring flame speed is based upon work supported by the U.S. Department of Energy's Office of Energy Efficiency and Renewable Energy (EERE) under Award Number DE-EE0007984 (Co-Optima). Jinhu Liang acknowledges the International Scientific Cooperation Projects of Key R&D Programs in Shanxi Province via project number 201803D421101 and Research Project Supported by Shanxi Scholaiship Council of Chinavia project number 2020-115. We want to acknowledge Tyler MacDougall of University of Central Florida for his help with LBV experiments. peer-reviewed

A study on performance of gerbera cultivars for different levels of silicic acid application was carried out under protected condition. The results revealed that among all seven cultivars, ‘Marinilla’ recorded with higher number of flowers (15.11) and lower number of flowers observed with cultivar ‘Vilassar’ (13.11). Cultivars ‘Vilassar’ and ‘Amelie’ recorded with higher flower diameter (11.88 mm) than ‘Natasha’ (10.47 mm). Stalk length was recorded higher with cultivar ‘Marinilla’ (70.16 cm) and lower stalk length was observed in cultivar ‘Nijela’ (64.16 cm) after fourth spray. Flowers of cultivars ‘Vilassar’ and ‘Amlet’ was recorded with higher vase life (13.88 days) compared to other cultivars. Silicic acid spray showed better results with respect to number of flowers, flower diameter, stalk length and vase life of flower. Foliar spray of silicic acid 2 ml/L of water was recorded with higher vase life of flower (14.33 days). Treatment without silicic acid (0 ml/L) recorded with lower vase life (12.76 days).

Use of nano-additives in biofuels is an important research and development topic for achieving optimum engine performance with reduced emissions. In this study, rice bran oil was converted into biodiesel and graphene oxide (GO) nanoparticles were infused into biodiesel-diesel blends. Two blends containing (i) 5% biodiesel, 95% diesel and 30 ppm GO (B5D95GO30) and (ii) 15% biodiesel, 85% diesel and 30 ppm GO (B15D85GO30) were prepared. The fuel properties like heating value, kinematic viscosity, cetane number, etc. of the nanoadditives–biodiesel-diesel blends (NBDB) were measured. Effects of injection timing (IT) on the performance, combustion and emission characteristics were studied. It was observed that both B15D85GO30 and B5D95GO30 blends at IT23° gave up to 13.5% reduction in specific fuel consumption. Compared to diesel, the brake thermal efficiency was increased by 7.62% for B15D85GO30 at IT23° and IT25°. An increase in IT from 23° to 25° deteriorated the indicated thermal efficiency by 6.68% for B15D85GO30. At maximum load condition, the peak heat release rates of NBDB were found to be lower than the pure diesel at both IT. The CO, CO2 & NOx emissions were reduced by 2–8%. The study concluded that B15D85GO30 at IT23° gave optimum results in terms of performance, combustion and emission characteristics.

A single-pulse shock tube study of the pyrolysis of 2% C-2 - C-6 1-alkenes is presented at 2 bar in the tem-perature range 900-1800 K in the current study. Reactant, intermediate and product species are obtained and quantified using gas chromatography-mass spectrometry (GC-MS) analysis. MS is used for species identification and a flame ionization detector is used for quantification. The experiments show the effect of carbon chain length on the production of smaller C 1-C-3 fragments. A new detailed kinetic mechanism, NUIGMech1.0, is used to simulate the data and the predictions for the major species are satisfactory. The improvement in predictions of the current mechanism, which includes C-6 and C-7 species, is substantial compared to AramcoMech3.0. Kinetic analyses are conducted with the current mechanism to identify the formation and consumption pathways of the quantified species. The experimental data are expected to contribute to a database for the validation of mechanisms at pyrolytic conditions. Additionally, the mech-anism aims to provide a fundamental understanding of the pyrolytic chemistry of olefins. (C) 2020 The Author(s). Published by Elsevier Inc. on behalf of The Combustion Institute. The authors would like to acknowledge Science Foundation Ireland for funding via project numbers 15/IA/3177 and 16/SP/3829. The work at LLNL was performed under the auspices of the U.S. Department of Energy (DOE), Contract DE-AC52-07NA27344, and was supported by the U.S. Department of Energy, Vehicle Technologies Office, program managers, Mike Weismiller and Gurpreet Singh. Jinhu Liang acknowledges the International Scientific Cooperation Projects of Key R&D Programs in Shanxi Province via project number 201803D421101. peer-reviewed

A comprehensive experimental and kinetic modeling study of the ignition delay time (IDT) characteristics of some binary blends of C1–C2 gaseous hydrocarbons such as methane/ethylene, methane/ethane, and ethane/ethylene was performed over a wide range of composition (90/10, 70/30, 50/50%), temperature (∼800–2000 K), pressure (∼1–40 bar), equivalence ratio (∼0.5–2.0), and dilution (∼75–90%). An extensive literature review was conducted, and available data were extracted to create a comprehensive database for our simulations. Based on the existing literature data, an experimental matrix was designed using the Taguchi approach (L9) in order to identify and complete the experimental matrix required to generate a comprehensive experimental IDT set necessary for the validation of a chemical kinetic model. The required high- and low-temperature IDTs were collected using low-/high-pressure shock tubes and rapid compression machines, respectively. The predictions of NUIGMech1.0 are examined versus all of the available experimental data, including those taken in the current study using the IDT simulations and a correlation technique. Moreover, the individual effect of the studied parameters, including mixture composition, pressure, equivalence ratio, and dilution on IDT, is investigated over the studied temperature range. Correlations that were developed based on NUIGMech1.0 are presented for each specific blended fuel over the conditions studied. These correlations show an acceptable performance versus the experimental data. The authors would like to express their gratitude to Shell Research Ltd. and Science Foundation Ireland (SFI) for funding via project numbers 15/IA/3177 and 16/SP/3829. The authors from PCFC, RWTH Aachen University, would like to recognize the funding support from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) through the project number – 322460823 (HE7599/2-1). peer-reviewed 2021-06-03